CAR-T细胞治疗儿童复发/难治性B-ALL感染并发症及免疫重建特征分析

Analysis of Infectious Complications and Immune Reconstitution Characteristics in Pediatric Relapsed/Refractory B-ALL Treated with CAR-T Cell Therapy

摘要: 目的：探讨接受嵌合抗原受体T细胞(CAR-T)治疗的儿童复发/难治性B细胞急性淋巴细胞白血病(r/r B-ALL)患者感染并发症的发生率、病原体分布、危险因素及免疫重建特征。方法：回顾性分析22例接受CAR-T治疗儿童的临床资料，根据回输后30天内是否发生感染分为早期感染组(n = 9)和非感染组(n = 13)。收集患者基线特征、CAR-T治疗参数、实验室指标及临床结局。采用Mann-Whitney U检验、Fisher精确检验及单因素Logistic回归分析早期感染的危险因素。动态监测CD4⁺、CD8⁺T细胞计数及免疫球蛋白水平。结果：早期感染发生率为40.9% (9/22)，晚期感染发生率为27.3% (6/22)。早期感染以呼吸道感染(67%)和细菌感染(75%)为主，晚期感染则以病毒感染(45%)占比升高为特征。单因素分析显示，CRS分级 ≥ 2 (OR = 40.11, 95%CI: 1.89~852.96, P = 0.002)、ICANS分级 ≥ 2 (OR = 22.09, 95%CI: 1.01~483.28, P = 0.017)、托珠单抗使用(OR = 29.36, 95%CI: 1.41~613.49, P = 0.006)及糖皮质激素使用(OR = 50.14, 95%CI: 2.24~1121.42, P = 0.001)与早期感染显著相关。感染组CAR-T前淋巴细胞计数显著低于非感染组[0.05 (0.03~0.09) vs 0.14 (0.07~0.18) × 10⁹/L, P = 0.016]，但因完全分离无法估计OR值。CAR-T输注后CD4⁺T细胞及免疫球蛋白水平持续低下，提示长期免疫缺陷，与晚期病毒感染风险升高相吻合。结论：CAR-T治疗后早期感染风险较高，CRS/ICANS分级 ≥ 2、托珠单抗及糖皮质激素的使用、基线淋巴细胞减少与早期感染风险显著相关，可能是潜在的预测指标；晚期感染以病毒感染为主，可能与持续的免疫重建延迟有关。CAR-T输注后观察到持续的CD4⁺T细胞减少和体液免疫缺陷，提示需加强感染监测和预防策略。

Abstract: Objective: To investigate the incidence, pathogen distribution, risk factors, and immune reconstitution features of infectious complications in pediatric patients with relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL) receiving chimeric antigen receptor T-cell (CAR-T) therapy. Methods: Clinical data of 22 children treated with CAR-T were retrospectively analyzed. Patients were divided into early infection group (n = 9) and non-infection group (n = 13) based on whether infection occurred within 30 days after infusion. Baseline characteristics, CAR-T treatment parameters, laboratory indicators, and clinical outcomes were collected. Mann-Whitney U test, Fisher’s exact test, and univariate logistic regression were used to analyze risk factors for early infection. Dynamic monitoring of CD4⁺ and CD8⁺ T-cell counts and immunoglobulin levels was performed. Results: The incidence of early infection was 40.9% (9/22), and that of late infection was 27.3% (6/22). Early infections were predominantly respiratory tract infections (67%) and bacterial infections (75%), while late infections were characterized by an increased proportion of viral infections (45%). Univariate analysis showed that CRS grade ≥ 2 (OR = 40.11, 95%CI: 1.89~852.96, P = 0.002), ICANS grade ≥ 2 (OR = 22.09, 95%CI: 1.01~483.28, P = 0.017), use of tocilizumab (OR = 29.36, 95%CI: 1.41~613.49, P = 0.006), and use of corticosteroids (OR = 50.14, 95%CI: 2.24~1121.42, P = 0.001) were significantly associated with early infection. The pre-CAR-T lymphocyte count in the infection group was significantly lower than that in the non-infection group [0.05 (0.03~0.09) vs 0.14 (0.07~0.18) × 10⁹/L, P = 0.016], but the odds ratio could not be estimated due to complete separation. Persistent low levels of CD4⁺ T cells and immunoglobulins after CAR-T infusion suggested long-term immune deficiency, consistent with the increased risk of late viral infections. Conclusion: The risk of early infection after CAR-T therapy appears to be elevated. CRS grade ≥ 2, ICANS grade ≥ 2, use of tocilizumab and corticosteroids, and baseline lymphopenia were significantly associated with early infection risk and may serve as potential predictive indicators. Late infections were predominantly viral and may be associated with delayed immune reconstitution. Persistent CD4⁺ T-cell lymphopenia and humoral immune deficiency following CAR-T infusion suggest the need for enhanced infection surveillance and preventive strategies.