Medical Policy: 07.03.11 

Original Effective Date: April 2018 

Reviewed: April 2021 

Revised: April 2021 

 

Notice:

This policy contains information which is clinical in nature. The policy is not medical advice. The information in this policy is used by Wellmark to make determinations whether medical treatment is covered under the terms of a Wellmark member's health benefit plan. Physicians and other health care providers are responsible for medical advice and treatment. If you have specific health care needs, you should consult an appropriate health care professional. If you would like to request an accessible version of this document, please contact customer service at 800-524-9242.

 

Benefit Application:

Benefit determinations are based on the applicable contract language in effect at the time the services were rendered. Exclusions, limitations or exceptions may apply. Benefits may vary based on contract, and individual member benefits must be verified. Wellmark determines medical necessity only if the benefit exists and no contract exclusions are applicable. This medical policy may not apply to FEP. Benefits are determined by the Federal Employee Program.

 

This Medical Policy document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy will be reviewed regularly and be updated as scientific and medical literature becomes available.

 

Description:

Traditionally, high-dose chemotherapy, also known as myeloablative therapy, and extensive radiation therapy have been used to treat certain drug-resistant cancers or relapsed diseases. High-dose chemotherapy and radiation generally affect cells that divide rapidly, and cancer cells divide more often than most healthy cells. High-dose chemotherapy involves the administration of cytotoxic agents at doses several times greater than the standard therapeutic dose.

 

The rationale for high-dose chemotherapy is that many chemotherapeutic agents act according to a steep dose-response curve. Small increments in drug dosage result in relatively large increases in tumor cell destruction. The limiting dynamic of high-dose chemotherapy and radiation therapy is the toxic effect that these treatments have on bone marrow cells. Although high-dose chemotherapy kills the tumor cells, it also increases the incidence and severity of adverse effects associated with chemotherapy, such as bone marrow destruction (myeloablation), opportunistic infection, hemorrhage, and organ failure.

 

Bone marrow is a soft, spongelike material found inside bones. Bone marrow contains cells known as hematopoietic, or blood-forming, cells. Hematopoietic stem cells either divide to form additional blood-forming stem cells, or they mature to form one of three types of cells: white cells (leukocytes), red blood cells (erythrocytes), or platelets. Most hematopoietic stem cells are found in bone marrow, but some are also found in the bloodstream and are known as peripheral blood stem cells. Blood in the umbilical cord also contains hematopoietic stem cells. In individuals who have undergone high-dose chemotherapy and/or radiation, hematopoietic stem cell transplantation can be used to regenerate bone marrow and aid in the development of mature blood cell products, thereby decreasing the incidence of life-threatening conditions and aiding in the individual's recovery.

 

Hematopoietic stem cell transplantation (also referred to as bone marrow transplantation; or peripheral blood stem cell transplantation) are used to restore stem cells destroyed by high-dose chemotherapy and/or radiation therapy. Transplantation is accomplished in the same manner as a blood transfusion.

 

The transplantation of hematopoietic stem cells is an adjunctive therapy and follows the administration of high-dose chemotherapy and/or whole-body or localized radiotherapy prior to the transplant. The transplantation of hematopoietic stem cells has been found to increase the efficacy of high-dose chemotherapy and/or radiotherapy in the treatment of certain conditions including but not limited to the following: leukemias, lymphomas (e.g, Hodgkin's lymphoma, Non-Hodkin’s lymphoma), central nervous system tumors (embryonal), multiple myeloma, solid tumors of childhood, amyloidosis, some genetic diseases and acquired anemias.

 

Transplants are classified as one of three types:

  • Autologous: An individual receives his or her own stem cells
  • Allogeneic: An individual receives stem cells from another individual. They can be from a matched related or unrelated donor or donor without a complete match
  • Syngeneic: An individual receive stem cells from his or her identical twin

 

Autologous Hematopoietic Stem Cell Transplantation (Bone Marrow Transplant)

In autologous hematopoietic stem cell transplantation, the individual receives his or her own stem cells, which were harvested prior to myeloablative therapy and are relatively cancer-free. Myeloablative chemotherapy is performed to eradicate cancerous cells from the blood and bone marrow, thereby permitting subsequent engraftment and repopulation of bone marrow space with presumably normal hematopoietic progenitor cells or cells that allow themselves to differentiate from other cells. As a result, autologous stem cell transplantation is typically performed as consolidation therapy when the individual's disease is in complete remission. Individuals who receive autologous stem cell transplantation are susceptible to chemotherapy-related toxicities and opportunistic infections prior to engraftment, but not graft-versus-host disease.

 

High-dose chemotherapy, in conjunction with autologous hematopoietic stem cell transplantation, is the established standard of therapy for various malignancies including but not limited to acute myelogenous leukemia, multiple myeloma, and non-Hodgkin's lymphoma. Autologous hematopoietic stem cell transplantation is also preferred for the elderly or for individuals who lack a donor with suitable HLA typing. Advantages of autologous transplants include the reduced toxicity that is associated with treatment and an extended, disease-free survival time, most often without the need for additional treatment.

 

Allogeneic Hematopoietic Stem Cell Transplantation (Bone Marrow Transplant)

Allogeneic hematopoietic stem cell transplantation involves using hematopoietic stem cells harvested from another individual. They can be from a matched related or unrelated donor or a donor without a complete match. The success of the transplant depends in part on how well the HLAs of the donor’s stem cells match those of the recipient’s stem cells. HLAs are a set of proteins that are found on the surface of cells and are identifiable by a special blood test, the higher the number of matching HLAs between the individuals, the greater the chance that the recipient will accept the donor’s stem cells. Close relatives, especially siblings, are more likely than unrelated individuals to be HLA-matched (6/6 HLA match); however, only 25 to 35 percent of transplant candidates have a sibling who is an HLA match.

 

A syngeneic allogeneic stem cell transplant is when the patient receives donor stem cells from his or her healthy identical twin.

 

For patients who lack an HLA-matched sibling (6/6 HLA match), alternative sources of donors include suitably HLA-matched unrelated donors, umbilical cord blood stem cells, and partially HLA-mismatched, or HLA-haploidentical related donors.

 

Allogeneic hematopoietic stem cell transplantation (bone marrow transplantation) consists of the following conditioning regimens:

  • Myeloablative is a severe form of myelosuppression. Myelosuppression is a condition in which bone marrow activity is decreased, resulting in fewer red blood cells, white blood cells, and platelets. It is a side effect of some cancer treatments prior to receiving the donor’s marrow or stem cells.
  • Non-myeloablative (also knowns as reduced intensity conditioning) is a bone marrow transplant in which the individual’s marrow is not completely destroyed prior to receiving the donor’s marrow or stem cells

 

Reduced intensity conditioning regimens (non-myeloablative) would be considered for individuals who would otherwise qualify for a myeloablative allogeneic hematopoietic stem cell transplantation (bone marrow transplantation) but would not tolerate standard myeloablative conditioning regimen. This may include the following: age typically > 60 years or comorbidities (e.g., liver or kidney dysfunction, generalized debilitation, prior intensive chemotherapy, low Karnofsky Performance Status score).

 

Umbilical Cord Stem Cells

Blood harvested from the umbilical cord shortly after delivery of neonates contains stem and progenitor cells capable of restoring hematopoietic function after myeloablation. This cord blood has been used as an alternative source of allogeneic stem cells. Cord blood is thought to be antigenically naïve, thus potentially minimizing the incidence of graft-versus-host disease and permitting the broader use of unrelated cord blood transplants. Unrelated donors are typically typed at low resolution for human leukocyte antigen (HLA) A and B and a high resolution only for HLA-DR; HLA matching at 4 of 6 loci is considered acceptable. Under this matching protocol, an acceptable donor can be identified for almost any patients. Cord blood requires no mobilization, once collected it is mixed in a preservation solution and stored at a very low temperature until needed.

 

Haploidentical Donor

An HLA-haploidentical donor is one who shares, by common inheritance, exactly one HLA haplotype with the recipient and is mismatched for a variable number of HLA genes, ranging from zero to six, on the unshared haplotype. Potential HLA-hapoidentical donors include biological parents, biological children, full or half siblings.

 

Only a related donor can be deemed to be HLA-haploidentical to a recipient because the Sanger-based sequencing methods widely used for high resolution HLA typing cannot determine whether nucleotides at polymorphic sites are located on the same (cis-position) or on different (trans-position) chromosome, and so alleles are assigned to haplotypes only with an assumption of relatedness.

 

When available a matched sibling is preferred over other donor sources due to clinical outcomes following transplant (e.g., less graft versus-host disease [GVHD] and the speed and cost-effectiveness of the search). When a matched sibling donor is not available, the transplant center usually proceeds with an unrelated donor search. Alternative donor sources i.e., HLA-haploidentical may be considered if there is an urgent need to proceed to transplantation or if the preliminary search indicates a low likelihood of finding an eight of eight allele-matched unrelated donor.

 

Haploidentical allogeneic stem cell transplant is a treatment option that is not offered in all transplant centers.

 

Tandem Transplantation

Tandem transplantation refers to a planned infusion (transplant) of previously harvested hematopoietic stem cells with a repeat hematopoietic stem cell infusion (transplant) that is performed within 6 months of the initial transplant. This is distinguished from a repeat transplantation requested or performed more than 6 months after the first transplant and is used as salvage therapy after failure of initial transplantation or relapsed disease.

 

Stages of Transplantation

Hematopoietic stem cell transplantation (bone marrow transplantation) involves the mobilization, harvesting, and transplantation of hematopoietic stem cells that have been collected from bone marrow or peripheral blood.

 

Mobilization

Preparing for a hematopoietic stem cell transplantation first requires stem cell mobilization. Mobilization makes harvesting more efficient and occurs when the accumulation of stem cells has reached its highest level.

 

Prior to harvesting, autologous blood stem cell donors are occasionally given a course of chemotherapy to destroy some of the malignant tumors in their body. This low-dose chemotherapy reduces the risk for tumor contamination and facilitates the filtering of stem cells for collection. Autologous donors may also receive injections of a colony-stimulating factor. Colony-stimulating factors are groups of proteins that cause blood cells to grow and mature, which facilitates mobilization. In some cases, a combination of chemotherapy and colony-stimulating factor is used.

 

In allogeneic donors, mobilization is accomplished through a series of subcutaneous injections of colony-stimulating factors (i.e., granulocyte colony-stimulating factor [G-CSF] or granulocyte-macrophage colony-stimulating factor [GM-CSF]). Typically, the colony-stimulating factor is administered for 4 to 5 days, followed by apheresis, which generally occurs over the next day or two. Apheresis, also called pheresis, is a procedure in which blood is collected, the stem cells are removed, and the remaining blood is given back to the donor. The stem cells are frozen until they are given to the recipient.

 

Harvesting

After mobilization, hematopoietic stem cells can be harvested from bone marrow and/or peripheral blood.

 

Harvesting from bone marrow involves inserting a hollow needle into the pelvic (hip) bone or, in rare cases, the sternum (breastbone), under general or regional anesthesia. The procedure takes about 1 hour. The cells are harvested prior to myeloablative therapy. The harvested cells can sometimes be treated before transplantation in a process known as purging. This process reduces the number of cancer cells, thereby minimizing the likelihood that cancer will recur. In most instances, the harvested marrow is filtered and given to the recipient on the same or next day. If the transplantation cannot occur within that timeframe, the marrow can be combined with a preservative solution and frozen until needed. Known as cryoablation, this technique can preserve the harvested marrow for years. When the recipient is ready to receive the marrow, it is thawed and transfused in a procedure which is similar to a blood transfusion. The hematopoietic stem cells are then drawn to the bone marrow, where they start to grow and produce new blood cells.

 

In individuals undergoing peripheral blood stem cell transplantation, stem cells are removed from the bloodstream via apheresis. The purpose of therapeutic apheresis is to remove a component of the blood that contributes to an illness. In apheresis, blood is removed through a large vein in the arm or a central venous catheter (a flexible tube that is placed in a large vein in the neck, chest, or groin area) and sent to sterile equipment, where it is separated into various components, such as red cells, white cells, and plasma. Healthy parts of the blood are then returned to the individual. Apheresis typically takes 4 to 6 hours. For 4 or 5 days before apheresis, the donor may be given a medication to increase the number of stem cells released into the bloodstream.

 

Transplantation

Upon entering the bloodstream, the stem cells travel to the bone marrow, where they begin to produce new white blood cells, red blood cells, and platelets in a process known as engraftment. Engraftment typically occurs within 2 to 4 weeks after transplantation, and is monitored by blood counts. Following the transplant, full recovery of the immune system may take several months for autologous transplantation recipients and as much as 1 to 2 years for individuals receiving allogeneic transplantation. A bone marrow aspiration may also be performed to determine the progress of the new marrow.

 

Practice Guidelines and Position Statements

National Comprehensive Cancer Network (NCCN)

Hematopoietic Cell Transplantation Version 2.2021

The purpose of this NCCN Guideline for Hematopoietic Cell Transplantation (HCT) focus on the management of adult patients with malignant diseases. The initial version of the Guidelines addresses pre-transplant recipient evaluation as well as the management of acute and chronic graft-versus-host disease (GVHD). Additional Topics will be addressed in subsequent versions.

 

Hematopoietic cell transplantation (HCT) involves the infusion of hematopoietic progenitor cells into patients with malignant or nonmalignant hematologic disorders with the goal or re-establishing normal hematopoietic and immune function. HCT is a potentially curative treatment option for patients with certain types of hematologic malignancies and is also used to support patients undergoing high-dose chemotherapy for the treatment of certain solid organs. HCT is classified as autologous or allogeneic based on the origin of hematopoietic cells. An autologous HCT uses the patient’s own cells while an allogeneic HCT uses hematopoietic cells from a human leukocyte antigen (HLA) compatible donor. Prior to HCT, most patients receive chemotherapy, serotherapy, and/or radiation for pre-transplant conditioning (preparative regimen) Allogeneic HCT, preparative regimens are administered in order to eradicate malignant cells in the bone marrow (if using myeloablative regimen) and induce immunosuppression so that engraftment of healthy donor cells occurs. In autologous HCT, high-dose myeloablative regimes are used to treat the malignancy. This is followed by rescue infusion of the patient’s own cells, which are harvested below high-dose therapy, in order to restore hematopoiesis and reconstitute the immune system. 

 

Pre-Transplant Recipient Evaluation

The pre-transplant recipient evaluation generates data to estimate risks of post-transplant complications including non-relapse mortality (NRM). It also generates information that may inform the choice of the preparative regimen (drug choice, dose intensity, and immunosuppressive regimen).

 

Clinical Assessment:

  • Confirm histologic diagnosis
  • History and physical exam, including evaluation of performance status (ECOG or KPS) and body mass index (BMI)
  • Assess disease status (including cytogenetic/molecular testing for risk stratification and assessment of minimal residual disease, if applicable)
  • Bone marrow aspiration and biopsy to confirm remission status (as indicated by underlying disease: pathology, flow cytometry, cytogenetics, molecular studies) and rule out other diseases
  • Pulmonary function tests (PFT) including spirometry, lung volumes, and diffusing capacity (DLCO)
  • ECG (with QTc interval assessment)
  • Measure left ventricular ejection fraction (LVEF) with echocardiogram (if valvular assessment required) or MUGA scan
  • Pyschosocial evaluation
  • HCT Comorbidity Index (HCT-CI) score (in particular for allogeneic HCT)

 

Imaging:

  • Disease – specific restaging studies (See NCCN Guidelines for Treatment of Cancer by Site)
  • Chest x-ray (if no other chest imaging done)

 

Laboratory Tests:

  • CBC with differential
  • ABO/Rh typing
  • Chemistry profile (including blood glucose, creatinine/GFR, electrolytes, and liver function tests [transaminases and bilirubin)]
  • Prothrombin time (PT)/partial thromboplastin time (PTT)
  • Urinalysis
  • Infectious disease testing: CMV, HSV, VZV, HBV, HCV, and HIV serology
  • HLA typing per FACT (Foundation for the Accreditation of Cellular Therapy) guidelines

 

Pre-Transplantation Recipient Evaluation – Additional Evaluation as Clinically Indicated

Additional Clinical Assessment

  • Lumbar puncture for cerebrospinal fluid (CSF) analysis
  • Discuss fertility preservation banking
  • Pregnancy test for women of child-bearing potential
  • Physical therapy evaluation (strength, flexibility, function)
  • Nutritional evaluation
  • Consider geriatric assessment for select patients (category 2B)
  • Dental evaluation (in particular for allogeneic HCT)

 

Additional Imaging

  • CT (chest and/or sinuses)

 

Additional Laboratory Tests

  • Epstein – Barr virus (EBV0 testing or other infectious disease testing (if high risk) (e.g., tuberculosis [TB]), toxoplasma, strongyloides, human T-cell lymphotropic virus (HTLV) types I and II (for allogeneic HCT)
  • Human leukocyte antigen (HLA) antibody assessment if using HLA-mismatched donor (allogeneic HCT)
  • 24- hour urine creating clearance (for borderline renal dysfunction or low muscle mass)
  • Urine toxicology screen if history of illicit drug use
  • Thyroid stimulating hormone (TSH) level
  • Iron profile (including ferritin level)
  • Blood lipid panel
  • Vitamin D level

 

Summary

The NCCN Guidelines for Hematopoietic Cell Transplantation provide an evidence and consensus- based approach for the pre-transplant evaluation of potential HCT recipients and the management of GVHD. HCT is a potentially curative treatment option or patients with certain types of malignancies. However, disease relapse and transplant-related complications often limit the long-term survival of HCT recipients. To determine whether HCT is a potential treatment option, the pre-transplant recipient evaluation should be performed in each patient to estimate the risk of relapse, NRM and overall mortality. Determining the HCT-CI score is essential to establish candidacy for HCT and has been validated to predict the risk of NRM and estimated survival after allogeneic transplant. The leading cause of NRM in allogeneic HCT recipients is the development of GVHD. Mild manifestations of GVHD limited to single organ are often managed with close observation, topical treatment, or by slowing the tapering of immunosuppressive agents. More severe manifestations of multi-organ involvement typically require systemic corticosteroid treatment (with or without secondary systemic agents). Despite these treatments, approximately 40% to 50% of patients with GVHD develop steroid-refractory disease. Steroid-refractory GVHD is associated with high mortality and no standard effective therapy has yet been identified. Therefore, the NCCN Panel strongly encourages patients with steroid-refractory acute or chronic GVHD to participate in well-designed clinical trials to enable further advancements for the management of these diseases and ultimately increase the long-term survival of HCT recipients.

 

Indications for hematopoietic cell transplantation (HCT) vary by disease. Indications for HCT are in the following NCCN Guidelines:

 

 

American Society of Blood and Marrow Transplantation

In 2019, the American Society of Blood and Marrow Transplantation issued a position statement on autologous hematopoietic cell transplantation for treatment-refractoryrRelapsing multiple sclerosis

 

Position Statement:

The ASBMT Task Force recommends revising the recommended indication for AHCT in MS to “standard of care, clinical evidence available”, for patients with relapsing forms of MS (RRMS or progressive MS with superimposed activity) who have prognostic factors that indicate a high risk of future disability, including ongoing clinical relapse or MRI lesion activity despite treatment with available DMTs, especially if disease activity continues despite treatment with high-efficacy DMTs and/or worsening disability. This revision of our previous “developmental” guideline is based on the evidence from retrospective studies, clinical trials, and meta-analyses/systematic reviews summarized above.

 

Conclusion:

In summary, the ASBMT endorses AHCT as a “standard of care, clinical evidence available” for treatment-refractory relapsing MS. This document is not a treatment guideline, but is intended to provide guidance to physicians, patients, payers, policy makers, and other stakeholders on coverage decisions and the appropriate use of this procedure for MS.

 

In 2015, the American Society of Blood and Marrow Transplantation issued a guideline indications for autologous and allogeneic hematopoietic stem cell transplantation. This guideline was developed in a response to a need identified by patients, providers, payers and policymakers, established a Task Force to provide guidance on indications for HCT, that is, which indications may be considered as routine care versus indications where evidence is emerging or insufficient.

 

Definitions for Classifying Indications
Standard of Care (S):
This category includes indications that are well defined and generally supported by evidence in the form of high quality clinical trials and/or observational studies.
Standard of Care, Clinical Evidence Available (C):
This category includes indications for which large clinical trials and observational studies are not available. However, HCT has been shown to be an effective therapy with acceptable risk or morbidity or mortality in sufficiently large single or multicenter cohort studies. HCT can be considered as a treatment option for individual patients after careful evaluation of risk and benefits. As more evidence becomes available, some indications may be reclassified as “S”.
Standard of Care, Rare Indication (R):
Indications included in this category are rare disease for which clinical trials and observational studies with sufficient number of patients are not currently feasible because of their very low incidence. However, single or multicenter or registry studies in relatively small cohorts of patients have shown HCT to be effective treatment with acceptable risks of morbidity and mortality. For patients with diseases in this category, HCT can be considered as a treatment option for individual patients after careful evaluation of risks and benefits.
Developmental (D):
Developmental indications include diseases where preclinical and/or early phase clinical studies show HCT to be a promising treatment option. HCT is best pursued for these indications as part of a clinical trial. As more evidence becomes available, some indications may be reclassified as “C” or “S”.
Not Generally Recommended (N):
Transplantation is not currently recommended for these indications where evidence and clinical practice do not support the routine use of HCT. This recommendation does not preclude investigation of HCT as a potential treatment, and transplantation may be pursued for these indications within the context of a clinical trial.

