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TP53改变对骨髓增生异常综合征异基因造血细胞移植结局的影响。

Impact of TP53 alteration on allogeneic hematopoietic cell transplantation outcomes for myelodysplastic syndromes.

作者信息

Zhou Cuiyan, Xu Lanping, Zhang Xiaohui, Chang Yingjun, Mo Xiaodong, Sun Yuqian, Huang Xiaojun, Wang Yu

机构信息

Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Research Unit of Key Technique for Diagnosis and Treatments of Hematologic Malignancies, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China; Collaborative Innovation Center of Hematology, Peking University, Beijing, China.

Peking-Tsinghua Center for Life Sciences, 100871, Beijing, China.

出版信息

Bone Marrow Transplant. 2025 Apr;60(4):467-473. doi: 10.1038/s41409-025-02511-7. Epub 2025 Jan 22.

Abstract

The poor outcome of TP53 alteration has been reported in myelodysplastic syndrome (MDS) patients. However, the role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in TP53 alteration patients remains debated. Previous studies showed that TP53 mutations had no effect on the prognosis of patients with acute leukemia after haploidentical HSCT (haplo-HSCT). The effect of haplo-HSCT on MDS patients with TP53 alterations remains to be further elucidated. We aimed to reveal the role of TP53 alterations in the prognosis of MDS patients undergoing allo-HSCT, especially haplo-HSCT. 261 MDS patients with known TP53 status were enrolled, including thirty-seven patients with TP53 mutation/deletion (TP53mut/del). TP53mut/del patients showed a worse rate of 2-year cumulative incidence of relapse (CIR) and 2-year disease-free survival (DFS) than TP53 wild type (TP53wt) patients (46.2% vs 17.0%, P < 0.001; 41.8% vs 68.9, P < 0.001) after allo-HSCT, even for those with haplo-HSCT (CIR: P < 0.001; DFS: P = 0.002). However, the prognostic effect of TP53 alteration on overall survival (OS) was not observed in patients with haplo-HSCT (66.7% vs 75.2%, P = 0.108). Positivity of post-transplantation measurable residual disease (post-MRD) and time from diagnosis to transplantation were independent risk factors for MDS patients. TP53 alterations do not affect OS in patients undergoing haplo-HSCT requires further validation.

摘要

骨髓增生异常综合征(MDS)患者中已报道TP53改变的预后较差。然而,异基因造血干细胞移植(allo-HSCT)在TP53改变患者中的作用仍存在争议。先前的研究表明,TP53突变对单倍体相合造血干细胞移植(haplo-HSCT)后急性白血病患者的预后没有影响。haplo-HSCT对TP53改变的MDS患者的影响仍有待进一步阐明。我们旨在揭示TP53改变在接受allo-HSCT尤其是haplo-HSCT的MDS患者预后中的作用。纳入了261例已知TP53状态的MDS患者,其中37例患者存在TP53突变/缺失(TP53mut/del)。allo-HSCT后,TP53mut/del患者的2年累积复发率(CIR)和2年无病生存率(DFS)均低于TP53野生型(TP53wt)患者(46.2%对17.0%,P<0.001;41.8%对68.9,P<0.001),即使是接受haplo-HSCT的患者也是如此(CIR:P<0.001;DFS:P=0.002)。然而,在接受haplo-HSCT的患者中未观察到TP53改变对总生存期(OS)的预后影响(66.7%对75.2%,P=0.108)。移植后可测量残留病(post-MRD)阳性和从诊断到移植的时间是MDS患者的独立危险因素。TP53改变不影响接受haplo-HSCT患者的OS这一结论需要进一步验证。

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