European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013

Michele Baccarani(IRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola), Michael Deininger(University of Utah), Gianantonio Rosti(IRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola), Andreas Hochhaus(Jena University Hospital), Simona Soverini(IRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola), Jane F. Apperley(Imperial College London), Francisco Cervantes(Universitat de Barcelona), Richard E. Clark(University of Liverpool), Jörge E. Cortes(The University of Texas MD Anderson Cancer Center), François Guilhot(Inserm), Henrik Hjorth‐Hansen(Norwegian University of Science and Technology), Timothy P. Hughes(South Australia Pathology), Hagop M. Kantarjian(The University of Texas MD Anderson Cancer Center), Dong‐Wook Kim(The Catholic University of Korea Seoul St. Mary's Hospital), Richard A. Larson(University of Chicago), Jeffrey H. Lipton(University of Toronto), François-Xavier Mahon(Université de Bordeaux), Giovanni Martinelli(IRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola), Jiřı́ Mayer(Central European Institute of Technology), Martin Müller(Heidelberg University), Dietger Niederwieser, Fabrizio Pane(Ceinge Biotecnologie Avanzate (Italy)), Jerald P. Radich(Fred Hutch Cancer Center), Philippe Rousselot(Université de Versailles Saint-Quentin-en-Yvelines), Giuseppe Saglio(University of Turin), Susanne Saußele(Heidelberg University), Charles A. Schiffer(Wayne State University), Richard T. Silver(Cornell University), Bengt Simonsson(Uppsala University Hospital), Juan-Luis Steegmann(Hospital Universitario de La Princesa), John M. Goldman(Imperial College London), Rüdiger Hehlmann(Heidelberg University)
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Abstract

Advances in chronic myeloid leukemia treatment, particularly regarding tyrosine kinase inhibitors, mandate regular updating of concepts and management. A European LeukemiaNet expert panel reviewed prior and new studies to update recommendations made in 2009. We recommend as initial treatment imatinib, nilotinib, or dasatinib. Response is assessed with standardized real quantitative polymerase chain reaction and/or cytogenetics at 3, 6, and 12 months. BCR-ABL1 transcript levels ≤10% at 3 months, <1% at 6 months, and ≤0.1% from 12 months onward define optimal response, whereas >10% at 6 months and >1% from 12 months onward define failure, mandating a change in treatment. Similarly, partial cytogenetic response (PCyR) at 3 months and complete cytogenetic response (CCyR) from 6 months onward define optimal response, whereas no CyR (Philadelphia chromosome-positive [Ph+] >95%) at 3 months, less than PCyR at 6 months, and less than CCyR from 12 months onward define failure. Between optimal and failure, there is an intermediate warning zone requiring more frequent monitoring. Similar definitions are provided for response to second-line therapy. Specific recommendations are made for patients in the accelerated and blastic phases, and for allogeneic stem cell transplantation. Optimal responders should continue therapy indefinitely, with careful surveillance, or they can be enrolled in controlled studies of treatment discontinuation once a deeper molecular response is achieved.


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