Despite the efficiency of fludarabine in the induction of clinical responses in B-cell chronic lymphocytic leukemia (B-CLL) patients, resistance to this drug has been documented. The present study tested whether resistance to fludarabine is related to the expression of inhibitor of apoptosis proteins (IAPs) family members. We analyzed the expression of c-IAP1, c-IAP2 and XIAP, by immunocytochemistry, in 30 blood samples from B-CLL patients and correlated protein expression to fludarabine-induced apoptosis estimated by an annexin-V assay. Expression of c-IAP1, c-IAP2 and XIAP were found predominantly in the cytoplasm, and a wide range of staining intensities was observed among distinct samples. No correlation was found between the levels of IAPs expression and prognostic factors such as age, gender, lymphocyte doubling time, white blood cell count or previous treatment. The expression of IAPs also failed to predict the sensitivity to fludarabine-induced apoptosis. Alternative pathways of cell death may explain the independence of fludarabine-induced apoptosis from the high expression of IAPs.

No abstract

No abstract

B-cell chronic lymphocytic leukemia (B-CLL) is the commonest leukemia occurring in Western countries, and arises predominantly in older age groups. Intravenous fludarabine phosphate offers the possibility of a prolonged progression-free interval, an increased response rate and a trend toward better tolerability in comparison with standard polychemotherapy regimens. A more convenient oral formulation of fludarabine phosphate, has been developed. We undertook a literature review that has demonstrated that oral fludarabine phosphate has a similar clinical efficacy and safety profile to the IV formulation and does not adversely affect quality of life. Also we performed a retrospective analysis of patients receiving IV fludarabine for (B-CLL) at our institution to determine the management and resource use of these patients. A cost minimization analysis was then conducted. The per patient costs for the treatment of drug-related adverse events were in local currence R$ 1.476,87 for oral fludarabine and R$ 2.119,64 for IV fludarabine. When costs of a full course of each treatment were compared, the costs per patient for oral fludarabine and IV fludarabine were R$ 22.152,43 and R$ 23.160,31 respectively. In this preliminary analysis, considering that oral fludarabine has a similar efficacy rate and tolerability profile to IV fludarabine, the oral formulation appeared to have a lower total cost per patient. These data require confirmation with formal assessment of cost-effectiveness.

No abstract