氟达拉滨耐药的慢性淋巴细胞白血病治疗进展

Therapeutic advances of Fludarabine-refractory chronic lymphocytic leukemia

对嘌呤类药物发生耐药为慢性淋巴细胞白血病(CLL)患者预后差的特征。虽然近年来免疫化疗联合应用如氟达拉滨(Fludarabine,Flu)、环磷酰胺(CTX)和利妥昔单抗(rituximab)已导致初治患者反应率达95%和无失败生存率增加,但因为缺乏治疗反应和对Flu耐药许多慢淋患者仍不能治愈。补救治疗的策略包括含阿来组单抗(alemtuzumab)的方案、靶向药物和异基因造血干细胞移植(allo-SCT)。单药alemtuzumab治疗Flu耐药的CLL患者反应率高达40%,但反应并不持久,中数生存期约1-2年。耐Flu-CLL患者亦可采用alemtuzumab与Flu、CTX和/或利妥昔单抗,或其他药物如雷利度胺(lenalidomide)、flavopiridol和靶向药物联用进行补救性治疗。包括alemtuzumab和/或利妥昔的免疫化疗方案和allo-SCT或可改善该病的预后,但对新的、更有效的治疗仍需要继续研究。

Although in recent years chemoimmunotherapeutic combinations such as fludarabine,cyclophosphamide,and rituximab have induced response rates of 95% in previously untreated patients and increased the rates of failure-free survival,Cll remains incurable for many patients because of a lack of disease response or the development of refractoriness to fludarabine.Salvage therapeutic strategies include alemtuzumab-containing regimens,targeted agents and allogeneic stem cell transplantation.Single-agent alemtuzumab induces response in up to 40% of patients with fludarabine-refractory CLL,but responses are not durable,and the median survival is approximately 1 to 2 years.Alemtuzumab is also combined with fludarabine,cyclophosphamide,and/or rituximab,and other agents such as lenalidomide and flavopiridol,as well as targeted agents,and used in fludarabine-refractory CLL.In conclusion,chemoimmunotherapy regimens that include alemtuzumab and/or rituximab and allogeneic stem cell transplantation improve the prognosis of this disease,but there is a need for novel,more effective therapies.