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Protective factors, management and prognosis of mixed chimerism after allogeneic hematopoietic stem cell transplantation for severe aplastic anemia in children

Abstract

Mixed chimerism (MC) frequently arises in children with severe aplastic anemia (SAA) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Nonetheless, there is a paucity of research regarding potential predictors and effective interventions. This retrospective study, performed on 150 pediatric patients with SAA who underwent allo-HSCT between December 2015 and June 2022, explored the characteristics, risk factors, treatment, and prognosis of MC. A total of 29 patients (19.3%) developed MC following allo-HSCT, with two individuals experiencing MC twice. The CTX + ATG regimen was associated with the development of MC. Peripheral blood (PB) + bone marrow (BM) stem cell graft and a high number of CD34+ cells were identified as independent protective factors for MC. The cumulative incidence of grade II-IV acute graft-versus-host disease was significantly elevated in donor chimerism (DC) relative to MC. Among MC patients with cytopenia, only two patients who received increased immunosuppression alone were effective. Complete DC was achieved in all four patients who received the second transplantation. In conclusion, we emphasize that prompt second transplantation is essential when cellular therapy and enhanced immunosuppression fail for MC patients with cytopenia.

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Fig. 1: Distribution characteristics of MC after allo-HSCT.
Fig. 2: Acute GVHD in DC and MC group.
Fig. 3
Fig. 4
Fig. 5: The trajectory tracking Sankey diagram among MC with cytopenia patients, interventions, and outcomes.

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Funding

This research was supported by the Basic Research and Cultivation Fund for Young Teachers of Zhengzhou University (grant number JC21854036).

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Jian Liu conceived and designed the study; Yumiao Mai analyzed the data, and wrote the draft; Zhaohe Jing, Linchao Zhao, Hongyun Niu, Simin Qiu, Pengpeng Dong collected the data. All authors have read and approved the final version of this article.

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Correspondence to Jian Liu.

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Ethics

This study has been approved by the Ethics Committee of the First Affiliated Hospital of Zhengzhou University (2024-KY-0934) and waived informed consent given the retrospective nature. The studies were conducted in accordance with the local legislation and institutional requirements, and all methods were performed in accordance with the relevant guidelines and regulations. All samples were collected as part of routine management/surveillance and were anonymized prior to research use.

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Liu, J., Mai, Y., Jing, Z. et al. Protective factors, management and prognosis of mixed chimerism after allogeneic hematopoietic stem cell transplantation for severe aplastic anemia in children. Bone Marrow Transplant 60, 811–819 (2025). https://doi.org/10.1038/s41409-025-02577-3

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