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Autologous Bone Marrow Mononuclear Cells Reduce Therapeutic Intensity for Severe Traumatic Brain Injury in Children*

Liao, George P. MD1; Harting, Matthew T. MD1; Hetz, Robert A. MD1; Walker, Peter A. MD1; Shah, Shinil K. DO1,2; Corkins, Christopher J. MD1; Hughes, Travis G. BS1; Jimenez, Fernando MS, RN1; Kosmach, Steven C. MSN, RN1; Day, Mary-Clare BSN, RN1; Tsao, KuoJen MD1; Lee, Dean A. MD, PhD3; Worth, Laura L. MD, PhD3; Baumgartner, James E. MD1; Cox, Charles S. Jr MD1,2

Pediatric Critical Care Medicine: March 2015 - Volume 16 - Issue 3 - p 245–255
doi: 10.1097/PCC.0000000000000324
Neurocritical Care
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Objectives: The devastating effect of traumatic brain injury is exacerbated by an acute secondary neuroinflammatory response, clinically manifest as elevated intracranial pressure due to cerebral edema. The treatment effect of cell-based therapies in the acute post–traumatic brain injury period has not been clinically studied although preclinical data demonstrate that bone marrow–derived mononuclear cell infusion down-regulates the inflammatory response. Our study evaluates whether pediatric traumatic brain injury patients receiving IV autologous bone marrow–derived mononuclear cells within 48 hours of injury experienced a reduction in therapeutic intensity directed toward managing elevated intracranial pressure relative to matched controls.

Design: The study was a retrospective cohort design comparing pediatric patients in a phase I clinical trial treated with IV autologous bone marrow–derived mononuclear cells (n = 10) to a control group of age- and severity-matched children (n = 19).

Setting: The study setting was at Children’s Memorial Hermann Hospital, an American College of Surgeons Level 1 Pediatric Trauma Center and teaching hospital for the University of Texas Health Science Center at Houston from 2000 to 2008.

Patients: Study patients were 5–14 years with postresuscitation Glasgow Coma Scale scores of 5–8.

Interventions: The treatment group received 6 million autologous bone marrow–derived mononuclear cells/kg body weight IV within 48 hours of injury. The control group was treated in an identical fashion, per standard of care, guided by our traumatic brain injury management protocol, derived from American Association of Neurological Surgeons guidelines.

Measurements and Main Results: The primary measure was the Pediatric Intensity Level of Therapy scale used to quantify treatment of elevated intracranial pressure. Secondary measures included the Pediatric Logistic Organ Dysfunction score and days of intracranial pressure monitoring as a surrogate for length of neurointensive care. A repeated-measure mixed model with marginal linear predictions identified a significant reduction in the Pediatric Intensity Level of Therapy score beginning at 24 hours posttreatment through week 1 (p < 0.05). This divergence was also reflected in the Pediatric Logistic Organ Dysfunction score following the first week. The duration of intracranial pressure monitoring was 8.2 ± 1.3 days in the treated group and 15.6 ± 3.5 days (p = 0.03) in the time-matched control group.

Conclusions: IV autologous bone marrow–derived mononuclear cell therapy is associated with lower treatment intensity required to manage intracranial pressure, associated severity of organ injury, and duration of neurointensive care following severe traumatic brain injury. This may corroborate preclinical data that autologous bone marrow–derived mononuclear cell therapy attenuates the effects of inflammation in the early post–traumatic brain injury period.

1Department of Pediatric Surgery, University of Texas Health Science Center at Houston, Houston, TX.

2Michael E DeBakey Institute for Comparative Cardiovascular Science and Biomedical Devices, Texas A&M University, College Station, TX.

3Division of Pediatrics, Department of Stem Cell Therapy, MD Anderson Cancer Center, Houston, TX.

* See also p. 294.

This work was performed at Department of Pediatric Surgery, University of Texas Health Science Center at Houston, Houston, TX.

Supported, in part, by grants M01 RR 02558, UL1 RR024148, and T32 GM 0879201 from the National Institutes of Health.

Dr. Liao and Ms. Day received support for article research from the National Institutes of Health (NIH). Their institutions received grant support from the NIH. Drs. Harting, Hetz, Shah, Jimenez, Tsao, Lee, and Worth received support for article research from the NIH. Dr. Kosmach received support for article research from the NIH. His institution received grant support from the NIH/National Institute of Neurological Disorders and Stroke. Dr. Cox consulted for CBR, lectured for CBR, has patents with Athersys and EMIT, and received support for article research from the NIH. Dr. Cox and his institution received grant support from the NIH, Athersys, and CBR; received royalties from EMIT; and has stock with EMIT. The remaining authors have disclosed that they do not have any potential conflicts of interest.

Address requests for reprints to: Charles S. Cox Jr, MD, Department of Pediatric Surgery, University of Texas Health Science Center at Houston, 6431 Fannin Street, MSB 5.236, Houston, Texas 77030. E-mail: Charles.S.Cox@uth.tmc.edu

©2015The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies