CLINICAL-EXPERIENCE WITH FLUDARABINE AND ITS IMMUNOSUPPRESSIVE EFFECTS IN PRETREATED CHRONIC LYMPHOCYTIC LEUKEMIAS AND LOW-GRADE LYMPHOMAS

Fludarabine monophosphate (FAMP) is a new adenine nucleoside analogue with a promising efficacy in B-cell chronic lymphocytic leukemia (B-CL L) and low-grade non-Hodgkin lymphomas (NHLs). Here, the clinical expe rience and side effects with FAMP are reported in 77 patients with pre treated CLL (59 B-CLL, 2 T-CLL) and low-grade NHLs (9 immunocytic lymp homas including 5 Waldenstrom's macroglobulinaemia, 2 centrocytic (cc) and 5 centroblastic-centrocytic (cb-cc) NHLs). 70/77 patients are eva luable for reponse. All except 8 patients were pretreated with one to four different regimens and had progressive disease. FAMP was administ ered at a dosage of 25 mg/m(2) daily for 5 days as 30 minute infusion every fifth week. Partial (PR) or complete remission (CR) was achieved in 38/56 (68%) and 3/56 (5%) of evaluable patients with CLL, respecti vely. In 7/8 (1 x CR, 6 x PR) evaluable patients with immunocytic lymp homa and in 3/6 (3 x PR) patients with cc or cb-cc lymphoma remissions were obtained. The probability of progression-free survival was 66% a nd the event-free survival was 25% and 22% at 12 and 18 months. The me dian progression-free survival until relapse or death, however, was on ly 7 months (2-20+). Major toxic effects included infections in 22 pat ients (grade 3 and 4 WHO), granulocytopenia (mainly grade 3) and nause a in 8 patients (mainly grade 1). 19/22 patients were in PR at the tim e of occurrence of infectious complications. Meanwhile, 14 patients di ed due to septicaemia, pneumonia or other infections. Nine patients de veloped severe septicaemia, 4 patients had pneumocystis carinii or asp ergillus pneumonias. The high infection rate may not only be due to hy pogammaglobulinaemia and granulocytopenia induced by FAMP but also to a remarkable decrease of CD4+ cells from a median of 2479 to 241 CD4cells/mu l after 6 cycles of FAMP. In one case a tumor lysis syndrome was observed. No CNS toxicity was noted. It is concluded that FAMP is effective even in patients with advanced CLL and low-grade NHLs refrac tory to multiple chemotherapy regimens. However, FAMP has a marked sup pressive effect on granulocytes and T-lymphocytes, predominantly CD4lymphocytes.