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Hematopoietic stem cell transplantation outcomes in pediatric acquired aplastic anemia with inherited bone marrow failure syndrome-associated genes

Bone Marrow Transplantation (2025)Cite this article

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Aplastic anemia (AA) is a life-threatening bone marrow failure disease characterized by cytopenia and hypocellular bone marrow, which is classified into inherited and acquired forms based on clinical manifestations and genomic background [1, 2]. Current literature on acquired AA highlights its multifactorial pathogenesis, integrating immune dysregulation, genetic predisposition, and environmental triggers [3, 4]. Inherited Bone Marrow Failure Syndrome (IBMFS) are genetic disorders causing hematopoietic failure due to inherited mutations. Hematopoietic stem cell transplantation (HSCT) is a curable treatment modality for both IBMFS and acquired AA. Nonetheless, patients with IBMFS still had worse survival after HSCT compared to patients who underwent allo-HSCT for acquired AA [5, 6]. In addition, some common post-HSCT effects may be more frequent or more complicated in those with an IBMFS. Whether the heterozygosity of IBMFS-associated genes in acquired AA impacts the outcome of HSCT has been attracting increasing attention.

A total of 117 pediatric acquired AA patients who received HSCT with available genetic testing results were identified at the First Affiliated Hospital of Zhengzhou University during June 2017-December 2023. We identified acquired AA patients carrying IBMFS-associated genes and the non-variant group and evaluated the effect of variant status on HSCT outcomes. Whole exome sequencing (WES) was performed on the patients DNA in the cohort. Carrier were defined as patients harboring a single variant in an autosomal recessive gene or females with an X-linked recessive variant. Our analysis revealed 36 single-nucleotide variants or small insertions/deletions and 1 copy number variant across 16 IBMFS-associated genes in 31 patients (26.5%), which we called carrier (Supplemental Fig. 1). Most of the variants in the carrier were related to DNA damage response genes (29/31, 93.5%), and one of them carried both DNA damage response genes and ribosome biology genes. The remaining 2 cases carry variants in telomere biology genes. Variants in FANCD2, BRCA2, BRIP1 and FANCA were common in the carrier (n = 5, 5, 4 and 4, respectively).

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Fig. 1: Post-HSCT effects in the non-variant and the carrier group.

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Data will be made available on request.

References

  1. Gale RP, Hinterberger W, Young NS, Gennery AR, Dvorak CC, Hebert KM, et al. What causes aplastic anaemia?. Leukemia. 2023;37:1191–3.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Young NS. Aplastic Anemia. N. Engl J Med. 2018;379:1643–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Wang PC, Jiang WZ, Lai TY, Liu Q, Shen YY, Ye BD, et al. Germline variants in acquired aplastic anemia: current knowledge and future perspectives. Haematologica. 2024;109:2778–89.

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Shen YY, Liu Q, Li HC, Liu WB, Hu HJ, Zhao YC, et al. Whole-exome sequencing identifies FANC heterozygous germline mutation as an adverse factor for immunosuppressive therapy in Chinese aplastic anemia patients aged 40 or younger: a single-center retrospective study. Ann Hematol. 2023;102:503–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Darrigo LG, Loth G, Kuwahara C, Vieira A, Colturato V, Rodrigues AL, et al. Hematopoietic cell transplantation for Diamond Blackfan anemia: a report from the Pediatric Group of the Brazilian Bone Marrow Transplantation Society. Eur J Haematol. 2020;105:426–33.

    Article  CAS  PubMed  Google Scholar 

  6. Murillo-Sanjuán L, González-Vicent M, Aparicio BA, Serra IB, Villa AR, Oficialdegui MLU, et al. Survival and toxicity outcomes of hematopoietic stem cell transplantation for pediatric patients with Fanconi anemia: a unified multicentric national study from the Spanish Working Group for Bone Marrow Transplantation in Children. Bone Marrow Transpl. 2021;56:1213–6.

    Article  Google Scholar 

  7. Zhang XH, Chen J, Han MZ, Huang H, Jiang EL, Jiang M, et al. The consensus from The Chinese Society of Hematology on indications, conditioning regimens and donor selection for allogeneic hematopoietic stem cell transplantation: 2021 update. J Hematol Oncol. 2021;14:20.

    Article  Google Scholar 

  8. Keel SB, Scott A, Sanchez-Bonilla M, Ho PA, Gulsuner S, Pritchard CC, et al. Genetic features of myelodysplastic syndrome and aplastic anemia in pediatric and young adult patients. Haematologica. 2016;101:1343–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Alter BP. Inherited bone marrow failure syndromes: considerations pre- and posttransplant. Hematol-Am Soc Hematol Educ Program. 2017;2017:88–95.

    Article  Google Scholar 

  10. Li BH, Meng LJ, Tian YY, Lu Q, Gao L, Xiao PF, et al. Outcomes and risk factors of hemorrhagic cystitis in pediatric allogeneic hematopoietic stem cell transplantation recipients using different graft source and condition with severe aplastic anemia. Hematology. 2022;27:714–22.

    Article  CAS  PubMed  Google Scholar 

  11. McReynolds LJ, Rafati M, Wang YJ, Ballew BJ, Kim J, Williams VV, et al. Genetic testing in severe aplastic anemia is required for optimal hematopoietic cell transplant outcomes. Blood. 2022;140:909–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Nie DJ, Wang F, Zhang J, Li XX, Liu LL, Zhang W, et al. Fanconi anemia gene associated germline predisposition in aplastic anemia and hematologic malignancies. Blood. 2020;136:3.

    Article  Google Scholar 

  13. Berwick M, Satagopan JM, Ben-Porat L, Carlson A, Mah K, Henry R, et al. Genetic heterogeneity among Fanconi anemia heterozygotes and risk of cancer. Cancer Res. 2007;67:9591–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Tischkowitz M, Easton DF, Ball J, Hodgson SV, Mathew CG. Cancer incidence in relatives of British Fanconi Anaemia patients. BMC Cancer. 2008;8:5.

    Article  Google Scholar 

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Acknowledgements

We thank Jian Liu for his intellectual advice. We also thank Yumiao Mai for her advice and assistance with the preparation of the figures.

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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Authors and Affiliations

  1. Department of Pediatrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China

    Zhaohe Jing, Linchao Zhao, Yumiao Mai, Pan Sun, Hongyun Niu, Simin Qiu & Jian Liu

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  1. Zhaohe Jing
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  2. Linchao Zhao
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  4. Pan Sun
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  5. Hongyun Niu
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Contributions

Zhaohe Jing and Jian Liu contributed to the study design. Zhaohe Jing wrote the main manuscript text and prepared the table. Linchao Zhao, Yumiao Mai, Pan Sun, Hongyun Niu, Simin Qiu, 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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The authors declare no competing interests.

Ethics approval and consent to participate

This study has been approved by the Ethics Committee of The First Affiliated Hospital of Zhengzhou University (2025-KY-0168) and waived informed consent given the retrospective nature. 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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Jing, Z., Zhao, L., Mai, Y. et al. Hematopoietic stem cell transplantation outcomes in pediatric acquired aplastic anemia with inherited bone marrow failure syndrome-associated genes. Bone Marrow Transplant (2025). https://doi.org/10.1038/s41409-025-02671-6

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