Model-based decision rules reduce the risk of molecular relapse after cessation of tyrosine kinase inhibitor therapy in chronic myeloid leukemia

Blood. 2013 Jan 10;121(2):378-84. doi: 10.1182/blood-2012-07-441956. Epub 2012 Nov 21.


Molecular response to imatinib (IM) in chronic myeloid leukemia (CML) is associated with a biphasic but heterogeneous decline of BCR-ABL transcript levels. We analyzed this interindividual heterogeneity and provide a predictive mathematical model to prognosticate the long-term response and the individual risk of molecular relapse on treatment cessation. The parameters of the model were determined using 7-year follow-up data from a randomized clinical trial and validated by an independent dataset. Our model predicts that a subset of patients (14%) achieve complete leukemia eradication within less than 15 years and could therefore benefit from discontinuation of treatment. Furthermore, the model prognosticates that 31% of the patients will remain in deep molecular remission (MR(5.0)) after treatment cessation after a fixed period of 2 years in MR(5.0), whereas 69% are expected to relapse. As a major result, we propose a predictor that allows to assess the patient-specific risk of molecular relapse on treatment discontinuation and to identify patients for whom cessation of therapy would be an appropriate option. Application of the suggested rule for deciding about the time point of treatment cessation is predicted to result in a significant reduction in rate of molecular relapse.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / administration & dosage*
  • Benzamides
  • Fusion Proteins, bcr-abl / analysis
  • Fusion Proteins, bcr-abl / biosynthesis
  • Humans
  • Imatinib Mesylate
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Models, Theoretical*
  • Neoplasm Recurrence, Local / prevention & control*
  • Piperazines / administration & dosage
  • Polymerase Chain Reaction
  • Protein Kinase Inhibitors / administration & dosage
  • Pyrimidines / administration & dosage
  • Reverse Transcriptase Polymerase Chain Reaction
  • Risk Factors


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