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 myel oid leukemia in first remission received marrow transplants from HLA-i dentical siblings after conditioning with 120 mg/kg of cyclophosphamid e and 12.0 Gy fractionated total body irradiation. Patients received e ither cyclosporine (CYA, n = 59), methotrexate (MTX, n = 82), or MTX CYA (n = 43 as graft-versus-host disease (GVHD) prophylaxis. The prob abilities 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-r elapse mortality was 0.53, 0.50 and 0.42 at 4 years in patients treate d with CYA, MTX, or MTX + CYA, respectively. The probability of relaps e was 0.24 in patients receiving CYA, 0.24 in patients receiving MTX a nd 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 MT X + 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 achi eve a remission, maintenance therapy, consolidation therapy, marrow ce ll dose, donor-recipient sex, GVHD prophylaxis regimen and isolation a nd decontamination in laminar airflow rooms. GVHD prophylaxis with MTX + CYA was independently significantly associated with an increased ri sk of relapse (relative risk 2.25, p = 0.01). Acute GVHD was associate d with increased non-relapse mortality (RR = 3.58, p < 0.0001). The ad ministration of MTX + CYA did not adversely affect survival because pa tients receiving this regimen experienced less mortality from causes o ther than relapse when compared with patients receiving either CYA or MTX alone.