 

Indications for HCT in Pediatric Patients (Generally Age < 18 years)
Indication and Disease Status Allogeneic HCT Autologous HCT
Acute myeloid leukemia
CR1 low risk Not Generally Recommended Not Generally Recommended
CR1 intermediate risk Standard of Care, Clinical Evidence Available Not Generally Recommended
CR1 high risk Standard of Care Not Generally Recommended
CR2+ Standard of Care Not Generally Recommended
Not in remission Standard of Care, Clinical Evidence Available Not Generally Recommended
Acute promyelocytic leukemia, relapse Standard of Care, Rare Indication Standard of Care, Rare Indication
Acute lymphoblastic leukemia
CR1 standard risk Not Generally Recommended Not Generally Recommended
CR1 high risk Standard of Care Not Generally Recommended
CR2 Standard of Care Not Generally Recommended
CR3+ Standard of Care, Clinical Evidence Available Not Generally Recommended
Not in remission Standard of Care, Clinical Evidence Available Not Generally Recommended
Chronic myeloid leukemia
Chronic phase Standard of Care, Clinical Evidence Available Not Generally Recommended
Accelerated phase Standard of Care, Clinical Evidence Available Not Generally Recommended
Blast phase Standard of Care, Clinical Evidence Available Not Generally Recommended
Myelodysplastic syndromes
Low risk Standard of Care, Clinical Evidence Available Not Generally Recommended
High risk Standard of Care Not Generally Recommended
Juvenile myelomonocytic leukemia Standard of Care Not Generally Recommended
Therapy related Standard of Care Not Generally Recommended
T-cell non-Hodgkin's Lymphoma
CR1 standard risk Not Generally Recommended Not Generally Recommended
CR1 high risk S Not Generally Recommended
CR2 Standard of Care Not Generally Recommended
CR3+ Standard of Care, Clinical Evidence Available Not Generally Recommended
Not in remission Standard of Care, Clinical Evidence Available Not Generally Recommended
Lymphoblastic B cell non-Hodgkin lymphoma (non-Burkitt)
CR1 standard risk Not Generally Recommended Not Generally Recommended
CR1 high risk Standard of Care Not Generally Recommended
CR2 Standard of Care Not Generally Recommended
CR3+ Standard of Care, Clinical Evidence Available Not Generally Recommended
Not in remission Standard of Care, Clinical Evidence Available Not Generally Recommended
Burkitt's lymphoma
First remission Standard of Care, Clinical Evidence Available Standard of Care, Clinical Evidence Available
First or greater relapse, sensitive Standard of Care, Clinical Evidence Available Standard of Care, Clinical Evidence Available
First or greater relapse resistant Standard of Care, Clinical Evidence Available Not Generally Recommended
Hodgkin lymphoma
CR1 Not Generally Recommended Not Generally Recommended
Primary refractory, sensitive Standard of Care, Clinical Evidence Available Standard of Care, Clinical Evidence Available
Primary refractory, resistant Standard of Care, Clinical Evidence Available Not Generally Recommended
First relapse, sensitive Standard of Care, Clinical Evidence Available Standard of Care, Clinical Evidence Available
First relapse, resistant Standard of Care, Clinical Evidence Available N
Second or greater relapse Standard of Care, Clinical Evidence Available Standard of Care, Clinical Evidence Available
Anaplastic large cell lymphoma
CR1 Not Generally Recommended Not Generally Recommended
Primary refractory, sensitive Standard of Care, Clinical Evidence Available Standard of Care, Clinical Evidence Available
Primary refractory, resistant Standard of Care, Clinical Evidence Available Not Generally Recommended
First relapse, sensitive Standard of Care, Clinical Evidence Available Standard of Care, Clinical Evidence Available
First relapse, resistant Standard of Care, Clinical Evidence Available Not Generally Recommended
Second or greater relapse Standard of Care, Clinical Evidence Available Standard of Care, Clinical Evidence Available
Solid tumors
Germ cell tumor, relapse Developmental Standard of Care, Clinical Evidence Available
Germ cell tumor, refractory Developmental Standard of Care, Clinical Evidence Available
Ewing's sarcoma, high risk or relapse Developmental Standard of Care
Soft tissue sarcoma, high risk or relapse Developmental Developmental
Neuroblastoma, high risk or relapse Developmental Standard of Care
Wilm's tumor, relapse Not Generally Recommended Standard of Care, Clinical Evidence Available
Osteosarcoma, high risk Not Generally Recommended Standard of Care, Clinical Evidence Available
Medulloblastoma, high risk Not Generally Recommended Standard of Care, Clinical Evidence Available
Other malignant brain tumors Not Generally Recommended Standard of Care, Clinical Evidence Available
Nonmalignant diseases
Severe aplastic anemia, new diagnosis Standard of Care Not Generally Recommended
Severe aplastic anemia, relapse/refractory Standard of Care Not Generally Recommended
Fanconi's anemia Standard of Care, Rare Indication Not Generally Recommended
Dyskeratosis congenital Standard of Care, Rare Indication Not Generally Recommended
Blackfan-Diamond anemia Standard of Care, Rare Indication Not Generally Recommended
Sickel cell disease Standard of Care, Clinical Evidence Available Not Generally Recommended
Thalassemia Standard of Care Not Generally Recommended
Congenital amegakaryocytic thromobocytopenia Standard of Care, Rare Indication Not Generally Recommended
Severe combined immunodeficiency Standard of Care, Rare Indication Not Generally Recommended
T-cell immunodeficiency, SCID variants Standard of Care, Rare Indication Not Generally Recommended
Wiskott-Aldrich syndrome Standard of Care, Rare Indication Not Generally Recommended
Hemophagocytic disorders Standard of Care, Rare Indication Not Generally Recommended
Lymphoproliferative disorders Standard of Care, Rare Indication Not Generally Recommended
Severe congenital neutropenia Standard of Care, Rare Indication Not Generally Recommended
Chronic granulomatous disease Standard of Care, Rare Indication Not Generally Recommended
Other phagocytic cell disorders Standard of Care, Rare Indication Not Generally Recommended
IPEX syndrome Standard of Care, Rare Indication Not Generally Recommended
Juvenile rheumatoid arthritis Developmental Standard of Care, Rare Indication
Systemic sclerosis Developmental Standard of Care, Rare Indication
Other autoimmune and immune dysregulation disorders Standard of Care, Rare Indication Not Generally Recommended
Mucopolysaccharoidoses (MPS-I and MPS-VI) Standard of Care, Rare Indication Not Generally Recommended
Other metabolic disorders Standard of Care, Rare Indication Not Generally Recommended
Osteoporosis Standard of Care, Rare Indication Not Generally Recommended
Globoid cell leukodystrophy (Krabbe) Standard of Care, Rare Indication Not Generally Recommended
Metachromatic leukodystrophy Standard of Care, Rare Indication Not Generally Recommended
Cerebal X-linked adrenoleukodystrophy Standard of Care, Rare Indication Not Generally Recommended

 

Indications for HCT in Adults (Generally Age ≥ 18 years)
Indication and Disease Status Allogeneic HCT Autologous HCT
Acute myeloid leukemia
CR1 low risk Not Generally Recommended Standard of Care, Clinical Evidence Available
CR1 intermediate risk Standard of Care Standard of Care, Clinical Evidence Available
CR1 high risk Standard of Care Standard of Care, Clinical Evidence Available
CR2 Standard of Care Standard of Care, Clinical Evidence Available
CR3+ Standard of Care, Clinical Evidence Available Standard of Care, Clinical Evidence Available
Not in remission Standard of Care, Clinical Evidence Available Not Generally Recommended
Acute promyelocytic leukemia
CR1 Standard of Care, Clinical Evidence Available Standard of Care
CR2, molecular remission Standard of Care Not Generally Recommended
CR2, not in molecular remission Standard of Care, Clinical Evidence Available Not Generally Recommended
CR3+ Standard of Care, Clinical Evidence Available Not Generally Recommended
Not in remission Standard of Care, Clinical Evidence Available Not Generally Recommended
Relapse after autologous transplant Standard of Care, Clinical Evidence Available Not Generally Recommended
Acute lymphoblastic leukemia
CR1 standard risk Standard of Care Standard of Care, Clinical Evidence Available
CR1 high risk Standard of Care Not Generally Recommended
CR2 Standard of Care Standard of Care, Clinical Evidence Available
CR3+ Standard of Care, Clinical Evidence Available Not Generally Recommended
Not in remission Standard of Care, Clinical Evidence Available Not Generally Recommended
Chronic myeloid leukemia
Chronic phase I, TKI intolerant Standard of Care, Clinical Evidence Available Not Generally Recommended
Chronic phase I, TKI refractory Standard of Care, Clinical Evidence Available Not Generally Recommended
Chronic phase 2+ Standard of Care Not Generally Recommended
Accelerated phase Standard of Care Not Generally Recommended
Blast phase Standard of Care Not Generally Recommended
Myelodysplastic syndromes
Low/intermediate Standard of Care, Clinical Evidence Available Not Generally Recommended
Intermediate -2/high risk Standard of Care Not Generally Recommended
Therapy related AML/MDS CR1 Standard of Care Not Generally Recommended
Myelofibrosis and myeloproliferative diseases
Primary low risk Standard of Care, Clinical Evidence Available Not Generally Recommended
Primary intermediate/high risk Standard of Care, Clinical Evidence Available Not Generally Recommended
Secondary Standard of Care, Clinical Evidence Available Not Generally Recommended
Hypereosinophilic syndromes, refractory Standard of Care, Rare Indication Not Generally Recommended
Plasma cell disorders
Myeloma, initial response Developmental Standard of Care
Myeloma, sensitive relapse Standard of Care, Clinical Evidence Available Standard of Care
Myeloma, refractory Standard of Care, Clinical Evidence Available Standard of Care, Clinical Evidence Available
Plasma cell leukemia Standard of Care, Clinical Evidence Available Standard of Care, Clinical Evidence Available
Primary amyloidosis Not Generally Recommended Standard of Care, Clinical Evidence Available
POEMS syndrome Not Generally Recommended Standard of Care, Rare Indication
Relapse after autologous transplant Standard of Care, Clinical Evidence Available Standard of Care, Clinical Evidence Available
Hodgkin lymphoma
CR1 (PET negative) Not Generally Recommended Not Generally Recommended
CR1 (PET positive) Not Generally Recommended Standard of Care, Clinical Evidence Available
Primary refractory, sensitive Standard of Care, Clinical Evidence Available Standard of Care
Primary refractory, resistant Standard of Care, Clinical Evidence Available Not Generally Recommended
First relapse, sensitive Standard of Care Standard of Care
First relapse, resistant Standard of Care, Clinical Evidence Available Not Generally Recommended
Second or greater relapse Standard of Care, Clinical Evidence Available Standard of Care
Relapse after autologous transplant Standard of Care, Clinical Evidence Available Not Generally Recommended
Diffuse large B cell lymphoma
CR1 (PET negative) Not Generally Recommended Not Generally Recommended
CR1 (PET positive) Not Generally Recommended Standard of Care, Clinical Evidence Available
Primary refractory, sensitive Standard of Care, Clinical Evidence Available Standard of Care
Primary refractory, resistant Standard of Care, Clinical Evidence Available Not Generally Recommended
First relapse, sensitive Standard of Care Standard of Care
First relapse, resistant Standard of Care, Clinical Evidence Available Not Generally Recommended
Second or greater relapse Standard of Care, Clinical Evidence Available Standard of Care
Relapse after autologous transplant Standard of Care, Clinical Evidence Available Not Generally Recommended
Follicular lymphoma
CR1 Not Generally Recommended Standard of Care, Clinical Evidence Available
Primary refractory, sensitive Standard of Care Standard of Care
Primary refractory, resistant Standard of Care Not Generally Recommended
First relapse, sensitive Standard of Care Standard of Care
First relapse, resistant Standard of Care Not Generally Recommended
Second or greater relapse Standard of Care Standard of Care
Transformation to high grade lymphoma Standard of Care, Clinical Evidence Available Standard of Care
Relapse after autologous transplant Standard of Care, Clinical Evidence Available Not Generally Recommended
Mantle cell lymphoma
CR1/PR1 Standard of Care, Clinical Evidence Available Standard of Care
Primary refractory, sensitive Standard of Care Standard of Care
Primary refractory, resistant Standard of Care, Clinical Evidence Available Not Generally Recommended
First relapse, sensitive Standard of Care Standard of Care
First relapse, resistant Standard of Care, Clinical Evidence Available Not Generally Recommended
Second or greater relapse Standard of Care, Clinical Evidence Available Standard of Care
Relapse after autologous transplant Standard of Care, Clinical Evidence Available Not Generally Recommended
T-cell lymphoma
CR1 Standard of Care, Clinical Evidence Available Standard of Care, Clinical Evidence Available
Primary refractory, sensitive Standard of Care, Clinical Evidence Available Standard of Care
Primary refractory, resistant Standard of Care, Clinical Evidence Available Not Generally Recommended
First relapse, sensitive Standard of Care, Clinical Evidence Available Standard of Care
First relapse, resistant Standard of Care, Clinical Evidence Available Not Generally Recommended
Second or greater relapse Standard of Care, Clinical Evidence Available Standard of Care, Clinical Evidence Available
Relapse after autologous transplant Standard of Care, Clinical Evidence Available Not Generally Recommended
Lymphoplasmacytic lymphoma
CR1 Not Generally Recommended Not Generally Recommended
Primary refractory, sensitive Not Generally Recommended Standard of Care, Clinical Evidence Available
Primary refractory, resistant Standard of Care, Rare Indication Not Generally Recommended
First relapse, sensitive Standard of Care, Rare Indication Standard of Care, Clinical Evidence Available
First relapse, resistant Standard of Care, Rare Indication Not Generally Recommended
Relapse after autologous transplant Standard of Care, Clinical Evidence Available Not Generally Recommended
Burkitt's lymphoma
First remission Standard of Care, Clinical Evidence Available Standard of Care, Clinical Evidence Available
First or greater relapse Standard of Care, Clinical Evidence Available Standard of Care, Clinical Evidence Available
First or greater relapse, resistant Standard of Care, Clinical Evidence Available Not Generally Recommended
Relapse after autologous transplant Standard of Care, Clinical Evidence Available Not Generally Recommended
Cutaneous T-cell lymphoma
Relapse Standard of Care, Clinical Evidence Available Standard of Care, Clinical Evidence Available
Relapse after autologous transplant Standard of Care, Clinical Evidence Available Standard of Care, Clinical Evidence Available
Plasmablastic lymphoma
CR1 Standard of Care, Rare Indication Standard of Care, Rare Indication
Relapse Standard of Care, Rare Indication Standard of Care, Rare Indication
Chronic lymphocytic leukemia
High risk, first or greater remission Standard of Care, Clinical Evidence Available Not Generally Recommended
T-cell prolymphocytic leukemia Standard of Care, Rare Indication Standard of Care, Rare Indication
B cell, prolymphocytic leukemia Standard of Care, Rare Indication Standard of Care, Rare Indication
Transformation to high grade lymphoma Standard of Care, Clinical Evidence Available Standard of Care, Clinical Evidence Available
Solid Tumors
Germ cell tumor, relapse Not Generally Recommended Standard of Care, Clinical Evidence Available
Germ cell tumor, refractory Not Generally Recommended Standard of Care, Clinical Evidence Available
Ewing's sarcoma, high risk Not Generally Recommended Standard of Care, Clinical Evidence Available
Breast cancer, adjuvant high risk Not Generally Recommended Developmental
Breast cancer, metastatic Developmental Developmental
Renal cancer, metastatic Developmental Not Generally Recommended
Nonmalignant diseases
Severe aplastic anemia, new diagnosis Standard of Care Not Generally Recommended
Severe aplastic anemia, relapse/refractory Standard of Care Not Generally Recommended
Fanconi's anemia Standard of Care, Rare Indication Not Generally Recommended
Dyskeratosis congenital Standard of Care, Rare Indication Not Generally Recommended
Sickel cell disease Standard of Care, Clinical Evidence Available Not Generally Recommended
Thalassemia Developmental Not Generally Recommended
Hemophagocytic syndromes, refractory Standard of Care, Rare Indication Not Generally Recommended
Mast cell diseases Standard of Care, Rare Indication Not Generally Recommended
Common variable immunodeficiency Standard of Care, Rare Indication Not Generally Recommended
Wiskott-Aldrich syndrome Standard of Care, Rare Indication Not Generally Recommended
Chronic granulomatous disease Standard of Care, Rare Indication Not Generally Recommended
Multiple sclerosis Not Generally Recommended Developmental
System sclerosis Not Generally Recommended Developmental
Rheumatoid arthritis Not Generally Recommended Developmental
Systemic lupus erythematosus Not Generally Recommended Developmental
Chron's disease Not Generally Recommended Developmental
Polymyositis-dermatomyositis Not Generally Recommended Developmental

 

In 2008, the American Society for Blood and Marrow Transplantation issued a position statement regarding collection and preservation of cord blood for personal use. The recommendations include the following:

 

  • Expectant parents are encouraged to donate their newborn’s UCB (umbilical cord blood) for public banking when that option is available. Donation makes the CB (cord blood), which is rich in HSCs (hematopoietic stem cells), available for life-saving treatments when there is a suitable match with a patient.
  • Private storage of CB for future use by a newborn is not routinely recommended. The likelihood of the stored blood being used for HSCT (hematopoietic stem cell transplantation) is very small, probably as low as 0.04% to 0.001% in the first 20 years of life. If later in life a transplant is required, there likely will be superior sources of suitable stem cells than the child’s own CB.
  • Family member banking (collecting and storing CB for a family member) may be recommended for a newborn who has a sibling with a disease that can be successfully treated with HSCT. Family member banking on behalf of a parent with a disease that may be treated successfully with allogeneic transplant is only recommended when there are shared HLA-antigens between the parents.
  • Accurate and complete information about UCB collection and banking should be available to expectant parents so that they can make informed decisions. Parents who choose to store CB for personal use should carefully review their contract and financial responsibilities, and inquire about quality standards, median nucleated cell dose of stored units and accreditation of the CB bank.

 

The committee acknowledges the potential for an expansion of indications for CB in the future, and these recommendations will be reviewed periodically so that they remain consistent with current medical knowledge.

 

American College of Rheumatology

In 2012, the American College of Rheumatology issued a guideline for screening, treatment and management of Lupus Nephritis which does not discuss hematopoietic stem cell transplantation as a therapeutic option.

 

In 2013, the American College of Rheumatology updated the 2011 guideline recommendations for the treatment of juvenile idiopathic arthritis which does not discuss hematopoietic stem cell transplantation as a therapeutic option.

 

In 2015, the American College of Rheumatology issued a guideline for the treatment of rheumatoid arthritis which does not discuss hematopoietic stem cell transplantation as a therapeutic option.

 

The American College of Obstetricians and Gynecologists

In 2015, the American College of Obstetricians and Gynecologists published a committee opinion (number 648) on umbilical cord blood banking. The recommendations regarding umbilical cord blood banking include the following:

  • Umbilical cord blood collection should not compromise obstetric or neonatal care or later routine practice for the timing of umbilical cord clamping.
  • In a patient requests information on umbilical cord blood banking, balanced and accurate information regarding the advantages and disadvantages of public and private umbilical cord blood banking should be provided.
  • The current indications for cord blood transplant are limited to select genetic, hematologic and malignant disorders.
  • Patients should be aware that in certain instances, use of one’s own stem cells is contraindicated. Most conditions potentially treated by a patient’s own umbilical cord blood already exist in his or her own cells and, therefore, the stored blood cannot be used to treat the same individual.
  • Counseling should include disclosure that the chance a child or family member develops a condition that could be treated with an autologous transfusion of umbilical blood is rare.
  • The routine storage of umbilical cord blood as “biologic insurance” against future disease is not recommended.
  • Directed cord blood banking is available through private and public umbilical cord blood banks for any pregnant patients who has a family member with a disease potentially treated by hematopoietic stem cell transplant.
  • Some states have passed legislation requiring physicians to inform their patients about umbilical cord blood banking options. Obstetricians-gynecologists and other obstetric care providers should consult their state medical associations for more information regarding state laws.
  • As a variety of circumstances may arise during the process of labor and delivery that may preclude collection, it is important to obtain well documented informed consent that various medical circumstances of the mother or the neonate may prevent umbilical cord blood collection.
  • Physicians or other professions who recruit pregnant women and their families for profit umbilical cord blood banking should disclose any financial interest or other potential conflicts of interest.

 

Prior Approval:

Prior approval is required.

 

Policy:

Coverage for hematopoietic stem cell transplantation is provided when both the type of transplant and the individual’s condition meet the medical necessity criteria outlined below.

 

For those indications in which the type of transplant and the individual’s condition does not meet fthe criteria outlined below the available evidence is insufficient and does not demonstrate improved net health outcomes and would be considered investigational.

 

Colony-stimulating Factors and Stem Cell Mobilizers

 

FDA-approved granulocyte colony-stimulating factor (G-CSF) agents and hematopoietic stem cell mobilizers are considered medically necessary when used to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent transplantation in individuals who meet medically necessary criteria for hematopoietic stem cell transplantation.

 

FDA-approved colony-stimulating factors (G-CSF) used to mobilize peripheral blood progenitor cells for hematopoietic stem cell transplantation include:

  • Granix® (tbo-filgrastim)
  • Leukine® (sargramostim)
  • Neupogen® (filgrastim)
  • Nivestym® (filgrastim-aafi)
  • Zarxio® (filgrastim-sndz)
  • Neulasta® (pegfilgrastim)
  • Fulphila® (pegfilgrastim-jmdp)
  • Udenyca® (pegfilgrastim-cbqv)
  • Ziextenzo® (pegfilgrastim-bmez)

 

For the preferred drug strategy policy on Granix® (tbo-filgrastim), Leukine® (sargramostim), and Neupogen® (filgrastim), refer to the Colony Stimulating Factor drug policy 05.02.41.

 

FDA-approved hematopoietic stem cell mobilizers used to mobilize peripheral blood progenitor cells for hematopoietic stem cell transplantation include:

  • Mozobil® (plerixafor)

 

Hematopoietic Stem Cell Transplantation: Non-cancer Disorders

Autoimmune Disease

Indication Hematopoietic Stem Cell Transplantation Coverage Criteria
Note: When considered medically necessary allogeneic transplantations must be from an appropriately HLA matched donor (related, unrelated matched, cord blood or haploidentical)
Multiple Sclerosis
Autologous Hematopoietic Stem Cell Transplantation
Autologous hematopoietic stem cell transplantation is considered medically necessary when ALL of the following criteria are met:
  • Adult patient age 18 to 55 years; AND
  • Relapsing-remitting* (RR) or secondary progressive* (SP) multiple sclerosis (MS); AND
  • Expanded Disability Status Scale (EDSS) score between 2.0 and 6.0; AND
  • Failed treatment with one or more disease-modifying therapy(ies) (DMT); AND
  • Evidence of any of the following while being treated with DMT:
    • Two or more clinical relapses* at separate times but within the previous 12 months
    • One relapse* and a magnetic resonance imaging (MRI) with enhancing lesion(s) with or without gadolinium at a separate time than the relapse but within the previous 12 months (Note: The use of gadolinium [contrast] in a patient already diagnosed with MS is up to the discretion of the neurologist and/or radiologist)
*Definitions:
  • Relapsing-remitting Multiple Sclerosis (RRMS): A multiple sclerosis course characterized by relapses with stable disability between episodes.
  • Secondary Progressive Multiple Sclerosis (SPMS): A progressive course (steadily increasing objectively documented neurological disability independent of relapses) following an initial relapsing-remitting course.
  • Relapse: a monophasic clinical episode with patient-reported symptoms and objective findings typical of multiple sclerosis, reflecting a focal or multifocal inflammatory demyelinating event in the central nervous system (CNS), developing acutely or subacutely, with a duration of at least 24 hours, with or without recovery, and in the absence of fever or infection.

