The pediatric and adult transplant programs at Duke University Medical Center have served as a core clinical center for the BMT-CTN since its establishment in 2001. As a core center, Duke has made significant contributions to the network, including enrollment of 117 patients on CTN protocols, chairing two protocols (Dr. Kurtzberg chairs 0501 and Dr. Horwitz chairs 0901);serving on 6 protocol committees and 2 disease committees, authoring manuscripts and establishing and managing the immune reconstitution core for protocol 0501. The center has been in compliance with accurate and timely data and bio-specimen submission. The PI and Co-PI have regularly attended steering committee meetings and conference calls. Duke brings two specialized types of expertise to the CTN, (1) a long-standing and pioneering role in cord blood transplantation and banking and (2) unique experience in the treatment of pediatric patients with hematopoietic stem cell transplantation for non-malignant diseases. The study concept proposed in this application, based on ongoing work at Duke, will serve as the foundation for a follow-on study to BMT-CTN 0501. It is focused on furthering the understanding of the mechanisms that underlie engraftment after UCBT. Through analyses of banking (from the Carolinas Cord Blood Bank) and transplant outcomes at Duke, we have shown that dosing of colony forming units (CFUs) in thawed cord blood units best correlates with engraftment. Further analyses of additional parameters characterizing cord blood units before cryopreservation and after thawing allowed us to develop a predictive scoring system, coined the """"""""cord blood apgar"""""""" (CBA) which, in a retrospective validation, most accurately determines cord blood potency and most closely correlates with engraftment potential. We propose to test and prospectively validate the CBA to optimize CBU selection in patients undergoing UCBT. The overarching goal of this work is to reduce engraftment delays and rates of primary graft failure after UCBT, increasing the overall success of UCBT.

Public Health Relevance

The BMT-CTN is a highly important network of transplant centers working together to identify best practices and best therapies for patients with malignant and non-malignant diseases treated with transplantation. Duke has participated in the CTN since 2001 and has contributed significantly to its mission. The research proposal in this application will increase safety and efficacy of cord blood transplantation.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Cooperative Clinical Research--Cooperative Agreements (U10)
Project #
5U10HL069274-13
Application #
8479407
Study Section
Special Emphasis Panel (ZHL1-CSR-K (M3))
Program Officer
Di Fronzo, Nancy L
Project Start
2001-09-30
Project End
2017-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
13
Fiscal Year
2013
Total Cost
$162,495
Indirect Cost
$58,995
Name
Duke University
Department
Pediatrics
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
Eapen, Mary; Kurtzberg, Joanne; Zhang, Mei-Jie et al. (2017) Umbilical Cord Blood Transplantation in Children with Acute Leukemia: Impact of Conditioning on Transplantation Outcomes. Biol Blood Marrow Transplant 23:1714-1721
Hope, William W; Walsh, Thomas J; Goodwin, Joanne et al. (2016) Voriconazole pharmacokinetics following HSCT: results from the BMT CTN 0101 trial. J Antimicrob Chemother 71:2234-40
Steering Committee Of The Blood And Marrow Transplant Clinical Trials Network (2016) The Blood and Marrow Transplant Clinical Trials Network: An Effective Infrastructure for Addressing Important Issues in Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant 22:1747-1757
Anderlini, Paolo; Wu, Juan; Gersten, Iris et al. (2015) Cyclophosphamide conditioning in patients with severe aplastic anaemia given unrelated marrow transplantation: a phase 1-2 dose de-escalation study. Lancet Haematol 2:e367-75
Wagner Jr, John E; Eapen, Mary; Carter, Shelly et al. (2014) One-unit versus two-unit cord-blood transplantation for hematologic cancers. N Engl J Med 371:1685-94
Mauskopf, Josephine; Chirila, Costel; Graham, Jon et al. (2013) Comparative cost-effectiveness analysis of voriconazole and fluconazole for prevention of invasive fungal infection in patients receiving allogeneic hematopoietic cell transplants. Am J Health Syst Pharm 70:1518-27
Tolar, Jakub; Deeg, H Joachim; Arai, Sally et al. (2012) Fludarabine-based conditioning for marrow transplantation from unrelated donors in severe aplastic anemia: early results of a cyclophosphamide dose deescalation study show life-threatening adverse events at predefined cyclophosphamide dose levels. Biol Blood Marrow Transplant 18:1007-11
Kamani, Naynesh R; Walters, Mark C; Carter, Shelly et al. (2012) Unrelated donor cord blood transplantation for children with severe sickle cell disease: results of one cohort from the phase II study from the Blood and Marrow Transplant Clinical Trials Network (BMT CTN). Biol Blood Marrow Transplant 18:1265-72
Wingard, John R; Carter, Shelly L; Walsh, Thomas J et al. (2010) Randomized, double-blind trial of fluconazole versus voriconazole for prevention of invasive fungal infection after allogeneic hematopoietic cell transplantation. Blood 116:5111-8