Ye Yishan, Yang Luxin, Yuan Xiaolin, Huang He, Luo Yi
First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Institute of Hematology, Zhejiang University, Hangzhou, China.
Front Oncol. 2022 Jan 27;11:790299. doi: 10.3389/fonc.2021.790299. eCollection 2021.
Donor lymphocyte infusion (DLI) is a key strategy for the treatment of AML relapse after allogeneic hematopoietic cell transplantation (allo-HCT) and has been used for either prophylactic, pre-emptive, or therapeutic purposes. However, the prognosis of these patients remains dismal even after DLI infusion (2-year overall survival, ~25%), and the efficacy is achieved at the cost of toxicities such as graft-versus-host (GVH) disease. Attempts to optimize DLI efficacy and safety, such as dose/timing modification and the use of cytoreduction, before DLI have been performed previously. Recently, a great number of novel targeted and immunomodulatory agents have emerged. Some of them, such as hypomethylating agents, FLT3 and Bcl-2 inhibitors, have been used in combination with DLI, aiming to enhance the graft-versus-leukemia effect. Moreover, manipulation of the DLI graft through cell selection (.., donor NK cells) or cell engineering (donor CAR-T cells) has shown potentially superior anti-tumor effects but less GVH effect than conventional DLI in clinical trials. This review summarizes the recent advances on the use of DLI for the prophylaxis/treatment of AML relapse and discusses future strategies which may further improve the treatment efficacy.
供体淋巴细胞输注（DLI）是异基因造血细胞移植（allo-HCT）后治疗急性髓系白血病（AML）复发的关键策略，已用于预防、抢先治疗或治疗目的。然而，即使在输注DLI后，这些患者的预后仍然很差（2年总生存率约为25%），且疗效是以移植物抗宿主（GVH）病等毒性为代价获得的。此前已尝试在DLI前优化其疗效和安全性，如调整剂量/时间以及使用细胞减灭法。最近，大量新型靶向和免疫调节药物出现。其中一些药物，如低甲基化剂、FLT3和Bcl-2抑制剂，已与DLI联合使用，旨在增强移植物抗白血病效应。此外，通过细胞选择（如供体NK细胞）或细胞工程（供体CAR-T细胞）对DLI移植物进行操作，在临床试验中显示出潜在的更优抗肿瘤效果，但与传统DLI相比，GVH效应较小。本综述总结了DLI用于预防/治疗AML复发的最新进展，并讨论了可能进一步提高治疗疗效的未来策略。
