Donor Lymphocyte Infusion for Hematologic Malignancies Treated with an Allogeneic Hematopoietic Stem-Cell Transplant
DESCRIPTION
Treatment options are very limited for individuals with a hematologic malignancy that relapses after an allogeneic peripheral blood stem cell (allo-PBSC) or bone marrow transplant (allo-BMT). Donor lymphocyte infusion (DLI), also referred to as donor leukocyte or buffy coat transfusion, which involves obtaining a concentrated sample of mononuclear cells from the original human leukocyte antigen (HLA) and then infusing it into the relapsed leukemic individual. To reduce the volume of transfused cells, hematopoietic stem cells that repopulate the bone marrow, are physically separated from other blood components in the blood processor. "Buffy coat" is defined as the layer of white blood cells remaining after centrifugation of the blood sample, which causes the red blood cells to settle. Hematopoietic stem cells are further concentrated by removing the platelets, unwanted granulocytes, and red blood cells. If not transfused immediately, the cells are cryopreserved.
Once the relapsed individual has received the DLI, there follows a period of myelosuppression and bone marrow aplasia or hypoplasia, which is related to the occurrence of graft versus host disease (GVHD). This may develop due to the elimination of leukemic hematopoiesis mediated by infused donor lymphocyte cells before adequate donor hematopoiesis is reestablished.
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 disease and non-Hodgkin's lymphoma. In contrast to nonmyeloablative allogeneic stem cell transplant (also referred to as a reduced intensity stem cell transplant), in the setting of a prior myeloablative allogeneic stem cell transplant, a donor lymphocyte infusion is not part of the initial therapy but is considered a salvage therapy at the time of relapse.
POLICY
Donor lymphocyte infusion following allogeneic-hematopoietic stem cell transplantation for the treatment of hematologic malignancies is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
Repeat donor lymphocyte infusion, if positive health benefit responses are not documented, is considered investigational.
See also:
Autologous Hematopoietic Stem-Cell Transplantation for Malignant Astrocytomas and Gliomas
Hematopoietic Stem Cell Transplantation for Central Nervous System Embryonal and Ependymoma Tumors
Hematopoietic Stem-Cell Transplantation for Miscellaneous Solid Tumors in Adults
Hematopoietic Stem Cell Transplantation in the Treatment of Germ Cell Tumors
Pancreas / Pancreas-Kidney / Pancreatic Islet Cell Transplantation
Tandem High Dose Chemotherapy with Hematopoietic Stem Cell Support
MEDICAL APPROPRIATENESS
Donor lymphocyte infusion for the treatment of hematologic malignancies is considered medically appropriate if ANY ONE of the following criteria are met:
Hematologic malignancy has relapsed or is refractory
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.
We develop Medical Policies to provide guidance to Members and Providers. This Medical Policy relates only to the services or supplies described in it. The existence of a Medical Policy is not an authorization, certification, explanation of benefits or a contract for the service (or supply) that is referenced in the Medical Policy. For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed. If there is a conflict between the Medical Policy and a health plan, the express terms of the health plan will govern.
SOURCES
BlueCross BlueShield Association. Medical Policy Reference Manual. (5:2012). Donor leukocyte infusion for malignancies treated with an allogeneic hematologic stem cell transplant (2.03.03). Retrieved December 28, 2012 from BlueWeb. (19 articles and/or guidelines reviewed)
Cattoglio, C., Maruggi, G., Bartholomae, C., Malami, N., Pellon, D., Cocchiarella, F., et al. (2010). High-definition mapping of retroviral integration sites defines the fate of allogeneic T cells after donor lymphocyte infusion. PLoS One, 5 (12), e15688. (Level 4 Evidence - Independent study)
Guide to Medicare Coverage Issues [Computer software]. (2012, July) Stem cell transplantation (NCD 110.8.1, p. 2-53 to 2-55). Ingenix.
Deol, A., & Lum, L. G. (2010). Role of donor lymphocyte infusions in relapsed hematological malignancies after stem cell transplantation revisited. Cancer Treatment Reviews, 36 (7), 528-538.
