Targeting SAMHD1 with hydroxyurea in first-line cytarabine-based therapy of newly diagnosed acute myeloid leukaemia: Results from the HEAT-AML trial.

ABSTRACT:

Background

Treatment of newly diagnosed acute myeloid leukaemia (AML) is based on combination chemotherapy with cytarabine (ara-C) and anthracyclines. Five-year overall survival is below 30%, which has partly been attributed to cytarabine resistance. Preclinical data suggest that the addition of hydroxyurea potentiates cytarabine efficacy by increasing ara-C triphosphate (ara-CTP) levels through targeted inhibition of SAMHD1.

Objectives

In this phase 1 trial, we evaluated the feasibility, safety and efficacy of the addition of hydroxyurea to standard chemotherapy with cytarabine/daunorubicin in newly diagnosed AML patients.

Methods

Nine patients were enrolled and received at least two courses of ara-C (1 g/m² /2 h b.i.d. d1-5, i.e., a total of 10 g/m^2<

SUBMITTER: Jadersten M 

PROVIDER: S-EPMC9643609 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature