Allogeneic cell-mediated immunotherapy using donor lymphocytes for prevention of relapse in patients treated with allogeneic bone marrow transplantation for hematological malignancies.
Two major causes of treatment failure in allogeneic BMT for leukemia are graft versus host disease (GVHD) and leukemic relapse. Acute GVHD, mediated by alloreactive donor T lymphocytes originating from the transfused marrow is the most significant cause of transplant-related morbidity and mortality, despite the use of combined prophylaxis with cyclosporine and methotrexate. Effective prevention of GVHD can be accomplished by depletion of donor immunocompetent T cells from the marrow prior to its infusion. Depletion of lymphocytes, however, prevents the immune mediated interaction of donor T cells against residual host tumor cells--the graft versus leukemia (GVL) effect, which significantly contributes to the curative effect of allogeneic BMT. It is still unsettled to what extent GVH and GVL are unseparable or closely related phenomena, and a major question remains whether it would be possible to retain the beneficial antileukemic effects of donor T cells and at the same time prevent or control the risk of GVHD. We have adopted a policy by which an allogeneic BMT is conducted with T cell depleted marrow to minimize the risk of severe acute GVHD, followed by stepwise administration of fresh unirradiated donor lymphocytes for prevention of leukemic relapse. Our data show that the overall relapse free survival was significantly better for patients receiving preventive posttransplant donor lymphocytes, predominantly when transplant was performed in 1st or 2nd CR.
Naparstek
E
E
Department of Bone Marrow Transplantation, Hadassah University Hospital, Jerusalem, Israel.
Nagler
A
A
Or
R
R
Kapelushnik
J
J
Slavin
S
S
D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation / Q000276:immunology* / Q000401:mortality; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control; D006785:Hospitals, University; D006801:Humans; D007111:Immunity, Cellular; D007223:Infant; D007557:Israel; D007938:Leukemia / Q000401:mortality / Q000628:therapy*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000628:therapy; D015470:Leukemia, Myeloid, Acute / Q000628:therapy; D008212:Lymphocyte Depletion; D017710:Lymphocyte Transfusion; D008297:Male; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000628:therapy; D012008:Recurrence; D012189:Retrospective Studies; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation*; D014019:Tissue Donors; D014184:Transplantation, Homologous