决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Hepatitis E Virus Infection in Cancer Patients.
共有 405 例患者接受了 HEV 检测,其中 63 例(16%)可检出 HEV IgG。
免疫功能正常者感染戊型肝炎病毒(HEV)可导致慢性肝炎和肝衰竭,但癌症患者中HEV感染的疾病负担仍鲜为人知。本研究考察了美国一家三级肿瘤中心患者HEV感染的特点。这项回顾性研究纳入2011年9月至2021年9月确诊HEV感染的成年癌症患者。共检测405例患者,其中63例(16%)可检出HEV IgG。患者中33例(52%)为男性,43例(68%)出生于美国;46例(73%)因既往肝脏疾病接受HEV筛查,22例(35%)患血液系统恶性肿瘤。仅2例患者检出HEV RNA。第一例患者患骨髓增生异常综合征,并接受异基因造血干细胞移植(HSCT);移植后13个月出现肝酶升高,HEV RNA为14,000 IU/mL(4.2 log IU/mL)。减少免疫抑制后,其HEV病毒血症消退。第二例患者患弥漫性大B细胞淋巴瘤,并接受抗CD19嵌合抗原受体(CAR)T细胞治疗;CAR-T治疗后12个月出现肝酶升高,HEV RNA达4,560,000 IU/mL(6.7 log IU/mL)。该患者发展为慢性HEV感染,利巴韦林治疗无效,目前正考虑使用聚乙二醇干扰素α-2a联合利巴韦林进行挽救治疗。本研究首次报告了CAR-T治疗后患者发生慢性HEV感染。癌症患者感染HEV似乎至少与普通人群同样常见;血液系统恶性肿瘤患者可能有HEV病毒血症和抗病毒治疗难治性慢性感染的风险。
Hepatitis E virus (HEV) infection in immunocompetent patients can lead to chronic hepatitis and liver failure. However, the burden of HEV infection in cancer patients is largely unknown. We studied the characteristics of HEV infection in patients at a tertiary care cancer center in the United States. This retrospective study included adult cancer patients with HEV infection diagnosed between September 2011 to September 2021. A total of 405 patients were tested for HEV, and 63 (16%) had detectable HEV IgG. Thirty-three patients (52%) were male, 43 were born in America (68%), 46 (73%) were screened for HEV because of pre-existing liver conditions, and 22 (35%) had hematological malignancies. Only 2 patients had detectable HEV RNA. The first patient had myelodysplastic syndrome and underwent allogeneic stem cell transplantation (HSCT). He developed elevated liver enzymes with HEV RNA 14,000 IU/mL (4.2 log IU/mL) 13 months after HSCT. After reducing immunosuppression, his HEV viremia resolved. The second patient had diffuse large B-cell lymphoma and underwent anti-CD19 chimeric antigen receptor (CAR) T-cell therapy. She had elevated liver enzymes with HEV RNA 4,560,000 IU/mL (6.7 log IU/mL) 12 months after CAR T-cell therapy. She developed chronic HEV infection, and ribavirin treatment failed. Now she is being considered for salvage treatment with peginterferon alfa-2a and ribavirin. This study is the first report of chronic HEV infection in patients who received CAR T-cell therapy. HEV infection in cancer patients appears to be at least as common as in the general population. Cancer patients with hematologic malignancies may be at risk for HEV viremia and chronic infection refractory to antiviral treatment.
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