Autologous bone marrow mononuclear cells to treat severe traumatic brain injury in children

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Posted on January 5, 2024 by childrenslearninginstitute

Published:

January 5, 2024

Publication:

Brain

CLI Author:

Linda Ewing-Cobbs, PhD

Abstract:

Autologous bone marrow mononuclear cells (BMMNCs) infused after severe traumatic brain injury have shown promise for treating the injury. We evaluated their impact in children, particularly their hypothesized ability to preserve the blood-brain barrier and diminish neuroinflammation, leading to structural central nervous system preservation with improved outcomes.

We performed a randomized, double-blind, placebo-sham-controlled Bayesian dose-escalation clinical trial at 2 children’s hospitals in Houston, TX and Phoenix, AZ, USA (NCT01851083). Patients 5-17 years of age with severe traumatic brain injury (Glasgow Coma Scale ≤ 8) were randomized to BMMNC or placebo (3:2). Bone marrow harvest, cell isolation, and infusion were completed by 48 hours post-injury. Bayesian continuous reassessment method was used with cohorts of size 3 in the BMMNC group to choose the safest between 2 doses. Primary endpoints were quantitative brain volumes using magnetic resonance imaging and microstructural integrity of the corpus callosum (CC; diffusivity and edema measurements) at 6 months and 12 months. Long-term functional outcomes and ventilator days, intracranial pressure monitoring days, intensive care unit days, and therapeutic intensity measures were compared between groups.

Forty-seven patients were randomized, with 37 completing 1-year follow-up (23 BMMNC, 14 placebo). BMMNC treatment was associated with an almost 3-day (23%) reduction in ventilator days, 1-day (16%) reduction in intracranial pressure monitoring, and 3-day (14%) reduction in intensive care unit (ICU) days. White matter volume at 1 year in the BMMNC group was significantly preserved compared to placebo (decrease of 19891 vs 40491, respectively; mean difference of -20600, 95% CI: -35868 to -5332; P = 0.01), and the number of CC streamlines was reduced more in placebo than BMMNC, supporting evidence of preserved CC connectivity in the treated groups (-431 streamlines placebo vs. -37 streamlines BMMNC; mean difference of -394, 95% CI: -803 to 15; P = 0.055), but this did not reach statistical significance due to high variability.

We conclude that autologous BMMNC infusion in children within 48 hours after severe traumatic brain injury is safe and feasible. Our data show that BMMNC infusion led to 1) shorter intensive care duration and decreased ICU intensity; 2) white matter structural preservation; and 3) enhanced CC connectivity and improved microstructural metrics.

Citation:

Charles S Cox, David M Notrica, Jenifer Juranek, Jeffrey H Miller, Fabio Triolo, Steven Kosmach, Sean I Savitz, P David Adelson, Claudia Pedroza, Scott D Olson, Michael C Scott, Akshita Kumar, Benjamin M Aertker, Henry W Caplan, Margaret L Jackson, Brijesh S Gill, Robert A Hetz, Michael S Lavoie, Linda Ewing-Cobbs, Autologous bone marrow mononuclear cells to treat severe traumatic brain injury in children, Brain, 2024;, awae005, https://doi.org/10.1093/brain/awae005

DOI:

https://doi.org/10.1093/brain/awae005