Acute Promyelocytic Leukemia (APL)
APL is highly curable with existing therapies; therefore, there has been
movement towards developing protocols that are less reliant on
potentially cardiotoxic anthracycline chemotherapy. AAML1331 evaluated
whether treating pediatric patients with APL using arsenic trioxide and
all-trans retinoic acid would allow for a reduced or eliminated need for
chemotherapy while maintaining high rates of event-free
survival.29 Environmental arsenic exposures confer
serious risks to the developing brain30,31 and, while
arsenic trioxide is not thought to cross the blood-brain barrier, there
have been reports of arsenic concentrations in the cerebrospinal fluid
of patients treated with arsenic trioxide.32,33
Neurocognitive aims were included in protocol AAML1331. This study
represented an important shift in approach that sought to demonstrate
the feasibility of incorporating the neurocognitive assessment battery
developed on ALTE07C1 into a therapeutic clinical trial rather than
enrolling patients separately on the standalone ALTE07C1 protocol. The
optional neurocognitive study was well-received by the AAML1331 study
committee and participating COG sites, as patients were enrolled at 73
different institutions (86% of all AAML1331 sites). There was also
strong interest from families, as the accrual target was reached early,
and the study was granted special permission to over-enroll. Data
collection is ongoing and, when complete, will clarify the short- and
long-term safety of arsenic trioxide for the treatment of pediatric APL.