JOPHON NCPD (2022 Nov/Dec) - Ifosfamide-Induced Neurotoxicity in Children with Solid Tumors: A Seven Year Retrospective Analysis of Incidence and Risk Factors-Ifosfamide-Induced Neurotoxicity in Children with Solid Tumors: A Seven Year Retrospective Analysis of Incidence and Risk Factors

Ifosfamide-Induced Neurotoxicity in Children with Solid Tumors: A Seven Year Retrospective Analysis of Incidence and Risk Factors

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This seven-year retrospective study examined ifosfamide-induced neurotoxicity (IIN) in pediatric patients with solid tumors treated at a large urban children’s hospital (CHOP) from 2011–2018. Ifosfamide can cause acute neurologic symptoms (from confusion and lethargy to twitching and seizures), likely related to accumulation of the metabolite chloroacetaldehyde. Because pediatric data—especially in solid tumors—are limited, the study aimed to measure IIN incidence, describe common symptoms, and identify risk factors.<br /><br />Records from 169 eligible patients (age ≤22 at diagnosis) were analyzed; leukemia/lymphoma and brain tumor patients were excluded to reduce confounding. Across these patients, 695 ifosfamide-containing cycles and 3,266 doses were administered. Overall, 22 patients (13%) developed IIN during 27 cycles, suggesting IIN occurs but may be less frequent than many adult reports. Common symptoms included muscle jerking (48%), confusion (37%), lethargy (26%), and muscle weakness (26%); falls/injury occurred in 7% of IIN cycles. Symptom resolution was generally rapid (average ~24 hours). About 41% received methylene blue, and one-third underwent brain imaging during evaluation. After an IIN episode, 37% received additional ifosfamide; 22% experienced recurrent toxicity with re-exposure.<br /><br />In logistic regression accounting for repeated measures, the key statistically significant risk factor was higher daily ifosfamide dose (≥2,000 mg/m²), associated with markedly increased odds of IIN (OR 17.82). Other group differences (race, diagnosis, relapsed disease, cisplatin exposure, infusion time) were observed but were likely confounded by treatment regimens that also deliver higher-dose ifosfamide (e.g., MAP/IE, salvage IE).<br /><br />The author concludes that pediatric IIN patterns should not be assumed to mirror adults and recommends heightened monitoring and further multi-site prospective research.

Keywords

ifosfamide-induced neurotoxicity

pediatric oncology

solid tumors

chloroacetaldehyde metabolite

incidence retrospective study

neurologic symptoms confusion lethargy seizures

high-dose ifosfamide risk factor

methylene blue treatment

re-exposure recurrence

Children's Hospital of Philadelphia CHOP