An Intestinal Health Approach to Eliminating Graft vs. Host Disease

Allogeneic hematopoietic stem cell transplantation (allo-HSCT), in which a patient receives blood-forming stem cells from a donor rather than from their own body, is a life-saving treatment. However, patients can experience severe disturbances in their immune systems and microbiomes as a result, such as infection or Graft vs. Host Disease (GvHD). The gastrointestinal tract is a particularly common site for post-transplant complications, both as the origin of complications and the target of them.

Mouse and human studies indicate that many critical clinical outcomes after allo-HSCT – including infections, GvHD, and overall survival – are closely linked to changes in intestinal flora. For example, the loss of intestinal diversity and the growth of opportunistic pathogens belonging to the phylum Proteobacteria and Enterococcus genus have been linked to increased treatment-related mortality.

The loss of beneficial intestinal bacteria, such as Blautia and Lactobacillus, has been associated with GvHD development. Since the gut microbiota and its metabolites have been reported to play pivotal roles in the success or failure of allo-HSCT, studying the intestinal microbiome in these patients could give us critical information on how to improve outcomes after transplantation.

GvHD, in particular, is a leading cause of mortality among patients undergoing allo-HSCT. It begins with the allo-activation of T-cells, which causes an autoimmune-like attack on recipient organs. Current immunosuppressive strategies are only partially effective and increase the risk of infection and recurrence.

Our goal is to describe the intestinal microbiome diversity in pediatric patients undergoing allo-HSCT, and explore associations between intestinal microbiome diversity and long term clinical HSCT outcomes (overall survival, infections, mortality, and GvHD). Ultimately, we hope to understand how to reduce GvHD while leaving immune function intact.

We are conducting our research at the Pediatric Hematology and Oncology Unit at the Pontificia Universidad Catolica, the only private center performing pediatric HSCT in Chile. Via uBiome’s academic grant program, uBiome awarded us more than 400 microbiome sampling kits for our study.

We recruited pediatric patients who received non T-cell depleted grafts for the study during a 3 month period in 2017. To begin, we gathered clinical data on each patient, including disease type, conditioning, HLA typing for both the recipient and donor, antibiotics received, diet, labs and pathology reports, and more. Then, with the kits provided by uBiome, we collected at least weekly fecal specimens beginning when GvHD was diagnosed until the condition was either resolved or we reached 100 days after diagnosis.

We are currently analyzing the results and plan to present the study at a national or international meeting as well as publish our findings in a major oncology journal.  

 

Dr. Andrea P. Salgado, MD, is a Pediatric Infectious Diseases specialist in the Pediatric Hematology and Oncology Unit at the Pontificia Universidad Catolica de Chile.