血液肿瘤患者回输嵌合抗原受体T细胞后28天内感染病原学和临床特征分析

Infectious complications following chimeric antigen receptor T-cell therapy for a hematologic malignancy within 28 days

目的探讨血液肿瘤患者在回输嵌合抗原受体T细胞(CAR-T细胞)后28 d内感染的发生率、临床和微生物学特征及危险因素。方法回顾性分析2016年1月至2020年12月在华中科技大学同济医学院附属协和医院血液科成功接受CAR-T细胞输注的170例血液肿瘤患者基线资料以及回输后28 d内发生感染的临床与病原菌特征。使用泊松回归评估基线特征与感染密度的相关性,单因素和多因素Cox比例风险回归模型评估CAR-T细胞回输后感染的高危因素。结果170例患者中急性淋巴细胞白血病(ALL)72例、非霍奇金淋巴瘤(NHL)56例、多发性骨髓瘤(MM)42例,99例患者在28 d内共发生119次感染,累积感染发生率为(58.2±3.8)%;其中细菌感染98次(45.9%),总感染密度为2.01,首次感染发生的中位时间为回输后12(1~18)d。多因素泊松回归显示ALL患者、难治性疾病、既往30 d内感染病史、回输前ANC<0.5×10^(9)/L、前期治疗方案≥4种的患者在28 d内与感染密度有更高的相关性;多因素Cox回归显示≥3级细胞因子释放综合征(CRS)是发生感染的独立危险因素(HR=3.74,95%CI 1.29~5.72,P<0.001)。结论感染是血液病患者CAR-T治疗后常见的并发症之一,不同肿瘤的感染发生率与类型有所差异,但均以细菌感染为主。ALL患者、难治性疾病、既往30天内感染病史、回输前ANC<0.5×10^(9)/L、前期治疗方案≥4种与感染密度相关;3级以上CRS是感染发生的独立危险因素。

Objective To explore the incidence,clinical and microbiological characteristics and risk factors of infection in patients with acute lymphoblastic(ALL),non-Hodgkin lymphoma(NHL),and multiple myeloma(MM)within 28 days after CAR-T cell infusion.It provides data support for early identification of infection and the rational use of antibacterial drugs in these patients.Methods We retrospectively analyzed the baseline data of 170 patients with ALL,NHL and MM who received chimeric antigen receptor-modified T(CAR-T)-cell treatment in the Department of Hematology of Wuhan Union Hospital from January 2016 to December 2020,and the clinical characteristics of infection within 28 days after infusion,including 72 patients with ALL,56 patients with NHL,and 42 patients with MM;we used Poisson regression and Cox proportional hazard regression models to assess high-risk factors for infection before and after infusion,respectively.Results Among 170 patients,119 infections occurred in 99 patients within 28 days,with a cumulative infection rate of 58.2%.Seventy-eight patients had 98 bacterial infections and the cumulative incidence of bacterial infection was 45.9%.The infection density was 2.01,and the median time for the first infection was about 12 days after infusion.The adjusted baseline characteristic model showed that ALL patients,previous 30 days of infection history,refractory disease,absolute neutrophil count(ANC)<0.5×10^(9)/L before infusion and≥4 prior antitumor treatment regimens had a higher infection density within 28 days;grade 3 or 4 CRS was the only high-risk factor related to infection after infusion in the multivariate analysis.Conclusion Infection is a common complication of CAR-T cell therapy in patients with hematologic malignancy.Bacterial infections occur in most patients regardless of the type of disease.ALL patients,previous 30 days of infection history,refractory disease,ANC<0.5×10^(9)/L before infusion and grade 3 or 4 CRS are risk factors for infection.