Donor Lymphocyte Infusion for Hematologic Malignancies Treated with an Allogeneic Hematopoietic Stem-Cell Transplant
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 mononuclear 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, multiple myeloma, myelodysplastic syndromes, chronic lymphocytic leukemia, Hodgkin's and non-Hodgkin's lymphoma.
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.
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 nonmyeloablative [reduced-intensity conditioning] allogeneic stem cell transplantation)
To convert an individual from mixed to full donor chimerism
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BlueCross BlueShield Association. Medical Policy Reference Manual. (9:2016). Donor lymphocyte infusion for malignancies treated with an allogeneic hematopoietic cell transplant (2.03.03). Retrieved August 25, 2017 from BlueWeb. (28 articles and/or guidelines reviewed)
British Committee for Standards in Haematology (BCSH). (2013). Guidelines for the diagnosis and management of multiple myeloma 2013. Retrieved October 14, 2016 from the National Guideline Clearinghouse (NGC: 009202).
Eefting, M., Halkes, C., de Wreede, L., van Pelt, C., Kersting, S., Marijt, E., et al. (2014). Myeloablative T cell-depleted alloSCT with early sequential prophylactic donor lymphocyte infusion is an efficient and safe post-remission treatment for adult ALL. Bone Marrow Transplantation, 49, 287-291. (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.
Liu, H. (2013) Prophylactic donor lymphocyte infusion to prevent relapse after allogeneic stem cell transplantation. Journal of Clinical & Medical Case Reports, 1 (1). (Level 5 evidence)
National Comprehensive Cancer Network. (2016, November). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Multiple myeloma (V. 3.2017). Retrieved August 25, 2017 from www.nccn.org.
National Comprehensive Cancer Network. (2017, August). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Chronic lymphocytic leukemia/small lymphocytic lymphoma (V. 1.2018). Retrieved August 25, 2017 from www.nccn.org.
National Comprehensive Cancer Network. (2017, February). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). T-cell lymphomas (V.2.2017). Retrieved August 25, 2017 from www.nccn.org.
National Comprehensive Cancer Network. (2017, June). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Acute lymphoblastic leukemia (V. 1.2017). Retrieved August 25, 2017 from www.nccn.org.
National Comprehensive Cancer Network. (2017, June). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Acute myeloid leukemia (V. 3.2017). Retrieved August 25, 2017 from www.nccn.org.
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 (2014), 1785-1790. (Level 4 evidence)
Warlick, E., DeFor, T., Blazar, B., Burns, L., Verneris, M., Uston., C., et al. (2012, March) Successful remission rates and survival after lymphodepleting chemotherapy for relapsed hematologic malignancies postallogeneic hematopoietic cell transplantation. Biology of Blood and Marrow Transplantation, 18 (3), 480-486. (Level 4 evidence)
Winifred S. Hayes, Inc. Medicl Technology Directory. (2017, August) Adoptive immunotherapy using genetically modified lymphocytes for lymphoproliferative disorders and hematological malignancies. Retrieved August 25, 2017 from www.hayesinc.com. (37 articles and/or guidelines reviewed)
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, (2016), 9, 87. (Level 4 evidence)
ORIGINAL EFFECTIVE DATE: 8/1/2000
MOST RECENT REVIEW DATE: 10/26/2017
Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.
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