EVOLUTION OF THE MODIFIED ENDOTHELIAL ACTIVATION AND STRESS INDEX AFTER PEDIATRIC ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR NON-MALIGNANT DISEASES
- 1Hospital das Clínicas da Faculdade de Medicina de Ribeirao Preto (HCFMRP), Universidade de São Paulo (USP), São Paulo, SP, Brazil
Abstract
Introduction: Endothelial injury is associated with complications after hematopoietic stem cell transplantation (HSCT). The modified endothelial activation and stress index (mEASIX), calculated from routine laboratory tests, has been studied as an indirect marker of endothelial injury. Data in pediatric patients undergoing HSCT for non-malignant diseases remain scarce. Objectives: To describe the evolution of mEASIX after HSCT and evaluate its association with endothelial complications. Materials and methods: We conducted a single-center retrospective cohort study and reviewed 39 consecutive HSCTs performed between January 2021 and January 2026. After excluding retransplants and cases with insufficient laboratory data, we analyzed 23 patients aged 0–18 years who underwent allogeneic HSCT for non-malignant diseases. Conditioning was myeloablative in 20 patients (87.0%); donors were HLA-matched related in 18 (78.3%), matched unrelated in 4 (17.4%), and haploidentical in 1 (4.3%); bone marrow was the stem cell source in all cases. mEASIX was calculated at preconditioning, D0, D+7, and D+30, and values were log₂-transformed. The composite endpoint comprised sinusoidal obstruction syndrome, transplant-associated thrombotic microangiopathy, or posterior reversible encephalopathy syndrome. The exact Mann–Whitney test compared log₂(mEASIX) values at each time point and interval changes between patients with and without endothelial complications. P values from the six interval comparisons were adjusted using the Benjamini–Hochberg method. The D0-to-D+7 change was prespecified as the primary comparison. Temporal evolution was assessed using a nonparametric longitudinal model for repeated measures. Results: Five patients (21.7%) developed endothelial complications. No statistically significant differences in log₂(mEASIX) were detected between groups at any time point. In the primary comparison, the median D0-to-D+7 change was 1.82 in the complication group and −0.18 in the non-complication group (Hodges–Lehmann shift, 2.07 log₂ units; 95% CI, 0.24–3.54; unadjusted p = 0.037; adjusted p = 0.137). Longitudinal analysis showed a significant time effect (p = 0.008), but no group effect (p = 0.117) or group × time interaction (p = 0.121). Discussion: Previous pediatric EASIX/mEASIX studies focused mainly on malignant or mixed cohorts. Uygun et al. (2026) showed in 475 non-malignant pediatric patients that a high pretransplant EASIX score independently predicted transplant-related mortality and inferior survival, based on a single pretransplant measurement. Cui et al. (2026) reported that D+7 mEASIX independently predicted survival and non-relapse mortality in pediatric acute leukemia patients undergoing haploidentical transplantation, using the same log2-transformed index and an overlapping timepoint. The numerically greater D0 to D+7 mEASIX rise observed here in patients with endothelial complications is directionally consistent with these reports, but did not retain significance after multiplicity correction, likely reflecting our smaller sample size and lower event rate. Conclusion: mEASIX changed significantly over time in the overall cohort, but no differences between groups were detected at individual time points or in temporal trajectories. The larger D0-to-D+7 increase in the complication group did not remain significant after adjustment and should be considered exploratory. Prospective multicenter studies should evaluate this finding.
