Medical Policy: 07.03.13 

Original Effective Date: November 2020 

Reviewed: November 2020 

Revised:  

 

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:

Donor Lymphocyte Infusion (DLI)

Donor lymphocyte infusion (DLI), also called donor leukocyte infusion, or buffy coat infusion, is a type of therapy in which lymphocytes from the blood of the donor are given to a patient who has already received allogeneic hematopoietic stem cell transplantation (HSCT) from the same donor. This therapy is based on the premise that the donor lymphocytes will recognize and kill the recipient’s cancer cells in a process known as the graft-versus-leukemia (GVL) or graft-versus-tumor (GVT) effect. It is now accepted that DLI, at a time remote from the transplant conditioning regimen, can treat infections and relapse successfully after allogeneic HSCT in selected patients with hematologic malignancies; however significant complications may result including acute and chronic graft-versus-host disease (GVHD), anemia, and infection. DLI is not used to promote engraftment or enhancement of chimerism. The intent is not to restore hematopoiesis. The recipient does not receive a preparative regimen but may require concomitant therapy for the underlying problem.

 

DLI has been researched as a treatment for a variety of hematologic malignancies, including most prominently chronic myeloid leukemia (CML), but also acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), multiple myeloma (MM), myelodysplastic syndromes (MDS), chronic lymphocytic leukemia (CLL), Hodgkin lymphoma (HL), and non-Hodgkin lymphoma (NHL). Studies are limited due to small numbers, but they have provided evidence that DLI can establish a graft-versus-leukemia/lymphoma effect.

 

Chronic Myelogenous Leukemia and Acute Myelogenous Leukemia

Donor lymphocyte infusion (DLI) has been most effective in chronic myelogenous leukemia (CML), inducing a molecular complete remission (CR) in up to 80% of patients who relapse in chronic phase. Only a 12% to 33% response rate has been reported in patents in accelerated or blast phase.   Infusions using lymphocytes obtained from the original hematopoietic progenitor cell donor can induce long-term, complete, hematological, cytogenetic, and molecular genetic remissions in individuals treated for relapsing CML after an allogeneic hematopoietic cell transplant (HCT). The National Comprehensive Cancer Network (NCCN) Guideline Version 2.2021 Chronic Myelogenous Leukemia (CML) states “donor lymphocyte infusion (DLI) is effective in inducing durable molecular remissions in the majority of patients with relapsed CML following allogeneic HCT though it is more effective in patients with chronic phase relapse rather than advanced phase relapse.”

 

These recommendations were based on 2A category of evidence and uniform consensus. The results from CML may be extrapolated to individuals with relapsed acute myelogenous leukemia (AML), since there is evidence of a graft-versus-leukemia effect in individuals with AML treated with allogeneic transplants.

 

Acute Lymphoblastic Leukemia, Lymphomas, Multiple Myeloma, and Myelodysplastic Syndromes

Donor lymphocyte infusion (DLI) therapy has also been found effective for relapse of hematologic malignant diseases other than CML, although response rates are lower. The medical evidence currently available for the use of donor lymphocyte infusions (DLI) in individuals with relapsed disease from other hematologic malignancies including, but not limited to, acute lymphoblastic leukemia (ALL), multiple myeloma (MM), Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) and myelodysplastic syndromes (MDS), consists mostly of multiple small case series.  However, there is a preponderance of these smaller studies in combination, demonstrate that DLI may induce an anti-tumor response in individuals who have relapsed disease following an allogeneic hematopoietic stem cell transplant (HSCT).

 

Acute Lymophoblastic Leukemia

Published case reports have suggested that the use of donor lymphocyte infusion (DLI) for residual disease or molecular relapse (as noted by levels of BCR-ABL fusion mRNA measured with PCR) after allogeneic HCT may eliminate residual leukemic clones and thereby prevent overt hematologic relapse. Additional case reports have described using newer TKIs such as dasatinib and nilotinib along with DLI to manage relapse after allogeneic HCT.

 

The clinically evident graft-versus-leukemia effect of DLI requires weeks to months to become apparent, and, because ALL is a rapidly proliferating disease, DLI only is unable to control the disease without a significant reduction in leukemia burden before DLI. Management of patients with relapsed ALL leading to the best overall survival (OS) is with a combination of salvage chemotherapy and DLI. Although it is not clear whether DLI adds benefit to salvage chemotherapy, long-term survivors have been reported with relapsed ALL who received both chemotherapy and DLI.

