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This study aimed to investigate the incidence of severe psychiatric disturbances in patients treated for childhood ALL.

We report the results of a retrospective analysis of the incidence of severe psychiatric disturbances, defined as behavioral and psychological changes which lead to dangerous or erratic behaviors requiring use of psychiatric medications, in patients treated for childhood ALL. All patients were treated in a single institution and followed the same chemotherapeutic protocol, according to which, corticosteroids are administered initially during the “induction” phase and then in multiple subsequent pulses.

Seventy patients (mean age:4.04 years old, range:1-16) were treated for ALL during the 4 years of the observation period. During that period, 9 (12.8%) children (6 boys, 3 girls) of mean age 12.3 years old (range: 10-15) experienced psychiatric - neurological symptoms and/or mental disorders, which included major depressive disorder, withdrawal, first psychotic episode, disorientation, visual hallucinations, mood swings and behavioral outbursts. The majority of the patients (8 patients, 6 at the Intermediate Risk group and 2 at the High Risk group) experienced disturbances during the reinduction phase, while treated with dexamethasone at 10 mg/m2 for 21 days. Two patients of the High Risk group presented with behavioral effects one during the second HR2 block.

Patients who had symptoms of major depression were treated with either fluoxetine, or/and risperidone, or/ and escitalopram for a period of time ranging of 5 days to 6 months. One patient experienced a psychotic episode during reinduction (Prot.II,phase 2) with aggression and violence towards others and had to be treated immediately with intramuscularly haloperidol and diazepam.

All of our patients are alive and in remission, 7 off therapy for a period of 3 years, and 2 receiving maintenance therapy.

Statistical analysis showed that severe psychiatric disturbances were observed more frequently in older patients and they were more common with the administration of dexamethasone than with prednisolone.

Severe psychiatric disturbances are not infrequent in children and adolescents receiving treatment for ALL. Awareness of this complication, appropriate parental education for identifying early signs, and prompt therapeutic interventions are essential for optimal outcome. Further studies are required for identifying patients at risk and best use of chemotherapeutic agents and of dexamethasone.