An Observational Analysis of Voriconazole Therapeutic Drug Concentration Monitoring, Pharmacogenomics and Clinical Outcome Correlations in High-risk Hematology Patients

Hematology patients are at high risk for invasive fungal infection (IFI) and are being treated with voriconazole (VOR) at Princess Margaret Hospital (PMH). It is critical that patients' serum drug levels are within therapeutic ranges when undergoing treatment. The primary objective of this study is to determine whether clinical responses (complete/partial/failure) directly correlate with patients' blood VOR drug levels. In patients whose disease progression is associated with inadequate voriconazole (VOR) drug levels, serum drug level determination can allow for dose adjustment, thereby preventing disease progression. Patients who are extensive metabolizers may have subtherapeutic VOR levels leading to treatment failure whereas, poor metabolizers may have high drug levels that cause toxicity. Isoenzyme such as CYP2C19 exhibits genetic polymorphism. Genotyping tests can also be helpful in determining patient risk subjecting to extreme spectrum of drug levels.

Sex

All

Inclusion Criteria:

* Acute leukemia (including myelogenous and lymphocytic) patients for remission induction chemotherapy, reinduction chemotherapy and consolidation chemotherapy whose antifungal treatment include voriconazole.
* Patients have been subscribed voriconazole for probable or proven fungal infections by microbiological/cytohistological evidence from fine needle aspirate or bronchoalveolarlavage means.
* Patients will also have imaging positive from lose dose CT results depicting halo signs or crescent signs suggestive of invasive fungal infections.
* Patients must be able to tolerate oral intake of medications.

Exclusion Criteria:

* Patients unable to tolerate oral administration with any combinations of severe mucositis (\> or = grade 3), nausea/vomiting (\> or = grade 3), diarrhea (\> or =grade 2), neutropenic enterocolitis (\> or = grade3).