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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.BB

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+Show Affiliations

University of Minnesota, Minneapolis, Minnesota 55455, USA. weisd001@umn.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Evaluation Study
Journal Article
Multicenter Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

19822308

Citation

Weisdorf, Daniel J., et al. "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." Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, vol. 15, no. 11, 2009, pp. 1475-8.
Weisdorf DJ, Nelson G, Lee SJ, et al. 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;15(11):1475-8.
Weisdorf, D. J., Nelson, G., Lee, S. J., Haagenson, M., Spellman, S., Antin, J. H., Bolwell, B., Cahn, J. Y., Cervantes, F., Copelan, E., Gale, R., Gratwohl, A., Khoury, H. J., McCarthy, P., Marks, D. I., Szer, J., Woolfrey, A., Cortes-Franco, J., Horowitz, M. M., & Arora, M. (2009). 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. Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, 15(11), 1475-8. https://doi.org/10.1016/j.bbmt.2009.06.016
Weisdorf DJ, et al. 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;15(11):1475-8. PubMed PMID: 19822308.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Weisdorf,Daniel J, AU - Nelson,Gene, AU - Lee,Stephanie J, AU - Haagenson,Michael, AU - Spellman,Stephen, AU - Antin,Joseph H, AU - Bolwell,Brian, AU - Cahn,Jean-Yves, AU - Cervantes,Francisco, AU - Copelan,Edward, AU - Gale,Robert, AU - Gratwohl,Alois, AU - Khoury,H Jean, AU - McCarthy,Philip, AU - Marks,David I, AU - Szer,Jeff, AU - Woolfrey,Ann, AU - Cortes-Franco,Jorge, AU - Horowitz,Mary M, AU - Arora,Mukta, AU - ,, Y1 - 2009/08/19/ PY - 2009/04/06/received PY - 2009/06/29/accepted PY - 2009/10/14/entrez PY - 2009/10/14/pubmed PY - 2009/12/16/medline SP - 1475 EP - 8 JF - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation JO - Biol Blood Marrow Transplant VL - 15 IS - 11 N2 - 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. SN - 1523-6536 UR - https://www.unboundmedicine.com/medline/citation/19822308/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_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1083-8791(09)00304-8 DB - PRIME DP - Unbound Medicine ER -