扶正解毒方辨治化疗后弥漫性大B细胞淋巴瘤患者的生存分析及其对淋巴细胞亚群的调控作用

李希; 周雯怡; 颛孙诗雅; 袁欣蓓; 杨轶杰; 傅华; 沈伟; 徐旻; 甘欣锦; 陆嘉惠

doi:10.3969/j.issn.1006-2157.2024.11.016

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扶正解毒方辨治化疗后弥漫性大B细胞淋巴瘤患者的生存分析及其对淋巴细胞亚群的调控作用

血液与肿瘤 | 更新时间：2024-12-02

- 扶正解毒方辨治化疗后弥漫性大B细胞淋巴瘤患者的生存分析及其对淋巴细胞亚群的调控作用
- Survival analysis of patients with diffuse large B-cell lymphoma after chemotherapy using Fuzheng Jiedu Formula and its mechanism of action on lymphocyte subsets
- 北京中医药大学学报 2024年47卷第11期页码：1603-1611
- 作者机构：
  
  1.上海中医药大学附属龙华医院　上海　200032
  2.上海中医药大学附属市中医医院
- 作者简介：
  
  李希，男，副主任医师，在读博士生
  #陆嘉惠，女，博士，主任医师，博士生导师，主要研究方向：中医药治疗血液病的临床与基础研究，E-mail：lujiahui73@163.com
- 基金信息：
  
  上海市科学技术委员会医学创新研究专项重大项目(21Y31920400)
- DOI：10.3969/j.issn.1006-2157.2024.11.016
  中图分类号： R273
- 收稿日期：2024-06-20，
  
  网络出版日期：2024-11-04，
  
  纸质出版日期：2024-11-30
- 稿件说明：
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李希, 周雯怡, 颛孙诗雅, 等. 扶正解毒方辨治化疗后弥漫性大B细胞淋巴瘤患者的生存分析及其对淋巴细胞亚群的调控作用[J]. 北京中医药大学学报, 2024,47(11):1603-1611.

LI Xi, ZHOU Wenyi, ZHUANSUN Shiya, et al. Survival analysis of patients with diffuse large B-cell lymphoma after chemotherapy using Fuzheng Jiedu Formula and its mechanism of action on lymphocyte subsets[J]. Journal of beijing university of traditional chinese medicine, 2024, 47(11): 1603-1611.
李希, 周雯怡, 颛孙诗雅, 等. 扶正解毒方辨治化疗后弥漫性大B细胞淋巴瘤患者的生存分析及其对淋巴细胞亚群的调控作用[J]. 北京中医药大学学报, 2024,47(11):1603-1611. DOI： 10.3969/j.issn.1006-2157.2024.11.016.

LI Xi, ZHOU Wenyi, ZHUANSUN Shiya, et al. Survival analysis of patients with diffuse large B-cell lymphoma after chemotherapy using Fuzheng Jiedu Formula and its mechanism of action on lymphocyte subsets[J]. Journal of beijing university of traditional chinese medicine, 2024, 47(11): 1603-1611. DOI： 10.3969/j.issn.1006-2157.2024.11.016.

摘要

目的

评价扶正解毒方辨治化学治疗(简称“化疗”)后弥漫性大B细胞淋巴瘤(DLBCL)患者的生存情况，并探究淋巴细胞亚群水平与化疗后DLBCL患者生存的关联。

方法

收集2013年1月1日—2023年12月31日就诊于上海中医药大学附属龙华医院、上海同济大学附属东方医院血液科门诊及病房所有确诊DLBCL并已完成化疗，且疗效达到完全缓解(CR)或部分缓解(PR)的患者，共234例。采用队列研究设计，将“化疗后是否连续接受≥6个月扶正解毒方治疗”作为暴露因素，将符合此暴露因素的患者分入中医队列，不符合此暴露因素的患者分入观察队列。比较2个队列患者1、2年无进展生存率、总生存率及持续缓解时间(DOR)，绘制2个队列无进展生存时间、总生存时间的生存曲线，并进行亚组生存分析，进一步筛选影响疾病进展的因素，并观察扶正解毒方对患者淋巴细胞亚群计数水平的影响。

结果

本研究共纳入234例化疗后DLBCL患者，其中，中医队列126例，观察队列108例。与观察队列比较，中医队列2年无进展生存率、2年总生存率、DOR升高(均

0.05)。中医队列的PFS高于观察队列[

＝0.542，95%

(0.345～0.853)，

0.01

]

