GIMEMA Working Party on CML. Front-line treatment of Philadelphia positive chronic myeloid leukemia with imatinib and interferon-alpha: 5-year outcome

Department of Hematology and Oncology "L. and A. Seràgnoli", St. Orsola-Malpighi University Hospital, via Massarenti 9, 40138 Bologna, Italy. .
Haematologica (Impact Factor: 5.81). 06/2008; 93(5):770-4. DOI: 10.3324/haematol.12265
Source: PubMed


In 2004, we reported the short-term results of a multicentric, phase 2 study of imatinib 400 mg daily and pegylated interferon-alpha in the treatment of 76 early chronic phase Philadelphia-positive chronic myeloid leukemia patients. In this report, we update the results with an observation time of five years. After two years of treatment, all but 10 patients (13%) had discontinued pegylated interferon-alpha. The complete cytogenetic response rate at five years was 87%, and 94% of complete cytogenetic responders maintained the complete cytogenetic response after five years. All but one complete cytogenetic response also achieved a major molecular response. These data confirm the excellent response to imatinib front-line and the stability of the complete cytogenetic response. Any possible additional benefit of the combination with interferon-alpha remains uncertain, due to low patient compliance.

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Available from: Massimo Breccia, Jun 11, 2014
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    • "doi:10.1016/j.canlet.2008.05.024 therapy for CML, producing an elevated rate of molecular response and event-free survival [5] [6] [7]. Possible additional benefits of the combination of imatinib with IFN-a have been described [8]. PU.1 is a transcription factor of the Ets family which is essential for myeloid and lymphoid cell development (for recent reviews see [9] [10] [11] [12]). "
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    ABSTRACT: The PU.1 transcription factor is a crucial regulator of hematopoiesis which expression is altered in various leukemic processes. Our previous work in chronic myeloid leukemia (CML) cells demonstrated that interferon-alpha upregulated PU.1 expression. Here we show that expression of PU.1 is severely impaired in patients with CML at diagnosis. However, the PU.1 suppression is abrogated in patients in remission, after interferon-alpha or imatinib treatment. These effects are not found in patients with other myeloproliferative diseases such as polycythemia vera or essential thrombocythemia. PU.1 could, therefore, be used as an additional marker of the response to the treatment of the CML.
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