Blood test may detect early signs of lung-transplant rejection

New blood test measures the DNA fragments of lung transplant donors in the blood of recipients, in hopes of preventing organ rejection and saving lives.

Image by kalhh

After receiving a lung transplant, patients face the likely chance that their body’s immune system will reject the transplanted organ. Rejection can happen at any time due to a variety of factors such as a lung infection or an injury to the lungs during transplant surgery. The most deadly type of rejection is chronic lung allograft rejection (CLAD), which develops slowly and often silently without obvious symptoms.

Now, researchers have developed a simple blood test that detects tissue graft injury within the first three months after lung transplant surgery. After further validation, this non-invasive test could identify patients with a high risk of CLAD or death due to graft failure, allowing doctors to intervene early and possibly prevent chronic rejection.

“This test solves a long-standing problem in lung transplants: detection of hidden signs of rejection,” said Hannah Valantine, MD, co-leader of the study and a senior investigator at the National Heart, Lung, and Blood Institute, in a recent news release. “We’re very excited about its potential to save lives, especially in the wake of a critical shortage of donor organs.”

Valantine is also a Stanford professor of medicine and Kiran Khush, MD, associate professor of medicine, is a co-senior author.

The new test measures the amount of DNA fragments circulating freely in a patient’s bloodstream. Since the lung donor and recipients have different genomes, the test can identify and quantify the fragments from both people. If there are a lot more donor DNA fragments, this indicates that the organ is injured.

As recently reported in EBioMedicine, the researchers regularly monitored blood samples from 106 lung transplant patients during the first three months after surgery at several institutions, including Stanford. After dividing the patients into three groups based on the level of donor-derived DNA fragments in their blood, the team found that patients with higher levels were six times more likely to subsequently develop transplant organ failure or die than those with lower levels. And many of these high-risk patients didn’t have symptoms.

“We showed for the first time that donor-derived DNA is a predictive marker for chronic lung rejection and death, and could provide critical time-points to intervene, perhaps preventing these outcomes,” Valantine said in the release. “Once rejection is detected early via this test, doctors would then have the option to increase the dosages of anti-rejection drugs, add new agents that reduce tissue inflammation, or take other measures to prevent or slow the progression.”

The researchers expect commercial versions of the blood test to be available for clinical use soon. They are also planning future studies to evaluate the blood test for other solid organ transplants.

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

After heart transplant, who survives? New study offers tools to tell

Photo by Ms. Phoenix
Photo by Ms. Phoenix

Despite careful patient selection, only about 75 percent of heart recipients survive three years after the transplant surgery. Identifying the patients most in need of additional care has always been tricky, but now Stanford researchers have found a better way to predict which heart transplant recipients have a higher risk of dying or needing another heart transplant, as reported in Circulation today.

One key reason transplant patients die is cardiac allograft vasculopathy, an accelerated and aggressive form of coronary artery disease.

William Fearon, MD, professor of cardiovascular medicine and senior author, explained the significance of their results in a recent email:

Identifying patients at higher risk of dying from cardiac allograft vasculopathy is helpful, because it allows the transplant physicians to be more aggressive with medical therapy and monitoring than they might otherwise be, in order to hopefully prevent adverse events.

The researchers conducted a clinical trial involving seventy-four heart transplant recipients, whose heart physiology was invasively assessed within eight weeks and one year after transplantation. They found that two particular diagnostic procedures were able to successfully identify high-risk recipients — fractional flow reserve and index of microcirculatory resistance.

Fractional flow reserve is a procedure that measures the blood pressure and flow through a specific part of the coronary artery. It is often used to determine whether blood flow is significantly obstructed by a blockage or lesion, guiding a cardiologist’s decision of whether to stent the blockage.

Fearon’s team determined that a low fractional flow reserve measured soon after the transplant independently predicted the heart transplant recipients’ risk of death or retransplantation.

Index of microcirculatory resistance measures the functionality of the tiny vessels that supply blood to the heart, such as capillaries, arterioles and venules. Fearon found that a higher than normal reading measured one year after the heart transplant was also an independent predictor of the recipients’ event-free survival.

The Stanford researchers hope that more emphasis will be placed on these two invasive assessments of cardiac physiology in heart transplant recipients, so their medical regimen can be adjusted to improve the odds of their survival.

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.