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
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,...
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| Published in | Journal of clinical oncology Vol. 28; no. 16; pp. 2748 - 2754 |
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| Main Authors | , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Alexandria, VA
American Society of Clinical Oncology
01.06.2010
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0732-183X 1527-7755 1527-7755 |
| DOI | 10.1200/JCO.2009.26.7963 |
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| Abstract | 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. |
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| AbstractList | 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.PURPOSEDeletions 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.PATIENTS AND METHODSTo 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.RESULTSA 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.CONCLUSIONOur 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. 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. |
| Author | Fabrizio Pane Francesca Palandri Francesco Albano Simona Luatti Elisabetta Abruzzese Giuseppe Saglio Marco Mancini Michele Baccarani Marilina Amabile Simonetta Kerim Fausto Castagnetti Giulia Marzocchi Giuliana Alimena Gianantonio Rosti Bruno Martino Emilia Giugliano Antonio Cuneo Nicoletta Testoni Ilaria Iacobucci Giovanni Martinelli |
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| Keywords | 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 |
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| Snippet | Deletions of the derivative chromosome 9 [der(9)] have been associated with a poor prognosis in chronic myeloid leukemia (CML) across different treatment... |
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| SubjectTerms | 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 |
| Title | 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 |
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