Purpose: Previous studies have shown that the replication checkpoint, which involves the kinases ataxia telangiectasiamutated andRad3 related (ATR) andChk1, contributes to cytarabine resistance in cell lines. In the present study, we examinedwhether this checkpoint is activated in clinical acutemyelogenous leukemia (AML) during cytarabine infusion in vivo and then assessed the impact of combini...

Central nervous system (CNS) prophylaxis has led to a significant improvement in the outcome of patients with acute lymphocytic leukemia (ALL). Liposomal cytarabine (Enzon Pharmaceuticals, Piscataway, NJ; Skye Pharma, San Diego, CA), an intrathecal (IT) preparation of cytarabine with a prolonged half-life, has been shown to be safe and effective in the treatment of neoplastic meningitis. Liposo...

Resistance to cytarabine remains a major challenge in the treatment of acute myeloid leukemia (AML). Based on previous studies implicating ABCC4/MRP4 in the transport of nucleosides, we hypothesized that cytarabine is sensitive to ABCC4-mediated efflux, thereby decreasing its cytotoxic response against AML blasts. The uptake of cytarabine and its monophosphate metabolite was found to be facilit...

Central nervous system (CNS) prophylaxis has led to a significant improvement in the outcome of patients with acute lymphocytic leukemia (ALL). Liposomal cytarabine (Enzon Pharmaceuticals, Piscataway, NJ; Skye Pharma, San Diego, CA), an intrathecal (IT) preparation of cytarabine with a prolonged half-life, has been shown to be safe and effective in the treatment of neoplastic meningitis. Liposo...

PURPOSE Previous studies have shown that the replication checkpoint, which involves the kinases ataxia telangiectasia mutated and Rad3 related (ATR) and Chk1, contributes to cytarabine resistance in cell lines. In the present study, we examined whether this checkpoint is activated in clinical acute myelogenous leukemia (AML) during cytarabine infusion in vivo and then assessed the impact of com...

The treatment of older patients with acute myeloid leukemia (AML) remains unsatisfactory, with complete remission (CR) achieved in only approximately 50% and long-term disease-free survival in 10% to 20%. Three hundred eighty-eight patients (60 years of age and older) with newly diagnosed de novo AML were randomly assigned to receive placebo (P) or granulocyte-macrophage colony-stimulating fact...

Cytarabine (cytosine arabinoside) is one of the most effective drugs for the treatment of acute myeloid leukemia. The standard dose of cytarabine used to treat this leukemia is 100 mg per square meter. In an attempt to improve the effectiveness of cytarabine against acute myeloid leukemia, a high-dose treatment (3,000 mg per square meter) was introduced into therapy. The side effects of high-do...

IMPORTANCE OF THE FIELD Cytarabine is a polar nucleoside drug used for the treatment of myeloid leukemia and non-Hodgkin's lymphoma. The drug has a short plasma half-life, low stability and limited bioavailability. Overdosing of patients with continuous infusions may lead to side effects. Thus, various prodrug strategies and delivery systems have been explored extensively to enhance the half-li...

BACKGROUND Acute pancreatitis in acute myeloid leukemia (AML) has been rarely associated with cytarabine therapy. This report attempts to characterize this toxicity. PATIENTS AND METHODS Criteria for pancreatitis was prospectively defined. Seven patients with pancreatitis were identified from an AML database and a clinical study at two tertiary care centers (n = 134). Their records were retro...

BACKGROUND Acute myeloid leukemia (AML) is a genetically heterogeneous cancer that frequently exhibits aberrant kinase signaling. We investigated a treatment strategy combining sorafenib, a multikinase inhibitor with limited single-agent activity in AML, and cytarabine, a key component of AML chemotherapy. METHODS Using 10 human AML cell lines, we determined the effects of sorafenib (10 μM) o...