Risk associations between HLA-DPB1 T-cell epitope matching and outcome of unrelated hematopoietic cell transplantation are independent of HLA-DPA1

K. Fleischhauer, M. A. Fernandez-Viña, T. Wang, M. Haagenson, M. Battiwalla, L. A. Baxter-Lowe, F. Ciceri, J. Dehn, J. Gajewski, G. A. Hale, M. B A Heemskerk, S. R. Marino, P. L. McCarthy, D. Miklos, M. Oudshoorn, M. S. Pollack, V. Reddy, D. Senitzer, B. E. Shaw, E. K. WallerS. J. Lee, S. R. Spellman

Research output: Contribution to journalArticle

Abstract

HLA-DP antigens are beta-alpha heterodimers encoded by polymorphic HLA-DPB1 and -DPA1 alleles, respectively, in strong linkage disequilibrium (LD) with each other. Non-permissive unrelated donor (UD)-recipient HLA-DPB1 mismatches across three different T-cell epitope (TCE) groups are associated with increased mortality after hematopoietic SCT (HCT), but the role of HLA-DPA1 is unclear. We studied 1281 onco-hematologic patients after 10/10 HLA-matched UD-HCT facilitated by the National Marrow Donor Program. Non-permissive mismatches defined solely by HLA-DPB1 TCE groups were associated with significantly higher risks of TRM compared to permissive mismatches (hazard ratio (HR) 1.30, confidence interval (CI) 1.06-1.53; P=0.009) or allele matches. Moreover, non-permissive HLA-DPB1 TCE group mismatches in the graft versus host (GvH) direction significantly decreased the risk of relapse compared to permissive mismatches (HR 0.55, CI 0.37-0.80; P=0.002) or allele matches. Splitting each group into HLA-DPA1*02:01 positive or negative, in frequent LD with HLA-DPB1 alleles from two of the three TCE groups, or into HLA-DPA1 matched or mismatched, did not significantly alter the observed risk associations. Our findings suggest that the effects of clinically non-permissive HLA-DPB1 TCE group mismatches are independent of HLA-DPA1, and that selection of donors with non-permissive DPB1 TCE mismatches in GvH direction might provide some protection from disease recurrence.

Original languageEnglish
Pages (from-to)1176-1183
Number of pages8
JournalBone Marrow Transplantation
Volume49
Issue number9
DOIs
Publication statusPublished - Sep 1 2014

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T-Lymphocyte Epitopes
Cell Transplantation
Alleles
Unrelated Donors
Linkage Disequilibrium
HLA-DP Antigens
Confidence Intervals
Transplants
Donor Selection
Recurrence
HLA-DPB1 antigen
HLA-DPA1 antigen
Bone Marrow
Tissue Donors
Mortality

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Fleischhauer, K., Fernandez-Viña, M. A., Wang, T., Haagenson, M., Battiwalla, M., Baxter-Lowe, L. A., ... Spellman, S. R. (2014). Risk associations between HLA-DPB1 T-cell epitope matching and outcome of unrelated hematopoietic cell transplantation are independent of HLA-DPA1. Bone Marrow Transplantation, 49(9), 1176-1183. https://doi.org/10.1038/bmt.2014.122

Risk associations between HLA-DPB1 T-cell epitope matching and outcome of unrelated hematopoietic cell transplantation are independent of HLA-DPA1. / Fleischhauer, K.; Fernandez-Viña, M. A.; Wang, T.; Haagenson, M.; Battiwalla, M.; Baxter-Lowe, L. A.; Ciceri, F.; Dehn, J.; Gajewski, J.; Hale, G. A.; Heemskerk, M. B A; Marino, S. R.; McCarthy, P. L.; Miklos, D.; Oudshoorn, M.; Pollack, M. S.; Reddy, V.; Senitzer, D.; Shaw, B. E.; Waller, E. K.; Lee, S. J.; Spellman, S. R.

In: Bone Marrow Transplantation, Vol. 49, No. 9, 01.09.2014, p. 1176-1183.

Research output: Contribution to journalArticle

Fleischhauer, K, Fernandez-Viña, MA, Wang, T, Haagenson, M, Battiwalla, M, Baxter-Lowe, LA, Ciceri, F, Dehn, J, Gajewski, J, Hale, GA, Heemskerk, MBA, Marino, SR, McCarthy, PL, Miklos, D, Oudshoorn, M, Pollack, MS, Reddy, V, Senitzer, D, Shaw, BE, Waller, EK, Lee, SJ & Spellman, SR 2014, 'Risk associations between HLA-DPB1 T-cell epitope matching and outcome of unrelated hematopoietic cell transplantation are independent of HLA-DPA1', Bone Marrow Transplantation, vol. 49, no. 9, pp. 1176-1183. https://doi.org/10.1038/bmt.2014.122
Fleischhauer, K. ; Fernandez-Viña, M. A. ; Wang, T. ; Haagenson, M. ; Battiwalla, M. ; Baxter-Lowe, L. A. ; Ciceri, F. ; Dehn, J. ; Gajewski, J. ; Hale, G. A. ; Heemskerk, M. B A ; Marino, S. R. ; McCarthy, P. L. ; Miklos, D. ; Oudshoorn, M. ; Pollack, M. S. ; Reddy, V. ; Senitzer, D. ; Shaw, B. E. ; Waller, E. K. ; Lee, S. J. ; Spellman, S. R. / Risk associations between HLA-DPB1 T-cell epitope matching and outcome of unrelated hematopoietic cell transplantation are independent of HLA-DPA1. In: Bone Marrow Transplantation. 2014 ; Vol. 49, No. 9. pp. 1176-1183.
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AU - Fernandez-Viña, M. A.

AU - Wang, T.

AU - Haagenson, M.

AU - Battiwalla, M.

AU - Baxter-Lowe, L. A.

AU - Ciceri, F.

AU - Dehn, J.

AU - Gajewski, J.

AU - Hale, G. A.

AU - Heemskerk, M. B A

AU - Marino, S. R.

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AU - Miklos, D.

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AU - Pollack, M. S.

AU - Reddy, V.

AU - Senitzer, D.

AU - Shaw, B. E.

AU - Waller, E. K.

AU - Lee, S. J.

AU - Spellman, S. R.

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