Adjunctive Dietary Therapy Is Associated With Improved Gastrointestinal Symptoms in Steroid-Refractory Gastrointestinal Graft-Versus-Host Disease: A Case Series

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TL;DR

This case series of 3 pediatric patients with steroid-refractory gastrointestinal graft-versus-host disease (SR-GVHD) found that adding dietary therapy—exclusive enteral nutrition (EEN) followed by the specific carbohydrate diet (SCD) or a whole foods diet—was associated with marked improvement in GI symptoms. All patients had resolution of hematochezia and reduced stool output after dietary therapy was initiated alongside ongoing immunosuppression. These findings suggest that adjunctive dietary therapy may be a safe and beneficial treatment strategy for intestinal GVHD, though larger prospective studies are needed.

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**Background:** Acute graft-versus-host disease (aGVHD) after hematopoietic cell transplant (HCT) is an inflammatory condition with significant morbidity and mortality, particularly when steroid-refractory (SR-aGVHD) and involving the gastrointestinal tract. Microbial dysbiosis in intestinal GVHD is an area of active investigation. Pediatric Crohn's disease (pediCD) shares inflammatory features with GI GVHD, and dietary therapies such as exclusive enteral nutrition (EEN) and the specific carbohydrate diet (SCD) have been shown to induce remission in pediCD, with EEN demonstrating equivalence to glucocorticoids and superior mucosal healing. This case series explores whether similar dietary approaches could benefit patients with SR-GVHD.

**Methods:** The authors conducted a retrospective chart review of 3 pediatric patients who developed SR-aGVHD after total body irradiation-based myeloablative conditioning and cord blood transplantation (CBT) between 2015 and 2020 at Seattle Children's Hospital. All patients received aGVHD prophylaxis with cyclosporine and mycophenolate mofetil (MMF). The study was approved by the Seattle Children's Hospital Institutional Review Board (STUDY00000391). Patients were treated with immunosuppression plus dietary therapy (EEN followed by SCD or a whole foods diet). The report expands on a prior publication from the same institution describing 2 additional patients with similar outcomes.

**Key Results:** Patient 1 was a 19-year-old female with relapsed diffuse large B-cell lymphoma who developed grade IV SR-aGVHD with hematochezia (>1 L/day). Seven months posttransplant, she received 2 weeks of EEN (polymeric formula 1.0 kcal/mL) by mouth, then a modified SCD for 8 weeks, followed by a whole foods diet. No total parenteral nutrition (TPN) was used. After maintaining this diet for 18 months posttransplant, she reported resolution of GI symptoms, with bowel movements reduced to 1–2 formed, nonbloody stools per day (down from >1 L/day with frank blood). Patient 2 was a 2-year-old female with infant ALL who developed grade IV SR-aGVHD with hematochezia (peak stool output 1.4 L/day, 110 mL/kg/day). Seventeen months posttransplant, she began EEN (elemental formula 1.0 kcal/mL) via nasogastric tube for a flare-up. After 3 weeks of EEN, symptomatic improvement prompted transition to a whole foods-based polymeric formula for 10 months, then to SCD. She continues SCD 2 years later, with 5–8 loose stools with scant blood per day (improved from peak). Patient 3 was a 19-year-old female with therapy-associated AML who developed grade IV SR-aGVHD with hematochezia (5 L/day, 80 mL/kg/day). Seven months posttransplant, she received 5 weeks of EEN (polymeric formula 1.5 kcal/mL) by mouth along with TPN. Intestinal symptoms resolved, and EEN was transitioned to SCD for 4 weeks before liberalizing to a whole foods diet. Post-dietary endoscopy showed no GVHD but mild focal active/chronic inflammation. Two years posttransplant, she is off immunosuppression and on a whole foods diet, with 1–2 nonbloody bowel movements per day. All 3 patients began dietary therapy in the context of poor response to immunosuppressive therapies, and no changes were made to pharmacologic regimens at the time of dietary therapy initiation.

**Clinical Implications:** This case series suggests that adjunctive dietary therapy—specifically EEN followed by SCD or a whole foods diet—may provide clinical benefit for patients with steroid-refractory GI GVHD. The improvement observed parallels the known efficacy of these dietary approaches in pediatric Crohn's disease, where they are thought to modulate intestinal dysbiosis, nourish the intestinal epithelium, and minimize deleterious dietary exposures. The authors note that no difference in feeding tolerance was observed between oral and enteral (NG) routes, and that standard polymeric formulas may be used if tolerated. Limitations include the small sample size, potential confounding by concurrent immunosuppressive therapies, lack of repeat endoscopic evaluation in all patients, and absence of microbiome specimens to corroborate hypothesized microbiome changes. Given the high mortality and morbidity of SR-GVHD, larger prospective studies are needed to elucidate the role of dietary therapy as a safe adjunctive treatment for intestinal GVHD.