Abstract

Summary Nearly all information about patients with chronic lymphocytic leukaemia ( CLL ) who develop diffuse large B ‐cell lymphoma [ R ichter syndrome ( RS )] is derived from retrospective case series or patients treated on clinical trials. We used the M ayo C linic CLL Database to identify patients with newly diagnosed CLL between J anuary 2000 and J uly 2011. Individuals who developed biopsy‐proven RS during follow‐up were identified. After a median follow‐up of 4 years, 37/1641 (2·3%) CLL patients developed RS . The rate of RS was approximately 0·5%/year. Risk of RS was associated with advanced R ai stage at diagnosis ( P < 0·001), high‐risk genetic abnormalitites on fluorescence in situ hybridization ( P < 0·0001), unmutated IGHV ( P = 0·003), and expression of ZAP 70 ( P = 0·02) and CD 38 ( P = 0·001). The rate of RS doubled in patients after treatment for CLL (1%/year). Stereotyped B‐cell receptors (odds‐ratio = 4·2; P = 0·01) but not IGHV 4‐39 family usage was associated with increased risk of RS . Treatment with combination of purine analogues and alkylating agents increased the risk of RS three‐fold (odds‐ratio = 3·26, P = 0·0003). Median survival after RS diagnosis was 2·1 years. The RS prognosis score stratified patients into three risk groups with median survivals of 0·5 years, 2·1 years and not reached. Both underlying characteristics of the CLL clone and subsequent CLL therapy influence the risk of RS . Survival after RS remains poor and new therapies are needed.