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

doi:10.12372/jcp.2025.24e0023

Abstract

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

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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References 43

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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	－

Clinical analysis of invasive fungal disease secondary to allogeneic hematopoietic stem cell transplantation in 424 children with thalassemia

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