 

Expanded Disability Status Scale (EDSS)
The Expanded Disability Status Scale (EDSS) is a method of quantifying disability in multiple sclerosis and monitoring changes in the level of disability over time.
The EDSS scale ranges from 0 to 10 in 0.5 unit increments that represent higher levels of disability. Scoring is based on an examination by a neurologist.
EDSS steps 1.0 to 4.5 refer to people with MS who are able to walk without any aid and is based on measures of impairment in eight functional systems (FS):
  • pyramidal – muscle weakness or difficulty moving limbs
  • cerebellar – ataxia, loss of balance, coordination or tremor
  • brainstem – problems with speech, swallowing and nystagmus
  • sensory – numbness or loss of sensations
  • bowel and bladder function
  • visual function - problems with sight
  • cerebral functions - problems with thinking and memory
  • other

A functional system (FS) represents a network of neurons in the brain with responsibility for particular tasks. Each FS is scored on a scale of 0 (no disability) to 5 or 6 (more severe disability).

 

EDSS steps 5.0 to 9.5 are defined by the impairment to walking and usual equivalents in Functional Sytem (FS) scores provided.

 

Autologous hematopoietic stem cell transplantation is considered investigational for the treatment of multiple sclerosis not meeting the above criteria and for all other indications. The evidence is insufficient in demonstrating improved net health outcomes.

 

Allogeneic Hematopoietic Stem Cell Transplantation

Allogeneic hematopoietic stem cell transplantation is considered investigational for the treatment of multiple sclerosis for all indications. The evidence is insufficient in demonstrating improved net health outcomes.

 

Other Autoimmune Diseases
Autologous Hematopoietic Stem Cell Transplantation or Allogeneic Hematopoietic Stem Cell Transplantation

Autologous or allogeneic hematopoietic stem cell transplantation is considered investigational as a treatment of autoimmune diseases, including, but not limited to the following:

  • Systemic lupus erythematosus
  • Juvenile idiopathic arthritis
  • Rheumatoid arthritis
  • Chronic inflammatory demyelinating polyneuropathy
  • Type 1 diabetes

 

Most patients with autoimmune disorders respond to conventional drug therapies, however, conventional drug therapies are not curative and a proportion of patients suffer from autoimmune diseases that range from severe to the recalcitrant to the rapidly progressive. It is in this group of patients with severe autoimmune disease that alternative therapies have been sought, including hematopoietic stem cell transplantation. The guideline from the American Society for Blood and Marrow Transplantation regarding indications for autologous and allogeneic hematopoietic stem cell transplantation (HSCT) states the following regarding rheumatoid arthritis and systemic lupus erythematous: allogeneic HSCT is not currently recommended for these indications and clinical practice does not support the routine use of HSCT, transplantation for these indications may be pursued within the context of a clinical trial; autologous HSCT developmental indications where pre-clinical and/or early phase clinical studies show HSCT to be a promising treatment option, but HSCT is best pursued for these indications as part of a clinical trial. Additional controlled trials (with appropriate comparator therapies) that report on clinical outcomes are needed to demonstrate efficacy. The evidence is insufficient to determine the safety and/or efficacy of autologous or allogeneic hematopoietic stem cell transplantation for the treatment of these autoimmune diseases.

 

Systemic Sclerosis/Scleroderma
Autologous Hematopoietic Stem Cell Transplantation

Autologous hematopoietic stem cell transplantation is considered medically necessary as a treatment for systemic sclerosis/scleroderma if ALL of the following criteria are met:

  • Adult patients < 60 years of age; AND
  • Maximum duration of condition of 5 years; AND
  • Modified Rodnan Scale Score > 15; AND
  • Internal organ involvement indicated by the following measurements:
    • Cardiac: abnormal electrocardiogram; OR
    • Pulmonary: diffusing capacity of carbon monoxide (DLCo) < 80% of predicted value; decline of forced vital capacity (FVC) of > 10% in last 12 months; pulmonary fibrosis; ground glass appearance on high resolution chest CT; OR
    • Renal: scleroderma related renal disease; AND
  • The individual does not have the following internal organ involvement indicated by the following measurements:
    • Cardiac: left ventricular ejection fraction < 50%; tricuspid annual plane systolic excursion < 1.8 cm; pulmonary artery systolic pressure >40 mm Hg; mean pulmonary artery pressure > 25 mm Hg
    • Pulmonary: DLCo < 40% of predicted value; FVC < 45% of predicted value
    • Renal: creatinine clearance < 40 ml/minute; AND
  • History of < 6 months treatment with cyclophosphamide.
Notes
  • Autologous HCT should be considered for patients with systemic sclerosis (SSc) only if the condition is rapidly progressing and the prognosis for survival is poor. An important factor influencing the occurrence of treatment-related adverse effects and response to treatment is the level of internal organ involvement. If organ involvement is severe and irreversible, HCT is not recommended.
  • Modified Rodnan Scale Score: This score consists of an evaluation of patient’s skin thickness rated by clinical palpation using a 0–3 scale (0=normal skin; 1=mild thickness; 2=moderate thickness; 3=severe thickness with inability to pinch the skin into a fold) for each of 17 surface anatomic areas of the body: face, anterior chest, abdomen, (right and left separately) fingers, forearms, upper arms, thighs, lower legs, dorsum of hands and feet. These individual values are added and the sum is defined as the total skin score.

 

Autologous hematopoietic stem cell transplantation as a treatment of systemic sclerosis/scleroderma is considered investigational not meeting the above criteria and for all other indications except as indicated above. The evidence is insufficient in demonstrating improved net health outcomes.

 

Allogeneic hematopoietic stem cell transplantation

Allogeneic hematopoietic stem cell transplantation as a treatment of systemic sclerosis/scleroderma is considered investigational. The evidence is insufficient in demonstrating improved net health outcomes.

 

 

Genetic Disorders, Acquired Anemias and Other Bone Marrow Failure Syndromes

Indication Hematopoietic Stem Cell Transplantation Coverage Criteria
Note: When considered medically necessary allogeneic transplantations must be from an appropriately HLA matched donor (related, unrelated matched, cord blood or haploidentical)
Acquired Anemias and Other Bone Marrow Failure Syndromes; and Genetic Disorders
Autologous Hematopoietic Stem Cell Transplantation

Autologous hematopoietic stem cell transplantation is considered investigational for the treatment of genetic diseases and acquired anemias and other bone marrow failure syndromes, including but not limited to the following indications because the evidence is insufficient in demonstrating improved net health outcomes:

  • Sickle cell anemia
  • Homozygous beta-thalassemia (i.e. thalassemia major)
  • Aplastic anemia severe or very severe
  • Faconi anemia
  • Dyskeratosis congenita
  • Shwachman-Diamond Syndrome
  • Diamond-Blackfan anemia
  • Acquired forms of aplastic anemia secondary to drug or toxin exposure
  • Primary immunodeficiencies
  • Lymphocytic immunodeficiencies
  • Phagocytic deficiencies
  • Inherited metabolic disorders
Acquired Anemias and Other Bone Marrow Failure Syndromes
Allogeneic Hematopoietic Stem Cell Transplantation

Allogeneic hematopoietic stem cell transplantation is considered medically necessary for the following indications:

  • Hemoglobinopathies
    • Sickle cell anemia for children or young adults with any of the following:
      • Stroke or central nervous system (CNS) event lasting >24 hours
      • Recurrent acute chest syndrome > 2 inone year
      • Recurrent vaso-occlusive pain > 2 episodes per year or recurrent priapism
      • Impaired neuropsychological function with abnormal brain MRI
      • Stage I or II sickle lung disease
      • Sickle nephropathy
      • Bilateral proliferative retinolpathy with major unilateral or bilateral visual impairment
      • Osteonecrosis of at least one joint
      • Red-cell alloimmunization during long-term transfusion therapy
    • Homozygous beta-thalassemia
  • Bone Marrow Failure Syndromes

    • Aplastic anemia severe or very severe including hereditary forms (e.g. Fanconi anemia, dyskeratosis congenita, Shwachman-Diamond, Diamond-Blackfan) or acquired forms (e.g. secondary to drug or toxin exposure)

Note: Aplastic anemia is divided into three categories:

  • Non-severe aplastic anemia
  • Severe aplastic anemia
  • Very severe aplastic anemia
    • The presence of two of the following criteria defines aplastic anemia: hemoglobin < 10,000 mm3, platelet count < 50,000 mm3, or neutrophil count < 1,500 mm3.
    • Severe aplastic anemia is defined by the presence of hypoplastic bone marrow two of the following: neutrophil count < 500 mm3, platelet count < 20,000 mm3, or reticulocyte count < 20,000 mm3.
    • A neutrophil count < 200 mm3 classifies very severe aplastic anemia.

Allogeneic hematopoietic stem cell transplantation is considered investigational for the treatment of acquired anemias and other bone marrow failure syndromes not meeting the above criteria and for all other indications. The evidence is insufficient in demonstrating improved net health outcomes.

 

Genetic Disorders
Allogeneic Hematopoietic Stem Cell Transplantation
Allogeneic hematopoietic stem cell transplantation is considered medically necessary for any of the following indications to include the indications under Guideline 1 and 2 (except for Hunter, Sanfilippo or Morquio syndromes as indicated below) :
  • Primary Immunodeficiencies
    • Absent or defective T-cell function (e.g. severe combined immunodeficiency (SCID), Wiscott-Aldrich syndrome, X-linked lymphoproliferative syndrome)
    • Absent or defective natural killer function (e.g. Chediak-Higashi syndrome)
    • Absent or defective neutrophil function (e.g. Kostmann syndrome, chronic granulomatous disease, leukocyte adhesion defect)
    • Note: Also see Guideline 1 below
  • Inherited Metabolic Disorders
    • Lysosomal and peroxisomal storage disorders; except Hunter, Sanfilippo and Morquio syndromes (see below statement)
    • Note: Also see Guideline 2 below

Allogeneic hematopoietic stem cell transplant has not been effective in Hunter, Sanfilippo or Morquio syndromes and would be considered investigational.  The evidence is insufficient in demonstrating improved net health outcomes.

 

Guideline 1

The following guideline lists immunodeficiencies that have been successfully treated by allogeneic hematopoietic cell transplantation:

 

Lymphocyte Immunodeficiencies

  • Adenosine deaminase deficiency
  • Artemis deficiency
  • Calcium channel deficiency
  • CD40 ligand deficiency
  • Cernunnos/X-linked lymphoproliferative disease deficiency
  • CHARGE syndrome with immune deficiency
  • Common gamma chain deficiency
  • Deficiencies in CD45, CD3, CD8
  • DiGeorge syndrome
  • DNA ligase IV deficiency syndrome
  • Interleukin-7 receptor alpha deficiency
  • Janus-associated kinase 3 deficiency
  • Major histocompatibility class II deficiency
  • Omenn syndrome
  • Purine nucleoside phosphorylase deficiency
  • Recombinase-activating gene 1/2 deficiency
  • Reticular dysgenesis
  • Winged helix deficiency
  • Wiskott-Aldrich syndrome
  • X-linked lymphoproliferative disease
  • Zeta-chain associated protein-70 deficiency

 

Phagocytic Deficiencies

  • Chédiak-Higashi syndrome
  • Chronic granulomatous disease
  • Griscelli syndrome type 2
  • Hemophagocytic lymphohistiocytosis
  • Interferon-gamma receptor deficiencies
  • Leukocyte adhesion deficiency
  • Severe congenital neutropenias
  • Shwachman-Diamond syndrome

 

Other Immunodeficiencies

  • Autoimmune lymphoproliferative syndrome
  • Cartilage hair hypoplasia
  • CD25 deficiency
  • Hyper IgD and IgE syndromes
  • Immunodeficiency, centromeric instability, and facial dysmorphism syndrome
  • Immunodysregulation polyendocrinopathy enteropathy X-linked syndrome
  • Nuclear factor-κ B (NF-κB) essential modulator deficiency
  • NF-κB inhibitor, NF-κB-α deficiency
  • Nijmegen breakage syndrome

 

Guideline 2
For inherited metabolic disorders, allogeneic hematopoietic cell transplantation (HCT) has been proven effective in some cases of the following:
  • Hurler, Maroteaux-Lamy and Sly syndromes
  • Childhood onset
    • Cerebral X-linked adrenoleukodystrophy
    • Globoid cell leukodystrophy
    • Metachromatic leukodystrophy
    • Alpha-mannosidosis and
    • Aspartylglucosaminuria.
Allogeneic HCT is possibly effective for the following:
  • Fucosidosis
  • Gaucher types 1 and 3
  • Farber lipogranulomatosis
  • Galactosialidosis
  • GM1 gangliosidosis
  • Mucolipidosis II (I-cell disease)
  • Multiple sulfatase deficiency
  • Niemann-Pick disease
  • Nuronal ceroid lipofuscinosis
  • Sialidosis
  • Wolman disease

 

Allogeneic HCT has not been effective in Hunter, Sanfilippo, or Morquio syndromes

 

 

 

Hematopoietic Stem Cell Transplantation: Solid Tumors

Indication Hematopoietic Stem Cell Transplantation Coverage Criteria
Note: When considered medically necessary allogeneic transplantations must be from an appropriately HLA matched donor (related, unrelated matched, cord blood or haploidentical)
Central Nervous System (CNS) Tumors
CNS cancers: pilocytic and infiltrative supratentorial astrocytomas; oligodendrogliomas; anaplastic gliomas and glioblastoma; ependymomas; medulloblastoma; brain metastases; leptomenigeal metastases; non-AIDS related primary CNS lymphoma (PCNSLs); metastatic spinal tumors; meningiomas; and primary spinal cord tumors (NCCN Version 1.2020)

Autologous Hematopoietic Stem Cell Transplantation

Autologous hematopoietic stem cell transplantation is considered medically necessary for the treatment of central nervous system (CNS) tumors for the following indications:

  • Primary CNS Lymphoma
    • Consolidation therapy; or
    • Relapsed or refractory disease
  • As consolidation therapy for embryonal tumors of the central nervous system (e.g., medulloblastoma, medulloepithelioma, supratentorial PNETs [sPNETs; pineoblastoma, cerebral neuroblastoma, ganglioneuroblastoma], ependymoblastoma, atypical teratoid/rhabdoid tumor) that show partial or complete response to induction chemotherapy, or stable disease after induction therapy
  • To treat recurrent embryonal tumors of the central nervous system (e.g., medulloblastoma, medulloepithelioma, supratentorial PNETs [sPNETs; pineoblastoma, cerebral neuroblastoma, ganglioneuroblastoma], ependymoblastoma, atypical teratoid/rhabdoid tumor) that show response to re-induction chemotherapy

*Tandem autologous hematopoietic stem cell transplantation is considered investigational for the treatment of central nervous (CNS) tumors, because the evidence is insufficient in demonstrating improved net health outcomes.

 

*Tandem transplantation refers to a planned infusion (transplant) of previously harvested hematopoietic stem cells with a repeat hematopoietic stem cell infusion (transplant) that is performed within 6 months of the initial transplant.  This is distinguished from a repeat transplantation requested or performed more than 6 months after the first transplant and is used as salvage therapy after failure of initial transplantation or relapsed disease.

 

Autologous hematopoietic stem cell transplantation is considered investigational for the treatment of central nervous (CNS) tumors, including but not limited to the following because the evidence is insufficient in demonstrating improved net health outcomes:

  • Central nervous system (CNS) tumors not meeting the above criteria
  • Astrocytomas
  • Oligodendrogliomas
  • Anaplastic gliomas and glioblastoma
  • Ependymomas
  • Meningiomas
  • Primary spinal cord tumors

 

Allogeneic Hematopoietic Stem Cell Transplantation

Allogeneic hematopoietic stem cell transplantation is considered investigational for the treatment of central nervous system (CNS) tumors for all indications. The evidence is insufficient in demonstrating improved net health outcomes.

 

Notes:

  • Classification of brain tumors is based on both histopathologic characteristics of the tumor and location in the brain. Central nervous system (CNS) embryonal tumors are more common in children and are the most common brain tumor in childhood. CNS embryonal tumors are primarily composed of undifferentiated round cells, with divergent patterns of differentiation.
    • Embryonal tumors of central nervous system (CNS) include medulloblastoma, medulloepithelioma, supratentorial PNETs (sPNETs; pineoblastoma, cerebral neuroblastoma, ganglioneuroblastoma), ependymoblastoma, atypical teratoid/rhabdoid tumor.
    • Ependymoma is a neuroepithelial tumor that arises from the ependymal lining cell of the ventricles and is, therefore, usually continguous with the ventricular system. An ependymoma tumor typically arises intracranially in children, while in adults a spinal cord location is more common. Ependymomas have access to the cerebrospinal fluid and may spread throughout the neuroaxis.
Germ Cell Tumors (Testicular and Ovarian)

Autologous Hematopoietic Stem Cell Transplantation

Testicular Germ Cell Tumors

Single autologous hematopoietic stem cell transplantation is considered medically necessary for the treatment of testicular germ cell tumors following prior chemotherapy as second-line and subsequent therapy for the following indication:

  • An individual with relapsed disease after completion of primary treatment

Single autologous hematopoietic stem cell transplantation is considered medically necessary for the treatment of testicular germ cell tumors as third-line therapy for the following indication: 

  • An individual with relapsed disease treated with conventional dose chemotherapy and no prior autologous stem cell transplant

Autologous hematopoietic stem cell transplant is considered investigational for the treatment of testicular germ cell tumors not meeting the above criteria and for all other indications. The evidence is insufficient in demonstrating improved net health outcomes.

 

*Tandem Autologous Hematopoietic Stem Cell Transplantation*

Tandem autologous hematopoietic stem cell transplant or transplant with sequential high dose chemotherapy may be considered medically necessary for the treatment of testicular tumors either as salvage therapy or with platinum-refractory disease.

 

All other uses of tandem autologous hematopoietic stem cell transplantation are considered investigational except as indicated above. The evidence is insufficient in demonstrating improved net health outcomes.

 

*Tandem transplantation refers to a planned infusion (transplant) of previously harvested hematopoietic stem cells with a repeat hematopoietic stem cell infusion (transplant) that is performed within 6 months of the initial transplant. This is distinguished from a repeat transplantation requested or performed more than 6 months after the first transplant and is used as salvage therapy after failure of initial transplantation or relapsed disease.

 

Ovarian Metastatic Germ Cell Tumors

Single autologous hematopoietic stem cell transplantation is considered medically necessary for the treatment of metastatic ovarian germ cell tumors (any stage embryonal tumor; any stage endodermal sinus tumor (yolk sac tumor); stage II-IV dysgerminoma; stage 1, grade II-IV immature teratoma; any stage nongestational choriocarcinoma) for the following indications:

  • For the treatment of recurrent disease following a complete response of induction chemotherapy; or
  • For the treatment of residual disease following induction chemotherapy.  

Autologous hematopoietic stem cell transplant is considered investigational for the treatment of metastic ovarian germ cell tumors not meeting the above criteria and for all other indications. The evidence is insufficient in demonstrating improved net health outcomes.

 

Autologous hematopoietic stem cell transplant is considered investigational for the treatment of germ cell tumors not meeting the above criteria. The evidence is insufficient in demonstrating improved net health outcomes.

Allogeneic Hematopoietic Stem Cell Transplants

Allogeneic hematopoietic stem cell transplantation is considered investigational to treat germ cell tumors, including but not limited to its use as therapy after a prior failed autologous hematopoietic stem cell transplant. The evidence is insufficient in demonstrating improved net health outcomes.

 

Notes:

  • Germ cell tumors are composed primarily of testicular neoplasms (seminomas or nonseminomatous tumors) as well as ovarian and extragonadal germ cell tumors (e.g. retroperitoneal or mediastinal tumors). Germ cell tumors are classified according to their histology, stage, prognosis and response to chemotherapy.
  • Germ cell tumor histologies include seminoma, embryonal carcinoma, teratoma, choriocarcinoma, yolk sac tumor, and mixed germ cell tumors. Seminomas are the most common; all other types are collectively referred to as nonseminomatous germ cell tumors.
  • Patients with favorable prognostic factors include those with a testis or retroperitoneal primary site, a complete response to initial chemotherapy, low levels of serum tumor markers, and low volume disease.
  • Patients with unfavorable prognostic factors are those with incomplete response to initial therapy, high levels of serum tumor markers and high-volume disease.
Definitions
  • Salvage therapy is treatment that is given after the cancer has not responded to other treatment.
  • Sequential chemotherapy is a chemotherapy regimen consisting of several (2 to 4) sequential monochemotherapies with only one chemotherapeutic agent per course. The idea behind this approach is that when using single-agent chemotherapy, the physician can easily escalate the dose of the drug to the maximum tolerable dose by the patient, avoiding hematological toxicity from chemotherapeutic combinations.
Small Cell Carcinoma Ovary, Hypercalcaemic Type (SCCHOT)

Small Cell carcinoma of the ovaray (SCCO) is a rare tumor and are highly undifferentiated, the histology remains obscure (epithelial, germinal or mesenchymatous) most tumors are immunoreative for epithelial markers and of the epithelial type at ultrastructural examination. This is suspected when there is undifferentiated ovarian carcinoma composed of small cells with scantly neoplasm  occurring in a young patient (mean age of 24 years) and associated with para-endocrine hypercalcemia which resaolves after tumor removal (small cell carcinoma ovary, hypercalcaemic type [SCCOHT]).

 

Ovarian Cancer NCCN Version 1.2021 – WHO Histological Classification

  • small cell carcinoma, hypercalcaemic type

 

Autologous Hematopoietic Stem Cell Transplantation

Single autologous hematopoietic stem cell transplantation is considered medically necessary for the treatment of small cell carcinoma ovary, hypercalcaemic type (SCCOHT) with persistently elevated tumor markers and residual disease post inducation therapy.

 

Autologous hematopoietic stem cell transplant is considered investigational for the treatment of small cell carcinoma ovary, hypercalcaemic type (SCCOHT) not meeting the above criteria and for all other indications. The evidence is insufficient in demonstrating improved net health outcomes.

 

Allogeneic Hematopoietic Stem Cell Transplants

Allogeneic hematopoietic stem cell transplantation is considered investigational for small cell carcinoma ovary, hypercalcaemic type (SCCOHT), including its use as therapy after a prior failed autologous hematopoietic stem cell transplant. The evidence is insufficient in demonstrating improved net health outcomes.

Solid Tumors in Adults

Autologous and Allogeneic Hematopoietic Stem Cell Transplantation

Autologous or allogeneic hematopoietic stem cell transplantation is considered investigational for the treatment of the following malignancies in adults, including, but not limited to the following:

  • Lung cancer (any histology)
  • Colon cancer
  • Rectal cancer
  • Pancreatic cancer
  • Stomach cancer
  • Esophageal cancer
  • Gallbladder cancer
  • Cancer of the bile duct
  • Renal cell cancer
  • Breast cancer
  • Cervical cancer
  • Uterine cancer
  • Cancer of the fallopian tubes
  • Ovarian cancer except for ovarian metastatic germ cell tumors and small cell carcinoma ovary, hypercalcaemic type (SCCOHT) as indicated above
  • Prostate cancer
  • Nasopharyngeal cancer
  • Paranasal sinus cancer
  • Neuroendocrine tumors
  • Soft tissue sarcomas
  • Thyroid cancer
  • Tumors of the thymus
  • Tumors of unknown primary origin
  • Malignant melanoma
  • Malignant astrocytomas and gliomas (e.g., gliobastoma multiforme, oligodendroglioma)

Based upon the review of the peer reviewed medical literature treatment with autologous and allogeneic hematopoietic stem cell transplantation for solid tumors in adults has not been medically proven outside the investigational setting for these patients. Current National Comprehensive Cancer Network (NCCN) guidelines do not discuss hematopoietic stem cell transplantation as a treatment option. Available evidence is insufficient and does not demonstrate improved net health outcomes. Additional controlled trials (with appropriate comparator therapies) that report on clinical outcomes are needed to demonstrate efficacy. The evidence is insufficient to determine the safety and/or efficacy of autologous or allogeneic hematopoietic stem cell transplantation for the treatment of solid tumors in adults.

