Patients undergoing treatment for glioblastoma multiforme are routinely placed 
on prophylactic treatment for Pneumocystis jirovecii pneumonia because of 
significant therapy-induced lymphopenia. In patients with sulfa allergies, 
dapsone prophylaxis is often used due to its efficacy, long half-life, cost 
effectiveness, and general safety at low doses. However, dapsone may uncommonly 
induce a hemolytic anemia, particularly in patients deficient of 
glucose-6-phosphate dehydrogenase. This hemolysis is thought to be a result of 
oxidative stress on red blood cells induced by dapsone metabolites which produce 
reactive oxygen species that disrupt the red blood cell membrane and promote 
splenic sequestration. A single case report of dapsone-induced hemolytic anemia 
in a patient with glioblastoma multiforme has been reported. We present two 
patients with glioblastoma multiforme who developed severe hemolytic anemia 
shortly after initiating therapy with vorinostat, a pan-active histone 
deacetylase inhibitor, while on prophylactic dapsone. There are several 
potential mechanisms by which histone deacetylase inhibition may alter dapsone 
metabolism including changes in hepatic acetylation or N-glucuronidation leading 
to an increase in the bioavailability of dapsone's hematotoxic metabolites. In 
addition, vorinostat may lead to increased hemolysis through inhibition of heat 
shock protein-90, a chaperone protein that maintains the integrity of the red 
blood cell membrane cytoskeleton. The potential interaction between dapsone and 
vorinostat may have important clinical implications as more than 10 clinical 
trials evaluating drug combinations with vorinostat in patients with malignant 
glioma are either ongoing or planned in North America.