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Annals of Hematology

, Volume 87, Issue 5, pp 361–367 | Cite as

Daunorubicin, cytarabine and fludarabine (DAF) for remission induction in relapsed or refractory acute myeloid leukemia. Evaluation of safety, tolerance and early outcome—Polish Adult Leukemia Group (PALG) pilot study

  • Jerzy Hołowiecki
  • Sebastian GrosickiEmail author
  • Sławomira Kyrcz-Krzemien
  • Aleksander B. Skotnicki
  • Beata Piatkowska-Jakubas
  • Krzysztof Warzocha
  • Ilona Seferynska
  • Barbara Zdziarska
Original Article

Abstract

In 1992–1993, synergistic interaction of ribonucleotide reductase inhibitors (fludarabine, cladribine) and cytarabine (Ara-C) increasing Ara-CTP concentration in myeloblasts was proved. Based on these findings and encouraging results of the addition of cladribine to standard daunorubicin+Ara-C induction regimen (DAC) in acute myeloid leukemia (AML), the Polish Adult Leukemia Group (PALG) conducted a pilot study on the administration of cytarabine, daunorubicin, and fludarabine (DAF) as a reinduction treatment of AML to assess tolerance, toxicity, and early outcome. The DAF regimen consisted of daunorubicine 60 mg m−2 day−1 iv on days 1–3 and fludarabine 25 mg m−2 day−1 iv on days 1–5 given before cytarabine 200 mg m−2 day−1 in ci on days 1–7. Thirty-four AML patients with median age 39, 24% relapsed and 76% refractory, were included into the study between September 2003 and August 2004. Achieved response rate in the whole study population was 56%; n = 16 patients with complete remission (CR), and n = 3 patients with partial remission (PR). Fifteen of 16 patients achieved CR after the first course of therapy. Only 9% of total population died before the assessment of remission. All patients developed severe neutropenia. Serious infections were observed in 47% of the cases. Severe thrombocytopenia was observed in 72% of the patients. All patients required substitution of platelet concentrates (median 4), and PRBC (median 5). Severe alopecia, mucositis, vomiting were of low frequency. Liver, kidney, or circulatory failure, diarrhea, or polyneuropathy were not observed. The probability of overall survival (OS) for 1 year for the whole study population (34 patients) and the group of 16 patients in CR was: 44% (95% confidence interval [CI] 36–52%) and 69% (95% CI 55–83%), respectively. The probability of leukemia-free survival (LFS) for 1 year was 38% (95% CI 22–54%). Summarizing, DAF regimen used as the induction therapy in relapsed/refractory AML was well tolerated with acceptable toxicity and early efficacy.

Keywords

Acute myeloid leukemia AML Induction Fludarabine 

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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Jerzy Hołowiecki
    • 1
  • Sebastian Grosicki
    • 1
    Email author
  • Sławomira Kyrcz-Krzemien
    • 1
  • Aleksander B. Skotnicki
    • 2
  • Beata Piatkowska-Jakubas
    • 2
  • Krzysztof Warzocha
    • 3
  • Ilona Seferynska
    • 3
  • Barbara Zdziarska
    • 4
  1. 1.Department of Haematology and BMTSilesian Medical UniversityKatowicePoland
  2. 2.Department of HaematologyCollegium Medicum, Jagiellonian UniversityCracowPoland
  3. 3.Department of HaematologyInstitute of Haematology and Transfusion MedicineWarsawPoland
  4. 4.Department of HaematologyPomeranian Medical UniversitySzczecinPoland

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