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Protective effect of HLA-DPB1 mismatch remains valid in reduced-intensity conditioning unrelated donor hematopoietic cell transplantation

Bone Marrow Transplantation volume 55, pages 409–418 (2020)Cite this article

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Abstract

A mismatch at HLA-DPB1 locus is associated with higher acute GVHD and lower relapse rate after myeloablative (MAC) allogeneic hematopoietic cell transplantation (alloHCT). Also, in MAC setting, mismatch permissiveness and expression level impact alloHCT outcomes. However, in reduced intensity conditioning (RIC), DP mismatch effect on transplant outcomes is unknown. We retrospectively evaluated DP mismatch influence (number, permissiveness, and expression) on HCT outcomes in 310 patients with high-resolution typing (HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1), who underwent RIC HCT. By multivariable analysis, 11/12 had better overall survival (OS) and relapse vs. 12/12 (HR = 1.61 and 2.02; p = 0.04 and 0.01, respectively) and better OS vs. 10/12 (HR = 1.68; p = 0.02). Within the 11/12, nonpermissive (NoPR) mismatch was associated with higher risk of grade II–IV acute GVHD (HR = 1.97; p = 0.005) and nonrelapse mortality (HR = 2.13; p = 0.02) vs. permissive (PR). Grouping 11/12 based on the DP expression conferred higher mortality (HR = 3.78; p = 0.003) when low expressers received a graft from high expressers (AG) vs. low expressers (AA). Better OS was achieved in PR 11/12, when expression was low in patient and donor (AA) vs. all other combinations. Therefore, in RIC HCT, a single-DP mismatch has a protective role, especially in permissive setting, when donor and recipient are low expressers.

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Acknowledgements

The authors would like to thank Dr Joycelynne Palmer for assistance with biostatistical data analysis and reviewing this manuscript. This study was partially funded by NIH P30 CA033572 (Biostatistics Core).

Authors Contribution

MMAM and KG designed and performed the research, analyzed the results, and wrote the manuscript. TS performed the biostatistical analysis and assisted with the writing. SM wrote the manuscript. CK, PP, DS, SJF, and RN contributed to the design of the experiments and assisted with the writing. AN helped with the study design and supervised the research, data analysis, and manuscript writing.

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Author notes

  1. These author contributed equally: Monzr M. Al Malki, Ketevan Gendzekhadze

Authors and Affiliations

  1. Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA, USA

    Monzr M. Al Malki, Chatchada Karanes, Pablo Parker, David Snyder, Stephen J. Forman, Ryotaro Nakamura & Auayporn Nademanee

  2. HLA Laboratory, City of Hope, Duarte, CA, USA

    Ketevan Gendzekhadze

  3. Division of Biostatistics, Department of Information Sciences, City of Hope, Duarte, CA, USA

    Tracey Stiller

  4. Department of Clinical Translational Program Development, City of Hope, Duarte, CA, USA

    Sally Mokhtari

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  1. Monzr M. Al Malki
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Correspondence to Monzr M. Al Malki.

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Malki, M.M.A., Gendzekhadze, K., Stiller, T. et al. Protective effect of HLA-DPB1 mismatch remains valid in reduced-intensity conditioning unrelated donor hematopoietic cell transplantation. Bone Marrow Transplant 55, 409–418 (2020). https://doi.org/10.1038/s41409-019-0694-y

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