 

NCCN Clinical Practice Guideline for Acute Lymphoblastic Leukemia (ALL) (adult and AYA version 2.2020) includes the use of a second allogeneic HCT and/or donor lymphocyte infusion (DLI) for individuals with relapsed disease after allogeneic HCT. This recommendation is based on 2A category of evidence and uniform consensus.

 

Lymphomas

Studies in which patients received donor lymphocyte infusion (DLI) for lymphomas consist of small numbers of patients with various histologies (both Hodgkin lymphoma [HL] and high- and- low grade non-Hodgkin lymphoma [NHL]). In general, the highest response rates have been seen in indolent lymphomas. For NHL too few patients have been reported with any single histologic subtype of lymphoma to give adequate information of the benefit for DLI for a specific lymphoma subtype.

 

The largest series reported for NHL (N=21) using DLI showed response rates in 3 of 9 patients with high grade NHL, 1 of 2 patients with mantle cell lymphoma, and 6 of 10 patients with low-grade disease.

 

A series of 14 patients with multiply relapsed HL who received reduced-intensity conditioning allogeneic HSCT and DLI showed a complete remission (CR) of 57% and 2- year survival of 35%.

 

Multiple Myeloma

Observational data suggest a graft-versus-tumor (GVT) effect in multiple myeloma because the development of GVHD has correlated with response in several analyses.

 

Five studies have reported on the role of donor lymphocyte infusion (DLI) in relapsed multiple myeloma consisting of patients ranging in number of 5 to 63 with the highest response to DLI being reported as 62% with approximately half of the responders attaining complete remission (CR). One confounding factor for high response rates for multiple myeloma treated with DLI following allogeneic HSCT is that corticosteroids used for treating GVHD have known antimyeloma effect which could potentially enhance response rates in these patients. 

 

NCCN Clinical Practice Guideline for Multiple Myeloma (version 3.2021) includes the use of donor lymphocyte infusion in individuals post allogeneic stem cell transplant with unresponsive (refractory) or relapsed disease in- order to stimulate a beneficial graft-versus-myeloma effect. This recommendation is based on 2A category of evidence and uniform consensus.

 

Myelodysplastic Syndromes

An observational study comparing different treatments for relapse reported on 147 consecutive patients who relapsed after allogeneic HSCT for myelodysplastic syndrome. Sixty-two patients received HSCT or donor lymphocyte infusion (DLI), 39 received cytoreductive treatment, and 46 were managed with palliative or supportive care. Two-year rates of overall (OS) were 32%, 6%, and 2%, respectively (p<.001). In multivariate analysis, 4 factors adversely influenced 2-year rates of OS: history of acute graft-versus-host disease (hazard ratio [HR], 1.83; 95% CI, 1.26 to 2.67; p=0.002), relapse within 6 months (HR=2.69; 95% CI, 0.82 to 3.98; p<0.001), progression to acute myelogenous leukemia (HR=2.59; 95% CI, 1.75 to 3.83; p<0.001), and platelet count less than 50 g/L at relapse (HR=1.68; 95% CI, 1.15 to 2.44; p=0.007). HSCT or DLI was found to be an independent factor that favorably impacts OS (HR=0.40; 95% CI, 0.26 to 0.63; p<0.001).

 

NCCN Clinical Practice Guideline for Myelodysplastic Syndromes (version 1.2021) includes the use of a second allogeneic HCT and/or donor lymphocyte infusion in individuals post allogeneic HCT with unresponsive (refractory) or relapsed disease. This recommendation is based on 2A category of evidence and uniform consensus.

 

Summary of Evidence

NCCN Clinical Practice Guideline for Multiple Myeloma (version 3.2021) includes the use of donor lymphocyte infusion in individuals post allogeneic stem cell transplant with unresponsive (refractory) or relapsed disease in- order to stimulate a beneficial graft-versus-myeloma effect. NCCN Clinical Practice Guideline for Acute Lymphoblastic Leukemia (ALL) (adult and AYA version 2.2020) includes the use of a second allogeneic HCT and/or donor lymphocyte infusion (DLI) for individuals with relapsed disease after allogeneic HCT. NCCN Clinical Practice Guideline for Myelodysplastic Syndromes (version 1.2021) includes the use of a second allogeneic HCT and/or donor lymphocyte infusion in individuals post allogeneic HCT with unresponsive (refractory) or relapsed disease. These recommendations were based on 2A category of evidence and uniform consensus.

