Report of 34 patients with clonal chromosomal abnormalities in Philadelphia-negative cells during imatinib treatment of Philadelphia-positive chronic myeloid leukemia

被引:124
作者
Terre, C
Eclache, V
Rousselot, P
Imbert, M
Charrin, C
Gervais, C
Mozziconacci, MJ
Maarek, O
Mossafa, H
Auger, N
Dastugue, N
Talmant, P
Van den Akker, J
Leonard, C
Khac, FN
Mugneret, F
Viguié, F
Lafage-Pochitaloff, M
Bastie, JN
Roux, GL
Nicolini, F
Maloisel, F
Vey, N
Laurent, G
Recher, C
Vigier, M
Yacouben, Y
Giraudier, S
Vernant, JP
Salles, B
Roussi, J
Castaigne, S
Leymarie, V
Flandrin, G
Lessard, M
机构
[1] Hop Andre Mignot, Dept Cytogenet, Versailles, France
[2] Hop Andre Mignot, Clin Dept, Versailles, France
[3] Hop Avicenne, Dept Cytogenet, Bobigny, France
[4] Hop Avicenne, Clin Dept, Bobigny, France
[5] Hop St Louis, Dept Cytogenet, Paris, France
[6] Hop St Louis, Clin Dept, Paris, France
[7] Hop Henri Mondor, Dept Cytogenet, Creteil, France
[8] Hop Henri Mondor, Clin Dept, Creteil, France
[9] Hop Edouard Herriot, Dept Cytogenet, Lyon, France
[10] Hop Edouard Herriot, Clin Dept, Lyon, France
[11] Hop Hautepierre, Dept Cytogenet, Strasbourg, France
[12] Hop Hautepierre, Clin Dept, Strasbourg, France
[13] Inst J Paoli I Calmettes, Dept Cytogenet, Marseille, France
[14] Inst J Paoli I Calmettes, Clin Dept, Marseille, France
[15] Cerba, Dept Cytogenet, Cergy Pontoise, France
[16] Cerba, Clin Dept, Cergy Pontoise, France
[17] Hop Pontchaillou, Dept Cytogenet, Rennes, France
[18] Hop Pontchaillou, Clin Dept, Rennes, France
[19] Hop Purpan, Dept Cytogenet, Toulouse, France
[20] Hop Purpan, Clin Dept, Toulouse, France
[21] Hop Hotel Dieu, Dept Cytogenet, Nantes, France
[22] Hop Hotel Dieu, Clin Dept, Nantes, France
[23] Hop St Antoine, Dept Cytogenet, Paris, France
[24] Hop St Antoine, Clin Dept, Paris, France
[25] Hop Kremlin Bicetre, Dept Cytogenet, Le Kremlin Bicetre, France
[26] Hop Kremlin Bicetre, Clin Dept, Le Kremlin Bicetre, France
[27] Hop La Pitie Salpetriere, Dept Cytogenet, Paris, France
[28] Hop La Pitie Salpetriere, Clin Dept, Paris, France
[29] Hop Bocage, Dept Cytogenet, Dijon, France
[30] Hop Bocage, Clin Dept, Dijon, France
[31] Hop Hotel Dieu, Dept Cytogenet, Paris, France
[32] Hop Hotel Dieu, Clin Dept, Paris, France
[33] Hop Necker Enfants Malad, Dept Cytogenet, Paris, France
[34] Hop Necker Enfants Malad, Clin Dept, Paris, France
关键词
CML; imatinib; clonal chromosomal abnormalities;
D O I
10.1038/sj.leu.2403399
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Imatinib mesylate (Gleevec(R)), 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.
引用
收藏
页码:1340 / 1346
页数:7
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