title: Marrow transplantation from unrelated donors for patients with severe aplastic anemia who have failed immunosuppressive therapy.
abstract: Allogeneic marrow transplantation offers curative therapy for patients with aplastic anemia. We analyzed retrospective results in 141 patients with severe aplastic anemia who received transplants between 1988 and 1995 from an unrelated volunteer donor identified through the National Marrow Donor Program (NMDP). All patients had failed one or more courses of immunosuppressive therapy. Of the patients, 121 (86%) received a radiation-containing conditioning regimen, and 20 (14%) were given chemotherapy only. Based on serologic human leukocyte antigen (HLA) typing (class I and II), 105 patients (74%) received HLA-matched marrow, and 36 (26%) received marrow mismatched for at least one HLA-A, -B, or -DR antigen. Allele-level (molecular) typing for HLA-DRB1 was available in 108 donor-recipient pairs; 77 patients received DRB -matched and 31 DRB1-mismatched transplants. All but 13% of patients were given a cyclosporine-containing regimen for graft-vs.-host disease (GVHD) prophylaxis, and 45 patients (32%) received marrow that was T cell-depleted. Among 131 evaluable patients, 116 (89%) achieved sustained engraftment and 15 (11%) did not. Among patients with engraftment, acute GVHD of grades II-IV developed in 60 patients (52%) and extensive chronic GVHD in 24 patients at risk (31%). Currently, 51 patients (36%) are surviving at 11-94 months (median 36) after transplantation. All but five have Karnofsky scores > or =80. Patients who received a serologically matched transplant fared somewhat better than did patients given a serologically mismatched transplant p = 0.03). Patients with donors matched by both serology and allele-level DRB1 typing had significantly better survival than DRB1-mismatched patients with 56 vs. 15% surviving at 3 years p = 0.001). Outcome in patients transplanted within 3 years of diagnosis was superior to that among patients transplanted with greater delay. Major causes of death were graft failure, GVHD, and infections. These data suggest that unrelated marrow transplantation offers successful therapy for a proportion of patients who have failed immunosuppressive therapy.
authors.affiliation: Fred Hutchinson Cancer Research Center, the Department of Medicine, University of Washington, Seattle, USA.
authors.forename: H J
authors.initials: HJ
authors.lastname: Deeg
authors.forename: K
authors.initials: K
authors.lastname: Seidel
authors.forename: J
authors.initials: J
authors.lastname: Casper
authors.forename: C
authors.initials: C
authors.lastname: Anasetti
authors.forename: S
authors.initials: S
authors.lastname: Davies
authors.forename: J L
authors.initials: JL
authors.lastname: Gajeweski
authors.forename: M
authors.initials: M
authors.lastname: Territo
authors.forename: N
authors.initials: N
authors.lastname: Ramsay
authors.forename: R E
authors.initials: RE
authors.lastname: Harris
authors.forename: H
authors.initials: H
authors.lastname: Catro-Malaspina
authors.forename: R
authors.initials: R
authors.lastname: Collins
authors.forename: R
authors.initials: R
authors.lastname: Champlin
authors.forename: G
authors.initials: G
authors.lastname: Schoch
authors.forename: R
authors.initials: R
authors.lastname: King
authors.forename: C
authors.initials: C
authors.lastname: Howe
mesh_terms: D000293:Adolescent; D000328:Adult; D000741:Anemia, Aplastic / Q000188:drug therapy / Q000401:mortality / Q000628:therapy*; D016026:Bone Marrow Transplantation / Q000401:mortality; D002648:Child; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease; D006801:Humans; D016130:Immunophenotyping / Q000379:methods; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis; D015996:Survival Rate; D014019:Tissue Donors; D014184:Transplantation, Homologous / Q000379:methods / Q000401:mortality; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents