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.
    Cancer letters 11/2008; 270(2):328-36. DOI:10.1016/j.canlet.2008.05.024 · 5.62 Impact Factor
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    ABSTRACT: Chronic myeloid leukemia (CML) is a malignant disorder in which the immune system has been described as important for the graft versus leukemia effect after stem cell transplantation. With imatinib at a dose of 400 mg, the current treatment of chronic phase CML does not eradicate the leukemic stem cells. Most of the patients in molecular response remain with leukemic stem cells responsible for relapse if the treatment is discontinued. Recent studies have suggested that interferon may be useful in order to eradicate the quiescent stem cells. The second-generation inhibitors like dasatinib, nilotinib or bosutinib do not eliminate either the stem cells; this leads to the conclusion that either there is a persistence of leukemic stem cells or there is a general phenomenon with TKI. The mechanisms of resistance include high activities of Bcr-Abl and CrkLPhospho, a weak expression ofOCT-1 and high levels of proteins ABCB1 and ABCG2. However, two scientific groups have recently demonstrated the value of interferon alpha as a molecule that may stimulate the turnover and proliferation of hematopoietic stem cells in vivo. This new approach to understanding the mechanism of action of interferon alpha on hematopoietic stem cells supports the use of combination therapy of TKI plus interferon.
    Oncologie 10/2012; 14(10-11). DOI:10.1007/s10269-012-2222-1 · 0.06 Impact Factor
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    ABSTRACT: Imatinib mesylate is the first line treatment for chronic myeloid leukemia. The advent of imatinib increased survival significantly in patients in an advanced phase of the disease. However, few long-term data on the outcome of these patients based on large, prospective and controlled trials are available. A phase 2 multicenter trial of the use of imatinib 600 mg/daily in patients with accelerated phase chronic myeloid leukemia was sponsored and promoted by the Italian Cooperative Study Group on Chronic Myeloid Leukemia in 2001. One hundred and eleven patients were enrolled; the median follow-up of the 41 living patients is 82 months (range, 73-87). One hundred and seven patients (96%) returned to chronic phase and 79 patients (71%) achieved a complete hematologic response. Cumulative best rates of major cytogenetic response and complete cytogenetic response were 30% and 21%, respectively. All responses were maintained for a minimum of 4 weeks. At last follow-up, four patients were alive in complete remission after allogeneic transplant, 16 patients (14%) had switched to a second generation tyrosine kinase inhibitor and 21 patients (19%) were alive on imatinib therapy. No late toxicities were observed. Progression-free survival and event-free survival rates were 36.5% and 15%, respectively, at 7 years. The median survival time was 37 months, and was significantly associated with the achievement of a complete hematologic response or a complete cytogenetic response. Imatinib may induce durable responses, associated with prolonged survival, in patients with accelerated phase chronic myeloid leukemia.
    Haematologica 02/2009; 94(2):205-12. DOI:10.3324/haematol.13529 · 5.81 Impact Factor
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