High-risk chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) is predominantly a disease of the elderly, with uniquely heterogeneous course. Advanced age has consistently been associated with a poor prognosis in patients with CLL, predominantly due to the frequent occurrence of comorbid conditions. Older and/or comorbid patients with CLL may not tolerate more aggressive approach and in these patients, chlorambucil, especially combined with anti-CD20 monoclonal antibodies, is recommended as the first-line treatment. In physically fit patients without deletion of 17p or TP53 deletion/mutation FCR (fludarabine, cyclophosphamide, rituximab) is the standard first-line therapy. Patients carrying deletion of 17p or mutations of TP53 have a poor response to chemoimmunotherapy. In these patients alemtuzumab-based regimens are frequently used but until recently only allogeneic stem cell transplantation holds the prospect for longer survival. Recently targeted therapies with B-cell receptor pathway inhibitors, ibrutinib and idelalisib or BCL-2 antagonist venetoclax (ABT-199) are associated with remarkable activity in patients with del(17p)