Ifosfamide-Induced Encephalopathy in Children and Young Adults: The MD Anderson Cancer Center Experience

Background: Ifosfamide, an alkylating agent used for treating various cancers, can cause encephalopathy in 10-30% of adults and 8% of children. Methylene blue has been used to treat ifosfamide-induced encephalopathy (IIE). This study aimed to describe our institutional experience with IIE in children and young adults with cancer, including its clinical manifestations, treatment, and outcomes. Methods: We reviewed the clinical records of patients with cancer aged up to 30 years who developed IIE over 10 years. Results: Twenty-four patients (median age: 17.6 years, range: 4-30 years) were included; 54% were male, and 71% had bone/soft tissue sarcomas. Ifosfamide was administered alone or with other drugs (dose range: 1.5-3.3 g/m²/day). Twelve patients developed IIE after short intermittent infusions (1-3 h), and twelve developed it after continuous infusions (12-24 h). IIE occurred at a median cumulative ifosfamide dose of 18 g/m². Symptoms appeared within hours to five days and resolved within 24-120 h. An altered mental status was present in all except one patient. Twelve patients had grade 3 IIE (severe somnolence, agitation, and confusion), and five had grade 4 IIE (coma and seizures). Twenty patients (83%) received methylene blue, with symptom resolution in nineteen patients (83%). Imaging studies showed nonspecific findings. Ten patients were re-challenged with ifosfamide; five received prophylactic methylene blue treatment, of whom three had recurrence. Conclusions: IIE can occur with both short intermittent and continuous ifosfamide infusions and presents as an altered mental status, seizures, and, rarely, hemiparesis. Symptoms are transient, and methylene blue may help alleviate this neurotoxicity, but it does not completely prevent its recurrence.