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Induction of long lasting complete remission is currently widely viewed as a potentially beneficial new goal in untreated CLL with indication for therapy. We devised a protocol for remission induction based on the FCR regimen, used for an initial 3 cycles to break potential resistance with an intensive regimen (phase I), followed by 3 cycles of FR (phase II), to limit toxicities of the induction phase. With the aim to maintain remissions longer we added a 2 year maintenance phase with rituximab in 3 monthly intervals. Here we report preliminary results from this non-randomized phase II study in previously untreated patients with CLL. Primary objective was the analysis of complete response rates, according to NCI-WG response criteria. Secondary goals included overall response rates, toxicity and remission quality using 4-color flow cytometric MRD analysis. Forty-three patients with a median age of 63 years (range 36 to 81) were recruited for the study. Median lymphocyte counts were 92 G/I and the median for bone marrow infiltration was greater than 80%. For this interim analysis 23 patients are evaluable for response after induction phase I and 16 patients for induction phase II. After 3 cycles of FCR we observed an 83% CR rate that was increased to 94% after addition of 3 cycles of FR. After 3 cycles of FCR 13/31 (42%) patients evaluable for MRD analysis showed less than 10−3 G/I CLL cells detectable (defined as a complete MRD response). After 6 cycles of therapy 10/17 (59%) were MRD negative. Of 12 patients evaluable after 6 months of maintenance 100% were in CR. However, in all stagings we observed about 25% of patients that clearly had no residual measurable disease (including CT scan and bone marrow biopsies) but had persistent cytopenias leading to their designation as CR with toxicity-associated cytopenias (CRtox). Scoring maximally observed toxicities across all cycles, we observed 28% grade 3 and 15% grade 4 hematotoxicities as main toxicity. Thirteen percent grade 3 infections were observed. One case of fatal herpes encephalitis was observed and occurred about one year after initiation of therapy. Two deaths were reported as not therapy related (malignant melanoma, one in the screening phase). Forty-one serious adverse events were reported, among which 10 led to a drop-out from the study. We present here a cohort of CLL patients in a multi-center setting receiving 3×FCR followed by 3×FR. We found excellent responses to initial treatment with close to 100% complete responses after 6 cycles of therapy. However, we also note an almost 25% drop-out rate, a not insignificant number of SAEs and a number of patients in CR that display long-lasting hematotoxic effects after the end of this treatment. This happened despite a de-escalation from the original FCR regimen, potentially indicating that such a dose reduction in late therapy may prevent additional toxicities without compromising efficacy. Still the efficacy of the induction regimen seems to generate a good starting point for the maintenance phase. Preliminary MRD analyses during the maintenance phase will be presented.