Deletions of the Derivative Chromosome 9 Do Not Influence the Response and the Outcome of Chronic Myeloid Leukemia in Early Chronic Phase Treated With Imatinib Mesylate: GIMEMA CML Working Party Analysis

• Published in: Journal of clinical oncology Vol. 28; no. 16; pp. 2748 - 2754
• Main Authors: Castagnetti, Fausto, Testoni, Nicoletta, Luatti, Simona, Marzocchi, Giulia, Mancini, Marco, Kerim, Simonetta, Giugliano, Emilia, Albano, Francesco, Cuneo, Antonio, Abruzzese, Elisabetta, Martino, Bruno, Palandri, Francesca, Amabile, Marilina, Iacobucci, Ilaria, Alimena, Giuliana, Pane, Fabrizio, Martinelli, Giovanni, Saglio, Giuseppe, Baccarani, Michele, Rosti, Gianantonio
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Society of Clinical Oncology 01.06.2010
• Subjects: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Benzamides; Biological and medical sciences; Chromosomes, Human, Pair 9 - genetics; Cytogenetic Analysis; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Gene Deletion; Hematologic and hematopoietic diseases; Humans; Imatinib Mesylate; In Situ Hybridization, Fluorescence; Italy; Kaplan-Meier Estimate; Leukemia, Myeloid, Chronic-Phase - drug therapy; Leukemia, Myeloid, Chronic-Phase - genetics; Leukemia, Myeloid, Chronic-Phase - mortality; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Logistic Models; Male; Maximum Tolerated Dose; Medical sciences; Middle Aged; Multivariate Analysis; Piperazines - administration & dosage; Piperazines - adverse effects; Probability; Prognosis; Prospective Studies; Pyrimidines - administration & dosage; Pyrimidines - adverse effects; Reference Values; Reverse Transcriptase Polymerase Chain Reaction; Risk Assessment; Severity of Illness Index; Statistics, Nonparametric; Survival Analysis; Treatment Outcome; Tumors; Young Adult; Italy; Antineoplastic agent; Imatinib; Prognosis; Enzyme; Tyrosine kinase inhibitor; Transferases; Early phase; Enzyme inhibitor; Chronic myelogenous leukemia; Malignant hemopathy; Myeloproliferative syndrome; Cancerology; Treatment; Chromosome 9; Deletion; Protein-tyrosine kinase; Cancer
• ISSN: 0732-183X; 1527-7755; 1527-7755
• DOI: 10.1200/JCO.2009.26.7963

Deletions of the derivative chromosome 9 [der(9)] have been associated with a poor prognosis in chronic myeloid leukemia (CML) across different treatment modalities. In the imatinib era, the prognostic impact of der(9) deletions has been evaluated mainly in patients with late chronic-phase (CP) CML, giving partially conflicting results. Few data are available in the early CP setting. For this reason, in 2006, the European LeukemiaNet recommendations still considered der(9) deletions as a candidate adverse prognostic factor and required a careful monitoring of the patient. To investigate the prognostic value of der(9) deletions in early CP CML, we performed an analysis of three prospective imatinib trials of the Italian Group for Hematological Malignancies of the Adult (GIMEMA) CML Working Party. A fluorescent in situ hybridization (FISH) analysis of bone marrow cells was performed at diagnosis; der(9) deletions were detected in 60 (12%) of 521 evaluable patients. At 60 months, the cumulative incidence of complete cytogenetic response and major molecular response-and the probability of event-free survival, failure-free survival, progression-free survival, and overall survival-in patients with and without deletions were not statistically different. Our data strongly support the notion that, when investigated by FISH, der(9) deletions are not a poor prognostic factor in patients with early CP CML treated with imatinib.