Original Article

Annals of Hematology

, Volume 88, Issue 2, pp 151-158

First online:

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

  • Andrea CameraAffiliated withHematology, Università Federico II
  • , Ciro R. RinaldiAffiliated withHematology, Università Federico II
  • , Salvatore PalmieriAffiliated withA.O.R.N. Cardarelli
  • , Nicola CantoreAffiliated withOspedale Civile
  • , Giuseppina MeleAffiliated withA.O.R.N. Cardarelli
  • , Vincenzo MettivierAffiliated withA.O.R.N. Cardarelli
  • , Eustachio MiragliaAffiliated withOspedale S.Giovanni Bosco
  • , Lucia MastrulloAffiliated withOspedale San Gennaro
  • , Francesco GrimaldiAffiliated withHematology, Università Federico II
    • , Luigia LucianoAffiliated withHematology, Università Federico II
    • , Anna GuerrieroAffiliated withHematology, Università Federico II
    • , Bruno RotoliAffiliated withHematology, Università Federico II Email author 
    • , Felicetto FerraraAffiliated withA.O.R.N. Cardarelli

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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 leukemia Relapsed acute myeloid leukemia Salvage treatment DaunoXome FLAD