Four Drugs Combination (Fludarabine, Cytarabine, Idarubicin, Etoposide) as Induction Therapy for Newly Diagnosed Acute Myeloid Leukemia Patients Younger Than 65 Ys: Response and Follow-up of 84 Patients.

Standard induction chemotherapy for Acute Myeloid Leukaemia (AML) is represented by a combination of cytarabine and antracyclin with or without the addition of a third drug (e.g. etoposide), with a Complete Remission (CR) rate of about 60-65%.

The main goal of adding further drugs to induction therapy is to increase the CR rate in order to extend the opportunity of intensification therapies (e.g. autologous or allogeneic stem cell transplantation).

Eighty-four consecutive AML patients younger than 65 yrs were treated with a four-drug induction regimen Fludarabine (25 mg/sqm), Ara-C (2 g/sqm), Etoposide 100 mg/sqm on days 1-5, Idarubicin (6 mg/sqm) on days 1, 3, and 5, between 2002 and 2008 in two Italian Hematological Centres. The median age of this series of patients was 45 years (range 18-65), 39 were males and 44 were females. According to karyotype at diagnosis, white blood count (WBC > 30.000/mmc) and secondary disease, 58/84 patients (69%) were considered at high risk Patients were evaluated for response rate and treatment-related adverse events. Stem cell transplantation was performed according to the risk stratification and donor availability.

After induction with FLAIE, CR occurred in 62 of 84 patients (74%). There were two death during induction (DDI 2 %). Six out of 22 resistant patients (7%) achieved CR after the second course of therapy, that was HD-Ara-c (2 g/sqm) on days 1-5 + idarubicine (12 mg/sqm) on days 1-3. Three patients were lost to follow up after induction, while in CR. The toxicity of FLAIE was acceptable, with grade III/IV hematological and extra-hematological adverse events comparable with standard induction therapy. Fifty-five patients of the 81 evaluable (68%) underwent transplant procedures while in first CR (22/81, 27 %, auto-SCT and 33/81, 41 %, allo-SCT). Five patients received allo-SCT in second CR, after early relapse. Three patients received allo-SCT with active disease and died because of disease progression. Sixteen patients (20%) received only chemotherapy-based consolidation because of either resistant disease or lack of donors or unsuccessful peripheral blood harvestt. After a median follow-up of 46 months (range 1-81), 40 of 81 evaluable patients (49%) are alive (40/40 in CR). Relapse rate is 32% at 4 yrs. These results suggest that a four drugs induction chemotherapy is feasible in young AML patients and can effectively permit intensification chemotherapy in at least 2/3 of the patients. A larger number of patients, in the context of a randomized trial may better define its efficacy with respect to standard 2 – 3 drugs induction therapy.

Baccarani:Novartis Pharma: Consultancy, Honoraria, Research Funding, Speakers Bureau; Bristol-Mayer Squibb: Consultancy, Honoraria, Research Funding, Speakers Bureau.