血液肿瘤患者嵌合抗原受体T细胞免疫治疗后侵袭性真菌感染的研究新进展

Research advances of invasive fungal infections in patients with hematologic neoplasms after chimeric antigen receptor T cell immunotherapy

嵌合抗原受体T细胞(CAR-T)免疫治疗复发/难治性血液肿瘤患者显著疗效。然而,由于患者合并基础疾病、免疫抑制、白细胞减少、细胞因子释放综合征(CRS),以及长期使用免疫抑制药物,其CAR-T免疫治疗后发生侵袭性真菌感染(IFI)风险增加。CAR-T免疫治疗后IFI发生率虽不高,但病死率高,严重影响患者预后。通过影像学检查、生物学标志物检测、PCR检测及时诊断CAR-T后IFI,并着重与CRS鉴别,有助于降低该病漏诊、误诊风险。对于IFI高风险人群进行抗真菌预防治疗,对于确诊IFI患者采取及时抗真菌和支持对症治疗及手术治疗,可使CAR-T免疫治疗后IFI的发生率与病死率降低,改善患者预后。笔者拟就血液肿瘤患者CAR-T免疫治疗后IFI流行病学、风险因素、诊断及治疗的研究新进展进行阐述,以期加深临床医师对该病的认识。

Chimeric antigen receptor T cell(CAR-T)immunotherapy has demonstrated significant efficacy in treatment of patients with relapsed or refractory hematologic neoplasms.However,patients after CAR-T immunotherapy are at increased risk of invasive fungal infections(IFI)due to underlying conditions,immunosuppression,leukopenia,cytokine release syndrome(CRS),and prolonged use of immunosuppressive agents.Although incidence of IFI post-CAR-T immunotherapy is relatively uncommon,it is associated with a high fatality rate and significantly impacts patient prognosis.Timely diagnosis of post-CAR-T immunotherapy IFI through imaging,biomarkers,PCR,and differentiation from CRS are essential to reduce missed and incorrect diagnoses.Implementing antifungal prophylaxis for high IFI-risk individuals and providing timely antifungal treatment,supportive symptomatic care,and surgical intervention for patients diagnosed with IFI can reduce both the incidence and fatality rate of post-CAR-T immunotherapy IFI,ultimately improving patients′prognosis.This article intends to elaborate on the latest research progress in epidemiology,risk factors,diagnosis and treatment of IFI in patients with hematologic neoplasms after CAR-T immunotherapy,to deepen clinical physicians′understanding of this disease.