Richter's syndrome: Biology and therapy

Karen W L Yee, Susan M. O'Brien, Francis J. Giles*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

18 Scopus citations

Abstract

Richter's syndrome, that is, transformation of chronic lymphocytic leukemia to a large cell or immunoblastic lymphoma, occurs in up to 10% of patients with chronic lymphocytic leukemia. The onset of Richter's syndrome is characterized by worsening systemic symptoms, rapid tumor growth, and/or extranodal involvement. Median survival with conventional chemotherapy is less than 6 months. Therapy with more recent therapeutic regimens, such as hyperCVXD (fractionated cyclophosphamide, vincristine, liposomal daunorubicin, and dexamethasone), augmented hyperCVXD, and yttrium-90 ibritumomab tiuxetan, has not produced major improvements in response rates or overall survival. Improvement in the outcome of patients with Richter's syndrome may be aided by a more comprehensive understanding of the pathogenesis of Richter's syndrome; therapy could then be targeted against specific abnormalities. Current data indicate that the transformation of chronic lymphocytic leukemia to a large-cell or immunoblastic lymphoma is associated with abnormalities in cell cycle regulation (e.g., loss of the cell cycle inhibitors p16INK4a and p27KIP1) and DNA repair (e.g., mutations and/or deletions of the p53, ATM, and p14ARF genes and epigenetic silencing of the MLH1 gene). However, the critical event leading to transformation is unclear. Given the poor prognosis of patients with Richter's syndrome, every effort should be made to enroll these patients into clinical trials evaluating novel agents with the appropriate correlative studies.

Original languageEnglish (US)
Pages (from-to)161-174
Number of pages14
JournalCancer Journal
Volume11
Issue number3
DOIs
StatePublished - May 1 2005

Keywords

  • Cell cycle
  • DNA repair
  • Epigenetic silencing
  • Novel targets
  • Richter's syndrome
  • Therapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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