Thursday, February 27, 2014
Memorial Sloan Kettering’s achievements in blood and marrow stem cell transplantation are center stage at the 2014 BMT Tandem Meeting, a joint conference of the American Society of Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research, taking place in the Dallas area through March 2. To help us understand how the meeting is unfolding, we asked several of our doctors to provide us with daily highlights.
Yesterday I presented the PROGRESS II trial (“BMT CTN 1301 – A Randomized, Multi-Center, Phase III Trial of Calcineurin Inhibitor-Free Interventions for Prevention of Graft-versus-Host Disease”) at the Blood and Marrow Clinical Trials Network investigators meeting.
Chronic graft-versus-host disease (GVHD) is a transplant complication that significantly affects quality of life, and results in decreased survival. Currently, the relapse-free, chronic GVHD-free survival rate is 22 percent, using standard approaches. We expect to significantly improve on these results with calcineurin inhibitor- (CNI-) free strategies, which should define a new standard of care.
The study is designed as a three-arm randomized phase III multicenter trial comparing two CNI-free strategies for GVHD prophylaxis to standard tacrolimus and methotrexate in patients with hematologic malignancies undergoing hematopoietic stem cell transplantation with myeloablative conditioning.
The CNI-free strategies include post-transplant cyclophosphamide, based on studies from Johns Hopkins, and CD34-selected grafts, based on a strategy pioneered at Memorial Sloan Kettering by Richard O’Reilly [Chair of the Department of Pediatrics]. Furthermore, the CD34-selected graft approach can serve as a platform for cell therapy to further improve outcomes.
Among the many interesting presentations yesterday was a session on emerging concepts in gastrointestinal GVHD. Alan Hanash from Memorial Sloan Kettering presented data from his lab and colleagues demonstrating that the intestinal stem cell compartment is damaged by GVHD, and that this damage is clinically relevant for bone marrow transplant patients.
He showed that intestinal stem cell numbers and function are reduced very early after allogeneic transplant, and that IL-22 [a protein secreted by cells in the thymus called lymphoid tissue inducer cells] may be able to promote epithelial recovery post-BMT by augmenting intestinal stem-cell-dependent regeneration. These results may have implications for future clinical trials in patients undergoing stem cell transplant.