title: Tacrolimus and minidose methotrexate for prevention of acute graft-versus-host disease after HLA-mismatched marrow or blood stem cell transplantation.
abstract: 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.
authors.affiliation: Department of Blood and Marrow Transplantation, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: D
authors.initials: D
authors.lastname: Przepiorka
authors.forename: I
authors.initials: I
authors.lastname: Khouri
authors.forename: C
authors.initials: C
authors.lastname: Ippoliti
authors.forename: N T
authors.initials: NT
authors.lastname: Ueno
authors.forename: R
authors.initials: R
authors.lastname: Mehra
authors.forename: M
authors.initials: M
authors.lastname: Körbling
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: M
authors.initials: M
authors.lastname: Donato
authors.forename: K
authors.initials: K
authors.lastname: Cleary
authors.forename: D
authors.initials: D
authors.lastname: Claxton
authors.forename: K W
authors.initials: KW
authors.lastname: Chan
authors.forename: I
authors.initials: I
authors.lastname: Braunschweig
authors.forename: K
authors.initials: K
authors.lastname: van Besien
authors.forename: B S
authors.initials: BS
authors.lastname: Andersson
authors.forename: P
authors.initials: P
authors.lastname: Anderlini
authors.forename: R
authors.initials: R
authors.lastname: Champlin
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000379:methods*; D004334:Drug Administration Schedule; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D012008:Recurrence; D015996:Survival Rate; D016559:Tacrolimus / Q000627:therapeutic use*
chemical_list: D016559:Tacrolimus; D008727:Methotrexate