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Clinical and experimental efficacy of gemtuzumab ozogamicin in core binding factor acute myeloid leukemia

Michele Gottardi, Federico Mosna, Sergio De Angeli, Cristina Papayannidis, Anna Candoni, Marino Clavio, Cristina Tecchio, Andrea Piccin, Marta Campo dell’Orto, Fabio Benedetti, Giovanni Martinelli, Filippo Gherlinzoni
  • Federico Mosna
    Department of Hematology, General Hospital, Treviso, Italy
  • Sergio De Angeli
    Laboratory of Cell Cryopreservation, General Hospital, Treviso, Italy
  • Cristina Papayannidis
    Department of Hematology, Institute “L.A. Seragnoli,” University of Bologna, Italy
  • Anna Candoni
    Department of Hematology, University of Udine, Italy
  • Marino Clavio
    Department of Hematology, University of Genoa, Italy
  • Cristina Tecchio
    Department of Hematology, University of Verona, Italy
  • Andrea Piccin
    Department of Hematology, General Hospital, Bolzano, Italy
  • Marta Campo dell’Orto
    Department of Pathology, General Hospital, Treviso, Italy
  • Fabio Benedetti
    Department of Hematology, University of Verona, Italy
  • Giovanni Martinelli
    Department of Hematology, Institute “L.A. Seragnoli,” University of Bologna, Italy
  • Filippo Gherlinzoni
    Department of Hematology, General Hospital, Treviso, Italy

Abstract

Leukemia-initiating cells of core binding factor (CBF) acute myeloid leukemia (AML) likely derive from early committed hematopoietic precursors expressing CD33. As such, targeting CD33 could ameliorate the chance of cure of CBF AML patients. We compared 12 CBF AML patients treated with Fludarabine, Cytarabine, Idarubicin and Gemtuzumab Ozogamicin (FLAI-GO regimen) with 25 CBF AML patients treated with the same schedule, but without GO. With the limit of small numbers, we observed a consistent trend toward better overall survival, disease free survival and event free survival in the FLAI-GO group. We also demonstrated the ability of GO to induce the disappearance in vitro of the AML1-ETO molecular transcript in a polymerase chain reaction-positive graft without decreasing the clonogenic potential of CD34+/CD38- cells. This represent the proof of principle for using GO in a purging strategy before autologous stem cell transplantation. Therefore, our data argue in favor of the reinstitution of GO in the therapy of CBF AML.

Keywords

Core binding factor; acute myeloid leukemia; gemtuzumab ozogamicin; immunotherapy; autologous stem cell transplantation

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Submitted: 2017-01-04 16:01:26
Published: 2017-09-26 14:48:46
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Copyright (c) 2017 Michele Gottardi, Federico Mosna, Sergio De Angeli, Cristina Papayannidis, Anna Candoni, Marino Clavio, Cristina Tecchio, Andrea Piccin, Marta Campo dell’Orto, Fabio Benedetti, Giovanni Martinelli, Filippo Gherlinzoni

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