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

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Abstract

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.

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Authors and Affiliations

  1. Hematology, Università Federico II, Via Pansini, 5, 80131, Naples, Italy

    Andrea Camera, Ciro R. Rinaldi, Francesco Grimaldi, Luigia Luciano, Anna Guerriero & Bruno Rotoli

  2. A.O.R.N. Cardarelli, Naples, Italy

    Salvatore Palmieri, Giuseppina Mele, Vincenzo Mettivier & Felicetto Ferrara

  3. Ospedale Civile, Avellino, Italy

    Nicola Cantore

  4. Ospedale S.Giovanni Bosco, Naples, Italy

    Eustachio Miraglia

  5. Ospedale San Gennaro, Naples, Italy

    Lucia Mastrullo

Authors
  1. Andrea Camera
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  2. Ciro R. Rinaldi
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  4. Nicola Cantore
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  13. Felicetto Ferrara
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Corresponding author

Correspondence to Bruno Rotoli.

Appendix: Participating centers and number (#) of patients enrolled

Appendix: Participating centers and number (#) of patients enrolled

Università Federico II, Napoli (Prof. Bruno Rotoli) #30

A.O.R.N. Cardarelli, XIX, Napoli (Dr. Felicetto Ferrara) #17

Ospedale Civile, Avellino (Dr. Nicola Cantore) #7

A.O.R.N. Cardarelli, TERE, Napoli (Dr. Vincenzo Mettivier) #2

Ospedale S. Giovanni Bosco, Napoli (Dr. Eustachio Miraglia) #2

Ospedale S. Gennaro, Napoli (Dr. Lucia Mastrullo) #2

Ospedale Civile, Arienzo (Caserta) (Dr. David Pagnini) #1

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Camera, A., Rinaldi, C.R., Palmieri, S. et al. Sequential continuous infusion of fludarabine and cytarabine associated with liposomal daunorubicin (DaunoXome®) (FLAD) in primary refractory or relapsed adult acute myeloid leukemia patients. Ann Hematol 88, 151–158 (2009). https://doi.org/10.1007/s00277-008-0571-z

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  • DOI: https://doi.org/10.1007/s00277-008-0571-z

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