Dear Colleagues, 

Chronic lymphocytic leukemia (CLL), the most common adult leukemia, is a clinically heterogeneous disease with an indolent course in some patients, while others show an aggressive disease and poor survival. More than 40 years ago, Rai and Binet developed a staging system that is still one of the mainstays to predict the outcome of CLL patients.

Recent advances in the knowledge of the biology of CLL have led to identifying some prognostic biomarkers that can better predict the outcome of patients. The most reliable prognostic markers, widely used in clinical practice, are the immunoglobulin heavy chain variable (IGHV) gene mutational status, TP53 mutations, and cytogenetic aberrations identified by fluorescence in situ hybridization (FISH;11q−, 13q−, +12 and 17p−). Some of these biomarkers, TP53 aberrations, and the IGHV gene mutational status, can also drive treatment decisions. A multitude of other biomarkers, such as CD38, CD49d, and ZAP70 expression, NOTCH1, SF3B1, and BIRC3 gene mutations, have also revealed a prognostic effect in CLL. A prognostic score system, the CLL International Prognostic Index (CLL-IPI), including clinical, biological, and genetic prognostic parameters, has stratified CLL patients into four groups with different survival probability and time to first treatment. Other groups have designed similar score systems with a significant prognostic effect. The prognostic evaluation should also consider some clinical characteristics of CLL patients. These include age, comorbidities, hypogammaglobulinemia, and the presence of bulky lymph-nodes with high FDG uptake at the CT/ PET scan.

In this Special Issue, we will review the extensive literature in the field of new prognostic markers in CLL and discuss their role in the clinical management of CLL patients.