IMPACT OF HLA-DPB1 INCOMPATIBILITY ON THE RESULTS OF ALLOGENEIC HEMATOPOIETIC STEM CELLS TRANSPLANTATION FROM HLA-A-B-C–DRB1-DQB1-COMPATIBLE UNRELATED DONOR

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Abstract

Introduction. An accepted fact in allogeneic hematopoietic stem cells transplantation (allo-HSCT) from unrelated donors is that matching for HLA genes is critical to ensure the best outcomes for patients. The current gold standard is an unrelated donor matched for 10/10 HLA alleles (HLA-A, -B, -C, -DRB1, -DQB1). In the HLA-mismatched setting graft-versus-host disease (GVHD) is increased, and overall survival becomes significantly worse. The importance of HLA-DPB1matching is more controversial.

The aim of our study was to evaluate the impact of HLA-DPB1 mismatches on outcome of patients who underwent 10/10 HLA matched unrelated HSCT.

Materials and methods. 49 patients treated with allo-HSCT in transplant center of National Research Center for Hematology from 10/10 HLA-matched unrelated donors were included in the study. High-resolution typing for HLA-DPB1 was done by PCR with sequence specific primers (SSP) using Olerup typing kits. HLA-DPB1 permissive/nonpermissive mismatches were examined according to TCE groups. Overall survival, event-free survival and survival without acute graft-versus-host disease were calculated by Kaplan–Meier method, and compared with log-rank test. Proportional hazard Cox models were used for multivariate analysis.

Results. The 3-year overall survival after allo-HSCT was 68 %, event-free survival – 51 %, acute GVHD-free survival – 62 %. No significant impacts of HLA-DPB1 disparities on overall, event-free survival and probability of acute graft-versus-host disease were observed. Patients with nonpermissive HLA-DPB1-incompatible donors had a tendency to increased event-free survival. The factors significantly increasing risk of acute GVHD were peripheral blood grafts, advanced-stage disease and male gender of recipients.

Conclusion. The factors associated with acute GVHD are peripheral blood grafts, advanced-stage disease and male sex of recipients. For more precise evaluation of impact of HLA-DPB1-incompatibility on results of allo-HSCT further investigations are needed.

About the authors

E. G. Khamaganova

National Research Center for Hematology

Author for correspondence.
Email: ekhamag@mail.ru
ORCID iD: 0000-0002-0110-3314
4 Novyi Zykovskiy proezd, 125167 Moscow Russian Federation

Е. N. Parovichnikova

National Research Center for Hematology

ORCID iD: 0000-0001-6177-3566
4 Novyi Zykovskiy proezd, 125167 Moscow Russian Federation

L. A. Kuzmina

National Research Center for Hematology

ORCID iD: 0000-0001-6201-6276
4 Novyi Zykovskiy proezd, 125167 Moscow Russian Federation

S. М. Kulikov

National Research Center for Hematology

ORCID iD: 0000-0002-6288-7570
4 Novyi Zykovskiy proezd, 125167 Moscow Russian Federation

E. Р. Kuzminova

National Research Center for Hematology

ORCID iD: 0000-0001-9473-4774
4 Novyi Zykovskiy proezd, 125167 Moscow Russian Federation

R. S. Chapova

National Research Center for Hematology

ORCID iD: 0000-0002-6749-8099
4 Novyi Zykovskiy proezd, 125167 Moscow Russian Federation

V. G. Savchenko

National Research Center for Hematology

ORCID iD: 0000-0001-8188-5557
4 Novyi Zykovskiy proezd, 125167 Moscow Russian Federation

