Many patients, particularly those from ethnic minorities, are unable to access the therapeutic benefit of allogeneic hematopoietic cell transplantation due to the lack of a suitable donor. For such patients, umbilical cord blood can offer an alternative source of hematopoietic cells. However, adults typically require the concurrent use of two cord blood units (DCBT) at considerable expense. In adults such transplants are also associated with delayed immune reconstitution, increased rate of infections and a higher treatment related mortality than transplants from conventional donors. Recently the use of haploidentical (partially matched related donor) hematopoietic cell transplants (haplo-HCT) using T-cell-replete marrow grafts and post- transplant cyclophosphamide (PTCy), have been shown to produce high rates of engraftment and low treatment related mortality (TRM) when used with a non-myeloablative preparative regimen, in patients who lack conventional donors. However, such transplants have limited efficacy in aggressive/advanced myeloid malignancies because of a high relapse rate. In an institutional pilot trial, we have assessed the use of T- replete mobilized peripheral blood (PBSC) and a myeloablative preparative regimen with haplo-HCT + PTCy. Despite the advanced and high-risk nature of the malignancies treated, estimated 6 month TRM was 14% and disease-free survival was 72%. All patients engrafted and developed full donor chimerism in CD3+ and CD33+ cells by day +30. A multi-institutional phase II trial is therefore proposed within the BMT CTN to confirm these encouraging results. The proposed trial will test the hypothesis that this novel approach to myeloablative haplo-HCT is safe and effective when used in a multi-institutional setting. Upon successful completion of this phase II trial, a randomized phase 111 comparison is proposed between this approach to haplo-HCT and myeloablative DCBT. The objective of this phase 111 study will be to directly compare these two approaches to alternative donor transplantation with respect to safety, toxicity, efficacy, cost and immune reconstitution. This trial would definitively determine the best option for myeloablative transplantation in patients with advanced malionancies who lack a matched-sibling or matched unrelated donor

Public Health Relevance

The proposed research addresses a significant current deficiency in public health. Specifically, it tests a novel strategy that will enable curative myeloablative blood stem cell transplants in patients (particularly those from underserved minorities) who are currently unable to access them due to lack of a conventional donor. If successful, it will transform the standard-of-care by offering life-saving therapy to patients who would have died from their cancer and close a major disparity in healthcare access for ethnic minorities.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Cooperative Clinical Research--Cooperative Agreements (U10)
Project #
Application #
Study Section
Special Emphasis Panel (ZHL1-CSR-K (M3))
Program Officer
Di Fronzo, Nancy L
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Northside Hospital Atlanta
United States
Zip Code
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
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; 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
BolaƱos-Meade, Javier; Logan, Brent R; Alousi, Amin M et al. (2014) Phase 3 clinical trial of steroids/mycophenolate mofetil vs steroids/placebo as therapy for acute GVHD: BMT CTN 0802. Blood 124:3221-7; quiz 3335
Eapen, Mary; O'Donnell, Paul; Brunstein, Claudio G et al. (2014) Mismatched related and unrelated donors for allogeneic hematopoietic cell transplantation for adults with hematologic malignancies. Biol Blood Marrow Transplant 20:1485-92
Jacobsen, Paul B; Le-Rademacher, Jennifer; Jim, Heather et al. (2014) Exercise and stress management training prior to hematopoietic cell transplantation: Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0902. Biol Blood Marrow Transplant 20:1530-6
McCarthy, Philip L; Owzar, Kouros; Hofmeister, Craig C et al. (2012) Lenalidomide after stem-cell transplantation for multiple myeloma. N Engl J Med 366:1770-81