Duke has been a core center of the BMT CTN since its inception in 2001. Dr. Joanne Kurtzberg from Duke’s pediatric BMT group served as PI of the core site until 2022 when Dr. Horwitz from Duke’s adult BMT group assumed the role. In an attempt to improve accrual to the network trials, the blood and marrow transplant program at the University of Virginia, under the direction of Dr. Karen Ballen, was added in 2017 to form the Duke Consortium. With successful renewal of this application, the Duke Consortium will add the Novant Health Transplantation and Cellular Therapy program. With FACT accredited treatment centers in both Charlotte and Winston Salem, North Carolina, the Novant Health program has the potential to add considerably to the accrual and scientific contributions of the Duke Consortium. Each site lead will make decisions as to which network studies are to be opened for accrual at their respective sites. Funds provided by the award will be distributed shared with consortium sites. The study proposed in this application is entitled A Phase III, randomized, double blinded placebo-controlled study of galactooligosaccaraide (GOS) in recipients of allogeneic hematopoietic stem cell transplantation. Justification for the trial is based on published pre-clinical and clinical data linking the composition of the intestinal microbiome with survival following allogeneic HCT. GOS is commercially available dietary supplement that has been shown to reduce gastrointestinal symptoms such as bloating and abdominal pain. Outcomes may also be mediated by the effect of GOS on commensal genera and butyrate producers such as Bacteroides and Bifidobacteria. In addition, GOS consumption has been shown to positively modulate immune function by improving NK cell activity, increasing production of the anti-inflammatory cytokine IL-10, and decreasing production of IL-1β. The trial is ideal for the BMTCTN in that: (1) it is a phase III trial that can only be accomplished in the multi-site, collaborative fashion, (2) has the potential to improve the outcome of allogeneic HCT by preventing GVHD, improving immune reconstitution and thus reducing relapse, all with a simple, inexpensive intervention, (3) the study drug will be provided by the manufacturer thereby mitigating the expense of the study, and (4) has the potential to enroll a racial and ethnically diverse population that includes children age > 4years. The study will leverage the expertise of Dr. Anthony Sung at Duke and Dr. Indumurthy Varadarajan at UVa, who have both established a basic and clinical research portfolio in the field of intestinal microbiome. If approved, Dr. Sung will serve as the protocol PI.