UNRELATED DONOR MARROW TRANSPLANTATION IN CHILDREN

Eighty-eight children 0.5 to 17 years of age (median, 9 years of age) received an unrelated donor marrow transplant for treatment of chronic myeloid leukemia (CML; n = 16), acute lymphoblastic leukemia (ALL) in first or second remission (9 = 15) or more advanced stage (n = 28), a cute myeloid leukemia (AML; n = 13), or other hematologic diseases (n = 16) between June 1985 and April 1993. All patients were conditioned with cyclophosphamide and total body irradiation and received a combin ation of methotrexate and cyclosporine as graft-versus-host disease (G VHD) prophylaxis. Fourty-six patients received transplants from HLA-id entical donors and 42 patients received transplants from donors who we re minor-mismatched at one HLA-A or B or D/DRB1 locus. The Kaplan-Meie r estimates of disease-free survival and relapse were 75% and 0% for p atients with CML, 47% and 20% for ALL in first or second remission, 10 % and 60% for ALL in relapse or third remission, 46% and 46% for AML i n first remission (n = 1) or more advanced disease (n = 12), and 29% a nd 69% for other diseases. HLA disparity was not significantly associa ted with lower disease-free survival, but the results suggest more rel apses in HLA-matched recipients and there was significantly more trans plant-related mortality in mismatched recipients (51% v 24%, P = .04). Most deaths were due to infections associated with acuteor chronic GV HD and occurred within the first 2 years after transplantation. Granul ocyte engraftment occurred in all evaluable patients. Sixty-three perc ent of HLA-matched and 57% of HLA-mismatched recipients were discharge d home disease-free at a median of 98 and 103 days, respectively, afte r transplantation (P = not significant [NS]). The incidence of grades Il-IV acute GVHD was 83% in HLA-matched and 98% in HLA-mismatched reci pients (P = .009). The incidence of chronic GVHD was 60% in HLA-matche d and 69% in HLA-mismatched recipients (P = NS). One or multiple late adverse events such as cataracts, osteonecrosis of the hip or knee, re strictive or obstructive pulmonary disease, and hypothyroidism have oc curred in 11 of 33 (33%) surviving patients. Immunosuppression was dis continued in 58% of surviving patients, including all 12 patients surv iving more than 3.2 years, all of whom have a Lansky or Karnofsky scor e of 100%. These data show that marrow transplantation from fully or p artially HLA-matched unrelated donors can be effective therapy for chi ldren with hematologic disorders and that pretransplantation disease s tatus and posttransplantation GVHD remain important factors affecting patient outcome. (C) 1995 by The American Society of Hematology.