Choosing first-line therapy for chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) exhibits a highly variable natural history, but the addition of genomic risk stratification to traditional clinical staging systems has begun to explain the heterogeneous clinical course. Overall response to treatment has significantly improved over the past three decades and for the first time, a survival benefit has been demonstrated with the use of monoclonal antibodies in combination with cytotoxic chemotherapy. Newer therapeutic strategies have abrogated the adverse prognosis associated with some higher risk features, but other genetic subgroups remain at high risk for rapid disease progression and early mortality. Patients at advanced age or with significant comorbidity constitute a large proportion of the CLL population and present unique clinical challenges. This article will discuss the evolution of contemporary therapeutic approaches to the initial treatment of CLL, and highlight the ways in which risk-adapted therapeutic strategies are improving clinical outcomes.     

Alemtuzumab is safe and effective as immunosuppressive treatment for aplastic anaemia and single‐lineage marrow failure: a pilot study and a survey from the EBMT WPSAA

An alemtuzumab‐based experimental immunosuppressive treatment (IST) regimen was investigated in 35 patients with severe aplastic anaemia (SAA), pure red cell (PRCA) or pure white cell aplasia (PWCA). Alemtuzumab total dose was 73–103 mg s.c., followed by cyclosporine. No serious toxicity due to the regimen was observed. Adverse events were clinically irrelevant; infectious events were rare. The total response rate was 58%, 84% and 100% in SAA, PRCA and PWCA, respectively, with corresponding 6 months cumulative response probabilities of 84%, 84% and 100%. Subcutaneous alemtuzumab is a feasible and sufficiently safe IST regimen for patients suffering from immune‐mediated marrow failures.     

An update on the management of chronic lymphocytic leukaemia

Despite the lack of long-term survival data, the impressive results obtained with fludarabine- and rituximab-based therapies have altered the philosophy of the management of patients with chronic lymphocytic leukaemia (CLL). Therapy with chemoimmunotherapy appears to give higher responses with more patients achieving complete remission and some molecular remission. This may potentially translate into improved disease-free survival, and potentially a ‘cure’. Treatment options for patients who develop resistance to fludarabine continue to be limited. This review summarises current chemo-, immuno-, and chemoimmunotherapeutic regimens that are being currently evaluated in patients with CLL.     

Pilot experience with continuous infusion alemtuzumab in patients with fludarabine-refractory chronic lymphocytic leukemia

We evaluated the activity and tolerability of alemtuzumab given as a continuous infusion for 7 d followed by subcutaneous administration for 11 wk as salvage therapy for 10 patients with fludarabine-refractory chronic lymphocytic leukemia. The continuous infusion of alemtuzumab was well tolerated. The typical infusion reaction seen with intravenous alemtuzumab was abolished. Two patients achieved a partial response with an overall response rate of 20%. Alemtuzumab levels were measured in four patients and detectable levels were obtained in three. Clinical activity needs to be confirmed in a larger patient population.