Phase 3 study comparing methotrexate and tacrolimus with methotrexate and cyclosporine for prophylaxis of acute graft-versus-host disease after marrow transplantation from unrelated donors

R. A. Nash, J. H. Antin, C. Karanes, J. W. Fay, B. R. Avalos, A. M. Yeager, D. Przepiorka, S. Davies, F. B. Petersen, P. Bartels, D. Buell, W. Fitzsimmons, C. Anasetti, R. Storb, V. Ratanatharathorn

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438 Scopus citations

Abstract

After the transplantation of unmodified marrow from human leukocyte antigen-matched unrelated donors receiving cyclosporine (CSP) and methotrexate (MTX), the incidence of acute graft-versus-host disease (GVHD) is greater than 75%. Tacrolimus is a macrolide compound that, in previous preclinical and clinical studies, was etfective in combination with MTX for the prevention of acute GVHD. Between March 1995 and September 1996, 180 patients were randomized in a phase 3, open-label, multicenter study to determine whether tacrolimus combined with a short course of MTX (n = 90), more than CSP and a short course of MTX (n = 90), would reduce the incidence of acute GVHD after marrow transplantation from unrelated donors. There was a significant trend toward decreased severity of acute GVHD across all grades (P = .005). Based on the Kaplan-Meier estimate, the probability of grade IMV acute GVHD in the tacrolimus group (56%) was significantly lower than in the CSP group (74%; P = .0002). Use of glucocorticoids for the management of GVHD was significantly lower with tacrolimus than with CSP (65% vs 81%, respectively; P = .019). The number of patients requiring dialysis in the first 100 days was similar (tacrolimus, 9; CSP, 8). Overall and relapse-free survival rates for the tacrolimus and CSP arms at 2 years was 54% versus 50% (P = .46) and 47% versus 42% (P = .58), respectively. The combination of tacrolimus and MTX after unrelated donor marrow transplantation significantly decreased the risk for acute GVHD than did the combination of CSP and MTX, with no significant increase in toxicity, infections, or leukemia relapse. (C) 2000 by The American Society of Hematology.

Original languageEnglish (US)
Pages (from-to)2062-2068
Number of pages7
JournalBlood
Volume96
Issue number6
StatePublished - Sep 15 2000

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Nash, R. A., Antin, J. H., Karanes, C., Fay, J. W., Avalos, B. R., Yeager, A. M., Przepiorka, D., Davies, S., Petersen, F. B., Bartels, P., Buell, D., Fitzsimmons, W., Anasetti, C., Storb, R., & Ratanatharathorn, V. (2000). Phase 3 study comparing methotrexate and tacrolimus with methotrexate and cyclosporine for prophylaxis of acute graft-versus-host disease after marrow transplantation from unrelated donors. Blood, 96(6), 2062-2068.