424例地中海贫血患儿异基因造血干细胞移植后继发侵袭性真菌病临床分析

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doi:10.12372/jcp.2025.24e0023

摘要：

目的探讨儿童输血依赖型地中海贫血（TDT）患者接受异基因造血干细胞移植（allo-HSCT）后继发侵袭性真菌病（IFD）的临床特征及危险因素。方法回顾性分析2021年1月至2022年12月共424例接受allo-HSCT的TDT患儿的临床资料，分析allo-HSCT后IFD发生的影响因素。结果共424例患儿纳入研究，其中男261例（61.6%）、女163例（38.4%），中位年龄8.0（5.0~11.0）岁；单倍体移植278例，亲缘全/良好相合移植116例，无关全/良好相合移植30例；所有移植患儿均进行抗真菌初级预防。IFD共发生30例（7.1%），男20例、女10例，临床诊断25例（83.3%）、确诊5例（16.7%），中位发生时间为移植后39.0（23.5~85.8）天；肺部为最常见的感染部位（24例，80.0%），咳嗽（15例，50.0%）和发热（10例，33.3%）为主要症状，肺部影像学以不典型表现为主（14例，46.7%）。主要真菌病原为曲霉菌（19例，63.3%）。17例（56.7%）检出合并感染，以合并病毒感染多见。中位随访时间为16.0（9.0~21.8）个月，OS率为（99.3±0.01）%。非IFD组与IFD组OS率分别为（99.7±0.003）%和（93.3±0.06）%，两组间差异有统计学意义（P<0.001）。二分类多因素logistic回归显示植入不良或植入失败、有急性移植物抗宿主病史、非泊沙康唑预防是IFD发生的危险因素（P<0.05）。结论接受allo-HSCT后经初级真菌预防的TDT儿童IFD发生率低。IFD与较高的死亡风险相关。植入不良或植入失败、有急性移植物抗宿主病史和未使用泊沙康唑预防的患儿发生IFD的风险更高。

关键词: 侵袭性真菌病, 地中海贫血, 异基因造血干细胞移植, 儿童

Abstract:

Objective This study aims to investigate the clinical characteristics and risk factors of invasive fungal disease (IFD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with transfusion-dependent thalassemia (TDT). Methods The clinical data of 424 children with TDT who received allo-HSCT from January 2021 to December 2022 were retrospectively analyzed, and the influencing factors of IFD after allo-HSCT were analyzed. Results A total of 424 TDT children undergoing allo-HSCT were included, 261 (61.6%) boys and 163(38.4%) girls, with a median age of 8.0 (5.0-11.0) years. Among them, there were 278 cases of haploidentical transplantation, 116 cases of matched or well matched related transplantation, and 30 cases of matched or well matched unrelated transplantation. All transplant patients received primary antifungal prophylaxis. A total of 30 patients (7.1%, 20 boys and 10 girls) had IFD, 25 patients (83.3%) were probable IFD and 5 (16.7%) were proven IFD. The median occurrence time of IFD was 39.0 (23.5-85.8) days after transplantation. The lung was the most common site of infection (24 cases, 80.0%). Cough (15 cases, 50.0%) and fever (10 cases, 33.3%) were the main symptoms. The pulmonary imaging findings were atypical (14 cases, 46.7%). The main fungal pathogen was Aspergillus (19 cases, 63.3%). Co-infection was detected in 17 cases (56.7%), and co-virus infection was most common. The median follow-up time was 16.0 (9.0-21.8) months, and the overall survival (OS) rate was (99.3±0.01) %. The OS rates of non-IFD group and IFD group were (99.7±0.003) % and (93.3±0.06)%, respectively, and the difference between the two groups was statistically significant (P<0.001). The results of binary logistic regression analysis indicated that poor graft function or graft failure, acute graft-versus-host disease (aGVHD) and antifungal prophylaxis of non-posaconazole were independent risk factors for development of IFD after allo-HSCT (P<0.05). Conclusions TDT children undergoing allo-HSCT and receiving primary fungal prophylaxis exhibited a low incidence of IFD, and IFD was associated with higher risk of death. Patients with a history of poor graft function/ graft failure, aGVHD or those receiving non-posaconazole prophylaxis faced a greater risk of developing IFD.

Key words: invasive fungal disease, thalassemia, allogeneic hematopoietic stem cell transplantation, child

罗明静, 余嘉明, 王晓东, 张小玲, 余阅, 张瑜, 文飞球, 刘四喜. 424例地中海贫血患儿异基因造血干细胞移植后继发侵袭性真菌病临床分析[J]. 临床儿科杂志, 2025, 43(1): 21-28.

LUO Mingjing, YU Jiaming, WANG Xiaodong, ZHANG Xiaoling, YU Yue, ZHANG Yu, WEN Feiqiu, LIU Sixi. Clinical analysis of invasive fungal disease secondary to allogeneic hematopoietic stem cell transplantation in 424 children with thalassemia[J]. Journal of Clinical Pediatrics, 2025, 43(1): 21-28.

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项目	非IFD组(n=394)	IFD组(n=30)	统计量	P
年龄[n(%)]			χ²=0.03	0.855
≤12岁	343(87.1)	27(90.0)
>12岁	51(12.9)	3(10.0)
男性[n(%)]	241(61.2)	20(66.7)	χ²=0.36	0.551
移植方案[n(%)]			χ²=3.23	0.199
亲缘全/良好相合	111(28.2)	5(16.7)
无关全/良好相合	26(6.6)	4(13.3)
亲缘单倍体	257(65.2)	21(70.0)
造血干细胞类型[n(%)]			－	0.378¹⁾
外周血	253(64.2)	23(76.7)
外周血+骨髓	126(32.0)	7(23.3)
外周血+脐血	15(3.8)	0(0)
GVHD预防方案[n(%)]			χ²=2.74	0.098
PT-CY+FK506+MMF	329(83.5)	29(96.7)
MTX+CSA+MMF	65(16.5)	1(3.3)
植入情况[M(P₂₅~P₇₅)]/d
中性粒细胞植活	17.0(15.0~20.0)	17.5(15.8~21.0)	Z=1.38	0.168
红细胞植活	15.0(12.0~18.0)	15.5(14.0~20.8)	Z=1.91	0.056
血小板植活	13.0(12.0~16.0)	13.0(12.0~19.5)	Z=1.09	0.277
急性GVHD[n(%)]	21(5.3)	5(16.7)	χ²=4.41	0.036
植入不良/失败[n(%)]	15(3.8)	4(13.3)	χ²=3.89	0.048
病毒感染[n(%)]
CMV	99(25.1)	14(46.7)	χ²=6.62	0.010
EBV	41(10.4)	3(10.0)	χ²=0.00	1.000
初级真菌预防[n(%)]			χ²=6.34	0.012
泊沙康唑	355(90.1)	22(73.3)
非泊沙康唑	39(9.9)	8(26.7)
随访时间[M(P₂₅~P₇₅)]/月	16.0(9.0~22.0)	17.0(9.8~21.3)	Z=0.20	0.842

变量	偏回归系数	标准误	χ²值	P	OR(95%CI)
植入不良/失败	1.29	0.61	4.44	0.035	3.64(1.09~12.11)
不含泊沙康唑	1.13	0.46	6.12	0.013	3.08(1.26~7.53)
急性GVHD	1.15	0.55	4.31	0.038	3.16(1.07~9.33)
常量	－2.98	0.24	149.14	<0.001	－