Solid Tumors in Childhood

Autologous Hematopoietic Stem Cell Transplantation

Autologous hematopoietic stem cell transplantation is considered medically necessary for the following indications:

  • Ewing’s sarcoma
    • Initial treatment of high-risk Ewing’s sarcoma
    • Relapsed or refractory Ewing’s sarcoma
  • Neuroblastoma
    • Initial treatment of high-risk neuroblastoma
    • Relapsed or refractory high-risk neuroblastoma
  • Retinoblastoma
    • In the treatment of metastatic retinoblastoma
  • Wilms Tumor
    • For the treatment of relapsed Wilms tumor

 

Note: For ovarian cancer small cell carcinoma ovary, hypercalcaemic type (SCCOHT) see specific  criteria above.

 

Autologous hematopoietic stem cell transplantation is considered investigational when the above criteria is not met and for the following indications because the evidence is insufficient in demonstrating improved net health outcomes:

  • Initial treatment of low or intermediate risk Ewing sarcoma
  • Initial treatment of low or intermediate risk neuroblastoma
  • For other solid tumors of childhood including, but not limited, to the following:
    • Rhabdomyosarcoma
    • Osteosarcoma
    • Retinoblastoma without metastases
    • Ovarian cancer except for small cell carcinoma ovary, hypercalcaemic type (SCCOHT) as indicated above

 

*Tandem Autologous Hematopoietic Stem Cell Transplantation*

A maximum of three tandem autologous hematopoietic stem cell transplantation is considered medically necessary for the treatment of high-risk neuroblastoma.

 

Note: Treatment options for recurrent or refractory neuroblastoma in patients initially classified as high risk may also include the following:

  • 131I-MIBG (MIBG therapy-infusion) alone, in combination with other therapy, or followed by stem cell rescue

 

*Tandem transplantation refers to a planned infusion (transplant) of previously harvested hematopoietic stem cells with a repeat hematopoietic stem cell infusion (transplant) that is performed within 6 months of the initial transplant. This is distinguished from a repeat transplantation requested or performed more than 6 months after the first transplant and is used as salvage therapy after failure of initial transplantation or relapsed disease.

 

*Tandem autologous hematopoietic stem cell transplantation is considered investigational when the criteira above is not met and for the treatment of all other types of solid tumors of childhood, including but not limited to the following indications because the evidence is insufficient in demonstrating improved net health outcomes:

  • Ewing Sarcoma
  • Neuroblastoma except as indicated above
  • Rhabdomyosarcoma
  • Wilms Tumor
  • Osteosarcoma
  • Retinoblastoma
  • Ovarian cancer except for small cell carcinoma ovary, hypercalcaemic type (SCCOHT) as indicated above

 

*Tandem transplantation refers to a planned infusion (transplant) of previously harvested hematopoietic stem cells with a repeat hematopoietic stem cell infusion (transplant) that is performed within 6 months of the initial transplant. This is distinguished from a repeat transplantation requested or performed more than 6 months after the first transplant and is used as salvage therapy after failure of initial transplantation or relapsed disease.

 

Allogeneic Hematopoietic Stem Cell Transplantation

Allogeneic (myeloablative or non-myeloablative) hematopoietic stem cell transplantation is considered investigational for the treatment of childhood solid tumors, including but not limited to the following indications because the evidence is insufficient in demonstrating improved net health outcomes:

  • Ewing Sarcoma
  • Neuroblastoma
  • Rhabdomyosarcoma
  • Wilms Tumor
  • Osteosarcoma
  • Retinoblastoma
  • Ovarian cancer except for small cell carcinoma ovary, hypercalcaemic type (SCCOHT) as indicated above

 

Salvage allogeneic hematopoietic stem cell transplantation for solid tumors of childhood, including but not limited to the following, that relapse after autologous hematopoietic stem cell transplantation or fail to respond is considered investigational because the evidence is insufficient in demonstrating improved net health outcomes:

  • Ewing Sarcoma
  • Neuroblastoma
  • Rhabdomyosarcoma
  • Wilms Tumor
  • Osteosarcoma
  • Retinoblastoma
  • Ovarian cancer except for small cell carcinoma ovary, hypercalcaemic type (SCCOHT) as indicated above

 

Definitions
  • Refractory is a cancer that does not respond to treatment. The cancer may be resistant at the beginning of treatment, or it may become resistant to treatment. Also called resistant cancer.
  • Relapse is a cancer that recurs after prior complete response
  • Salvage therapy is treatment that is given after the cancer has not responded to other treatment.

 

 

 

In the INRG classification system, a combination of clinical, pathologic and genetic markers is used to predict whether the tumor will grow and how it will respond to treatment. These markers are used to define risk. Using the following factors, neuroblastoma is classified into 1 of 4 categories: very low-risk, low-risk, intermediate-risk, or high risk.

  • The stage of the disease according to the INRG staging system
  • Age at the time of diagnosis
  • Histologic category such as maturing ganglioneuroma versus ganglioneuroblastoma, intermixed versus ganglioneuroblastoma or nodular versus neuroblastoma
  • Grade or how cells of the tumor are differentiated
  • MYCN gene status
  • Chromosome 11q status
  • Tumor cell ploidy, which is the DNA content of tumor cells

High risk neuroblastoma is characterized by age older than 1 year, disseminated disease, MYCN oncogene amplification, and unfavorable histopathologic findings

 

Hematopoietic Stem Cell Transplantation: Blood Cancers

Indication Hematopoietic Stem Cell Transplantation Coverage Criteria
Note: When considered medically necessary allogeneic transplantations must be from an appropriately HLA martched donor (related, unrelated matched, cord blood or haploidentical)
Acute Lymphoblastic Leukemia (ALL) – Adult
NCCN: Practice patterns vary with regard to AYA patients in terms of whether ALL patients are treated primarily by pediatric or adult oncologists. AYA patients treated in a pediatric oncology setting may include patients up to age 30 years. AYA patients treated in an adult oncology setting would follow the adult criteria. Pediatric is any patient age 18 years or younger.
  • See also medical policies
    • 08.01.29 Yescarta (Axicabtagene Ciloleucel)*
    • 08.01.30 Kymriah (Tisagenleleucel)*

Autologous Hematopoietic Stem Cell Transplantation

Note: Based on NCCN guidelines Allogeneic HSCT is the preferred transplant for the treatment of acute lymphoblastic leukemia. However, additional studies have shown patients who lack a suitable HLA allogeneic donor that autologous HSCT can result in a prolonged and sustained leukemia free and average survival versus just chemotherapy alone.

 

Autologous hematopoietic stem cell transplantation is considered medically necessary to treat adult acute lymphoblastic leukemia (ALL) in first complete remission when there is no suitable allogeneic donor available.

 

Autologous hematopoietic stem cell transplantation is considered medically necessary to treat adult acute lymphoblastic leukemia (ALL) with relapsed or refractory disease if complete remission is achieved following subsequent therapy when there is no suitable allogeneic donor available.

 

Autologous hematopoietic stem cell transplantation is considered investigational to treat adult acute lymphoblastic leukemia (ALL) not meeting the above criteria for all other indications except as indicated above. The evidence is insufficient in demonstrating improved net health outcomes.

 

Allogeneic Hematopoietic Stem Cell Transplantation

Allogeneic hematopoietic stem cell transplantation is considered medically necessary to treat adult acute lymphoblastic leukemia (ALL) in first complete remission.

 

Allogeneic hematopoietic stem cell transplantation is considered medically necessary to treat adult acute lymphoblastic leukemia (ALL) in second or greater complete remission following subsequent therapy in adults with relapsed or refractory acute lymphoblastic leukemia (ALL).

 

Allogeneic hematopoietic stem cell transplantation is considered medically necessary to treat adult acute lymphoblastic leukemia (ALL) in relapse or refractory disease after prior autologous hematopoietic stem cell transplantation.

 

Allogeneic hematopoietic stem cell transplantation reduced intensity conditioning (non-myeloablative) is considered medically necessary as a treatment for adult acute lymphoblastic leukemia (ALL) in patients who are in complete marrow and extramedullary first or second remission, and who, for medical reasons would be unable to tolerate a standard myeloablative conditioning regimen.

 

Note: Reduced intensity conditioning regimens (non-myeloablative allogeneic transplantation) would be considered for individuals who would otherwise qualify for a myeloablative allogeneic hematopoietic stem cell transplantation but would not tolerate the standard myeloablative conditioning regimen. This may include the following age typically > 60 years or comorbidities (e.g. liver or kidney dysfunction, generalized debilitation, prior intensive chemotherapy, low Karnofsky Performance Status score).

 

Allogeneic hematopoietic stem cell transplantation is considered investigational not meeting the above criteria and for all other indications except as indicated above. The evidence is insufficient in demonstrating improved net health outcomes.

 

Definitions
  • Complete response (also known as complete remission) is the disappearance of all signs of cancer in response to treatment; this does not always mean the cancer has been cured.
  • Karnofsky Performance Status Score is a standard way of measuring the ability of individuals with cancer to perform ordinary tasks. The scores on the scale range from 0 to 100. A higher score means the individual is better able to carry out daily activities. The Karnofsky Performance Status may be used to determine an individua’ls prognosis, to measure changes in an individual’s ability to function, or to decide whether an individual could be included in a clinical trial.
    • 100 – normal no complaints
    • 90 – able to carry on normal activities. Minor signs or symptoms of disease
    • 80 – normal activity with effort
    • 70 – care for self, unable to carry on normal activity or do active work
    • 60 – requires occasional assistance, but able to care for most of his or her needs
    • 50 – requires considerable assistance and frequent medical care
    • 40 – disabled requires special care and assistance
    • 30 – severely disabled, hospitalization indicated though death not imminent
    • 20 – very sick, hospitalization necessary, active supportive treatment necessary
    • 10 - moribund (approaching death, deepening stupor and coma)
  • Myeloablative is a severe form of myelosuppression. Myelosuppression is a condition in which bone marrow activity is decreased, resulting in fewer red blood cells, white blood cells, and platelets. It is a side effect of some cancer treatments.
  • Non-myeloablative (also knowns as reduced intensity conditioning) is a bone marrow transplant in which the individual’s marrow is not completely destroyed prior to receiving the donor’s marrow or stem cells
  • Refractory is a cancer that does not respond to treatment. The cancer may be resistant at the beginning of treatment, or it may become resistant to treatment. Also called resistant cancer.
  • Relapse is a cancer that recurs after prior complete response

 

Response Assessment
Response Criteria for Blood and Bone Marrow
  • Complete Response (Complete Remission)
    • No circulating blasts or extramedullary disease
      • No lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/CNS involvement
    • Marrow with trilineage hematopoiesis (TLH) and < 5% (M1) or <1% by low or molecular testing
    • With blood count recovery = absolute neutrophil count (ANC) > 1000/uL and platelets > 100,000/uL
    • No recurrence in 4 weeks
  • Complete Response (Complete Remission) with incomplete blood count recovery (CRi)
    • Meets all criteria for CR except platelet count and/or ANC
  • Overall response rate (ORR=CR + CR)
  • Note: MRD assessment is not included in the morphologic assessment and should be obtained
  • Refractory disease
    • Failure to achieve CR at the end of induction
  • Progressive disease (PD)
    • Increase at least 25% in the absolute number of circulating or bone marrow blasts or development of extramedullary disease
  • Relapsed disease
    • Reappearance of blasts in the blood or bone marrow > 5% or any extramedullary site after a CR

 

Response Criteria for CNS Disease
  • CNS remission: Achievement of CNS1 status in a patient with CNS-2 or CNS-3 status of diagnosis
  • CNS relapse: New development of CNS-3 status or clinical sgins of CNS leukemia such as facila nerve palsy, brain/eye involvement, or hypothalamic syndrome without another explanation.

 

Response Criteria for Lymphomatous Extramedullary Disease
  • CT of neck/chest/abdomen/pelvis with IV contrast and PET/CT should be performed to assess response for extramedullary disease
  • CR: Complete resolution fo lymphomatous enlargement by CT. For patients with a previous PET scan, a post-treatment residual mass of any size is considered a CR as long as it is PET negative.
  • PR: >50% decrease in the sum of the product of the greatest perpendicular diameters (SPD) of the mediastinal enlargement. For patietns with a previous positive PET scan, post treatment PET must be positive in at least one previously involved site.
  • PD: > 25% increase in the SPD of the mediastinal enlargement. For patients with a previous positive PET scan, post-treatment PET must be positive in at least one previously involved site.
  • No response NR: failure eto quality for PR or PD.
  • Relapse: Recurrence of mediastinal enlargement after achieving CR. For patients with a previous positive PET scan, post-treatment PET must be positive in at least one previously involved site.
Acute Lymphoblastic Leukemia (ALL) – Childhood
NCCN: Practice patterns vary with regards to AYA patients in terms of whether ALL patients are treated primarily by pediatric or adult oncologists. AYA patients treated in a pediatric oncology setting may include patients up to age 30 years. AYA patients treated in an adult oncology setting would follow the adult criteria. Pediatric is any patient age 18 years or younger.
  • See also medical policies
    • 08.01.29 Yescarta (Axicabtagene Ciloleucel)*
    • 08.01.30 Kymriah (Tisagenleleucel)*

Pediatric and AYA Patients being Treated in the Pediatric Setting

B-ALL (B-cell ALL) and T-ALL (T-cell ALL)
  • B-ALL: includes early precursor B-cell (early pre-B-cell) and pre-B-cell. Early pre-B-cell ALL is characterized by the presence terminal deoxynucleotidyl transferase (TdT), the expression of CD19/CD22/CD79a, and the absence of CD10 (formerly termed common ALL antigen) or surface immunoglobulins. CD10 negativity correlates with KMT2A rearrangement and poor prognosis. Pre-B-cell ALL is characterized by the presence of cytoplasmic immunoglobulins and CD10/CD19/CD22/CD79a expression and as previously termed common B-ALL due to the expression of CD10 at diagnosis.
  • T-ALL: is typically associated with the presence of cytoplasmic CD3 (T-cell lineage blasts) or cell surface CD3 (mature T-cells) in addition to variable expression of Cd1a/CD2/CD5/CD7 and expression of TdT.
Autologous Hematopoietic Stem Cell Transplantation

Note: Based on NCCN guidelines Allogeneic HSCT is the preferred transplant for the treatment of acute lymphoblastic leukemia. However, additional studies have shown patients who lack a suitable HLA allogeneic donor that autologous HSCT can result in a prolonged and sustained leukemia free and average survival versus just chemotherapy alone.

 

Autologous hematopoietic stem cell transplantation is considered medically necessary to treat childhood acute lymphoblastic leukemia (ALL) in first complete remission when there is no suitable allogeneic donor available.

 

Autologous hematopoietic stem cell transplantation is considered medically necessary to treat childhood acute lymphoblastic leukemia (ALL) following induction failure when there is no suitable allogeneic donor available.

 

Autologous hematopoietic stem cell transplantation is considered medically necessary to treat childhood acute lymphoblastic leukemia (ALL) for relapsed disease following subsequent therapy experiencing second or greater complete remission when there is no suitable allogeneic donor available.

 

Autologous hematopoietic stem cell transplantation is considered medically necessary to treat childhood acute lymphoblastic leukemia (ALL) with multiple relapses that is responsive to subsequent therapy achieving complete remission when there is no suitable allogeneic donor available.

 

Autologous hematopoietic stem cell transplantation is considered medically necessary to treat childhood acute lymphoblastic leukemia (ALL) for refractory disease achieving complete remission following subsequent therapy when there is no suitable allogeneic donor available.

 

Autologous hematopoietic stem cell transplantation is considered investigational not meeting the above criterai and for all other indications except as indicated above. The evidence is insufficient in demonstrating improved net health outcomes.

 

Allogeneic Hematopoietic Stem Cell Transplantation

Allogeneic hematopoietic stem cell transplantation is considered medically necessary to treat childhood acute lymphoblastic leukemia (ALL) in first complete remission.

 

Allogeneic hematopoietic stem cell transplantation is considered medically necessary to treat childhood acute lymphoblastic leukemia (ALL) following induction failure.

 

Allogeneic hematopoietic stem cell transplantation is considered medically necessary to treat childhood acute lymphoblastic leukemia (ALL) for relapsed disease following subsequent therapy experiencing second or greater complete remission.

 

Allogeneic hematopoietic stem cell transplantation is considered medically necessary to treat childhood acute lymphoblastic leukemia (ALL) with multiple relapses that is responsive to subsequent therapy achieving complete remission.

 

Allogeneic hematopoietic stem cell transplantation is considered medically necessary to treat childhood acute lymphoblastic leukemia (ALL) for refractory disease achieving complete remission following subsequent therapy.

 

Allogeneic hematopoietic stem cell transplantation is considered medically necessary to treat childhood lymphoblastic leukemia (ALL) in relapse or refractory disease after prior autologous hematopoietic stem cell transplantation.

 

Allogeneic hematopoietic stem cell transplantation is considered investigational not meeting the above criteria and for all other indications except as indicated above. The evidence is insufficient in demonstrating improved net health outcomes.

 

Definitions
  • Complete response (also known as complete remission) is the disappearance of all signs of cancer in response to treatment; this does not always mean the cancer has been cured.
  • Refractory is a cancer that does not respond to treatment. The cancer may be resistant at the beginning of treatment, or it may become resistant to treatment. Also called resistant cancer.
  • Relapse is a cancer that recurs after prior complete response

 

Response Assessment
Response Criteria for Blood and Bone Marrow
  • Complete Response (Complete Remission)
    • No circulating blasts or extramedullary disease
      • No lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/CNS involvement
    • Marrow with trilineage hematopoiesis (TLH) and < 5% (M1) or <1% by low or molecular testing
    • With blood count recovery = absolute neutrophil count (ANC) > 1000/uL and platelets > 100,000/uL
    • No recurrence in 4 weeks
  • Complete Response (Complete Remission) with incomplete blood count recovery (CRi)
    • Meets all criteria for CR except platelet count and/or ANC
  • Overall response rate (ORR=CR + CR)
    • Refractory disease
      • Failure to achieve CR at the end of induction
    • Progressive disease (PD)
      • Increase at least 25% in the absolute number of circulating or bone marrow blasts or development of extramedullary disease
    • Relapsed disease
      • Reappearance of blasts in the blood or bone marrow > 5% (M2 or greater) or >1% with previous/supportive molecular findings or any extramedullary site after a CR 

 

Response Criteria for CNS Disease
  • CNS remission: Achievement of CNS1 status in a patient with CNS-2 or CNS-3 status of diagnosis
  • CNS relapse: New development of CNS-3 status or clinical sgins of CNS leukemia such as facila nerve palsy, brain/eye involvement, or hypothalamic syndrome without another explanation. New development of CNS-2 status on 2 consequtive lumbar punctures (between 2-4 weeks apart) with confirmation by immunophenotyping or with molecular testing methods.

 

 

Acute Myeloid Leukemia (AML) Note: Acute myeloid leukemia includes the following: acute promyelocytic Leukemia (APL), acute myeloid leukemia (AML) and Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)

Autologous Hematopoietic Stem Cell Transplantation

Autologous Hematopoietic Stem Cell Transplantation is considered medically necessary for the treatment of acute myeloid leukemia (AML) when donor for allogeneic hematopoietic stem cell transplantation is unavailable for the following indications:

  • First complete remission for a high-risk individual; or
  • Second or subsequent remission
High-risk includes any of the following:
  • Multiple cytogenetic abnormalities
  • Requiring more than one cycle to achieve remission
  • Disease refractory to chemotherapy
  • White blood cell (WBC) count > 100,000/ml3
  • French-American-British (FAB) subtype M4 and M5
  • Chromosome translocations t(10;11), t(1;22), t(6;9), t(9;22)
  • Abnormalities of chromosome 7 or 5, the long arm of chromosome 3, or 11q23
  • Trisomy 8
  • Antigen CD34 and/or P-glycoprotein (MDR1 gene product)
  • Internal tandem duplication mutations of the FLT3 gene
  • History of CNS involvement
  • Systemic infection at diagnosis
  • Treatment-induced AML
  • History of myelodysplastic syndrome

 

Autologous hematopoietic stem cell transplantation is considered investigational for the treatment of acute myeloid leukemia (AML) not meeting the above criteria and for all other indications. The evidence is insufficient in demonstrating improved net health outcomes.

 

Allogeneic Hematopoietic Stem Cell Transplantation

Allogeneic hematopoietic stem cell transplantation using a myeloablative conditioning regimen is considered medically necessary for the treatment of patients with acute myeloid leukemia (AML) with one of the following:

  • Acute myeloid leukemia (AML) in first complete remission following induction therapy; or
  • Acute myeloid leukemia (AML) that is refractory to standard induction chemotherapy (failed induction therapy); or
  • Acute myeloid leukemia (AML) with relapsed or refractory disease; or
  • Acute myeloid leukemia (AML) who have relapsed or refractory disease and is following a prior autologous hematopoietic stem cell transplantation, and the patient can be brought into complete remission with intensified induction chemotherapy and are medically able to tolerate the procedure.

 

Allogeneic hematopoietic stem cell transplantation reduced intensity conditioning regimen (non-myeloablative) as a treatment for acute myeloid leukemia (AML) is considered medically necessary when the above criteira for an allogeneic transplant is met and the myeloablative regimen is contraindicated because of age or comorbidity.

 

Note: Reduced intensity conditioning regimens (non-myeloablative allogeneic transplantation) would be considered for individuals who would otherwise qualify for a myeloablative allogeneic hematopoietic stem cell transplantation but would not tolerate standard myeloablative conditioning regimen. This may include the following age typically > 60 years or comorbidities (e.g. liver or kidney dysfunction, generalized debilitation, prior intensive chemotherapy, low Karnofsky Performance Status score).

 

Allogeneic hematopoietic stem cell transplantation is considered investigational not meeting above criteria and for all other indications. The evidence is insufficient in demonstrating improved net health outcomes.

