Prognostication of chronic lymphocytic leukemia in the era of new agents

The prognosis of chronic lymphocytic leukemia (CLL) is very heterogeneous. Therefore, a plethora of prognostic factors has been identified to allow a better prediction of the individual prognosis of a given patient. The clinical staging systems by Rai and Binet have been the backbone of clinical management for several decades. The advent of genetic and biochemical markers, as well as next-generation sequencing has provided several markers that can predict the prognosis of patients with CLL. Using this knowledge, several scores have been created to improve predicting overall survival and/or treatment-free survival. These prognostic scores were developed in the era of chemotherpay/chemoimmunotherapy. Therefore, they now need to be tested with novel agents. However, despite tremendously improved therapeutic options, CLL patients with TP53 dysfunction or a complex karyotype remain at very high risk and seem to have a shorter (treatment-free) survival. The recently published international prognostic index (CLL IPI) incorporates most of these factors and provides a tool to analyze outcome in the modern era of targeted therapies.