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.

Public Health Relevance

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.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Cooperative Clinical Research--Cooperative Agreements (U10)
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Special Emphasis Panel (ZHL1-CSR-K (M3))
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Di Fronzo, Nancy L
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University of Minnesota Twin Cities
Internal Medicine/Medicine
Schools of Medicine
United States
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D'Souza, Anita; Pasquini, Marcelo; Logan, Brent et al. (2017) Heavy/light chain ratio normalization prior to transplant is of independent prognostic significance in multiple myeloma: a BMT CTN 0102 correlative study. Br J Haematol 178:816-819
Scott, Bart L; Pasquini, Marcelo C; Logan, Brent R et al. (2017) Myeloablative Versus Reduced-Intensity Hematopoietic Cell Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndromes. J Clin Oncol 35:1154-1161
Laport, Ginna G; Wu, Juan; Logan, Brent et al. (2016) Reduced-Intensity Conditioning with Fludarabine, Cyclophosphamide, and High-Dose Rituximab for Allogeneic Hematopoietic Cell Transplantation for Follicular Lymphoma: A Phase Two Multicenter Trial from the Blood and Marrow Transplant Clinical Trials Networ Biol Blood Marrow Transplant 22:1440-1448
Young, Jo-Anne H; Logan, Brent R; Wu, Juan et al. (2016) Infections after Transplantation of Bone Marrow or Peripheral Blood Stem Cells from Unrelated Donors. Biol Blood Marrow Transplant 22:359-370
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O'Donnell, P V; Eapen, M; Horowitz, M M et al. (2016) Comparable outcomes with marrow or peripheral blood as stem cell sources for hematopoietic cell transplantation from haploidentical donors after non-ablative conditioning: a matched-pair analysis. Bone Marrow Transplant 51:1599-1601
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
Holtan, Shernan G; DeFor, Todd E; Lazaryan, Aleksandr et al. (2015) Composite end point of graft-versus-host disease-free, relapse-free survival after allogeneic hematopoietic cell transplantation. Blood 125:1333-8
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
Levine, John E; Braun, Thomas M; Harris, Andrew C et al. (2015) A prognostic score for acute graft-versus-host disease based on biomarkers: a multicentre study. Lancet Haematol 2:e21-9

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