Scientists identify biomarkers that predict graft-versus-host disease after stem cell transplants
INDIANAPOLIS -- Researchers have identified biomarkers that could serve to predict which patients are more likely to be affected by chronic graft-versus-host disease following stem cell transplants. The identification of the four-biomarker panel could impact early detection and eventually treatment of the disease.
Chronic graft-versus-host disease remains the most common long-term complication of allogeneic hematopoietic cell transplantation -- the transplant of stem cells from one person to another. Allogeneic transplants are used to treat blood and bone marrow cancers such as leukemia and multiple myeloma, often as a last resort. Graft-versus-host disease occurs when immune cells from the transplant interpret the patient's body as foreign and attack it. Chronic graft-versus-host disease occurs in up to 70 percent of patients who survive 100 days past transplant, and is also the leading cause of non-relapse mortality.
The biomarkers were identified and validated by a national team of researchers comprising the Chronic Graft-Versus-Host Disease Consortium, including study co-lead author, Sophie Paczesny, M.D., Ph.D., professor of pediatrics and immunology at the IU School of Medicine. The study was published in the Journal of Clinical Oncology.
Chronic graft-versus-host disease can act like an autoimmune disease, affecting several organs of the body, inhibiting mobility, limiting quality of life, and can last throughout a patient’s life.
“Currently, the only way to diagnose chronic graft-versus-host disease is a complex clinical evaluation of the patient for any symptoms of the disease after the transplant,” said Dr. Paczesny. “With the discovery of a biomarker for the disease, a blood test can be created to replace this clinical evaluation, saving time and hopefully, providing more accuracy in predicting the occurrence of disease.”
The researchers analyzed proteins in the blood plasma of patients with and without the disease to determine which proteins differed most significantly between the two groups. Protein analysis identified a four-biomarker panel that was significantly associated with subsequent development of chronic graft-versus-host disease. Researchers also analyzed proteins in patients three months before they showed clinical signs of the disease, discovering that these patients already showed elevated levels of the biomarkers.
“This means that even before the clinical signs of the disease were present, the biomarkers were elevated. This discovery provides us with even more information about the disease and suggests that we may be able to intervene earlier in patients with elevated biomarkers and prevent tissue damage,” Dr. Paczesny said.
With the biomarkers providing some indication that a patient is likely to develop chronic graft-versus-host disease, researchers hope to be able to develop more targeted treatment options. Current treatment for the disease includes the administration of steroids, which must be tapered off slowly to avoid flare-ups of the disease. The identification of the four proteins in the biomarker panel will assist scientists in developing more targeted therapies to treat chronic graft-versus-host disease.
“Much like chemotherapy is a global treatment for cancer, steroids are a general treatment for complications of chronic graft-versus-host disease, but they’re not specific,” Dr. Paczesny said. “These biomarkers will make it possible for us to discover more targeted treatments in the future.”
Other researchers contributing to the study included first author Jeffrey Yu, Kushi Kushekhar and Mohammad Abu Zaid of the IU School of Medicine; study co-lead author Stephanie J. Lee, Barry E. Storer, Paul J. Martin, Mary E. Flowers, John A. Hansen, Qing Zhang, Philip R. Gafken and Yuko Ogata of the Fred Hutchinson Cancer Research Center; Mukta Arora of the University of Minnesota; Corey Cutler of the Dana-Farber Cancer Institute; Madan Jagasia of Vanderbilt University; Joseph Pidala of the H. Lee Moffitt Cancer Center; Betty K. Hamilton of the Cleveland Clinic Foundation and George L. Chen of the Roswell Park Cancer Institute.
Dr. Paczesny is an investigator with the Herman B Wells Center for Pediatric Research and the Indiana University Melvin and Bren Simon Cancer Center.
The research was funded by grants (R01CA174667, R01CA118953, and U54CA163438) from the National Institutes of Health.
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