 

The National Cancer Institute (NCI) regarding the treatment with donor lymphocytes includes the following:

  • Acute myelogenous leukemia (AML): Patients who relapse following an allogeneic bone marrow transplant (BMT) may undergo an infusion of lymphocytes from the donor (donor lymphocyte infusion or DLI).
  • Chronic myelogenous leukemia (CML): Treatment of relapsed chronic myelogenous leukemia (CML) may include donor lymphocyte infusion. 
  • Multiple Myeloma (MM): A definite graft-versus-myeloma effect has been demonstrated, including regression of myeloma relapses following the infusion of donor lymphocytes.
  • Non-Hodgkin Lymphoma (NHL) in Children: Treatment of post-transplant lymphoproliferative disease may include donor lymphocyte infusion.  

 

Based on the review of the peer reviewed medical literature the evidence for donor lymphocyte infusion (DLI) for hematologic malignancies in individuals who have been treated with an allogeneic hematopoietic stem cell transplant (HSCT) includes few nonrandomized comparative studies and numerous case series. In various hematologic malignancies and for various indications such as planned or preemptive DLI, treatment of relapse, or conversion of mixed to full donor chimerism, patients have shown evidence of response to DLI. The response rates to DLI for relapsed hematologic malignancies following allogeneic HSCT are best in chronic myelogenous leukemia (CML), followed by lymphomas (Hodgkin and non-Hodgkin), multiple myeloma (MM), and acute leukemias, respectively. The evidence is sufficient to determine the effects of the technology on net health outcomes. 

 

Genetic Modification of Donor Lymphocytes

There is also a research interest in the genetic modification of donor lymphocytes in an effort to control graft versus host disease (GVHD). For example, it has been proposed that donor lymphocytes can be modified by insertion of a thymidine kinase gene, rendering the cells susceptible to ganciclovir therapy.  If the infusion of the genetically modified donor lymphocytes results in severe graft versus. host disease (GVHD), the transplant recipient can then be treated with ganciclovir to selectively destroy the donor lymphocytes.  However, further investigation and data regarding the safety and efficacy of genetic modifications of DLI on GVHD and/or graft-versus-leukemia (GVL) are needed. The evidence is insufficient to determine the effects of the technology on net health outcomes.

 

Donor Lymphocyte Infusion (DLI) for Nonmalignant Disease

Donor lymphocyte infusion (DLI) is used in hematologic malignancies as a means of increasing graft versus tumor effect, however, experience with DLI to improve engraftment in nonmalignant disease is extremely limited. The evidence is insufficient to determine the effects of the technology on net health outcomes.

 

Hematopoietic Progenitor Cell (HPC) Boost

A boost of hematopoietic progenitor cell (HPC) (also known as stem cells) from the original HCST donor is intended to restore hematopoiesis or augment poor graft function after hematopoietic stem cell transplantation (HSCT). Poor graft function is a severe complication of HSCT which is defined as persistent cytopenias and/or transfusion dependence. The cell product used for a HPC boost may be a previously cryopreserved cell product, or alternatively, the donor may need to undergo additional evaluation, stem cell mobilization, and cell harvest. A boost is not preceded by a preparative regimen. A potential source of confusion is that a boost is often required when additional conventional chemotherapy is given to treat relapse and reestablish remission after transplantation. Prolonged cytopenias and immunosuppression may result, requiring additional HPC boost, which is typically given days to weeks after reinduction chemotherapy.

 

Although data are not robust, several prospective and retrospective clinical trials demonstrate beneficial effects of HPC boost after HSCT.

