title: Results of allogeneic bone marrow transplants for leukemia using donors other than HLA-identical siblings.
abstract: OBJECTIVE
  To compare outcomes of bone marrow transplants for leukemia from HLA-identical siblings, haploidentical HLA-mismatched relatives, and HLA-matched and mismatched unrelated donors.
  
  
  METHODS
  A total of 2,055 recipients of allogeneic bone marrow transplants for chronic myelogenous leukemia (CML), acute myelogenous leukemia (AML), and acute lymphoblastic leukemia (ALL) were entered onto the study. Transplants were performed between 1985 and 1991 and reported to the International Bone Marrow Transplant Registry (IBMTR). Donors were HLA-identical siblings (n = 1,224); haploidentical relatives mismatched for one (n = 238) or two (n = 102) HLA-A, -B, or -DR antigens; or unrelated persons who were HLA-matched (n = 383) or mismatched for one HLA-A, -B, or -DR antigen (n = 108). HLA typing was performed using serologic techniques.
  
  
  RESULTS
  Transplant-related mortality was significantly higher after alternative donor transplants than after HLA-identical sibling transplants. Among patients with early leukemia (CML in chronic phase or acute leukemia in first remission), 3-year transplant-related mortality (+/-SE) was 21% +/- 2% after HLA-identical sibling transplants and greater than 50% after all types of alternative donor transplants studied. Among patients with early leukemia, relative risks of treatment failure (inverse of leukemia-free survival), using HLA-identical sibling transplants as the reference group, were 2.43 (P < .0001) with 1-HLA-antigen-mismatched related donors, 3.79 (P < .0001) with 2-HLA-antigen-mismatched related donors, 2.11 (P < .0001) with HLA-matched unrelated donors, and 3.33 (P < .0001) with 1-HLA-antigen-mismatched unrelated donors. For patients with more advanced leukemia, differences in treatment failure were less striking: 1-HLA-antigen-mismatched relatives, 1.22 (P = not significant [NS]); 2-HLA-antigen-mismatched relatives, 1.81 (P < .0001); HLA-matched unrelated donors, 1.39 (P = .002); and 1-HLA-antigen-mismatched unrelated donors, 1.63 (P = .002).
  
  
  CONCLUSIONS
  Although transplants from alternative donors are effective in some patients with leukemia, treatment failure is higher than after HLA-identical sibling transplants. Outcome depends on leukemia state, donor-recipient relationship, and degree of HLA matching. In early leukemia, alternative donor transplants have a more than twofold increased risk of treatment failure compared with HLA-identical sibling transplants. This difference is less in advanced leukemia.
authors.affiliation: International Bone Marrow Transplant Registry, Health Policy Institute, Medical College of Wisconsin, Milwaukee, USA.
authors.forename: R
authors.initials: R
authors.lastname: Szydlo
authors.forename: J M
authors.initials: JM
authors.lastname: Goldman
authors.forename: J P
authors.initials: JP
authors.lastname: Klein
authors.forename: R P
authors.initials: RP
authors.lastname: Gale
authors.forename: R C
authors.initials: RC
authors.lastname: Ash
authors.forename: F H
authors.initials: FH
authors.lastname: Bach
authors.forename: B A
authors.initials: BA
authors.lastname: Bradley
authors.forename: J T
authors.initials: JT
authors.lastname: Casper
authors.forename: N
authors.initials: N
authors.lastname: Flomenberg
authors.forename: J L
authors.initials: JL
authors.lastname: Gajewski
authors.forename: E
authors.initials: E
authors.lastname: Gluckman
authors.forename: P J
authors.initials: PJ
authors.lastname: Henslee-Downey
authors.forename: J M
authors.initials: JM
authors.lastname: Hows
authors.forename: N
authors.initials: N
authors.lastname: Jacobsen
authors.forename: H J
authors.initials: HJ
authors.lastname: Kolb
authors.forename: B
authors.initials: B
authors.lastname: Lowenberg
authors.forename: T
authors.initials: T
authors.lastname: Masaoka
authors.forename: P A
authors.initials: PA
authors.lastname: Rowlings
authors.forename: P M
authors.initials: PM
authors.lastname: Sondel
authors.forename: D W
authors.initials: DW
authors.lastname: van Bekkum
authors.forename: J J
authors.initials: JJ
authors.lastname: van Rood
authors.forename: M R
authors.initials: MR
authors.lastname: Vowels
authors.forename: M J
authors.initials: MJ
authors.lastname: Zhang
authors.forename: M M
authors.initials: MM
authors.lastname: Horowitz
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D016026:Bone Marrow Transplantation; D006086:Graft vs Host Disease / Q000276:immunology; D006648:Histocompatibility; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000628:therapy*; D015470:Leukemia, Myeloid, Acute / Q000628:therapy*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000628:therapy*; D012008:Recurrence; D014019:Tissue Donors; D016896:Treatment Outcome