Effect of graft-versus-host disease prophylaxis on relapse in patients transplanted for acute myeloid leukemia.
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.
Weaver
C H
CH
Fred Hutchinson Cancer Research Center, Seattle, WA 98104.
Clift
R A
RA
Deeg
H J
HJ
Storb
R
R
Appelbaum
F R
FR
Bensinger
W
W
Doney
K
K
Hansen
J A
JA
Martin
P O
PO
Sanders
J
J
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
D003520:Cyclophosphamide; D008727:Methotrexate