Acute leukemia (AL), including Acute Lymphoblastic Leukemia (ALL), Acute Myeloid Leukemia
(AML) and myeloproliferative neoplasms (MPN) are among the most common childhood cancers,
the 5-year overall survival of children with leukemia has significantly improved with the
current treatment methods, and is now ~90 % for ALL participants and ~70 % for AML
participants. There has been a remarkable shift in the treatment strategy for childhood
acute leukemia to reduce the burden of therapy related complications. Most notably, the
addition of central nervous system (CNS)-directed, intensified intravenous and
intrathecal chemotherapy regimens for most standard risk participants has obviated the
need for craniospinal radiation therapy (CRT), thus reserving CRT for high-risk
participants. With the improved overall survival rates, there is an increasing focus on
characterizing and mitigating the long-term effects of the disease and therapy that may
affect the quality of life of these participants. The results of multiple studies have
indicated that the long-term survivors of ALL and AML experience varying degrees of
neurocognitive deficits including memory loss, poor concentration, deficits in executive
functioning and personality changes5-9. Methotrexate which is an important
chemotherapeutic agent in the treatment of acute leukemia is known to cause chemotherapy
induced cognitive impairment (CICI), by causing complex glial dysfunction leading to
disruption of activity-dependent myelination in the CNS.
Studies designed to characterize normal brain development in early childhood have not
only contributed significantly to our understanding of healthy neurodevelopment, but have
also helped to identify neurodevelopmental problems at an early stage, enabling the
application of treatment interventions in a timely fashion. Although magnetic resonance
imaging (MRI) has been used for this purpose, its application has been hampered by
several limitations including the sensitivity to motion artifact, the length of time
required to perform a scan, and the requirement for sedation for younger participants.
These limitations can be overcome using a new technology known as magnetic resonance
fingerprinting (MRF), which allows for rapid, efficient and simultaneous quantification
of multiple tissue properties, and quantifies T1, T2 and Myelin Water Fraction (MWF)
simultaneously. Sedation is not necessary since whole brain MRF imaging takes
approximately 5 minutes to complete and is resistant to motion artifacts.
These properties position MRF for use to assess multiple tissue properties in both
pediatric and AYA participants diagnosed with acute leukemia, before, during and after
exposure to CNS directed chemotherapy. The investigator proposes to use MRF to monitor
demyelination, which has been documented as an underlying mechanism contributing to the
long-term neurocognitive deficits seen in participantsundergoing chemotherapy. The goal
of using MRF in this context is that it might ultimately serve as a valuable imaging
biomarker that would enable early detection of the participants that are at an increased
risk of developing neurocognitive deficits due to exposure to anti-neoplastic
chemotherapy, by detecting the myelin changes as defined by MRF quantification of myelin
water fraction. The capacity for detection would facilitate development of early
interventions for these high-risk participants, so that their quality of life can be
preserved as much as possible.
The study will evaluate the feasibility of obtaining MRF imaging data along with
assessments of neurocognitive function. Chanages/decline in neurocognitive function in
pediatric participants undergoing treatment for acute leukemia have been tested,
validated and reported by the Children's Oncology Group using a battery of assessment
developed by Cogstate®. The computerized cognitive tests are rapid, reliable, and have
demonstrated sensitivity to drug related changes in cognition. The tests have been
designed and validated to withstand operational challenges during the conduction of
clinical trials. The data system is HIPAA compliant U.S. FDA Class II Exempt Digital
Medical Device.