Platinum and high-dose cytarabine-based regimens are efficient in ultra high/high-risk chronic lymphocytic leukemia and Richter's syndrome: results of a French retrospective multicenter study

Ultra high-risk chronic lymphocytic leukemia (CLL) and Richter's syndrome (RS) usually display a poor prognosis. Platinum and cytarabine-based regimens have not been evaluated in large cohorts of patients with CLL or RS. This retrospective study was aimed to assess the efficacy of these regimens in 75 patients with relapsed/refractory (R/R) CLL or RS. Forty-seven patients had R/R CLL (including 36 ultra high-risk CLL) and 28 had RS. Median age was 62years (range, 18-79years). Median number of previous therapies was 3 (range, 1-7), including fludarabine-based regimens (75%) and alemtuzumab (32%), and 61% of patients were refractory to their last treatment. Deletions of chromosomes 17p and 11q were found in 40% and 39% of cases, respectively. The overall response rates were 60% with 24% complete response (CR) in CLL, and 43% with 25% CR in RS. The median progression-free survival and overall survival were 11 and 14.6months, respectively. Fludarabine refractoriness and 17p deletion were not associated with a poorer outcome. The only factors predicting shorter survival were performance status 2 (P=0.04) and albumin level <3.5g/dL (P=0.0004). Toxicities were mainly myelosuppression and infectious complications. Platinum and high-dose cytarabine-based regimens provide high response rates in high-risk CLL and in RS. However, these results will be challenged by the new arriving agents at least in non-transformed CLL.