The natural history of fludarabine-refractory chronic lymphocytic leukemia patients who fail alemtuzumab or have bulky lymphadenopathy

The natural history and outcome of salvage treatment for patients with fludarabine-refractory chronic lymphocytic leukemia who are either refractory to alemtuzumab (double-refractory'') or ineligible for alemtuzumab due to bulky lymphadenopathy (bulky fludarabine-refractory'') have not been described. We present the outcomes of 99 such patients ( double-refractory n = 58, bulky fludarabine-refractory n = 41) undergoing their first salvage treatment at our center. Patients received a variety of salvage regimens including monoclonal antibodies ( n = 15), single-agent cytotoxic drugs ( n 14), purine analogue combination regimens ( n = 21), intensive combination chemotherapy ( n = 36), allogeneic stem cell transplantation ( SCT; n = 4), or other therapies ( n = 9). Overall response to first salvage therapy other than SCT was 23%, with no complete responses. All four patients who underwent SCT as first salvage achieved complete remission. Early death ( within 8 weeks of commencing first salvage) occurred in 13% of patients, and 54% of patients experienced a major infection during therapy. Overall survival was 9 months, with hemoglobin <11 g/ dL ( hazard ratio 2.3), hepatomegaly ( hazard ratio 2.4), and performance status >= 2 ( hazard ratio 1.9) being significant independent predictors of inferior survival.