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. 2025 Jun;121(6):848-856.
doi: 10.1007/s12185-025-03952-y. Epub 2025 Mar 20.

Engraftment outcome of patients with anti-HLA antibodies in HLA-mismatched peripheral blood stem cell transplantation

Takeshi Hagino  1 , Kazuhiro Ikegame  2 , Hidenori Tanaka  3 , Yoshinobu Kanda  4 , Katsuji Kaida  5 , Takahiro Fukuda  6 , Yukio Kondo  7 , Maho Sato  8 , Noriko Doki  9 , Hirohisa Nakamae  10 , Ken-Ichi Matsuoka  11   12 , Yasuo Mori  13 , Hideki Sano  14 , Tetsuya Eto  15 , Toshiro Kawakita  16 , Yoshiko Hashii  17 , Tatsuo Ichinohe  18 , Yoshiko Atsuta  19   20 , Junya Kanda  21 ; HLA Working Group of Japanese Society for Transplantation, Cellular Therapy
Affiliations

Engraftment outcome of patients with anti-HLA antibodies in HLA-mismatched peripheral blood stem cell transplantation

Takeshi Hagino et al. Int J Hematol. 2025 Jun.

Abstract

Anti-human leukocyte antigen (HLA) antibodies, particularly donor-specific HLA antibodies (DSA), negatively impact engraftment in hematopoietic cell transplantation. Past studies have proposed various interventions to reduce DSA, but these were primarily from single centers and not from large-scale registry data. Therefore, we conducted a retrospective analysis of nationwide registry data to examine the effects of anti-HLA antibodies on engraftment. Evaluable patients were classified into an anti-HLA antibody-negative group (n = 3657), an anti-HLA antibody-positive group (without high DSA) (n = 137), and a high-DSA (MFI > 5000) group (n = 8). Patient characteristics differed significantly between the anti-HLA antibody-negative and anti-HLA antibody-positive groups, and the number of patients with DSA was lower than expected. Statistical analyses revealed that the anti-HLA antibody-positive group had better neutrophil engraftment than the anti-HLA antibody-negative group (94.0% vs 84.2%, p < 0.001) but worse platelet engraftment (60.3% vs 64.9%, p = 0.047). In the high DSA group, two patients received a DSA-depleting intervention. Only one patient with an MFI of 5832 (without intervention) developed primary graft failure, while the remaining seven achieved engraftment. In this study, the effect of anti-HLA antibodies remained inconclusive, and the possibility of neutrophil engraftment with high-DSA levels was confirmed.

Keywords: Anti-HLA antibody; DSA; Engraftment; MFI; PBSCT.

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Conflict of interest statement

Declarations. Conflict of interest: Hirohisa Nakamae received research funding from Astellas Pharma Inc. and Novartis Pharma K.K., and honoraria from Astellas Pharma Inc., Kyowa Kirin Co., Ltd., NIPPON SHINYAKU Co., Ltd., and Novartis Pharma K.K. The authors declare no competing financial interests. One of the authors, Yoshinobu Kanda, is the editor of the International Journal of Hematology.

Figures

Fig. 1
Fig. 1
Consort diagram. Consort diagram for grouping of “anti-HLA antibodies negative,” “high DSA,” and “anti-HLA antibody-positive (low DSA)” is shown. HLA, human leukocyte antigen; DSA, donor-specific antibody
Fig. 2
Fig. 2
Neutrophil and platelet engraftments. Cumulative incidences of neutrophil (A) and platelet (B) engraftment are described in three groups: anti-HLA antibody-negative group (n = 3,657, green), anti-HLA antibody-positive group (n = 137, red), and high-DSA group (n = 8, black). Death before engraftment was defined as the competing risk. The at-risk numbers are shown in the figure. HLA: human leukocyte antigen; DSA, donor specific anti-HLA antibody; DSA, high-DSA group; Ab ( +), anti-HLA antibody-positive group; Ab (-), anti-HLA antibody-negative group
See this image and copyright information in PMC

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