Abstract：
Anti-CD19 chimeric antigen receptor T-cell therapy (CART) has revolutionized the outcomes of relapsed and/or refractory B-cell non-Hodgkin lymphoma. However, CART is still limited by its availability, toxicity, and response durability. Not all patients make it to the CART infusion phase due to disease progression. Among those who receive CART, a significant number of patients experience life-threatening cytokine release syndrome toxicity, and less than half maintain a durable response with the majority relapsing in pre-existing sites of disease present pre-CART. Radiation therapy stands as a promising peri-CART and salvage treatment that can improve the outcomes of these patients. Evidence suggests that bridging radiotherapy prior to CART controls the disease during the manufacturing period, augments response rates and local control, cytoreduces/debulks the disease and decreases the severity of cytokine release syndrome, and may prolong disease-free intervals and survival especially in patients with bulky disease. Consolidative radiotherapy for residual post-CART disease alters the pattern of relapse and improves local recurrence-free and progression-free survivals. Salvage radiotherapy for relapsed post-CART disease has favorable survival outcomes when delivered comprehensively for patients with limited relapsed disease and palliates symptoms for patients with diffuse relapsed disease. The biology of the disease during the peri-CART period is poorly understood, and further studies investigating the optimal timing and dosing of radiation therapy (RT) are needed. In this review, we tackle the most significant challenges of CART, review and propose how RT can help mitigate these challenges, and provide The Mayo Clinic experts\' approach on incorporating RT with CART.
摘要：
抗CD19嵌合抗原受体T细胞疗法（CART）彻底改变了复发性和/或难治性B细胞非霍奇金淋巴瘤的结果。然而,CART仍然受到其可用性的限制，毒性,和响应耐久性。由于疾病进展，并非所有患者都进入CART输注阶段。在那些接受CART的人中，大量患者经历危及生命的细胞因子释放综合征毒性，不到一半的人保持持久的反应，大多数人在CART之前存在的疾病部位复发。放射治疗是一种有前途的CART和挽救性治疗，可以改善这些患者的预后。证据表明，CART之前的桥接放射治疗在制造期间控制了疾病，提高反应率和本地控制，细胞减少/消除疾病并降低细胞因子释放综合征的严重程度，并可能延长无病间隔和生存期，尤其是在患有大病患者中。CART后残留疾病的综合放疗改变了复发模式，并改善了无局部复发和无进展生存率。CART后复发疾病的挽救性放射治疗对有限复发疾病的患者进行全面治疗时具有良好的生存结果，对弥漫性复发性疾病的患者缓解症状。在CART期间，对该疾病的生物学了解甚少，需要进一步研究放射治疗（RT）的最佳时机和剂量。在这次审查中,我们应对CART最重大的挑战，回顾并提出RT如何帮助缓解这些挑战，并提供梅奥诊所专家关于将RT与CART相结合的方法。
