Blood Journal
Leading the way in experimental and clinical research in hematology

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

  1. Matthias Horn1,*,
  2. Ingmar Glauche2,
  3. Martin C. Müller3,
  4. Rüdiger Hehlmann3,
  5. Andreas Hochhaus4,
  6. Markus Loeffler1, and
  7. Ingo Roeder2
  1. 1 Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany;
  2. 2 Institute for Medical Informatics and Biometry, Faculty of Medicine Carl Gustav Carus, Dresden University of Technology, Dresden, Germany;
  3. 3 III. Medizinische Klinik, Medizinische Fakultaet Mannheim, University of Heidelberg, Mannheim, Germany;
  4. 4 Abt. Haematologie/Onkologie, Universitaetsklinikum Jena, Jena, Germany
  1. * Corresponding author; email: matthias.horn{at}imise.uni-leipzig.de

Abstract

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 inter-individual heterogeneity and provide a predictive mathematical model to prognosticate the long-term response and the individual risk of molecular relapse upon treatment cessation. The parameters of the model were determined using seven-year follow-up data from a randomized clinical trial and validated by an independent data set. 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 (MR5.0) following treatment cessation after a fixed period of two years in MR5.0, while 69% are expected to relapse. As a major result, we propose a predictor that allows to assess the patient-specific risk of molecular relapse upon 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.

  • Submitted July 6, 2012.
  • Accepted November 10, 2012.