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Intensive chemotherapy with mitoxantrone administered as a single injection in patients with high-risk acute myeloid leukemia: results of the EMA 2000 trial

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Abstract

Following a dose-escalation study performed to assess the maximally tolerated dose of high-dose mitoxantrone in a single injection combined with chemotherapy, a phase II trial (EMA 2000 regimen) was performed in patients with refractory or relapsed acute myelogenous leukemia (AML) between October 2000 and December 2003. Sixty-two patients entered the study and received mitoxantrone 45 mg/m2 on day 1 in combination with cytarabine and etoposide. Overall, 39 patients (63%) achieved complete remission (CR). Four patients died during remission induction, and 19 patients had resistant disease. Median time to granulocyte and platelet recovery was 34 and 39 days, respectively. The predominant non-hematologic toxicity was infection, with 53% severe infections. Thirty-three of the 39 remitters received subsequent treatment consisting of maintenance chemotherapy courses in 17 patients, allogeneic stem cell transplantation (SCT) in 7 patients, and autologous SCT in 9 patients. The median overall survival of the entire cohort was 8.1 months, with 18% at 2.5 years. EMA chemotherapy using a single injection of mitoxantrone is effective in the treatment of high-risk AML. CR proportion was significantly higher in patients with a first CR duration ≥6 months when compared with those from a control trial using standard-dose mitoxantrone (90 vs 70%, p=0.03).

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Authors and Affiliations

  1. Service d’Hématologie, Hôpital Edouard Herriot, 69437, Lyon cedex 03, France

    Xavier Thomas, Mohamed Elhamri, Youcef Chelghoum, Quoc-Hung Le, Emmanuelle Tavernier & Mauricette Michallet

  2. Service d’Hématologie, Hôpital Georges Clémenceau, Caen, France

    Oumedaly Reman

  3. Service d’Hématologie, Institut Gustave Roussy, Villejuif, France

    Philippe Arnaud

  4. Service d’Hématologie, Hôpital Saint-Louis, Paris, France

    Emmanuel Raffoux & Hervé Dombret

  5. Département de Biostatistiques, Centre Hospitalier Lyon-Sud, Pierre Bénite, France

    Quoc-Hung Le

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  1. Xavier Thomas
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Thomas, X., Elhamri, M., Chelghoum, Y. et al. Intensive chemotherapy with mitoxantrone administered as a single injection in patients with high-risk acute myeloid leukemia: results of the EMA 2000 trial. Ann Hematol 84, 376–382 (2005). https://doi.org/10.1007/s00277-005-1037-1

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