中剂量依托泊苷（ETP）、环磷酰胺（CY）和全身照射（TBI）是对于成年急性淋巴细胞性白血病（ALL）患者的异基因造血干细胞移植（allo-HCT）的一种有益的预处理方案，尤其对于高危ALL而言，与CY和TBI预处理方案相比。ETP可以通过增加主要组织相容性抗原复合物Ⅰ类的表达，提高白血病相关抗原的免疫原性，通过树突状细胞交叉启动T细胞，产生针对白血病特异性的细胞毒性T细胞。此外，ETP可以消除活化效应T细胞，保留免疫原和记忆T细胞，同时降低调节性T细胞的数量。这些机制被认为能够抑制白血病细胞的免疫逃逸，增强抗白血病免疫力，除了ETP的直接细胞毒性之外，实现对白血病细胞的高效消除。根据药代动力学研究的结果，将低剂量ETP的给药延展可能比非延展给药更具疗效，能够在不加重移植物抗宿主病和移植相关毒性的情况下诱导强效的抗白血病免疫力。在本综述中，我们将讨论将中剂量ETP添加到CY/TBI预处理方案中所引发的免疫学方面，并考虑到包括双特异性抗体治疗在内非移植相关治疗的最新进展，分析该预处理方案在成年ALL患者中的潜力位置。版权所有 © 2023 国际细胞与基因治疗学会。由Elsevier Inc.出版。保留所有权利。

Medium-dose etoposide (ETP), cyclophosphamide (CY) and total body irradiation (TBI) is a beneficial conditioning regimen for allogeneic hematopoietic cell transplantation (allo-HCT) in adults with acute lymphoblastic leukemia (ALL), especially with high-risk ALL, as compared with CY and TBI conditioning. ETP may enhance immunogenicity of leukemia-associated antigens through increased expression of major histocompatibility antigen complex class I, leading to cross-priming of T cells by dendritic cells and generating leukemia-specific cytotoxic T cells. Furthermore, ETP can eliminate activated effector T cells, sparing naïve and memory T cells, accompanied with depletion of regulatory T cells. These mechanisms are supposed to lead to inhibit immune escape of leukemia cells and enhance anti-leukemia immunity in addition to direct cytotoxicity of ETP, followed by an efficient eradication of leukemia cells. According to the findings of pharmacokinetics studies, spreading the administration of low-dose ETP may be more efficacious than non-spreading administration, to induce a potent anti-leukemia immunity without aggravating graft-versus-host disease and transplant-related toxicity. In the present review, I discuss the immunological aspects elicited by the addition of medium-dose ETP to the CY/TBI conditioning and the possible positioning of allo-HCT with this conditioning in adults with ALL, considering recent progress in non-HCT treatment including bispecific antibody-based therapy.Copyright © 2023 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.