Clinical outcomes of HLA-DPB1 mismatches in 10/10 HLA-matched unrelated donor-recipient pairs undergoing allogeneic stem cell transplant

Ann Moyer, Shahrukh K. Hashmi, Cynthia M. Kroning, Walter K Kremers, Steven R. De Goey, Mrinal M Patnaik, Mark R Litzow, Dennis A. Gastineau, William Hogan, Eapen K. Jacob, Justin D. Kreuter, Laurie L. Wakefield, Manish J. Gandhi

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Objective: HLA-DPB1 matching may impact allogeneic hematopoietic stem cell transplantation (ASCT) outcomes; however, this locus is not in linkage disequilibrium with the remainder of the HLA genes. After classifying HLA-DPB1 mismatches based on T-cell epitope, avoiding non-permissive mismatches may impact survival. We tested this hypothesis at a single academic institution. Methods: Retrospective HLA-DPB1 genotyping was performed on 153 adult patients who underwent ASCT and unrelated donors matched for HLA-A, B, C, DRB1, and DQB1 loci (10/10). Using the ImMunoGeneTics/HLA T-cell epitope matching algorithm, mismatch status was classified as permissive or non-permissive. Results: Of 153 donor-recipient pairs, 22 (14.4%) were HLA-DPB1 matches, 64 (42.8%) permissive mismatches, and 67 (43.8%) non-permissive mismatches. DPB1 mismatch increased risk of chronic graft-versus-host disease (cGVHD; RR 2.89 [1.19-9.53], P=.016) compared with DPB1-matched transplants, but there were no differences in overall mortality, risk of relapse, or acute GVHD (aGVHD). Combining matches and permissive mismatches and comparing to non-permissive mismatches, there was no significant difference in overall survival or relapse; however, patients receiving non-permissive mismatched transplants experienced greater risk of aGVHD overall and severe aGVHD (RR 1.66 [1.13-2.44], P=.010 and RR 1.97 [1.10-3.59], P=.024, respectively). Conclusion: In this single-center study, HLA-DPB1 matching influenced outcomes of patients undergoing ASCT for hematologic malignancy.

Original languageEnglish (US)
Pages (from-to)275-282
Number of pages8
JournalEuropean Journal of Haematology
Volume99
Issue number3
DOIs
StatePublished - Sep 1 2017

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Unrelated Donors
Stem Cells
Hematopoietic Stem Cell Transplantation
Transplants
T-Lymphocyte Epitopes
Recurrence
Immunogenetics
HLA-A Antigens
HLA-B Antigens
Survival
Linkage Disequilibrium
Graft vs Host Disease
Hematologic Neoplasms
HLA-DPB1 antigen
Tissue Donors
Mortality
Genes

Keywords

  • bone marrow transplantation
  • transplantation

ASJC Scopus subject areas

  • Hematology

Cite this

Clinical outcomes of HLA-DPB1 mismatches in 10/10 HLA-matched unrelated donor-recipient pairs undergoing allogeneic stem cell transplant. / Moyer, Ann; Hashmi, Shahrukh K.; Kroning, Cynthia M.; Kremers, Walter K; De Goey, Steven R.; Patnaik, Mrinal M; Litzow, Mark R; Gastineau, Dennis A.; Hogan, William; Jacob, Eapen K.; Kreuter, Justin D.; Wakefield, Laurie L.; Gandhi, Manish J.

In: European Journal of Haematology, Vol. 99, No. 3, 01.09.2017, p. 275-282.

