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Staging and Prognostic Factors in Chronic Lymphocytic Leukemia: Current Status

Tadeusz Robak

Chronic Lymphocytic Leukemia (CLL) is a B-cell malignant disease characterized by a progressive accumulation of B cells in the blood, bone marrow and lymphatic tissue, and which follows an extended disease course [1]. The diagnosis of CLL requires the presence in the peripheral blood of ≥ 5,000 monoclonal B-lymphocytes/μL for duration of at least 3 months. It is the most prevalent leukemia in the Western World with an estimated 15,720 new cases in 2014 and almost 4600 attributable deaths per year in the United States [2]. Chronic lymphocytic leukemia is predominantly a disease of the elderly, with a median age of 70 years at diagnosis. It is a slowly progressive disease, with an 82% five-year survival rate [3]. However, several patients have advanced and progressive disease and a poor prognosis at diagnosis. The management of CLL is determined by the stage and activity of the disease, as well as age and comorbidities. Randomized studies and a meta-analysis indicate that early initiation of chemotherapy does not show benefit in CLL and may increase mortality. There is no evidence that cytotoxic therapy based on alkylating agents has beneficial effects in patients with the indolent form of the disease [4]. The strategy of watchful waiting or observation, i.e. closely monitoring patient status without giving any treatment until progression, may be adopted [5]. However, patients with symptomatic and/or progressive disease should be immediately treated. Chronic lymphocytic leukemia displays a high heterogeneity in its clinical course, which makes the onset time and the choice of therapy difficult to determine [6]. For this reason, recent research on this disease focuses simultaneously on understanding its biology, discovering novel prognostic factors and on incorporating new therapeutic agents in the treatment of CLL. There is increasing interest in the use of prognostic markers which may predict survival and guide management in patients diagnosed with the early stages of CLL. These efforts also aim at proposing new prognostic systems which combine clinical and biological aspects of the disease with special consideration of the results of cytogenetic and molecular tests.