melphalan, single-fraction total-body irradiation and allogeneic bone marrow transplantation for acute leukemia: review of transplant-related mortality.

Causes of treatment-related death were studied amongst 138 patients with acute myeloid (n = 90) or lymphoblastic (n = 48) leukemia allografted from HLA-identical siblings in first (n = 107) or second (n = 31) remission after a conditioning regimen comprising 110 mg/m2 melphalan and 1050 cGy single-fraction total-body irradiation (TBI) prescribed as maximum lung dose. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine (n = 78) or cyclosporine-methotrexate (n = 60). Eighty-one patients died of causes other than relapse 16-2917 days (median 77) after transplantation. The actuarial probability of non-relapse mortality was 62% at 5 years. The major primary causes of death were pneumonitis (n = 38, 47%), GVHD (n = 18, 22%), and sepsis (n = 11, 14%). Pneumonitis contributed to 42 of the deaths (52%), and its etiology was infective (n = 27), idiopathic (n = 14), or a combination of the two (n = 1). On multivariate analysis, GVHD prophylaxis with cyclosporine alone was associated with a higher overall toxic death rate. The use of cyclosporine alone and a low infused cell dose (<2.5 x 10(8) total nucleated cells/kg or <0.6 x 10(8) mononuclear cells/kg) were associated with a higher risk of death from pneumonitis. We conclude that the use of cyclosporine alone as GVHD prophylaxis is associated with increased transplant-related toxicity, and the addition of methotrexate and infusion of a higher number of cells decrease the incidence of fatal pneumonitis.