TY - JOUR
T1 - Tacrolimus and minidose methotrexate for prevention of acute graft- versus-host disease after matched unrelated donor marrow transplantation
AU - Przepiorka, Donna
AU - Ippoliti, Cindy
AU - Khouri, Issa
AU - Woo, Michael
AU - Mehra, Rakesh
AU - Le Bherz, Donna
AU - Giralt, Sergio
AU - Gajewski, James
AU - Fischer, Harald
AU - Fritsche, Herbert
AU - Deisseroth, Albert B.
AU - Cleary, Karen
AU - Champlin, Richard
AU - Van Besien, Koen
AU - Andersson, Borje
AU - Maher, Rochelle
AU - Fitzsimmons, William
PY - 1996/12/1
Y1 - 1996/12/1
N2 - 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.
AB - 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.
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U2 - 10.1182/blood.v88.11.4383.bloodjournal88114383
DO - 10.1182/blood.v88.11.4383.bloodjournal88114383
M3 - Article
C2 - 8943876
AN - SCOPUS:10544224147
SN - 0006-4971
VL - 88
SP - 4383
EP - 4389
JO - Blood
JF - Blood
IS - 11
ER -