Diffuse large B-cell lymphoma (Richter syndrome) in patients with chronic lymphocytic leukaemia (CLL): A cohort study of newly diagnosed patients

Sameer A Parikh, Kari G. Rabe, Timothy G. Call, Clive S. Zent, Thomas Matthew Habermann, Wei D Ding, Jose F. Leis, Susan M. Schwager, Curtis A. Hanson, William R. Macon, Neil Elliot Kay, Susan L Slager, Tait D. Shanafelt

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)774-782
Number of pages9
JournalBritish Journal of Haematology
Volume162
Issue number6
DOIs
StatePublished - Sep 2013

Fingerprint

Lymphoma, Large B-Cell, Diffuse
B-Cell Chronic Lymphocytic Leukemia
Cohort Studies
Survival
Odds Ratio
Alkylating Agents
Therapeutics
Fluorescence In Situ Hybridization
B-Lymphocytes
Clone Cells
Clinical Trials
Databases

Keywords

  • Aggressive lymphoma
  • Purine analogues
  • Richter syndrome survival score
  • Stem cell transplantation
  • Transformation

ASJC Scopus subject areas

  • Hematology

Cite this

Diffuse large B-cell lymphoma (Richter syndrome) in patients with chronic lymphocytic leukaemia (CLL) : A cohort study of newly diagnosed patients. / Parikh, Sameer A; Rabe, Kari G.; Call, Timothy G.; Zent, Clive S.; Habermann, Thomas Matthew; Ding, Wei D; Leis, Jose F.; Schwager, Susan M.; Hanson, Curtis A.; Macon, William R.; Kay, Neil Elliot; Slager, Susan L; Shanafelt, Tait D.

In: British Journal of Haematology, Vol. 162, No. 6, 09.2013, p. 774-782.

Research output: Contribution to journalArticle

Parikh, Sameer A ; Rabe, Kari G. ; Call, Timothy G. ; Zent, Clive S. ; Habermann, Thomas Matthew ; Ding, Wei D ; Leis, Jose F. ; Schwager, Susan M. ; Hanson, Curtis A. ; Macon, William R. ; Kay, Neil Elliot ; Slager, Susan L ; Shanafelt, Tait D. / Diffuse large B-cell lymphoma (Richter syndrome) in patients with chronic lymphocytic leukaemia (CLL) : A cohort study of newly diagnosed patients. In: British Journal of Haematology. 2013 ; Vol. 162, No. 6. pp. 774-782.
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