Discontinuation of tyrosine kinase inhibitors and new approaches to target leukemic stem cells: treatment-free remission as a new goal in chronic myeloid leukemia

Cancer Lett. 2014 May 28;347(1):22-8. doi: 10.1016/j.canlet.2014.01.033. Epub 2014 Feb 4.

Abstract

Only a small fraction of chronic phase chronic myeloid leukemia patients (CP-CML) achieves a very deep reduction of residual disease with imatinib. Second-generation tyrosine kinase inhibitors administered as front-line therapy for CP-CML have improved the rates and degree of deeper molecular responses. Owing to this improvement, new standardized definition of complete molecular remission has been provided, which allowed plan of prospective strategies to definitively discontinue therapy in the long-term. In this review, we report the results of several published discontinuation studies and critically discuss the new approaches and tools to monitor residual disease during treatment and new strategies to target leukemic stem cells to reach a potential "operational" cure and persistent long-term leukemia-free survival.

Keywords: Chronic myeloid leukemia; Discontinuation; Relapse.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Benzamides / pharmacology
  • Benzamides / therapeutic use
  • Female
  • Humans
  • Imatinib Mesylate
  • Interferon-alpha / administration & dosage
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
  • Male
  • Neoplastic Stem Cells / drug effects*
  • Piperazines / pharmacology
  • Piperazines / therapeutic use
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use*
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Pyrimidines / pharmacology
  • Pyrimidines / therapeutic use
  • Remission Induction*

Substances

  • Antineoplastic Agents
  • Benzamides
  • Interferon-alpha
  • Piperazines
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Imatinib Mesylate
  • Protein-Tyrosine Kinases