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BibTeX
@article{santana2026evolution,
title = {{EVOLUTION OF THE MODIFIED ENDOTHELIAL ACTIVATION AND STRESS INDEX AFTER PEDIATRIC ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR NON-MALIGNANT DISEASES}},
author = {Diego SANTANA and Joana Teresa Bisinella DE FARIA and Annie Karoline Feijó COSTA and Renata Fittipaldi da Costa GUIMARÃES and Carlos Eduardo Setanni GRECCO and Gabriela Ventura de Almeida SILVA and Francisco Rômulo Cordeiro DA SILVA and Pedro Augusto de Oliveira VALERI and Ana Beatriz Pereira Lima STRACIERI and Thalita Cristina de Mello COSTA and Fabíola TRAINA and Luiz Guilherme Darrigo JÚNIOR},
journal = {Hematology, Transfusion and Cell Therapy},
year = {2026},
month = oct,
doi = {10.1016/j.htct.2026.106868},
url = {https://doi.org/10.1016/j.htct.2026.106868},
note = {CC BY},
}
RIS
TY - JOUR
TI - EVOLUTION OF THE MODIFIED ENDOTHELIAL ACTIVATION AND STRESS INDEX AFTER PEDIATRIC ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR NON-MALIGNANT DISEASES
AU - Diego SANTANA
AU - Joana Teresa Bisinella DE FARIA
AU - Annie Karoline Feijó COSTA
AU - Renata Fittipaldi da Costa GUIMARÃES
AU - Carlos Eduardo Setanni GRECCO
AU - Gabriela Ventura de Almeida SILVA
AU - Francisco Rômulo Cordeiro DA SILVA
AU - Pedro Augusto de Oliveira VALERI
AU - Ana Beatriz Pereira Lima STRACIERI
AU - Thalita Cristina de Mello COSTA
AU - Fabíola TRAINA
AU - Luiz Guilherme Darrigo JÚNIOR
PY - 2026
DA - 2026/10/23
JO - Hematology, Transfusion and Cell Therapy
DO - 10.1016/j.htct.2026.106868
UR - https://doi.org/10.1016/j.htct.2026.106868
AB - Introduction: Endothelial injury is associated with complications after hematopoietic stem cell transplantation (HSCT). The modified endothelial activation and stress index (mEASIX), calculated from routine laboratory tests, has been studied as an indirect marker of endothelial injury. Data in pediatric patients undergoing HSCT for non-malignant diseases remain scarce. Objectives: To describe the evolution of mEASIX after HSCT and evaluate its association with endothelial complications. Materials and methods: We conducted a single-center retrospective cohort study and reviewed 39 consecutive HSCTs performed between January 2021 and January 2026. After excluding retransplants and cases with insufficient laboratory data, we analyzed 23 patients aged 0–18 years who underwent allogeneic HSCT for non-malignant diseases. Conditioning was myeloablative in 20 patients (87.0%); donors were HLA-matched related in 18 (78.3%), matched unrelated in 4 (17.4%), and haploidentical in 1 (4.3%); bone marrow was the stem cell source in all cases. mEASIX was calculated at preconditioning, D0, D+7, and D+30, and values were log₂-transformed. The composite endpoint comprised sinusoidal obstruction syndrome, transplant-associated thrombotic microangiopathy, or posterior reversible encephalopathy syndrome. The exact Mann–Whitney test compared log₂(mEASIX) values at each time point and interval changes between patients with and without endothelial complications. P values from the six interval comparisons were adjusted using the Benjamini–Hochberg method. The D0-to-D+7 change was prespecified as the primary comparison. Temporal evolution was assessed using a nonparametric longitudinal model for repeated measures. Results: Five patients (21.7%) developed endothelial complications. No statistically significant differences in log₂(mEASIX) were detected between groups at any time point. In the primary comparison, the median D0-to-D+7 change was 1.82 in the complication group and −0.18 in the non-complication group (Hodges–Lehmann shift, 2.07 log₂ units; 95% CI, 0.24–3.54; unadjusted p = 0.037; adjusted p = 0.137). Longitudinal analysis showed a significant time effect (p = 0.008), but no group effect (p = 0.117) or group × time interaction (p = 0.121). Discussion: Previous pediatric EASIX/mEASIX studies focused mainly on malignant or mixed cohorts. Uygun et al. (2026) showed in 475 non-malignant pediatric patients that a high pretransplant EASIX score independently predicted transplant-related mortality and inferior survival, based on a single pretransplant measurement. Cui et al. (2026) reported that D+7 mEASIX independently predicted survival and non-relapse mortality in pediatric acute leukemia patients undergoing haploidentical transplantation, using the same log2-transformed index and an overlapping timepoint. The numerically greater D0 to D+7 mEASIX rise observed here in patients with endothelial complications is directionally consistent with these reports, but did not retain significance after multiplicity correction, likely reflecting our smaller sample size and lower event rate. Conclusion: mEASIX changed significantly over time in the overall cohort, but no differences between groups were detected at individual time points or in temporal trajectories. The larger D0-to-D+7 increase in the complication group did not remain significant after adjustment and should be considered exploratory. Prospective multicenter studies should evaluate this finding.
SN - 2531-1379
SN - 2531-1387
ER -