Multicenter collaboration to reduce the risks inherent in allogeneic hematopoietic cell transplantation (HCT) is essential to dampen the dangers of regimen toxicity, infection, transfusion dependence, graft vs. host disease (GVHD) and malignant relapse. Ongoing efforts to address all these risks have been a focus of Network participation for investigators at the University of Minnesota. Our commitment to the Network has included participation as Steering Committee chair, national PI of four protocols, leading the first four Network publications and committing institutional resources to develop and successfully execute Network trials. Because umbilical cord blood (UCB) transplantation is still limited by delayed or failed engraftment, we initiated studies to augment the homing and hematopoietic recovery of UCB grafts based on preclinical data suggesting that complement fragment C3a can accomplish these goals. An ongoing University of Minnesota phase 1 trial testing C3a priming of one of a pair of UCB units to augment engraftment and enhance predominance of the primed unit provides the clinical background for a proposed multicenter phase 11. We propose a protocol testing whether C3a priming of one UCB unit can increase the likelihood of that unit's predominance as the engrafting hematopoietic source;can augment and accelerate multilineage hematopoietic recovery;and can enhance immune reconstitution thereby lessening risks of infection without excess graft vs. host disease. We offer our continued commitment to the Network's success in developing new protocols, identifying patients suitable for Network trial enrollment and performing protocol specific procedures. We will try to exceed the Network's standards in our commitment to enhance multicenter trial success and advance scientific progress within the Network. Multicenter collaborative trials are essential to formally test new ways to enhance the safety of allotransplantation and improve outcomes for our patients.
Improvement in the outcomes of allergenic transplantation requires control of early toxicity, risks of infection, transfusion dependence, graft vs. host disease and relapse. Multicenter trials within the BMT CTN have tackled all these areas and at the University of Minnesota we are committed to advancing the development and execution of high-quality Network trials. We propose augmenting the success of umbilical cord blood engraftment by priming one of a pair of UCB units with complement fragment C3a, to extend preliminary University of Minnesota data to a multicenter phase II trial. Improving engraftment and post transplant immune recovery may limit these hazards and augment the success of all transplantation.
|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 22:1747-57|
|MacMillan, Margaret L; Robin, Marie; Harris, Andrew C et al. (2015) A refined risk score for acute graft-versus-host disease that predicts response to initial therapy, survival, and transplant-related mortality. Biol Blood Marrow Transplant 21:761-7|
|Holtan, Shernan G; Verneris, Michael R; Schultz, Kirk R et al. (2015) Circulating angiogenic factors associated with response and survival in patients with acute graft-versus-host disease: results from Blood and Marrow Transplant Clinical Trials Network 0302 and 0802. Biol Blood Marrow Transplant 21:1029-36|
|MacMillan, Margaret L; DeFor, Todd E; Weisdorf, Daniel J (2012) What predicts high risk acute graft-versus-host disease (GVHD) at onset?: identification of those at highest risk by a novel acute GVHD risk score. Br J Haematol 157:732-41|
|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|