具有特定突变的骨髓增生异常综合征患者的临床结局及特征

Clinical outcomes and characteristics of patients with -mutated myelodysplastic syndromes.

作者信息

Zhang Lijuan, Chen Kankan, Li Yingying, Chen Qiuni, Shi Wenting, Ji Tingting, Tao Hong, He Zhengmei, Wang Chunling, Yu Liang

机构信息

Department of Hematology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an, People's Republic of China.

Department of Hematology, The Huai'an Clinical College of Xuzhou Medical University, Huai'an, People's Republic of China.

出版信息

Hematology. 2023 Dec;28(1):2181773. doi: 10.1080/16078454.2023.2181773.

DOI:10.1080/16078454.2023.2181773

PMID:36892252

Abstract

OBJECTIVE

To explore the clinical outcomes and characteristics of -mutated primary myelodysplastic syndromes (MDS).

METHODS

A total of 74 primary MDS patients who were diagnosed and treated in the Department of Hematology of our hospital from January 2018 and September 2021 were analyzed retrospectively. All patients had evaluable blood cell counts, mean corpuscular volume (MCV), lactate dehydrogenase (LDH), bone marrow (BM) morphology, biopsy, and MDS-related 20-gene mutations sequencing. In addition, 69 of 74 patients had complete cytogenetic analysis through conventional chromosome analysis and fluorescence hybridization.

RESULTS

Patients were divided into two cohorts, the mutated type (TP53) group ( = 19) and wild type (TP53 group ( = 55). Compared with the TP53 group, patients in the TP53 group had higher ratios of cytogenetic abnormalities (82.4% vs. 30.8%, < 0.001), with 5q- karyotype (64.70% vs. 38.5%, < 0.001), complex karyotype(CK) (64.70% vs. 38.5%, < 0.001), HR-MDS (94.7% vs. 61.8%, = 0.008), and acute myelogenous leukemia (AML) transformation (26.3% vs. 12.7%, < 0.001). Interestingly, patients in the TP53 group had lower median MCV than the TP53 group (94.40 fl vs. 101.90 fl, 0.008). Furthermore, MCV = 100 fl as cutoff, and found that MCV ≤ 100 fl was more common in the TP53 group (73.7% vs. 38.2%, < 0.001). After 1-4 courses of HMA ± chemotherapy, the overall response rate of the TP53 group was higher than the TP53 group (83.3% vs. 71.4%, = 0.012). With the median follow-up 12.0 months (1-46 months), the results show that the median OS and leukemia-free survival (LFS) of TP53 group was significantly shorter than the TP53 group (= 0.0018; = 0.0310). Results of multivariate Cox proportional hazard analyses show mutation was an independent prognostic factor for the OS (HR 2.724, 95%CI 1.099-6.750, = 0.030).

CONCLUSION

-mutated primary MDS patients were associated with higher frequency of cytogenetic abnormalities, with 5q- karyotype, CK, AML transformation, higher risk IPSS-R, lower MCV and sensitive to HMA treatment, but worse survival.

摘要

目的

探讨TP53突变的原发性骨髓增生异常综合征（MDS）的临床结局及特征。

方法

回顾性分析2018年1月至2021年9月在我院血液科诊断并治疗的74例原发性MDS患者。所有患者均有可评估的血细胞计数、平均红细胞体积（MCV）、乳酸脱氢酶（LDH）、骨髓（BM）形态、活检及MDS相关的20基因突变测序。此外，74例患者中的69例通过传统染色体分析和荧光原位杂交进行了完整的细胞遗传学分析。

结果

患者分为两个队列，即突变型（TP53）组（n = 19）和野生型（TP53）组（n = 55）。与TP53野生型组相比，TP53突变组患者的细胞遗传学异常比例更高（82.4%对30.8%，P < 0.001），其中5q-核型（64.70%对38.5%，P < 0.001）、复杂核型（CK）（64.70%对38.5%，P < 0.001）、高危MDS（HR-MDS）（94.7%对61.8%，P = 0.008）及急性髓系白血病（AML）转化比例更高（26.3%对12.7%，P < 0.001）。有趣的是，TP53突变组患者的中位MCV低于TP53野生型组（94.40 fl对101.90 fl，P = 0.008）。此外，以MCV = 100 fl为界值发现，MCV≤100 fl在TP53突变组更常见（73.7%对38.2%，P < 0.001）。在接受1 - 4个疗程的HMA±化疗后，TP53突变组的总缓解率高于TP53野生型组（83.3%对71.4%，P = 0.012）。中位随访12.0个月（1 - 46个月），结果显示TP53突变组的中位总生存期（OS）和无白血病生存期（LFS）显著短于TP53野生型组（P = 0.0018；P = 0.0310）。多因素Cox比例风险分析结果显示TP53突变是OS的独立预后因素（风险比2.724，95%置信区间1.099 - 6.750，P = 0.030）。