PROGNOSTIC SIGNIFICANCE OF INTESTINAL PERMEABILITY IN BRAZILIAN PATIENTS UNDERGOING ALLOGENEIC STEM CELL TRANSPLANTATION

In patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), intestinal permeability has emerged as a potential prognostic marker for adverse clinical outcomes. International studies have linked increased permeability to gastrointestinal toxicity, more severe Graft-versus-host disease (GvHD), and reduced gut microbiota diversity. However, its impact on clinical outcomes in Brazilian patients remains largely unexplored. In this study, using a cohort of Brazilian patients, we sought to evaluate the impact of intestinal permeability on mortality and GvHD incidence. This multicenter prospective cohort study, approved by the Research Ethics Committee, included allo-HSCT patients aged > 12 years. Only patients with blood samples collected before conditioning (D-7) and on the day of infusion (D0) were included. Zonulin, a regulator of intestinal permeability via tight junctions, was measured by ELISA. The association between zonulin levels, mortality and GvHD was evaluated using the independent samples t-test, chi-square test, and Fisher’s exact test. Zonulin levels at both timepoints (D-7 and D0) were analyzed as continuous variables and as categorical variables based on predefined cutoff values. Blood samples at D-7 and D0 were analyzed from 46 patients enrolled in the study. Among them, 14 developed GvHD and 6 died. Zonulin levels, assessed as a continuous variable, showed no significant differences between patients with or without GvHD (D–7: 64.2 vs. 58.6 ng/mL, p = 0.559; D0: 64.2 vs. 58.3 ng/mL, p = 0.726) or between survivors and non-survivors (D–7: 56.6 vs. 61.5 ng/mL, p = 0.664; D0: 64.6 vs. 52.5 ng/mL, p = 0.527). By stratifying patients based on median zonulin levels, we also found no significant association with GvHD (D–7: 35.0% vs. 36.8%, p =0.905; D0: 39.1% vs. 33.3%, p = 0.717) or mortality (D–7: 14.2% vs. 12.5%, p = 1.000; D0: 16.0% vs. 9.5%, p = 0.673). Our findings indicate a lack of association between zonulin levels and key clinical outcomes such as GvHD and mortality in this cohort. This divergence from previously reported associations may reflect differences in patient populations, timing of sample collection, or the limitations of zonulin as a marker of intestinal permeability in this setting. While zonulin may not serve as a relevant prognostic factor in Brazilian patients undergoing allo-HSCT, larger multicenter studies using different intestinal permeability assessment methods are required to confirm these findings.

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Journal
Hematology Transfusion and Cell Therapy
Published
2025-10-01
DOI
https://doi.org/10.1016/j.htct.2025.105545
Primary Topic
Barrier Structure and Function Studies
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article
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article

PROGNOSTIC SIGNIFICANCE OF INTESTINAL PERMEABILITY IN BRAZILIAN PATIENTS UNDERGOING ALLOGENEIC STEM CELL TRANSPLANTATION

Gabriela Fernandes de Barros, Arymar Júnior, LS Souza, Peritz Scheinberg et al.
Hematology Transfusion and Cell Therapy
Barrier Structure and Function Studies
article

PROGNOSTIC SIGNIFICANCE OF INTESTINAL PERMEABILITY IN BRAZILIAN PATIENTS UNDERGOING ALLOGENEIC STEM CELL TRANSPLANTATION

Gabriela Fernandes de Barros, Arymar Júnior, LS Souza, Peritz Scheinberg, NL Silva, Iago Colturato, Danielle Amanda Niz Alvarez, G. Oliveira, J Feliciano, BF Silva
article en

Abstract

In patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), intestinal permeability has emerged as a potential prognostic marker for adverse clinical outcomes. International studies have linked increased permeability to gastrointestinal toxicity, more severe Graft-versus-host disease (GvHD), and reduced gut microbiota diversity. However, its impact on clinical outcomes in Brazilian patients remains largely unexplored. In this study, using a cohort of Brazilian patients, we sought to evaluate the impact of intestinal permeability on mortality and GvHD incidence. This multicenter prospective cohort study, approved by the Research Ethics Committee, included allo-HSCT patients aged > 12 years. Only patients with blood samples collected before conditioning (D-7) and on the day of infusion (D0) were included. Zonulin, a regulator of intestinal permeability via tight junctions, was measured by ELISA. The association between zonulin levels, mortality and GvHD was evaluated using the independent samples t-test, chi-square test, and Fisher’s exact test. Zonulin levels at both timepoints (D-7 and D0) were analyzed as continuous variables and as categorical variables based on predefined cutoff values. Blood samples at D-7 and D0 were analyzed from 46 patients enrolled in the study. Among them, 14 developed GvHD and 6 died. Zonulin levels, assessed as a continuous variable, showed no significant differences between patients with or without GvHD (D–7: 64.2 vs. 58.6 ng/mL, p = 0.559; D0: 64.2 vs. 58.3 ng/mL, p = 0.726) or between survivors and non-survivors (D–7: 56.6 vs. 61.5 ng/mL, p = 0.664; D0: 64.6 vs. 52.5 ng/mL, p = 0.527). By stratifying patients based on median zonulin levels, we also found no significant association with GvHD (D–7: 35.0% vs. 36.8%, p =0.905; D0: 39.1% vs. 33.3%, p = 0.717) or mortality (D–7: 14.2% vs. 12.5%, p = 1.000; D0: 16.0% vs. 9.5%, p = 0.673). Our findings indicate a lack of association between zonulin levels and key clinical outcomes such as GvHD and mortality in this cohort. This divergence from previously reported associations may reflect differences in patient populations, timing of sample collection, or the limitations of zonulin as a marker of intestinal permeability in this setting. While zonulin may not serve as a relevant prognostic factor in Brazilian patients undergoing allo-HSCT, larger multicenter studies using different intestinal permeability assessment methods are required to confirm these findings.

Hematology Transfusion and Cell TherapyVol. 47
Faculdade de Medicina de São José do Rio Preto (BR), Hospital de Câncer de Barretos (BR), Hospital Amaral Carvalho (BR), Beneficência Portuguesa de São Paulo (BR), Fundação Faculdade de Medicina (BR), Universidade Estadual Paulista (Unesp) (BR)
Openalex Percentile: Top 61%
Barrier Structure and Function Studies
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