International Journal of Hematology

DOI: 10.1007/s12185-019-02606-0 Pages: 418-425

Phase II study of FLAGM (fludarabine + high-dose cytarabine + granulocyte colony-stimulating factor + mitoxantrone) for relapsed or refractory acute myeloid leukemia

1. Saiseikai Maebashi Hospital, Leukemia Research Center

2. Tokyo Metropolitan Ohtsuka Hospital, Division of Hematology

3. University of Fukui, First Department of Internal Medicine, Faculty of Medical Sciences

4. Hamamatsu University School of Medicine, Department of Medicine III

5. Jichi Medical University, Division of Hematology

6. Jikei University School of Medicine, Division of Clinical Oncology and Hematology, Department of Internal Medicine

7. Dokkyo University School of Medicine, Department of Hematology

8. Shinshu University School of Medicine, Department of Internal Medicine

9. Nara Medical University, The Second Department of Internal Medicine

10. Tochigi Cancer Center, Division of Hematology

11. Nagoya Daini Red Cross Hospital, Department of Hematology and Oncology

12. Kasugai Municipal Hospital, Department of Hematology and Oncology

13. Tokai University School of Medicine, Department of Hematology and Oncology

14. Mie University Graduate School of Medicine, Hematology and Oncology

15. Nagasaki University Graduate School of Biomedical Sciences, Department of Public Health

16. Hamamatsu University School of Medicine, Oncology Center

17. Nagoya University Graduate School of Medicine, Oncology

Correspondence to:
Shuichi Miyawaki
Tel: +81-3-3941-3211
Email: miyawaki@mail.wind.ne.jp

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Abstract

Given the poor prognosis of patients with relapsed/refractory acute myeloid leukemia (AML), better therapy is needed. Fludarabine enhances the efficacy of Ara-C (cytarabine) by increasing intracellular Ara-C-triphosphate. The FLAG (fludarabine, high-dose Ara-C, supported with granulocyte colony-stimulating factor) regimen has been tested for use in AML patients by other investigators. In the phase II study reported here, we evaluated the efficacy and toxicity of FLAGM therapy (FLAG with mitoxantrone), further intensified by adding mitoxantrone, based on the results of a phase I study by our group. The major endpoints were complete remission (CR) rate and early death. From June 2004 to February 2008, 41 patients (median age 52 years; range 18–64 years) were enrolled. Thirty (73% 95% CI 58–84%) patients achieved CR, which met the primary endpoint; there was a single case of early death from pneumonia. Two-year overall survival was 39.4% (95% CI 25.2–55.6%). Of those who achieved CR, 27 underwent allogeneic stem cell transplantation (SCT), and 12 SCT recipients showed long-term survival. Grade 3/4 non-hematological adverse events included infection (59%), nausea/vomiting (15%), diarrhea (7%), and elevated liver enzymes (7%). In conclusion, FLAGM is an effective and safe salvage therapy for patients with relapsed/refractory AML, and facilitated SCT for a large proportion of patients.

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