title: Methotrexate and cyclosporine versus cyclosporine alone for prophylaxis of graft-versus-host disease in patients given HLA-identical marrow grafts for leukemia: long-term follow-up of a controlled trial.
abstract: Patients with acute nonlymphoblastic leukemia (ANL) in first remission (n = 38) or chronic myelocytic leukemia (CML) (n = 55) were given cyclophosphamide and total body irradiation, followed by marrow infusion from HLA-identical siblings. To evaluate postgrafting prophylaxis for acute graft-versus-host disease (GVHD), the patients were randomized to receive either methotrexate and cyclosporine (n = 43) or cyclosporine alone (n = 50). Methotrexate/cyclosporine significantly reduced the incidence and severity of acute GVHD, and improved early survival. This report updates the results with a 3.0 to 4.5 year follow-up. Methotrexate/cyclosporine did not interfere with sustained hematopoietic engraftment, although granulocyte recovery to 1,000/microL was delayed by five days on the average. The incidence of chronic GVHD was identical in the two groups (26% v 24%). Disease-free 3-year survival was slightly better in the methotrexate/cyclosporine group (65% v 54%), but this benefit was restricted to patients with CML (73% v 54%), while no improvement was seen in patients with ANL (41% v 41%). In contrast to patients with CML (relapse rates 8% v 9%), the early survival benefit among patients with ANL given methotrexate/cyclosporine was offset by an increase in leukemic relapses (29% v 16%).
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98104.
authors.forename: R
authors.initials: R
authors.lastname: Storb
authors.forename: H J
authors.initials: HJ
authors.lastname: Deeg
authors.forename: M
authors.initials: M
authors.lastname: Pepe
authors.forename: F
authors.initials: F
authors.lastname: Appelbaum
authors.forename: C
authors.initials: C
authors.lastname: Anasetti
authors.forename: P
authors.initials: P
authors.lastname: Beatty
authors.forename: W
authors.initials: W
authors.lastname: Bensinger
authors.forename: R
authors.initials: R
authors.lastname: Berenson
authors.forename: C D
authors.initials: CD
authors.lastname: Buckner
authors.forename: R
authors.initials: R
authors.lastname: Clift
mesh_terms: D000208:Acute Disease; D016026:Bone Marrow Transplantation; D002908:Chronic Disease; D003524:Cyclosporins / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000517:prevention & control*; D006680:HLA Antigens / Q000032:analysis; D006801:Humans; D007938:Leukemia / Q000628:therapy*; D008727:Methotrexate / Q000008:administration & dosage*; D011379:Prognosis; D013997:Time Factors
chemical_list: D003524:Cyclosporins; D006680:HLA Antigens; D008727:Methotrexate