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. 2024 Sep;205(3):1077-1096.
doi: 10.1111/bjh.19630. Epub 2024 Jul 7.

Effect of peptide-binding motif on survival of HLA-haploidentical transplantation with post-transplant cyclophosphamide

Kentaro Ido  1 , Hirohisa Nakamae  1 , Norimichi Hattori  2 , Minoru Kanaya  3 , Kaoru Morita  4 , Masayuki Hino  1 , Hiroyuki Ohigashi  5 , Takahiro Fukuda  6 , Tetsuya Eto  7 , Koji Nagafuji  8 , Nobuhiro Hiramoto  9 , Yumiko Maruyama  10 , Shuichi Ota  11 , Ken-Ichi Matsuoka  12 , Toshihiko Ando  13 , Takashi Akasaka  14 , Yasuo Mori  15 , Tomohiko Kamimura  16 , Toshiro Kawakita  17 , Koji Kawamura  18 , Junya Kanda  19 , Makoto Onizuka  20 , Yoshiko Atsuta  21   22 , Makoto Murata  23
Affiliations

Effect of peptide-binding motif on survival of HLA-haploidentical transplantation with post-transplant cyclophosphamide

Kentaro Ido et al. Br J Haematol. 2024 Sep.

Abstract

Peptide-binding motif (PBM) model, a hierarchical clustering of HLA class I based on their binding specificity, was developed to predict immunopeptidome divergence. The effect of PBM mismatches on outcomes is unknown in HLA-haploidentical haematopoietic cell transplantation with post-transplant cyclophosphamide (PTCy-haplo). We therefore conducted a retrospective study using national registry data in PTCy-haplo. Overall, 1352 patients were included in the study. PBM-A bidirectional mismatch was associated with an increased risk of overall mortality in multivariable analysis (hazard ratio, 1.26; 95% confidence interval, 1.06 to 1.50; p = 0.010). None of relapse, non-relapse mortality (NRM) and graft-versus-host disease showed significant differences according to PBM-A bidirectional mismatch status in the entire cohort. The impact of PBM-A bidirectional mismatch on overall survival (OS) was preserved within the HLA-A genotype bidirectional mismatch population, and their lower OS stemmed from higher relapse rate in this population. The worse OS due to high NRM with PBM-A bidirectional mismatch was prominent in lymphoid malignancies receiving reduced-intensity conditioning. The PBM model may predict outcomes more accurately than HLA genotype mismatches. In conclusion, this study demonstrated that the presence of PBM-A bidirectional mismatch elevated the risk of mortality of PTCy-haplo. Avoiding PBM-A bidirectional mismatch might achieve better outcomes in PTCy-haplo.

Keywords: HLA; HLA‐haploidentical haematopoietic cell transplantation with post‐transplant cyclophosphamide; peptide‐binding motif.

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References

REFERENCES

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