Annals of Hematology

, Volume 88, Issue 2, pp 151–158

Sequential continuous infusion of fludarabine and cytarabine associated with liposomal daunorubicin (DaunoXome®) (FLAD) in primary refractory or relapsed adult acute myeloid leukemia patients


  • Andrea Camera
    • HematologyUniversità Federico II
  • Ciro R. Rinaldi
    • HematologyUniversità Federico II
  • Salvatore Palmieri
    • A.O.R.N. Cardarelli
  • Nicola Cantore
    • Ospedale Civile
  • Giuseppina Mele
    • A.O.R.N. Cardarelli
  • Vincenzo Mettivier
    • A.O.R.N. Cardarelli
  • Eustachio Miraglia
    • Ospedale S.Giovanni Bosco
  • Lucia Mastrullo
    • Ospedale San Gennaro
  • Francesco Grimaldi
    • HematologyUniversità Federico II
  • Luigia Luciano
    • HematologyUniversità Federico II
  • Anna Guerriero
    • HematologyUniversità Federico II
    • HematologyUniversità Federico II
  • Felicetto Ferrara
    • A.O.R.N. Cardarelli
Original Article

DOI: 10.1007/s00277-008-0571-z

Cite this article as:
Camera, A., Rinaldi, C.R., Palmieri, S. et al. Ann Hematol (2009) 88: 151. doi:10.1007/s00277-008-0571-z


A large proportion of adult patients with acute myeloid leukemia (AML) relapse after treatment, and some of them are resistant to primary induction chemotherapy. Sixty-one patients from seven hematological centers with poor-risk AML, primary refractory (n = 16), or relapsed (n = 45) were treated with a salvage regimen, including fludarabine (2 days) and cytarabine (3 days) in a sequential continuous infusion, associated with liposomal daunorubicin (3 days) (FLAD). Complete response rate was 44% and 56% for refractory and relapsed patients, respectively, with an overall response rate of 52% (32 of 61). Twenty-two patients (36%) were resistant to the salvage therapy. Seven patients (12%) died early during chemotherapy, four of them because of sepsis. Nineteen patients in complete remission (CR) underwent a stem-cell transplant (SCT) procedure: five autologous, nine from a HL-A identical sibling, and five from HL-A matched unrelated donors. Post-treatment aplasia and mucositis were major toxicities. Twenty patients (62.5%) relapsed after this treatment in a median of 7.3 months; ten patients relapsed after a SCT procedure. Nine patients are alive and disease free; three of them were rescued after a further cytotoxic treatment. The FLAD regimen proved to be an effective and well-tolerated treatment, with acceptable toxicity in this group of high-risk patients. A better response rate was obtained in the subgroup of relapsed patients, compared to patients treated for refractory disease. More then half (five of nine) of long-surviving patients are those who were submitted to a transplant procedure; thus, the main indication for FLAD seems to be to try to induce a rapid CR with minimum toxicity in order to perform a transplant as soon as possible.


Refractory acute myeloid leukemiaRelapsed acute myeloid leukemiaSalvage treatmentDaunoXomeFLAD

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© Springer-Verlag 2008