 

In 2017, Ghobadi et. al. performed single institution study at the Washington University School of Medicine. A pilot trial was conducted to study three different sources of CD34+ cells for treatment of poor graft function (PGF): (1) fresh mobilized product using G-CSF only, (2) fresh mobilized products using G-CSF and plerixafor, and (3) cryopreserved cells mobilized with G-CSF. Seventeen donor-recipient pairs were enrolled onto this prospective study. A retrospective review of similar patients treated off protocol with the same regimen was conducted. From June 2010 through June 2015, 17 donor-recipient pairs were enrolled in the prospective study and 9 donor-recipient pairs were treated off protocol. Together 26 donor-patient pair were analyzed and reported in this manuscript. The primary objective was the hematologic response rate. Secondary objectives included: (1) CD34+ yields; (2) incidence and severity of acute and chronic GVHD; (3) Overall survival (OS) and relapse free survival (RFS). The Washington University Institutional Review Board (IRB) approved the study. The prospective trial was registered at ClinicalTrials.gov as NCT01026987. PGF was defined as having cytopenia (ANC < 0.5k/μL, platelets < 30k/μL or platelet transfusion dependence, or red blood cell transfusion dependence) for two consecutive weeks in the absence of relapse/persistent hematologic disorder, incomplete (< 90%) donor chimerism, active infectious diseases, or drug related myelosuppression. Primary PGF was defined as PGF in the absence of full engraftment. Secondary PGF was defined as PGF after full engraftment. Complete response was defined as improvement of all involved cells lineages; partial response was defined as improvement of platelets and/or neutrophils with continuing RBC transfusion dependence. Neutrophil improvement was defined as an absolute neutrophil count > 500/μl without growth factor support for >7 days; platelet improvement was defined as platelet count ≥ 50,000/μl without platelet transfusion support for > 7 days; and RBC improvement was defined as hemoglobin > 9 g/dL and transfusion independence. CD34+ yield was defined as the number of CD34+ cells after selection/CD34+ cells in the mobilized product prior to CD34+ selection. Overall survival (OS) was defined as time from SCB to death. Relapse-free survival (RFS) was defined as time from stem cell boost (SCB) to relapse or death. Eligible patients were those who were at least 18 years old, had an ECOG performance status of 2 or below, and had poor graft function (PGF) following allo-HSCT (more than 60 days post allo-HSCT). Patients with poor graft function secondary to relapse/persistent disease, incomplete (< 90%) donor chimerism, or active infectious diseases were excluded, as were patients with significant medical, psychiatric, or social conditions that contraindicated the procedure. Previous allo-HSCT may have been performed using a related or unrelated donor; however, the original donor was required to undergo additional PBSC collection or authorize that cryopreserved cells from a previous PBSC collection be used. Blood counts were performed at least weekly through Day +14 then at least every other week through Day +100, monthly thereafter for patients on the prospective trial; patients reviewed retrospectively were followed per institutional guidelines. Incidence and severity of acute GVHD was defined according to Glucksberg criteria, chronic GVHD as limited or extensive. Patients were monitored for acute GVHD through Day +100 and for chronic GVHD through Day +365 following SCB. The median age at SCB was 52.5 years (range 25–68) and 16 of 26 were male. Twelve patients underwent allo-HSCT for acute myelogenous leukemia, 6 for myelodysplastic syndrome, 4 for acute lymphoblastic leukemia, 2 for aplastic anemia, and 1 for Hodgkin’s lymphoma, and 1 for Diamond-Blackfan Anemia. Sixteen patients had related donors (11 HLA-matched siblings, 5 haplo-identical donors). Ten had unrelated donors (9 HLA-matched and 1 HLA-mismatch). All received peripheral blood stem cell products. Sixteen patients had primary PGF, 10 secondary. The median time from allo-HSCT to SCB was 4.6 months (range 2.1–23.6). At time of SCB 6 had PGF involving neutrophils, 25 platelets, and 23 red blood cells. Twenty-six recipients of SCB for the treatment of PGF following allo-HSCT. The complete response rate was 62% and overall response rate was 81%. Six of the 10 patients who failed to achieve a complete response suffered from disease relapse while only one of 17 patients with complete hematologic response suffered from disease relapse within 3 months of SCB; Treatment was well tolerated; there was no TRM and no grade III–IV acute GVHD. The authors concluded our data suggests that cryopreserved products can be an effective and viable source of cells for SCB (stem cell boost).

