FLUDARABINE AND CYCLOPHOSPHAMIDE FOR THE TREATMENT OF PATIENTS WITH INDOLENT NON-FOLLICULAR (INFL) B-CELL NON-HODGKIN'S LYMPHOMAS. PRELIMINARY RESULTS OF A PHASE II TRIAL OF THE 'GRUPPO ITALIANO PER LO STUDIO DEI LINFOMI (GISL)

Introduction: INFL comprises a rather heterogeneous subgroup of lymphomas,including small lymphocytic lymphoma (SLL), immunocytoma (IC) and marginalzone lymphomas (MZL). In April 2002, the GISL started a phase II trial to verifythe efficacy of fludarabine and cyclophosphamide (Flu–Cy) combination in this subsetof NHL, in terms of response, survival and toxicity.Patients and methods: Patients should have a diagnosis of SLL, IC, MZL or CD5negative mature B-cell leukemia (MBCL), supported by morphologic, phenotypicand molecular data; patients should also be untreated for lymphoma and have activedisease defined by the presence of anemia, thrombocytopenia, bulky disease, rapidlyincreasing lymphocytosis or enlarging masses. Treatment consisted of fludarabine25 mg/m2 i.v. day 1–3 and cyclophosphamide 250 mg/m2 i.v. days 1–3, to berepeated every 28 days for six cycles; an intermediate evaluation of response afterthree cycles was planned and an adequate anti-infective prophylaxis was mandatory.Results: As of March 2004, 44 patients were registered into the trial; one patientwas excluded from the study due to incorrect histology. Median age was 63 years(range 39–75), M/F ratio was 1.9. The diagnosis was SLL in 11 patients, IC in 7,MZL in 19 and MBCL in 5. All patients had stage IV disease. Anemia was presentin 32%, elevated b2 microglobulin in 56%, abnormal LDH in 32%. At the time ofthe present analysis, 24 patients completed the treatment program with 13 CR (52%)and 11 PRs (44%). Three patients died during treatment, one after the second cycledue to erosive pulmonary aspergillosis, the others due to bone marrow aplasiaoccurred after the 4th and 5th cycle, respectively. Overall, grade III or IV hematologicaltoxicity was observed in 44% of the patients. After a median follow-up of9 months, OS was 81%.Conclusion: The preliminary results of our study demonstrate that the Flu–Cycombination is effective in the treatment of patients with INFL but has also shown arelevant toxicity profile suggesting the need for extensive antimicrobial prophylaxis