Clinical observation of serious adverse events in children with acute lymphoblastic leukemia during chemotherapy

doi:10.3969/j.issn.1004-583X.2023.02.009

Abstract

Abstract:

Objective To analyze the risk factors of severe adverse event(SAE)-related deaths in children with acute lymphoblastic leukemia (ALL) by summarizing the incidence of SAE during chemotherapy in patients receiving SCCLG-all-2016 regimen. Methods A retrospective analysis was performed on 82 ALL children admitted to the Department of Pediatrics of Affiliated Hospital of Guangdong Medical University, those children were treated with SCCLG-ALL-2016 regimen from December 2017 to January 2021, totally 21 children with SAE were assinged to death group (n=6) and survival group (n=15) to investigate the risk factors of SAE-related deaths during chemotherapy. Results Among the treatment stages, the largest number of SAEs was recorded in the stage of induction remission(30.9%). Hematology-related SAEs (60.3%) accounted for the majority of all SAEs. Among the non-hematology related SAEs, infection-related SAE accounted for the largest proportion (76.1%), and respiratory infection was the most frequent. Among the 6 children in the death group, 5 died of infection or co-infection factors, accounting for 83.3% of the causes of death. Conclusion For ALL children treated with SCCLG-ALL-2016 regimen, SAEs occurre mainly in the induced remission stage, mainly manifested as hematology-related SAE. Infection-related SAEs account for the highest proportion of non-hematology-related SAEs and are also important causes of death during chemotherapy. Positive chromosome results may be associated with death outcomes.

Key words: precursor cell lymphoblastic leukemia-lymphoma, child, severe adverse reactions, infection, risk factors

CLC Number:

R733.7

Du Jiayi, Liu Lili, He Yongzhong, Tian Chuan, Lan Xiang, Ye Zhonglyu. Clinical observation of serious adverse events in children with acute lymphoblastic leukemia during chemotherapy[J]. Clinical Focus, 2023, 38(2): 149-154.

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URL: https://huicui.hebmu.edu.cn/EN/10.3969/j.issn.1004-583X.2023.02.009

https://huicui.hebmu.edu.cn/EN/Y2023/V38/I2/149

Figures/Tables 6

Tab. 1 The incidence of SAE in different chemotherapy stages

化疗阶段	平均发生事件数	最少事件数	最多事件数	SAE [例(%)]	死亡 [例(%)]
诱导缓解	13.67	6	20	287(30.9)	2(33.3)
巩固	11.29	3^*	34	237(25.5)	1(16.7)
再诱导	11	2^*	25	231(24.9)	2(33.3)
维持	8.24	2^*	26	173(18.6)	1(16.7)

Tab. 2 Comparison of the incidence of hematology-related SAEs in different chemotherapy stages [cases (%)]

化疗阶段	例次	中性粒细胞绝对计数减少	血小板减少	贫血	纤维蛋白原减少	活化部分凝血活酶时间延长	溶血
诱导缓解	197	67(34.0)	60(30.5)	54(27.4)	14(7.1)	1(0.5)	1(0.5)
巩固	155	64(41.3)	46(29.7)	36(23.2)	8(5.2)	1(0.6)	0(0)
再诱导	126	41(32.5)	46(36.5)	35(27.8)	4(3.2)	0(0)	0(0)
维持	82	57(69.5)	15(18.3)	8(9.8)	1(1.2)	0(0)	1(1.2)

Tab. 3 Comparison of cases of infectious SAE in different chemotherapy stages [cases (%)]

化疗阶段	例次	呼吸系统	消化系统	泌尿系统	败血症	发热性中性粒细胞减少	其他部位
诱导缓解	68	23(33.8)	7(10.3)	2(2.9)	4(5.9)	26(38.3)	6(8.8)
巩固	62	24(38.7)	4(6.5)	7(11.2)	4(6.5)	19(30.6)	4(6.5)
再诱导	76	20(26.3)	6(7.9)	6(7.9)	7(9.2)	30(39.5)	7(9.2)
维持	74	51(68.9)	2(2.7)	5(6.7)	3(4.1)	11(14.9)	2(2.7)

Tab. 4 Comparison of SAE cases between groups [cases (%)]

组别	例数	导缓解阶段	巩固阶段	再诱导阶段	维持阶段
死亡组	6	97(38.8)^*	81(32.4)^#	46(18.4)	26(10.4)
存活组	15	190(28.0)^*	156(23.0)^#	185(27.3)	147(21.7)
χ²值		0.008	12.037	1.611	19.410
$P$ 值		0.927	0.000	0.204	0.000

Tab. 4 Comparison of SAE cases between groups [cases (%)]

