Daunorubicin 90 mg/m2 in Acute Myeloid Leukemia Induction: Increased Toxicity in Young Patients

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Background:The combination of an anthracycline and cytosine arabinoside has been the standard induction therapy for acute myeloid leukemia for more than 3 decades. The clinical benefit of intensification of the daunorubicin dose to 90 mg/m2 has been supported by randomized trials. Based on these promising results, in 2010 we changed our induction protocol of acute myeloid leukemia, increasing the dose of daunorubicin.Patients and Methods:We retrospectively analyzed the treatment outcome of patients treated with high-dose daunorubicin (90 mg/m2 on days 1-3) and cytosine arabinoside (200 mg/m2/day continuous infusion on days 1-7) compared with patients receiving 45 to 60 mg/m2 of daunorubicin. Twenty-six previously untreated patients younger than 60 years of age were included. Twelve received high-dose daunorubicin (HD) and 14 the low-dose (LD). Seventeen patients were in complete remission after 1 induction cycle.Results:There was no overall difference in complete remission rate between HD and LD (66% vs. 64%; P = 1.0). Thirty-day induction mortality was 15.3% overall, with a nonsignificant difference between groups (25% vs. 7.1%; P = .3). Relapses were observed in 9 (53%) patients: 3 (37.5%) in the HD group and in 6 (66.6%) in the LD group (P = .34). Invasive fungal disease (41.6% vs. 0%; P = .012), creatinine elevation (P = .001), abdominal pain (33% vs. 0%; P = .033), and need for intensive care unit admission (33.3% vs. 0%; P = .033) were more frequent in the HD group. Four patients in the HD group developed neutropenic enterocolitis (P = .033).Conclusion:These data indicate that 90 mg/m2 of daunorubicin increased the toxicity compared with lower doses.We evaluated the outcome of AML patients treated with daunorubicin 90 mg/m2. Higher rates of invasive fungal disease, antifungal therapy, creatinine elevation, gastrointestinal toxicity and intensive care unit admissions were observed with increased anthracycline dose. The daunorubicin induction dose should be greater than 45 mg/m2 but escalation to 90 mg/m2 seems excessive.

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