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.
Hjiyiannakis
P
P
Department of Clinical Oncology, Royal Marsden NHS Trust, Sutton, Surrey, UK.
Mehta
J
J
Milan
S
S
Powles
R
R
Hinson
J
J
Tait
D
D
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects* / Q000627:therapeutic use; D016026:Bone Marrow Transplantation / Q000009:adverse effects* / Q000276:immunology / Q000379:methods; D002648:Child; D002675:Child, Preschool; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000401:mortality; D006801:Humans; D007951:Leukemia, Myeloid / Q000628:therapy*; D017563:Lung Diseases, Interstitial / Q000209:etiology / Q000401:mortality; D008297:Male; D008558:Melphalan / Q000009:adverse effects* / Q000627:therapeutic use; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000628:therapy*; D018805:Sepsis / Q000209:etiology / Q000401:mortality; D019172:Transplantation Conditioning / Q000009:adverse effects* / Q000379:methods; D014916:Whole-Body Irradiation / Q000009:adverse effects*
D018906:Antineoplastic Agents, Alkylating; D008558:Melphalan