Treatment Options for Patients with Fludarabine-Refractory Chronic Lymphocytic Leukemia

Treatment of chronic lymphocytic leukemia (CLL) has evolved over the past decade. A purine nucleoside analogue, alone or combined with other drugs, including monoclonal antibodies, is becoming the preferred first-line regimen for patients with CLL. Becoming refractory to a purine nucleoside analogue poses an important challenge, which has led to innovative approaches combining different chemotherapeutic drugs, monoclonal antibodies, and new experimental agents. Despite these advances, allogeneic hematopoietic stem cell transplantation remains the only option with curative potential. Hence, many investigators have worked on modifying the conditioning regimens, introducing reduced-intensity conditioning, in an attempt to decrease treatment-related mortality as well as the risk of graft-versus-host disease. Hand-in-hand with this therapeutic advancement, progress has been made in risk stratifying patients with CLL based on biologic markers. This has resulted in better analysis of the effectiveness of different therapeutic interventions administered to patients with CLL in the newly diagnosed and refractory settings. Individualized therapy based on molecular identity, other disease characteristics and response to previous therapy might improve outcomes for patients who develop fludarabine-refractory CLL.