Autologous Hematopoietic Stem Cell Transplant*

Medical Policy: 08.01.03 
Original Effective Date: March 2004 
Reviewed: October 2011 
Revised: October 2011 

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: 

Hematopoietic stem cell transplant (HSCT) refers to a procedure in which hematopoietic stem cells are infused to restore stem cell function in patients who receive bone marrow –toxic doses of cytotoxic drugs, with or without whole-body radiation therapy. In an autologous HSCT, stem cells are obtained from the patient. The success of autologous HSCT is predicated on the ability of the cytotoxic chemotherapy with or without radiation to eradicate cancerous cells from the blood and bone marrow. This permits subsequent engraftment and repopulation of bone marrow space with presumably normal hematopoietic stem cells obtained from the patient prior to undergoing bone marrow ablation. As a consequence, autologous HSCT is typically performed as consolidation therapy when the patient’s disease is in complete remission. Patients who undergo autologous HSCT are susceptible to chemotherapy-related toxicities and opportunistic infections prior to engraftment. Because immunologic compatibility between infused hematopoietic stem cells and the recipient is not an issue, patients undergoing autologous HSCT do not experience graft-versus-host disease.

Top

Prior Approval: 

Prior approval is recommended. Submit a prior approval now.

Top

Policy: 

Autologous hematopoietic stem cell transplant, in conjunction with a myeloablative conditioning regimen consisting of chemotherapy with or without total body irradiation, may be considered medically necessary for the following indications:

Acute Lymphoblastic Leukemia (ALL)

• Adults and children in first complete remission at high risk of relapse
• Adults and children in second or greater remission
• Adults and children with relapsed or refractory ALL

Several risk stratification schema exist, but, in general, the following findings help define children at high risk of relapse:

• Poor response to initial therapy including poor response to prednisone prophase defined as an absolute blast count of 1000/µL or greater, or poor treatment response to induction therapy at 6 weeks with high risk having ≥1% minimal residual disease measured by flow cytometry
• All children with T-cell phenotype
• Patients with either the t(9;22) or t(4;11) regardless of early response measures

Risk factors for relapse are less well-defined in adults, but a patient with any of the following may be considered at high risk for relapse:

• Age greater than 35 years
• Leukocytosis at presentation of >30,000/µ/L (B-cell lineage) and >100,000/µ/L (T-cell lineage)
• “Poor prognosis” genetic abnormalities like the Philadelphia chromosome (t(9;22))
• Extramedullary disease
• Time to attain complete remission longer than 4 weeks

Acute Myelogenous Leukemia (AML)

• AML in any stage for patients who have not had previous HDC with stem cell support 

Pediatric Neuroblastoma

• Initial treatment of high-risk neuroblastoma  (Determination of risk includes such variables as age at diagnosis, clinical stage of disease, tumor histology, and certain molecular characteristics including presence of the MYCN oncogene)
• Refractory or recurrent neuroblastoma
• Tandem transplant up to a maximum of 3 cycles
• Repeat transplant due to primary graft failure or failure to engraft

Ewing's Sarcoma

• Recurrent or refractory

Primitive Neuroectodermal Tumors (PNET)

• Recurrent or refractory medulloblastoma and other PNETS (tumors arising from the neuroepithelium, including central nervous system neuroblastoma, ependymoblastoma, and pinealoblastoma)

Germ Cell Tumors (testicular, mediastinal, retroperitoneal, ovarian)

• Patients with favorable prognostic factors that have failed a previous course of conventional-dose salvage chemotherapy
• Patients with unfavorable prognostic factors as initial treatment of first relapse and in patients with platinum refractory disease
• Tandem or sequential autologous transplantation for testicular tumors either as salvage therapy or with platinum-refractory disease

Patients with favorable prognostic factors include those with a testis or retroperitoneal primary site, a complete response to initial chemotherapy, low levels of serum markers and low volume disease.

Patients with unfavorable prognostic factors are those with an incomplete response to initial therapy or relapsing mediastinal nonseminomatous germ-cell tumors

Multiple Myeloma

• Single or second (salvage) transplant
• Tandem transplant in patients who fail to achieve at least a near-complete or very good partial response after the first transplant in the tandem sequence
• Tandem transplant with an initial round of autologous transplantation followed by a non-marrow-ablative conditioning regimen and allogeneic transplantation (i.e., reduced intensity conditioning transplant)

Tandem transplants usually are defined as the planned administration of 2 successive cycles of high-dose myeloablative chemotherapy, each followed by infusion of autologous stem cells, whether or not there is evidence of persistent disease following the first treatment cycle. Sometimes, the second cycle may use non-myeloablative immunosuppressive conditioning followed by infusion of allogeneic stem cells.

