Adverse prognostic features in chronic lymphocytic leukemia

Patients with chronic lymphocytic leukemia (CLL) can have variable courses, from indolent disease to rapid progression with limited response to treatment. The Rai and Binet staging systems were the first to classify patients into prognostic categories. Newer prognostic markers that correlate with shorter time to progression and time to treatment include elevated serum beta2M, TK, ZAP-70, and CD38, as well as unmutated IgV(H). Abnormal cytogenetics are found in the majority of patients with CLL. Del(17p), as well as mutations of TP53, is associated with an aggressive clinical course and short overall survival. Nearly one-fifth of patients have del(11q) and have a significantly shorter median progression-free survival; mutations in the ATM gene, located on 11q, may also have adverse prognostic implications. Intermediate-risk cytogenetic findings include trisomy 12 and del(6q). Patients with del(17p) should be evaluated for novel agents and/or allogeneic stem cell transplantation in first remission. Patients with del(11q) require treatment with an alkylating agent in addition to nucleoside analogs and rituximab, and patients with trisomy 12q may express higher levels of CD20, thereby making the malignant cells more susceptible to biologic agents that target CD20. Despite advances in stratifying patients and improved chemoimmunotherapeutic regimens, additional research in prognostication and treatment is needed.