Current and future management of Ph/BCR-ABL positive ALL

Expert Rev Anticancer Ther. 2014 Jun;14(6):723-40. doi: 10.1586/14737140.2014.895669. Epub 2014 Mar 10.

Abstract

Following the introduction of targeted therapy with tyrosine kinase inhibitors (TKI) at the beginning of the past decade, the outcome of patients with Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph+ ALL) has dramatically improved. Presently, the use of refined programs with first/second generation TKI's and chemotherapy together with allogeneic stem cell transplantation allow up to 50% of all patients to be cured. Further progress is expected with the new TKI ponatinib, overcoming resistance caused by T315I point mutation, other targeted therapies, autologous transplantation in molecularly negative patients, therapeutic monoclonal antibodies like inotuzumab ozogamicin and blinatumomab, and chimeric antigen receptor-modified T cells. Ph+ ALL could become curable in the near future even without allogeneic stem cell transplantation, minimizing the risk of therapy-related death and improving greatly the quality of patients' life.

Keywords: BCR-ABL rearrangement; MRD monitoring; Philadelphia chromosome; acute lymphoblastic leukemia; experimental therapy; prognosis; therapy.

Publication types

  • Review

MeSH terms

  • Age of Onset
  • Antibodies, Monoclonal / therapeutic use
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Benzamides / therapeutic use
  • Chromosome Aberrations
  • Clinical Trials as Topic
  • Cytogenetic Analysis
  • Disease Management
  • Drug Resistance, Neoplasm
  • Drugs, Investigational / therapeutic use
  • Forecasting
  • Fusion Proteins, bcr-abl / antagonists & inhibitors
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Imatinib Mesylate
  • Immunophenotyping
  • Incidence
  • Molecular Targeted Therapy
  • Piperazines / therapeutic use
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / epidemiology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy
  • Protein Kinase Inhibitors / classification
  • Protein Kinase Inhibitors / therapeutic use
  • Pyrimidines / therapeutic use
  • Recurrence
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Benzamides
  • Drugs, Investigational
  • Piperazines
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Imatinib Mesylate
  • Fusion Proteins, bcr-abl