吉林大学学报(医学版) ›› 2022, Vol. 48 ›› Issue (3): 783-789.doi: 10.13481/j.1671-587X.20220328

• 临床研究 • 上一篇    

新药时代多发性骨髓瘤患者早期死亡原因及其危险因素分析

高珊,王宇彤,陆敏秋,石磊,褚彬,丁月华,王梦真,鲍立()   

  1. 北京积水潭医院血液科,北京 100096
  • 收稿日期:2021-09-28 出版日期:2022-05-28 发布日期:2022-06-21
  • 通讯作者: 鲍立 E-mail:baolilq909@sina.com
  • 作者简介:高 珊 (1985-),女,山东省日照市人,主治医师,医学硕士,主要从事多发性骨髓瘤和淋巴瘤临床治疗方面的研究。
  • 基金资助:
    北京市市委组织部优秀人才培养资助青年骨干个人项目(2018000021469G223)

Analysis on causes for early death and its risk factors of patients with multiple myeloma in era of novel drugs

Shan GAO,Yutong WANG,Minqiu LU,Lei SHI,Bin CHU,Yuehua DING,Mengzhen WANG,Li BAO()   

  1. Department of Hematology,Beijing Jishuitan Hospital,Beijing 100096,China
  • Received:2021-09-28 Online:2022-05-28 Published:2022-06-21
  • Contact: Li BAO E-mail:baolilq909@sina.com

摘要: 目的

探讨在新药时代多发性骨髓瘤(MM)患者早期死亡的原因及其危险因素,为早期识别高危人群和指导治疗提供依据。

方法

回顾性分析采用蛋白酶体抑制剂或免疫调节剂为基础化疗方案的新诊断多发性骨髓瘤(NDMM)患者的临床资料,根据总生存期(OS)是否超过24个月分为早期死亡组(OS<24个月)和对照组(OS≥24个月),统计分析2组患者的高危因素,包括年龄、国际分期系统(ISS)分期、修订国际分期系统(R-ISS)分期、贫血、肾功能不全、高钙血症、乳酸脱氢酶(LDH)水平升高、骨髓浆细胞比例>60%、髓外浆细胞瘤、荧光原位杂交(FISH)检测结果及疗效,生存分析采用Kaplan-Meier法绘制生存曲线,采用Logistic回归模型逐步法筛选危险因素,筛选出有意义的临床指标并采用多因素分析探讨早期死亡的高危因素。

结果

共纳入237例NDMM患者,其中早期死亡组53例,对照组184例。早期死亡组患者中位OS为16个月,对照组至随访截止时中位OS仍未达到,2组患者中位OS比较差异有统计学意义(P<0.01)。早期死亡组患者死亡原因包括疾病进展死亡(77.4%)和非疾病进展死亡(22.6%),非疾病进展死亡中包括肺炎4例、急性心肌梗塞3例、急性脑梗塞1例和自动放弃治疗死因不祥4例。单因素分析,早期死亡组患者中高龄(>65岁)、ISS分期Ⅲ期、R-ISS分期Ⅲ期、贫血、LDH水平升高、骨髓浆细胞比例>60%、髓外浆细胞瘤、FISH检测17P缺失和最佳疗效未达部分缓解(PR)的百分率均高于对照组(P<0.05)。多因素回归分析,高龄(P=0.007)、R-ISS分期Ⅲ期(P=0.003)、髓外浆细胞瘤(P=0.008)和最佳疗效未达PR(P<0.01)是新药时代NDMM患者早期死亡的独立危险因素。

结论

新药时代下早期死亡的原因为疾病进展,年龄>65岁、R-ISS分期Ⅲ期、髓外浆细胞瘤和最佳疗效未达PR仍是NDMM患者早期死亡的独立危险因素,对具有上述特征的NDMM患者进行强化治疗有可能改善患者预后。

关键词: 多发性骨髓瘤, 早期死亡, 预后, 危险因素, 总生存期

Abstract: Objective

To explore the causes and risk factors of early death in the patients with multiple myeloma (MM) in the era of novel drugs, and to provide the basis for the early identification of the high-risk patiens and guiding the treatment.

Methods

The clinical data of the patients with newly diagnosed multiple myeloma (NDMM) treated with proteasome inhibitor or immunomodulator-based chemotherapy were retrospectively analyzed. According to whether the overall survival (OS) was more than 24 months, they were divided into early death group (OS < 24 months) and control group (OS ≥ 24 months). The high-risk factors of the patients in two groups were statistically analyzed, including age, International Staging System(ISS) stage, Revised Intenational Staging System (R-ISS) stage, anemia, renal insufficiency, hypercalcemia, increasing of lactate dehydrogenase(LDH) level, bone marrow plasma cell ratio, extramedullary plasmacytoma, detection results of fluorescence in situ hybridization(FISH),and efficacy.Kaplan Meier method was used to draw the survival curves for survival analysis, Logistic regression analysis was used for stepwise screening for the risk factors, and the meaningful clinical indicators were screened, and multivariate analysis was used to explore the high-risk factors of early death.

Results

A total of 237 patients with NDMM were included, including 53 cases in early death group and 184 cases in control group. The median OS of the patients in early death group was 16 months, but the median OS of the patients in control group had not been reached by the end of follow-up. There was significant difference in OS of the patients between two groups (P<0.01). The causes for death of the patients in early death group included disease progression death (77.4%) and non-disease progression death (22.6%). The non-disease progression death included 4 cases of pneumonia, 3 cases of acute myocardial infarction, 1 case of acute cerebral infarction and 4 cases of ominous causes of death due to automatic abandonment of treatment. The univariate analysis results showed that the percentages of elderly patients (>65 years old), ISS stage Ⅲ, R-ISS stage Ⅲ, anemia, increasing of LDH level,bone marrow plasma cells ratio> 60%, extramedullary plasma cell tumor, 17p deficiency detected by FISH and failure to reach partial response(PR) in early death group were higher than those in control group (P<0.05).The multivariate regression analysis results showed that old age (P=0.007), R-ISS stage Ⅲ (P=0.003), extramedullary plasmacytoma (P=0.008) and failure to reach PR (P<0.01) were the independent risk factors for early death of the NDMM patients in the era of novel drugs.

Conclusion

The cause for early death in the era of novel drugs is disease progression; age> 65 years old, R-ISS stage Ⅲ, extramedullary plasmacytoma and the best curative effect not reaching PR are still the independent risk factors for early death of the NDMM patients. The intensive treatment of the NDMM patients with the above characteristics may improve the prognosis of the patients.

Key words: Multiple myeloma, Early death, Prognosis, Risk factor, Overall survival

中图分类号: 

  • R733.3