Component of Breast Milk Yields Reduced GI GVHD in Pediatric Patients

Receipt of human milk oligosaccharide (2’-fucosyllactose; 2’-FL) yielded reduced intestinal dysbiosis, incidence of acute gastrointestinal graft-versus-host disease (GVHD), and incidence of adenoviral reactivation in evaluable pediatric and adult patients.¹ These results came from a first-in-pediatrics phase 2 study shared at the 2026 American Society of Pediatric Hematology/Oncology (ASPHO) Annual Meeting.

Transplant Outcomes

By day +100, acute GVHD events from grade 2 to 4 included skin, gastrointestinal tract, and liver. In the 2’-FL arm, gastrointestinal tract events occurred in 0% of patients vs 17% in the control arm (P = .009); skin events occurred in 5% vs 14%, respectively (P = .21); and liver events occurred in 0% vs 3% (P = .41). Modified Glucksberg criteria were used to grade GVHD.

There was also reduced viral reactivation in evaluable 2’FL recipients. By day +100, any viral reactivation occurred in 70% of the 2’-FL arm vs 66% of the control arm (P = .80). Specifically, Ebstein-Barr virus occurred in 26% vs 28%, respectively (P >.99), cytomegalovirus occurred in 28% vs 28% (P >.99), BK virus occurred in 33% vs 45% (P = .33), and human herpes virus 6 occurred in 12% vs 7% (P = .69). Notably, adenovirus occurred in 0% of the 2’-FL arm vs 17% of the control arm (P = .009).

No difference was indicated between the 2’FL arm and control arm with regards to bloodstream infection (BSI) or mucosal barrier injury laboratory-confirmed BSI.

Additional Analyses

The microbiome analyses revealed preserved Shannon Diversity index among evaluable 2’FL recipients vs control (P = .04).

Metabolomic analyses demonstrated higher fecal isoleucine (P = .005) and fecal leucine (P = .04) at day 7 in evaluable 2’FL recipients. With regards to these findings, the investigators noted that pre-clinical studies have demonstrated that dietary supplementation of the fecal isoleucine and fecal leucine metabolites protect and regenerate intestinal epithelial structure, among other things. Higher fecal phosphocholine (P = .007), fecal taurine (P = .04), and fecal tyrosine (P = .05) were also observed at day +7 in evaluable 2’-FL recipients.

The investigators noted that specific results—higher levels of fecal aspartate (P = .02), fecal proline (P = .05), fecal phenylamine (P = .04), and fecal valine (P = .03) at day +7 in evaluable 2’-FL recipients—warrant further studies.

At day +7, evaluable 2’-FL recipients demonstrated lower levels of plasma reg3α (P = .053) and plasma ST2 (P = .038). No difference was observed in plasma cytokines IL-6 (P = .66) and IL-8 (P = .71).

How was the study structured?

Across phase 1 and phase 2 of the trial, a total of 43 evaluable 2’-FL recipients and 29 contemporary controls were included in the analyses. There were 16 evaluable patients between 0 and 5 years included. Eligible patient were between 0 and 35 years of age with all underlying diagnoses, conditioning regimens, and acute GVHD prophylaxes.

Exclusion criteria included being unable to tolerate enteral medications, actively breastfeeding infants, gastrointestinal infection within the week prior to enrollment, and use of anti-diarrheal medications.

2’-FL was administered orally or via enteral tube once daily as a powder mixed with 4 to 5 mL of water or juice. Dosing was previously established on the phase 1 study, which was estimated based on varying factors. For patients 0 to 5 years of age, dosing was 2.5 g of 2‘-FL daily; for patients 5.1 to 10 years, dosing was 5 g daily, and for patients older than 10 years, dosing was 10 g daily.

Samples were collected at different time points in the study. Stool samples were collected at baseline, day +7, day +14, and day +28, whereas blood samples were collected at baseline and day +7.

Patients were considered evaluable based on achieving at least 60% adherence with prescribed 2'-FL doses during the study period.

The hypothesis that the investigators sought to answer was that peri-transplant of oral 2’-FL would reduce dysbiosis and acute gastrointestinal GVHD.

The clinical primary end point of the trial was acute gastrointestinal GVHD by day +100; the secondary end point was infections by day +100. The correlative primary end point was Shannon Diversity from baseline to day +30; the secondary end point was fecal metabolites at day +7.

References

Ramos KN, Langenberg L, Lake K, et al. Human milk oligosaccharide (2-fucosyllactose) modifies the gut microbiome and reduces acute GI GVHD: results of a prospective, first-in-pediatrics phase II study. Presented at the 2026 ASPHO Conference; April 29-May 2, 2026; Minneapolis, MN. Plenary Paper #267779.