Efficacy and Safety of Fludarabine and Cyclophosphamide Combined Therapy in Patients with Refractory/Recurrent B-Cell Chronic Lymphocytic Leukaemia (B-CLL)—Polish Multicentre Study

Abstract

The aim of this study was to investigate the efficacy of a combination of fludarabine (F) and cyclophosphamide (C) in the treatment of patients with refractory/recurrent B-cell chronic lymphocytic leukaemia (B-CLL). Between November 1999 and December 2001, 63 patients with B-CLL (median age 60 years) received a regimen that consisted of F 25 mg/m2 and C 250 mg/m2, days 1-3, intravenously, every 4 weeks, for a maximum of 6 courses, Response and toxicity were assessed according to current criteria (NCI-WG and WHO). Complete and partial remissions were achieved in 17.5% and 55.6% of patients, respectively; 19% of patients had stable disease and 7.9% of patients showed disease progression. The median follow-up was 16.5 (range 1.5-32) months. The median duration of progression-free survival (PFS) has not been reached among patients treated with FC regimen as second-line therapy. The median PFS was 13 (range 8-26) months in the 19 responding patients treated with FC regimen as third-line therapy. The most frequent side-effects were neutropenia (45%), thrombocytopenia (42%) and infections (57%). We conclude that the combination of fludarabine and cyclophosphamide demonstrated significant efficacy in pretreated, advanced B-CLL patients, with tolerable toxicity.

Management of Infectious Complications in Patients with Chronic Lymphocytic Leukemia

“…In one series, 57% of patients receiving FC had infections or fever of unknown origin, of which 26% were caused by herpesviruses and 7% by fungal pathogens. 26 The incidence of these complications in the first 3 cycles of therapy was 74%. Last, the occurrence of Epstein-Barr virus-associated lymphoproliferative disorders has been reported in patients who received FC therapy followed by autologous stem cell transplantation.…”

Phase II study of single‐agent bortezomib for the treatment of patients with fludarabine‐refractory B‐cell chronic lymphocytic leukemia

“…[11][12][13][14] Therapy for relapsed CLL patients continues to be challenging and the prognosis is poor when standard combination chemotherapy is used. 5,15,16 With response rates hardly exceeding 20% and median survival times of approximately 10 months, prognosis is particularly poor for those patients who have become refractory to treatment with fludarabine-based regimens. 1,17 Alemtuzumab, a humanized monoclonal antibody against the CD52 antigen, has shown encouraging activity as a single agent and in a range of combination regimens in patients with relapsed and refractory CLL, and is the only agent currently approved for the treatment of fludarabinerefractory B-cell CLL.…”

Immunosuppression Associated With Novel Chemotherapy Agents and Monoclonal Antibodies

“…Adding cyclophosphamide to fludarabine (FC), compared to fludarabine, resulted in comparable rates of severe and opportunistic infections in treatment-naive patients [4]. In previously treated CLL patients receiving FC, 57% had infections or fever of unknown origin, including 26% herpesvirus and 7% fungal infections; 74% of infections occurred in the first 3 months of therapy [5]. A 20% grade 3/4 infection rate, including localized herpesvirus and 2 Pneumocystis cases, occurred with initial rituximab plus fludarabine (FR) CLL therapy [6].…”