 

In 2018, Mainardi et. al. reported retrospective study results involving 50 children with acute lymphatic leukemia, acute myeloid leukemia and severe aplastic anemia who received 61 boosts with CD34+ selected peripheral blood stem cells after transplantation from matched unrelated (n = 25) or mismatched related (n = 25) donors. No conditioning was performed prior and no immunosuppressive therapy was administered post the allogeneic HSCT. Within 8 weeks, a significant increase in median neutrophil counts (p < 0.05) and a decrease in red blood cell and platelet transfusion requirement (p < 0. 0001 and <0.001) respectively, were observed. 78.8% of patients resolved one or two of their cytopenias and 36.5% had a complete hematological response. The rate of de novo acute graft-versus-host disease (GVHD) grade I–III was only 6% and resolved completely. No GVHD grade IV or chronic GVHD occurred. Patients who responded to hematopoietic progenitor cell (HPC) displayed a trend toward better overall survival (OS) (P = 0.07). Data suggest improved graft function with HPC boost in this cohort of patients.

 

Summary of Evidence

A boost of hematopoietic progenitor cell (HPC) (also known as stem cells) from the original HCST donor is intended to restore hematopoiesis or augment poor graft function after hematopoietic stem cell transplantation (HSCT). Poor graft function is a severe complication of HSCT which is defined as persistent cytopenias and/or transfusion dependence. The cell product used for a HPC boost may be a previously cryopreserved cell product, or alternatively, the donor may need to undergo additional evaluation, stem cell mobilization, and cell harvest. A boost is not preceded by a preparative regimen. A potential source of confusion is that a boost is often required when additional conventional chemotherapy is given to treat relapse and reestablish remission after transplantation. Prolonged cytopenias and immunosuppression may result, requiring additional HPC boost, which is typically given days to weeks after reinduction chemotherapy. Based on review of the peer reviewed medical literature, although the evidence is not robust, several prospective and retrospective clinical trials demonstrate beneficial effects of HPC boost after HSCT. The evidence is sufficient to determine the effects of the technology on net health outcomes. 

 

Practice Guideline and Position Statements

National Comprehensive Cancer Network (NCCN)

Acute Lymphoblastic Leukemia (Adult and AYA) Version 2.2020

For patients with relapsed disease after allogeneic HCT, a second allogeneic HCT and/or donor lymphocyte infusion (DLI) can be considered.

 

Chronic Myeloid Leukemia Version 2.2021

Management of Post-Transplant Relapse: Donor lymphocyte infusion (DLI) is effective in inducing durable molecular remissions in the majority patients with relapsed CML following allogeneic HCT, though it is more effective in patients with chronic phase relapse then advanced phase relapse. 

 

Multiple Myeloma Version 3.2021

Management of Post-Allogeneic Hematopoietic Stem Cell Transplant: Includes the use of donor lymphocyte infusion in individuals post allogeneic stem cell transplant with unresponsive (refractory) or relapsed disease.

 

Myelodysplastic Syndromes Version 1.2021

Consider second transplant or donor lymphocyte infusion immune-based therapy for appropriate patients who had a prolonged remission after first transplant.

 

T-Cell Lymphomas Version 1.2021

Donor lymphocyte infusion (DLI) has been shown to induce long-term remissions in a few patients with PD (progressive disease) or disease relapse after allogeneic HCT. An analysis showed that induction of GVL effect via DLI may provide long-lasting remission in selected patients with relapsed ATLL.

 

Regulatory Status

The U.S. Food and Drug Administration regulates certain human cells, tissues, and cellular and tissue-based products under the legal authority of section 361 of the Public Health Service Act (42 USC 264). This section authorizes the Surgeon General, with the approval of the Secretary of the U.S. Department of Health and Human Services, to make and enforce such regulations as judged necessary to prevent the introduction, transmission, or spread of communicable diseases from foreign countries into the United States or from state to state. According to Addendum 7342.007—Imported Human Cells, Tissues, and Cellular and Tissue-based Products (HCT/Ps), umbilical cord blood stem cells, peripheral blood stem cells, lymphocytes (donor lymphocytes for infusion, T cells) are identified by product code 57M.P.

 

Prior Approval:

Not applicable.

 

Policy:

Donor Lymphocyte Infusion (DLI)

Donor lymphocyte infusion (DLI) is considered medically necessary following an allogeneic (myeloablative or non-myeloablative) hematopoietic stem cell transplant that was originally considered medically necessary for the treatment of hematologic malignancy that has relapsed or is refractory (disease that does not respond), or to prevent relapse in the setting of a high risk of relapse (T-cell depleted grafts or non-myeloablative [reduced intensity conditioning] allogeneic transplant) or to convert an individual from a mixed to full donor chimerism.

 

Note: The donor for the lymphocytes is the same individual whose stem cells (hematopoietic progenitor cells) were used for the transplant procedure.

