Tacrolimus and minidose methotrexate for prevention of acute graft- versus-host disease after matched unrelated donor marrow transplantation

Donna Przepiorka, Cindy Ippoliti, Issa Khouri, Michael Woo, Rakesh Mehra, Donna Le Bherz, Sergio Giralt, James Gajewski, Harald Fischer, Herbert Fritsche, Albert B. Deisseroth, Karen Cleary, Richard Champlin, Koen Van Besien, Borje Andersson, Rochelle Maher, William Fitzsimmons

    Research output: Contribution to journalArticle

    110 Scopus citations

    Abstract

    Thirty adults with leukemia or lymphoma undergoing marrow transplantation from HLA-compatible unrelated donors received tacrolimus (FK506), a new immunosuppressive macrolide lactone, and minidose methotrexate to prevent acute graft-versus-host disease (GVHD). The group had a median age of 36 years (range 21 to 49 years). Twenty-four patients had advanced disease, and 11 were resistant to conventional therapy. Tacrolimus was administered at 0.03 mg/kg/d intravenously (IV) by continuous infusion from day -2, converted to oral at four times the IV dose following engraftment, and continued through day 180 posttransplant. Methotrexate 5 mg/m2 was given IV on days 1, 3, 6, and 11. All patients engrafted. Grades 2-4 GVHD occurred in 34% (95% CI, 17% to 52%), and grades 3-4 GVHD in 17% (95% CI, 3% to 31%). Mild renal toxicity was common before day 100; 63% of patients had a doubling of creatinine, and 52% had a peak creatinine greater than 2 mg/dL, but only one patient was dialyzed. The median last IV dose of tacrolimus was 53% of the scheduled dose, and the median oral dose on day 100 was 41% of that scheduled. Overall survival at 1 year was 47% (95% CI, 27% to 66%). We conclude that tacrolimus can be combined safely with minidose methotrexate, and the combination has substantial activity in preventing acute GVHD after unrelated donor marrow transplantation.

    Original languageEnglish (US)
    Pages (from-to)4383-4389
    Number of pages7
    JournalBlood
    Volume88
    Issue number11
    DOIs
    StatePublished - Dec 1 1996

    ASJC Scopus subject areas

    • Biochemistry
    • Immunology
    • Hematology
    • Cell Biology

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  • Cite this

    Przepiorka, D., Ippoliti, C., Khouri, I., Woo, M., Mehra, R., Le Bherz, D., Giralt, S., Gajewski, J., Fischer, H., Fritsche, H., Deisseroth, A. B., Cleary, K., Champlin, R., Van Besien, K., Andersson, B., Maher, R., & Fitzsimmons, W. (1996). Tacrolimus and minidose methotrexate for prevention of acute graft- versus-host disease after matched unrelated donor marrow transplantation. Blood, 88(11), 4383-4389. https://doi.org/10.1182/blood.v88.11.4383.bloodjournal88114383