Preconditioning Modified-Easix as a Predictor of Prognosis in Allogeneic Hematopoietic Stem Cell Transplant Recipients

Yeğin, Zeynep Arzu; Savaş, Emine Merve; Yıldız, Şeyma; Kök, Münevver İrem; Erdemir, Meltem Büşra; Değirmenci, Başak Bostankolu; Yağcı, Münci

doi:10.1007/s12288-022-01623-0

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“…Approaches using flexible laboratory and clinical variables have been assessed to predict complications during allo-HSCT. These variables such as ferritin ( 11 ) and other surrogate markers of inflammation have been used to calculate scores like the Endothelial Activation and Stress Index (EASIX) or the Modified-EASIX (M-EASIX) ( 12 , 13 ). Both scores, first introduced to predict the cytokine release syndrome during chimeric antigen receptor (CAR) T cell therapy, seek to determine inflammation and endothelium damage.…”

Section: Introductionmentioning

confidence: 99%

Plasma from patients undergoing allogeneic hematopoietic stem cell transplantation promotes NETOSIS in vitro and correlates with inflammatory parameters and clinical severity

López-Andrade,

Cunill,

Andreu

et al. 2024

Front. Immunol.

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IntroductionNETosis, the mechanism by which neutrophils release extracellular traps (NETs), is closely related to inflammation. During the allogeneic hematopoietic stem cell transplantation (allo-HSCT), different stimuli can induce NETs formation. Inflammation and endothelial injury have been associated with acute graft-versus-host disease (aGVHD) and complications after allo-HSCT. We focus on the study of NETosis and its relation with cytokines, hematological and biochemical parameters and clinical outcomes before, during and after allo-HSCT.MethodsWe evaluate the capacity of plasma samples from allo-HSCT patients to induce NETosis, in a cell culture model. Plasma samples from patients undergoing allo-HSCT had a stronger higher NETs induction capacity (NETsIC) than plasma from healthy donors throughout the transplantation process. An optimal cut-off value by ROC analysis was established to discriminate between patients whose plasma triggered NETosis (NETs+IC group) and those who did not (NETs-IC group).ResultsPrior to conditioning treatment, the capacity of plasma samples to trigger NETosis was significantly correlated with the Endothelial Activation and Stress Index (EASIX) score. At day 5 after transplant, patients with a positive NETsIC had higher interleukin (IL)-6 and C-reactive protein (CRP) levels and also a higher Modified EASIX score (M-EASIX) than patients with a negative NETsIC. EASIX and M-EASIX scores seek to determine inflammation and endothelium damage, therefore it could indicate a heightened immune response and inflammation in the group of patients with a positive NETsIC. Cytokine levels, specifically IL-8 and IL-6, significantly increased after allo-HSCT with peak levels reached on day 10 after graft infusion. Only, IL-10 and IL-6 levels were significantly higher in patients with a positive NETsIC. In our small cohort, higher IL-6 and IL-8 levels were related to early severe complications (before day 15 after transplant).DiscussionAlthough early complications were not related to NETosis by itself, NETosis could predict overall non-specific but clinically significant complications during the full patient admission. In summary, NETosis can be directly induced by plasma from allo-HSCT patients and NETsIC was associated with clinical indicators of disease severity, cytokines levels and inflammatory markers.

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Section: Introductionmentioning

confidence: 99%