| Popis: |
Treatment results in patients with refractory and relapsed acute myeloid leukemia (AML) need to be improved. The current study aimed at enhancing the anti-leukemic efficacy of the sequential high-dose AraC and idarubicin (S-HAI) regimen by the addition of fludarabine as a chemo-modulator. High-dose AraC was applied q 12 hours on days on days 1, 2, 8, and 9 and idarubicin on days 3, 4, 10, and 11. Patients were randomized to receive fludarabine q 12 hours on days 1, 2, 8, and 9 in addition to S-HAI or S-HAI alone. Of 179 patients having entered the study 120 are fully evaluable at the present time (median age 55 years, range 20–77). Thirty-eight percent of the patients had refractory disease or early relapses, 59% had relapses after a preceding CR of more than six months duration and 2% had a second relapse. Fifty percent achieved a remission (CR, 47%; PR, 3%) while the non-response rate was 33% and 18% suffered from early death. Patients with prognostically unfavorable karyotype aberrations at relapse (n=25) had an inferior response to therapy as compared to patients with prognostically intermediate (n=59) or favorable karyotypes (n=10) (CR, 24% vs. 53% vs. 70%; non-response, 40% vs. 36% vs. 10%). The long-term outcome was also inferior in these patients (survival, 4.1 vs. 7.8 months, p=0.01; time to treatment failure, 1.2 vs. 3.1 months, p=0.002). The application of fludarabine had no significant impact on the duration of neutropenia (median, 34 vs. 37 days). Severe nonhematologic toxicity (WHO III°/IV°) consisted mainly of diarrhea (18%), mucositis (16%), nausea/vomiting (14%), and bleeding (9%) and infectious complications included FUO (51%), pneumonia (49%), and bacteremia (33%), both being not influenced significantly by the application of fludarabine. The sequential testing for the comparison of the efficacy of both study arms is ongoing. |
