Abstract
Background: The use of cranial radiotherapy for central nervous system (CNS) prophylaxis in children
with acute lymphoblastic leukemia (ALL) is debated owing to its effect on neurocognitive
functioning, as only <30% of the patients present with low risk in India and majority
of the patients with high risk have to be treated with cranial radiation therapy (CRT)
to prevent relapse. Given the increasing number of ALL survivors in India, the effect
of CRT on neurocognitive functioning in children with ALL needs to be studied. Methods: Children (n = 44) with ALL who received CRT, intrathecal methotrexate (IT-MTX), and high-dose
methotrexate (HD-MTX) for CNS prophylaxis as part of the modified Berlin-Frankfurt-Munster
95 protocol were included. Neurocognitive assessments and magnetic resonance image
were performed to assess neurocognitive functioning and neuroanatomical structures,
respectively. Five assessments were performed during the induction, end of re-induction
I and II, commencement of maintenance, and end of maintenance phases of the modified
BFM-95 protocol. Neurocognitive data of children with ALL were compared with those
of healthy children (n = 60) at the baseline and after the final assessment. Results: A significant deterioration was observed in the performance intelligence, visuospatial
ability, processing speed, and verbal retention domains after the completion of CNS
prophylaxis. Three children had white matter changes on magnetic resonance imaging
and showed reduced functioning in performance intelligence quotient, working memory,
visual immediate and delayed memory, processing speed, verbal retention, visuospatial
ability, processing speed, attention, planning and fine motor skills, and verbal comprehension.
Children with ALL had poorer neuropsychological functioning when compared with healthy
children. Conclusion: CNS prophylactic therapy as part of the BFM-95 protocol had an adverse effect on
the neuropsychological functioning of children with ALL, and the effect was more pronounced
when CRT was added to the treatment.
Keywords
Acute lymphoblastic leukemia - BFM-95 protocol - central nervous system prophylactic
treatment - chemotherapy - childhood cancer - cranial irradiation - neuropsychological
functioning
