Correlating TCR diversity to immune reconstitution after cord blood transplant

Information

  • Research Project
  • 8731965
  • ApplicationId
    8731965
  • Core Project Number
    R44HL106868
  • Full Project Number
    5R44HL106868-03
  • Serial Number
    106868
  • FOA Number
    PA-12-088
  • Sub Project Id
  • Project Start Date
    12/1/2010 - 14 years ago
  • Project End Date
    10/31/2017 - 7 years ago
  • Program Officer Name
    MITCHELL, PHYLLIS
  • Budget Start Date
    3/1/2015 - 9 years ago
  • Budget End Date
    10/31/2016 - 8 years ago
  • Fiscal Year
    2015
  • Support Year
    03
  • Suffix
  • Award Notice Date
    3/5/2015 - 9 years ago

Correlating TCR diversity to immune reconstitution after cord blood transplant

DESCRIPTION (provided by applicant): Many patients requiring stem cell transplantation for hematological malignancies are unable to find a suitable HLA-matched sibling or unrelated donor. Transplants using stem cells from umbilical cord blood provide an alternative for these patients, allowing transplantation to proceed with less stringent HLA-matching requirements. Unfortunately, in addition to the risk of relapsed disease, patients undergoing cord blood transplants have a high risk of death from infections due to slow reconstitution of their immune system. In this clinical observational study, we propose to use high-throughput DNA sequencing of T- Cell Receptor (TCR) and Immunoglobulin heavy chain (IgH) genes from peripheral blood to study the reconstitution of the adaptive immune system following cord blood transplant. We will use high-throughput sequencing to estimate the diversity of T- and B-cell receptors in each of approximately 240 patients at defined time-points following transplant, and demonstrate a correlation between our measure of adaptive immune receptor diversity and subsequent morbidity and mortality from infectious complications. Further development of this technique would lead to a Phase III application with a clinical intervention study in which this assay would provide a diagnostic method to identify patients at high risk for infectious complications soon after transplant. Clinical care would be administered for an increased-intensity regimen of antimicrobial prophylaxis to high-risk patients. We expect that early identification of high-risk patients, combined with more aggressive prophylaxis for these patients, will reduce the high treatment-related mortality present in cord blood transplants.

IC Name
NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
  • Activity
    R44
  • Administering IC
    HL
  • Application Type
    5
  • Direct Cost Amount
  • Indirect Cost Amount
  • Total Cost
    1057509
  • Sub Project Total Cost
  • ARRA Funded
    False
  • CFDA Code
    837
  • Ed Inst. Type
  • Funding ICs
    NHLBI:1057509\
  • Funding Mechanism
    SBIR-STTR RPGs
  • Study Section
    ZRG1
  • Study Section Name
    Special Emphasis Panel
  • Organization Name
    ADAPTIVE BIOTECHNOLOGIES CORPORATION
  • Organization Department
  • Organization DUNS
    832591544
  • Organization City
    SEATTLE
  • Organization State
    WA
  • Organization Country
    UNITED STATES
  • Organization Zip Code
    981027402
  • Organization District
    UNITED STATES