References

  1. Program treatment of blood system diseases. Ed.: Savchenko V. G. 2012, Moscow: Praktika. 1056 p. (In Russ.).
  2. Shaw B. E., Mayor N. P., Russell N. H. et al. Diverging effects of HLA-DPB1 matching status on outcome following unrelated donor transplantation depending on disease stage and the degree of matching for other HLA alleles. Leukemia 2010;24(1):58–65. doi: 10.1038/leu.2009.239. PMID: 19924143.
  3. Pidala J., Lee S. J., Ahn K. W., et al. Nonpermissive HLA-DPB1 mismatch increases mortality after myeloablative unrelated allogeneic hematopoietic cell transplantation. Blood 2014;124(16):2596–606. doi: 10.1182/blood-2014‑05‑576041. PMID: 25161269.
  4. Gagne K., Loiseau P., Dubo V. et al. Is there any impact of HLA-DPB1 disparity in 10/10 HLA-matched unrelated hematopoietic SCT? Results of a French multicentric retrospective study. Bone Marrow Transplant 2015;50(2):232–6. doi: 10.1038/bmt.2014.253. PMID: 25365066.
  5. Crivello P., Zito L., Sizzano F. et al. The impact of amino acid variability on alloreactivit defines a functional distance predictive of permissive HLADPB1 mismatches in hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2015;21(2):233–41. doi: 10.1016/j.bbmt.2014.10.017. PMID: 25445022.
  6. Zino E., Vago L., Di Terlizzi S. et al. Frequency and targeted detection of HLA-DPB1 T cell epitope disparities relevant in unrelated hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2007;13(9):1031–40. doi: 10.1016/j.bbmt.2007.05.010. PMID: 17697965.
  7. Crocchiolo R., Zino E., Vago L. et al. Nonpermissive HLA-DPB1 disparity is a significant independent risk factor for mortality after unrelated hematopoietic stem cell transplantation. Blood 2009;114(7):1437–44. doi: 10.1182/blood-2009‑01‑200378. PMID: 17697965.
  8. Fleischhauer K., Shaw B. E., Gooley T. et al. Effect of T-cell-epitope matching at HLA-DPB1 in recipients of unrelateddonor haemopoietic-cell transplantation: a retrospective study. Lancet Oncol 2012;13(4):366–74. doi: 10.1016/S1470-2045(12)70004-9. PMID: 22340965.
  9. Crivello P., Heinold A., Rebmann V. et al. Functional distance between recipient and donor HLA-DPB1 determines nonpermissive mismatches in unrelated HCT. Blood 2016;128(1):120–9. doi: 10.1182/blood-2015‑12‑686238. PMID: 27162243.
  10. Shaw B. E., Robinson J., Fleischhauer K. et al. Translating the HLA-DPB1 T-cell epitope-matching algorithm into clinical practice. Bone Marrow Transplant 2013;48(12):1510–2. doi: 10.1038/bmt.2013.91. PMID: 23811815.
  11. Fleischhauer K., Fernandez-Viña M. A., Wang T. et al. Risk associations between HLA-DPB1 T-cell epitope matching and outcome of unrelated hematopoietic cell transplantation are independent of HLA-DPA1. Bone Marrow Transplant 2014;49(9):1176–83. doi: 10.1038/bmt.2014.122. PMID: 24955785.
  12. Glucksberg H., Storb R., Fefer A. et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation 1974;18(4):295–304. PMID: 4153799.
  13. Lee S. J., Klein J., Haagenson M. et al. High-resolution donor-recipient HLA matching contributes to the success of unrelated donor marrow transplantation. Blood 2007;110:4576–83. doi: 10.1182/blood-2007‑06‑097386. PMID: 17785583.
  14. Rutten C. E., van Luxemburg-Heijs S. A., Halkes C. J. et al. Patient HLA-DP-specific CD4+ T cells from HLA-DPB1-mismatched donor lymphocyte infusion can induce graft-versus-leukemia reactivity in the presence or absence of graft-versushost disease. Biol Blood Marrow Transplant 2013;19(1):40–8. doi: 10.1016/j.bbmt.2012.07.020. PMID: 22871556.
  15. Eapen M., Logan B. R., Confer D. L. et al. Peripheral Blood Grafts from Unrelated Donors Are Associated with Increased Acute and Chronic Graft-versus-Host Disease without Improved Survival. Biol Blood Marrow Transplant 2007;13(12):1461–8. DOI :10.1016/j.bbmt.2007.08.006. PMID: 18022576.
  16. Anasetti C., Logan B. R. Lee S. J. et al. Peripheral-blood stem cells versus bone marrow from unrelated donors. N Engl J Med 2012;367(16):1487–96. doi: 10.1056/NEJMoa1203517. PMID: 23075175.
  17. Holtan S. G., DeFor T.E., Lazaryan A. et al. Composite end point of graft-versushost disease-free, relapse-free survival after allogeneic hematopoietic cell transplantation. Blood 2015;125(8):1333–8. doi: 10.1182/blood-2014‑10‑609032. PMID: 25593335.
  18. Inamoto Y., Kimura F., Kanda J. et al. Comparison of graft-versus-host diseasefree, relapse-free survival according to a variety of graft sources: antithymocyte globulin and single cord blood provide favorable outcomes in some subgroups. Haematologica 2016;101(12):1592–602. doi: 10.3324/haematol.2016.149427. PMID: 27662017.
  19. Spierings E., Kim Y. H., Hendriks M. et al. Multicenter analyses demonstrate significant clinical effects of minor histocompatibility antigens on GvHD and GvL after HLA-matched related and unrelated hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2013;19(8):1244–53. doi: 10.1016/j.bbmt.2013.06.001. PMID: 23756210.
  20. Popli R., Sahaf B., Nakasone H. et al. Clinical impact of H-Y alloimmunity. Immunol Res 2014;58(0):249–58. doi: 10.1007/s12026‑014‑8514‑3. PMID: 24781195.

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