TY - JOUR
T1 - Tacrolimus and minidose methotrexate for prevention of acute graft-versus-host disease after HLA-mismatched marrow or blood stem cell transplantation
AU - Przepiorka, D.
AU - Khouri, I.
AU - Ippoliti, C.
AU - Ueno, N. T.
AU - Mehra, R.
AU - Körbling, M.
AU - Giralt, S.
AU - Gajewski, J.
AU - Fischer, H.
AU - Donato, M.
AU - Cleary, K.
AU - Claxton, D.
AU - Chan, K. W.
AU - Braunschweig, I.
AU - Van Besien, K.
AU - Andersson, B. S.
AU - Anderlini, P.
AU - Champlin, R.
N1 - Funding Information:
We are grateful to the Transplant Clinical Nurse Specialists and the Nursing Staffs of P11 and P14 for excellent patient care. This work was supported in part by The Tony Anderson Fund, Fujisawa USA, Inc and Grant No. CA-16672 from the National Institutes of Health.
PY - 1999
Y1 - 1999
N2 - Thirty adults with leukemia or lymphoma transplanted with marrow or blood stem cells from 1-antigen mismatched related donors received tacrolimus and minidose methotrexate to prevent acute graft-versus-host disease (GVHD). The group had a median age of 42 years (range 18-56 years). Twenty-seven patients had advanced disease, and 13 were resistant to conventional therapy. Tacrolimus was administered at 0.03 mg/kg/day i.v. by continuous infusion from day -2, converted to oral at four times the i.v. dose following engraftment, and continued to day 180 post-transplant. Methotrexate 5 mg/m2 was given i.v. on days 1, 3, 6 and 11. Mild nephrotoxicity was common before day 100; 69% of patients had a doubling of creatinine, 56% had a peak creatinine greater than 2 mg/dl, and two patients were dialyzed. Other toxicities prior to day 100 thought to be related to tacrolimus included hypertension (45%), hyperkalemia (17%), hyperglycemia (14%), seizures (13%), headache (3%) and hemolytic uremic syndrome (3%). Grades 2-4 GVHD occurred in 59% (95% CI, 38-70%), and grades 3-4 GVHD in 17% (95% CI, 1-32%). Overall survival at 1 year was 29% (95% CI, 12-45%). We conclude that tacrolimus and minidose methotrexate is active post-transplant immunosuppression for patients with 1-antigen mismatched donors.
AB - Thirty adults with leukemia or lymphoma transplanted with marrow or blood stem cells from 1-antigen mismatched related donors received tacrolimus and minidose methotrexate to prevent acute graft-versus-host disease (GVHD). The group had a median age of 42 years (range 18-56 years). Twenty-seven patients had advanced disease, and 13 were resistant to conventional therapy. Tacrolimus was administered at 0.03 mg/kg/day i.v. by continuous infusion from day -2, converted to oral at four times the i.v. dose following engraftment, and continued to day 180 post-transplant. Methotrexate 5 mg/m2 was given i.v. on days 1, 3, 6 and 11. Mild nephrotoxicity was common before day 100; 69% of patients had a doubling of creatinine, 56% had a peak creatinine greater than 2 mg/dl, and two patients were dialyzed. Other toxicities prior to day 100 thought to be related to tacrolimus included hypertension (45%), hyperkalemia (17%), hyperglycemia (14%), seizures (13%), headache (3%) and hemolytic uremic syndrome (3%). Grades 2-4 GVHD occurred in 59% (95% CI, 38-70%), and grades 3-4 GVHD in 17% (95% CI, 1-32%). Overall survival at 1 year was 29% (95% CI, 12-45%). We conclude that tacrolimus and minidose methotrexate is active post-transplant immunosuppression for patients with 1-antigen mismatched donors.
KW - Graft-versus-host disease
KW - Mismatched marrow transplantation
KW - Tacrolimus
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U2 - 10.1038/sj.bmt.1701983
DO - 10.1038/sj.bmt.1701983
M3 - Article
C2 - 10516680
AN - SCOPUS:0032884873
SN - 0268-3369
VL - 24
SP - 763
EP - 768
JO - Bone marrow transplantation
JF - Bone marrow transplantation
IS - 7
ER -