Induction Intensified Regimens Including Fludarabine or Mylotarg for Acute Myeloid Leukemia Patients: Comparison by Response and Follow-up.

Background. Conventional induction treatment in young Acute Myeloid Leukemia (AML) patients (<= 60 years old) is still represented by the association of antracycline and cytarabine, which offers a complete remission (CR) rate not inferior to 63%. Since many non-randomized trials have recently demonstrated the superiority of intensified regimens, the present gold standard therapy includes the addition of at least a third drug to the classic 3/7 schedule.

Aim of the study. We evaluated the safety profile and the efficacy of two four-drugs induction schedules, adding either fludarabine (25 mg/sqm days 1–5) or mylotarg (3 mg/sqm day 6) to idarubicin (6 mg/sqm days 1, 3, 5), cytarabine (1 g/sqm days 1–5), etoposide (100 mg/sqm days 1–5) (FLAIE and MyAIE, respectively).

Methods. Sixty-six consecutive AML patients were enrolled either in the FLAIE (N=44, from 2002 to 2005) or in the MyAIE (N=22, from 2005 to April 2007) schedule, with similar clinical and biological characteristics. The median age was 45 and 48 years, respectively. According to kariotype, WBC count and FLT3 status, seventy and sixty-four percent of cases, respectively, were considered at high risk. Consolidation therapy consisted of 2 cycles of ID-AraC and Ida.

Results. The complete remission rate was 75% and 59% for FLAIE and MyAIE, respectively (p=n.s.). Death during treatment rates were 5% and 0. After 1 consolidation course the overall CR rate was 80% and 73%. After a similar median follow up, 27 months (1–62) and 21 months (5–42) respectively, 41% of patients are alive in CR in the FLAIE group (12 SCT and 3 ASCT) and 64% in the MyAIE group (7 SCT and 4 ASCT) (p=n.s.; Chi-square, Fisher’s exact test). Toxicity was comparable in the two regimens. The median time to ANC recovery (>1.0 x 10^9/L) was 31 and 23 days for FLAIE and MyAIE, respectively. The median time to PLT recovery (>100 x 10^9/L) was 28 and 24 days, respectively. The median time of neutropenic fever episodes for patients was 1 and 1.4 in the 2 groups, respectively. Grade III/IV GI toxicities occurred in 11% and 22% of cases, respectively.

Conclusions. These data showed that four-drugs intensified induction therapy is a feasible approach in young AML patients. Recent published trials have demonstrated that fludarabine-based induction chemotherapy in high risk AML patients is able to increase the CR rate offered by conventional treatment. Therefore, the limited number of patients involved in this study, the low administration dosage of idarubicin, and the relevant role of fludarabine in induction therapy, can reasonably justify the lower CR rate obtained in patients treated in the MyAIE schedule, if compared with FLAIE regimen and, above all, with standard chemotherapy. In the light of their efficacy and safety profile, fludarabine and mylotarg, in combination with conventional chemotherapy, represent a promising induction regimen in young AML patients; further analyses and randomized pilot trials will define their definite role.