Primary Amyloidosis

Patients in whom the following criteria is met:

• Two or fewer organs involved with amyloid deposits

• Serum creatinine of 2.0 mg/dL or less

• No evidence of advanced cardiomyopathy as evidenced by ejection fraction of 45% or greater

Lymphoma (Hodgkin's Disease)

• Primary refractory
• Relapsing after an initial course of chemotherapy

Non-Hodgkin Lymphoma (NHL)

For patients with non-Hodgkin lymphoma B-cell subtypes considered aggressive (except mantle cell lymphoma):

• As salvage therapy for patients who do not achieve a complete remission after first-line treatment (induction) with a full course of standard-dose chemotherapy
• To achieve or consolidate a complete remission for those in a chemosensitive first or subsequent relapse
• To consolidate a first complete remission in patients with diffuse large B-cell lymphoma, with an age-adjusted International Prognostic Index score that predicts a high- or high-intermediate risk of relapse

For patients with mantle cell lymphoma:

• To consolidate a first remission

For patients with non-Hodgkin lymphoma B-cell subtypes considered indolent:

• As salvage therapy for patients who do not achieve complete remission after first-line treatment (induction) with a full course of standard-dose chemotherapy
• To achieve or consolidate complete remission for those in a first or subsequent chemosensitive relapse, whether or not their lymphoma has undergone transformation to a higher grade

For patients with peripheral T-cell lymphoma:

• To consolidate a first complete remission in high-risk peripheral T-cell lymphoma
• As salvage therapy

The term salvage therapy describes chemotherapy given to patients who have either failed to achieve complete remission after initial treatment for newly diagnosed lymphoma; or, relapsed after an initial complete first remission.

A chemosensitive relapse is defined as relapsed non-Hodgkin lymphoma that does not progress during or immediately after standard-dose induction chemotherapy (i.e., achieves stable disease or partial response).

Transformation describes a lymphoma whose histologic pattern has evolved to a higher-grade lymphoma. Transformed lymphoma typically evolves from a nodular pattern to a diffuse pattern.

High-risk peripheral T-cell lymphoma is defined as one of the following histologic subtypes:

Nodal: peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), anaplastic lymphoma kinase-negative anaplastic large cell lymphoma (ALK-ALCL) or angioimmunoblastic lymphoma (AIL). High-risk patients may also include the rare patient with ALK+ALCL who is refractory to conventional chemotherapy.

Extranodal: T/NK cell lymphoma nasal type, enteropathy-type T-cell lymphoma, hepatosplenic T-cell lymphoma and subcutaneous panniculitis-like T-cell lymphoma.

Autologous hematopoietic stem cell transplant associated with a myeloablative conditioning regimen consisting of high-dose chemotherapy with or without total body irradiation is considered investigational for the following indications:

• Epithelial ovarian cancer
• Malignant astrocytomas and gliomas
• Autoimmune diseases including, but not limited to:
  • Multiple Sclerosis
  • Systemic Lupus Erythematosus
  • Aplastic Anemia
  • Rheumatoid and Juvenile idiopathic arthritis
• Diabetes mellitus
• Stage I, II, III, or refractory Stage IV breast cancer, single or tandem transplant
• Initial therapy of all non-Hodgkin's lymphomas
• Initial treatment of germ cell tumors or as treatment following a first relapse
• Tandem transplants for all germ cell tumors except testicular cancer
• Ependymoma
• Initial treatment of low or intermediate risk Ewing sarcoma
• Wilms' tumor
• Retinoblastoma
• Osteosarcoma
• Rhabdomyosarcoma
• Amyloidosis with involvement of greater than two organ systems and/or advanced cardiac involvement as evidenced by an ejection fraction less than 55%
• Chronic myelogenous leukemia in patients not meeting the criteria identified above
• Repair of damaged myocardium

Top

Procedure Codes and Billing Guidelines: 

The following CPT codes may be used to report services/procedures related to autologous peripheral blood stem cell support or bone marrow transplant:

• 38206 Blood-derived hematopoietic progenitor cell harvesting for transplantation, per collection; autologous
• 38207 Transplant preparation of hematopoietic progenitor cells; cryopreservation and storage
• 38208 Transplant preparation of hematopoietic progenitor cells; thawing of previously frozen harvest, without washing
• 38209 Transplant preparation of hematopoietic progenitor cells; thawing of previously frozen harvest, with washing
• 38210 Transplant preparation of hematopoietic progenitor cells; specific cell depletion within harvest, T-cell depletion
• 38211 Transplant preparation of hematopoietic progenitor cells; tumor cell depletion
• 38212 Transplant preparation of hematopoietic progenitor cells; red blood cell removal
• 38213 Transplant preparation of hematopoietic progenitor cells; platelet depletion
• 38214 Transplant preparation of hematopoietic progenitor cells; plasma (volume) depletion
• 38215 Transplant preparation of hematopoietic progenitor cells; cell concentration in plasma, mononuclear, or buffy coat layer
• 38220 Bone marrow; aspiration only
• 38221 Bone marrow; biopsy, needle or trocar
• 38230 Bone marrow harvesting for transplantation
• 38232 Bone marrow harvesting for transplantation; autologous
• 38241 Bone marrow or blood-derived peripheral stem cell transplantation; autologous

