Treatment of Patients with Chronic Lymphoproliferative Disorders (CLPD) with Fludarabine, Cyclophosphamide, and Rituximab (FCR) Combination.

The FCR combination in a phase III study (Blood 102, abstract #373, p110a,2003) has shown promising results in the treatment of chronic lymphocytic leukemia (CLL) patients leading in increase of proportion of complete remissions and improved survival. Based on these encouraging results we tried to study the efficacy and safety of the FCR combination in patients of our Haematologic Unit. Seventeen patients, 8 males and 9 females with a median age of 69,5 years old, with relapsed/refractory or de novo CLPD ( 9 CLL and 8 NHL patients) were enrolled in this study between February 2002 and August 2004. Fifty percent of CLL patients had Rai stage I/II and the rest 50% had Rai stage III/IV disease. Four NHL patients had also Ann Arbor stage I/II and the rest four Ann Arbor stage III/IV disease. They were treated with Rituximab 375 mg/m2 on day1 in combination with Fludarabine and Cyclophosphamide ( 25 mg/m2 and 250 mg/m2 respectively) for days 2 to 4, every 4 weeks, for 6 consecutive cycles. Nine patients had a history of a prior unsuccessful treatment. Overall, 14 out of 17 evaluable patients were responsive to the treatment [12 patients complete response (CR) and 2 patients partial response (PR), overall response rate (ORR) 82%]. The remaining 3 patients did not show any response (NR), 2 progressive and 1 stable disease. Hematological toxicity was acceptable ( grade 2–3 neutropenia in 6/17 patients, grade 2–3 anemia and thrombocytopenia in 2/17 patients). There were no septic episodes except one case with neutropenic fever. There were no adverse events like nausea or vomiting except one patient with a serious anaphylactic reaction due to Rituximab administration. Three CLL patients died because of stable or progressive disease. In conclusion, this preliminary report suggests that the FCR regimen is an effective and safe treatment for CLPD patients, achieving higher CR rates than previous treatments. A longer follow up of a larger number of patients is required to confirm an improved survival in these patients.