Patients undergoing bone marrow transplantation from different donors need to receive immunosuppressants to prevent the attack of their own cells by the donor cells; the ensuing immunosuppression state predisposes them to fungal infections that mandate addition of antifungal agents on a preventive basis. Cyclosporine and voriconazole are two medications that belong to the two categories respectively. These two medications are known to interact because of the complex process of drug metabolism, drug efflux into the cell. Nowadays, it is well known that “Pharmacogenomics”, the variability of the genetic background of individuals, implies the presence of a different set of enzymes that determine the fate of these two medications. Clinically, it is observed that the pattern of interaction is distinct among different individuals with some individuals sustaining toxicity from cyclosporine when receiving voriconazole concomitantly. This interaction might lead to subtherapeutic dosing of cyclosporine and the need to escalate the prescribed dose to achieve a therapeutic concentration with the possibility of higher risk in terms of decrease in renal function, elevation in blood pressure.. This study aims at understanding the role of pharmacogenomics in the different pattern of interaction among voriconazole and cyclosporine.
Blood sample will be collected and DNA will be extracted then process in a special kit designed to probe for the different mutations in the genes coding for the enzymes in charge of metabolism of these medications. In parallel, the medical records of the patients will be reviewed and specific parameters related to cyclosporine toxicity will be recorded such as: blood pressure, change in creatinine, prescribed dose, serum trough concentration..
Finally, clinical and laboratory data will be pooled together and analysis will be run to detect any association between the pharamacogenomic profile and the clinical data. This study will be the first of its kind in looking into this complex interaction and will pave the way for the future integration of pharmacogenomics in the practice of prescribing of medications with highly interactions pharmacokinetic profiles.
1) Adult patients
2) Patient undergoing first allogeneic peripheral stem cell transplantation
3) Indication for transplantation is hematological malignancy
4) Transplantation is based on a matched related donor
5) Conditioning regimen includes fludarabin/IV busulfan and thymoglobulin
6) Cyclosporine is used for GVHD prophylaxis
7) Voriconazole is used as primary prophylaxis with no past history of IFI
8) Patients who have a DNA sample available in the Molecular Diagnostics Laboratory