title: Sibling versus unrelated donor allogeneic hematopoietic cell transplantation for chronic myelogenous leukemia: refined HLA matching reveals more graft-versus-host disease but not less relapse.
abstract: Unrelated donor (URD) hematopoietic cell transplantation (HCT) can eradicate chronic myelogenous leukemia (CML). It has been postulated that greater donor-recipient histoincompatibility can augment the graft-versus-leukemia (GVL) effect. We previously reported similar, but not equivalent, outcomes of URD versus sibling donor HCT for CML using an older, less precise classification of HLA matching. Here, we used our recently refined HLA-matching classification, which is suitable for interpretation when complete allele-level typing is unavailable, to reanalyze outcomes of previous HCT for CML. We found that using our new matching criteria identifies substantially more frequent mismatching than older, less precise "6 of 6 antigen-matched" URD-HCT. Under the new criteria, only 37% of those previously deemed "HLA- matched" were HLA well matched, and 44% were partially matched. Using our refined matching criteria confirms the greater risk of graft failure in partially matched or mismatched URD-recipient pairs compared with either sibling or well-matched URD-recipient pairs. Acute and chronic graft-versus-host disease (aGVHD, cGVHD) are significantly more frequent with all levels of recategorized URD HLA matching. Importantly, overall survival (OS) and leukemia-free survival (LFS) remain significantly worse after URD-HCT at any matching level. No augmented GVL effect accompanied URD HLA mismatch. Compared with sibling donor transplants, we observed only marginally increased (not statistically significant) risks of relapse in well-matched, partially matched, and mismatched URD-HCT. These data confirm the applicability of revised HLA-matching scheme in analyzing retrospective data sets when fully informative, allele-level typing is unavailable. In this analysis, greater histoincompatibility can augment GVHD, but does not improve protection against relapse; thus the best donor remains the most closely matched donor.
authors.affiliation: University of Minnesota, Minneapolis, Minnesota 55455, USA. weisd001@umn.edu
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Weisdorf
authors.forename: Gene
authors.initials: G
authors.lastname: Nelson
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Lee
authors.forename: Michael
authors.initials: M
authors.lastname: Haagenson
authors.forename: Stephen
authors.initials: S
authors.lastname: Spellman
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Antin
authors.forename: Brian
authors.initials: B
authors.lastname: Bolwell
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Cahn
authors.forename: Francisco
authors.initials: F
authors.lastname: Cervantes
authors.forename: Edward
authors.initials: E
authors.lastname: Copelan
authors.forename: Robert
authors.initials: R
authors.lastname: Gale
authors.forename: Alois
authors.initials: A
authors.lastname: Gratwohl
authors.forename: H Jean
authors.initials: HJ
authors.lastname: Khoury
authors.forename: Philip
authors.initials: P
authors.lastname: McCarthy
authors.forename: David I
authors.initials: DI
authors.lastname: Marks
authors.forename: Jeff
authors.initials: J
authors.lastname: Szer
authors.forename: Ann
authors.initials: A
authors.lastname: Woolfrey
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes-Franco
authors.forename: Mary M
authors.initials: MM
authors.lastname: Horowitz
authors.forename: Mukta
authors.initials: M
authors.lastname: Arora
mesh_terms: D000328:Adult; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000453:epidemiology* / Q000209:etiology; D020544:Graft vs Leukemia Effect / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006648:Histocompatibility; D006650:Histocompatibility Testing / Q000379:methods; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology / Q000601:surgery*; D019520:Living Donors / Q000706:statistics & numerical data*; D008297:Male; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012008:Recurrence; D012189:Retrospective Studies; D035781:Siblings; D014184:Transplantation, Homologous / Q000276:immunology
chemical_list: D006680:HLA Antigens