Jiang Bingqian, Yang Tingting, Zhao Yanmin, Luo Yi, Ouyang Guifang, Yu Jian, Ye Yishan, Lan Jianping, Lu Ying, Lai Xiaoyu, Ye Baodong, Chen Yi, Liu Lizhen, Xu Yang, Shi Pengfei, Xiao Haowen, Hu Huixian, Guo Qunyi, Fu Huarui, Wang Xinyu, Sun Jie, Zheng Weiyan, He Jingsong, Zhao Yi, Wu Wenjun, Cai Zhen, Wei Guoqing, Huang He, Shi Jimin
Bone Marrow Transplantation Center of The First Affiliated Hospital & Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou, China.
Institute of Hematology, Zhejiang University, Hangzhou, China.
Bone Marrow Transplant. 2025 Mar;60(3):326-334. doi: 10.1038/s41409-024-02486-x. Epub 2024 Dec 4.
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.
TP53基因发生突变的骨髓增生异常综合征（MDS）患者预后不佳；造血干细胞移植（HSCT）前进行减瘤治疗的益处存在争议。我们回顾性分析了284例接受异基因HSCT的MDS患者；其中49例有TP53基因突变，38例在移植前接受了减瘤治疗，11例仅接受最佳支持治疗（BSC）。无论TP53等位基因状态如何，TP53基因突变的患者总生存率低于野生型TP53患者，复发率高于野生型TP53患者（分别为P＜0.001，P = 0.002）。在TP53基因突变队列中，减瘤治疗组的2年总生存率与BSC组相当（34.6%对45.5%，P = 0.53），且未观察到其他预后益处（所有P＜0.05）。此外，化疗亚组、去甲基化药物亚组和BSC亚组之间未发现预后差异（所有P＞0.05）。HSCT前微小残留病（MRD）阴性亚组、HSCT前MRD阳性亚组和BSC亚组的患者预后相似（所有P＞0.05）。多变量分析显示，HSCT前减瘤治疗与移植后生存率无关（所有P＞0.05）。总之，TP53基因突变的MDS患者HSCT后预后较差；与BSC相比，HSCT前减瘤治疗不能改善预后，即使是移植前MRD阴性的患者。
