The Treatment of Complicated and High Risk Chronic Lymphocytic Leukemia (CLL) with Fludarabine, Cyclophosphamide and Rituximab (FCR).

Between November 2000 and November 2004, we treated 11 patients with the FCR regimen for complicated CLL. The median age was 64 years (51–80 years) and the median number of prior regimens received was 1(0–4). Median number of FCR cycles delivered was 4 (2–6). Four patients were treated due to active autoimmune hemolytic anemia (AIHA), three patients due to massive lymphadenopathy, two patients for short lymphocyte doubling time, one patient for active AIHA and immune thrombocytopenia and one patient for progressive splenomegaly. Two patients received only 2 cycles of FCR due to prolonged pancytopenia secondary to hypoplastic bone marrow. Four of the patients with AIHA had prior splenectomies. Overall response rate, according to NCIWG criteria, was 100% including the patients who had received only 2 cycles. One patient achieved a complete remission, seven patients achieved nodular partial remissions and three achieved partial remissions. Among the 7 patients with nodular PR’s, 4 had no evidence of residual CLL by flow cytometry and are continuing to be in remission at a median follow up of 53 months. The other 3 patients with nPR who had evidence of disease by flow cytometry relapsed at a median of 23 months (16–33 months). The patient who had a CR by NCIWG criteria, still had evidence of disease by flow cytometry and relapsed at 35 months. All patients with AIHA and immune thrombocytopenia achieved a remission of their autoimmune processes, including those who failed splenectomy. Grade 3–4 neutropenia, thrombocytopenia and anemia occurred in 8, 2 and 2 patients respectively. The median progression free interval was 33 months (9+ to 54 m) and the overall survival was 56 months (9+ to 56m). Four patients had expired at the time of this report due to progression of CLL(1), sepsis while still in remission(1), high grade transformation and subsequent sepsis(1) and complications of allogeneic transplant(1). Cytogenetic remissions were achieved in 7/9 patients. Three of them continue to be in remission at the time of this report with a median follow up of 53 months since initiation of therapy.

Conclusion: FCR is an effective treatment regimen for CLL associated AIHA, even after failing splenectomy and can result in high response rates and prolonged remissions. Flow cytometry remission seems to correlate with prolonged disease free survival in patients achieving nodular partial remissions according to the NCIWG criteria. We suggest treatment with FCR until elimination of minimal residual disease by flow cytometry irrespective of histopathological remission.