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

Serious adverse events associated with chemotherapy in children with acute lymphoblastic leukemia

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.