VIDEO: Older age, stem cell sources and other GVHD risk factors

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There are several known risk factors for graft-versus-host disease and potentially some of these are not modifiable — starting with the age of the patient. You know, the older the patients are, we know the more they are at risk for graft-versus-host disease. And once again, I think about this more as a pediatric bone marrow transplanter, whereas an adult bone marrow transplanter may not mention this particular variable to you. But then the donor match and the stem cell source are important considerations as well. The more the degree of HLA mismatch, the greater the risk of graft-versus-host disease. Specific stem cell sources are associated more with graft-versus-host disease such as peripheral blood stem cells. Within pediatrics, we are fortunate that we can use bone marrow grafts and cord blood grafts. However, there are instances in older adolescents where we need to use peripheral blood stem cells. So, we do also face this challenge.

And then there are a lot of additional factors like the strength of your conditioning regimen, which is really dictated by the type of disease that patients have that we are transplanting them for. The stronger that strength of conditioning regimen, the greater the tissue damage and the more inflammatory pathways are activated. An important role, how also is the gut microbiome and how it plays a very important role in the pathogenesis of graft-versus-host disease. And just in general where my research interest is and what we know is the disruption of intestinal homeostasis. This is really the hallmark of ultimately developing graft-versus-host disease. And, unfortunately, in this immune-compromised population, there is a lot of use of antibiotics which further predispose patients to dysbiosis and augment the entire pathophysiology of graft-versus-host disease. So, several factors predispose our patients to risk.