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Decitabine in the treatment of acute myeloid leukemia in elderly patients.

ABSTRACT: The majority of patients with acute myeloid leukemia (AML) are elderly and have a poor prognosis despite induction therapy. Decitabine, a DNA-hypomethylating agent that induces differentiation and apoptosis of leukemic cells, is a well-tolerated alternative to aggressive chemotherapy. It is currently FDA-approved for myelodysplastic syndrome, including patients with 20%-30% bone marrow blasts. Recent clinical attention has focused on evaluating decitabine as frontline therapy for untreated high-risk elderly AML patients. A large randomized international phase III study comparing decitabine to supportive care and cytarabine in elderly AML patients demonstrated significantly improved complete remission rates, but the survival difference did not reach significance. Due to this, decitabine did not achieve FDA approval for AML, but continues to be used off-label. Current research is focused on further defining subgroups of elderly AML patients who may derive greater benefit from decitabine therapy and combining it with other low-intensity active agents for AML.

SUBMITTER: Malik P

PROVIDER: S-EPMC3917925 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Decitabine in the treatment of acute myeloid leukemia in elderly patients.

Malik Priya P Cashen Amanda F AF

Cancer management and research 20140203

The majority of patients with acute myeloid leukemia (AML) are elderly and have a poor prognosis despite induction therapy. Decitabine, a DNA-hypomethylating agent that induces differentiation and apoptosis of leukemic cells, is a well-tolerated alternative to aggressive chemotherapy. It is currently FDA-approved for myelodysplastic syndrome, including patients with 20%-30% bone marrow blasts. Recent clinical attention has focused on evaluating decitabine as frontline therapy for untreated high- ...[more]

PMID: 24520204

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Project description:Hematologic responses to hypomethylating agents are often delayed in patients with myelodysplastic syndrome or acute myeloid leukemia. Fetal hemoglobin is a potential novel bio-marker of response: recently, we demonstrated that a high fetal hemoglobin level prior to decitabine treatment was associated with superior outcome. Here we investigated whether early fetal hemoglobin induction during decitabine treatment also had prognostic value, and studied the potential of decitabine to induce erythroid differentiation and fetal hemoglobin expression in vitro Fetal hemoglobin levels were measured by high-performance liquid chromatography in patients with higher-risk myelodysplastic syndrome (n=16) and acute myeloid leukemia (n=37) before treatment and after each course of decitabine. Levels above 1.0% were considered induced. Patients achieving complete or partial remission as best response had attained a median fetal hemoglobin of 1.9% after two courses of treatment, whereas the median value in patients who did not reach complete or partial remission was 0.8% (P=0.015). Fetal hemoglobin induction after two courses of decitabine treatment was associated with early platelet doubling (P=0.006), and its subsequent decrease with hematologic relapse. In patients with myelodysplastic syndrome, induction of fetal hemoglobin after course 2 of treatment was associated with longer overall survival: median of 22.9 versus 7.3 months in patients with or without induction of fetal hemoglobin, respectively [hazard ratio=0.2 (95% confidence interval: 0.1-0.9); P=0.03]. In vitro decitabine treatment of two bi-potential myeloid leukemia cell lines (K562 and HEL) resulted in induction of an erythroid (not megakaryocytic) differentiation program, and of fetal hemoglobin mRNA and protein, associated with GATA1 gene demethylation and upregulation. In conclusion, fetal hemoglobin may provide a useful dynamic biomarker during hypomethylating agent therapy in patients with myelodysplastic syndrome or acute myeloid leukemia.

Dataset Information

Decitabine in the treatment of acute myeloid leukemia in elderly patients.

Publications

Decitabine in the treatment of acute myeloid leukemia in elderly patients.

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