Huang, X. J., Liu, D. H., Liu, K. Y., Xu, L. P., Chen, H., & Han, W. (2007). (2007). Donor lymphocyte infusion for the treatment of leukemia relapse after HLA-mismatched/haploidentical T-cell-replete hematopoietic stem cell transplantation. Haematologica, 92 (3), 414-417. (Level 3 Evidence - Independent study)
Lansigan, F., Choi, J., & Foss, F. M. (2008). Cutaneous T-cell lymphoma. Hematology/Oncology Clinics of North America, 22 (5), 979-996.
National Cancer Institute. (2010, September). Fact sheet. Bone marrow transplantation and peripheral blood stem cell transplantation. Received July 28, 2010 from http://www.cancer.gov/cancertopics/factsheet/Therapy/fs7_41.pdf.
National Cancer Institute. (2011, April). Adult acute myeloid leukemia treatment (PDQ®). Retrieved July 28, 2011 from http://www.cancer.gov/cancerinfo/pdq/treatment/adultAML/HealthProfessional.
National Cancer Institute. (2011, January). Adult non-hodgkin lymphoma treatment (PDQ®). Retrieved July 28, 2011 from http://www.cancer.gov/cancertopics/pdq/treatment/adult-non-hodgkins/healthprofessional.
National Cancer Institute. (2011, January). Plasma cell neoplasms (including multiple myeloma) treatment (PDQ®). Retrieved July 29, 2011 from http://www.cancer.gov/cancertopics/pdq/treatment/myeloma/healthprofessional/AllPages.
National Cancer Institute. (2011, July). Childhood acute lymphoblastic leukemia treatment (PDQ®). Retrieved July 28, 2011 from http://www.cancer.gov/cancertopics/pdq/treatment/childALL/healthprofessional.
National Cancer Institute. (2011, July). Chronic myelogenous leukemia treatment (PDQ®). Retrieved July 28, 2011 from http://www.cancer.gov/cancertopics/pdq/treatment/CML/healthprofessional.
National Comprehensive Cancer Network. (2011, August). NCCN clinical practice guidelines in oncology™. Non-Hodgkin’s lymphoma. (V.4.2011). Retrieved August 26, 2011 from http://www.nccn.org/professionals/physician_gls/pdf/nhl.pdf.
National Comprehensive Cancer Network. (2011, July). NCCN clinical practice guidelines in oncology™. Chronic myelogenous leukemia. (V.2.2012). Retrieved August 26, 2011 from http://www.nccn.org/professionals/physician_gls/pdf/cml.pdf.
National Comprehensive Cancer Network. (2011, July). NCCN clinical practice guidelines in oncology™. Multiple myeloma. (V.1.2012). Retrieved August 26, 2011 from http://www.nccn.org/professionals/physician_gls/pdf/myeloma.pdf.
Tomblyn, M., & Lazarus, H. M. (2008). Donor lymphocyte infusions: The long and winding road: How should it be traveled? Bone Marrow Transplantation, 42 (9), 569-579.
Toor, A., Rodriguez, T., Baumi, M., Matthews, H., Shanti, S., Senitzer, D., et al. (2008). Feasibility of conditioning with thymoglobulin and reduced intensity TBI to reduce acute GVHD in recipients of allogeneic SCT. Bone Marrow Transplant, 42 (11), 723-731. (Level 3 Evidence - Independent study)
Villalobos, I., Takahashi, Y., Akatsuka, Y., Muramatsu, H., Nishio, N., Hama, A., et al. (2010). Relapse of leukemia with loss of mismatched HLA resulting from uniparental disomy after haploidentical hematopoietic stem cell transplantation. Blood, 115 (15), 3158-3161.
Wrench, D., & Gribben, J. G. (2008). Stem cell transplantation for non-Hodgkin’s lymphoma. Hematology/Oncology Clinics of North America, 22 (5), 1051-1079.
Zhang, W., Choi, J., Zeng, W., Rogers, S. A., Alyea, E. P., Rheinwald, J. G., et al. (2010). Graft-versus-leukemia antigen CML66 elicits coordinated B-cell and T-cell immunity after donor lymphocyte infusion. Clinical Cancer Research, 16 (10), 2729-2739.
ORIGINAL EFFECTIVE DATE: 8/1/2000
MOST RECENT REVIEW DATE: 2/14/2013
ID_BA
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.
This document has been classified as public information.