 

Definitions
  • Karnofksy Performance Status is a standard way of measuring the ability of individuals with cancer to perform ordinary tasks. The scores on the scale range from 0 to 100. A higher score means the individual is better able to carry out daily activities. The Karnofsky Performance Status may be used to determine an individual’s prognosis, to measure changes in an individual’s ability to function, or to decide whether an individual could be included in the clinical trial.
    • 100 – normal no complaints
    • 90 – able to carry on normal activities. Minor signs or symptoms of disease
    • 80 – normal activity with effort
    • 70 – care for self, unable to carry on normal activity or do active work
    • 60 – requires occasional assistance, but able to care for most of his or her needs
    • 50 – requires considerable assistance and frequent medical care
    • 40 – disabled requires special care and assistance
    • 30 – severely disabled, hospitalization indicated though death not imminent
    • 20 – very sick, hospitalization necessary, active supportive treatment necessary
    • 10 - moribund (approaching death, deepening stupor and coma)
  • Myeloablative is a severe form of myelosuppression. Myelosuppression is a condition in which bone marrow activity is decreased, resulting in fewer red blood cells, white blood cells, and platelets. It is a side effect of some cancer treatments.
  • Non-myeloablative (also knowns as reduced intensity conditioning) is a bone marrow transplant in which the individual’s marrow is not completely destroyed prior to receiving the donor’s marrow or stem cells
  • Primary refractory acute myeloid leukemia (AML) is defined as leukemia that does not achieve a complete remission after conventionally dosed (nonmarrow ablative) chemotherapy.
Amyloidosis (Systemic Light Chain)

Autologous Hematopoietic Stem Cell Transplantation

Autologous hematopoietic stem cell transplantation is considered medically necessary as part of the primary treatment for amyloidosis (systemic light chain).

 

Autologous hematopoietic stem cell transplantation is considered investigational not meeting the above criteria and for all all other indications. The evidence is insufficient in demonstrating improved net health outcomes.

 

Allogeneic Hematopoietic Stem Cell Transplantation

Allogeneic hematopoietic stem cell transplantation is considered investigational for all indications. The evidence is insufficient in demonstrating improved net health outcomes.

Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)

Autologous Hematopoietic Stem Cell Transplantation

Autologous hematopoietic stem cell transplantation is considered investigational to treat patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) for all indications. The evidence is insufficient in demonstrating improved net health outcomes.

 

Allogeneic Hematopoietic Stem Cell Transplantation

Allogeneic hematopoietic stem cell transplantation is considered medically necessary for chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) in relapsed or refractory disease meeting one of the following indications:

  • Chronic lymphocytic leukemia or small lymphocytic lymphoma without del(17p)/TP53 mutations
  • Chronic lymphocytic leukemia or small lymphocytic lymphoma with del (17p)/TP53 mutations

 

Allogeneic hematopoietic stem cell transplantation is considered investigational when the above criteria is not met and for all other indications. The evidence is insufficient in demonstrating improved net health outcomes.

 

Richter’s Transformation (Diffuse large B-cell lymphoma): Transformed Chronic Lymphcytic Leukemia (Richter’s Syndrome)

Either an autologous or allogeneic hemopoietic stem cell transplantation is considered medically necessary for chemotherapy sensitive transformed chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) (Richter’s transformation into diffuse large B-cell lymphoma [DLBCL])

 

Classification Staging Systems (NCCN)
CLL Staging Systems

 

 

 

Prognostic Information for CLL/SLL (NCCN)
(Markers of Poor Prognosis in CLL/SLL)

 

 

Chronic Myeloid Leukemia (CML)

Autologous Hematopoietic Stem Cell Transplantation

Autologous hematopoietic stem cell transplantation is considered investigational for the treatment of chronic myeloid leukemia (CML). The evidence is insufficient in demonstrating improved net health outcomes.

 

Allogeneic Hematopoietic Stem Cell Transplantation

Allogeneic hematopoietic stem cell transplantation using a myeloablative conditioning regimen is considered medically necessary for the treatment of chronic myeloid leukemia (CML) for any of the following indications:

  • Remission not reached after three months of tyrosine kinase inhibitor (TKI) therapy; or
  • No cytogenetic response or those in cytogenetic relapse at 6, 12, or 18 months after achieving remission after three months of tyrosine kinase inhibitor (TKI) therapy; or
  • Remission not reached by 12 months of tyrosine kinase inhibitor (TKI) therapy; or
  • Disease progression on tyrosine kinase inhibitor (TKI) therapy to accelerated or blast crisis; or
  • An individual who is not a candidate for tyrosine kinase inhibitor (TKI) therapy

Allogeneic hematopoietic stem cell transplantation using a reduced intensity conditioning regimen (non-myeloablative) is considered medically necessary for the treatment of chronic myeloid leukemia (CML) when the above criteria for an allogeneic transplant is met and the myeloablative regimen is contraindicated because of age or comorbidity.

 

Note: Reduced intensity conditioning regimens (non-myeloablative allogeneic transplantation) would be considered for individuals who would otherwise qualify for a myeloablative allogeneic hematopoietic stem cell transplantation but would not tolerate standard myeloablative conditioning regimen. This may include the following age typically > 60 years or comorbidities (e.g. liver or kidney dysfunction, generalized debilitation, prior intensive chemotherapy, low Karnofsky Performance Status score).

 

Allogeneic hematopoietic stem cell transplantation is considered investigational when the above criteria is not met and for all other indications. The evidence is insufficient in demonstrating improved net health outcomes.

 

Definitions
  • Karnofksy Performance Status is a standard way of measuring the ability of individuals with cancer to perform ordinary tasks. The scores on the scale range from 0 to 100. A higher score means the individual is better able to carry out daily activities. The Karnofsky Performance Status may be used to determine an individual’s prognosis, to measure changes in an individual’s ability to function, or to decide whether an individual could be included in the clinical trial.
    • 100 – normal no complaints
    • 90 – able to carry on normal activities. Minor signs or symptoms of disease
    • 80 – normal activity with effort
    • 70 – care for self, unable to carry on normal activity or do active work
    • 60 – requires occasional assistance, but able to care for most of his or her needs
    • 50 – requires considerable assistance and frequent medical care
    • 40 – disabled requires special care and assistance
    • 30 – severely disabled, hospitalization indicated though death not imminent
    • 20 – very sick, hospitalization necessary, active supportive treatment necessary
    • 10 - moribund (approaching death, deepening stupor and coma)
  • Myeloablative is a severe form of myelosuppression. Myelosuppression is a condition in which bone marrow activity is decreased, resulting in fewer red blood cells, white blood cells, and platelets. It is a side effect of some cancer treatments.
  • Non-myeloablative (also knowns as reduced intensity conditioning) is a bone marrow transplant in which the individual’s marrow is not completely destroyed prior to receiving the donor’s marrow or stem cells
Hodgkin Lymphoma

Autologous Hematopoietic Stem Cell Transplantation

Autologous hematopoietic stem cell transplantation is considered medically necessary for the treatment of patients with primary refractory (may be defined as disease regression less than 50% after 4 to 6 cycles of doxorubicin-containing chemotherapy or disease progression during induction or within 90 days after the end of the first-line treatment)  or relapsed Hodgkin lymphoma.

 

All other uses of autologous hematopoietic stem cell transplantation for patients with Hodgkin lymphoma is considered investigational including, but not limited to, initial or up-front therapy for newly diagnosed disease to consolidate a first complete remission. The evidence is insufficient in demonstrating improved net health outcomes.

 

*Tandem autologous hematopoietic stem cell transplantation is considered medically necessary for the following indications:

  • In patients with primary refractory (may be defined as disease regression less than 50% after 4 to 6 cycles of doxorubicin-containing chemotherapy or disease progression during induction or within 90 days after the end of the first-line treatment) Hodgkin lymphoma; or
  • In patients with relapsed disease with poor risk features who do not attain a complete remission after cytoreductive chemotherapy prior to transplantation.

 

*Tandem transplantation refers to a planned infusion (transplant) of previously harvested hematopoietic stem cells with a repeat hematopoietic stem cell infusion (transplant) that is performed within 6 months of the initial transplant.  This is distinguished from a repeat transplantation requested or performed more than 6 months after the first transplant and is used as salvage therapy after failure of initial transplantation or relapsed disease.

 

Tandem autologous hematopoietic stem cell transplantation is considered investigational not meeting the above criteria and for all other indications. The evidence is insufficient in demonstrating improved net health outcomes. 

 

Allogeneic Hematopoietic Stem Cell Transplantation

Allogeneic hematopoietic stem cell transplantation using either myeloablativbe or reduced intensity conditioning regimens (non-myeloablative) is considered medically necessary for the following:

  • Individuals with primary refractory (may be defined as disease regression less than 50% after 4 to 6 cycles of doxorubicin-containing chemotherapy or disease progression during induction or within 90 days after the end of the first-line treatment) or relapsed Hodgkin lymphoma; or
  • Individuals who relapse after prior autologous hematopoietic stem cell transplantation that was used to treat primary refractory (may be defined as disease regression less than 50% after 4 to 6 cycles of doxorubicin-containing chemotherapy or disease progression during induction or within 90 days after the end of the first-line treatment) or relapsed disease

Note: Reduced intensity conditioning regimens (non-myeloablative allogeneic transplantation) would be considered for individuals who would otherwise qualify for a myeloablative allogeneic hematopoietic stem cell transplantation (bone marrow transplantation), but would not tolerate standard myeloablative conditioning regimen. This may include the following age typically > 60 years or comorbidities (e.g. liver or kidney dysfunction, generalized debilitation, prior intensive chemotherapy, low Karnofsky Performance Status score).

 

Allogeneic hematopoietic stem cell transplantation for the treatment of Hodgkin lymphoma is considered investigational when the above criteira is not met and for all other indications to include initial or up-front therapy for newly diagnosed disease to consolidate a first complete remission.

 

Definitions
Karnofsky Performance Status is a standard way of measuring the ability of individuals with cancer to perform ordinary tasks. The scores on the scale range from 0 to 100. A higher score means the individual is better able to carry out daily activities. The Karnofsky Performance Status
  • may be used to determine the individuals prognosis, to measure changes in an individual’s ability to function or to decide whether an individual could be included in a clinical trial.
    • 100 – normal no complaints
    • 90 – able to carry on normal activities. Minor signs or symptoms of disease
    • 80 – normal activity with effort
    • 70 – care for self, unable to carry on normal activity or do active work
    • 60 – requires occasional assistance, but able to care for most of his or her needs
    • 50 – requires considerable assistance and frequent medical care
    • 40 – disabled requires special care and assistance
    • 30 – severely disabled, hospitalization indicated though death not imminent
    • 20 – very sick, hospitalization necessary, active supportive treatment necessary
    • 10 - moribund (approaching death, deepening stupor and coma)
  • Myeloablative is a severe form of myelosuppression. Myelosuppression is a condition in which bone marrow activity is decreased, resulting in fewer red blood cells, white blood cells, and platelets. It is a side effect of some cancer treatments.
  • Non-myeloablative (also knowns as reduced intensity conditioning) is a bone marrow transplant in which the individual’s marrow is not completely destroyed prior to receiving the donor’s marrow or stem cells.
  • Poor-risk relapsed Hodgkin lymphoma may be defined as 2 or more of the following risk factors at first relapse: time to relapse less than 12 months, stage III or IV at relapse, and relapse within previously irradiated sites.
  • Primary refractory Hodgkin lymphoma may be defined as disease regression less than 50% after 4 to 6 cycles of doxorubicin-containing chemotherapy or disease progression during induction or within 90 days after the end of the first-line treatment.
Multiple Myeloma

See also medical policy

08.01.35 Abecma (Decabtaegne Vicleucel)*

Autologous Hematopoietic Stem Cell Transplantation

A single autologous hematopoietic stem cell transplantation is considered medically necessary for the treatment of multiple myeloma following primary therapy.

 

Autologous hematopoietic stem cell transplantation is considered medically necessary for the treatment of progressive or relapsed multiple myeloma who did not receive an autologous hematopoietic stem cell transplant as part of their initial treatment.

 

A repeat autologous hematopoietic stem cell transplantation is considered medically necessary to treat responsive multiple myeloma that has relapsed after a complete response (CR) or very good partial response (VGPR) following an initial autologous hematopoietic stem cell transplantation.

 

Autologous hematopoietic stem cell transplantation is considered investigational for the treatment of multiple myeloma not meeting the above criteria and for all other indications to include a third autologous hematopoietic stem cell transplantation for salvage therapy. The evidence is insufficient in demonstrating improved net health outcomes.

 

Tandem Transplantation*

Tandem autologous hematopoietic stem cell transplantation is considered medically necessary to treat multiple myeloma after primary therapy.

 

Tandem autologous hematopoietic stem cell transplantation is considered medically necessary in patients who fail to achieve at least a near complete response (CR) or very good partial response (VGPR) after the first transplant in the tandem sequence.

 

Tandem autologous hematopoietic stem cell transplantation is considered investigational for the treatment of multiple myeloma when the above criteria is not met and for all other indications to include a third autologous hematopoietic stem cell transplantation for salvage therapy. The evidence is insufficient in demonstrating improved net health outcomes.

 

* Tandem transplantation refers to a planned infusion (transplant) of previously harvested hematopoietic stem cells with a repeat hematopoietic stem cell infusion (transplant) that is performed within 6 months of the initial transplant. This is distinguished from a repeat transplantation requested or performed more than 6 months after the first transplant and is used as salvage therapy after failure of initial transplantation or relapsed disease.

 

Allogeneic Hematopoietic Stem Cell Transplantation

Allogeneic hematopoietic stem cell transplantation is considered medically necessary following a single or tandem autologous hematopoietic stem cell transplantation for the treatment of progressive disease (PD).

 

Note: Myeloablative allogeneic transplant is preferred but if based on age and/or comorbidities a non-myeloablative conditioning regimen allogeneic hematopoietic stem cell transplantation (i.e. reduced-intensity conditioning regimen) may be utilized and considered medically necessary if meets the above criteira for allogeneic hematopoietic stem cell transplantation.

 

Allogeneic hematopoietic stem cell transplantation myeloablative or non-myeloablative is considered investigational for all other indications not meeting the criteria above. The evidence is insufficient in demonstrating improved net health outcomes.

 

Definitions
  • Myeloablative is a severe form of myelosuppression. Myelosuppression is a condition in which bone marrow activity is decreased, resulting in fewer red blood cells, white blood cells, and platelets. It is a side effect of some cancer treatments.
  • Non-myeloablative (also knowns as reduced intensity conditioning) is a bone marrow transplant in which the individual’s marrow is not completely destroyed prior to receiving the donor’s marrow or stem cells.

 

Response criteria for multiple myeloma by International Myeloma Working Group (NCCN)

  • Complete response: negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow aspirates.
  • Very good partial response (VGPR): Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein plus urine M-protein level < 100 mg per 24 h.
  • Partial response: ≥ 50% reduction of serum M-protein please reduction in 24 h urinary M-protein by ≥ 90% or to < 200 mg per 24 h. If the serum and urine M-protein are unmeasurable, a ≥ 50% decrease in the difference between involved and uninvolved FLC levels is required in place of the M-protein criteria.
    • If serum and urine M-protein are unmeasurable, and serum-free light assay is also unmeasurable, ≥ 50% reduction in plasma cells is required in place of M-protein, provided baseline bone marrow plasma cell percentage was ≥ 30%. In addition to these criteria, if present at baseline, a ≥ 50% reduction in the size (sum of the products of the maximal perpendicular diameters (SPD) of measure lesions) of soft tissue plasmacytomas is also required.
  • Minimal response: ≥ 25% but 49% reduction of serum M-protein and reduction in 24 h urine M-protein by 50%-89%. In addition to the above listed criteria, if present at baseline, a 25%-49% reduction in SPD of soft tissue plasmacytomas is also required.
  • Progressive disease: Increase of 25% from lowest confirmed response value in one or more of the following criteria:
    • Serum M-protein (absolute increase must be ≥ 0.5 g/dL);
    • Serum M-protein increase ≥ 1g/dL, if the lowest M component was ≥ 0.5 g/dL;
    • Urine M-protein (absolute increase must be ≥ 200 mg/24 h;
    • In patients without measurable serum and urine M-protein levels, the difference between involved and uninvolved FLC levels (absolute increase must be > 10 mg/dL);
    • In patients without measurable serum and urine M-protein levels and without measurable involved FLC levels, bone marrow plasma-cell percentage irrespective of baseline status (absolute increase must be ≥ 10%);
    • Appearance of a new lesion(s), ≥ 50% increase from nadir in SPD of > 1 lesion, or ≥ 50% increase in the longest diameter of a previous lesion > 1 cm in short axis;
    • ≥ 50% increase in circulating plasma cells (minimum of 200 cells per uL) if this is the only measure of disease.
  • Clinical relapse: Clinical relapse requires one or more of the following criteria:
    • Direct indicators of increasing disease and/or end organ dysfunction (calcium elevation, renal failure, anemia, lytic bone lesions [CRAB features] related to the underlying clonal plasma-cell proliferative disorder. It is not used in calculation of time to progression or progression-free survival but is listed as something that can be reported optionally or for use in clinical practice;
    • Development of new soft tissue plasmacytomas or bone lesions (osteoporotic fractures do not constitute progression);
    • Definite increase in the size of existing plasmacytomas or bone lesions. A definite increase is defined as a 50% (and ≥ 1cm) increase as measured serially by the SPD of the measurable lesion;
    • Hypercalcemia (>11 mg/dL);
    • Decrease in hemoglobin of ≥ 2 g/dL not related to therapy or other non-myeloma related conditions;
    • Rise in serum creatinine by 2 mg/dL or more from the start of therapy and attributable to myeloma;
    • Hyperviscosity related to serum paraprotein.
  • Relapse from complete response (to be used only if the endpoint is disease-free survival) any one of the following criteria:
    • Reappearance of serum or urine M-protein by immunofixation or electrophoresis;
    • Developmental of ≥ 5% plasma cells in the bone marrow;
    • Appearance of any other sign of progression (i.e. new plasmacytoma, lytic bone lesion, or hypercalcemia).
  • Relapse from MRD negative (to be used only if the endpoint is disease-free survival) any one of the following criteria:
    • Loss of MRD negative state (evidence of clonal plasma cells on NGF or NGS, or positive imaging study for recurrence of myeloma);
    • Reappearance of serum or urine M-protein by immunofixation or electrophoresis;
    • Development of ≥ 5% clonal plasma cells in the bone marrow;
    • Appearance of any other sign of progression (i.e. new plasmacytoma, lytic bone lesion; or hypercalcemia).
Myeloid/Lymphoid Neoplasms with Eosinophilia and Tyrosine Kinase Fusion Genes

Clonal eosinophilia associated with tyrosine kinase (TKI) fusion gene rearrangements (PDGFRA, PGGFRB, FGFR1, Jak2, ABL1 or FLT3) can have diverse clinical presentations including Ph-negative myeloproliferative neoplasm (MPN) with eosinophilia, myelodysplastic syndromes (MDS)/MPN with eosinophilia, acute myeloid leukemia (AML), B-cell or T-cell lymphomas with eosinophilia, acute lymphoblastic leukemia (ALL) with eosinophilia or mixed lineage leukemias/lymphomas with eosinophilia.

 

Eosinophilic disorders and related syndromes represent a heterogenous group of neoplastic and non-neoplastic conditions characterized by an increased number of eosinophils in the peripheral blood and may involve eosinophil-induced organ damage.

The identification of specific TK fusion genes and the emergence of tyrosine kinase inhibitors (TKIs) has significantly improved the diagnosis and treatment of some patients with MLN-EO. The management of patients with MLN-EO, requires a multidisciplinary team approach preferably in specialized medical centers.

 

A diagnosis of myeloid/lymphoid neoplasma with eosinophilia should be suspected in the following clinical situations:

  • Sustained eosinophilia (> 1.5 x 109/L) or tissue eosinophila (any eosinophil count) in a target organ, with the occurrence of characteristic genetic breakpoints, with some not always visible by standard cytogenetics (e.g., FIP1L1-PDGFRA, ETV6-ABL1);
  • Clinical features such as splenomegaly, anemia, thromobocytopenia, leukoerythroblastosis, circulating dysplastic cells, elevated serum vitamin B12 and/or tryptae levels, and abnormal mast cell proliferation in the bone marrow (BM);
  • Features of systemic mastocytosis (SM) with eosinophilia with with interstitial, not dense aggregates of atypical mast cells (FIP1L1-PDGFRA rearrangement);
  • Features of chronic myelomonocytic leukemia (CMML) with eosinophilia (PDGFRB rearrangement);
  • Persistent eosinophilia after intensive treatment of AML, ALL, B-cell lymphoma, or T-cell lymphoma.

 

2017 WHO Diagnostic Criteria for Myeloid/Lymphoid Neoplasms with Eosinophilia and Rearrangement of PDGFRA, PDGFRB, or FGFR1, or with PCM1-JAK2

  • Myeloid/Lymphoid Neoplasms with Eosinophilia Associated with FIP1L1-PDGRFA or a Variant Fusion Gene*
    • A myeloid or lymphoid neoplasm usually with prominent eosinophila; and
    • Presence of a FIP1L1-PDGFRA fusion gene or a variant fusion gene with rearrangement of PDGFRA or an activating mutation of PDGFRA+
  • Myeloid/Lymphoid Neoplasms with Eosinophilia Associated with ETV6-PDGFRB or Other Rearrangements of PDGFRB++
    • A myeloid or lymphoid neoplasm often with prominent eosinophial and sometimes with neutrophilia or monocytosis; and
    • Presence of t(5;12)(q31-q33;p13) or a variant translocation+++ or demonstration of an ETV6-PDGFRB fusion gene or other rearrangement of PDGFRB
  • Myeloid/Lymphoid Neoplasms with Eosinophilia Associated with FGFR1 Rearrangement 
    • A myeloproliferative or myelodysplastic/myeloproliferative neoplasm with prominent eosinophilia, and sometimes with neutrophilia or monocytosis; or
    • Acute myeloid leukemia or T-cell or B-cell lymphoblastic leukemia/lymphoma or mixed phenotype acute leukemia (usually associated with peripheral blood or bone marrow eosinophilia); and
    • Presence of t(8;9)(p11;q12) or variant translocation leading to FGFR1 rearrangement demonstrated in myeloid cells, lymphblasts, or both
  • Myeloid/Lymphoid Neoplasms with Eosinophilia Associated with PCM1-JAK2 Rearrangement
    • A myeloid or lymphoid neoplasm often with prominent eosinophilia; and
    • Presence of t(8;9)(p22;p24.1) or a variant translocation leading to JAK2 rearrangement++++

 

Footnotes:

*Patients presenting with myeloproliferative neoplasm, acute myeloid leukemia, or lymphoblastic leukemia/lymphoma with eosinophilia and a FIP1L1-PDGFRA fusion gene are also assigned to this category.
+If appropriate molecular analysis is not possible, this diagnosis should be suspected if there is a Ph chromosome - negative myeloproliferative neoplasm with hematologic features of chronic eosinophilic leukemia associated with splenomegaly, a marked elevation of serum vitamin B12, elecation of serum tryptase, and an increased number of bone marrow mast cells.
++Cases with fusion genes typically associated only with BCR-ABL1-like B-lymphoblastic leukemia are specifically excluded.
+++Because t95;12)(q31;q33,p12) does not always lead to an EVT-6-PDGFRB fusion gene, molecular confirmation is highly desirable. If molecular analysis is not possible, this diagnosis should be suspected if there is a Ph chromosome – negative myeloproliferative neoplasm associated with eosinophilia and with translocation with a 5q31;33 breakpoint.
++++Other variants giving rise to a fusion gene between JAK2 and an alternative partner include ETV6-Jak2 [t(9;12)p24.1;p13.2)] or BCR-JAK2 [t(9;22)(p24.1;q11.2)]

 

Autologous Hematopoietic Stem Cell Transplantation

Autologous hematopoietic stem cell transplantation is considered investigational for the treatment of myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase fusion genes. The evidence is insufficient in demonstrating improved net health outcomes.

