title: Effect of graft-versus-host disease prophylaxis on relapse in patients transplanted for acute myeloid leukemia.
abstract: Between November 1978 and September 1988, 184 patients with acute myeloid leukemia in first remission received marrow transplants from HLA-identical siblings after conditioning with 120 mg/kg of cyclophosphamide and 12.0 Gy fractionated total body irradiation. Patients received either cyclosporine (CYA, n = 59), methotrexate (MTX, n = 82), or MTX + CYA (n = 43 as graft-versus-host disease (GVHD) prophylaxis. The probabilities of grades II-IV acute GVHD after CYA, MTX or MTX+CYA were 0.43, 0.48 and 0.28, respectively (p = 0.06). The probability of non-relapse mortality was 0.53, 0.50 and 0.42 at 4 years in patients treated with CYA, MTX, or MTX + CYA, respectively. The probability of relapse was 0.24 in patients receiving CYA, 0.24 in patients receiving MTX and 0.44 in patients receiving MTX + CYA (p = 0.02). The probability of survival at 4 years was 0.54 with CYA, 0.51 with MTX and 0.45 with MTX + CYA. A multivariate analysis of risk factors for relapse examined age, WBC at diagnosis, blast count at diagnosis, percentage of marrow blasts, FAB subtype, the number of remission induction courses to achieve a remission, maintenance therapy, consolidation therapy, marrow cell dose, donor-recipient sex, GVHD prophylaxis regimen and isolation and decontamination in laminar airflow rooms. GVHD prophylaxis with MTX + CYA was independently significantly associated with an increased risk of relapse (relative risk 2.25, p = 0.01). Acute GVHD was associated with increased non-relapse mortality (RR = 3.58, p < 0.0001). The administration of MTX + CYA did not adversely affect survival because patients receiving this regimen experienced less mortality from causes other than relapse when compared with patients receiving either CYA or MTX alone.
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA 98104.
authors.forename: C H
authors.initials: CH
authors.lastname: Weaver
authors.forename: R A
authors.initials: RA
authors.lastname: Clift
authors.forename: H J
authors.initials: HJ
authors.lastname: Deeg
authors.forename: R
authors.initials: R
authors.lastname: Storb
authors.forename: F R
authors.initials: FR
authors.lastname: Appelbaum
authors.forename: W
authors.initials: W
authors.lastname: Bensinger
authors.forename: K
authors.initials: K
authors.lastname: Doney
authors.forename: J A
authors.initials: JA
authors.lastname: Hansen
authors.forename: P O
authors.initials: PO
authors.lastname: Martin
authors.forename: J
authors.initials: J
authors.lastname: Sanders
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D016026:Bone Marrow Transplantation / Q000379:methods*; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage*; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control*; D006801:Humans; D007223:Infant; D007951:Leukemia, Myeloid / Q000628:therapy*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D015999:Multivariate Analysis; D012189:Retrospective Studies; D016019:Survival Analysis
chemical_list: D003520:Cyclophosphamide; D008727:Methotrexate