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Therapeutic Activity of Cladribine in Patients with B-cell Chronic Lymphocytic Leukemia (pp. 139-161) $25.00
Authors:  Robak, Tadeusz (Medical University of Lodz, Poland)
Abstract:
B-cell chronic lymphocytic leukemia (B-CLL) is the most common form of adult leukemia in the Western world. Chlorambucil has been for many years the drug of choice in the treatment of progressive disease. More recently newer purine nucleoside analogues, fludarabine (FA) and cladribine (2-CdA), have been synthesized and introduced into the treatment of this leukemia. 2-CdA is structurally similar to FA. However, there is less experience with the use of this agent than FA in patients with B-CLL. Nevertheless, similarly to FA, 2-CdA has been found to be more effective in previously untreated B-CLL patients, than in patients refractory to, or relapsing after conventional therapy. In different studies the overall response (OR) rate ranged from 75 to 85% and complete response (CR) from 10 to 47%. High CR and OR rates in B-CLL following 2-CdA as first line therapy were confirmed in a multicenter study. The results indicate, that OR rate after 2-CdA and prednisone therapy was significantly higher than that after chlorambucil and prednisone treatment (87% and 57%, respectively, p<0.001). Moreover, the clinical CR rate after 2-CdA therapy was also significantly higher (47%) than that after chlorambucil treatment (12%) (p<0.001). Despite the fact, that 2-CdA induces higher OR and higher CR rates in patients with B-CLL, its influence on survival duration is still uncertain and complete recovery is not probable. The results of recent studies indicate that combined use of 2-CdA with other agents may increase the CR rate and possibly reduce minimal residual disease (MRD), and prolong survival. Some preclinical in vitro and in vivo studies, as well as early clinical reports, may support such a hypothesis. Bone marrow suppression, with anemia, neutropenia and thrombocytopenia are the dose limiting factors for 2-CdA use. Moreover, treatment with 2-CdA leads to a decrease in the CD4+/CD8+ ratio for an extensive period of time exceeding even 24 months. In consequence, infections, including opportunistic ones, are frequent events and infections with fatal outcome have been reported. In conclusion 2-CdA, similarly to FA, is highly active drug in the patients with B-CLL. This agent alone or in combination with other agents can be routinely used as second line treatment and possibly as first line therapy in younger patients, who are candidates for potentially curative treatment, such as stem cell transplantation and/or monoclonal antibodies. 


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Therapeutic Activity of Cladribine in Patients with B-cell Chronic Lymphocytic Leukemia (pp. 139-161)