布尔基特淋巴瘤（BL）是儿童非霍奇金淋巴瘤（NHL）最常见的肿瘤，约占病例的40%。尽管采用不同的联合短程化疗方案取得了良好的效果，但难治性/复发性BL的预后不佳，治愈率不足30%。嵌合抗原受体T细胞（CAR-T）疗法近年来得到了迅速发展，并在急性淋巴细胞白血病（ALL）中取得了优异的疗效。然而，在某些情况下，由于T细胞功能障碍而无法产生自体CAR-T细胞。在这种情况下，不得不考虑异体CAR-T疗法。 一名17岁的男孩患有II期BL，对广泛化疗和连续自体CAR-T疗法没有反应。使用包含抗CD20-BB-ζ（20CAR）和抗CD22-BB-ζ（22CAR）转基因的慢病毒载体修饰了一个人类白细胞抗原匹配的无亲缘关系供体的T细胞。使用流式细胞仪评估了细胞因子分析和周围血液中CAR-T细胞的持续性，通过qPCR计数为每ug DNA的拷贝数。从患者及其法定监护人处获得了自体/异体CAR-T治疗的知情同意。在环磷酰胺和氟达拉滨的淋巴清除化疗后，注入了未编辑HLA匹配的抗CD20和抗CD22 CAR-T细胞。患者出现了Ⅳ级细胞因子释放综合征（CRS），在抗炎治疗包括托珠单抗后完全缓解（CR）。由于持续的全血细胞减少和完全供体嵌合，相同供体的无调节外周血干细胞成功移植于CAR-T后55天。中性粒细胞于+11天移植并再生，血小板于+47天重新生成，没有明显的急性移植物抗宿主病（GVHD），但皮肤和眼睛有轻度慢性GVHD。目前，仍在进行积极的抗排斥治疗。无调节HLA匹配的异体CAR-T细胞治疗可以成为一种创新的、有效且安全的治疗儿童难治性/复发性BL的方法，不会明显引起急性GVHD。在全供体T细胞嵌合移植后，从相同供体进行非调节造血干细胞移植（HSCT）是可行的。值得注意的是，需在HSCT后进行密切监测以预防GVHD的发生。 版权所有©2023年，杨，罗，钱，黄，张，王，罗，秦，李和陈。

Burkitt lymphoma (BL) is the most common tumor of non-Hodgkin's lymphoma (NHL) in children, accounting for about 40% of cases. Although different combined short-course chemotherapies have achieved a good effect, refractory/relapsed BL has a poor prognosis with cure rates less than 30%. Chimeric antigen receptor T cell (CAR-T) therapy has developed rapidly in recent years and achieved excellent results in acute lymphoblastic leukemia (ALL). However, in some cases, there is a failure to produce autologous CAR-T cells because of T-cell dysfunction. In such cases, allogeneic CAR-T therapy has to be considered.A 17-year-old boy with stage II BL did not respond to extensive chemotherapy and sequential autologous CAR-T therapy. Lentiviral vectors containing anti-CD20-BB-ζ (20CAR) and anti-CD22-BB-ζ (22CAR) transgenes were used to modify the T cells from an HLA-identical matched unrelated donor. Flow cytometry was used to assess the cytokine analyses and CAR-T cell persistence in peripheral blood, enumerated by qPCR as copies per ug DNA. Informed consent for autologous/allogeneic CAR-T therapy was obtained from the patient and his legal guardian.Unedited HLA-matched allogeneic CD20 and CD22 CAR-T cells were infused after lymphodepletion chemotherapy with cyclophosphamide and fludarabine. The patient experienced Grade IV cytokine release syndrome (CRS) and went into complete remission (CR) after anti-inflammatory treatment including tocilizumab. Because of persistent pancytopenia and full donor chimerism, the same donor's conditioning-free peripheral blood stem cells were successfully transplanted 55 days post CAR-T. Neutrophils were engrafted at day +11 and platelets were rebuilt at day +47 without obvious acute graft-versus-host disease (GVHD), but there was mild chronic GVHD in the skin and eyes. Currently, active anti-rejection therapy is still underway.Unedited HLA-matched allogeneic CAR-T cell therapy could be an innovative, effective, and safe treatment for children with refractory/relapse BL without obvious acute GVHD. Conditioning-free allogeneic hematopoietic stem cell transplantation (HSCT) from the same donor is feasible for a patient with full donor T-cell chimerism after allogeneic CAR-T. It cannot be ignored that close GVHD monitoring is needed post HSCT.Copyright © 2023 Yang, Luo, Qian, Huang, Zhang, Wang, Luo, Qin, Li and Chen.