title: Unrelated donor marrow transplantation in children.
abstract: 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 (n = 15) or more advanced stage (n = 28), acute 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 combination of methotrexate and cyclosporine as graft-versus-host disease (GVHD) prophylaxis. Fourty-six patients received transplants from HLA-identical donors and 42 patients received transplants from donors who were minor-mismatched at one HLA-A or B or D/DRB1 locus. The Kaplan-Meier estimates of disease-free survival and relapse were 75% and 0% for patients 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 in first remission (n = 1) or more advanced disease (n = 12), and 29% and 69% for other diseases. HLA disparity was not significantly associated with lower disease-free survival, but the results suggest more relapses in HLA-matched recipients and there was significantly more transplant-related mortality in mismatched recipients (51% v 24%, P = .04). Most deaths were due to infections associated with acute or chronic GVHD and occurred within the first 2 years after transplantation. Granulocyte engraftment occurred in all evaluable patients. Sixty-three percent of HLA-matched and 57% of HLA-mismatched recipients were discharged home disease-free at a median of 98 and 103 days, respectively, after transplantation (P = not significant [NS]). The incidence of grades II-IV acute GVHD was 83% in HLA-matched and 98% in HLA-mismatched recipients (P = .009). The incidence of chronic GVHD was 60% in HLA-matched and 69% in HLA-mismatched recipients (P = NS). One or multiple late adverse events such as cataracts, osteonecrosis of the hip or knee, restrictive or obstructive pulmonary disease, and hypothyroidism have occurred in 11 of 33 (33%) surviving patients. Immunosuppression was discontinued in 58% of surviving patients, including all 12 patients surviving more than 3.2 years, all of whom have a Lansky or Karnofsky score of 100%. These data show that marrow transplantation from fully or partially HLA-matched unrelated donors can be effective therapy for children with hematologic disorders and that pretransplantation disease status and posttransplantation GVHD remain important factors affecting patient outcome.
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98104, USA.
authors.forename: A
authors.initials: A
authors.lastname: Balduzzi
authors.forename: T
authors.initials: T
authors.lastname: Gooley
authors.forename: C
authors.initials: C
authors.lastname: Anasetti
authors.forename: J E
authors.initials: JE
authors.lastname: Sanders
authors.forename: P J
authors.initials: PJ
authors.lastname: Martin
authors.forename: E W
authors.initials: EW
authors.lastname: Petersdorf
authors.forename: F R
authors.initials: FR
authors.lastname: Appelbaum
authors.forename: C D
authors.initials: CD
authors.lastname: Buckner
authors.forename: D
authors.initials: D
authors.lastname: Matthews
authors.forename: R
authors.initials: R
authors.lastname: Storb
authors.forename: K M
authors.initials: KM
authors.lastname: Sullivan
authors.forename: J A
authors.initials: JA
authors.lastname: Hansen
mesh_terms: D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation / Q000706:statistics & numerical data; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000517:prevention & control; D006680:HLA Antigens / Q000276:immunology; D006402:Hematologic Diseases / Q000401:mortality / Q000628:therapy*; D006648:Histocompatibility; D006801:Humans; D015994:Incidence; D007223:Infant; D007938:Leukemia / Q000401:mortality / Q000628:therapy*; D015993:Life Tables; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D012074:Remission Induction; D016879:Salvage Therapy; D016019:Survival Analysis; D014019:Tissue Donors; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D006680:HLA Antigens