Efficacy of fludarabine, a new adenine nucleoside analogue, in patients with prolymphocytic leukemia and the prolymphocytoid variant of chronic lymphocytic leukemia

PURPOSE: To describe the results of fludarabine therapy in patients with prolymphocytic leukemia (PLL) and the prolymphocytoid variant of chronic lymphocytic leukemia (CLL-Pro). PATIENTS AND METHODS: Seventeen patients with a diagnosis of PLL or CLL-Pro received fludarabine 30 mg/m[sup. 2] over 30 minutes daily for 5 days every 4 weeks alone (12 patients), or with prednisone (five patients). Previously defined criteria for response were used. Differences in response rates according to various characteristics were evaluated by chi-square test. RESULTS: Three patients (18%) achieved complete remission, and three (18%) had a partial remission, for an overall response rate of 35%. Responses were durable and occurred in all involved organ sites. Lower response rates were observed in patients with anemia, thrombocytopenia, advanced Rai stages, and primary resistance to prior therapy. Toxicities were minimal except for febrile episodes associated with therapy. CONCLUSION: Fludarabine has shown encouraging results in these patients and deserves further investigation in combination with other active agents, and in the setting of front-line therapy.
Prolymphocytic leukemia (PLL) is a type of cancer of the blood cells that is associated with proliferation of prolymphocytes, a type of white blood cell, in the blood and bone marrow; involvement of the spleen; less frequent accumulation of cancer cells in the lymph nodes and liver; and a poor outcome. An intermediate form of PLL is chronic lymphocytic leukemia (CLL-Pro), in which there is a lower percentage of prolymphocytes as compared with that in PLL. Patients with more than 30 percent prolymphocytes had a higher death rate than patients with fewer prolymphocytes. The anticancer agents chlorambucil, cyclophosphamide, and fludarabine monophosphate, and steroids have been used to treat patients with CLL. The effectiveness of fludarabine in treating 17 patients with PLL and CLL-Pro was assessed. Remission was complete in three patients and partial in three other patients, producing an overall response rate of 35 percent. The response to treatment was enduring and evident in all affected tissues. Patients with anemia (decreased numbers of red blood cells), thrombocytopenia (abnormal decrease in blood platelets, involved in clotting), advanced cancer, and initial resistance to prior therapy were less responsive to treatment with fludarabine. Side effects of fludarabine were few and included the development of fever. These results show that fludarabine may be beneficial in treating patients with PLL and CLL-Pro, and should be tested in additional studies. (Consumer Summary produced by Reliance Medical Information, Inc.)