 

Allogeneic Hematopoietic Stem Cell Transplantation

Allogeneic hematopoietic stem cell transplantation is considered medically necessary for the treatment of myeloid/lymphoid neoplasms with eosinophilia (sustained eosinophilia > 1.5 x 109/L or tissue eosinophilia [any eosinophil count] in a target organ) and one of the following rearrangements FGFR1, JAK2, FLT3 or ABL1 for the following indications:

  • Initial treatment; or
  • Individual in chronic phase (may present in the bone marrow or peripheral blood with or without eosinophilia; bone marrow may exhibit an atypical mast cell proliferation often in an interstitial pattern but not the typical aggregates found in SM [systemic mastocytosis]) receiving TKI induction chemotherapy to be followed by allogeneic hematopoietic stem cell transplantation; or
  • Individual in blast phase (> 20% blasts in bone marrow and/or peripheral blood (may present as AML, ALL or mixed lineage disease) and/or extramedullary myeloid sarcoma, T-cell or B-cell lymphoblastic lymphoma, or myeloid//T-cell or B-cell lymphoid mixed lineage blast phase disease. Blast phase may also present as an EMD [extra medullary disease] with an “myeloproliferative neoplasm-like” picture in blood and marrow) receiving TKI induction chemotherapy to be followed by allogeneic hematopoietic stem cell transplantation.

 

Allogeneic hematopoietic stem cell transplantation is considered medically necessary for the treatment of myeloid/lymphoid neoplasms with eosinophilia (sustained eosinophilia > 1.5 x 109/L or tissue eosinophilia [any eosinophil count] in a target organ) and one of the following rearrangements PDGFRA or PDGFRB for relapsed disease following a complete hematologic response ([CHR] – defined as the normalization of peripheral blood counts and esosinophilia) and complete cytogenetic response (CCyR).

 

Allogeneic hematopoietic stem cell transplantation is considered investigational for indications not meeting the criteria above and for all other indications. The evidence is insufficient in demonstrating improved net health outcomes.

 

Classification and Definition of Hypereosinophlia
Proposed Terminology Proposed Abbreviation Definition and Criteira
Blood eosinophila   >0.5 eosinophils x 109/L blood
Hypereosinophilia HE

>1.5 x 109/L eosinophils in the blood on 2 examination (interval > 1 montha) and/or tissue HE defined by the followingb

  1. Percentage of esosinophils in bone marrow exceeds 20% of nucleated cells; and/or
  2. Pathologist is of the opinion that tissue infiltration by eosinophils is extensive; and/or
  3. Marked deposition of eosinophil granule proteins is found (in the absence or presence of major tissue infiltration by eosinophils)
Hereditary (familial) HE HEFA Pathogenesis unknown; familial clustering, no signs or symptoms of hereditary immunodeficiency, and no evidence of a reactive or neoplastic condition/disorder underlying HE
HE of undetermined significance HEUS No underlying cause of HE, no family history, no evidence of reactive or neoplastic condition/disorder underlying HE, and no end -organ damage attributable to HE
Primary (clonal/neoplastic) HEc HEN Underlying stem cell, myeloid, or eosinophilic neoplasm, as classifed by WHO criteria; eosinophils considered neoplastic cellsd
Secondary (reactive) HEc HER Underlying conditions/disease in which eosinophils are considered nonclonal cells;d HE considered cytokine-driven in most casese
Eosinophil-associated single – organ diseases   Criteria of HE fulfilled and single-organ disease

 

Footnotes:

a In the case of evolving life-threatening end-organ damage, the diagnosis can be made immediately to avoid delay in therapy.
b Validated quantitative criteria for tissue HE do not exist for most tissues at the present time. Consequently, tissue HES is defined by a combination of qualitative and semiquantitative findings that will require revision as new information becomes available.
c HEN and HER are prediagnostic checkpoints that should guide further diagnostic evaluations but cannot serve as final diagnoses.
d Clonality of eosinophils is often difficult to demonstrate or is not examined. However, if a myeloid or stem cell neoplasm known to present typically with clonal HE is present or a typical molecular defect is demonstrable (e.g. PDGFR or FGFR mutations or BCR/ABL 1), eosinophilia should be considered clonal.
e In a group of patients, HER might be caused/triggered by other as yet unknown process because no increase in eosinophilopoietic cytokine levels can be documented.

Myelodysplastic Syndromes (MDS) and Myeloproliferative Neoplasms

Myelodysplastic Syndromes (MDS)

Myelodysplastic syndromes (MDS) represent myeloid clonal hemopathies with a relative heterogenous spectrum of presentation. The major clinical problems in these disorders are morbidities caused by cytopenias and the potential of MDS to evolve into acute myeloid leukemia (AML).

The category of myelodysplastic/myeloproliferative neoplasm (MDS/MPN) was added to the 2008 update of the WHO classification of myeloid neoplasm. This category includes chronic myelomonocytic leukemia (CMML), atypical chronic myeloid leukemia (aCML), BCR-ABL1 negative, and juvenile myelomonocytic leukemia (JMML) as disorders having over-lapping dysplastic and proliferative features. The MDS/MPN with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T) and the MDS/MPN unclassified groups are also included in this category.

 

Myelofibrosis (MF)

Myelofibrosis (MF), polycythemia vera (PV) and essential thrombocythemia (ET) are a group of heterogenous disorders of the hematopoietic system collectively known as Philadelphia-chromosome-negative myeloproliferative neoplasm (MPN).

 

Autologous Hematopoietic Stem Cell Transplantation

Autologous hematopoietic stem cell transplantation is considered investigational for the treatment of myelodysplastic syndromes and myeloproliferative neoplasms (e.g., myelofibrosis). The evidence is insufficient in demonstrating improved net health outcomes.

 

Allogeneic Hematopoietic Stem Cell Transplantation

Allogeneic hematopoietic stem cell transplantation is considered medically necessary for the treatment of juvenile myelomonocytic leukemia (JMML).

 

Allogeneic hematopoietic stem cell transplantation is considered medically necessary for the treatment of chronic myelomonocytic leukemia (CMML).

 

Allogeneic hematopoietic stem cell transplantation is considered medically necessary for the treatment of individuals who have myelodysplastic disease with an intermediate IPSS (International Prognostic Scoring System) overall score of 1.5 to 2.0 or high IPPS overall score of > 2.5; or an intermediate IPSS-R (Revised International Prognostic Scoring System) overall score of >3.0 - ≤4.5 or high IPSS-R overall score of >4.5 - < 6.0, or very high IPSS-R overall score of > 6.0; or an intermediate WHO-Based Prognostic Scoring System (WPSS) overall score of 2, or high WPSS overall score 3-4, or a very high WPSS overall score of 5.6 and have not responded to prior therapy.

 

Allogeneic hematopoietic stem cell transplantation is considered medically necessary for the treatment of myelodysplastic disease progressing into advanced phase AML.

 

A second allogeneic hematopoietic stem cell transplantation is considered medically necessary for the treatment of relapsed myelodysplastic disease after a remission following the first allogeneic hematopoietic stem cell transplant.

 

Allogeneic hematopoietic stem cell transplantation is considered medically necessary for the treatment of myeloproliferative neoplasms (e.g. myelofibrosis (MF) in intermediate and high-risk individuals. (IPSS [International Prognostic Scoring System: intermediate-risk 1-2 or high-risk ≥3] DIPSS [Dynamic International Prognostic Scoring System] intermediate risk 1-4 points; high-risk ≥ 5 points])

 

Reduced Intensity Allogeneic Hematopoietic Stem Cell Transplantation

Reduced-intensity (non-myeloablative) conditioning allogeneic hematopoietic stem cell transplantation is considered medically necessary for the treatment of myelodysplastic syndromes and myeloproliferative neoplasms (e.g., myelofibrosis) meeting the above criteria for allogeneic hematopoietic stem cell transplantation and the myeloablative regimen is contraindicated because of age or comorbidity.

 

Note: Reduced intensity conditioning regimens (non-myeloablative allogeneic transplantation) would be considered for individuals who would otherwise qualify for a myeloablative allogeneic hematopoietic stem cell transplantation but would not tolerate standard myeloablative conditioning regimen. This may include the following age typically > 60 years or comorbidities (e.g., liver or kidney dysfunction, generalized debilitation, prior intensive chemotherapy, low Karnofsky Performance Status score).

 

Allogeneic hematopoietic stem cell transplantation is considered investigational for indications not meeting the criteria above and for all other indications. The evidence is insufficient in demonstrating improved net health outcomes.

 

International Working Group (IWG) Response Criteria for MDS
IWG Criteria for Response
Category Original (Sustained > Weeks) Modified (Sustained > 4 weeks)
CR: Marrow < 5% blasts; no dysplasia; normal maturation of all cell lines ≤ 5% blasts; normal maturation of all cells lines
CR: Peripheral Blood Hgb ≥ 11 g/dL;
ANC ≥ 1,500/mL;
platelets ≥ 100,000/mL;
0% blasts;
no dysplasia
Hgb ≥ 11 g/dL;
ANC ≥ 1000/mL;
platelets ≥ 100,000/mL;
0% blasts;
hematologic improvement responses noted in addition to marrow CR
PR Same as CR, except blasts by ≥ 50% or lower FAB Same as CR, except blasts by ≥ 50%, still greater than 5% in marrow

 

IWG Criteria for Hematologic Improvement
Category Pretreatment Modified IWG Response Criteria* (>8 weeks)
Erythroid (HI-E) Hgb < 11 g/dL Hgb of ≥ 1.5 g/dL
of ≥ 4 RBC transfusions/8 weeks versus pretreatment requirement in previous 8 weeks; only RBC transfusions given for a pretreatment Hgb of ≤ 9.0 g/dL count
Platelet (HI-P) < 100,000/mL of ≥ 30,000/mL (starting with > 20,000/mL
from < 20,000/mL to > 20,000/mL by ≥ 100%
Neutrophil (HI-N) < 1,000/mL of ≥ 100% and > 500/μ L
Progression/Relapse after hematological improvement   ≥ 1 of the following: ≥ 50% decrement from maximum response levels in granulocytes or platelets; in Hgb by ≥ 1.5 g/dL; transfusion dependence

 

2017 WHO Diagnostic Criteria for Primary Myelofibrosis

WHO prePMF Criteria:
(Diagnosis of prePMF requires all 3 major criteria, and at least 1 minor criterion)
  • Major criteria
    • Megakaryocytic proliferation and atypia, without reticulin fibrosis > grade 1, accompanied by increased age-adjusted BM cellularity, granulocytic proliferation, and often decreased erythropoiesis
    • No meeting WHO criteria for BCR-ABL1 + CML, PV, ET, myelodysplastic syndromes, or other myeloid neoplasms.
    • Presence of JAK2, CALR, or MPL mutation or in the absence of these mutations, presence of another clonal marker, or absence of minor reactive BM reticulin fibrosis
  • Minor criteria
    • Presence of at least one of the following, confirmed in 2 consecutive determinations:
      • Anemia not attributed to a comorbid condition
      • Leukocytosis ≥ 11 x 109/L
      • Palpable splenomegaly
      • LDH increased to above upper normal limit of institutional reference range
WHO Overt PMF Criteria:
(Diagnosis of overt PMF requires meeting all 3 major criteria, and at least 1 minor criteria)
  • Major criteria
    • Presence of megakaryocytic proliferation and atypia, accompanied by either reticulin and/or collagen fibrosis grades 2 or 3
    • Not meeting WHO criteria for ET, PV, BCR-ABL + CML, myelodysplastic syndromes, or other myeloid neoplasms
    • Presence of JAK2, CALR, or MPL mutation or in the absence of these mutations, presence of another clona markers, or absence of reactive myelofibrosis
  • Minor criteria
    • Presence of at least one of the following, confirmed in 2 consecutive determinations:
      • Anemia not attributed to a comorbid condition
      • Leukocytosis ≥ 11 x 109L
      • Palpable splenomegaly
      • LDH increased to above upper normal limit of institutional reference range
      • Leukerythroblastosis
Myelofibrosis Grading
  • MF-0
    • Scattered linear reticulin with no intersections (crossovers) corresponding to normal BM
  • MF-1
    • Loose network or reticulin with many intersections, especially in perivascular areas
  • MF-2
    • Diffuse and dense increase in reticulin with extensive intersections, occasionally with focal bundles of thick fibers mostly consistent with collagen, and/or focal osterosclerosis
  • MF-3
    • Diffused and dense increase in reticulin

2017 WHO Diagnostic Criteria for Polycythermia Vera and Essential Thrombocythemia

Polycythemia Vera (PV)
(Diagnosis requires meeting either all 3 major criteria, or the first 2 major criteria and the minor criterion)
  • Major criteria
    • Hemoglobin > 16.5 g/dL in men, >16.0 g/dL in women; OR Hematocrit > 49% in men, > 48 men in women; OR Increased cell mass (RCM)
    • Bone marrow biopsy showing hypercellularity for age with trilineage growth (pathmyelosis) including prominent erythroid, granulocytic, and megakaryocytic proliferation with pleomorphic, mature magakaryocytes (differences in size)
    • Presence of JAK2V617F or JAK2 exon 12 mutation
  • Minor criteria
    • Subnormal serum EPO level
Essential Thrombocythemia (ET)
(Diagnosis requires meeting all 4 major criteria or the first 3 major criteria and the minor criterion)
  • Major criteria
    • Platelet count ≥ 450 x 109/L
    • Bone marrow biopsy showing proliferation mainly of the megakaryocyte lineage with increased numbers of enlarged, mature megakaryocytes with hyperlobulated nuclei. No significant increase of left shift in neutrophil granulopoiese or erythopoises and very rarely minor (grade 1) increase in reticulin fibers
    • Note meeting WHO criteria for CML, PV, PMF, myelodysplastic syndromes or other myeloid neoplasms
    • Presence of JAK2, CALR, or MPL mutation
  • Minor criterion
    • Presence of a clonal marker or absence of evidence for reactive thrombocytosis

IWG-MRT Diagnostic Criteria for Post-Polycythemia Vera (PV) and Post-Essential (ET) Myelofribrosis

Criteria for Post-PV Myelofibrosis
  • Required criteria
    • Documentation of a previous diagnosis of PV as defined by the WHO criteria
    • Bone marrow fibrosis grade 2-3 (on 0-3 scale) or grade 3-4 (on 0-4 scale)
  • Additional criteria (two are required)
    • Anemia or sustained loss of requirement of either phlebotomy (in the absence of cytoreductive therapy) or cytoreductive treatment for erythrocytes
    • A leukoerythrobalstic peripheral blood picture
    • Increasing splenomegaly defined as either an increase in palpable splenomegaly of ≥ 5 cm (distance of the tipe of the spleen from the left costal margin) or the appearance of a newly palapable splenomegaly
    • Development of ≥ 1% of three constitutional symptoms: > 10% weight loss in 6 months, night sweats, unexplained fever (> 37.5 degrees Celsius)
Criteria for Post-ET Myelofibrosis
  • Required criteria
    • Documentation of a previous diagnosis of ET as defined by WHO criteria
    • Bone marrow fibrosis grade 2-3 (on 0-3 scale) or grade 3-4 (on 0-4 scale)
  • Additional criteria (two are required)
    • Anemia and ≥ 2g/dl decrease from baseline hemoglobin level
    • A leukoerythoblastic peripheral blood picture
    • Increasing splenomegaly defined as either an increase in palpable splenomegaly of ≥ 5cm (distance of the tip of the spleen from the lest cost margin) or the appearance of a newly palpable splenomegaly
    • Increased LDH (above reference level)
    • Development of ≥ 1 of 3 constitutional symptoms: > 10% weight loss in 6 months, night sweats, unexplained fever (37.5 degrees Celsius)
Definitions
  • Karnofosky Performance Status is a standard way of measuring the ability of individuals with cancer to perform ordinary tasks. The scores on the scale range from 0 to 100. A higher score means the individual is better able to carry out daily activities. The Karnofsky Performance Status may be used to determine an individual’s prognosis, to measure changes in an individual’s ability to function, or to decide whether an individual could be included in a clinical trial.
    • 100 – normal no complaints
    • 90 – able to carry on normal activities. Minor signs or symptoms of disease
    • 80 – normal activity with effort
    • 70 – care for self, unable to carry on normal activity or do active work
    • 60 – requires occasional assistance, but able to care for most of his or her needs
    • 50 – requires considerable assistance and frequent medical care
    • 40 – disabled requires special care and assistance
    • 30 – severely disabled, hospitalization indicated though death not imminent
    • 20 – very sick, hospitalization necessary, active supportive treatment necessary
    • 10 - moribund (approaching death, deepening stupor and coma)
  • Myeloablative is a severe form of myelosuppression. Myelosuppression is a condition in which bone marrow activity is decreased, resulting in fewer red blood cells, white blood cells, and platelets. It is a side effect of some cancer treatments.
  • Non-myeloablative (also knowns as reduced intensity conditioning) is a bone marrow transplant in which the individual’s marrow is not completely destroyed prior to receiving the donor’s marrow or stem cells
Non-Hodgkin Lymphoma B-Cell Lymphomas
  • See also medical policies
    • 08.01.29 Yescarta (Axicabtagene Ciloleucel)*
    • 08.01.30 Kymriah (Tisagenleleucel)*
    • 08.01.33 Tecartus (Brexucabtagene Autoleucel)*
    • 08.01.31 Breyanzi (Lisocabtagene Maraleucel)*

 

The most common B-cell lymphoma subtypes include the following: 
• Diffuse large B-cell lymphoma (DLBCL)
• Follicular lymphoma (FL)
• Mantle cell lymphoma (MCL)
• Burkitt lymphoma (BL)
• AIDs related B-cell lymphomas
• Post-transplant lymphoproliferative disorders
• Castleman’s disease 
• Marginal zone lymphomas (MZLs)
• Gastric MALT lymphomas
• Non gastric MALT lymphoma
• Nodal MZL
• Splenic MZL

 


Follicular Lymphoma with Histological Transformation to Diffuse Large B-cell Lymphoma (DLBCL)

 

Autologous hematopoietic stem cell transplantation or allogeneic hematopoietic stem cell transplantation is considered medically necessary for patients with follicular lymphoma with histological transformation to diffuse large B-cell lymphoma (DLBCL) with responsive disease (complete response [CR] or partial response [PR]) to prior chemotherapy. 

 

Autologous hematopoietic stem cell transplantation or allogeneic hematopoietic stem cell transplantation for patients with follicular lymphoma with histological transformation to diffuse large B-cell lymphoma (DLBCL) not meeting the above criteria is considered investigational. The evidence is insufficient in demonstrating improved net health outcomes.

 

Nodal Marginal Zone Lymphomas with Histological Transformation to Diffuse Large B-cell Lymphoma (DLBCL)

 

Autologous hematopoietic stem cell transplantation or allogeneic hematopoietic stem cell transplantation is considered medically necessary for patients with nodal marginal zone lymphomas with histological transformation to diffuse large B-cell lymphoma (DLBCL) with responsive disease (complete response [CR] or partial response [PR]) to prior chemotherapy. 

 

Autologous hematopoietic stem cell transplantation or allogeneic hematopoietic stem cell transplantation for patients with nodal marginal zone lymphomas with histological transformation to diffuse large B-cell lymphoma (DLBCL) not meeting the above criteria is considered investigational. The evidence is insufficient in demonstrating improved net health outcomes.

 

Mantle Cell Lymphoma
Autologous hematopoietic stem cell transplantation is considered medically necessary for patients with mantel cell lymphoma to consolidate a first complete remission (CR) following induction therapy.

 

Autologous hematopoietic stem cell transplantation is considered medically necessary for patients with indolent mantle cell lymphoma positive for TP53 mutation following induction therapy. 

 

Note: Indolent mantle cell lymphoma most common biomarker is SOX11-IGHV mutated. Typical clinical presentation: Leukemia non-nodal CLL-like with splenomegaly, low tumor burden, Ki-67 proliferation fraction <10%.

 

Allogeneic hematopoietic stem cell transplantation is considered medically necessary for patients with relapsed mantel cell lymphoma following autologous hematopoietic stem cell transplant using myeloablative or reduce intensity conditioning (non-myeloablative). 

 

Autologous and allogeneic hematopoietic stem cell transplantation is considered investigational for the treatment of mantel cell lymphoma not meeting the criteria above and for all other indications. The evidence is insufficient in demonstrating improved net health outcomes.

 

Diffuse Large B-Cell Lymphoma (DLBCL)
Autologous hematopoietic stem cell transplantation is considered medically necessary for patients with diffuse large B-cell lymphoma (DLBCL) as salvage therapy for patients who do not achieve a complete remission (CR) after first line treatment (induction therapy).

 

Autologous hematopoietic stem cell transplantation is considered medically necessary for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) responsive to second line therapy (complete response [CR] or partial response [PR]) as consolidation therapy

 

Allogeneic hematopoietic stem cell transplantation is considered medically necessary for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) with mobilization failure, persistent bone marrow involvement or lack of adequate response to second line therapy.

 

Autologous and allogeneic hematopoietic stem cell transplantation is considered investigational for the treatment of diffuse large B-cell lymphoma (DLBCL) not meeting the criteria above and for all other indications. The evidence is insufficient in demonstrating improved net health outcomes.

