Seminal research led by James Ferrara, MD, DSc, Ward-Coleman Chair in Cancer Medicine, has produced a promising approach to treating patients with graft-versus-host disease (GVHD)—a sometimes fatal complication of bone marrow transplantation in which the donor’s immune cells attack the recipient’s body. Bone marrow transplants are often used to treat patients with leukemia, lymphoma, and other blood diseases.
At the core of this research is a new diagnostic test in the form of a scoring system that predicts each patient’s response to GVHD treatment and helps guide the physician. Using several cutting-edge proteomic techniques, Dr. Ferrara and his team discovered three plasma biomarkers (TNFR1, ST2, and Reg3 alpha), which led to a grading system to calculate patient responsiveness.
The new diagnostic vastly improves upon the traditional treatment that has changed little in 40 years, which calls for patients to be given high doses of systemic steroids that are effective only about half of the time.
“Our new scoring system provides for a personalized approach to transplantation so that each patient gets the right treatment at the right time,” says Dr. Ferrara, a leading authority on the immunologic complications of bone marrow transplantation, who is also Director of the Hematologic Malignancies Translational Research Center at the Mount Sinai Health System. “People with low-risk GVHD are often overtreated, exposing them to significant side effects. And those with high-risk GVHD are often undertreated, allowing the disease to progress.”
Equally important, the diagnostic scoring test is paving the way for a new generation of clinical trials that will also test investigative agents for the prevention and treatment of acute GVHD.
To advance the science, Dr. Ferrara recently created the Mount Sinai Acute GVHD International Consortium (MAGIC), comprised of 10 major stem cell transplant centers in the United States and Europe. Later this year, the consortium expects to launch a clinical trial approved by the U.S. Food and Drug Administration, making it the first to treat GVHD using the biomarker grading system.
In addition, Dr. Ferrara plans to actively collaborate with Mount Sinai researchers in the area of Inflammatory Bowel Disease (IBD), which has similar types of inflammation and disease pathways. He hopes to explore ways to genetically engineer bacteria to secrete proteins such as the GVHD biomarker Reg3 alpha, for example, to help protect the gastrointestinal tract.
“We’re gathering a critical mass of investigators at Mount Sinai with the ability to push the boundaries of immunotherapy and immunobiology further than ever before,” he says.