Therapeutic advances of Fludarabine-refractory chronic lymphocytic leukemia

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.