Evaluation of cyclosporine levels in pediatric patients submitted to hematopoietic stem cell transplantation in the Hospital de Clínicas de Porto Alegre

Abstract

Introduction: Hematopoietic stem cell transplantation (HSCT) is a complex procedure, in which stem cells from the bone marrow, peripheral blood or umbilical cord are inserted in the recipient. In order for the recipient receive these cells without developing Graft versus Host Disease (GvHD), immunosuppressive therapy should be followed. A well known drug used in this therapy is cyclosporine (Cya), whose mechanism of action is the T cells proliferation reduction, by the inhibition of interleukin-2. This drug presents high variability in the absorption rate, plus it follows metabolism by the cytochrome enzymes. Pharmacokinetic studies in the pediatric population using this drug are scarce. There are main differences in the pharmacokinetic parameters between solid organs and hematopoietic stem cells recipients. Materials and Methods: In this study we reviewed the medical records from the pediatric patients at the Hematological Service of the Hospital de Clínicas de Porto Alegre. We divided these patients into two groups: a) patients whose Cya levels were not used to dose adjustment based on pharmacokinetic analysis (n= 11) and b) patients whose Cya levels were used to dose adjustment based on pharmacokinetic analysis (n =11). Results: The medical records were accessed in order to obtain the patients’ demographics data and other relevant information such as renal function, grafting day and Cya mode of use and concomitant drugs intake. The indication for the treatment with intravenous (IV) Cya was the prophylaxis against GvHD. Most patients from both monitored and non-monitored groups presented CyA seric levels between the expected therapeutic window (100 ng/ml – 400 ng/ml), however in the literature it was found that in the period just after HSCT these levels should be higher (>200 ng/ml), in order to prevent the GvHD event. Conclusions: We observed that in the monitored group the levels out of the therapeutic window were above the expected, while in the non monitored group these levels were below the accepted ones. Our hypothesis is that due to the Pharmaceutical Service there was a better awareness by the health professionals in not letting Cya levels below 100ng/ml, as this could lead to GvHD development.