Doctors are one step closer to creating a risk biomarker that will warn them which of their pediatric stem cell transplant patients are likely to experience sinusoidal obstruction syndrome (SOS), a potentially fatal side effect.
A team led by MUSC Hollings Cancer Center researcher Sophie Paczesny, M.D., Ph.D., published the results of their biomarker study in JCI Insight this month.
There is a drug, defibrotide, approved to treat SOS. Paczesny hopes the results of the biomarker study will encourage the maker of defibrotide to conduct a multicenter clinical trial to test whether giving it to patients who test positive for risk biomarkers before they start showing symptoms can prevent the development of SOS.
“This is my dream. These patients really need it,” she said. “Most of my colleagues in this study are doctors, so they really want me to move this forward because they still see a lot of patients who are affected by this.”
Stem cell transplants can cure blood cancers and other blood disorders, but as with other cancer treatments, they have side effects.
SOS, sometimes called hepatic veno-occlusive disease, means that the veins in the liver are blocked. It’s not the most common side effect after an allogeneic hematopoietic cell transplant or stem cell transplant using donor cells: that would likely be the graft-versus-host reaction that Paczesny is primarily targeting.
However, SOS occurs in a significant number of patients 12.5% in this study and can lead to multiorgan failure and death.
In addition, it can be harder to diagnose in children than in adults, and there are no clear risk factors that indicate who is likely to develop the condition, Paczesny said.
Previous studies looked at proactively giving defibrotide to all patients, but those studies showed no clear benefit, she said. The drug is also quite expensive, so limiting it to those who would really benefit from it makes sense.
In a previous study, Paczesny’s team collected samples from children who developed SOS and identified potential biomarkers based on unusually high or unusually low levels. These potential biomarkers included ST2, a receptor also used as a biomarker of cardiac stress; hyaluronic acid, best known as an anti-aging ingredient in skin care products, but also a component of connective tissue used as a biomarker of liver fibrosis; and L-ficolin, a protein expressed in the liver that plays a role in the innate immune system.
In this study, conducted at four academic medical centers across the country, researchers wanted to determine at what point potential risk biomarkers begin to show abnormal levels. They tested the plasma of 80 patients at two time points: three days after the stem cell transplant and seven days after the stem cell transplant.
SOS usually occurs within a month of transplant, so these two time points would likely give doctors plenty of time to intervene. And in fact, the researchers found that measuring these biomarkers on the third day after the hematopoietic cell transfer showed which patients would develop SOS.