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Methotrexate, cyclosporine, or both to prevent graft-versus-host disease
after HLA-identical sibling bone marrow transplants for early leukemia?
O Ringden, MM Horowitz, P Sondel, RP Gale, JC Biggs, RE Champlin, HJ Deeg, K Dicke, T Masaoka and RL Powles
International Bone Marrow Transplant Registry, Medical College of
Wisconsin, Milwaukee 53226.
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.
Volume 81,
Issue 4,
pp. 1094-1101,
02/15/1993
Copyright © 1993 by The American Society of Hematology
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