Blood Journal
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Monitoring CML patients responding to treatment with tyrosine kinase inhibitors: review and recommendations for harmonizing current methodology for detecting BCR-ABL transcripts and kinase domain mutations and for expressing results

  1. Timothy Hughes,
  2. Michael Deininger,
  3. Andreas Hochhaus,
  4. Susan Branford,
  5. Jerald Radich,
  6. Jaspal Kaeda,
  7. Michele Baccarani,
  8. Jorge Cortes,
  9. Nicholas C. P. Cross,
  10. Brian J. Druker,
  11. Jean Gabert,
  12. David Grimwade,
  13. Rüdiger Hehlmann,
  14. Suzanne Kamel-Reid,
  15. Jeffrey H. Lipton,
  16. Janina Longtine,
  17. Giovanni Martinelli,
  18. Giuseppe Saglio,
  19. Simona Soverini,
  20. Wendy Stock, and
  21. John M. Goldman
  1. From the Institute of Medical and Veterinary Science, Adelaide, Australia; Department of Hematology/Medical Oncology, Oregon Health & Science University Cancer Institute, Portland, OR; Faculty of Clinical Medicine Mannheim, University of Heidelberg, Mannheim, Germany; Fred Hutchinson Cancer Research Center, Seattle, WA; Department of Haematology, Imperial College at Hammersmith Hospital, London, United Kingdom; Institute of Hematology and Medical Oncology “Seragnoli,” University of Bologna, Italy; Department of Leukemia, The University of Texas, M. D. Anderson Cancer Center, Houston, TX; National Genetics Reference Laboratory, University of Southampton, Salisbury, United Kingdom; Assistance Publique des Hopitaux de Marseille (APHM) and Equipe de Recherche Technologique (ERT), University de la Mediterranée, Marseille, France; Department of Medical and Molecular Genetics, King's College, London, United Kingdom; Department of Medical Oncology and Hematology, Princess Margaret Hospital, University of Toronto, Toronto, ON, Canada; Department of Pathology, Brigham and Women's Hospital, Boston, MA; Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy; Department of Medicine, University of Chicago, Chicago, IL; and the Hematology Branch, National Heart, Lung & Blood Institute, National Institutes of Health (NIH), Bethesda, MD.

Abstract

The introduction in 1998 of imatinib mesylate (IM) revolutionized management of patients with chronic myeloid leukemia (CML) and the second generation of tyrosine kinase inhibitors may prove superior to IM. Real-time quantitative polymerase chain reaction (RQ-PCR) provides an accurate measure of the total leukemiacell mass and the degree to which BCR-ABL transcripts are reduced by therapy correlates with progression-free survival. Because a rising level of BCR-ABL is an early indication of loss of response and thus the need to reassess therapeutic strategy, regular molecular monitoring of individual patients is clearly desirable. Here we summarize the results of a consensus meeting that took place at the National Institutes of Health (NIH) in Bethesda in October 2005. We make suggestions for (1) harmonizing the differing methodologies for measuring BCR-ABL transcripts in patients with CML undergoing treatment and using a conversion factor whereby individual laboratories can express BCR-ABL transcript levels on an internationally agreed scale; (2) using serial RQ-PCR results rather than bone marrow cytogenetics or fluorescence in situ hybridization (FISH) for the BCR-ABL gene to monitor individual patients responding to treatment; and (3) detecting and reporting Philadelphia (Ph) chromosome-positive subpopulations bearing BCR-ABL kinase domain mutations. We recognize that our recommendations are provisional and will require revision as new evidence emerges. (Blood. 2006;108:28-37)

  • Submitted January 10, 2006.
  • Accepted February 18, 2006.
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