Dataset Information

Immune Mediated Disorders after Allo-HCG

ABSTRACT:

Allogeneic hematopoietic cell transplantation (HCT) is the only known curative option for many hematologic disorders. After transplantation, many patients develop immune mediated disorders that may be life-threatening. Post-HCT immune mediated disorders are rare relative to other diseases but the prototype of graft versus host disease (GVHD) develops in 30-70% of patients. The morbidity and mortality associated with these HCT-associated immune mediated disorders are major barriers to successful use of transplantation to cure rare hematologic malignancies such as leukemia, lymphoma, multiple myeloma, myelodysplastic/myeloproliferative syndromes amongst other diseases.

The purpose of this study is to characterize and more completely define the onset and course of immune mediated disorders after allogeneic HCT, focusing on participants who develop cutaneous sclerosis, bronchiolitis obliterans syndrome (BOS), late acute graft-vs.-host disease (GVHD), and chronic GVHD.

Of the participants undergoing allogeneic hematopoietic cell transplantation (HCT), can we, the researchers better identify who will develop immune-mediated disorders, what types of disorders participants will have, and whether these disorders will be severe or respond to currently available therapies?

This is a longitudinal study of 1118 individuals (1081 adults and 100 children). Those participating in this study will be evaluated over a 3 year period at 9 study sites. Participants will be enrolled pre-transplant, or up to day 121 post transplantation. This wide enrollment window will allow sites to use recruitment methods that are most efficient at their institutions. At least 2 years of follow-up will ensure an adequate sample size, and sufficient time for observation of the full spectrum of immune mediated disorders. The data of 1023 individuals have been submitted to dbGaP.

PROVIDER: phs001331 | dbGaP |

SECONDARY ACCESSION(S): PRJNA378820PRJNA378819

REPOSITORIES: dbGaP

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			Action	DRS
	GapExchange_phs001331.v1.p1.xml	Xml
	dbGaPEx2.1.5.xsd	Other
	phs001331.v1-Documents.zip	Other
	Study_Report.phs001331.cGVHD_6501.v1.p1.MULTI.pdf	Pdf
	manifest_phs001331.cGVHD_6501.v1.p1.c1.GRU-IRB-PUB.pdf	Pdf

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Project description:BACKGROUND: Hematopoietic stem cell transplantation is a curative procedure for a variety of conditions. Despite major advances, a plethora of adverse clinical outcomes can develop post-transplantation including graft-versus-host disease and infections, which remain the major causes of morbidity and mortality. There is increasing evidence that the gastrointestinal microbiota is associated with clinical outcomes post-hematopoietic stem cell transplantation. Herein, we investigated the longitudinal dynamics of the gut microbiota and metabolome and potential associations to clinical outcomes in pediatric hematopoietic stem cell transplantation at a single centre.RESULTS: On admission (baseline), the majority of patients presented with a different gut microbial composition in comparison to healthy control children with a significantly lower alpha diversity. A further, marked decrease in alpha diversity was observed immediately post-transplantation and in most microbial diversity, and composition did not return to baseline status while hospitalized. Longitudinal trajectories identified continuous fluctuations in microbial composition, with the dominance of a single taxon in a significant proportion of patients. Using pam clustering, three clusters were observed in the dataset. Cluster 1 was common pre-transplantation, characterized by a higher abundance of Clostridium XIVa, Bacteroides and Lachnospiraceae; cluster 2 and cluster 3 were more common post-transplantation with higher abundance of Streptococcus and Staphylococcus in the former whilst Enterococcus, Enterobacteriaceae and Escherichia predominated in the latter. Cluster 3 was also associated with a higher risk of viraemia. Likewise, further multivariate analysis reveals Enterobacteriaceae, viraemia, use of total parenteral nutrition and various antimicrobials contributing towards cluster 3, Streptococcaceae, Staphylococcaceae, Neisseriaceae, vancomycin and metronidazole contributing towards cluster 2. Lachnospiraceae, Ruminococcaceae, Bifidobacteriaceae and not being on total parenteral nutrition contributed to cluster 1. Untargeted metabolomic analyses revealed changes that paralleled fluctuations in microbiota composition; importantly, low fecal butyrate was associated with higher risk of viraemia.CONCLUSIONS: These findings highlight the frequent shifts and dominations in the gut microbiota of pediatric patients undergoing hematopoietic stem cell transplantation. The study reveals associations between the fecal microbiota, metabolome and viraemia. To identify and explore the potential of microbial biomarkers that may predict risk of complications post-HSCT, larger multi-centre studies investigating longitudinal microbial profiling in pediatric hematopoietic stem cell transplantation are warranted.

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Immune Mediated Disorders after Allo-HCG

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