title: Autologous bone marrow mononuclear cells reduce therapeutic intensity for severe traumatic brain injury in children.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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).
  
  
  METHODS
  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.
  
  
  METHODS
  Study patients were 5-14 years with postresuscitation Glasgow Coma Scale scores of 5-8.
  
  
  METHODS
  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.
  
  
  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.
authors.affiliation: 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.
authors.forename: George P
authors.initials: GP
authors.lastname: Liao
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Harting
authors.forename: Robert A
authors.initials: RA
authors.lastname: Hetz
authors.forename: Peter A
authors.initials: PA
authors.lastname: Walker
authors.forename: Shinil K
authors.initials: SK
authors.lastname: Shah
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Corkins
authors.forename: Travis G
authors.initials: TG
authors.lastname: Hughes
authors.forename: Fernando
authors.initials: F
authors.lastname: Jimenez
authors.forename: Steven C
authors.initials: SC
authors.lastname: Kosmach
authors.forename: Mary-Clare
authors.initials: MC
authors.lastname: Day
authors.forename: KuoJen
authors.initials: K
authors.lastname: Tsao
authors.forename: Dean A
authors.initials: DA
authors.lastname: Lee
authors.forename: Laura L
authors.initials: LL
authors.lastname: Worth
authors.forename: James E
authors.initials: JE
authors.lastname: Baumgartner
authors.forename: Charles S
authors.initials: CS
authors.lastname: Cox
mesh_terms: D000293:Adolescent; D016026:Bone Marrow Transplantation / Q000379:methods*; D001930:Brain Injuries / Q000503:physiopathology / Q000628:therapy*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D015600:Glasgow Coma Scale; D006801:Humans; D007262:Infusions, Intravenous; D007427:Intracranial Pressure; D008297:Male; D009000:Monocytes / Q000166:cytology / Q000637:transplantation*; D012189:Retrospective Studies; D013997:Time Factors; D014182:Transplantation, Autologous / Q000379:methods*; D015599:Trauma Severity Indices; D016896:Treatment Outcome