Front-Line Therapy of Acute Myeloid Leukemia in Elderly Patients. Safety and Efficacy of Two Different Schedules of Fludarabine-Based Regimens.

Association between fludarabine (Fluda) and cytosine arabinoside (ARA-C) have shown in a variety of single arm studies an effective antileukemic effect with acceptable toxicity in high risk myelodisplasias and acute myeloid leukemias in elderly patients. In order to increase the synergistic effect of fluda and ARA-C further association (i.e. anthracyclines) or different schedules of administration (i.e. continous infusion) have been performed but not compared. In order to asses if there is an advantage of an association or schedule compared to another we retrospectively analyzed results from two different fludarabine-based regimens administered as front-line therapy in patients with acute myeloid leukemias aged up to 60 years. A total of 42 patients were treated with fluda 25 mg/m2, ARA-C 1 gr/m2 and idarubicin 5 mg/m2 as single day administration for three days (FLAI) or fluda 20 mg/m2 and ARA-C 1,4 mg/m2 as continuous infusion for three days fluda and 4 days ARA-C (c.i.FLA). Total dosage of fluda was 75 mg/m2 in FLAI and 70 mg/m2 in c.i.FLA, while ARA-C total dose was 3 gr/m2 in FLAI and 6,15 gr/m2 in c.i.FLA. Dose administered of idarubicin in FLAI was 15 mg/m2. Patients who obtained complete remission (CR) defined as less of 5% of bone marrow blasts received a second course of the same chemotherapy as consolidation, reduced at 3 days in c.i.FLA. 19 patients were treated with FLAI regimen, 9 males and 10 females, mean age 69,3 years (range 61–75) and 23 received c.i.FLA regimen, 12 male and 11 female, mean age 69,4 years (range 61–84). 4 patients in each group showed unfavourable kariotype. Results were as follows: 8/19 (42%) patients obtained CR after induction with FLAI while 11/23 (48%) were in CR after first course c.i.FLA. Difference is not statistically significative. Median disease free survival (DFS) was 9,53 months for FLAI and 7,67 months for c.i.FLA (p=NS) and median overall survival (OS) in the group in CR was 10.8 in the FLAI group and 10 months in c.i.FLA group (p=NS). Induction deads were 1/19 in FLAI group (5%) and 3/23 in c.i.FLA group (13%). The global median OS, including resistant patients was 6,57 months for FLAI and 6 months for c.i.FLA (p=NS). Two patients in each group underwent autologous bone marrow transplantation in complete remission. Results of the comparison of this two different regimens suggest that there is no substantial difference between single daily administration added of idarubicin and continuous infusion of fluda and ARA-C. Both cycles seem to have the same antileukemic activity with overlapping toxicity. Median time to neutrophil recovery (> 1000/mmc) was 16 in c.i.FLA and 14,5 in FLAI while platelets recovery (> 20000/mmc) was 18 in c.i.FLA and 13 in FLAI. Both schedules can be, in our opinion, safely used as front-line therapy in elderly patients affected by acute myeloid leukemias. What is to underline in this setting of patients is the short duration of the CR. Probably some kind of maintenance or association without increasing toxicity is needed, and experience with monoclonal antibodies are an interesting way to follow.