儿童急性淋巴细胞白血病化疗相关严重不良反应的临床分析

许凤玲, 管贤敏, 温贤浩, 沈亚莉, 肖剑文, 郭玉霞, 邓梦月, 于洁

中国当代儿科杂志 ›› 2020, Vol. 22 ›› Issue (8) : 828-833.

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中国当代儿科杂志 ›› 2020, Vol. 22 ›› Issue (8) : 828-833. DOI: 10.7499/j.issn.1008-8830.2003253
论著·临床研究

儿童急性淋巴细胞白血病化疗相关严重不良反应的临床分析

  • 许凤玲, 管贤敏, 温贤浩, 沈亚莉, 肖剑文, 郭玉霞, 邓梦月, 于洁
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Serious adverse events associated with chemotherapy in children with acute lymphoblastic leukemia

  • XU Feng-Ling, GUAN Xian-Min, WEN Xian-Hao, SHEN Ya-Li, XIAO Jian-Wen, GUO Yu-Xia, DENG Meng-Yue, YU Jie
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摘要

目的 分析CCCG-ALL-2015方案治疗儿童急性淋巴细胞白血病(ALL)合并严重不良反应(SAE)的临床特点,探讨患儿发生SAE后死亡的危险因素。方法 回顾性分析2015年1月至2019年6月确诊并接受CCCG-ALL-2015方案化疗的734例ALL患儿化疗过程中发生SAE的临床特点,将发生SAE的ALL患儿分为死亡组(n=25)和存活组(n=31),采用多因素logistic回归分析ALL患儿发生SAE后死亡的危险因素。结果 734例ALL患儿中,56例(7.6%)化疗后发生SAE(66例次),高发于诱导缓解治疗阶段(41例次)。感染相关SAE发生46例次(70%),包括脓毒性休克25例次(38%),重症肺炎20例次(30%),重症水痘1例次(2%);感染相关SAE患儿中多数存在中性粒细胞缺乏(87%)。最常见的感染部位为血液系统和呼吸系统,最常见的病原微生物依次是革兰阴性菌、病毒、真菌和革兰阳性菌。出血相关SAE发生16例次(24%),包括消化道出血11例次(17%),肺出血4例次(6%),颅内出血1例次(2%)。734例ALL患儿中死亡66例(9.0%),25例患儿因SAE死亡,治疗相关病死率为3.4%,感染(72%)和出血(24%)是主要原因,合并重症肺炎是ALL患儿发生治疗相关死亡的独立危险因素(OR=4.087,95% CI:1.161~14.384,P=0.028)。结论 CCCG-ALL-2015方案治疗儿童ALL相关SAE主要发生于诱导缓解化疗阶段,感染相关SAE较多见。重症肺炎是ALL患儿发生治疗相关死亡的独立危险因素,需重视合并重症肺炎的治疗。

Abstract

Objective To study the occurrence of serious adverse events (SAEs) related to chemotherapy with CCCG-ALL-2015 regimen in children with acute lymphoblastic leukemia (ALL) and the risk factors for death after the SAEs. Methods A retrospective analysis was performed on the medical data of 734 children with ALL. They were treated with CCCG-ALL-2015 regimen from January 2015 to June 2019. The occurrence of SAEs during the treatment was investigated. The children with SAEs were divided into a death group with 25 children and a survival group with 31 children. A multivariate logistic regression analysis was used to analyze the risk factors for death after the SAEs. Results Among the 734 children with ALL, 56 (7.6%) experienced SAEs (66 cases) after chemotherapy, among which 41 cases occurred in the stage of remission induction therapy. Of all 66 cases of SAEs, 46 (70%) were infection-related SAEs, including 25 cases of septic shock (38%), 20 cases of severe pneumonia (30%), and 1 case of severe chickenpox (2%), and 87% of the children with infection-related SAEs had neutrophil deficiency. The most common infection sites were blood and the lungs. The most common pathogens were Gram-negative bacteria, viruses, fungi, and Gram-positive bacteria. There were 16 cases (24%) of hemorrhage-related SAEs, with 11 cases of gastrointestinal bleeding (17%), 4 cases of pulmonary bleeding (6%), and 1 case of intracranial bleeding (2%). Of all 734 children with ALL, 66 (9.0%) died, among whom 25 died due to SAEs. The treatment-related mortality rate was 3.4%, and infection (72%) and bleeding (24%) were the main causes of death. Severe pneumonia was an independent risk factor for treatment-related death in ALL children (OR=4.087, 95% CI: 1.161-14.384, P=0.028). Conclusions SAEs often occur in the stage of remission induction therapy, and infection-related SAEs are more common in ALL children accepting chemotherapy with CCCG-ALL-2015 regimen. The development of severe pneumonia suggests an increased risk for death in these children.

关键词

急性淋巴细胞白血病 / 严重不良反应 / 治疗相关死亡 / 儿童

Key words

Acute lymphoblastic leukemia / Severe adverse event / Treatment-related mortality / Child

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许凤玲, 管贤敏, 温贤浩, 沈亚莉, 肖剑文, 郭玉霞, 邓梦月, 于洁. 儿童急性淋巴细胞白血病化疗相关严重不良反应的临床分析[J]. 中国当代儿科杂志. 2020, 22(8): 828-833 https://doi.org/10.7499/j.issn.1008-8830.2003253
XU Feng-Ling, GUAN Xian-Min, WEN Xian-Hao, SHEN Ya-Li, XIAO Jian-Wen, GUO Yu-Xia, DENG Meng-Yue, YU Jie. Serious adverse events associated with chemotherapy in children with acute lymphoblastic leukemia[J]. Chinese Journal of Contemporary Pediatrics. 2020, 22(8): 828-833 https://doi.org/10.7499/j.issn.1008-8830.2003253

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