Objective: This study aimed to analyze cytomegalovirus (CMV) reactivation and its influencing factors in patients with B-lymphocyte malignancy who received chimeric antigen receptor T (CAR-T) cell therapy. Methods: This study retrospectively reviewed patients with B-lymphocyte malignancy who received CAR-T cell therapy in the First Affiliated Hospital of Soochow University from January 2021 to December 2023. The data of patients who underwent CMV-DNA detection and/or pathogen metagenomic sequencing twice or more within 100 days after CAR-T cell therapy were analyzed. The clinical characteristics of the CMV reactivation and non-activation groups were compared. The factors related to CMV reactivation were analyzed with the Chi-square test and nonparametric rank sum test, and the risk factors were examined with Logistic regression. Results: This study included 86 patients, among whom 18 (20.9%) had CMV reactivation, and the median time of reactivation was 20 (1-95) days. All of the 18 patients had CMV viremia, and no CMV disease was observed. Seven patients turned to the latent state after continuing acyclovir antiviral therapy, and 11 patients returned to the latent state after upgrading the antiviral therapy to first-line drugs, including ganciclovir and foscarnet sodium. Six or more courses of anti-tumor treatment before CAR-T cell therapy, allogeneic hematopoietic stem cell transplantation within 2 years before CAR-T cell therapy, non-remission before treatment, and the use of high-dose glucocorticoids and/or tocilizumab were related to CMV reactivation, among which allogeneic hematopoietic stem cell transplantation within 2 years pre-treatment and the use of high-dose glucocorticoids and/or tocilizumab treatment were independent risk factors for CMV reactivation. Conclusion: Patients with B-lymphocyte malignancy who received CAR-T cell therapy have the risk of CMV reactivation, especially for those who received allogeneic hematopoietic stem cell transplantation within 2 years pre-treatment and those who received high-dose glucocorticoids and/or tocilizumab treatment.
目的: 分析接受嵌合抗原受体T(CAR-T)细胞治疗的B淋巴细胞肿瘤患者巨细胞病毒(CMV)再激活情况及其影响因素。 方法: 回顾性分析2021年1月至2023年12月于苏州大学附属第一医院接受CAR-T细胞治疗后100 d内进行2次及以上CMV DNA检测和(或)病原体宏基因组测序的B淋巴细胞肿瘤患者的临床资料,比较CMV再激活组和未激活组的临床特征,通过卡方检验和非参数秩和检验分析影响CMV再激活的因素,通过Logistic回归进行危险因素分析。 结果: 共纳入86例患者,其中18例(20.9%)发生了CMV再激活,再激活的中位时间为治疗后20(1~95)d,均为CMV血症,未观察到CMV病的发生。7例患者CMV自然转阴,11例患者抗病毒治疗升级为更昔洛韦、膦甲酸钠等一线药物后CMV转为潜伏状态。CAR-T细胞治疗前抗肿瘤治疗疗程数≥6、CAR-T细胞治疗前2年内行allo-HSCT、治疗前肿瘤未缓解、使用大剂量糖皮质激素和(或)托珠单抗与CMV再激活相关,其中治疗前2年内行allo-HSCT和使用大剂量糖皮质激素和(或)托珠单抗治疗是CMV再激活的独立危险因素。 结论: 接受CAR-T细胞治疗的B淋巴细胞肿瘤患者存在CMV再激活风险,特别是治疗前2年内行allo-HSCT和接受大剂量糖皮质激素和(或)托珠单抗治疗的患者。.
Keywords: Cytomegalovirus; Leukemia, B-cell; Lymphoma, B-cell; Receptors, chimeric antigen.