الفهرس 
Pharmacological Study on the Effectiveness of High Dose Cytarabine Arabinoside as a Consolidation Therapy in Patients with Adult Acute Myeloid Leukemia
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Abstract
Background: Cytosine Arabinoside (AraC) is an effective agent in consolidation therapy and in acute myeloid leukemia (AML) relapse. In consolidation therapy, AraC plays an important role in preventing relapses for AML patients who achieved complete remission, but the optimum dose remains elusive.This study compared the pharmacokinetic (PK) profile, efficacy and safety of high (3 g/m2, twice daily) and low dose Ara-C (1.5 g/m2, twice daily) in consolidation phase of treatment. Methods: This study included 39 adult AML patients presented to Medical Oncology Department, National Cancer Institute (Cairo University, Cairo, Egypt). Patients were randomly assigned into 2 arms of 20 patients each. In the first arm, patients received consolidation AraC at a low dose of 1.5 g/m² for 3 h infusion every 12 hours on days 1, 3, and 5; similarly in the second arm, patients received 3.0 g/m². Blood samples were withdrawn after reaching steady state, on the third day before the infusion (trough level) and at the end of the infusion (peak level). The plasma levels of AraC and its metabolite uridine arabinoside (AraU) were measured using HPLC/MS/MS and the PK profiles of the two regimens were compared. Survival analysis after one year and toxicities for both regimens were recorded. Expressions of deoxycytidine kinase (DCK) and activation-induced deaminase (AID) genes were detected using Real-Time PCR technique and DCK and cytidine deaminase (CDA) genes polymorphisms were detected using PCR-RFLP technique. Results: There was insignificant difference (P=0.105) between the median age of patients who received the low 39 years (21-60) and high dose and 33 years (18-53). Eligible patients were distributed equally in terms of weight, height, and body surface area with 58.9% total male patients. There was a significant increase in the median plasma peak of AraC level (P=0.002) in high dose AraC (n = 20) to reach 97.1 versus 40.8æg/ml for the low dose of AraC (n=19)