Research Reports - Autologous bone marrow mononuclear cells reduce therapeutic intensity for severe traumatic brain injury in children
Pediatr Crit Care Med. 2015 Jan 9
Liao GP(1), Harting MT, Hetz RA, Walker PA, Shah SK, Corkins CJ, Hughes TG,
Jimenez F, Kosmach SC, Day MC, Tsao K, Lee DA, Worth LL, Baumgartner JE, Cox CS
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
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.