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      Dasatinib in high-risk core binding factor acute myeloid leukemia in first complete remission: a French Acute Myeloid Leukemia Intergroup trial.

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          Abstract

          Core-binding factor acute myeloid leukemia is a favorable acute myeloid leukemia subset cytogenetically defined by t(8;21) or inv(16)/t(16;16) rearrangements, disrupting RUNX1 (previously CBFA/AML1) or CBFB transcription factor functions. The receptor tyrosine kinase KIT is expressed in the vast majority of these acute myeloid leukemias and frequent activating KIT gene mutations have been associated with a higher risk of relapse. This phase II study aimed to evaluate dasatinib as maintenance therapy in patients with core-binding factor acute myeloid leukemia in first hematologic complete remission, but at higher risk of relapse due to molecular disease persistence or recurrence. A total of 26 patients aged 18-60 years old previously included in the CBF-2006 trial were eligible to receive dasatinib 140 mg daily if they had a poor initial molecular response (n=18) or a molecular recurrence (n=8). The tolerance of dasatinib as maintenance therapy was satisfactory. The 2-year disease-free survival in this high-risk population of patients was 25.7%. All but one patient with molecular recurrence presented subsequent hematologic relapse. Patients with slow initial molecular response had a similar disease-free survival when treated with dasatinib (40.2% at 2 years) or without any maintenance (50.0% at 2 years). The disappearance of KIT gene mutations at relapse suggests that clonal devolution may in part explain the absence of efficacy observed with single-agent dasatinib in these patients (n. EudraCT: 2006-006555-12).

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          Author and article information

          Journal
          Haematologica
          Haematologica
          Ferrata Storti Foundation (Haematologica)
          1592-8721
          0390-6078
          Jun 2015
          : 100
          : 6
          Affiliations
          [1 ] Service d'Hématologie Adulte, Hôpital Saint-Louis, Paris EA-3518, Université Paris 7 nicolas.boissel@sls.aphp.fr.
          [2 ] Laboratoire d'hématologie, Centre de Biologie-Pathologie, CHRU de Lille Equipe 3 INSERM U837, JPARC Lille.
          [3 ] Service d'Hématologie, Hôpital Haut-Lévèque, Bordeaux.
          [4 ] Laboratoire Central d'Hématologie, CHU de Reims - Hôpital Robert Debré
          [5 ] Service d'Hématologie, CHU Purpan, Toulouse.
          [6 ] Service des Maladies du Sang, INSERM U892/CNRS 6299, CHU Angers.
          [7 ] Laboratoire d'Hématologie, CHU Purpan, Toulouse.
          [8 ] Service des Maladies du Sang, CHU de Lille.
          [9 ] Laboratoire d'Hématologie, CHU Angers.
          [10 ] Service d'Hématologie, Institut Paoli Calmettes, Marseille.
          [11 ] Service d'Hématologie, CHU Henri Mondor, Créteil.
          [12 ] Service d'Hématologie, CHU de Nantes.
          [13 ] Service d'Hématologie, Centre de Lutte Contre le Cancer, Rouen.
          [14 ] Service d'Hématologie, CHU Dupuytren, Limoges.
          [15 ] Service d'Hématologie Adulte, Hôpitaux de Brabois, Nancy.
          [16 ] Service d'Hématologie, CHU de Clermont Ferrand.
          [17 ] Service d'Hématologie, CHU de Reims - Hôpital Robert Debré
          [18 ] Service d'Hématologie, CHU de Poitiers.
          [19 ] Hématologie Clinique et Oncologie Médicale, CHU de Nîmes, France.
          [20 ] Service d'Hématologie Adulte, Hôpital Saint-Louis, Paris EA-3518, Université Paris 7.
          Article
          haematol.2014.114884
          10.3324/haematol.2014.114884
          4450623
          25715404
          98ac014f-6e2d-497a-baad-64fdbbc417b6
          History

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