 

Collection and Cryopreservation of donor lymphocytes is considered medically necessary prior to, at the time of, or after a medically necessary allogeneic (myeloablative or non-myeloablative) hematopoietic stem cell transplant.  

 

Donor lymphocyte infusion (DLI) is considered investigational including but not limited to the following as there is insufficient scientific evidence to permit conclusions concerning the health outcomes or benefits associated with this procedure:

  • Donor lymphocyte infusion (DLI) as a treatment of nonhematologic malignancies. 
  • Donor lymphocyte infusion (DLI) following allogeneic (myeloablative or non-myeloablative) hematopoietic stem cell transplant that was originally considered investigational for the treatment of hematologic malignancy.  
  • Genetic modification of donor lymphocytes (donor lymphocytes can be modified by insertion of a thymidine kinase gene).

 

Hematopoietic Progenitor Cell (HPC) Boost

Hematopoietic progenitor cell (HPC) boost is considered medically necessary following autologous or an allogeneic (myeloablative or non-myeloablative) hematopoietic stem cell transplant that was originally considered medically necessary for the treatment of hematologic malignancy for either of the following indications:

  • Promote engraftment 
  • Enhancement of chimerism when studies reveal <100% donor cells

 

Hematopoietic progenitor cell (HPC) boost is considered investigational for all other indications as there is insufficient scientific evidence to permit conclusions concerning the health outcomes or benefits associated with this procedure.

 

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.

  • 38242 Allogeneic lymphocyte infusions 
  • 38243 Hematopoietic progenitor cell (HPC); HPC boost

 

Selected References:

