Acute graft-versus-host disease (aGVHD) is a major cause of death after allogeneic hematopoietic cell transplantation, and patients with steroid-refractory aGVHD have a dismal prognosis. We have previously shown that the enteroendocrine hormone glucagon-like peptide-2 has tissue regenerative activity in the lower gastrointestinal tract in mice and patients with steroid-refractory aGVHD. Here, we explored the tissue protective effect of the enteroendocrine hormone gastrin for aGVHD of the stomach. We observed that aGVHD caused a loss of gastrin-producing G-cells and parietal cells (PCs) and an increase in pH in the stomach, and allogeneic T cells had infiltrated the stomach wall. Pentagastrin treatment of aGVHD mice rescued the loss of PCs, normalized the pH in the stomach, increased stomach stem cell marker expression and abundance of LGR5+ cells. Gastrin also increased the viability of stomach and small intestine organoids in vitro. Compared with wild-type mice, Gast−/− mice experienced more severe aGVHD in the intestine and liver, which was rescued by pentagastrin treatment. In patients developing aGVHD, low gastrin levels in stomach biopsies were connected to reduced survival. Moreover, gastrin expression in the stomach correlated with aGVHD severity and tissue damage scores in independent patient cohorts. This study delineates the protective role of gastrin in aGVHD of the stomach in mice and patients and provides a rationale for the therapeutic use of pentagastrin in a clinical trial of patients with aGVHD.

Background: Rising survival rates have created a growing population of childhood cancer survivors (CCSs) who have an increased risk of late effects and require long-term follow-up (LTFU) care. Existing services are often fragmented and may not reflect survivors’ priorities; optimizing such care requires understanding not only the self-reported burden of late effects and their impact on daily lives but also survivors’ information status and their preferences for future care. Methods: Survivor Deutschland e.V. conducted a nationwide cross-sectional online survey assessing the current late effects, daily-life impairments, subjective information statuses, current follow-up structures, and preferences for future LTFU care. A total of 339 CCSs were included, covering all childhood cancer entities, most frequently leukemia (30.7%), central nervous system tumors (18.3%), and lymphoma (16.5%). Data were analyzed descriptively and supplemented by paired non-parametric analyses. Results: Overall, 74.3% (252/339) reported at least one late effect. Self-rated limitations in daily life had a median of five (Q1–Q3 3–7) on a 1–10 scale, which increased with the number of reported late effects. The most frequently affected domains were endocrine (36.3%, n = 123), fertility (33.6%), psychological (30.4%, n = 103), neurocognitive (26.0%, n = 88), and orthopedic (24.8%, n = 84) problems. A majority (69.3%, n = 235) knew that late effects existed yet felt insufficiently informed, and 4.4% only learned of these through the survey. Among 172 survivors in adult follow-up care, only 26.8% (46/172) reported access to structured, specialized LTFU care, whereas 56.4% (97/172) preferred this model. Survivors rated the importance of LTFU care highly (median 9/10) but rated satisfaction with their current care as much lower (median 3/10). The most valued components were the coverage of follow-up costs, sufficient consultation time, a dedicated contact person, and clear communication of results. Psychological support was a notable gap (5.8%, 10/172 current access vs. 17.9% 31/172 preferred), and 84.1% were willing to travel up to two hours or more for high-quality care. Conclusions: German CCSs report a high late-effect burden, meaningful impairment of their daily lives, a pronounced information gap, and substantial unmet care needs. These patient-centered findings support structured, risk-adapted LTFU with proactive information, integrated psychological support, and sustainable financing at specialized LTFU centers.