James Ferrara, MD, DSc
Physician-scientists at The Tisch Cancer Institute have been awarded $10 million from the National Cancer Institute to continue their novel research into therapies that improve the standard of care for patients who develop acute graft-versus-host disease (GVHD) following bone marrow transplantation. Bone marrow transplantation (BMT) is often successfully used to treat diseases such as leukemia and lymphoma. Acute GVHD, which affects approximately 50 percent of patients, occurs when the donor’s immune cells attack the patient’s tissues, producing potentially fatal results.
Led by world-renowned GVHD researchers James L. Ferrara, MD, DSc, and John E. Levine, MD, the five-year grant will enable the Icahn School of Medicine at Mount Sinai to spearhead a consortium of 20 major medical centers in the United States and Europe that will share patient data.
With Mount Sinai coordinating the information, the researchers plan to examine blood samples from 1,000 bone marrow transplant patients
A gastrointestinal crypt is under attack from donor T cells (red globules), which destroy intestinal stem cells (ISCs) and adjacent Paneth cells that protect them. When the ISCs disintegrate, bacteria (enterococcus, bacillus) from the intestinal lumen enter the bloodstream, causing widespread infection and inflammation. An antimicrobial peptide made by Paneth cells (Reg3a) also enters the bloodstream at the same time, acting as a biomarker of crypt damage.
each year to learn more about the disease and refine new diagnostics and treatments. U.S. participants will include Massachusetts General Hospital, Mayo Clinic, the Ohio State University Medical Center, and Vanderbilt University Medical Center. Several German academic medical centers, including University Hospital Regensburg, also will be sharing data with Mount Sinai.
“Our grant proposal was very enthusiastically received by the National Cancer Institute, which was impressed with the support that Mount Sinai has provided to run this international consortium,” says Dr. Ferrara, the Ward-Coleman Chair in Cancer Medicine and Professor of Medicine (Hematology and Medicine Oncology), Pediatrics, and Oncological Sciences.
Dr. Levine is a Professor of Medicine, and Pediatrics, at the Icahn School of Medicine at Mount Sinai. He and Dr. Ferrara have been long-time colleagues in the study of GVHD, first at the University of Michigan and for the past couple of years at Mount Sinai, where their groundbreaking research is now being used to inform patient care.
Early diagnosis is the key to successfully treating GVHD, says Dr. Ferrara. To that end, he and Dr. Levine have discovered and validated a biomarker signature in the blood of two plasma proteins that can predict which patients will develop the most severe disease. They are now testing a new treatment that, if given early enough, should keep the disease from spreading through the patient’s gastrointestinal tract to the rest of the body, which is the normal course that GVHD takes.
With the new protocols in place, Mount Sinai has become the first health system in the world to test patients for early signs of GVHD—usually within the first month after a bone marrow transplant—and to offer them the new treatment. Mount Sinai recently treated its first high-risk patient with positive results.
“This is the beginning of precision medicine for BMT patients,” Dr. Ferrara says.
For the past 40 years, physicians have treated patients with a range of high-dose steroids that differed in type and dose, depending on the medical center. The large number and variety of centers participating in the consortium will allow clinicians to standardize the treatment of GVHD for the first time.