# The timing of concurrent intrathecal chemotherapy during blinatumomab infusion influences neurotoxicity in pediatric acute lymphoblastic leukemia

## TL;DR

Administering intrathecal chemotherapy on the same day as blinatumomab increases neurotoxicity risk in children with acute lymphoblastic leukemia.

## Contribution

Identifies Day 1 concurrent IT chemotherapy as a novel independent risk factor for neurotoxicity during blinatumomab treatment.

## Key findings

- Neurotoxic events occurred in 8.8% of patients, with no overall difference between concurrent IT and control groups.
- Day 1 concurrent IT chemotherapy was strongly associated with neurotoxicity (OR = 15.6).
- Multivariate analysis confirmed Day 1 IT as an independent risk factor (OR = 12.5).

## Abstract

To assess the safety profile of administering intrathecal (IT) chemotherapy concurrently with blinatumomab in pediatric patients with acute lymphoblastic leukemia (ALL).

This retrospective analysis included 93 pediatric ALL patients treated between February 2021 and May 2025 who received blinatumomab.

Of the 93 enrolled patients (median [Q1, Q3] age, 6 [4, 12] years), 42 (45%) were given IT chemotherapy concurrently, while the remaining 51 (55%) served as controls. Neurotoxic events occurred in eight patients (8.8%) overall, with no statistically significant difference between the concurrent IT and control groups (12% vs. 6%, p = 0.461). However, receiving IT chemotherapy on Day 1 of blinatumomab was strongly associated with neurotoxicity (OR = 15.6; 95% CI: 2.96–87.8; p = 0.001). Additional univariate predictors included CD4+ T-cell count (OR = 0.03; 95% CI: 0.00–0.50; p = 0.045), serum albumin (OR = 1.17; 95% CI: 1.02–1.39; p = 0.042), and bone marrow blast percentage (OR = 1.05; 95% CI: 1.01–1.09; p = 0.017). Multivariate analysis identified Day 1 concurrent IT administration as an independent risk factor (OR = 12.5; 95% CI: 1.45–131; p = 0.023).

Initiating IT chemotherapy on the same day as blinatumomab infusion significantly increases the risk of neurotoxicity in pediatric ALL patients.