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 (1) , Ciro R. Rinaldi (1) , Salvatore Palmieri (2) , Nicola Cantore (3) , Giuseppina Mele (2) , Vincenzo Mettivier (2) , Eustachio Miraglia (4) , Lucia Mastrullo (5) , Francesco Grimaldi (1) , Luigia Luciano (1) , Anna Guerriero (1) , Bruno Rotoli (1) , Felicetto Ferrara (2)

1 Hematology
2 A.O.R.N. Cardarelli
3 Ospedale Civile
4 Ospedale S.Giovanni Bosco
5 Ospedale San Gennaro

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 ( = 16), or relapsed ( = 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.

Mots clés: Refractory acute myeloid leukemia; Relapsed acute myeloid leukemia; Salvage treatment; DaunoXome; FLAD

Andrea Camera, Ciro R. Rinaldi, Salvatore Palmieri, Nicola Cantore, Giuseppina Mele, 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. Annals of Hematology, 2008, 88 (2), pp.151-158. ⟨10.1007/s00277-008-0571-z⟩. ⟨hal-00477967⟩