  • National Comprehensive Cancer Network (NCCN) Acute Lymphoblastic Leukemia (Adult and AYA) Version 2.2020. 
  • National Comprehensive Cancer Network (NCCN) Chronic Myeloid Leukemia Version 2.2021. 
  • National Comprehensive Cancer Network (NCCN) Multiple Myeloma Version 3.2021. 
  • National Comprehensive Cancer Network (NCCN) Myelodysplastic Syndromes Version 1.2021. 
  • National Comprehensive Cancer Network (NCCN) T-cell Lymphoma Version 1.2021. 
  • National Cancer Institute (NCI) Health Professional Version Acute Myelogenous Leukemia (AML). 
  • National Cancer Institute (NCI) Health Professional Version Chronic Myelogenous Leukemia (CML).  
  • National Cancer Institute (NCI) Health Professional Version Plasma Cell Neoplasms (Including Multiple Myeloma).      
  • National Cancer Institute (NCI) Health Professional Version Non-Hodgkin Lymphoma in Children.   
  • UpToDate. Immunotherapy for the prevention and treatment of relapse following allogeneic hematopoietic cell transplantation. Robert S. Negrin M.D., Topic last updated November 1, 2018. 
  • UpToDate. Treatment of Relapsed or Refractory Acute Myeloid Leukemia. Richard A. Larson M.D., Topic last updated November 5, 2019.  
  • UpToDate. Multiple Myeloma: use of allogeneic hematopoietic cell transplantation. S. Vincent Rajkumar M.D., Topic last updated April 8, 2020. 
  • UpToDate. Hematopoietic stem cell transplantation in sickle cell disease. Shakila Khan M.D., Griffin P. Rodgers M.D., Topic last updated September 23, 2019. 
  • UptoDate. Hematopoietic cell transplantation in chronic myeloid leukemia. Robert S. Negrin M.D., Topic last updated May 2, 2019. 
  • UpToDate. Strategies for immune reconstitution following allogeneic hematopoietic cell transplantation. Marcel RM van den Brink M.D., PhD, Jarrod A. Dudakov PhD., Topic last updated February 26, 2020. 
  • Morris E, Thomson K, Craddock C, et al. Outcomes after alemtuzumab-containing reduced-intensity allogeneic transplantation regimen for relapsed and refractory non-Hodgkin lymphoma. Blood. Dec 15 2004;104(13):3865-3871. PMID 15304395
  • Peggs KS, Sureda A, Qian W, et al. Reduced-intensity conditioning for allogeneic haematopoietic stem cell transplantation in relapsed and refractory Hodgkin lymphoma: impact of alemtuzumab and donor lymphocyte infusions on long-term outcomes. Br J Haematol. Oct 2007;139(1):70-80. PMID 17854309
  • Tomblyn M, Lazarus HM. Donor lymphocyte infusions: the long and winding road: how should it be traveled? Bone Marrow Transplant. Nov 2008;42(9):569-579. PMID 18711351
  • Radujkovic A, Guglielmi C, Bergantini S, et al. Donor lymphocyte infusions for chronic myeloid leukemia relapsing after allogeneic stem cell transplantation: may we predict graft-versus-leukemia without graft-versus-host disease? Biol Blood Marrow Transplant. Mar 19 2015. PMID 25797175
  • Guieze R, Damaj G, Pereira B, et al. Management of myelodysplastic syndrome relapsing after allogeneic hematopoietic stem cell transplantation: a study by the French Society of Bone Marrow Transplantation and Cell Therapies. Biol Blood Marrow Transplant. Aug 6 2015. PMID 26256942
  • Schroeder T, Rachlis E, Bug G, et al. Treatment of acute myeloid leukemia or myelodysplastic syndrome relapse after allogeneic stem cell transplantation with azacitidine and donor lymphocyte infusions-a retrospective multicenter analysis from the German Cooperative Transplant Study Group. Biol Blood Marrow Transplant. Apr 2015;21(4):653-660. PMID 25540937
  • Hashimoto H, Kitano S, Ueda R, et al. Infusion of donor lymphocytes expressing the herpes simplex virus thymidine kinase suicide gene for recurrent hematologic malignancies after allogeneic hematopoietic stem cell transplantation. Int J Hematol. Jul 2015;102(1):101-110. PMID 25948083
  • Merker M, Salzmann-Manrique E, Katzki V, et. al. Clearance of hematologic malignancies by allogeneic cytokine-induced killer cell or donor lymphocyte infusions. Biol Blood Marrow Transplant 2019 Jul;25(7):1281-1292. doi: 10.1016/j.bbmt.2019.03.004. Epub 2019 Mar 13  
  • Schuler E, Boughoufala S, Rautenberg C, et. al. Release patterns and treatment strategies in patients receiving allogeneic hematopoietic stem cell transplantation for myeloid malignancies. Ann Hematol 2019 May;98(5):1225-1235. doi: 10.1007/s00277-019-03670-6. Epub 2019 Mar 29 
  • Ghobadi A, Fiala MA, Ramsingh G, Gao F, Abboud CN, Stockerl-Goldstein K, et al. Fresh or Cryopreserved CD34(+)-Selected Mobilized Peripheral Blood Stem and Progenitor Cells for the Treatment of Poor Graft Function after Allogeneic Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant. 2017 Jul;23(7):1072-1077. PMID 28323004   
  • Mainardi C, Ebinger M, Enkel S, Feuchtinger T, Teltschik HM, Eyrich M, et al. CD34(+) selected stem cell boosts can improve poor graft function after paediatric allogeneic stem cell transplantation. Br J Haematol. 2018 Jan;180(1):90-99 
  • Caldemeyer LE, Akard LP, Edwards JR, Tandra A, Wagenknecht DR, Dugan MJ. DonorLymphocyte Infusions Used to Treat Mixed-Chimeric and High-Risk Patient Populations in the Relapsed and Nonrelapsed Settings after Allogeneic Transplantation for Hematologic Malignancies Are Associated with High Five-YearSurvival if Persistent Full Donor Chimerism Is Obtained or Maintained. Biol Blood Marrow Transplant. 2017 Nov;23(11):1989-1997. PMID 28712934 
  • Kerbage F, Sakr R, Lapierre V, et al. Donor Lymphocyte Infusions After Allogeneic Transplantation: A Single-Center Experience. Clin Lymphoma Myeloma Leuk. 2020;20(4):209–2 
  • Mohammadi S, Norooznezhad AH, Mohammadi AM, Nasiri H, Nikbakht M, Saki N, Optimizing peripheral blood stem cells transplantation outcome through amend relapse and graft failure: a review of current literature. Exp Hematol Oncol. 2017 Aug 9;6:24 
  • Dholaria B, Savani B, Labopin M. et. al. Clinical applications of donor lymphocyte infusion from an HLA-haploidentical donor: consensus recommendations from the Acute Leukemia Working Party of the EBMT. Haematologica Vol 105 No. 1 January 2020

 

Policy History:

  • November 2020, New Policy

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.