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After a first course of induction chemotherapy, 30-40% of patients with acute myeloid leukemia (AML) do not achieve a complete response (CR). A second course of an anthracycline and intermediate-dose cytarabine (IDAC) allows a significant number of patients with persistent AML at day 14 to finally achieve a CR. We hypothesized that use of a topotecan and cytarabine combination in this setting might improve tolerance and efficacy. Cytarabine (1000 mg/m2/12 h days 1-4) was combined with topotecan (TA, 1.25 mg/m2/day by continuous intravenous infusion [CIV] days 1-4) in 31 consecutive patients with ≥ 5% marrow blasts by day 14 of induction. The median follow-up was 36 months. The CR rate was 81%, and the 2-year probability of overall survival and cumulative incidence of relapse were 66% and 38%, respectively. No unexpected toxicity was observed. Comparison with historical controls treated with the combination of a similar schedule of cytarabine and an anthracycline showed a better CR rate ( p = 0.054), overall survival ( p = 0.03) and cumulative incidence of relapse ( p = 0.03). These results were confirmed in a multivariate analysis model. This work shows that the substitution of an anthracycline by topotecan is feasible and associated with significant efficacy for patients with AML with persistent leukemia at day 14 after standard-dose anthracycline induction. [ABSTRACT FROM AUTHOR]

The prognosis of patients older than 50 with relapsed or refractory AML is dismal. Azacitidine has been investigated in older AML patients. Here we report the outcome of 130 patients older than 50 years included in a multicenter patient named program of azacitidine after relapse ( n = 67) or induction failure ( n = 63) of intensive chemotherapy. Median age was 67 years, cytogenetic risk was high in 28% and performance status ≥2 in 15% of cases. Most (72%) patients received azacitidine at the standard schedule (75 mg/m 2 /d, 7 days/month) for a median of 4 courses. The overall response rate was 17% (CR: 10%, CRi: 7%). Median overall survival was 8.4 months. Achievement of CR/CRi was associated with prolonged survival ( P = 0.0001), whereas hematological improvement according to MDS criteria, achieved in 36% of patients with resistant disease, did not improve survival. In multivariate analysis, high risk cytogenetics ( P = 0.022) and peripheral blasts >10% ( P < 0.0001) at onset of azacitidine were independently predictive of poor prognosis. Combining these two factors, we identified a subgroup of 48% of patients with intermediate risk cytogenetics and peripheral blasts ≤10% and a median OS of 11.3 months. These results warrant further investigation of azacitidine-based regimens in this subgroup of patients. [ABSTRACT FROM AUTHOR]