How best to manage patients with chronic lymphocytic leuekmia with 17p deletion and/or TP53 mutation?

Leuk Lymphoma. 2015 Mar;56(3):587-93. doi: 10.3109/10428194.2015.1011641. Epub 2015 Feb 17.

Abstract

Patients with chronic lymphocytic leukemia (CLL) carrying deletion of 17p (17p-) or mutations of TP53 have a uniquely poor prognosis related to increased propensities to progress to symptomatic disease, poor responses to chemo(immuno)therapy and high rates of Richter transformation. Both traditional fludarabine, cyclophosphamide and rituximab (FCR)-based chemoimmunotherapy and alemtuzumab-based regimens are inadequate in controlling 17p- CLL durably, and allogeneic stem cell transplant holds the only prospect for long-term survival. Recent advances in targeted therapies have resulted in novel agents such as B-cell receptor pathway and BCL2 antagonists yielding high response rates in 17p- CLL, but these patients continue to relapse at an increased rate when compared to patients without 17p-. In this review, we discuss the current evidence base for making therapeutic decisions in this difficult disease.

Keywords: 17p; Fludarabine; TP53; alemtuzumab; fluorescence in situ hybridization.

Publication types

  • Review

MeSH terms

  • Chromosome Deletion*
  • Chromosomes, Human, Pair 17
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy*
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics*
  • Mutation*
  • Smith-Magenis Syndrome*
  • Tumor Suppressor Protein p53 / genetics*

Substances

  • TP53 protein, human
  • Tumor Suppressor Protein p53

Supplementary concepts

  • Chromosome 17 deletion