Prognostic factors and risk stratification in chronic lymphocytic leukemia

There is considerable heterogeneity in the clinical outcome of patients with chronic lymphocytic leukemia (CLL). While some patients live for decades without any therapy, others die within years of diagnosis despite multiple treatments. To better counsel newly diagnosed CLL patients about their disease course, the Rai and Binet staging systems were developed four decades ago. A deeper understanding of the biologic and molecular aberrations contributing to the pathogenesis of CLL led to identification of novel prognostic markers such as immunoglobulin heavy-chain variable gene (IGHV) mutation status, leukemia-cell expression of CD38, ZAP-70, and CD49d, and cytogenetic abnormalities detected by fluorescent in situ hybridization (FISH). The advent of next-generation sequencing has provided unprecedented insights into the subclonal architecture of CLL and its impact on disease progression and survival. More recently, integrated prognostic scoring systems that incorporate clinical, biologic and genetic characteristics into a single risk score have been developed and appear to improve the accuracy of prognostication for individual patients. This review summarizes the state-of-the-art prognostic factors and will guide the practicing clinician in their care of patients with CLL.