Management of chronic lymphocytic leukemia

Abstract

In the last decade, the management of chronic lymphocytic leukemia has undergone profound changes that have been driven by an improved understanding of the biology of the disease and the approval of several new drugs. Moreover, many novel drugs are currently under evaluation for rapid approval or have been approved by regulatory agencies, further broadening the available therapeutic armamentarium for patients with chronic lymphocytic leukemia. The use of novel biological and genetic parameters combined with a careful clinical evaluation allows us to dissect some of the heterogeneity of the disease and to distinguish patients with a very mild onset and course, who often will not need any treatment, from those with an intermediate prognosis and a third group with a very aggressive course (high-risk leukemia). On this background, it becomes increasingly challenging to select the right treatment strategy. In this paper, we describe our own approach to the management of different patients with chronic lymphocytic leukemia. ABSTRACT © F e r r a t a S t o r t i F o u n d a t i o n guidelines 1). In short, treatment should be applied in the presence of cytopenias (anemia and/or thrombocytopenia) due to bone marrow failure, or if bulky (>10 cm) or rapidly progressing lymphadenopathy occurs, or if a rapid increase (doubling within 6 months) of the lymphocyte counts or severe constitutional symptoms (night sweats, fever, weight loss, fatigue) occur.A few comments might help to interpret these recommendations. First, it should be pointed out that the absolute lymphocyte count is not a criterion for initiation of treatment. Lymphocyte counts of even a few hundred thousand lymphocytes per μL cause no harm, and both patients and doctors should be reassured at this point. LDT should be evaluated only if the level of lymphocytes is above 30x10 9 /L, because values may fluctuate at lower levels with no clinical significance.1 Moreover, it is important to remember that LDT is rarely an indication to initiate treatment. An isolated, rapid rise in lymphocyte count without any other symptom rarely occurs, and other reasons should be excluded (e.g. use of corticosteroids for unrelated causes). Similarly, severe constitutional symptoms are rarely the only criterion to start therapy and are often associated with other signs of the disease (cytopenia, lymphadenopathy). Management of autoimmune cytopeniasChronic lymphocytic leukemia is characterized by the potential appearance of autoimmune cytopenias (hemolytic anemia 7,8 in 7-10% of the cases and immune thrombocytopenia 7,9 in 2-5%). Neither situation signals progressive disease and, therefore, they do not justify the initiation of a cytoreductive treatment.10 Accordingly, autoimmune cytopenias are often listed as exclusion criteria for enrollment in clinical trials. Indeed, both manifestations should initially be treated independently of the leukemia itself. Therefore, the presence of autoimmune cytopenias should be ruled out, in particular in cases of rapid onset of anemia or thromboc...

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