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EBMT 2018 | GvHD biology: tissue tolerance, the micriobiome & biomarkers

Speaking from the 2018 European Society for Blood and Marrow Transplantation (EBMT) Annual Meeting in Lisbon, Portugal, Ernst Holler, MD, of University Hospital Regensberg, Regensberg, Germany, briefly outlines the mechanisms behind GvHD, before describing research currently being undertaken to decrease the risk of this condition developing and improve its management.

Transcript (edited for clarity)

Now this regard to GvH biology, I think it’s important that we realize that GvH is not only activation of alloreactive T cells but it’s also a loss of the regulation in the tissue and loss of tissue tolerance, and so my focus is to keep attraction to this aspect but is important that the tissue can regenerate in GvHD but is needed for tissue tolerance.

And so I talked today about regulatory t-cells which help to dampen the inflammation, I talked about molecules which counteract the the tissue damage and my favorite topic is the role of microbiota, so the whole intestinal bacteria because we more and more realize that wherever the immune system is activated, there is not only the target of the immune system but there is a third player; the bacteria, the so-called microbiota...

Now this regard to GvH biology, I think it’s important that we realize that GvH is not only activation of alloreactive T cells but it’s also a loss of the regulation in the tissue and loss of tissue tolerance, and so my focus is to keep attraction to this aspect but is important that the tissue can regenerate in GvHD but is needed for tissue tolerance.

And so I talked today about regulatory t-cells which help to dampen the inflammation, I talked about molecules which counteract the the tissue damage and my favorite topic is the role of microbiota, so the whole intestinal bacteria because we more and more realize that wherever the immune system is activated, there is not only the target of the immune system but there is a third player; the bacteria, the so-called microbiota. And I think this is extremely important for graft-versus-host disease as we and others have shown, early damage of the microbiota occurs due to the use of antibiotics, and this disturbs the whole immuno-regulation. And so early damage to the microbiota induces long term poor outcome with a high incidence of graft versus host disease and we are thinking about new strategies; how to modulate the microbiota in order to prevent the long-term damage.

So this will be one topic of my talks, the other topic is about what is the standard of care in treatment of graft versus host disease, what are new approaches for treatment of steroid resistant GvHD. Here we have the opinion that we come always too late with our treatment, if the patient is sick we first give steroids and then we wait if he responds and then we give the next drug, but we know that already a lot of damage has occurred even if the patient presents was the first symptom.

And therefore our group cooperates within the magic consortium with Jamie Ferrara and Levine’s group from New York and we develop biomarkers of graft versus host disease which indicate very early whether the patient will have severe cause of GvHD or less dangerous GvHD, and we developed these biomarkers in a way that we can now trigger treatment by biomarkers. So we are working on new clinical trials with intensified treatment as soon as GvH starts if the patient is high biomarkers and we even go a step further. We have now shown biomarkers which already indicated day seven, after transplantation before the patient is sick at all, that this patients will do worse and will have severe GVHD and we are now starting to develop clinical strategies of pre-emptive strategies. So treatment before the patient even has symptoms because we have an indicator that GvH starts and we hope by this approach we can improve the outcome of GvH patients in the future.

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