6533b82ffe1ef96bd1294f91

RESEARCH PRODUCT

Oral Idarubicin in Maintenance Therapy of Acute Myeloid Leukemia

subject

description

More than half of all acute myeloid leukaemia (AML) patients are over 60 years. The disease free survival (DFS) and overall survival (OS) rate of these patients is poor. These unsatisfactory results are associated with adverse cytogenetic characteristics, prior myelods-plasia, adverse phenotypic features, MDR and BCL2 overexpression. Furthermore a large fraction of patients achieving CR early relapses. This is due to two factors: acquired tumor cell drug resistance and tumor re-growth. Maintenance therapy could provide a means to keep leukemic growth under control. We enrolled 31 elderly previous responder patients to standard induction therapy to receive maintenance oral IDA 3mg/m2 daily d 1-14 at a 2 weeks interval for a total of 12 cycles or until disease progression. We also evaluated the cell cycle and apoptosis in leukemic cells from PR patients after IDA administration, and as a control from HL60 cell line exposed to IDA and idarubicinol in vitro. DNA analysis showed an increase of G2/M cell frequencies and evidence of apoptosis (sub Gl peak). In CR patients the median DFS and OS was 8 months and 12.5 months respectively. In PR patient the median OS was 9 months. In contrast comparing these results with an historical control group we observe a lower median cumulative OS (3 vs 11 months) and in CR patients a DFS and OS of 4 and 7 months. The treatment was well tolerated. Low haematological and extrahaematological toxicity were observed. In conclusion, longterm low doses of oral IDA would appear valuable as a maintenance regimen for elderly AML patients.