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:Omicron related COVID-19 prevention and treatment measures for patients with hematological malignancy and strategies for modifying hematologic treatment regimes.
SARS-CoV-2 的 Omicron 变异株因其高传播性已迅速成为全球优势流行株,尽管其致病性似乎低于此前的毒株。
SARS-CoV-2奥密克戎变异株因传播力强而迅速成为全球优势株,尽管其致病性似乎低于此前变异株。然而,血液系统恶性肿瘤患者感染COVID-19后仍易发生重症和死亡,慢性淋巴细胞白血病(CLL)患者及接受CAR-T 细胞治疗者尤为如此。血液科医师在启动化疗或免疫抑制治疗前,应全面评估患者血液病严重程度及SARS-CoV-2感染的潜在风险。强烈建议接种疫苗并接受加强针;疫苗应答不佳者可能受益于长效COVID-19中和单克隆抗体(如Evusheld)。建议血液恶性肿瘤患者及严重免疫缺陷者发生轻症COVID-19时尽早使用小分子抗病毒药物;严重免疫缺陷者还可考虑SARS-CoV-2中和单克隆抗体治疗及高滴度COVID-19康复者血浆(CCP)。中重症患者可采用低剂量糖皮质激素联合早期抗病毒治疗;若病情持续或恶化,可加用细胞因子受体拮抗剂或JAK抑制剂。血液恶性肿瘤治疗方面,CLL、急性白血病(AL)和低危骨髓增生异常综合征(MDS)宜优先考虑推迟化疗;若疾病进展,则需适当调整治疗剂量和频率,并避免使用抗CD20单克隆抗体、CAR-T及造血干细胞移植(HSCT)。慢性髓性白血病(CML)和骨髓增殖性肿瘤(MPN)患者可继续现行治疗。此外,非药物防护措施、新型疫苗和抗病毒药物的研发,以及免疫功能低下人群中的变异株监测,均尤为重要。
The Omicron variant of SARS-CoV-2 has rapidly become the dominant strain worldwide due to its high transmissibility, although it appears to be less pathogenic than previous strains. However, individuals with hematological malignancy (HM) and COVID-19 remain susceptible to severe infection and mortality, especially those with chronic lymphocytic leukemia (CLL) and those undergoing chimeric antigen receptor T-cell (CAR-T) treatment. Hematologists should thoroughly assess the severity of the patient's hematological disease and the potential risk of SARS-CoV-2 infection before initiating chemotherapy or immunosuppressive treatment. Vaccination and booster doses are strongly recommended and patients with a poor vaccine response may benefit from long-acting COVID-19 neutralizing monoclonal antibodies (such as Evusheld). Early use of small molecule antiviral drugs is recommended for managing mild COVID-19 in HM patients and those with severe immunodeficiency may benefit from SARS-CoV-2 neutralizing monoclonal antibody therapy and high-titer COVID-19 convalescent plasma (CCP). For moderate to severe cases, low-dose glucocorticoids in combination with early antiviral treatment can be administered, with cytokine receptor antagonists or JAK inhibitors added if the condition persists or worsens. In the treatment of hematological malignancies, delaying chemotherapy is preferable for CLL, acute leukemia (AL), and low-risk myelodysplastic syndrome (MDS), but if the disease progresses, appropriate adjustments in dosage and frequency of treatment are required, with the avoidance of anti-CD20 monoclonal antibody, CAR-T and hematopoietic stem cell transplantation (HSCT). Patients with chronic myelocytic leukemia (CML) and myeloproliferative neoplasms (MPNs) can continue current treatment. What's more, non-drug protective measures, the development of new vaccines and antiviral drugs, and monitoring of mutations in immunocompromised populations are particularly important.
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