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Impact of HLA disparity on the risk of overall mortality in patients with grade II–IV acute GVHD on behalf of the HLA Working Group of Japan Society for Hematopoietic Cell Transplantation


Acute graft-versus-host disease (aGVHD) is a major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). Stem cell source or HLA disparity may exert a significant impact on the overall survival (OS) after the development of aGVHD. In order to clarify this point, we performed a retrospective analysis using a database of the Japan Society for HCT. We analyzed the clinical outcomes of 10,035 patients who developed grade II–IV aGVHD. The median age of the patients was 48 years. The probability of 2-year OS after the onset of grade II–IV aGVHD in the study cohort was 54.1%. The multivariate analysis showed that the HLA ≥2-loci mismatched related donor and HLA 1-locus mismatched unrelated donor were significantly associated with an inferior OS after grade II–IV aGVHD. In a subgroup analysis, peripheral blood stem cells and HLA disparity were associated with an inferior OS in patients who received related or unrelated HCT. Thus, the clinical outcome after grade II–IV aGVHD significantly varied as per the combination of the presence of HLA disparity and stem cell source. Further research using other databases is necessary to confirm our findings.

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Fig. 1: Overall survival in the whole cohort.
Fig. 2: Overall survival in patients who received a related HSCT.
Fig. 3: Overall survival in patients who received an unrelated HSCT.
Fig. 4: Overall survival in patients who received a cord blood transplant.


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This study was partly supported by Health, Labor and Welfare Sciences Research Grants (20FF1002).

Author information




MY, AU, SF, HF, TF, and KK designed the research, organized the project, and wrote the paper. MY performed the statistical analyses. H Ogawa, YT, KI, AY, H Okumura, KI, AN, TE, AY, KM, J Tsukada, J Tanaka, and YA gathered the data. All authors contributed to the final version of the manuscript and have approved it for submission for publication.

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Correspondence to Shigeo Fuji.

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Competing interests

HN received honoraria from Amgen Astellas BioPharma K.K., Astellas Pharma Inc., Otsuka Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Kyowa-Hakko Kirin Co., Ltd., Shire Japan KK., Celgene Corporation, Daiichi Sankyo Company., Ltd., Takeda Pharmaceutical Company Limited., Chugai Pharmaceutical Co., Ltd., Japan Blood Products Organization, Nippon Shinyaku Co., Ltd., Novartis, Pfizer Japan Inc, Bristol-Myers Squibb Company, and research funding from Astellas Pharma Inc, Otsuka Pharmaceutical Co. Ltd., Novartis and Bristol-Myers Squibb Company.

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Fuji, S., Hakoda, A., Kanda, J. et al. Impact of HLA disparity on the risk of overall mortality in patients with grade II–IV acute GVHD on behalf of the HLA Working Group of Japan Society for Hematopoietic Cell Transplantation. Bone Marrow Transplant (2021).

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