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

Bingqian Jiang; Tingting Yang; Yanmin Zhao; Yi Luo; Guifang Ouyang; Jian Yu; Yishan Ye; Jianping Lan; Ying Lu; Xiaoyu Lai; Baodong Ye; Yi Chen; Lizhen Liu; Yang Xu; Pengfei Shi; Haowen Xiao; Huixian Hu; Qunyi Guo; Huarui Fu; Xinyu Wang; Jie Sun; Weiyan Zheng; Jingsong He; Yi Zhao; Wenjun Wu; Zhen Cai; Guoqing Wei; He Huang; Jimin Shi

doi:10.1038/s41409-024-02486-x

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

Bone Marrow Transplant. 2024 Dec 4. doi: 10.1038/s41409-024-02486-x. Online ahead of print.

Authors

Bingqian Jiang^#^{1

2

3}, Tingting Yang^#^{1

2

3}, Yanmin Zhao^{1

2

3}, Yi Luo^{1

2

3}, Guifang Ouyang⁴, Jian Yu^{1

2

3}, Yishan Ye^{1

2

3}, Jianping Lan⁵, Ying Lu⁶, Xiaoyu Lai^{1

2

3}, Baodong Ye⁷, Yi Chen⁸, Lizhen Liu^{1

2

3}, Yang Xu⁹, Pengfei Shi¹⁰, Haowen Xiao¹¹, Huixian Hu¹², Qunyi Guo¹³, Huarui Fu^{1

2

3}, Xinyu Wang^{1

2

3}, Jie Sun^{1

2

3}, Weiyan Zheng^{1

2

3}, Jingsong He^{1

2

3}, Yi Zhao^{1

2

3}, Wenjun Wu^{1

2

3}, Zhen Cai^{1

2

3}, Guoqing Wei^{1

2

3}, He Huang^{14

15

16}, Jimin Shi^{17

18

19}

Affiliations

¹ Bone Marrow Transplantation Center of The First Affiliated Hospital & Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou, China.
² Institute of Hematology, Zhejiang University, Hangzhou, China.
³ Zhejiang Province Engineering Research Center for Stem Cell and Immunity Therapy, Hangzhou, China.
⁴ Department of Hematology, Ningbo First Hospital, Ningbo, China.
⁵ Department of Hematology, Zhejiang Provincial People's Hospital, Hangzhou, China.
⁶ Department of Hematology, Yinzhou People's Hospital, Ningbo, China.
⁷ Department of Hematology, The First Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, China.
⁸ Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
⁹ Department of Hematology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
¹⁰ Department of Hematology, The Affiliated Hangzhou First People's Hospital, Westlake University School of Medicine, Hangzhou, China.
¹¹ Department of Hematology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
¹² Department of Hematology, Jinhua Central Hospital, Jinhua, China.
¹³ Department of Hematology, Taizhou Hospital of Zhejiang, Wenzhou Medical University, Taizhou, China.
¹⁴ Bone Marrow Transplantation Center of The First Affiliated Hospital & Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou, China. huanghe@zju.edu.cn.
¹⁵ Institute of Hematology, Zhejiang University, Hangzhou, China. huanghe@zju.edu.cn.
¹⁶ Zhejiang Province Engineering Research Center for Stem Cell and Immunity Therapy, Hangzhou, China. huanghe@zju.edu.cn.
¹⁷ Bone Marrow Transplantation Center of The First Affiliated Hospital & Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou, China. shijimin@zju.edu.cn.
¹⁸ Institute of Hematology, Zhejiang University, Hangzhou, China. shijimin@zju.edu.cn.
¹⁹ Zhejiang Province Engineering Research Center for Stem Cell and Immunity Therapy, Hangzhou, China. shijimin@zju.edu.cn.

^# Contributed equally.

PMID: 39627346
DOI: 10.1038/s41409-024-02486-x

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.

Abstract

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