Neurocognitive Outcome of Childhood ALL Survivors Using Three Different Protocols Over a Decade

A cross-sectional study including 60 ALL survivors aged 5–16 years at enrollment; 2–9 years at diagnosis, CNS1, treated through 1998–2008 and regularly followed up in childhood cancer survivors clinic;. They were compared to 20 healthy age and sex matched controls. Grade of school, scholastic achievement in the previous year were reported followed by revision of hospital records including type and risk of ALL, protocol of treatment, number, type and dose of intrathecal chemotherapy, number and doses of high dose I.V methotrexate, data of cranial radiotherapy. Three different protocols were applied to these patients according to the time of diagnosis, patients diagnosed between January 1998 to December 2000 were treated with Modified BFM 83. Those diagnosed between January 2001 to June2004 were treated with BFM 90 protocol, and those diagnosed From July 2004 to June 2008 were treated with CCG 1991 for standard risk and CCG 1961 for high risk patients.Neurocognitive functions were tested using Wechsler Intelligence Scale for Children,Benton visual retention (BVR) test and Trail making test (part A and B were done. MRI Brain was performed to the patients and control group using diffusion weighed images and diffusion tensor magnetic resonance imaging (DTI).

Survivors treated with CCG protocol showed a significant decrease in all cognitive tests results compared to control (p<0.05). Survivors treated with BFM 90 protocol had a significant lower total IQ, verbal IQ, TMT-partA, compared to both control and survivors treated with Modified BFM 83, and a significant decrease in performance IQ, BVRT and TMT-partB compared to control only. No significant difference between results of cognitive tests in survivors treated with Modified BFM 83 and control group. Both left and right frontal cortex apparent diffusion coefficient (ADC) was significantly higher in CCG(.88±.060.91±.028) treated group compared to control(.695±.0018.684±.0018), BFM 90(.79±.071.76±.048) and modified BFM 83(.76±.030.83±.023×10&minus;3mm2/s) groups (p<0.05) yet a significant decrease in FA of right frontal cortex only in CCG (.250±.039)treated group compared to control(.684±.0018), BFM 90(.450±.042) and Modified BFM 83(.41±.028) groups(p<0.05). FA of right frontal, was significantly lower in BFM 90 and Modified BFM 83 treated group compared to control group. No significant correlation was found between cognitive tests results with age at diagnosis, time since the end of therapy, total number of intrathecal injections, age at radiotherapy treatment, dose and time of radiotherapy. Cognitive tests didn’t differ between survivors treated with triple intrathecal therapy(ITTT) compared to those treated with intrathecal methotrexate, yet significant decrease in FA of right hippocampus in survivors who received ITTT compared to survivors treated with intrathecal monotherapy,

Neurocognitive dysfunction was a common sequelae of childhood ALL treatment. It was more related to protocol of therapy rather than the duration of follow-up since end of chemotherapy. Frontal lobe FA may be a clinically useful biomarker for the assessment of neurotoxicity in post-treatment childhood ALL survivors.

No relevant conflicts of interest to declare.