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Phase I Trial of FLAGM with High Doses of Cytosine Arabinoside for Relapsed, Refractory Acute Myeloid Leukemia: Study of the Japan Adult Leukemia Study Group (JALSG)

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Abstract

This study was designed to determine the optimal high dose for cytosine arabinoside (ara-C) in combination with fludarabine, granulocyte colony-stimulating factor, and mitoxantrone (FLAGM) in adult patients with relapsed or refractory acute myeloid leukemia. Nine patients were enrolled at increasing dosage levels of ara-C (8,12, and 16 g/m2 per dose level). Ara-C and fludarabine were administered once a day at level 1, once or twice a day at level 2, and twice a day at level 3. All patients had grade 4 hematologic toxicity.The most common adverse events were of grade 2 or less, with nausea and vomiting being the most common (6 events), followed by diarrhea (5 events), and rash (5 events). Of the 13 grade 3 nonhematologic toxicities reported, the 2 most common were febrile neutropenia (6 events) and disseminated intravascular coagulation (3 events). No early deaths were observed. FLAGM with high-dose ara-C was considered safe for patients, and the recommended dosage of ara-C in this study was 2 g/m2 every 12 hours for a total dose of 16 g/m2.

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Authors and Affiliations

  1. Leukemia Research Center, Saiseikai Maebashi Hospital, 564-1, Kamisindencho, Maebashi, 371-0821, Gunma, Japan

    Shuichi Miyawaki & Noriko Doki

  2. Divison of Hematology and Oncology University of Fukui Hospital, Fukui, Japan

    Yasukazu Kawai

  3. Department of Medicine III, Hamamatsu University School of Medicine, Shizuoka, Japan

    Akihiro Takeshita

  4. Division of Hematology, Department of Internal Medicine, Jichi Medical University, Tochigi, Japan

    Norio Komatsu

  5. Division of Oncology and Hematology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan

    Noriko Usui

  6. Department of Hematology, Dokkyo Medical University School of Medicine, Tochigi, Japan

    Yukihiro Arai

  7. 2nd Department of Internal Medicine, Shinshu University School of Medicine, Nagano, Japan

    Fumihiro Ishida

  8. 2nd Department of Internal Medicine, Nara Medical University, Nara, Japan

    Takeshi Morii

  9. Division of Hematology, Tochigi Cancer Center, Tochigi, Japan

    Yasuhiko Kano

  10. Department of Hematology and Cell Therapy, Aichi Cancer Center, Aichi, Japan

    Michinori Ogura

  11. Aichi Cancer Center, Aichi, Japan

    Ryuzo Ohno

Authors
  1. Shuichi Miyawaki
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  2. Yasukazu Kawai
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  3. Akihiro Takeshita
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  4. Norio Komatsu
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  5. Noriko Usui
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  6. Yukihiro Arai
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  7. Fumihiro Ishida
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  8. Takeshi Morii
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  9. Yasuhiko Kano
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  10. Michinori Ogura
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  11. Noriko Doki
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  12. Ryuzo Ohno
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Corresponding author

Correspondence to Ryuzo Ohno.

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Miyawaki, S., Kawai, Y., Takeshita, A. et al. Phase I Trial of FLAGM with High Doses of Cytosine Arabinoside for Relapsed, Refractory Acute Myeloid Leukemia: Study of the Japan Adult Leukemia Study Group (JALSG). Int J Hematol 86, 343–347 (2007). https://doi.org/10.1532/IJH97.07072

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  • DOI: https://doi.org/10.1532/IJH97.07072

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