Richter's syndrome – update on biology and management

Abstract

Introduction: Richter's syndrome (RS) refers to a histological transformation of chronic lymphocytic leukemia (CLL) into an aggressive lymphoma, most commonly diffuse large B-cell lymphoma (DLBCL) and rarely Hodgkin's lymphoma. Patients with RS can present with rapidly enlarging lymph nodes, worsening ‘B’ symptoms, progressive organomegaly and elevated serum lactate dehydrogenase, erythrocyte sedimentation rate and β₂-microglobulin levels. Recently, it was demonstrated that RS has molecular and cytogenetic characteristics distinct from de novo DLBCL and untransformed CLL. Some of the predisposing factors for RS include use of prior multiple chemotherapies for CLL, the presence of CDKN2A, TP53 mutations, NOTCH1 mutations, c-MYC abnormalities, unmutated immunoglobulin heavy chain, non-del13q cytogenetics, CD38 gene polymorphisms, stereotypy of subset 8 of B-cell receptor (BCR) and VH 4 – 39 gene usage. Patients with RS have a poor prognosis (median survival 1 – 2 years). These patients achieve short lasting responses to chemoimmunotherapy (rituximab combined with chemotherapy). Stem-cell transplantation is beneficial for patients who achieve remission after first therapy. Further understanding of the molecular pathogenesis of RS may identify newer therapeutic targets.

Areas covered: This article focuses on the treatment options for patients with RS. A thorough literature search has been undertaken and only the most relevant references are included.

Expert opinion: Clear understanding of pathogenesis of RS and effective treatment of RS remains a challenge. Since there is no standard-of-care treatment for patients with RS, all the patients should preferentially enroll into clinical trials.

Keywords::

• chemo-immunotherapy
• chronic lymphocytic leukemia
• lymphoma
• Richter's syndrome
• Richter's transformation
• rituximab

Declaration of interest

The authors have no conflict of interest and have received no payment in preparation of this manuscript.

Notes

This box summarizes key points contained in the article.