组别	例数	导缓解阶段	巩固阶段	再诱导阶段	维持阶段
死亡组	6	97(38.8)^*	81(32.4)^#	46(18.4)	26(10.4)
存活组	15	190(28.0)^*	156(23.0)^#	185(27.3)	147(21.7)
χ²值		0.008	12.037	1.611	19.410
$P$ 值		0.927	0.000	0.204	0.000

Tab. 5 Comparison of the occurrence of hematology-related SAE between groups [cases (%)]

组别	例数	诱导缓解	巩固	再诱导	维持
死亡组	5	65(44.8)^*	51(35.2)^#	14(9.7)	15(10.3)
存活组	15	132(31.8)^*	104(25.1)^#	112(27.0)	67(16.1)
χ²值		0.000	18.563	2.135	6.119
$P$ 值		0.986	0.000	0.144	0.013

Tab. 5 Comparison of the occurrence of hematology-related SAE between groups [cases (%)]

组别	例数	诱导缓解	巩固	再诱导	维持
死亡组	5	65(44.8)^*	51(35.2)^#	14(9.7)	15(10.3)
存活组	15	132(31.8)^*	104(25.1)^#	112(27.0)	67(16.1)
χ²值		0.000	18.563	2.135	6.119
$P$ 值		0.986	0.000	0.144	0.013

Tab. 6 Single factor analysis of SAE-related deaths [cases (%)]

变量	存活组( $n$ =15)	死亡组( $n$ =5)	$P$ 值	$O R$ 值	95% $C I$
变量	存活组( $n$ =15)	死亡组( $n$ =5)	$P$ 值	$O R$ 值	下限	上限
年龄
>10岁 1~10岁	14(93.3) 1(6.7)	4(80.0) 1(20.0)	0.999	0.000	0.000	0.000
性别
男女	12(80.0) 3(20.0)	2(40.0) 3(60.0)	0.109	6.000	0.671	53.681
危险分层
标危中/高危	5(33.3) 10(66.7)	0(0) 5(100.0)	0.206	2.000	0.000	0.000
基因检查是否阳性
是否	8(53.3) 7(46.7)	2(40.0) 3(60.0)	0.608	1.714	0.219	13.406
染色体检查是否阳性
是否	0(0) 15(100.0)	2(40.0) 3(60.0)	0.011	5.000	0.000	0.000
初诊时白细胞计数
≤50×10⁹/L >50×10⁹/L	10(66.7) 5(33.3)	5(100.0) 0(0)	0.206	2.000	0.000	0.000
初诊时是否有肝脾肿大
是否	10(66.7) 5(33.3)	4(80.0) 1(20.0)	0.518	0.500	0.044	5.737
初诊时是否有多处(≥3)淋巴结肿大
是否	5(33.3) 10(66.7)	1(20.0) 4(80.0)	1.0	1.000	0.080	12.557
d15MRD
≥0.1% <0.1%	10(66.7) 5(33.3)	4(80.0) 1(20.0)	0.578	5.000	0.440	5.737
化疗过程是否出现败血症
是否	9(60.0) 6(40.0)	5(100.0) 0(10.0)	0.999	0.000	0.000	0.000

Tab. 6 Single factor analysis of SAE-related deaths [cases (%)]

变量	存活组( $n$ =15)	死亡组( $n$ =5)	$P$ 值	$O R$ 值	95% $C I$
变量	存活组( $n$ =15)	死亡组( $n$ =5)	$P$ 值	$O R$ 值	下限	上限
年龄
>10岁 1~10岁	14(93.3) 1(6.7)	4(80.0) 1(20.0)	0.999	0.000	0.000	0.000
性别
男女	12(80.0) 3(20.0)	2(40.0) 3(60.0)	0.109	6.000	0.671	53.681
危险分层
标危中/高危	5(33.3) 10(66.7)	0(0) 5(100.0)	0.206	2.000	0.000	0.000
基因检查是否阳性
是否	8(53.3) 7(46.7)	2(40.0) 3(60.0)	0.608	1.714	0.219	13.406
染色体检查是否阳性
是否	0(0) 15(100.0)	2(40.0) 3(60.0)	0.011	5.000	0.000	0.000
初诊时白细胞计数
≤50×10⁹/L >50×10⁹/L	10(66.7) 5(33.3)	5(100.0) 0(0)	0.206	2.000	0.000	0.000
初诊时是否有肝脾肿大
是否	10(66.7) 5(33.3)	4(80.0) 1(20.0)	0.518	0.500	0.044	5.737
初诊时是否有多处(≥3)淋巴结肿大
是否	5(33.3) 10(66.7)	1(20.0) 4(80.0)	1.0	1.000	0.080	12.557
d15MRD
≥0.1% <0.1%	10(66.7) 5(33.3)	4(80.0) 1(20.0)	0.578	5.000	0.440	5.737
化疗过程是否出现败血症
是否	9(60.0) 6(40.0)	5(100.0) 0(10.0)	0.999	0.000	0.000	0.000

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