Methotrexate, cyclosporine, or both to prevent graft-versus-host disease after HLA-identical sibling bone marrow transplants for early leukemia?

Abstract

Optimal prophylaxis of graft-versus-host disease (GVHD) is controversial. We compared efficacy of three posttransplant immune suppressive regimens in 2,286 recipients of HLA-identical sibling bone marrow transplants for acute lymphoblastic leukemia (ALL) in first remission, acute myelogenous leukemia (AML) in first remission, or chronic myelogenous leukemia (CML) in first chronic phase. Six hundred forty received methotrexate, 977 received cyclosporine, and 669 received combined cyclosporine and methotrexate. In children, the three regimens resulted in similar outcomes. In adults, cyclosporine and methotrexate had comparable risks of acute and chronic GVHD. Compared with methotrexate, cyclosporine was associated with less interstitial pneumonia (relative risk [RR] = 0.6; P < .001), less treatment-related mortality (RR = 0.6; P < .001), more relapses (RR = 1.6; P < .05), and less treatment failure (relapse or death from any cause; RR = 0.7; P < .001). Different effects were observed in different leukemias. In ALL, the rate of leukemia relapse was increased with cyclosporine versus methotrexate, with no effect on other outcomes. In AML and CML, interstitial pneumonia, treatment-related mortality, and treatment failures were decreased with cyclosporine, with no increase in relapse. Similar analyses comparing cyclosporine plus methotrexate with cyclosporine alone showed that adults receiving the combination had less acute GVHD (RR = 0.5; P < .001), less chronic GVHD (RR = 0.7; P < .01), and less interstitial pneumonia (RR = 0.7; P < .001). Treatment failure (RR = 0.8; P < .05) was marginally reduced. Separate analyses in ALL and AML showed less acute GVHD with combined therapy, but no significant effect on other outcomes. In CML, acute GVHD, interstitial pneumonia, treatment-related mortality, and treatment failure were decreased with combined therapy.

GVHD prophylaxis using low‐dose cyclosporine improves survival in leukaemic recipients of HLA‐identical sibling transplants

“…Immunosuppression remains crucial for the clinical outcome of allogeneic haematopoietic stem cell transplantation (HSCT). Since the late 1980s, cyclosporine A (CsA) and a short course of methotrexate (MTX) have been the most common immunosuppressive regimen to prevent graft-versus-host disease (GVHD) (1)(2)(3)(4). In these protocols, treatment with CsA has mostly been initiated on day 1 with intravenous doses of 3-5 mg ⁄ kg per day.…”

Allogeneic blood or marrow transplantation for chronic lymphocytic leukaemia: timing of transplantation and potential effect of fludarabine on acute graft‐versus‐host disease

“…Despite the use of intensive immunosuppression, acute graft-versus-host disease (aGVHD) remains a major cause of mortality and morbidity in humans receiving allogeneic marrow or peripheral blood stem cell transplantation (Storb et al, 1986;Ringdén et al, 1993). Fludarabine is a potent immunosuppressive agent producing marked reduction of CD4 þ and CD8 þ cells (Keating et al, 1989).…”

Alternative Donor Graft Sources for Adults with Hematologic Malignancies: A Donor for All Patients in 2017!

“…Overall survival, disease-free survival, TRM, and relapse are now similar in MSD and MUD HSCT recipients [9,15]. A calcineurin inhibitor plus methotrexate combination for GVHD prophylaxis has decreased the rates of acute and chronic GVHD in patients who have had a MUD HSCT [16,17]. When antithymocyte globulin was added to cyclosporine and methotrexate GVHD prophylaxis, a reduction in acute and chronic GVHD was seen, as well as decreased immunosuppression use at 1 year without an increase in morbidity or mortality [18,19].…”