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:Herpes Zoster in Hematological Disorders: Pathogenesis, Risk Stratification, and Emerging Strategies for Prevention and Immunization.
血液系统疾病患者尤其易患 HZ。
背景:带状疱疹(HZ)由潜伏的水痘-带状疱疹病毒(VZV)再激活引起,对免疫功能低下患者造成显著负担,尤其是血液系统恶性肿瘤患者和造血干细胞移植(HSCT)受者。这些人群发生播散性疾病和带状疱疹后神经痛等严重并发症的风险明显升高。目的:本综述考察血液系统疾病患者HZ的发病机制、流行病学、风险因素及不断发展的预防策略,重点关注抗病毒预防和疫苗接种。方法:批判性回顾近期临床试验、观察性研究和国际指南数据,以评估免疫功能低下人群的HZ负担及预防干预效果。结果:无论由基础疾病还是移植后免疫重建导致的免疫抑制,都会损害VZV特异性细胞免疫,从而增加HZ易感性。HSCT受者以及接受蛋白酶体抑制剂、JAK2抑制剂或CAR-T治疗患者等高危人群,发病率可超过每1,000人年30–60例。抗病毒预防仍是基本预防措施。佐剂重组带状疱疹疫苗(aRZV)即使在重度免疫抑制患者中也显示出68%–87%的有效率。包括mRNA疫苗在内的新型疫苗平台,有望进一步提高免疫原性和可规模化生产能力。结论:血液系统疾病患者尤其易患HZ。有效预防需要结合个体情况采用抗病毒预防和aRZV免疫接种。开发mRNA疫苗可能进一步强化这一高危人群的预防策略。
BACKGROUND: Herpes zoster (HZ), resulting from reactivation of latent varicella-zoster virus (VZV), imposes a significant burden on immunocompromised patients, particularly those with hematological malignancies and recipients of hematopoietic stem cell transplants (HSCT). These populations face markedly increased risks of severe complications, including disseminated disease and postherpetic neuralgia. OBJECTIVE: This review examines the pathogenesis, epidemiology, risk factors, and evolving preventive strategies for HZ in patients with hematological disorders, with an emphasis on antiviral prophylaxis and vaccination. METHODS: Relevant data from recent clinical trials, observational studies, and international guidelines were critically reviewed to evaluate the burden of HZ and the effectiveness of prophylactic interventions in immunocompromised populations. RESULTS: Immunosuppression-whether due to the underlying disease or post-transplant immune reconstitution-compromises VZV-specific cellular immunity, thereby increasing HZ susceptibility. Incidence rates in high-risk groups, such as HSCT recipients or patients treated with proteasome inhibitors, JAK2 inhibitors, or CAR-T therapies, may exceed 30-60 per 1000 person-years. Antiviral prophylaxis remains a fundamental preventive approach. The adjuvanted recombinant zoster vaccine (aRZV) demonstrates 68%-87% efficacy even in heavily immunosuppressed individuals. Emerging vaccine platforms, including mRNA-based formulations, offer promising improvements in immunogenicity and scalability. CONCLUSION: Patients with hematological conditions are particularly vulnerable to HZ. Effective prevention requires a tailored combination of antiviral prophylaxis and aRZV immunization. The development of mRNA-based vaccines may further enhance preventive strategies for this at-risk population.
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