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Better pre-transplant treatment options for TP53-mutated MDS: cytoreductive or non-cytoreductive therapy?

Bone Marrow Transplantation volume 60, pages 326–334 (2025)Cite this article

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Abstract

Patients with TP53-mutated myelodysplastic neoplasms (MDS) have unfavorable prognoses; the benefit of cytoreductive treatment before hematopoietic stem cell transplantation (HSCT) is debated. We retrospectively analyzed 284 MDS patients undergoing allogeneic HSCT; among which 49 had TP53 mutation, with 38 receiving cytoreduction and 11 treated exclusively with best supportive care (BSC) before transplantation. Regardless of TP53 allelic state, patients with mutated-TP53 had a lower overall survival rate and higher relapse rate than those with wild-type TP53 (P < 0.001, P = 0.002, respectively). Among the TP53-mutated cohort, the 2-year overall survival rate in the cytoreduction group was comparable to that in the BSC group (34.6% vs. 45.5%, P = 0.53), and no other prognostic benefit was observed as well (all P < 0.05). Moreover, no prognostic difference was found among the chemotherapy subgroup, hypomethylating agent subgroup, and BSC subgroup (all P > 0.05). Patients in the pre-HSCT measurable residual disease (MRD) negative subgroup, pre-HSCT MRD-positive subgroup, and BSC subgroup exhibited similar prognoses (all P > 0.05). Multivariate analyses showed that pre-HSCT cytoreduction was not associated with post-transplant survival (all P > 0.05). In conclusion, TP53-mutated MDS patients have poor post-HSCT outcomes; compared to BSC, pre-HSCT cytoreduction doesn’t improve prognosis, even in those with MRD negative before transplantation.

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Fig. 1: Outcomes of patients with TP53-mutated myelodysplastic neoplasms receiving cytoreduction or best supportive care before transplantation.
Fig. 2: Outcomes of patients with TP53-mutated myelodysplastic neoplasms according to different pre-transplant therapies.
Fig. 3: Outcomes of patients with TP53-mutated myelodysplastic neoplasms according to pre-transplant measurable residual disease status.

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Data availability

All data used and analyzed are available from the corresponding author upon reasonable request.

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Funding

The study was supported by the National Natural Science Foundation of China (grant numbers: 82070179, 82170210, and 81970158) and the Zhejiang Province Vanguard Goose-Leading Initiative (grant number: 2024SSYS0023).

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Author notes

  1. These authors contributed equally: Bingqian Jiang, Tingting Yang.

Authors and Affiliations

  1. Bone Marrow Transplantation Center of The First Affiliated Hospital & Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou, China

    Bingqian Jiang, Tingting Yang, Yanmin Zhao, Yi Luo, Jian Yu, Yishan Ye, Xiaoyu Lai, Lizhen Liu, Huarui Fu, Xinyu Wang, Jie Sun, Weiyan Zheng, Jingsong He, Yi Zhao, Wenjun Wu, Zhen Cai, Guoqing Wei, He Huang & Jimin Shi

  2. Institute of Hematology, Zhejiang University, Hangzhou, China

    Bingqian Jiang, Tingting Yang, Yanmin Zhao, Yi Luo, Jian Yu, Yishan Ye, Xiaoyu Lai, Lizhen Liu, Huarui Fu, Xinyu Wang, Jie Sun, Weiyan Zheng, Jingsong He, Yi Zhao, Wenjun Wu, Zhen Cai, Guoqing Wei, He Huang & Jimin Shi

  3. Zhejiang Province Engineering Research Center for Stem Cell and Immunity Therapy, Hangzhou, China

    Bingqian Jiang, Tingting Yang, Yanmin Zhao, Yi Luo, Jian Yu, Yishan Ye, Xiaoyu Lai, Lizhen Liu, Huarui Fu, Xinyu Wang, Jie Sun, Weiyan Zheng, Jingsong He, Yi Zhao, Wenjun Wu, Zhen Cai, Guoqing Wei, He Huang & Jimin Shi

  4. Department of Hematology, Ningbo First Hospital, Ningbo, China

    Guifang Ouyang

  5. Department of Hematology, Zhejiang Provincial People’s Hospital, Hangzhou, China

    Jianping Lan

  6. Department of Hematology, Yinzhou People’s Hospital, Ningbo, China

    Ying Lu

  7. Department of Hematology, The First Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, China

    Baodong Ye

  8. Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

    Yi Chen

  9. Department of Hematology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China

    Yang Xu

  10. Department of Hematology, The Affiliated Hangzhou First People’s Hospital, Westlake University School of Medicine, Hangzhou, China

    Pengfei Shi

  11. Department of Hematology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China

    Haowen Xiao

  12. Department of Hematology, Jinhua Central Hospital, Jinhua, China

    Huixian Hu

  13. Department of Hematology, Taizhou Hospital of Zhejiang, Wenzhou Medical University, Taizhou, China

    Qunyi Guo

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Contributions

SJM, JBQ, and YTT designed the whole study. ZYM, LY, OYGF, YJ, YYS, LJP, LY, LXY, YBD, CY, LLZ, XY, SPF, XHW, HHX, GQY, FHR, SJ, ZWY, HJS, ZY, WWJ, CZ, and WGQ collected data; JBQ, YTT and WXY organized data. JBQ and YTT analyzed and interpreted the data, and wrote the manuscript, which was proofreaded by HH and SJM. All authors have read and approved the final version of the manuscript.

Corresponding authors

Correspondence to He Huang or Jimin Shi.

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The authors declare no competing interests.

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All methods were performed in accordance with the relevant guidelines and regulations. Ethical approval was obtained from the Clinical Research Ethics Committee of the First Affiliated Hospital, Zhejiang University School of Medicine (No. IIT20240717B). Informed consent was obtained from each participant or their legal guardians in accordance with the Declaration of Helsinki.

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41409_2024_2486_MOESM1_ESM.docx

Figure S1. Outcomes after hematopoietic stem cell transplantation of patients with myelodysplastic neoplasms according to different TP53 allelic state.

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Jiang, B., Yang, T., Zhao, Y. et al. Better pre-transplant treatment options for TP53-mutated MDS: cytoreductive or non-cytoreductive therapy?. Bone Marrow Transplant 60, 326–334 (2025). https://doi.org/10.1038/s41409-024-02486-x

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