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.