Response to fludarabine in B-cell chronic lymphocytic leukemia patients previously treated with chlorambucil as up-front therapy and a CHOP-like regimen as second line therapy

Background and Objectives. Fludarabine (FAMP) is the most active single age nt in relapsed and refractory patients with B-cell chronic lymphocytic leuk emia (B-CLL). However, it is not clear whether it should be used immediatly after failure of chlorambucil (CLB). We addressed such an issue retrospect ively analyzing a series of patients in whom FAMP was used as third-line th erapy after a sequential use of CLB and CHOP (cyclophosphamide, doxorubicin , vincristine, prednisone) or CHOP-like regimen, respectively. Design and Methods. On a retrospective basis, 57 B-CLL patients fulfilling the above mentioned criteria and followed-up in seven different hematologic institutions, were evaluated. Results. Of 57 patients who were evaluated for response, 3 (5.2%) achieved a complete response (CR), 30 (52.6%) had a partial response (PR) and the re maining 24 (42.1%) failed to respond to FAMP Overall median survival from t he start of FAMP therapy was 30 months. Survival by tumor response did not show any difference between responders and non-responders (p = 0.536). The survival was significantly shorter in the group of patients with progressiv e disease than in all other patients included in our study (p = 0.05). Usin g each patient as his own control (McNemar test) we attempted to evaluate t he value of FAMP in inducing a therapeutic response after failure of previo us therapies. Among the 37 patients resistant to CLB the response rate was 40.3% with FAMP (p 0.037) and only 17.5% with CHOP (p = 1.0). Among 35 pati ents resistant to a CHOP-like regimen, the response rate was 29.8% (p = 0.0 66) after FAMP therapy. Interpretation and Conclusions. From our results, it seems that FAMP works better than a CHOP-like regimen in patients resistant to CLB although resul ts do not translate into a survival advantage for responders. (C) 2001, Fer rata Storti Foundation.