Additional chromosomal abnormalities in Philadelphia-positive clone: adverse prognostic influence on frontline imatinib therapy: a GIMEMA Working Party on CML analysis

Simona Luatti, Fausto Castagnetti, Giulia Marzocchi, Carmen Baldazzi, Gabriele Gugliotta, Ilaria Iacobucci, Giorgina Specchia, Lucia Zanatta, Giovanna Rege-Cambrin, Marco Mancini, Elisabetta Abruzzese, Alfonso Zaccaria, Maria Grazia Grimoldi, Alessandro Gozzetti, Gaia Ameli, Maria Adele Capucci, Giandomenico Palka, Paolo Bernasconi, Francesca Palandri, Fabrizio Pane, Giuseppe Saglio, Giovanni Martinelli, Gianantonio Rosti, Michele Baccarani, Nicoletta Testoni, Gruppo Italiano Malattie Ematologiche dell'Adulto (GIMEMA) Working Party on CML, Simona Luatti, Fausto Castagnetti, Giulia Marzocchi, Carmen Baldazzi, Gabriele Gugliotta, Ilaria Iacobucci, Giorgina Specchia, Lucia Zanatta, Giovanna Rege-Cambrin, Marco Mancini, Elisabetta Abruzzese, Alfonso Zaccaria, Maria Grazia Grimoldi, Alessandro Gozzetti, Gaia Ameli, Maria Adele Capucci, Giandomenico Palka, Paolo Bernasconi, Francesca Palandri, Fabrizio Pane, Giuseppe Saglio, Giovanni Martinelli, Gianantonio Rosti, Michele Baccarani, Nicoletta Testoni, Gruppo Italiano Malattie Ematologiche dell'Adulto (GIMEMA) Working Party on CML

Abstract

Additional chromosomal abnormalities (ACAs) in Philadelphia-positive cells have been reported in ∼ 5% of patients with newly diagnosed chronic myeloid leukemia (CML) in chronic phase (CP). Few studies addressing the prognostic significance of baseline ACAs in patients treated with imatinib have been published previously. The European LeukemiaNet recommendations suggest that the presence of ACAs at diagnosis is a "warning" for patients in early CP, but there is not much information about their outcome after therapy with tyrosine kinase inhibitors. To investigate the role of ACAs in early CP CML patients treated with imatinib mesylate, we performed an analysis in a large series of 559 patients enrolled in 3 prospective trials of the Gruppo Italiano Malattie Ematologiche dell'Adulto Working Party on CML: 378 patients were evaluable and ACAs occurred in 21 patients (5.6%). The overall cytogenetic and molecular response rates were significantly lower and the time to response was significantly longer in patients with ACAs. The long-term outcome of patients with ACAs was inferior, but the differences were not significant. The prognostic significance of each specific cytogenetic abnormality was not assessable. Therefore, we confirm that ACAs constitute an adverse prognostic factor in CML patients treated with imatinib as frontline therapy.

Trial registration: ClinicalTrials.gov NCT00510926 NCT00514488.

Source: PubMed

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