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Blood, 15 October 2007, Vol. 110, No. 8, pp. 2991-2995.
Prepublished online as a Blood First Edition Paper on July 11, 2007; DOI 10.1182/blood-2007-01-070045.
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Submitted January 30, 2007
Accepted June 16, 2007
Chromosomal abnormalities in Philadelphia chromosome-negative metaphases appearing during imatinib mesylate therapy in patients with newly diagnosed chronic myeloid leukemia in chronic phase
Elias Jabbour, Hagop M Kantarjian, Lynne Abruzzo, Susan O'Brien, Guillermo Garcia-Manero, Srdan Verstovsek, Jianqin Shan, Mary Beth Rios, and Jorge Cortes*
Dept of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, United States
* Corresponding author; email: jcortes{at}mdanderson.org.
The development of chromosomal abnormalities (CA) in the Philadelphia chromosome (Ph)-negative metaphases during imatinib (IM) therapy in patients with newly diagnosed CML has been reported only anecdotally. We assessed the frequency and significance of this phenomenon among 258 patients with newly diagnosed CML in chronic phase receiving IM. After a median follow-up of 37 months, 21 (9%) patients developed 23 CA in Ph-negative cells; excluding -Y, this incidence was 5%. Sixteen (70%) of all CA were observed in  2 metaphases. The median time from start of IM to the appearance of CA was 18 months. The most common CA was -Y and +8 in nine and three patients, respectively. CA were less frequent in young patients (p=0.02) and those treated with high-dose IM (p=0.03). In all but three, CA were transient and disappeared after a median of 5 months. One patient developed acute myeloid leukemia (associated with -7). At last follow-up, three patients died from transplantation-related complications, myocardial infarction, and progressive disease, respectively, and two lost cytogenetic response. CA occur in Ph-negative cells in a small percentage of patients with newly diagnosed CML treated with IM. In rare instances, these could reflect the emergence of a new malignant clone. The patients here reported were treated in 3 different clinical trials for patients with newly diagnosed chronic myeloid leukemia in chronic phase, registered at http://clinicaltrials.gov (Study IDs: NCT00048672, NCT00038649, NCT00050531).
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