Damaj Nahed, Elias Nadim, Zeidan Toufic, Kattan Joseph
Department of Hematology-Oncology, Faculty of Medicine, Hotel Dieu de France University Hospital, Saint Joseph University of Beirut, Beirut, Lebanon.
Invest New Drugs. 2025 Jun 25. doi: 10.1007/s10637-025-01556-1.
The concept of differentiation therapy emerged from the fact that hormones or cytokines may promote differentiation ex vivo, thereby irreversibly changing the phenotype of cancer cells. Its hallmark success has been the treatment of acute promyelocytic leukemia (APL), a condition that is now highly curable by the combination of retinoic acid (RA) and arsenic. Differentiation syndrome (DS) is a common and potentially life-threatening condition that was initially described with the induction therapy of targeted agents in acute promyelocytic leukemia (APL). DS is typically marked by symptoms such as fever, difficulty breathing, low blood pressure, weight gain, fluid buildup in the pleural or pericardial cavities, and acute kidney failure. The incidence of DS in APL patients varies from 2 to 27% reflecting the discrepancies in diagnostic criteria, in various treatment protocols, and sometimes the use of preventive treatments. Corticosteroids, with or without cytoreductive therapy, should be initiated immediately upon suspicion of DS to mitigate related morbidity and mortality. In cases of severe DS, targeted anti-leukemic therapy should be halted. This review will cover the pathogenesis of DS, its clinical presentations, diagnostic criteria, management approaches, and the importance of implementing prospective tracking in clinical trials.
分化疗法的概念源于这样一个事实，即激素或细胞因子可能在体外促进分化，从而不可逆地改变癌细胞的表型。其标志性的成功案例是急性早幼粒细胞白血病（APL）的治疗，现在通过维甲酸（RA）和砷的联合使用，这种疾病已具有很高的治愈率。分化综合征（DS）是一种常见且可能危及生命的病症，最初是在急性早幼粒细胞白血病（APL）的靶向药物诱导治疗中被描述的。DS的典型症状包括发热、呼吸困难、低血压、体重增加、胸腔或心包腔积液以及急性肾衰竭。APL患者中DS的发生率在2%至27%之间，这反映了诊断标准、各种治疗方案以及有时预防性治疗使用方面的差异。一旦怀疑患有DS，应立即开始使用皮质类固醇，无论是否进行细胞减灭治疗，以减轻相关的发病率和死亡率。在严重DS的情况下，应停止靶向抗白血病治疗。本综述将涵盖DS的发病机制、临床表现、诊断标准、管理方法以及在临床试验中实施前瞻性跟踪的重要性。
