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.