title: Diffuse large B-cell lymphoma (Richter syndrome) in patients with chronic lymphocytic leukaemia (CLL): a cohort study of newly diagnosed patients.
abstract: Nearly all information about patients with chronic lymphocytic leukaemia (CLL) who develop diffuse large B-cell lymphoma [Richter syndrome (RS)] is derived from retrospective case series or patients treated on clinical trials. We used the Mayo Clinic CLL Database to identify patients with newly diagnosed CLL between January 2000 and July 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 Rai 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 ZAP70 (P = 0·02) and CD38 (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 IGHV4-39 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.
authors.affiliation: Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Sameer A
authors.initials: SA
authors.lastname: Parikh
authors.forename: Kari G
authors.initials: KG
authors.lastname: Rabe
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Call
authors.forename: Clive S
authors.initials: CS
authors.lastname: Zent
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Habermann
authors.forename: Wei
authors.initials: W
authors.lastname: Ding
authors.forename: Jose F
authors.initials: JF
authors.lastname: Leis
authors.forename: Susan M
authors.initials: SM
authors.lastname: Schwager
authors.forename: Curtis A
authors.initials: CA
authors.lastname: Hanson
authors.forename: William R
authors.initials: WR
authors.lastname: Macon
authors.forename: Neil E
authors.initials: NE
authors.lastname: Kay
authors.forename: Susan L
authors.initials: SL
authors.lastname: Slager
authors.forename: Tait D
authors.initials: TD
authors.lastname: Shanafelt
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000150:complications* / Q000188:drug therapy / Q000601:surgery; D016403:Lymphoma, Large B-Cell, Diffuse / Q000150:complications* / Q000188:drug therapy / Q000601:surgery; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D033581:Stem Cell Transplantation / Q000379:methods; D015996:Survival Rate; D055815:Young Adult
keywords: Richter syndrome survival score; aggressive lymphoma; purine analogues; stem cell transplantation; transformation