 

Notes
• Patients are not candidates for transplant with partial response (PR) to second line therapy or those with progressive or refractory disease to second line therapy (regardless of transplant eligibility) or those with disease relapse following high dose therapy autologous stem cell rescue or allogenic HCT should be managed with third-line systemic therapy, palliative ISRT or best supportive care. (NCCN Version 3.2021 B-Cell lymphomas)
• Patients with progressive disease after > 2 prior lines of systemic therapy regimens are unlikely to derive additional benefit from currently available systemic therapy options, except for patients who have experienced a long disease-free interval. (NCCN Version 3.2021 B-Cell lymphomas)
• Relapse #2 or greater (NCCN version 3.2021 B-Cell Lymphomas)
 Anti-CD19 CAR T-cell therapy (if not previously given); or 
 Clinical trial; or 
 Alternative second line therapy; or 
 Palliative ISRT; or 
 Best supportive care

 

Burkitt Lymphoma
Autologous hematopoietic stem cell transplantation or allogeneic hematopoietic stem cell transplantation is considered medically necessary for patients with relapsed Burkitt lymphoma responsive to second line therapy (complete response [CR] or partial response [PR]) as consolidation therapy 

 

Autologous and allogeneic hematopoietic stem cell transplantation is considered investigational for the treatment of Burkitt lymphoma not meeting the criteria above and for all other indications. The evidence is insufficient in demonstrating improved net health outcomes.

 

AIDS Related B-cell Lymphomas – Plasmablastic Lymphoma
Autologous hematopoietic stem cell transplantation is considered medically necessary in patients with AIDS related plasmablastic lymphoma in first complete remission (CR) in high- risk patients 

 

Note: High risk features include an age-adjusted IPI higher then 2, presence of MYC gene rearrangement, or TP53 gene deletion. HIV negative patients with plasmablastic lymphoma are generally considered to have higher risk disease. Optimization of HIV control with antiretroviral therapy is important.

 

Autologous hematopoietic stem cell transplantation is considered investigational for the treatment of AIDS related plasmablastic lymphoma not meeting the criteria above and for all other indications for AIDS related B-cell lymphomas. The evidence is insufficient in demonstrating improved net health outcomes.

 

Allogeneic hematopoietic stem cell transplantation is considered investigational for the treatment of AIDS related B-cell lymphomas. The evidence is insufficient in demonstrating improved net health outcomes.

 

Castleman’s Disease
Autologous hematopoietic stem cell transplantation is considered medically necessary for patients with Castleman’s Disease for the treatment of  refractory or progressive disease. 

 

Autologous hematopoietic stem cell transplantation is considered investigational for the treatment of Castleman’s Disease not meeting the criteria above and for all other indications. The evidence is insufficient in demonstrating improved net health outcomes.

 

Allogeneic hematopoietic stem cell transplantation is considered investigational for the treatment of Castleman’s Disease for all indications. The evidence is insufficient in demonstrating improved net health outcomes.

 

Reduced Intensity Conditioning (Non-Myeloablative) Allogeneic Stem Cell Transplantation

Reduced intensity conditioning (non-myeloablative) allogeneic hematopoietic stem cell transplantation is considered medically necessary for the treatment of non-Hodgkin lymphoma B-cell lymphomas in patients who meet the criteria for an allogeneic hematopoietic stem cell transplantation above but do not qualify for myeloablative allogeneic hematopoietic stem cell transplantation due to age or comorbidities.

 

Note: Reduced intensity conditioning regimens (non-myeloablative allogeneic transplantation) would be considered for individuals who would otherwise qualify for a myeloablative allogeneic hematopoietic stem cell transplantation but would not tolerate standard myeloablative conditioning regimen. This may include the following age typically > 60 years or comorbidities (e.g. liver or kidney dysfunction, generalized debilitation, prior intensive chemotherapy, low Karnofsky Performance Status score)

 

Autologous hematopoietic stem cell transplantation and allogeneic hematopoietic stem cell transplantation is considered investigational for the treatment of non-Hodgkin lymphoma B-cell lymphomas when the above criteira is not met and for all other indications. The evidence is insufficient in demonstrating improved net health outcomes.

 

Definitions
  • Aggressive NHL these types of non-Hodgkin’s lymphoma (NHL) may develop rapidly, and treatment is usually started immediately.
  • Chemosensitive relapse is defined as relapsed non-Hodgkin’s lymphoma that does not progress during or immediately after standard dose chemotherapy (i.e. achieve stable disease or a partial response).
  • Complete response (also known as complete remission) is the disappearance of all signs of cancer in response to treatment; this does not always mean the cancer has been cured.
  • Indolent cancer is a type of cancer that grows slowly.
  • Karnofsky Performance Status is a standard way of measuring the ability of individuals with cancer to perform ordinary tasks. The scores on the scale range from 0 to 100. A higher score means the individual is better able to carry out daily activities. The Karnofsky Performance Status may be used to determine an individual’s prognosis, to measure changes in an individual’s ability to function, or to decide whether an individual could be included in the clinical trial.
    • 100 – normal no complaints
    • 90 – able to carry on normal activities. Minor signs or symptoms of disease
    • 80 – normal activity with effort
    • 70 – care for self, unable to carry on normal activity or do active work
    • 60 – requires occasional assistance, but able to care for most of his or her needs
    • 50 – requires considerable assistance and frequent medical care
    • 40 – disabled requires special care and assistance
    • 30 – severely disabled, hospitalization indicated though death not imminent
    • 20 – very sick, hospitalization necessary, active supportive treatment necessary
    • 10 - moribund (approaching death, deepening stupor and coma
  • Myeloablative is a severe form of myelosuppression. Myelosuppression is a condition in which bone marrow activity is decreased, resulting in fewer red blood cells, white blood cells, and platelets. It is a side effect of some cancer treatments.
  • Non-myeloablative (also knowns as reduced intensity conditioning) is a bone marrow transplant in which the individual’s marrow is not completely destroyed prior to receiving the donor’s marrow or stem cells.
  • Salvage therapy is a treatment that is given after the cancer has not responded to other treatments i.e. refractory or relapsed disease. For patients with peripheral T-cell lymphomas, salvage therapy includes patients who do not achieve a complete response (e.g. achieve only a partial response, have no response or have progressive disease) with first-line induction chemotherapy (refractory disease) or who relapse after achieving a complete response with first-line induction chemotherapy. For mantel cell lymphoma, salvage therapy includes patients with progressive disease with first-line induction chemotherapy (refractory disease) or in patients who relapse after a complete response or partial response after initial induction chemotherapy, or patients who fail a previous autologous hematopoietic stem cell transplantation.
  • Transformation describes a lymphoma whose histologic pattern has evolved to a higher-grade lymphoma. Transformed lymphomas typically evolve from a nodular pattern to a diffuse pattern.

 

International Prognostic Index:
Low Risk = 0-1 points; Low Intermediate = 2 points; High Intermediate = 3 points; High Risk = 4-5 points.
0 Points for any of the following:
  • Age less than 60 years
  • Tumor stage I or II
  • Extranodal involvement (ENI) 0-1
  • Performance status (PS) Eastern Cooperative Oncology Group (ECOG) 0-1
  • Lactate dehydrogenase (LDH) normal
1 Point for presence of each
  • Age greater than 60 years
  • Tumor stage III or IV
  • Extranodal involvement (ENI) greater than 1
  • Performance status (PS) Eastern Cooperative Oncology Group (ECOG) 2-4
  • Lactate dehydrogenase (LDH) greater than normal
Eastern Cooperative Oncology Group (ECOG) Performance Status
  • 0 - Fully active able to carry on all pre-disease performance without restriction
  • 1 - Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature (e.g. light housework, office work)
  • 2 - Ambulatory and capable of all self-care, but unable to carry out any work activities. Up and about more than 50% of waking hours.
  • 3 - Capable of only limited self-care. Confined to bed or chair more than 50% of waking hours.
  • 4 - Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair.
  • 5 - Dead

 

*Extent of disease is determined by PET/CT for avid lymphomas, and CT for non-avid histologies.
**Whether II bulky is treated as limited or advanced disease may be determined by histology and a number of prognostic factors.
Non-Hodgkin Lymphoma Pediatric Aggressive Mature B-cell Lymphomas

Autologous Hematopoietic Stem Cell Transplantation or Allogeneic Hematopoietic Stem Cell Transplantation

 

Autologous hematopoietic stem cell transplantation or allogeneic hematopoietic stem cell transplantation is considered medically necessary for the treatment of pediatric aggressive non-Hodgkin Lymphoma (pediatric Burkitt lymphoma or pediatric diffuse large B-cell lymphomas) that is relapsed or refractory as consolidation therapy.

 

Notes:

  • NCCN defines pediatric as any patient age 18 years or younger.
  • There is no data to support autologous versus allogeneic HSCT; therefore, the decision to regarding transplant should be based on physician preference.

 

Autologous hematopoietic stem cell transplantation or allogeneic hematopoietic stem cell transplantation is considered investigational for the treatment of pediatric aggressive non-Hodgkin Lymphoma (pediatric Burkitt lymphoma or pediatric diffuse large B-cell lymphomas) when the above criteria is not met and for all other indications. The evidence is insufficient in demonstrating improved net health outcomes.

Non-Hodgkin Lymphoma Primary Cutaneous Lymphomas

The updated WHO-EORTC classification for cutaneous lymphoma in 2018 includes the most common subtypes of Primary Cutaneous Lymphomas:

  • Cutaneous B-cell Lymphomas
    • Primary cutaneous marginal zone lymphoma (PCMZL)
    • Primary cutaneous follicle center lymphoma (PCFCL); and
    • Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL, leg type)
  • Cutaneous T-cell Lymphomas
    • Mycosis fungoides (MF) and Sezary Syndrome (SS)
    • Primary cutaneous CD30+ T-cell lymphoproliferative disorders (PCTLD)

 

Autologous Hematopoietic Stem Cell Transplantation

 

Autologous hematopoietic stem cell transplantation is considered investigational for the treatment of primary cutaneous lymphomas for all indications. The evidence is insufficient in demonstrating improved net health outcomes.

 

Allogeneic Hematopoietic Stem Cell Transplantation

 

Allogeneic hematopoietic stem cell transplantation is considered medically necessary for patients with stage IIB-IV Mycosis fungoides (MF)/Sezary Syndrome (SS) disease that is refractory to multiple previous therapies.

 

Allogeneic hematopoietic stem cell transplantation is considered medically necessary for patients with large cell transformation (LCT) for the following indications:

  • Limited cutaneous lesions with large cell transformation (LCT) following primary treatment and with refractory disease; or
  • Generalized cutaneous lesions with large cell transformation (LCT) with relapsed disease following previous complete response (CR) or partial response (PR); or
  • Generalized cutaneous lesions with large cell transformation (LCT) with refractory disease to multiple previous therapies

 

Allogeneic hematopoietic stem cell transplantation is considered investigational for the treatment of primary cutaneous lymphomas for all indications. The evidence is insufficient in demonstrating improved net health outcomes.

 

Reduced Intensity Conditioning (Non-Myeloablative) Allogeneic Stem Cell Transplantation

Reduced intensity conditioning (non-myeloablative) allogeneic hematopoietic stem cell transplantation is considered medically necessary for the treatment of non-Hodgkin lymphoma primary cutaneous lymphomas in patients who meet the criteria for an allogeneic hematopoietic stem cell transplantation above but do not qualify for myeloablative allogeneic hematopoietic stem cell transplantation due to age or comorbidities.

 

Note: Reduced intensity conditioning regimens (non-myeloablative allogeneic transplantation) would be considered for individuals who would otherwise qualify for a myeloablative allogeneic hematopoietic stem cell transplantation but would not tolerate standard myeloablative conditioning regimen. This may include the following age typically > 60 years or comorbidities (e.g., liver or kidney dysfunction, generalized debilitation, prior intensive chemotherapy, low Karnofsky Performance Status score

 

Definitions

  • Karnofsky Performance Status is a standard way of measuring the ability of individuals with cancer to perform ordinary tasks. The scores on the scale range from 0 to 100. A higher score means the individual is better able to carry out daily activities. The Karnofsky Performance Status may be used to determine an individual’s prognosis, to measure changes in an individual’s ability to function, or to decide whether an individual could be included in the clinical trial.  
  • 100 – normal no complaints
  • 90 – able to carry on normal activities. Minor signs or symptoms of disease
  • 80 – normal activity with effort
  • 70 – care for self, unable to carry on normal activity or do active work
  • 60 – requires occasional assistance, but able to care for most of his or her needs
  • 50 – requires considerable assistance and frequent medical care
  • 40 – disabled requires special care and assistance
  • 30 – severely disabled, hospitalization indicated though death not imminent
  • 20 – very sick, hospitalization necessary, active supportive treatment necessary
  • 10 - moribund (approaching death, deepening stupor and coma)

 

Eastern Cooperative Oncology Group (ECOG) Performance Status

  • 0 - Fully active able to carry on all pre-disease performance without restriction
  • 1 - Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature (e.g., light housework, office work)
  • 2 - Ambulatory and capable of all self-care, but unable to carry out any work activities. Up and about more than 50% of waking hours.
  • 3 - Capable of only limited self-care. Confined to bed or chair more than 50% of waking hours.
  • 4 - Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair.
  • 5 - Dead

 

  • Myeloablative is a severe form of myelosuppression. Myelosuppression is a condition in which bone marrow activity is decreased, resulting in fewer red blood cells, white blood cells, and platelets. It is a side effect of some cancer treatments.
  • Non-myeloablative (also knowns as reduced intensity conditioning) is a bone marrow transplant in which the individual’s marrow is not completely destroyed prior to receiving the donor’s marrow or stem cells.
  • Transformation describes a lymphoma whose histologic pattern has evolved to a higher-grade lymphoma. Transformed lymphomas typically evolve from a nodular pattern to a diffuse pattern.

Non-Hodgkin Lymphoma – T-Cell Lymphomas

Non-Hodgkin’s lymphoma are a heterogenous group of lymphoproliferative disorders originating in B-lymphocytes, T-lymphocytes, or natural killer (NK) cells

 

 Peripheral T-cell Lymphoma Subtypes Include:

  • Peripheral T-Cell lymphoma (PTCL), NOS;
  • Angioimmunoblastic T-Cell Lymphoma (AITL);
  • Anaplastic Large Cell Lymphoma (ALCL), anaplastic lymphoma kinase (ALK) positive;
  • ALCL, ALK Negative;
  • Enteropathy-Associated T-Cell Lymphoma (EATL);
  • Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma (MEITL);
  • Nodal Peripheral T-Cell Lymphoma with TFH Phenotype (PTCL,TFH);
  • Follicular T-Cell Lymphoma (FTCL)

 

Subtypes not included in Peripheral T-cell Lymphoma:

  • Primary cutaneous ALCL;
  • All other T-cell lymphomas:
  • T-cell large granular lymphocytic leukemia;
  • Adult T-cell leukemia/lymphoma;
  • T-cell prolymphocytic leukemia;
  • Extranodal NK/T-cell lymphoma, nasal type; Hepatosplenic T-cell lymphoma

 

Autologous Hematopoietic Stem Cell Transplantation for Primary T-Cell Lymphomas

Autologous hematopoietic stem cell transplantation is considered medically necessary for patients with stage I-IV peripheral T-cell lymphomas indicated below when end of treatment response results in a complete response (CR)  (i.e. PET negative):

 

  • Peripheral T-Cell lymphoma (PTCL), NOS
  • Angioimmunoblastic T-Cell Lymphoma (AITL)
  • Anaplastic Large Cell Lymphoma (ALCL), anaplastic lymphoma kinase (ALK) positive
  • Anaplastic Large Cell Lymphoma (ALCL), ALK Negative
  • Enteropathy-Associated T-Cell Lymphoma (EATL)
  • Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma (MEITL)
  • Nodal Peripheral T-Cell Lymphoma with TFH Phenotype (PTCL,TFH); Follicular T-Cell Lymphoma (FTCL)

 

Autologous hematopoietic stem cell transplantation is considered medically necessary for patients with stage I-IV peripheral T-cell lymphomas indicated below for the treatment of refractory or relapsed disease following second line therapy with complete response (CR) or partial response (PR) as consolidation therapy:

 

  • Peripheral T-Cell lymphoma (PTCL), NOS
  • Angioimmunoblastic T-Cell Lymphoma (AITL)
  • Anaplastic Large Cell Lymphoma (ALCL), anaplastic lymphoma kinase (ALK) positive
  • Anaplastic Large Cell Lymphoma (ALCL), ALK Negative
  • Enteropathy-Associated T-Cell Lymphoma (EATL)
  • Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma (MEITL)
  • Nodal Peripheral T-Cell Lymphoma with TFH Phenotype (PTCL,TFH); Follicular T-Cell Lymphoma (FTCL)

 

 Allogeneic Hematopoietic Stem Cell Transplantation for Primary T-Cell Lymphomas

 

Allogeneic hematopoietic stem cell transplantation is considered medically necessary for patients with stage I-IV peripheral T-cell lymphomas indicated below for the treatment of refractory or relapsed disease following second line therapy with complete response (CR) or partial response (PR) as consolidation therapy: 

  • Peripheral T-Cell lymphoma (PTCL), NOS
  • Angioimmunoblastic T-Cell Lymphoma (AITL)
  • Anaplastic Large Cell Lymphoma (ALCL), anaplastic lymphoma kinase (ALK) positive
  • Anaplastic Large Cell Lymphoma (ALCL), ALK Negative
  • Enteropathy-Associated T-Cell Lymphoma (EATL)
  • Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma (MEITL)
  • Nodal Peripheral T-Cell Lymphoma with TFH Phenotype (PTCL,TFH); Follicular T-Cell Lymphoma (FTCL)

 

Autologous hematopoietic stem cell transplantation and allogeneic hematopoietic stem cell transplantation for patients with peripheral T-cell lymphomas is considered investigational not meeting the above criteria and for all other indications. The evidence is insufficient in demonstrating improved net health outcomes.

 

Adult T-cell Leukemia/Lymphoma

 

Autologous Hematopoietic Stem Cell Transplantation

Autologous hematopoietic stem cell transplantation is considered investigational for the treatment of adult T-cell leukemia/lymphoma for all indications. The evidence is insufficient in demonstrating improved net health outcomes.

 

Allogeneic Hematopoietic Stem Cell Transplantation

Allogeneic hematopoietic stem cell transplantation is considered medically necessary for the treatment of acute adult T-cell leukemia or lymphoma with response after 2 cycles of first line therapy.

 

Allogeneic hematopoietic stem cell transplantation is considered medically necessary for the treatment of adult T-cell lymphoma for a patient with no response to first line therapy but responds to second line therapy.

 

Allogeneic hematopoietic stem cell transplantation is considered investigational for the treatment of adult T-cell leukemia/lymphoma not meeting the above criteria and for all indications. The evidence is insufficient in demonstrating improved net health outcomes.

 

T-cell Prolymphocytic Leukemia

 

Autologous Hematopoietic Stem Cell Transplantation

Autologous hematopoietic stem cell transplantation is considered medically necessary for the treatment of T-cell prolymphocytic leukemia when there is not a suitable donor available for allogeneic hematopoietic stem cell transplantation and patient has had a complete response (CR) or partial response (PR) to first line therapy.

 

Allogeneic Hematopoietic Stem Cell Transplantation

Allogeneic hematopoietic stem cell transplantation is considered medically necessary for the treatment of T-cell prolymphocytic leukemia for patients with complete response (CR) or partial response (PR) to first line therapy.

 

Autologous hematopoietic stem cell transplantation and allogeneic hematopoietic stem cell transplantation for patients with T-cell prolymphocytic leukemia is considered investigational not meeting the above criteria and for all other indications. The evidence is insufficient in demonstrating improved net health outcomes.

 

Extranodal NK/T-Cell Lymphoma, Nasal Type

 

Autologous and Allogeneic Hematopoietic Stem Cell Transplantation

Autologous hematopoietic stem cell transplantation and allogeneic hematopoietic stem cell transplantation is considered medically necessary for the treatment of extranodal NK/T-cell lymphoma nasal type stage IV or extranasal disease stage I-IV for the following indications:

  • Achieving complete response (CR) and biopsy negative following induction therapy; or
  • Achieving a partial response (PR) and biopsy negative following induction therapy; or 
  • In patients with a partial response (PR) and biopsy positive following induction therapy and receive additional therapy and achieve a partial response (PR)

 

Note: Per current NCCN guidelines there is no clear data to suggest whether allogeneic or autologous HCT is preferred, and treatment should be individualized.

 

Relapsed or Refractory Nasal or Extranasal Disease

 

Autologous Hematopoietic Stem Cell Transplantation

Autologous hematopoietic stem cell transplantation for patients with relapsed or refractory extranodal nasal NK/T-cell lymphoma disease following pembrolizuman is considered medically necessary when here is no suitable allogeneic donor available.

 

Autologous hematopoietic stem cell transplantation for patients with relapsed or refractory extranasal disease following asparaginase-based regimens is considered medically necessary when here is no suitable allogeneic donor available.

 

Autologous hematopoietic stem cell transplantation for patients with extranodal NK/T-cell lymphoma, nasal type is considered investigational not meeting the above criteria and for all other indications. The evidence is insufficient in demonstrating improved net health outcomes.

 

Allogeneic Hematopoietic Stem Cell Transplantation

Allogeneic hematopoietic stem cell transplantation for patients with relapsed or refractory extranodal nasal NK/T-cell lymphoma disease following pembrolizuman is considered medically necessary.

 

Allogeneic hematopoietic stem cell transplantation for patients with relapsed or refractory extranasal disease following asparaginase-based regimens is considered medically necessary.

 

Allogeneic hematopoietic stem cell transplantation for patients with extranodal  NK/T-cell lymphoma, nasal type is considered investigational not meeting the above criteria and for all other indications. The evidence is insufficient in demonstrating improved net health outcomes.

 

Hepatosplenic T-cell Lymphoma

 Autologous hematopoietic stem cell transplantation is considered medically necessary for the treatment of hepatosplenic T-cell lymphoma when there is not a suitable donor available for allogeneic hematopoietic stem cell transplantation and patient has had a complete response (CR) or partial response (PR) to first line therapy.

 

Allogeneic hematopoietic stem cell transplantation is considered medically necessary for the treatment of hepatosplenic T-cell lymphoma for patients with complete response (CR) or partial response (PR) to first line therapy.

 

Autologous hematopoietic stem cell transplantation and allogeneic hematopoietic stem cell transplantation for patients with hepatosplenic T-cell lymphoma is considered investigational for all other indications to include when the criteria above is not met. The evidence is insufficient in demonstrating improved net health outcomes.

 

All Other Non-Hodgkin Lymphoma – T-Cell Lymphomas

 

Autologous hematopoietic stem cell transplantation and allogeneic hematopoietic stem cell transplantation for patients for the treatment of T-cell lymphomas not included above as medically necessary is considered investigational for all indications. The evidence is insufficient in demonstrating improved net health outcomes.

 

Reduced Intensity Conditioning (Non-Myeloablative) Allogeneic Stem Cell Transplantation

Reduced intensity conditioning (non-myeloablative) allogeneic hematopoietic stem cell transplantation is considered medically necessary for the treatment of non-Hodgkin lymphoma/T-cell lymphomas in patients who meet the criteria for an allogeneic hematopoietic stem cell transplantation above but do not qualify for myeloablative allogeneic hematopoietic stem cell transplantation due to age or comorbidities.

