Genetics and risk-stratified approach to therapy in chronic lymphocytic leukemia

The clinical staging systems developed by Rai and Binet have remained the mainstay for clinical decision-making in patients with chronic lymphocytic leukemia (CLL). However, there is substantial heterogeneity in the course of the disease. In recent years molecular and cellular markers have helped to predict the prognosis of patients with CLL. Ig V(H) status and genomic aberrations subdivide CLL into distinct clinical subgroups. Fluorescence in-situ hybridization (FISH) can identify genomic aberrations in approximately 80% of CLL cases. The most frequent aberrations are deletions in 13q, 11q, or 17p, and trisomy 12. Apart from providing insights into the pathogenesis, genomic aberrations identify subgroups of patients with distinct clinical pictures: lymphadenopathy (11q-) or resistance to therapy (17p-). Deletions at 11q and particularly 17p are associated with rapid disease progression or inferior survival. Patients with these genetic abnormalities may be candidates for clinical trials investigating alternative treatments and stem-cell transplantation.