儿童异基因造血干细胞移植100天后闭塞性细支气管炎综合征临床特点及危险因素分析

doi:10.12372/jcp.2024.22e1533

摘要/Abstract

摘要：

目的分析儿童异基因造血干细胞移植（allo-HSCT）后闭塞性细支气管炎综合征（BOS）的临床特点及危险因素，以进一步优化治疗方案。方法回顾性分析2010年10月至2018年12月在苏州大学附属儿童医院接受allo-HSCT患儿的临床资料。结果共纳入351例患儿，男213例、女138例。截止至2019年9月1日，共29例（8.3%）患儿发生BOS，男11例、女18例，中位年龄92.0（67.0~132.0）月。移植至发生BOS的中位时间为10.0（8.5~20.0）月。移植后1、2、3年BOS累积发生率分别为（6.0±1.3）%、（10.0±1.8）%、（10.7±2.0）%。29例BOS患儿中，28例BOS发病前合并其他靶器官慢性移植物抗宿主病（cGVHD）。多因素logistic回归分析结果显示年龄较大、女性、移植后100天内有呼吸系统疾病以及合并其他靶器官cGVHD是BOS发生的独立危险因素（P<0.05）。结论 BOS是HSCT后的严重并发症。女性、年龄较大、合并其他靶器官cGVHD、移植后100天内有呼吸系统疾病的患儿发生BOS的风险更大。

关键词: 造血干细胞移植, 闭塞性细支气管炎综合征, 移植物抗宿主病, 儿童

Abstract:

Objective To analyse the clinical characteristics and risk factors of occlusive bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children in order to further optimize the treatment protocol.Methods Clinical data of children who received allo-HSCT from October 2010 to December 2018 at Children's Hospital of Soochow University were retrospectively analysed. Results A total of 351 children were included, 213 males and 138 females. Until September 1, 2019, a total of 29 (8.3%) children developed BOS, 11 males and 18 females, with a median age of 92.0 (67.0-132.0) months. The median time from transplantation to the development of BOS was 10.0 (8.5-20.0) months. The cumulative incidence of BOS at 1, 2, and 3 years after transplantation was (6.0±1.3)%, (10.0±1.8)%, and (10.7±2.0)%, respectively. 28 of the 29 children with BOS had comorbidities with chronic graft-versus-host disease (cGVHD) in other target organs prior to the onset of BOS. The results of multifactorial logistic regression analysis showed that older age, female gender, respiratory disease within 100 days after transplantation, and comorbidities with other target organ cGVHD were independent risk factors for the development of BOS (P<0.05). Conclusion BOS is a serious complication after HSCT. Children who were female, older, had a combination of other target organ cGVHD, and had respiratory disease within 100 days of transplantation were at greater risk of developing BOS.

Key words: hematopoietic stem cell transplantation, bronchiolitis obliterans syndrome, graft-versus-host disease, child

孙若楠, 李泊涵, 郑德菲, 赵夏莹, 林子云, 胡昳歆, 高莉, 高静, 李捷, 卢俊, 肖佩芳, 潘健, 凌婧, 方芳, 胡绍燕. 儿童异基因造血干细胞移植100天后闭塞性细支气管炎综合征临床特点及危险因素分析[J]. 临床儿科杂志, 2024, 42(2): 139-145.

SUN Ruonan, LI Bohan, ZHENG Defei, ZHAO Xiaying, LIN Ziyun, HU Yixin, GAO Li, GAO Jing, LI Jie, LU Jun, XIAO Peifang, PAN Jian, LING Jing, FANG Fang, HU Shaoyan. Factors related to bronchiolitis obliterans syndrome in pediatric patients survived longer than 100 days after hematopoietic stem cell transplantation[J]. Journal of Clinical Pediatrics, 2024, 42(2): 139-145.

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项目	Non-BOS组(n=322)	BOS组(n=29)	统计量	P
年龄[M(P₂₅~P₇₅)]/月	75.0(38.0~119.0)	92.0(67.0~132.0)	Z=2.18	0.029
男性[n(%)]	202(62.7)	11(37.9)	χ²=8.88	0.009
ABO血型相合[n(%)]	159(49.4)	14(48.3)	χ²=0.01	0.909
疾病为恶性疾病[n(%)]	208(64.6)	22(75.9)	χ²=1.73	0.221
供体类型[n(%)]			χ²=2.05	0.613
脐带血移植	97(30.1)	8(27.6)
单倍体移植	145(45)	11(37.9)
同胞全相合移植	42(13)	4(13.8)
无关供体移植	38(11.8)	6(20.7)
干细胞来源[n(%)]			χ²=4.80	0.230
脐带血	97(30.1)	8(27.6)
骨髓	15(4.7)	0
外周血	62(19.3)	10(34.5)
外周血+骨髓	148(46.0)	11(37.9)
预处理方案[n(%)]			χ²=0.40	0.530
清髓预处理	147(45.7)	15(51.7)
减低剂量预处理	175(54.3)	14(48.3)
预处理方案中有全身照射[n(%)]	29(9.0)	1(3.4)	-	0.492¹⁾
预处理方案中有白消安[n(%)]	264(82.0)	27(93.1)	-	0.195¹⁾
预处理方案中有ATG[n(%)]	161(50.0)	14(48.3)	χ²=0.03	0.859
发生BOS前有CMV血症[n(%)]	212(65.8)	22(75.9)	χ²=1.20	0.273
发生BOS前有细小病毒血症[n(%)]	87(27.0)	12(41.4)	χ²=2.71	0.100
移植后100天内有呼吸系统疾病[n(%)]	84(26.1)	16(55.2)	χ²=17.87	0.001
aGVHD[n(%)]			χ²=0.00	0.947
0 ~Ⅰ度	235(73.0)	21(72.4)
Ⅱ~Ⅳ度	87(27.0)	8(27.6)
合并其他靶器官cGVHD[n(%)]	115(35.7)	28(96.6)	χ²=36.37	<0.001
总单个核细胞数[M(P₂₅~P₇₅)]/×10⁸·kg^-1	7.9(2.0~12.1)	4.1(3.2~12.3)	Z=0.29	0.880
总CD34⁺细胞数[M(P₂₅~P₇₅)]/×10⁶·kg^-1	7.4(3.2~7.0)	4.1(2.4~9.0)	Z=0.77	0.397

项目	偏回归系数	标准误	χ²值	OR(95%CI)	P
年龄	0.89	0.45	3.87	1.01(1.01~1.02)	0.039
女性	0.01	0.01	4.41	3.21(1.40~7.37)	0.006
移植后100天内有呼吸系统疾病	1.58	0.45	12.25	5.04(2.24~11.35)	<0.001
合并其他靶器官cGVHD	3.09	0.75	16.86	22.80(5.31~98.20)	<0.001
常量	-7.34	1.13	42.12	0.001	<0.001