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Intensive chemotherapy with idarubicin, cytarabine, etoposide, and G-CSF priming in patients with advanced myelodysplastic syndrome and high-risk acute myeloid leukemia

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Abstract

In an attempt to improve the complete remission (CR) rates and to prolong the remission duration especially in elderly patients >50 years of age, we have used a combination chemotherapy of idarubicin (10 mg/m2 IV×3 days), cytarabine (AraC, 100 mg/m2 CIVI×7d), and etoposide (100 mg/m2×5 days) in combination with granulocyte colony-stimulating factor (G-CSF) priming [5 mg/kg SQ day 1 until absolute neutrophil count (ANC) recovery] for remission induction. Responding patients received two consolidation courses of idarubicin, AraC, and etoposide, followed by a late consolidation course of intermediate-dose AraC (600 mg/m2 IV every 12 h×5 days) and amsacrine (60 mg/m2 IV×5 days). A total of 112 patients (57 male/55 female) with a median age of 58 years (range: 22–75) have been entered and are evaluable for response: 19 refractory anemia with excess of blast cells in transformation (RAEB-T), 84 acute myeloid leukemia (AML) evolving from myelodysplastic syndrome (MDS), and 9 secondary AML after chemotherapy/radiotherapy. The overall CR rate was 62%, partial remission (PR) rate 10%, treatment failure 16%, and early death rate 12%. The CR rate was higher in patients ≤60 years (68 vs 55%), mainly due to a lower early death rate (5 vs 21%, p<0.001). After a median follow-up of 58 months, the median overall survival is 14.5% and median duration of relapse-free survival 8 months. After 60 months, the probability of CR patients to still be in CR and alive is 16% (20% in patients ≤60 years and 13% in patients >60 years), while the probability of overall survival is 12% (15% in patients ≤60 years and 9% in patients >60 years). Compared to our previous trial (AML-MDS Study 01-92) which was done with identical chemotherapy but no G-CSF priming in 110 patients with RAEB-T, AML after MDS, or secondary AML (identical median age, age range, and distribution of subtypes), the CR rate in all patients, as well as CR rate, overall survival, and relapse-free survival in patients >60 years have significantly been improved. Thus, intensive chemotherapy with G-CSF priming is both well tolerated and highly effective for remission induction in these high-risk patients.

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Authors and Affiliations

  1. Department of Hematology/Oncology, Johann Wolfgang Goethe University Hospital, University of Frankfurt/Main, Theodor-Stern-Kai 7, 60596, Frankfurt/Main, Germany

    W. K. Hofmann, C. Zander, O. G. Ottmann & D. Hoelzer

  2. Department of Hematology/Oncology, Hannover Medical School, Hannover, Germany

    G. Heil, S. Wiebe & A. Ganser

  3. Department of Hematology/Oncology, University of Ulm, Ulm, Germany

    L. Bergmann

  4. Department of Hematology/Oncology, University of Jena, Jena, Germany

    K. Hoeffken

  5. Department of Hematology/Oncology, Community Hospital, Karlsruhe, Germany

    J. T. Fischer

  6. Department of Hematology/Oncology, North-West Hospital, Frankfurt/Main, Germany

    A. Knuth

  7. Department of Hematology/Oncology, University of Mainz, Mainz, Germany

    K. Kolbe

  8. Department of Hematology/Oncology, University of Halle/Saale, Halle/Saale, Germany

    H. J. Schmoll

  9. Community Hospital, Essen-Werden, Germany

    W. Langer

  10. Community Hospital, Duisburg, Germany

    M. Westerhausen

  11. Community Hospital, Trier, Germany

    C. B. Koelbel

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  1. W. K. Hofmann
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  2. G. Heil
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  3. C. Zander
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  9. A. Knuth
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  10. K. Kolbe
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  15. D. Hoelzer
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Correspondence to W. K. Hofmann.

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Hofmann, W.K., Heil, G., Zander, C. et al. Intensive chemotherapy with idarubicin, cytarabine, etoposide, and G-CSF priming in patients with advanced myelodysplastic syndrome and high-risk acute myeloid leukemia. Ann Hematol 83, 498–503 (2004). https://doi.org/10.1007/s00277-004-0889-0

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  • DOI: https://doi.org/10.1007/s00277-004-0889-0

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