Methods: We retrospectively reviewed the records of adult pts with HM who had a random VRC level > 5.5mcg/mL at MD Anderson Cancer Center (January 2010 to December 2015). VRC was used for IFI prophylaxis or treatment. Pts with any documented CNS neurotoxicity at the time the VRC level was obtained were excluded. The neurologic status was assessed using neurotoxicity NCI grading scales. Demographic and clinical characteristics, including potentially interacting medications, were correlated with the development of toxicity.
Results: We identified 320 patients (mean age 57 ± 15 y; 63% male). 67.2% had acute leukemia, 33.1% had prior hematopoietic stem cell transplant and 73.1% were receiving VRC for treatment of an IFI. Median follow up was 103 days (IQR 36-314 days). Subsequent CNS toxicity was documented in only 16 patients (5.0%). The most common CNS toxicities were visual disturbances (56.3%), depressed level of consciousness (37.5%) and cognitive disturbance (18.8%). Pts with CNS toxicity tended to be older than those without (64 ± 8 vs 57 ± 15 y, p = 0.08). The use of one or more concomitant neurotoxic drugs was comparable in pts with developed new CNS toxicity than those without (87.5% vs. 79.3%, p = 0.43).
Conclusion: The development of subsequent CNS toxicity is uncommon in pts with supra-therapeutic VRC serum levels who had no evidence of toxicity at the time VRC level was obtained. Automatic VRC dose reduction for the concern for impending CNS toxicity might not be justified in such pts.
S. T. Heo,
F. P. Tverdek, Astellas: Scientific Advisor , Consulting fee
D. P. Kontoyiannis, â¢: Advisory Board , Research support
Pfizer: Research grant , Research support
Gilead: Invited lecturer , Speaker honorarium
Astellas: Consultant , Research support and Speaker honorarium
F2G: Consultant , Consulting fee
T2 Biosystems: Invited lecturer , Speaker honorarium
Mylan Inc: Invited lecturer , Speaker honorarium