DYNAMICS OF INTESTINAL PERMEABILITY IN PATIENTS UNDERGOING ALLOGENEIC STEM CELL TRANSPLANTATION

The gastrointestinal barrier is frequently disrupted in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), leading to increased intestinal permeability. This alteration is primarily driven by the conditioning regimen and may be further aggravated by infections and intestinal dysbiosis. Although increased intestinal permeability has been reported in international allo-HSCT studies, its temporal behavior across different post-transplantation phases remains poorly characterized, particularly in Brazilian populations. In this study, using a cohort of Brazilian patients undergoing allo-HSCT, we aimed to identify the dynamics of intestinal permeability. This is a multicenter, prospective cohort study, approved by the Research Ethical Committee. Patients > 12 years old undergoing allo-HSCT were included. Blood samples were collected longitudinally at 7 time points: Prior to conditioning regimen (D-7); At the day of stem cell infusion (D0); 30 days after stem cell infusion (D+30); D+60, D+90, D+180, and at acute Graft-versus-host disease (GvHD) diagnosis. Zonulin, a key regulator of intestinal permeability via tight junction modulation, was measured by ELISA. A group of 15 healthy individuals were used as a control group. Non-parametric tests with multiple comparisons were used for statistical analysis. During the study, 494 blood samples were collected from 136 patients. The highest median zonulin level occurred before conditioning (64 ng/mL), and the lowest at D+30 (55 ng/mL). Compared with controls (21 ng/mL), zonulin was significantly increased as early as pre-conditioning (64 ng/mL, p < 0.0001), and remained high at D0 (59 ng/mL, p < 0.0001), D+30 (55 ng/mL, p = 0.0007), D+60 (60 ng/mL, p = 0.0002), and D+90 (61 ng/mL, p = 0.0002). Levels were also increased at D+180 (60 ng/mL, p = 0.0004) and at GvHD diagnosis (55 ng/mL, p = 0.0084). Brazilian patients undergoing allo-HSCT showed persistently elevated zonulin concentrations, when compared with controls, pointing to sustained intestinal mucosal injury throughout the allo-HSCT. This persistence suggests that factors beyond conditioning, such as infections and transplant-related complications, contribute to ongoing barrier disruption. Persistent elevated zonulin may also reflect limited mucosal regeneration during allo-HSCT. Further studies are needed to clarify the mechanisms and clinical impact of this intestinal damage.