[1]陈 平,环亚红.伴p53缺失/突变的双打击多发性骨髓瘤的临床特征及患者预后风险评分模型与验证[J].现代检验医学杂志,2025,40(02):17-23.[doi:10.3969/j.issn.1671-7414.2025.02.004]
　CHEN Ping,HUAN Yahong.Clinical Characteristics and Prognostic Risk Score Model of Double Hit Multiple Myeloma with p53 Deletion/Mutation[J].Journal of Modern Laboratory Medicine,2025,40(02):17-23.[doi:10.3969/j.issn.1671-7414.2025.02.004]
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伴p53缺失/突变的双打击多发性骨髓瘤的临床特征及患者预后风险评分模型与验证()
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《现代检验医学杂志》[ISSN:/CN:]

卷:
第40卷
期数:
2025年02期
页码:
17-23
栏目:
论著
出版日期:
2025-03-15

文章信息/Info

Title:
Clinical Characteristics and Prognostic Risk Score Model of Double Hit Multiple Myeloma with p53 Deletion/Mutation
文章编号:
1671-7414（2025）02-017-08
作者:
陈 平; 环亚红
（南京中医药大学附属南京中医院血液科，南京 210022）
Author(s):
CHEN Ping; HUAN Yahong
（Department of Hematology, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine，Nanjing 210022，China）
关键词:
p53 缺失/ 突变; 双打击; 多发性骨髓瘤; 临床特征; 预后因素
分类号:
R733.3；R730.43
DOI:
10.3969/j.issn.1671-7414.2025.02.004
文献标志码:
A
摘要:
目的 分析伴p53 缺失/ 突变的双打击多发性骨髓瘤（MM）患者的临床特征及预后影响因素。方法 以2017 年6 月～ 2023 年6 月南京中医药大学附属南京中医院收治的MM 患者为研究对象。采用荧光原位杂交技术（FISH）检测染色体变化，基因测序检测p53 基因突变情况，根据检测结果选择p53 缺失或突变患者共180 例，将这180 例患者分为仅p53 缺失/ 突变组( 对照组，n=73) 和伴p53 缺失/ 突变双打击组( 研究组，n=107)。对两组患者的临床特征和疗效进行比较，分析MM 患者预后影响因素，建立评估MM 患者预后的风险评分模型并进行验证。结果 研究组髓外病变（46.73%）、骨病变（42.06%）、处于DS Ⅲ期（70.09%）、ISS Ⅲ期（64.49%）、R-ISS Ⅲ期（59.81%）的患者比例明显高于对照组（28.77%，19.18%，45.21%，39.73%，32.88%），差异具有统计学意义（χ2=5.861 ～ 12.600，均P ＜ 0.05）。研究组患者治疗后的临床总有效率（OR）为52.34%，低于对照组的65.75%，但两组间比较差异无统计学意义（χ2=3.202，P=0.074）。研究组MM患者无进展生存期（PFS）及总体生存期（OS）均明显短于对照组，差异具有统计学意义（χ2=15.522，16.973，均P ＜ 0.05）。多因素COX 回归分析显示，骨髓浆细胞比例≥ 30%，β2-MG ≥ 5.5mg/L，PLT<125×109/L，LDH ≥ 240U/L 和伴p53 缺失/ 突变双打击是MM 患者PFS 率的危险因素（Wald χ2=2.983 ～ 3.942，均P ＜ 0.05）。R-ISS 分期Ⅲ期、骨髓浆细胞比例≥ 30%，β2-MG ≥ 5.5mg/L，LDH ≥ 240U/L 和伴p53 缺失/ 突变双打击是MM 患者OS 率的危险因素（Wald χ2=3.389 ～ 3.971，均P ＜ 0.05）。建立评估MM 患者预后的风险评分模型，并且ROC 曲线结果显示风险评分模型具有较好的区分度。两年PFS，OS 在低危组、中危组及高危组中依次缩短，差异具有统计学意义（F=23.629，17.664，均P<0.05）。结论 伴p53 缺失/ 突变的双打击MM 患者临床表现主要为髓外病变、骨病变、处于DS Ⅲ期、ISS Ⅲ期、R-ISS Ⅲ期居多。伴p53 缺失/ 突变双打击是MM 患者预后的重要影响因素。
Abstract:
Objective To analyze the clinical characteristics and prognostic factors of patients with double hit multiple myeloma (MM) patients with p53 deletion/mutation. Methods MM patients admitted to Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine from June 2017 to June 2023 were selected as the study subjects. They used fluorescence in situ hybridization (FISH) to detect chromosomal changes and gene sequencing to detect p53 gene mutations. According to the detection results, a total of 180 patients with p53 deletion/mutation were selected, and these 180 patients were divided into a p53 deletion/mutation-only group (control group, n=73) and a dual strike group with p53 deletion/mutation (research group , n=107). Compared the clinical characteristics and efficacy of two groups of patients, and analyzed the factors influencing the prognosis of MM patients. Established a risk-scoring model for evaluating and validating the prognosis of MM patients. Results The proportion of patients with extramedullary lesions(46.73%), bone lesions(42.06%), DS stage III(70.09%), ISS stage III(64.49%) and R-ISS stage III(59.81%) in research group with p53 deletion/mutation was significantly higher than that in conctrol group(28.77%, 19.18%, 45.21%, 39.73%, 32.88%)，and the differences were statistically significant (χ2=5.861~12.600, all P<0.05). The OR of patients in research group with p53 deletion/mutation after treatment was 52.34%, lower than 65.75% in conctrol group. Still, there was no statistically significant difference between the two groups (χ2=3.202, P=0.074). The PFS and OS of MM patients with research group were significantly shorter than those with conctrol group，and the differences were statistically significant (χ2 =15.522, 16.973, all P ＜ 0.05).Multivariate COX proportional hazards results, bone marrow plasma cell ratio ≥ 30%，β2-MG ≥ 5.5mg/L，PLT<125×109/L，LDH ≥ 240U/L and dual strikes with p53 deletion/mutation were risk factors for PFS rate in MM patients(Wald χ2=2.983 ～ 3.942, all P ＜ 0.05). R-ISS stage III, bone marrow plasma cell ratio ≥ 30%，β2-MG ≥ 5.5mg/L，LDH ≥ 240U/L and dual strikes with p53 deletion/mutation were risk factors for OS rate in MM patients(Wald χ2=3.389 ～ 3.971, all P ＜ 0.05). Establishing a risk scoring model for evaluating the prognosis of MM patients, and the ROC curve results show that the risk scoring model has good discrimination. The 2-year PFS and OS were shortened sequentially in the low-risk group, medium-risk group and high-risk group, and the differences were statistically significant (F=23.629, 17.664, all P<0.05). Conclusion The clinical manifestations of MM patients with double-hit p53 deletion/mutation are mainly extramedullary lesions, bone lesions, DS staging, ISS staging, and R-ISS staging, with stage III being the most common. The double-hit of p53 deletion/mutation and accompanying is an important prognostic factor for MM patients.

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备注/Memo

备注/Memo:
作者简介：陈平（1990-），女，博士研究生，主治中医师，研究方向：血液病学，E-mail:15150678965@163.com。
通讯作者：环亚红（1985-），女，副主任医师，研究方向：血液病学，E-mail:675128515@qq.com。
更新日期/Last Update: 2025-03-15