Research output: Contribution to journalArticle

Moyer, Ann ; Hashmi, Shahrukh K. ; Kroning, Cynthia M. ; Kremers, Walter K ; De Goey, Steven R. ; Patnaik, Mrinal M ; Litzow, Mark R ; Gastineau, Dennis A. ; Hogan, William ; Jacob, Eapen K. ; Kreuter, Justin D. ; Wakefield, Laurie L. ; Gandhi, Manish J. / Clinical outcomes of HLA-DPB1 mismatches in 10/10 HLA-matched unrelated donor-recipient pairs undergoing allogeneic stem cell transplant. In: European Journal of Haematology. 2017 ; Vol. 99, No. 3. pp. 275-282.
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abstract = "Objective: HLA-DPB1 matching may impact allogeneic hematopoietic stem cell transplantation (ASCT) outcomes; however, this locus is not in linkage disequilibrium with the remainder of the HLA genes. After classifying HLA-DPB1 mismatches based on T-cell epitope, avoiding non-permissive mismatches may impact survival. We tested this hypothesis at a single academic institution. Methods: Retrospective HLA-DPB1 genotyping was performed on 153 adult patients who underwent ASCT and unrelated donors matched for HLA-A, B, C, DRB1, and DQB1 loci (10/10). Using the ImMunoGeneTics/HLA T-cell epitope matching algorithm, mismatch status was classified as permissive or non-permissive. Results: Of 153 donor-recipient pairs, 22 (14.4{\%}) were HLA-DPB1 matches, 64 (42.8{\%}) permissive mismatches, and 67 (43.8{\%}) non-permissive mismatches. DPB1 mismatch increased risk of chronic graft-versus-host disease (cGVHD; RR 2.89 [1.19-9.53], P=.016) compared with DPB1-matched transplants, but there were no differences in overall mortality, risk of relapse, or acute GVHD (aGVHD). Combining matches and permissive mismatches and comparing to non-permissive mismatches, there was no significant difference in overall survival or relapse; however, patients receiving non-permissive mismatched transplants experienced greater risk of aGVHD overall and severe aGVHD (RR 1.66 [1.13-2.44], P=.010 and RR 1.97 [1.10-3.59], P=.024, respectively). Conclusion: In this single-center study, HLA-DPB1 matching influenced outcomes of patients undergoing ASCT for hematologic malignancy.",
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AU - Moyer, Ann

AU - Hashmi, Shahrukh K.

AU - Kroning, Cynthia M.

AU - Kremers, Walter K

AU - De Goey, Steven R.

AU - Patnaik, Mrinal M

AU - Litzow, Mark R

AU - Gastineau, Dennis A.

AU - Hogan, William

AU - Jacob, Eapen K.

AU - Kreuter, Justin D.

AU - Wakefield, Laurie L.

AU - Gandhi, Manish J.

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N2 - Objective: HLA-DPB1 matching may impact allogeneic hematopoietic stem cell transplantation (ASCT) outcomes; however, this locus is not in linkage disequilibrium with the remainder of the HLA genes. After classifying HLA-DPB1 mismatches based on T-cell epitope, avoiding non-permissive mismatches may impact survival. We tested this hypothesis at a single academic institution. Methods: Retrospective HLA-DPB1 genotyping was performed on 153 adult patients who underwent ASCT and unrelated donors matched for HLA-A, B, C, DRB1, and DQB1 loci (10/10). Using the ImMunoGeneTics/HLA T-cell epitope matching algorithm, mismatch status was classified as permissive or non-permissive. Results: Of 153 donor-recipient pairs, 22 (14.4%) were HLA-DPB1 matches, 64 (42.8%) permissive mismatches, and 67 (43.8%) non-permissive mismatches. DPB1 mismatch increased risk of chronic graft-versus-host disease (cGVHD; RR 2.89 [1.19-9.53], P=.016) compared with DPB1-matched transplants, but there were no differences in overall mortality, risk of relapse, or acute GVHD (aGVHD). Combining matches and permissive mismatches and comparing to non-permissive mismatches, there was no significant difference in overall survival or relapse; however, patients receiving non-permissive mismatched transplants experienced greater risk of aGVHD overall and severe aGVHD (RR 1.66 [1.13-2.44], P=.010 and RR 1.97 [1.10-3.59], P=.024, respectively). Conclusion: In this single-center study, HLA-DPB1 matching influenced outcomes of patients undergoing ASCT for hematologic malignancy.

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