GvHD Prophylaxis,   aGvHD,  cGvHD

Highlights from the 1st EBMT GvHD Summit 2019

The 1st EBMT GvHD Summit took place in Warsaw from 16–18 May 2019 at the Radisson Blu Sobieski Hotel. The aim of the Congress was to present the latest scientific developments in biology, prophylaxis, and treatment of graft-versus-host disease (GvHD) through dynamic discussions and cutting-edge presentations by experts in the field.

On Thursday, the GvHD Summit began with a talk by Bruce Blazar, who provided an overview of the mechanisms of GvHD – from murine models to clinical significance highlighting the limitations of extrapolating murine to human GvHD. Professor Blazar explained the differences between mouse and human immunology including the balance of leukocyte subsets, defensins, NK inhibitor receptor family as well as T cell signaling, just to mention some. He added that “the quality, intensity, and type of immune response of the donor-recipient being modeled is key.”

Nicolaus Kröger was the first speaker of Friday with a presentation about the epidemiology of GvHD, sharing preliminary data of a study which investigated the development, regarding the incidence and outcome, of acute GvHD in a large cohort of patients who underwent allogeneic stem cell transplantation between 1990 and 2015 and were reported to the Registry of EBMT. Pavan Reddy then spoke about the diagnosis and severity grading of GvHD providing thoughts on why hematologists mainly focus on three organs, however, GvHD also targets the lungs, kidneys, heart, or CNS. Dr. Reddy concluded by sharing her motto, based on a William Osler quote: GvHD diagnosis “…is an art, based on science.”

Daniel Wolff continued the session by outlining how to diagnose chronic GvHD based on the NIH consensus criteria and the CIBMTR-EBMT consensus 2018 updated guidelines, also focusing on histological confirmation which is urgently required if the diagnostic symptoms are lacking or clinical suspected chronic GvHD is refractory to treatment. Steven Pavletic then explained the staging of chronic GvHD based on a three-step assessment of the disease by NIH criteria. Finally, Hélène Schoemans spoke about the use of the eGvHD app.

John Levine introduced the second session on biomarkers and pathophysiology of GvHD and spoke about the role of biomarkers in acute GvHD which may have value as a response endpoint in clinical trials. Kirk Schultz then explained the current landscape of biomarkers in chronic GvHD highlighting that these algorithms must be comprehensive and multifaceted. Thomas Luft then gave a presentation about biomarkers and genetic risk of endothelial complications and endothelial markers associated with acute GvHD. Finally, Olaf Penack provided an analysis of the pathophysiology of the endothelium during GvHD introducing ongoing and future research followed by Christian Koenecke’s talk about T-cell receptor repertoire in GvHD.

In the afternoon, Rafael Duarte spoke about infectious complications and prophylaxis options in GvHD based on NCCN guidelines. Anita Lawitschka then took to the podium and outlined the differences and challenges with pediatric GvHD patients stating that pediatric patients are growing and developing organisms. Zinaida Peric then provided a fascinating talk including a case study addressing the need for a multidisciplinary approach when it comes to GvHD management. It was interesting to see how the quality of life can be improved based on their approach. Following this, the role of artificial intelligence in GvHD was outlined by Shahrukh Hashmi, who explained that how “machine learning based programming is helping transplant clinicians in predicting GvHD, prognosticating GvHD and in donor selection.”

The final session of the day began with Marcel van den Brink’s presentation on the emerging role of the microbiome, concluding that changes in intestinal flora are associated with overall survival, lethal GvHD, bacteremia, sepsis, engraftment, and relapse in patients receiving allogeneic transplantation. He further added that antibiotics, certain drugs, diet, and conditioning regimens can affect flora changes, as well as enterococcus domination, is associated with GvHD. Ernst Holler then addressed the topic of microbiome and antibiotics, providing insights into how to overcome the negative impact of antibiotics and protect the intestinal microbiota.

Takanori Teshima followed with an overview of restoration of gut microbial ecology and concluded by stating that “GvHD target tissue stem cells, microbial homeostasis, and impairs tissue lead to amplification of GvHD”. Nevertheless, novel strategies may serve as an effective adjunct to immunosuppressive GvHD prophylaxis or treatment. Grzegorz Basak gave a talk about fecal microbiota transplantation for GvHD, concluding that the procedure is relatively safe after allogeneic transplant, however, serious adverse events can occur which should be also considered. The day concluded with a presentation by Jérôme Le Goff, who spoke about the emerging role of virome in GvHD as viral infection may be a trigger of GvHD.

Saturday morning began with a “Meet the expert” breakfast where Pavan Reddy spoke about the current challenges of the treatment of chronic GvHD, Madan Jagasia gave an extensive overview how to use extracorporeal photopheresis, the emerging second-line treatment of GvHD. Hélène Schoemans then provided another detailed guidance of the EBMT GvHD App.

The breakfast session was followed by a special lecture on “EBMT recommendations on prophylaxis and treatment of GvHD.” Olaf Penack presented the recommendations for standardized practice of the EBMT-ELN working group regarding the prevention, drug management, and treatment of acute and chronic GvHD. The presentation included new aspects of disease management highlighting anti-T cell globulin as GvHD prophylaxis, the utilization of lower steroid doses (1mg/kg/day MP or prednisone) in Grade II acute GvHD with isolated skin or upper GI tract manifestations, and the recommendation of the FAM regimen (fluticasone, azithromycin, montelukast) for the initial treatment of Bronchiolitis Obliterans Syndrome in combination with systemic steroid. Dr. Penack added that “in the setting of steroid-refractory acute and chronic GvHD, we have added newer substances to the available treatment options, notably JAK inhibitors, vedolizumab, and ibrutinib.”

At the 1st EBMT GvHD Summit, physicians, researchers, and health care professionals learned about the latest advances in the treatment of GvHD. The meeting featured state-of-the-art methods in biology, prevention, and treatment of GvHD to provide clinicians, scientists, nurses, and young investigators with up-to-date knowledge and newer diagnostic as well as treatment strategies to help them to deliver the best outcome for patients with GvHD.

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