title: Tacrolimus and minidose methotrexate for prevention of acute graft-versus-host disease after matched unrelated donor marrow transplantation.
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 (i.v.) by continuous infusion from day -2, converted to oral at four times the i.v. dose following engraftment, and continued through day 180 posttransplant. Methotrexate 5 mg/m2 was given i.v. 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 i.v. 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.
authors.affiliation: Department of Hematology, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
authors.forename: D
authors.initials: D
authors.lastname: Przepiorka
authors.forename: C
authors.initials: C
authors.lastname: Ippoliti
authors.forename: I
authors.initials: I
authors.lastname: Khouri
authors.forename: M
authors.initials: M
authors.lastname: Woo
authors.forename: R
authors.initials: R
authors.lastname: Mehra
authors.forename: D
authors.initials: D
authors.lastname: Le Bherz
authors.forename: S
authors.initials: S
authors.lastname: Giralt
authors.forename: J
authors.initials: J
authors.lastname: Gajewski
authors.forename: H
authors.initials: H
authors.lastname: Fischer
authors.forename: H
authors.initials: H
authors.lastname: Fritsche
authors.forename: A B
authors.initials: AB
authors.lastname: Deisseroth
authors.forename: K
authors.initials: K
authors.lastname: Cleary
authors.forename: R
authors.initials: R
authors.lastname: Champlin
authors.forename: K
authors.initials: K
authors.lastname: Besien
authors.forename: B
authors.initials: B
authors.lastname: Andersson
authors.forename: R
authors.initials: R
authors.lastname: Maher
authors.forename: W
authors.initials: W
authors.lastname: Fitzsimmons
mesh_terms: D000206:Actuarial Analysis; D000284:Administration, Oral; D000328:Adult; D000754:Anemia, Refractory, with Excess of Blasts / Q000628:therapy; D016026:Bone Marrow Transplantation / Q000009:adverse effects* / Q000276:immunology / Q000401:mortality; D003404:Creatinine / Q000097:blood; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D007674:Kidney Diseases / Q000097:blood / Q000139:chemically induced; D007938:Leukemia / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D008223:Lymphoma / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D016879:Salvage Therapy; D016019:Survival Analysis; D016559:Tacrolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019172:Transplantation Conditioning
chemical_list: D007166:Immunosuppressive Agents; D003404:Creatinine; D016559:Tacrolimus; D008727:Methotrexate