 

Note: Reduced intensity conditioning regimens (non-myeloablative allogeneic transplantation) would be considered for individuals who would otherwise qualify for a myeloablative allogeneic hematopoietic stem cell transplantation but would not tolerate standard myeloablative conditioning regimen. This may include the following age typically > 60 years or comorbidities (e.g., liver or kidney dysfunction, generalized debilitation, prior intensive chemotherapy, low Karnofsky Performance Status score

 

Definitions

  • Karnofsky Performance Status is a standard way of measuring the ability of individuals with cancer to perform ordinary tasks. The scores on the scale range from 0 to 100. A higher score means the individual is better able to carry out daily activities. The Karnofsky Performance Status may be used to determine an individual’s prognosis, to measure changes in an individual’s ability to function, or to decide whether an individual could be included in the clinical trial. 
  • 100 – normal no complaints
  • 90 – able to carry on normal activities. Minor signs or symptoms of disease
  • 80 – normal activity with effort
  • 70 – care for self, unable to carry on normal activity or do active work
  • 60 – requires occasional assistance, but able to care for most of his or her needs
  • 50 – requires considerable assistance and frequent medical care
  • 40 – disabled requires special care and assistance
  • 30 – severely disabled, hospitalization indicated though death not imminent
  • 20 – very sick, hospitalization necessary, active supportive treatment necessary
  • 10 - moribund (approaching death, deepening stupor and coma)

 

Eastern Cooperative Oncology Group (ECOG) Performance Status

  • 0 - Fully active able to carry on all pre-disease performance without restriction
  • 1 - Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature (e.g. light housework, office work)
  • 2 - Ambulatory and capable of all self-care, but unable to carry out any work activities. Up and about more than 50% of waking hours.
  • 3 - Capable of only limited self-care. Confined to bed or chair more than 50% of waking hours.
  • 4 - Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair.
  • 5 - Dead 
  • Myeloablative is a severe form of myelosuppression. Myelosuppression is a condition in which bone marrow activity is decreased, resulting in fewer red blood cells, white blood cells, and platelets. It is a side effect of some cancer treatments.
  • Non-myeloablative (also knowns as reduced intensity conditioning) is a bone marrow transplant in which the individual’s marrow is not completely destroyed prior to receiving the donor’s marrow or stem cells.
POEMS Syndrome (Polyneuropathy, Organmegaly, Endocrinopathy, Monoclonal Gammopathy and Skin Abnormalities)

Autologous Hematopoietic Stem Cell Transplantation

Autologous hematopoietic stem cell transplantation is considered medically necessary for the treatment of disseminated POEMS syndrome.

 

Note: Patients with disseminated POEMS syndrome may have diffuse sclerotic lesions or disseminated bone marrow involvement.

 

Autologous hematopoietic stem cell transplantation is considered investigational not meeting the above criteria and for all other indications except as indicated above. The evidence is insufficient in demonstrating improved net health outcomes.

 

*Tandem autologous hematopoietic stem cell transplantation is considered investigational for the treatment of POEMS syndrome. The evidence is insufficient in demonstrating improved net health outcomes.

 

*Tandem transplantation refers to a planned infusion (transplant) of previously harvested hematopoietic stem cells with a repeat hematopoietic stem cell infusion (transplant) that is performed within 6 months of the initial transplant. This is distinguished from a repeat transplantation requested or performed more than 6 months after the first transplant and is used as salvage therapy after failure of initial transplantation or relapsed disease. 

Allogeneic Hematopoietic Stem Cell Transplantation

Allogeneic hematopoietic stem cell transplantation is considered investigational for the treatment of POEMS syndrome. The evidence is insufficient in demonstrating improved net health outcomes.
Systemic Mastocytosis

Autologous Hematopoietic Stem Cell Transplantation

Autologous hematopoietic stem cell transplantation is considered investigational for the treatment of any subtype of systemic mastocytosis. The evidence is insufficient in demonstrating improved net health outcomes.

 

Allogeneic Hematopoietic Stem Cell Transplantation

Allogeneic hematopoietic stem cell transplantation is considered medically necessary for the treatment of aggressive systemic mastocytosis (ASM) as a first line treatment when ALL of the following criteria are met:
  • Patient ≤ 60 years of age; and
  • The patient meets the diagnostic criteria for systemic mastocytosis below; and
  • The patient has one or more “C-finding” per WHO Criteria below; or
  • Eligible organ damage finding per IWG-MRT-ECNM criteria below; and
  • Does not meet the criteria for mast cell leukemia below.

 

Allogeneic hematopoietic stem cell transplantation is considered medically necessary for the treatment of systemic mastocytosis with an associated hematologic neoplasm (SM-AHN) when ALL of the following criteria are met:
  • Patient ≤ 60 years of age; and
  • The patient meets the diagnostic criteria for systemic mastocytosis below; and
  • Systemic mastocytosis (SM) component is requiring more immediate treatment (e.g., 1 or more “C Findings” below); and
  • There is also progression of AHN (associated hematologic neoplasm) (i.e., myelodysplastic syndrome, myeloproliferative neoplasm, acute myeloid leukemia, lymphoma) requiring treatment.

 

Allogeneic hematopoietic stem cell transplantation is considered medically necessary for the treatment of acute mast cell leukemia (MCL) when ALL of the following criteria are met:
  • Patient ≤ 60 years of age; and
  • The patient meets the diagnostic criteria for systemic mastocytosis below; and
  • Bone marrow biopsy shows diffuse infiltration (usually dense) by atypical immature mast cells; and
  • Bone marrow aspirate smears show ≥ 20% mast cells; and
  • The patient has one or more “C-findings” per WHO Criteria below due to mast cell infiltration.

 

Allogeneic hematopoietic stem cell transplantation is considered investigational when the above criteria is not met and for all other indications. The evidence is insufficient in demonstrating improved net health outcomes.

 

2017 WHO Diagnostic Criteria for Cutaneous and Systemic Mastocytosis

Systemic Mastocytosis (SM)
The diagnosis of SM can be made when the major criterion and at least one minor criterion are present, or when three or more minor criteria are present.

 

Major Criterion:
Multifocal, dense infiltrates of mast cells (≥ 15 mast cells in aggregates) detected in sections of bone marrow and/or other extracutaneous organ(s).

 

Minor Criteria:
  • In biopsy sections of bone marrow or other extracutaneous organs, > 25% of the mast cells in the infiltrate are spindle-shaped or have atypical morphology of > 25% of all mast cells in bone marrow aspirate smears, are immature or atypical.
  • Detection of an activating point mutation at codon 816 of KIT in the bone marrow, blood, or another extracutaneous organ.
  • Mast cells in bone marrow, blood or other extracutaneous organs express CD25, with or without CD2, in addition to normal mast cell markers.
  • Serum total tryptase persistently > 20 ng/ml (unless there is an associated myeloid neoplasm, in which case this parameter is not valid).

 

Systemic Mastocytosis with an Associated Hematological Neoplasm
  • Meets the general criteria for systemic mastocytosis
  • Meets the criteria for an associated hematologic neoplasm (i.e., a myelodysplastic syndrome, myeloproliferative neoplasm, acute myeloid leukemia, lymphoma or another hematological neoplasm classified as a distinct entity in the WHO classification)

 

Aggressive Systemic Mastocytosis
  • Meets the general criteria for systemic mastocytosis
  • ≥ 1 C finding
  • Does not meet the criteria for mast cell leukemia
  • Skin lesions are usually absent

 

Mast Cell Leukemia
  • Meets the general criteria for systemic mastocytosis
  • Bone marrow biopsy shows diffuse infiltration (usually dense) by atypical, immature mast cells
  • Bone marrow aspirate smears show ≥ 20% mast cells
  • In classic cases, mast cells account for ≥ 10% of the peripheral blood white blood cells, but the aleukaemic variant (in which mast cells account for < 10% is more common)
  • Skin lesions are usually absent

 

World Health Organization (WHO) Criteria for B-Findings and C-Findings in Patients with Systemic Mastocytosis (SM)
B-Findings: Indicate a high burden of mast cells (MCs) and expansion of the neoplastic process into multiple hematopoietic lineages, without evidence of organ damage
  • High mast cells burden (shown on bone marrow biopsy): > 30% infiltration of cellularity by mast cells and (focal dense aggregates) AND serum total tryptase > 200 ng/ml
  • Signs of dysplasia or myeloproliferation in non-mast cell lineage(s), but criteria are not met for definitive diagnosis of an associated hematological neoplasm, with a normal or only slightly abnormal blood counts
  • Hepatomegaly without impairment of liver function, palpable splenomegaly without hyperslenism, and/or lymphadenopathy on palpation or imaging.
C-Findings: Are indicative of organ damage produced by MC infiltration (should be confirmed by biopsy if possible)
  • Bone marrow dysfunction caused by neoplastic mast cell infiltration, manifested by ≥ 1 cytopenia; absolute neutrophil count < 1.0 x109/L, hemoglobin level <10 g/dl, and/or platelet count < 100 x 109/L
  • Palpable hepatomegaly with impairment of liver function, ascites, and/or portal hypertension
  • Skeletal involvement, with large osteolytic lesions with or without pathologic fractures (pathologic fractures caused by osteoporosis do not qualify as a C finding)
  • Palpable splenomegaly with hypersplenism
  • Malabsorption with weight loss due to gastrointestinal mast cell infiltrates

 

 

Waldenstrom Macroglobulinemia

Autologous Hematopoietic Stem Cell Transplantation

Autologous hematopoietic stem cell transplantation is considered medically necessary for salvage therapy for chemosensitive Waldenstrom macroglobulinemia.

 

Autologous hematopoietic stem cell transplantation is considered investigational when the above criteria is not met and for all other indications. The evidence is insufficient in demonstrating improved net health outcomes.

 

Allogeneic Hematopoietic Stem Cell Transplantation

Allogeneic hematopoietic stem cell transplantation is considered investigational for the treatment to treat Waldenstrom macroglobulinemia for all indications. The evidence is insufficient in demonstrating improved net health outcomes.

 

Definitions

Salvage therapy is treatment that is given after the cancer has not responded to other treatments.

 

Umbilical Cord Blood

The collection and storage of cord blood stem cells from a newborn may be considered medically necessary when an allogeneic hematopoietic stem cell transplantation is imminent in an identified recipient with a condition that is medically appropriate for allogeneic hematopoietic stem cell transplantation.

 

For patients who do not have a hematopoietic stem cell donor, transplantation of cord blood stem cells from a related or unrelated donor is considered medically necessary if the patient meets the medical necessity criteria outlined above for both the medical condition and allogeneic hematopoietic stem cell transplantation.

 

Prophylactic collection and storage of cord blood stem cells for future allogeneic or autologous hematopoietic stem cell transplantation is considered not medically necessary when proposed for an unspecified future use as an autologous hematopoietic stem cell transplantation in the original donor, or in a related or unrelated donor for allogeneic hematopoietic stem cell transplantation.

 

Transplantation of cord blood stem cells from related or unrelated donors in all other situations is considered investigational because the safety and/or efficacy cannot be established by review of the available peer reviewed medical literature.

 

Syngeneic Transplantation

Syngeneic hematopoietic stem cell transplantation (transplantation between identical twins) is considered medically necessary when the patient’s condition meets the medical necessity criteria outlined above for allogeneic hematopoietic stem cell transplantation.

 

Haploidentical Transplantation

Haploidentical hematopoietic stem transplantation is considered medically necessary when ALL of the following criteria is met:

  • The patient’s condition meets the medical necessity criteria outlined above for an allogeneic hematopoietic stem cell transplantation and there is an urgent need for transplant; AND
  • There is not a fully HLA matched sibling available (6/6 HLA match); AND
  • The unrelated donor search does not identify an alternative donor source i.e. a low likelihood of finding an eight- of- eight- allele matched unrelated donor; AND
  • The HLA-haploidentical donor is one of the following: a biological parent, a biological child or a full or half sibling.

 

Policy Guidelines

Note: If for any reason the below information is factored into the medical review decision and the patient meets the medical necessity criteria above for an autologous or allogeneic hematopoietic stem cell transplantation, but the patient does not meet one or more of the criteria as it relates to the below information this would result in the proposed autologous or allogeneic hematopoietic stem cell transplant being not medically necessary.

 

The following factors may be considered as part of the patient’s eligibility for the proposed transplant subject to the judgement of the transplant center:

  • Karnofsky score ≥ 70, Eastern Cooperative Oncology Group (ECOG) 0-2 or for pediatric patients 16 years or less Lansky Score ≥ 50% 
  • No active infection or infection treated
  • No pulmonary insufficiency
  • No drug or alcohol misuse by history or drug and alcohol free period ≥ 4 weeks
  • Patient understands procedural risk and post procedure compliance of follow-up
  • Patient has adequate social and family support
      

Notes:

  • Karnofsky Performance Status Score is a standard way of measuring the ability of individuals with cancer to perform ordinary tasks. The scores on the scale range from 0 to 100. A higher score means the individual is better able to carry out daily activities. The Karnofsky Performance Status may be used to determine an individua’ls prognosis, to measure changes in an individual’s ability to function, or to decide whether an individual could be included in a clinical trial
    • 100 – normal no complaints
    • 90 – able to carry on normal activities. Minor signs or symptoms of disease
    • 80 – normal activity with effort
    • 70 – care for self, unable to carry on normal activity or do active work
    • 60 – requires occasional assistance, but able to care for most of his or her needs
    • 50 – requires considerable assistance and frequent medical care
    • 40 – disabled requires special care and assistance
    • 30 – severely disabled, hospitalization indicated though death not imminent
    • 20 – very sick, hospitalization necessary, active supportive treatment necessary
    • 10 - moribund  (approaching death, deepening stupor and coma) 
  • Eastern Cooperative Oncology Group (ECOG) status
    • 0- fully active, able to carry on all pre-disease performance without restriction
    • 1 – restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature e.g. light house work, office work
    • 2 – ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours
    • 3 – capable of only limited selfcare, confined to bed or chair more than 50% of waking hours
    • 4 – Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair
  • Lansky Score
    • The Lansky Performance Scale is used to assess performance status of patients under 16 years old. The scale ranges from 0% to 100% representing patients with no evidence of disease; 0% is allocated if the patient is dead. A status score of 50% denotes those patients that are able to dress themselves but not be able to actively play. They may be able to participate in quiet activities. Patients with an irreversible score less than 50% generally have a poor prognosis
  • Prior to transplantation, all active infections should be treated. Fungal infections often require long-term treatment, however, stem cell transplantation may be appropriate under the guidance of infectious disease specialist if the infection is responding to treatment.
  • Pulmonary insufficiency (abnormal lung function) is a risk factor for poor outcomes following hematopoietic stem cell transplantation
    • Pulmonary insufficiency as evidenced by either forced expiratory volume in one second (FEV1) or diffusing capacity of the lung for carbon monoxide (DLCO) ≤ 50% of predicted value (when applicable DLCO is corrected for hemoglobin level).
      • A left ventricular shortening fraction considered in the normal range at the ordering institution may be substituted in the pediatric population.
      • Pulmonary function tests are generally not performed in the pediatric population given the difficulty in cooperating with the test. Provided the child has an adequate oxygen saturation on room air, a transplant program would consider the child eligible as far as lung function is concerned.    
  • A psychosocial evaluation assesses the ability of the patient and his or her support system to cope and adhere to the treatment plan. A psychiatric or substance abuse disorder warrants further evaluation and follow-up.
  • The benefits and potential risks associated with transplantation should be fully explained to patients both verbally and in writing. Patients need to understand the importance of adherence to treatment protocols and follow-up appointments.

 

 

Procedure Codes and Billing Guidelines:

To report provider services, use appropriate CPT* codes, Alpha Numeric (HCPCS level 2) codes, Revenue codes and / or diagnosis codes.

  • 38240 Hematopoietic progenitor cell (HPC); allogeneic transplantation per donor
  • 38241 Hematopoietic progenitor cell (HPC); autologous transplantation

 

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  • Lazarus HM, Stiff PJ, Carreras J, et al. Utility of single versus tandem autotransplants for advanced testes/germ cell cancer: a center for international blood and marrow transplant research (CIBMTR) analysis. Biol Blood Marrow Transplant. Jul 2007;13(7):778-789. PMID 17580256
  • Einhorn LH, Williams SD, Chamness A, et al. High-dose chemotherapy and stem-cell rescue for metastatic germ-cell tumors. N Engl J Med. Jul 26 2007;357(4):340-348. PMID 17652649
  • Suleiman Y, Siddiqui BK, Brames MJ, et al. Salvage therapy with high-dose chemotherapy and peripheral blood stem cell transplant in patients with primary mediastinal nonseminomatous germ cell tumors. Biol Blood Marrow Transplant. Jan 2013;19(1):161-163. PMID 22892555
  • Burt RK, Balabanov R, Burman J, et. al. Effect of nonmyeloablative hematopoietic stem cell transplantation vs continued disease modifying therapy on disease progression in patients with relapsing-remitting multiple sclerosis. JAMA 2019;321(2):165-174
  • Optum Transplant Review Guidelines Hematopoietic Stem Cell Transplantation. Effective July 1, 2019
  • Mancusi A, Ruggeri L, Velardi A. Hapolidentical hematopoietic transplantation for the cure of leukemia: from its biology to clinical translation. Blood 2016 128: 2616-2623
  • Ciurea S, Cao K, Fernandez-Vina M,e t. al. The European Society for Blood and Marrow Transplantation (EBMT) Consensus Guidelines for the Detection and Treatment o Donor-Specific Anti-HLA Antibodies (DSA) in Haploidentical Hematopoietic Cell Transplantation. Bone Marrow Transplantation
  • UpToDate. HLA-Haploidentical Hematopoietic Cell Transplantation. Ephraim J. Fuchs M.D., MBA, Leo Luznik M.D., Topic last updated July 2, 2019.
  • Bishop MR, Logan BR Long term outcomes of adults with acute lymphoblastic leukemia after autologous or unrelated donor bone marrow transplant. Bone Marrow Transplantation 2008 Apr 41(7) 635-642
  • Burt RK, Balabanov R, Burman J, Sharrack B, Snowden JA, et al. Effect of Nonmyeloablative Hematopoietic Stem Cell Transplantation vs Continued Disease-Modifying Therapy on Disease Progression in Patients With Relapsing-Remitting Multiple Sclerosis: A Randomized Clinical Trial. JAMA. 2019 Jan 15;321(2):165-174
  • Cohen JA, Baldassari LE, Atkins HL, Bowen JD, Bredeson C, et al. Autologous Hematopoietic Cell Transplantation for Treatment-Refractory Relapsing Multiple Sclerosis: Position Statement from the American Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2019 May;25(5):845-854
  • Dunn-Pirio AM, Heyman BM, Kaufman DS, Kinkel RP. Outcomes and Cost-Effectiveness of Autologous Hematopoietic Cell Transplant for Multiple Sclerosis. Curr Treat Options Neurol. 2019 Oct 17;21(10):53. Review PMID 31624926
  • Ge F, Lin H, Li Z, Chang T. Efficacy and safety of autologous hematopoietic stem-cell transplantation in multiple sclerosis: a systematic review and meta-analysis. Neurol Sci. 2019 Mar;40(3):479-487 PMID 30535563
  • Moore JJ, Massey JC, Ford CD, Khoo ML, Zaunders JJ, et al. Prospective phase II clinical trial of autologous haematopoietic stem cell transplant for treatment refractory multiple sclerosis. J Neurol Neurosurg Psychiatry. 2019 May;90(5):514-521. Epub 2018 Dec 11. PMID 30538138
  • Sharrack B, Saccardi R, Alexander T, European Society for Blood and Marrow Transplantation (EBMT) Autoimmune Diseases Working Party (ADWP) and the Joint Accreditation Committee of the International Society for Cellular Therapy (ISCT) and EBMT (JACIE), et al. Autologous haematopoietic stem cell transplantation and other cellular therapy in multiple sclerosis and immune-mediated neurological diseases: updated guidelines and recommendations from the EBMT Autoimmune Diseases Working Party (ADWP) and the Joint Accreditation Committee of EBMT and ISCT (JACIE). Bone Marrow Transplant. 2019 Sep 26. [Epub ahead of print] PMID 31558790
  • Sullivan KM, Majhail NS, Bredeson C, Carpenter PA, Chatterjee S, et al. Systemic Sclerosis as an Indication for Autologous Hematopoietic Cell Transplantation: Position Statement from the American Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2018 Oct;24(10):1961-1964. PMID 29953945
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  • Fish JD  et. al. Stem cell transplantation for neuroblastoma Bone Marrow Transplant. 2008 Jan; 41(2): 159–165.
  • Witoweksi L, Goudie C, Ramos P, et. al. The influence of clinical and genetic factors on patient outcomes in small cell carcinoma of the ovary, hypercalcemic type. Gyneol Oncol 2016 June; 141(3): 454-460
  • Final Diagnosis – Small Cell Carcinoma of the Ovary, Hypercalcemic Type
  • Bingjian Lu, Shi H. An In-Depth Look at Small Cell Carcinoma of the Ovary, Hypercalcemic Type (SCCOHT): Clinical Implications from Recent Molecular Findings. Journal of Cancer 2019;10(1):223-237
  • Pautier P, Ribrag V, Duvillard P, et. al. Results of a prospective dose-intensive regiment in 27 patients with small call carcinoma of the ovary of the hypercalcemic type. Annals of Oncology 18:1985-1989 2007
  • International Working Grouping (IWG) Response Criteria for MDS
  • Lu B, Shi H, An in-depth look at small cell carcinoma of the ovary, hypercalcemic type (SCCOHT): Clinical implications from recent molecular findings. Journal of Cancer 2019; 10(1):223-237
  • Pautier P, Ribrag V, Duvillard P, et. al. Results of a prospective dose-intensive regimen in 27 patitns with small cell carcinoma of the ovary of the hypercalcemic type. Annals of Oncology 18: August 2007
  • Witkowski L, Goudle C, Ramos P, et. al. The influence of clinical and genetic factros on patient outcome in small cell carcinoma o fhte ovaray, hypercalcemic type. Gynecol Oncol 2016 June; 141(3):454-460
  • Final Diagnosis – Small Cell Carcinoma of the Ovary, Hypercalcemic Type

 

Policy History:

  • April 2021 - Annual Review, Policy Revised
  • November 2020 - Interim Review, Policy Revised
  • August 2020 - Interim Review, Policy Revised
  • July 2020 - Interim Review, Policy Revised
  • April 2020 - Annual Review, Policy Revised
  • September 2019 - Interim Review, Policy Revised
  • July 2019 - Interim Review, Policy Revised
  • April 2019 - Annual Review, Policy Revised
  • April 2018 - New Medical Policy Created

Wellmark medical policies address the complex issue of technology assessment of new and emerging treatments, devices, drugs, etc.   They are developed to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. Wellmark medical policies contain only a partial, general description of plan or program benefits and do not constitute a contract. Wellmark does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Wellmark or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. Our medical policies may be updated and therefore are subject to change without notice.

 

*CPT® is a registered trademark of the American Medical Association.