Management of patients with chronic lymphocytic leukemia with a high risk of adverse outcome: The Mayo Clinic approach

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) is usually an incidental diagnosis in patients with earlyintermediate stage disease. However, most patients with a diagnosis of CLL will subsequently have significant morbidity and die from their disease and its complications. For these patients, CLL is not the ?good leukemia? with a predictably ?benign? outcome. Indeed, we can now identify a cohort of patients with high-risk CLL at diagnosis who will have rapid disease progression, poor response to treatment, and poor survival based on prognostic methods developed from an improved understanding of the biology of CLL. The concomitant development of improved treatments has led to risk-adjusted management approaches that could improve outcomes. We discuss the clinical and laboratory components of comprehensive risk evaluation of patients with CLL and our approach to the management of patients with a high to very high risk of disease progression and poor outcome. In addition, we review the challenges and prospects for improving prognostic precision and the development of new drugs to improve the treatment of patients with CLL with a high risk of adverse outcome.