。亚组分析结果显示，年龄≥60岁、安娜堡(AA)分期Ⅲ～Ⅳ期、CD4

＋

正常范围下限(LLN)亚组中，中医队列的无进展生存时间高于观察队列(均

0.05)。COX回归结果显示，AA分期Ⅲ～Ⅳ期[

＝2.180，95%

(1.064～4.466)，

0.05

]

、CD4

＋

LLN [

＝2.840，95%

(1.253～6.434)，

0.05

]

是化疗后DLBCL疾病进展的独立危险因素；中医队列为保护性因素[

＝0.538，95%

(0.297～0.974)，

0.05

]

，可将疾病进展风险降低46.2%。淋巴细胞亚群绝对计数分析结果显示，中医队列治疗前后比较，诱导化疗结束后2年较诱导化疗结束时CD3

＋

、CD4

＋

、CD19

＋

升高(均

0.05)；2个队列比较，中医队列CD3

＋

、CD4

＋

差值扩大，观察队列CD3

＋

、CD4

＋

差值缩小，2个队列的变化差异有统计学意义(均

0.05)。

结论

扶正解毒方维持治疗可以提高化疗后DLBCL患者的生存率，延长生存时间，在年龄≥60岁、AA分期Ⅲ～Ⅳ期、CD4

＋

LLN的人群中获益更加明显。扶正解毒方可明显降低化疗后DLBCL患者的疾病进展风险，并改善患者的免疫细胞水平。在西医化疗结束后，序贯维持扶正解毒方治疗可以为DLBCL患者带来更好的疗效。

Abstract

Objective

To evaluate the survival of patients with diffuse large B-cell lymphoma (DLBCL) after chemotherapy using

Fuzheng Jiedu

Formula and to explore the intrinsic correlation between the lymphocyte subset level and the survival of patients with DLBCL.

Methods

A total of 234 patients with DLBCL who had completed chemotherapy and achieved complete or partial response in the Department of Hematology

Longhua Hospital Shanghai University of Traditional Chinese Medicine and Shanghai East Hospital

Tongji University from January 1

2013

to December 31

2023

were recruited. A cohort study design was adopted

with " whether to receive continuous

Fuzheng Jiedu

Formula treatment for ≥ 6 months after chemotherapy" as the exposed factor. Patients meeting this exposed factor were divided into the traditional Chinese medicine (TCM) cohort

whereas those who did not meet this exposed factor were divided into the observation cohort. The 1- and 2-year progression-free survival (PFS) rate

overall survival (OS) rate

and duration of response (DOR) of the two cohorts were compared. The survival curves of PFS and OS of the two cohorts were drawn

and subgroup survival ana

lysis was performed to determine factors affecting disease progression. The effect of

Fuzheng Jiedu

Formula on lymphocyte subset count level was observed.

Results

The study included 126 and 108 patients in the TCM and observation cohorts

respectively. Compared with the observation cohort

the 2-year PFS rate

2-year OS rate

and DOR were increased in the TCM cohort (

0.05). The PFS in the TCM cohort was higher than that in the observation cohort [

=0.542

95%

(0.345-0.853)

0.01

]

. The result of subgroup analysis showed that PFS in the TCM cohort was higher than that in the observation cohort in the age ≥60 years

AA stage Ⅲ-Ⅳ

CD4

lower limits of normal(LLN) subgroup(

0.05). COX regression result showed that AA stage Ⅲ-Ⅳ[

=2.180

95%

(1.064-4.466)

0.05

]

and CD4

LLN [

=2.840

95%

(1.253-6.434)

0.05

]

were independent risk factors for DLBCL progression after chemotherapy. The TCM cohort had a protective factor [

=0.538

95%

(0.297-0.974)

0.05

]

that could reduce the risk of disease progression by 46.2%. The result of absolute lymphocyte subset count analysis showed that in the TCM cohort

CD3

CD4

and CD19

levels were significantly higher 2 years after end of induction therapy(EOI) compared to at EOI (

0.05). When comparing the two cohorts

the differences in CD3

and CD4

levels widened in the TCM cohort while narrowing in the observation cohort

and these changes between the two cohorts were statistically significant (

0.05).

Conclusion

Maintenance treatment with

Fuzheng Jiedu

Formula can improve the survival rate of p

atients with DLBCL after chemotherapy and prolong their survival time. The benefits of this treatment are apparent in the age ≥ 60 years

AA stage Ⅲ-Ⅳ

and CD4

LLN cohort.

Fuzheng Jiedu

Formula can significantly reduce the risk of disease progression in patients with DLBCL after chemotherapy and increase the immune cell level. After completing chemotherapy

the sequential maintenance treatment with

Fuzheng Jiedu

Formula can offer significant survival benefits for patients with DLBCL.

关键词

Keywords

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