Donor Lymphocyte Infusion for Hematologic Malignancies Treated with an Allogeneic Hematopoietic Stem-Cell Transplant
DESCRIPTION
Treatment options are limited for individuals with a hematologic malignancy that relapses after an allogeneic peripheral blood stem cell or bone marrow transplant. Donor lymphocyte infusion (DLI), also referred to as donor leukocyte infusion, involves obtaining a concentrated sample of cells from the original donor and then infusing it into the relapsed individual. The DLI therapeutic effect results from a graft-versus-leukemic or graft-versus-tumor effect due to recognition of certain antigens on the cancer cells by the donor lymphocytes and the resultant elimination of the tumor cells.
Donor lymphocyte infusions have been investigated for a variety of hematologic malignancies, including chronic myeloid leukemia, acute myeloid leukemia, acute lymphocytic leukemia, and multiple myeloma.
POLICY
Donor lymphocyte infusion following allogeneic hematopoietic stem cell transplantation is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
Donor lymphocyte infusion for all other conditions, including, but not limited to, the following is considered investigational:
Following allogeneic hematopoietic stem cell transplantation that was originally considered investigational for the treatment of a hematologic malignancy
As a treatment of nonhematologic malignancies following a prior allogeneic stem cell transplantation
Genetic modification of donor lymphocytes is considered investigational.
MEDICAL APPROPRIATENESS
Donor lymphocyte infusion for the treatment of hematologic malignancies is considered medically appropriate if ANY ONE of the following are met:
Hematologic malignancy has relapsed or is refractory
To prevent a high risk of relapse (i.e., T-cell depleted grafts or non-myeloablative [reduced-intensity conditioning] allogeneic stem cell transplantation)
To convert an individual from mixed to full donor chimerism*
*Full chimerism refers to an individual who exhibits post-transplant characteristics, (phenotype) in hematopoietic cells that are all of donor origin. Mixed chimerism refers to an individual who exhibits a mixture of their own and donor characteristics, (phenotype) in hematopoietic cells after hematopoietic stem-cell transplant.
IMPORTANT REMINDERS
Any specific products referenced in this policy are just examples and are intended for illustrative purposes only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available. These examples are contained in the parenthetical e.g. statement.
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SOURCES
Caldemeyer, L.E., Akard, L.P., Edwards, J.R., Tandra, A., Wagenknecht, D.R., & Dugan, M.J. (2017). Donor lymphocyte 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-year survival if persistent full donor chimerism is obtained or maintained. Biology of Blood and Marrow Transplantation, 23 (11), 1989-1997. (Level 4 evidence).
Dholaria, B., Savani, B.N., Labopin, M., Luznik, L., Ruggeri, A., Mielke, S., et al. (2020). Clinical applications of donor lymphocyte infusion from an HLA-haploidentical donor: consensus recommendations from the acute leukemia working party of the EBMT. Haematologica, 105 (1), 47-58. (Level 3 evidence)
Durer, S., Durer, C., Shafqat, M., Comba, IY., Malik, S., Faridi, W., et al. (2019). Concomitant use of blinatumomab and donor lymphocyte infusion for mixed-phenotype acute leukemia: A case report with literature review. Immunotherapy, 11 (5), 373-378. (Level 4 evidence)
El-Jurdi, N., Reljic, T., Kumar, A., Pidala, J., Bazarbachi, A., Djulbegovic, B., & Kharfan-Dabaja, M. (2013). Efficacy of adoptive immunotherapy with donor lymphocyte infusion in relapsed lymphoid malignancies. Immunotherapy, 5 (5), 457-466. Abstract retrieved October 14, 2016 from PubMed database.
Liou, A., Wahlstrom, J.T., Dvorak, C.C., & Horn, B.N. (2017). Safety of pre-emptive donor lymphocyte infusions (DLI) based on mixed chimerism (MC) in peripheral blood or bone marrow subsets in children undergoing hematopoietic stem cell transplant (HSCT) for hematologic malignancies. Bone Marrow Transplantation, 52 (7), 1027-1059. (Level 3 evidence)
National Comprehensive Cancer Network. (2023, December). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Chronic myeloid leukemia (V. 2.2024). Retrieved May 14, 2024 from the National Comprehensive Cancer Network.
National Comprehensive Cancer Network. (2024, April). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Multiple myeloma (V. 4.2024). Retrieved May 14, 2024 from the National Comprehensive Cancer Network.
National Comprehensive Cancer Network. (2024, February). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Acute lymphoblastic leukemia (V. 4.2023). Retrieved May 14, 2024 from the National Comprehensive Cancer Network.
National Comprehensive Cancer Network. (2024, March). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Acute myeloid leukemia (V. 2.2024). Retrieved May 14, 2024 from the National Comprehensive Cancer Network.
Rettig, A. R., Ihorst, G., Bertz, H., Lübbert, M., Marks, R., Waterhouse, M., et al. (2021). Donor lymphocyte infusions after first allogeneic hematopoietic stem-cell transplantation in adults with acute myeloid leukemia: a single-center landmark analysis. Annals of Hematology, 100 (9), 2339–2350, doi: 10.1007/s00277-021-04494-z. (Level 2 evidence)
Takami, A., Yano, S., Yokoyama, H., Kuwatsuka, Y., Yamaguchi, T., Kanda, Y., et al. (2014). Donor lymphocyte infusion for the treatment of relapsed acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation: a retrospective analysis by the adult acute myeloid leukemia working group of the Japan Society for Hematopoietic Cell Transplantation. Biology of Blood and Marrow Transplantation, 20, 1785-1790. (Level 4 evidence)
Vaezi, M., Zokaasadi, M., Pour, S.S., Kasaeian, A., Nikbakht, M., Fumani, K., et al. (2018). The role of donor leukocyte infusions in the treatment of relapsed acute leukemia after allogeneic stem cell transplantation: a retrospective analysis. International Journal of Hematology-Oncology and Stem Cell Research, 12 (3), 185-191. (Level 4 evidence)
Yan, C., Wang, Y., Wang, J., Chen, Y., Chen, Y., Wang, F., et al. (2016). Minimal residual disease- and graft-vs.-host disease-guided multiple consolidation chemotherapy and donor lymphocyte infusion prevent second acute leukemia relapse after allotransplant. Journal of Hematology & Oncology, 9, 87. (Level 4 evidence)
ORIGINAL EFFECTIVE DATE: 8/1/2000
MOST RECENT REVIEW DATE: 6/13/2024
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