Low-dose fludarabine and cyclophosphamide in elderly patients with B-cell chronic lymphocytic leukemia refractory to conventional therapy

Background and Objectives. In recent years fludarabine alone or in combinat ion with other drugs has been reported to be effective in the treatment of B-cell chronic lymphocytic leukemia (B-CLL), both as first line and salvage therapy. Among the different combination regimens, the association of flud arabine and cyclophosphamide has shown a considerable therapeutic efficacy although a relevant number of infectious complications have been described, particularly In elderly patients. The aim of this work was to evaluate the efficacy, the toxicity, and the Incidence of Infectious episodes of a regi men combining lower doses of fludarabine and cyclophosphamide in elderly pa tients with B-CLL. refractory to conventional therapy. Design and Methods. Twenty patients with progressive B-CLL with a median ag e of 75 years (4 in stage B and 16 in stage C) and refractory to convention al therapy were enrolled In this study. The combination regimen was as foll ows: fludarabine 15 mg/m(2)/day i.v. [max 25 mg] and cyclophosphamide 200 m g/m(2)/day i.v. for four days. Results. All patients enrolled were evaluable for response. Three out of 20 (15%) patients achieved a complete remission (CR), 14/20 (70%) a partial r esponse (PR) with an overall response rate (CR+PR) of 85%, according to Nat ional Cancer Institute-Working Group response criteria. Three patients were considered resistant In four out of 20 patients (20%), a severe neutropeni a (neutrophils < 0.5x10(9)/L) occurred and one of them developed an infecti ous complication which required treatment with systemic antibiotics and gra nulocyte colony- stimulating factor (G-CSF). Non-hematologic toxicity was n egligible in all patients but one, who despite a adequate therapy with allo purinol and hydration, experienced a tumor lysis syndrome with transient bu t severe renal impairment Interpretation and Conclusions. The association of low-dose fludarabine end cyclophosphamide appeared to be effective in this subset of B-CLL patients , reproducing a similar overall response rate obtained with other fludarabi ne-based combination therapies. In addition, In this group of elderly patie nts, toxic side effects were negligible and infectious complications remark ably low. (C) 2000, Ferrata Storti Foundation.