The following HCPCS code may be used to report autologous peripheral blood stem cell support or bone marrow transplant:

• S2150 Bone marrow or blood-derived peripheral stem cell harvesting and transplantation, allogenic or autologous, including pheresis, high-dose chemotherapy, and the number of days of post-transplant care in the global definition (including drugs; hospitalization; medical, surgical, diagnostic and emergency services)

Top

Selected References: 

• Attal M, Harousseau JL, Facon T, et al. Single versus double autologous stem-cell transplantation for multiple myeloma. N Engl J Med 2003 Dec 25: 349(26):2495-502.
• Tallman MS, Gray R, Robert NJ, et al. Conventional adjuvant chemotherapy with or without high-dose chemotherapy and autologous stem-cell transplantation in high-risk breast cancer. N Engl J med. 2003 Jul 3; 349(1):17-26.
• Federico M, Bellei M, Brice P, et al. High-dose therapy and autologous stem cell transplantation versus conventional therapy for patients with advanced Hodgkin's lymphoma responding to front line therapy. J Clin Oncol. 2003 Jun 15; 21(12):2320-5. Comment in: Cancer Treat Rev 2003 Dec; 29(6):555-9.
• Kaiser U, Uebelacker I, Abel U, et al. Randomized study to evaluate the use of high-dose therapy as part of primary treatment for “aggressive” lymphoma. J Clin Oncol. 2002 Nov 15; 20(22): 4413-9.
• Kottaridis PD, Peggs K, Schmitz N, et al. Survival and freedom from progression in autotransplant lymphoma patients is independent of stem cell source: further follow up from the original randomized study to assess engraftment. Leuk Lymphoma. 2002 Mar; 43(3):531-6.
• Marcus KJ, Shamberger R, Litman H, et al. Primary tumor control in patients with stage ¾ unfavorable neuroblastoma treated with tandem double autologous stem cell transplants. J Pediatr Hematol Oncol. 2003 Dec; 25(12):934-40.
• Imrie K, Esmail R, Meyer RM, et al. The role of high-dose chemotherapy and stem-cell transplantation in patients with multiple myeloma: a practice guideline of the Cancer Care Ontario Practice Guidelines Initiative. Ann Intern Med. 2002 Apr 16; 136(8): 619-29.
• Bhatia R, Verfaillie CM, Miller JS et al. Autologous Transplantation Therapy for Chronic Myelogenous Leukemia. Blood. The Journal of the American Society of Hematology. 1997; 89(8):2623-34.
• Chronic Myelogenous Leukemia. National Comprehensive Cancer Network Clinical Practice Guidelines. v.2.2005.
• Skinner M et al. High-dose melphalan and autologous stem cell transplantation in patients with AL amyloidosis: an 8 year study. Ann Intern Med. 2004 Jan 20; 140(2):85-93.
• ECRI. High-Dose Chemotherapy with Autologous Bone marrow or peripheral Stem Cell Transplant for Epithelial Ovarian Cancer. Plymouth Meeting (PA): ECRI Health Technology Assessment Information Service; 2004. Windows on Medical Technology No. 117.
• ECRI. High-dose chemotherapy (immunosuppression) with stem cell transplantation for treatment of multiple sclerosis. Plymouth Meeting (PA): ECRI Health Technology Assessment Information Service; 2005. Health Technology Forecast.
• ECRI Autologous stem cell transplantation for myocardial repair. Plymouth Meeting (PA): ECRI Health Technology Assessment Information Services; 2005. Health Technology Forecast.
• Abbott JD, Giordano FJ. Stem cells and cardiovascular disease. J Nucl Cardiol 2003: 10(4):403-12.
• Smits PC, van Geuns RJ, Poldermans D et al. Catheter-based intramyocardial  injection of autologous skeletal myoblasts as a primary treatment of ischemic heart failure: clinical experience with six-month follow-up. J Am Coll Cardiol 2003; 42(12):2063-9.
• Cogliatti S, Schmid U. Who is WHO and what was REAL? A review of the new WHO classification (2001) for malignant lymphoma. Swiss Med Wkly 2002;132:607-617.
• Hahn T, Wingard JR, Anderson KC et al. The role of cytotoxic therapy with hematopoietic stem cell transplantation in the therapy of multiple myeloma: an evidence-based review. Biol Blood Marrow Transplant. 2003 Jan;9(1);4-37.
• Einhorn LH, Williams SD, Chamness A et al. High-dose chemotherapy and stem cell rescue for metastatic germ-cell tumors. N Engl J Med 2007;357:340-8.
