Researchers at the University of Missouri School of Medicine have discovered potential treatments for two different types of common complications after bone marrow transplants.
Bone marrow transplantation is a treatment that potentially cures leukemia and other blood cancers by transferring a type of stem cell from a donor to a patient. However, a common complication of bone marrow transplants is something called graft-versus-host disease (GvHD), in which the donated cells treat the recipient’s cells as an unknown threat or attack.
Acute GvHD occurs immediately after transplantation and often affects the skin, intestines, and liver. Chronic GvHD can occur at any time after transplantation and usually affects the skin, mouth, lungs, intestines, muscles, or joints.
In a recent study, the MU research team administered a drug called defibrotide, which is commonly used to treat blocked blood vessels in the liver, to mice undergoing bone marrow transplants. Researchers found that the drug protected cells lining blood vessels that are typically damaged in patients with acute GvHD.
“Treatment with defibrotide reduced acute GvHD and significantly improved survival,” said Dr. Senthilnathan Palaniyandhi, assistant professor of medicine at the University of Missouri School of Medicine. “Through its anti-inflammatory and endothelial protective effects, this treatment reduced the severity of acute GvHD without compromising the transplanted immune cells that fight leukemia.”
In another study, the research team targeted chronic GvHD. They found that introducing different types of BTK/ITK kinase inhibitors reduced the severity of chronic GvHD and improved mouse survival.
“We found that a complex kinase inhibitor is effective in skin diseases caused by chronic GVHD.” Dr. Gerhard HildebrandChief of the Division of Hematology and Medical Oncology, University of Missouri School of Medicine, Director, MU Health Care Ellis Fischel Cancer Center. “Mice treated with a combination of kinase inhibitors showed a significant reduction in chronic complications associated with bone marrow transplantation.”
These findings demonstrate that drugs that protect the cells lining blood vessels are effective in reducing acute GvHD, and that kinase inhibition holds promise as a treatment for chronic GvHD.
“A better understanding of how to manage GvHD is essential for clinically effective bone marrow transplantation at Ellis Fischel Cancer Center and around the world,” Hildebrandt said. “Our laboratory is one of a small number of laboratories dedicated to solving the mysteries of GVHD to make bone marrow transplantation more effective, advancing research, saving lives, and making improvements.” This demonstrates the University of Missouri Health System’s commitment to
The University of Missouri, one of the region’s leading academic health systems, is poised to lead cancer research, with the Roy Brandt Precision Health Building and Ellis Fischel Cancer Center bridging laboratory and clinical research on one clinical campus. It’s in a suitable location.
Role of defibrotide in preventing graft-versus-host disease in a mouse model after allogeneic hematopoietic cell transplantation Published in “Transplantation and Cellular Therapy” magazine. Combined inhibition of Tec kinases BTK and ITK is beneficial in ameliorating chronic graft-versus-host disease in murine scleroderma Published in “Bone Marrow Transplant.”
