Neutrophil Extracellular Trap Formation in Patients Undergoing Bone Marrow Transplant

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by University of Utah
Sponsor:
Information provided by (Responsible Party):
University of Utah
ClinicalTrials.gov Identifier:
NCT01735565
First received: November 22, 2012
Last updated: July 30, 2014
Last verified: July 2014
  Purpose

This is a prospective observational study to determine the point after bone marrow transplant in adults and children at which the neutrophils derived from the transplanted stem cells are competent to form functional neutrophil extracellular traps (NETs). Furthermore, given the importance of platelet function for NET formation, we also plan to examine platelet activation and function as well as the platelet transcriptome using the same clinical samples.


Condition
Bone Marrow Transplant

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Neutrophil Extracellular Trap Formation in Patients Undergoing Bone Marrow Transplant

Resource links provided by NLM:


Further study details as provided by University of Utah:

Primary Outcome Measures:
  • Post-engraftment maturation of NET formation [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    The time to post-engraftment maturation of NET formation capability in PMNs isolated from pediatric and adult patients undergoing bone marrow transplantation will be measured by serial blood sampling/analysis over the course of a year after transplant.


Secondary Outcome Measures:
  • Post-engraftment platelet function [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Post-engraftment platelet function, transcriptome, and their potential influence on NET formation by PMNs will be measured by serial blood sampling/analysis over the course of a year after transplant.


Biospecimen Retention:   Samples With DNA

Whole blood


Estimated Enrollment: 90
Study Start Date: June 2012
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts
Post bone marrow transplant
Patients who are undergoing bone marrow transplant, as well as patients who have completed a bone marrow transplant within the previous year.

Detailed Description:

Background and Introduction

The role of the human polymorphonuclear leukocytes (PMNs) in the acute inflammatory response is well documented. PMNs play a fundamental role in the innate immune response and are rapidly recruited to areas of injury or inflammation where they participate in bacterial phagocytosis and killing. Disorders associated with a deficiency or impairment of PMN function (neutropenia, chronic granulomatous disease (CGD), leukocyte adhesion deficiency) predispose to infections with bacteria and fungi. Regulation of this potent component of the acute inflammatory response is imperative to prevent overwhelming infections often associated with morbidity and mortality.

Recently, neutrophils isolated from healthy adult donors were shown to undergo programmed cell death distinct from apoptosis and necrosis to form neutrophil extracellular traps (NETs). NETs are extensive lattices of extracellular DNA and chromatin decorated with anti-microbial proteins and degradative enzymes such as myeloperoxidase and neutrophil elastase (NE). NETs effect extracellular killing of bacteria and fungi. The laboratory of Christian Yost, MD recently characterized impaired NET formation as a novel innate immune deficiency of human newborn infants and showed that PMNs isolated from the cord blood of newborn infants, both term and preterm, demonstrated impaired NET formation and extracellular bacterial killing as compared to PMNs isolated from healthy adults. However, the timing for developmental maturation of newborn infant PMN NET formation remains unknown.

Stem cells for bone marrow transplants originate from cord blood, peripheral stem cells, or bone marrow stem cells. Regardless of the source of these stem cells, patients receiving a bone marrow transplant are essentially building a new immune system, as if they were a newborn baby. Immune system reconstitution is a continuous process whose components can take up to 1 to 2 years to fully recover. Severe infections in bone marrow transplant patients occur and may be associated with deficient PMN NET formation by way of impaired extracellular bacterial containment and killing. We hypothesize that the increased risk of infection attributed to bone marrow transplant recipients results, in part, from deficient PMN NET formation by the nascent, post-engraftment immune system which is molecularly and functionally similar to that of a newborn baby. We plan to determine the point after transplant at which the neutrophils derived from the transplanted stem cells are competent to form functional NETs. Furthermore, given the importance of platelet function for NET formation, we also plan to examine platelet activation and function as well as the platelet transcriptome using the same clinical samples.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Patients who are undergoing bone marrow transplant, as well as patients who have completed a bone marrow transplant within the previous year at Huntsman Cancer Institute and Primary Children's Medical Center will be identified as possible participants.

Criteria

Inclusion Criteria:

  • Within one year of bone marrow transplant
  • Informed consent

Exclusion Criteria:

  • No specific exclusion criteria
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01735565

Contacts
Contact: Christian Yost, MD 801-587-3498 christian.yost@u2m2.utah.edu

Locations
United States, Utah
University of Utah Recruiting
Salt Lake City, Utah, United States, 84132
Contact: Christian Yost, MD    801-587-3498    christian.yost@u2m2.utah.edu   
Principal Investigator: Christian Yost, MD         
Primary Children's Medical Center Recruiting
Salt Lake City, Utah, United States, 84113
Contact: Christian Yost, MD    801-587-3498    christian.yost@u2m2.utah.edu   
Contact: Michael Pulsipher, MD    801-662-4732    michael.pulsipher@imail.org   
Principal Investigator: Christian Yost, MD         
Sub-Investigator: Michael Pulsipher, MD         
Sub-Investigator: Meghann McManus, D.O.         
Huntsman Cancer Institute Recruiting
Salt Lake City, Utah, United States, 84112
Contact: Christian Yost, MD    801-587-3498    christian.yost@u2m2.utah.edu   
Contact: Joshua Schiffman, MD    801-587-4745    joshua.schiffman@hci.utah.edu   
Principal Investigator: Christian Yost, MD         
Sub-Investigator: Joshua Schiffman, MD         
Sponsors and Collaborators
University of Utah
Investigators
Principal Investigator: Christian Yost, MD University of Utah
  More Information

Publications:
Bianchi, M., Niemiec, M.J., Siler, U., Urban, C.F. & Reichenbach, J. Restoration of anti-Aspergillus defense by neutrophil extracellular traps in human chronic granulomatous disease after gene therapy is calprotectin-dependent. J Allergy Clin Immunol 127, 1243-1252 e1247 (2011).
Rondina, M.T., et al. In Vivo Platelet Activation in Critically-Ill Patients with Primary H1N1 Influenza. Chest (2012).

Responsible Party: University of Utah
ClinicalTrials.gov Identifier: NCT01735565     History of Changes
Other Study ID Numbers: 56286
Study First Received: November 22, 2012
Last Updated: July 30, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Utah:
NET formation
neutraphil extracellular traps
post-engraftment immune system

ClinicalTrials.gov processed this record on September 29, 2014