Chronic Lymphocytic Leukemia (CLL): Biology and Therapy

Chronic lymphocytic leukemia (CLL), the most common leukemia in the western world, is characterized by the accumulation of monoclonal B-lymphocytes in the bone marrow and lymphoid organs. Signaling via the B-cell receptor and Bruton tyrosine kinase (BTK) as well as resistance to apoptosis mediated by Bcl-2 are hallmarks of CLL biology and have been exploited in recent years to revolutionize management. As a result of the development of novel therapies, most CLL patients now can be spared conventional chemotherapy and can be treated using highly effective regimens consisting of BTK inhibitors, the Bcl-2 inhibitor venetoclax, and anti -CD20 monoclonal antibodies. The impact of novel therapies is particularly pronounced for high-risk cases including those with TP53 deletions/mutations who previously had a dismal outcome with conventional chemoimmunotherapy. Allogeneic HCT is a potentially curative option for selected younger patients with multiply relapsed high-risk disease.