1. ¹Cytogenetic and Clinical Departments, Hôpital André Mignot, Versailles, France
2. ²Cytogenetic and Clinical Departments, Hôpital Avicenne, Bobigny, France
3. ³Cytogenetic and Clinical Departments, Hôpital St-Louis, Paris, France
4. ⁴Cytogenetic and Clinical Departments, Hôpital Henri Mondor, Créteil, France
5. ⁵Cytogenetic and Clinical Departments, Hôpital Edouard Herriot, Lyon, France
6. ⁶Cytogenetic and Clinical Departments, Hôpital de Hautepierre, Strasbourg, France
7. ⁷Cytogenetic and Clinical Departments, Institut Paoli-Calmettes, Marseille, France
8. ⁸Cytogenetic and Clinical Departments, Cerba, Cergy-Pontoise, France
9. ⁹Cytogenetic and Clinical Departments, Hôpital Pontchaillou, Rennes, France
10. ¹⁰Cytogenetic and Clinical Departments, Hôpital Purpan, Toulouse, France
11. ¹¹Cytogenetic and Clinical Departments, Hôpital Hôtel-Dieu, Nantes, France
12. ¹²Cytogenetic and Clinical Departments, Hôpital St-Antoine, Paris, France
13. ¹³Cytogenetic and Clinical Departments, Hôpital Kremlin-Bicêtre, Kremlin-Bicêtre, France
14. ¹⁴Cytogenetic and Clinical Departments, Hôpital Pitié-Salpétrière, Paris, France
15. ¹⁵Cytogenetic and Clinical Departments, Hôpital du Bocage, Dijon, France
16. ¹⁶Cytogenetic and Clinical Departments, Hôpital Hôtel-Dieu, Paris, France
17. ¹⁷Cytogenetic and Clinical Departments, Hôpital Necker, Paris, France

Correspondence: Dr C Terre, Laboratoire de cytogénétique, Hôpital A.Mignot, 177, rue de Versailles, Le Chesnay 78 150, France. Fax: +1 33 1 39 63 80 38; E-mail: cterre@ch-versailles.fr

Received 24 November 2003; Accepted 19 April 2004; Published online 10 June 2004.

Abstract

Imatinib mesylate (Gleevec^®), an inhibitor of the BCR-ABL tyrosine kinase, was introduced recently into the therapy of chronic myeloid leukemia (CML). Several cases of emergence of clonal chromosomal abnormalities after therapy with imatinib have been reported, but their incidence, etiology and prognosis remain to be clarified. We report here a large series of 34 CML patients treated with imatinib who developed Philadelphia (Ph)-negative clones. Among 1001 patients with Ph-positive CML treated with imatinib, 34 (3.4%) developed clonal chromosomal abnormalities in Ph-negative cells. Three patients were treated with imatinib up-front. The most common cytogenetic abnormalities were trisomy 8 and monosomy 7 in twelve and seven patients, respectively. In 15 patients, fluorescent in situ hybridization with specific probes was performed in materials archived before the initiation of imatinib. The Ph-negative clone was related to previous therapy in three patients, and represented a minor pre-existing clone that expanded after the eradication of Ph-positive cells with imatinib in two others. However, in 11 patients, the new clonal chromosomal abnormalities were not detected and imatinib may have had a direct effect. No myelodysplasia was found in our cohort. With a median follow-up of 24 months, one patient showed CML acceleration and two relapsed.