Oct 14, 2009 - The Beatson West of Scotland Cancer Centre and Section of Experimental Haematology, Faculty of Medicine, University of. Glasgow, Glasgow ...
Published Ahead of Print on October 14, 2009, as doi:10.3324/haematol.2009.012781. Copyright 2009 Ferrata Storti Foundation.
Early Release Paper
Early prediction of success or failure using second generation tyrosine kinase inhibitors for chronic myeloid leukemia
Haematologica 2009 [Epub ahead of print]
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doi:10.3324/haematol.2009.012781
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by Dragana Milojkovic, Emma Nicholson, Jane Apperley, Tessa Holyoake, Pat Shepherd, Mark Drummond, Richard Szydlo, Marco Bua, Letizia Foroni, Alistair Reid, Jamshid Khorashad, Hugues de Lavallade, Katie Rezvani, Christos Paliompeis, John Goldman, and David Marin
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Original Article
Early prediction of success or failure using second generation tyrosine kinase inhibitors for chronic myeloid leukemia Dragana Milojkovic,1 Emma Nicholson,2 Jane F Apperley,1 Tessa L Holyoake,2 Pat Shepherd,3 Mark W Drummond,2 Richard Szydlo,1 Marco Bua,1 Letizia Foroni,1 Alistair Reid,1 Jamshid S. Khorashad,1 Hugues de Lavallade,1 Katie Rezvani,1 Christos Paliompeis,1 John M Goldman,1 and David Marin1 1 Department of Haematology, Hammersmith Hospitals Trust, Imperial College London, London, UK; 2Department of Haematology, The Beatson West of Scotland Cancer Centre and Section of Experimental Haematology, Faculty of Medicine, University of Glasgow, Glasgow, UK, and 3Department of Haematology, Western General Hospital, Edinburgh, UK
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ABSTRACT
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Background Second generation tyrosine kinase inhibitors (2G-TKI) induce cytogenetic responses in approximately 50% of chronic myeloid leukemia (CML) chronic phase who fail imatinib. However, it has not yet been established which of the patients that fail imatinib are predicted to benefit from 2G-TKI therapy.
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Design and Methods We analyzed a cohort of 80 CML patients resistant to imatinib who were treated with dasatinib or nilotinib while still in first chronic phase and devised a scoring system to predict the probability of achieving complete cytogenetic response (CCyR) to second generation tyrosine kinase inhibitors (2G-TKI).
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Results The system was based on three factors, namely cytogenetic response to imatinib, Sokal score and recurrent neutropenia on imatinib. We validated the score with an independent sample of 28 Scottish patients. We also studied the relationship between cytogenetic responses at 3, 6 and 12 months and subsequent outcome. We classified the 80 patients into 3 categories, good risk (n=24), intermediate risk (n=27) and poor risk (n=29) with 2.5 year cumulative incidences of CCyR of 100%, 52.2% and 13.8% respectively (p
