急性淋巴细胞白血病儿童治疗失败原因的分析

doi:10.3969/j.issn.1674-8115.2021.06.010

摘要/Abstract

摘要：

目的·分析急性淋巴细胞白血病（acute lymphocytic leukemia，ALL）儿童治疗失败的原因，探讨减少治疗失败的策略。方法·回顾性研究2006年1月至2017年6月于上海市儿童医院初诊的330例ALL患儿中的治疗失败者，分析其治疗失败的原因；并按不同原因分别分析这些患儿的临床特征。采用Kaplan-Meier生存曲线及COX回归模型分析患儿的复发率、复发患儿的总生存（overall survival，OS）率及影响复发的危险因素；采用χ²检验分析不同危险度患儿感染出现阶段的差异。结果·330例ALL患儿中治疗失败84例，治疗失败原因包括疾病复发（58例）、因严重感染死亡（19例）、第二肿瘤发生（2例）和其他原因导致死亡（5例）。58例复发患儿的中位复发时间为27（2~95）个月，5年累积复发率为（18.2 ± 2.3）%，10年累积复发率为（22.4 ± 2.9）%。多因素COX回归分析发现，早期泼尼松治疗反应不佳（HR=5.43，P=0.000）、疾病中高危险度（HR=2.26，P=0.017）是复发的独立危险因素。按复发时间分析，很早期复发患儿的5年OS率为（16.7±10.2）%，显著低于早期复发和晚期复发患儿（均P=0.000）。按复发部位分析，单纯骨髓复发患儿的5年OS率为（42.0±10.2）%，显著低于单纯髓外复发患儿（P=0.044）。55例并发严重感染的患儿中，26例为脓毒症，20例为呼吸道感染合并急性呼吸窘迫综合征，9例为严重肠道感染。不同危险度患儿感染出现阶段的分布差异有统计学意义（P=0.019），低危患儿在诱导巩固治疗阶段更易并发严重感染（P=0.022），中高危患儿在中期强化治疗阶段更易并发严重感染（P=0.044）。结论·复发及因感染死亡是ALL患儿治疗失败的主要原因；积极预防并治疗很早期复发及感染可降低治疗失败发生率，提高患儿长期生存率。

关键词: 急性淋巴细胞白血病, 儿童, 治疗失败, 复发, 感染

Abstract:

Objective·To analyze the reasons for the treatment failure of childhood acute lymphoblastic leukemia (ALL), and explore the strategy in failure reduction.

Methods·A retrospective study was conducted on the cases with treatment failure in 330 children who were initially diagnosed as having ALL in Shanghai Children's Hospital from January 2006 to June 2017 to analyze the reasons for failure. The clinical characteristics of the children with different reasons were analyzed respectively. Kaplan-Meier survival curve analysis and COX regression model were used to explore the recurrence rate, overall survival (OS) rate and risk factors of recurrence. The difference of the stages of infection occurrence in the children with different risk levels was explored by χ² test.

Results·Among the 330 children with ALL, 84 cases failed in treatment. The reasons for treatment failure included disease recurrence (58 cases), death due to severe infection (19 cases), second tumor occurrence (2 cases), and death from other causes (5 cases). Totally 58 ALL children relapsed, whose median recurrence time was 27 (2-95) months. The 5-year cumulative recurrence rate was (18.2 ± 2.3)%, and the 10-year cumulative recurrence rate was (22.4 ± 2.9)%. Multivariate analysis showed that poor treatment response in the early stage (HR=5.43, P=0.000) and medium and high risk of disease (HR=2.26, P=0.017) were independent risk factors for recurrence. According to the recurrence time, the 5-year OS rate of children with very early recurrence was (16.7±10.2)%, significantly lower than that of children with early and late recurrence (P=0.000). According to the location of recurrence, the 5-year OS rate of children with simple bone marrow recurrence was (42.0±10.2)%, significantly lower than that of children with simple extramedullary recurrence (P=0.044). Of the 55 children with severe infection, 26 cases had sepsis, 20 cases had respiratory infection with acute respiratory distress syndrome, and 9 cases had severe intestinal infection. There were statistically significant differences in the stage distribution of infection occurrence in the children with different risk levels (P=0.019). Low-risk children were more likely to have serious infection during the induction and consolidation treatment phase (P=0.022), and medium-and-high-risk children were more likely to have serious infection in the mid-stage of intensive treatment (P=0.044).

