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 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 PUBLIC HEALTH RELEVANCE The goal of this Phase II SBIR submission is to evaluate the ability of high throughput T and B Cell Receptor sequencing to predict the risk of infectious complications in patients recovering from umbilical cord blood derived stem cell transplants Such transplants carry a high risk of patient mortality but if successful this study will lead to improved management of infectious disease based on each patientandapos s individual risk and improved overall patient survival