Role of Tyrosine Kinase Inhibitors in the Management of Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia

  • Michael S. Mathisen
  • Susan O’Brien
  • Deborah Thomas
  • Jorge Cortes
  • Hagop Kantarjian
  • Farhad Ravandi
Article

Abstract

The Philadelphia chromosome is the most common cytogenetic abnormality found in adult patients diagnosed with acute lymphoblastic leukemia. The result of this abnormality is the BCR-ABL protein, a constitutively active kinase involved in cell signaling and survival. When managed with multiagent chemotherapy regimens alone, patients have traditionally had an inferior outcome in terms of remission duration and overall survival when compared with patients who are Philadelphia chromosome–negative. Small-molecule tyrosine kinase inhibitors, such as imatinib and dasatinib, directly inhibit the BCR-ABL kinase, offering a targeted approach as a therapeutic option. As a result of several clinical trials with adequate follow-up, imatinib combined with chemotherapy represents the current standard of care for patients with newly diagnosed disease. Allogeneic stem cell transplantation has previously been the only modality to offer the potential for a cure, and it still should be considered for all patients deemed able to tolerate such an intervention. Second-generation tyrosine kinase inhibitors, such as dasatinib, may further improve the outcome in these patients. The role of molecular monitoring and the use of tyrosine kinase inhibitors after stem cell transplantation are areas of active investigation, and the results of ongoing trials will help to clarify the optimal management of these patients.

Keywords

Philadelphia chromosome Acute lymphoblastic leukemia ALL Ph+ ALL Therapy Treatment Tyrosine kinase inhibitors Imatinib Dasatinib Complications Stem cell transplantation Chemotherapy 

Notes

Disclosure

Conflicts of Interest: M. Mathisen: none; S. O’Brien: none; D. Thomas: Consulting fees from Pfizer and payment for speaking from Novartis and Bristol-Myers-Squibb; J. Cortes: Consulting fees from Novartis, Bristol-Myers-Squibb, Ariad, Chemgenex, and Pfizer; H. Kantarjian: Grants or consulting fees from Novartis, Bristol-Myers-Squibb, and Pfizer; F. Ravandi: Research grants and consulting fees from Novartis and Bristol-Myers-Squibb.

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Michael S. Mathisen
    • 1
  • Susan O’Brien
    • 1
  • Deborah Thomas
    • 1
  • Jorge Cortes
    • 1
  • Hagop Kantarjian
    • 1
  • Farhad Ravandi
    • 1
  1. 1.Department of Leukemia, Unit 428The University of Texas – M D Anderson Cancer CenterHoustonUSA

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