• Abdelkefi A, Ladeb S, Torjman L et al. Single autologous stem-cell transplantation followed by maintenance therapy with thalidomide is superior to double autologous transplantation in multiple myeloma: results of a multicenter randomized clinical trial. Blood 2008; 111(4):1805-10.
• Gill P, Litzow M, Buckner J et al. High-dose chemotherapy with autologous stem cell transplantation in adults with recurrent embryonal tumors of the central nervous system. Cancer 2008 Apr 15;112-(8):1805-11.
• Shih CS, Hale GA, Gronewald L et al. High-dose chemotherapy with autologous stem cell rescue for children with recurrent malignant brain tumors.
• Sung KW, Lee SH, Yoo KH et al. Tandem high-dose chemotherapy and autologous stem cell rescue in patients over 1 year of age with stage 4 neuroblastoma. Bone Marrow Transplant. 2007 Jul;40(1):37-45 Epub 2007 Apr 30.
• George RE, Li S, Medeiros-Nancarrow C et al. High-risk neuroblastoma treated with tandem autologous peripheral-blood stem cell-supported transplantation: long-term survival update. J Clin Oncol. 2006 Jun 20; 24(18):2891-6.
• von Alleman D, Grupp S, Diller L et al. Aggressive surgical therapy and radiotherapy for patients with high-risk neuroblastoma treated with rapid sequence tandem transplant. J Pediatr Surg 2005 Jun; 40(6): 936-41; discussion 941.
• Kletzel M, Katzenstein HM, Haut PR et al. Treatment of high-risk neuroblastoma with triple-tandem high-dose therapy and stem-cell rescue: results of the Chicago Pilot II Study. J Clin Oncol. 2002 May 1; 20(9): 2284-92.
• Couri CE, Oliveira MC, Stracieri AB et al. C-peptide levels and insulin independence following autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus. JAMA 2009; 301(15):1573-9.
• Laport GG. The role of hematopoietic cell transplantation for follicular non-Hodgkin’s lymphoma. Biol Blood Marrow Transplant 2006; 12(1 suppl 1):59-65.
• The International Non-Hodgkin’s Lymphoma Prognostic Factors Project: a predictive model for aggressive non-Hodgkin’s lymphoma. N Engl J Med 1993; 329(14):987-94.
• Jaffe ES. The 2008 WHO classification of lymphomas: implications for clinical practice and translational research. Hematology Am Soc Hematol Educ Program 2009:523-31.
• Tam CS, Bassett R, Ledesma C et al. Mature results of the MD Anderson Cancer Center risk-adapted transplantation strategy in mantle cell lymphoma. Blood 2009; 113(18):4144-52.
• Geisler C. Mantle cell lymphoma: are current therapies changing the course of the disease? Curr Oncol Rep 2009; 11(5):371-7.
• Rodriquez J, Gutierrez A, Martinez-Delgado B et al. Current and future aggressive peripheral T-cell lymphoma treatment paradigms, biological features and therapeutic molecular targets. Crit Rev Oncol Hematol 2009; 71(3):181-98.
• Reimer P, Rudiger T, Geissinger E et al. Autologous stem-cell transplantation as first-line therapy in peripheral T-cell lymphomas: results of a prospective multicenter study. J Clin Oncol 2009; 27(1):106-13.
• Corradini P, Tarella C, Zallio F et al. Long-term follow-up of patients with peripheral T-cell lymphoma treated up front with high-dose chemotherapy followed by autologous stem cell transplantation. Leukemia 2006; 20(9):1533-8.
• Mercadal S, Briones J, Xicoy B et al. Intensive chemotherapy (high dose CHOP/ESHAP regimen) followed by autologous stem-cell transplantation in previously untreated patients with peripheral T-cell lymphoma. Ann Oncol 2008; 19(5):958-63.
• Shafey M, Duan Q, Russell J et al. Double high-dose therapy with dose-intensive cyclophosphamide, etoposide, cisplatin (DICEP) followed by high-dose melphalan and autologous stem cell transplantation for relapsed/refractory Hodgkin lymphoma.
• Siegel DS, Vij R, Jakubowiak AJ. Clinical roundtable monograph. Emerging treatment options for relapsed and refractory multiple myeloma. Clin Adv Hematol Oncol. 2011 Apr; 9(4):1-15.  

Top

Policy History: 

Date                                         Reason                              Action

September 2010                      Interim review                    Policy revised

October 2011                          Annual review                    Policy revised

Top

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.

*Current Procedural Terminology © 2010 American Medical Association. All Rights Reserved.