Conclusion·Recurrence and death from infection are the main causes for treatment failure in childhood ALL. Active prevention and treatment of very early recurrence and infection can reduce the incidence of treatment failure and improve the long-term survival rate of the children.

Key words: acute lymphocytic leukemia (ALL), children, treatment failure, recurrence, infection

中图分类号:

R733.71

朱嘉莳, 李红, 邵静波, 张娜, 杨静薇, 陈凯, 王真, 蒋慧. 急性淋巴细胞白血病儿童治疗失败原因的分析[J]. 上海交通大学学报(医学版), 2021, 41(6): 764-769.

Jia-shi ZHU, Hong LI, Jing-bo SHAO, Na ZHANG, Jing-wei YANG, Kai CHEN, Zhen WANG, Hui JIANG. A clinical study on treatment failure of childhood acute lymphoblastic leukemia[J]. JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE), 2021, 41(6): 764-769.

图/表 5

参考文献 23

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Factor	Recurrent patient/n	5-year RFS rate/%	χ² (P value)
Gender			0.015 (0.903)
Male (n=194)	34	83.5±2.8
Female (n=136)	24	83.6±3.4
Age			6.585 (0.037)
<10 years (n=286)	45	84.3±2.7
≥10 years(n=44)	13	65.9±7.8
Blast count of PB			7.413(0.006)
Positive (n=143)	35	74.9±4.0
Negative (n=187)	23	87.1±2.6
Early response to prednisone treatment			58.287(0.000)
Poor (n=41)	21	41.1±8.9
Good (n=289)	37	87.1±2.1
WBC			2.709 (0.100)
<50×10⁹/L^-1 (n=282)	47	83.3±2.4
≥50×10⁹/L^-1 (n=48)	11	72.2±7.3
Immunophenotyping			0.000 (0.985)
B-ALL (n=306)	54	81.8±2.4
T-ALL (n=24)	4	81.8±8.2
Extramedullary infiltration			0.045 (0.833)
Positive (n=13)	2	81.9±2.3
Negative (n=317)	56	83.3±10.8
Clinical risk group			13.906 (0.000)
Low (n=137)	12	91.0±2.8
Medium-and-high (n=193)	46	74.9±3.4

Factor	Recurrent patient/n	5-year RFS rate/%	χ² (P value)
Gender			0.015 (0.903)
Male (n=194)	34	83.5±2.8
Female (n=136)	24	83.6±3.4
Age			6.585 (0.037)
<10 years (n=286)	45	84.3±2.7
≥10 years(n=44)	13	65.9±7.8
Blast count of PB			7.413(0.006)
Positive (n=143)	35	74.9±4.0
Negative (n=187)	23	87.1±2.6
Early response to prednisone treatment			58.287(0.000)
Poor (n=41)	21	41.1±8.9
Good (n=289)	37	87.1±2.1
WBC			2.709 (0.100)
<50×10⁹/L^-1 (n=282)	47	83.3±2.4
≥50×10⁹/L^-1 (n=48)	11	72.2±7.3
Immunophenotyping			0.000 (0.985)
B-ALL (n=306)	54	81.8±2.4
T-ALL (n=24)	4	81.8±8.2
Extramedullary infiltration			0.045 (0.833)
Positive (n=13)	2	81.9±2.3
Negative (n=317)	56	83.3±10.8
Clinical risk group			13.906 (0.000)
Low (n=137)	12	91.0±2.8
Medium-and-high (n=193)	46	74.9±3.4

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