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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. Biol Blood Marrow Transplant 2009 Nov;15(11):1475-8 PMID: 19822308 PMCID: PMC2929002

Pubmed ID

19822308

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.

Author List

Weisdorf DJ, Nelson G, Lee SJ, Haagenson M, Spellman S, Antin JH, Bolwell B, Cahn JY, Cervantes F, Copelan E, Gale R, Gratwohl A, Khoury HJ, McCarthy P, Marks DI, Szer J, Woolfrey A, Cortes-Franco J, Horowitz MM, Arora M, Chronic Leukemia Working Committee

Author

Mary M. Horowitz MD, MS Center Director, Professor in the Medicine department at Medical College of Wisconsin




Scopus

2-s2.0-70350619476   30 Citations

MESH terms used to index this publication - Major topics in bold

Adult
Disease-Free Survival
Female
Graft vs Host Disease
Graft vs Leukemia Effect
HLA Antigens
Hematopoietic Stem Cell Transplantation
Histocompatibility
Histocompatibility Testing
Humans
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Living Donors
Male
Proportional Hazards Models
Prospective Studies
Recurrence
Retrospective Studies
Siblings
Transplantation, Homologous
jenkins-FCD Prod-300 626508253d14e4184314fb9f66322a03a5906796