Abou Dalle Iman, El Cheikh Jean, Bazarbachi Ali
Hematology-Oncology Division, Department of Internal Medicine, American University of Beirut Medical Center, Beirut 1107 2020, Lebanon.
Cancers (Basel). 2022 Mar 15;14(6):1490. doi: 10.3390/cancers14061490.
Patients with high-risk acute myeloid leukemia are offered allogeneic hematopoietic cell transplantation (allo-HCT) in first remission to reduce risk of relapse. However, disease recurrence remains the major reason of allo-HCT failure, occurring in around 35-45% of patients, and leading to dismal outcomes. Strategies to reduce the risk of relapse are greatly needed, especially in the early post-transplant phase where the graft-versus-leukemia (GVL) effect is not yet activated. Some practices include the use of myeloablative conditioning regimens, close monitoring of measurable residual disease and donor chimerism, rapid tapering of immunosuppression, and implementation of pre-emptive strategies as the use of donor lymphocyte infusion. However, it's time to consider prophylactic pharmacologic interventions post allo-HCT that aim at maintaining leukemic clones under control by both direct cytotoxic activity and by enhancing the GVL effect. In this current review, available data on drugs targeting epigenetic pathways like azacitidine, or actionable mutations like FLT3 and IDH1/2 inhibitors used as maintenance post allo-HCT, will be discussed.
高危急性髓系白血病患者在首次缓解期接受异基因造血细胞移植（allo-HCT）以降低复发风险。然而，疾病复发仍是allo-HCT失败的主要原因，约35%-45%的患者会出现复发，并导致预后不良。非常需要降低复发风险的策略，尤其是在移植后早期阶段，此时移植物抗白血病（GVL）效应尚未激活。一些做法包括使用清髓性预处理方案、密切监测可测量的残留疾病和供体嵌合状态、快速减少免疫抑制以及实施如使用供体淋巴细胞输注等抢先策略。然而，现在是时候考虑allo-HCT后的预防性药物干预了，其目的是通过直接细胞毒性活性和增强GVL效应来控制白血病克隆。在本综述中，将讨论有关靶向表观遗传途径的药物（如阿扎胞苷）或用作allo-HCT后维持治疗的可操作突变（如FLT3和IDH1/2抑制剂）的现有数据。
