IMMUNOSUPPRESSIVE EFFECTS AND CLINICAL-RESPONSE OF FLUDARABINE IN REFRACTORY CHRONIC LYMPHOCYTIC-LEUKEMIA

Background: Fludarabine monophosphate is a new adenine nucleoside anal ogue with a promising efficacy in B-cell chronic lymphocytic leukemia (B-CLL) with response rates, including hematological complete remissio ns, of 50%-60% in previously treated and 75%-80% in previously untreat ed patients. Patients and methods: Here, the clinical experience with and side effects of fludarabine are reported in 19 patients with refra ctory CLL (17 B-CLL, 2 T-CLL). All patients were pretreated with one t o four different regimens and had progressive disease. Fludarabine was administered at a dosage of 25 mg/m2 daily for 5 days as a 30-minute intravenous infusion. This course was repeated every fifth week. Dosag e and time course were adapted to toxicity. Results: 12/18 (67%) evalu able patients achieved partial remissions (PR), 1/18 (6%) had stable d isease (SD) and 5/18 (28%) were progressive. The median duration of pa rtial remission until relapse or death was 6 months. Most responses to fludarabine occurred within two treatment courses. Major toxic effect s included infections in 11 patients and nausea in 8 (mainly grade 1). Meanwhile, three patients died of progressive disease and 8 of pneumo nias or other infections. Two patients had pneumocystis carinii pneumo nias and one an aspergillus pneumonia. The high infection rate may be due not only to hypogammaglobulinaemia or fludarabine-induced granuloc ytopenia but also to a remarkable decrease of CD4+-cells during fludar abine therapy. In one case a tumor lysis syndrome was observed. No CNS toxicity was noted. Conclusion: It is concluded that fludarabine is e ffective even in patients with advanced chronic lymphocytic leukemia r efractory to multiple chemotherapy regimens. However, fludarabine has a remarkable suppressive effect on T-lymphocytes, predominantly CD4+-l ymphocytes. Long-term antibiotic prophylaxis is recommended.