Prognostic and predictive indicators in chronic lymphocytic leukemia

Several prognostic factors are available for patients with CLL who require therapy. Of these, high levels of β2 microglobulin, adverse cytogenetics and high expression levels of CD38 and ZAP70 surface markers are well described and mark patients with unfavorable prognosis [1]. In approximately 50% of patients, more than 2% of the immunoglobulin variable heavy-chain gene (IGHV) nucleotide sequence differs from that of germ-line non-clonal DNA [2]. Patients with mutated IGHV respond better to chemo-immunotherapy [3], and patients with unmutated IGHV have a shorter time to treatment, shorter time to next treatment, inferior response to chemotherapy, higher rates of chemotherapy resistance, and lower survival rates [4-6]. Until recently, CLL was considered an incurable disease. However, two recent studies found that with the combination of fludarabine, cyclophosphamide and rituximab (FCR) a fraction of patients with CLL achieve long-term disease-free survival and are probably cured [7, 8]. Because none of the novel agents that have been approved or are currently being tested cures CLL, it has been argued that chemoimmunotherapy will remain the treatment of choice, in particular for patients with mutated IGHV in the foreseen future. In this chapter we will review the various prognostic markers that help clinicians predict the clinical course and response to therapy of treatment naïve CLL patients. We will highlight IGHV mutation status as a predictive marker that could assist in selecting treatment from the growing arsenal of available drugs for CLL.