Identifying Early Biomarkers for Chronic Graft-Versus-Host Disease: A Promising Breakthrough
Patients undergoing allogeneic hematopoietic cell transplantation, a procedure that offers the possibility of a cure for blood cancer, also face the risk of developing graft-versus-host disease (GVHD). In this condition, the donated cells mistakenly attack the patient’s healthy cells, leading to severe complications and even death. While treatments for chronic GVHD are improving, there is a pressing need to identify patients at high risk of developing this condition to ensure early intervention.
Researchers at the MUSC Hollings Cancer Center have made a significant breakthrough in this regard. Leading a multicenter team, Dr. Sophie Paczesny and her colleagues have identified three potential biomarkers that could be measured just 90 days after transplantation, allowing for early detection and treatment of chronic GVHD. This is a crucial development as a clinical diagnosis of chronic GVHD typically takes longer.
Surprisingly, two of the identified biomarkers are associated with fibrosis – a condition characterized by tissue scarring or hardening. The enzyme MMP3 and the glycoprotein DKK3, both involved in fibrosing lung diseases, were found to be early indicators of chronic GVHD. The team also discovered that CXCL9, a protein that attracts immune cells to the affected organs, could indicate the presence of the disease.
Traditionally, inflammatory markers are expected to be present at the 90-day mark, but the identification of tissue regeneration markers like DKK3 at this early stage is groundbreaking. Previous studies have only detected DKK3 in late-stage chronic GVHD when sclerotic disease has already set in. This study is the first to demonstrate an early measurable increase in fibrotic markers as potential signs of chronic GVHD.
Chronic GVHD can affect various organs in the body, resulting in a range of symptoms from mild to severe. Common manifestations include dry eyes, rashes, joint pain, breathing difficulties, and sclerosis of the skin. Current diagnosis relies on clinical signs, often requiring invasive biopsies that may only reveal late-stage fibrotic lesions. Therefore, the discovery of these risk biomarkers offers the potential for earlier intervention and more effective treatment.
While this research provides a valuable step forward in managing chronic GVHD, further studies are necessary. The study’s patient samples were collected between 2004 and 2018, and since then, a new prophylaxis treatment known as post-transplant cyclophosphamide (PTCy) has gained popularity. PTCy has been shown to improve survival rates and is proposed as the new standard of care. However, the need for risk biomarkers remains, as PTCy does not eliminate GVHD entirely.
Dr. Paczesny emphasized the importance of creating an algorithm with a cutoff score to identify high-risk patients. The ultimate goal is to use this algorithm in a clinical trial that provides preemptive treatment to individuals deemed high risk. As the field continues to advance, it will be interesting to see how these risk biomarkers translate into patients who receive the new PTCy regimen.
This breakthrough research brings hope to patients undergoing allogeneic hematopoietic cell transplantation. By identifying early biomarkers associated with chronic GVHD, doctors can intervene swiftly, potentially reducing the debilitating impact of the disease. As research in this field progresses, it promises to improve patient outcomes and provide a brighter future for those in need of stem cell transplants to combat blood cancer.
