sVEGF-R1 in acute non-infectious toxicity syndromes after pediatric allogeneic hematopoietic stem cell transplantation.

Autor: Horan DE; Department of Pediatrics and Adolescent Medicine, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark; Institute for Inflammation Research, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark. Electronic address: Denise.elbaek.horan@regionh.dk., Kielsen K; Department of Pediatrics and Adolescent Medicine, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark; Department of Clinical Immunology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark. Electronic address: katrine.kielsen@regionh.dk., Weischendorff SW; Department of Pediatrics and Adolescent Medicine, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark; Institute for Inflammation Research, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark. Electronic address: sarah.wegener.weischendorff@regionh.dk., Sørum ME; Department of Pediatrics and Adolescent Medicine, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark; Institute for Inflammation Research, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark. Electronic address: ebbesen.soerum@regionh.dk., Kammersgaard MB; Department of Pediatrics and Adolescent Medicine, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark; Institute for Inflammation Research, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark. Electronic address: marteb91@online.no., Ifversen M; Department of Pediatrics and Adolescent Medicine, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark. Electronic address: marianne.ifversen@regionh.dk., Nielsen C; Institute for Inflammation Research, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark. Electronic address: claus.nielsen.03@regionh.dk., Ryder LP; Department of Clinical Immunology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark., Johansson PI; Section for Transfusion Medicine, Capital Region Blood Bank, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. Electronic address: per.johansson@regionh.dk., Müller K; Department of Pediatrics and Adolescent Medicine, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark; Institute for Inflammation Research, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark; Institute of Clinical Medicine, University of Copenhagen, Denmark. Electronic address: klaus.mueller@regionh.dk.
Jazyk: angličtina
Zdroj: Transplant immunology [Transpl Immunol] 2024 Feb; Vol. 82, pp. 101975. Date of Electronic Publication: 2023 Dec 19.
DOI: 10.1016/j.trim.2023.101975
Abstrakt: Background: Allogeneic hematopoietic stem cell transplantation (HSCT) is challenged by acute non-infectious toxicities, including sinusoidal obstruction syndrome (SOS), engraftment syndrome (ES) and capillary leak syndrome (CLS) among others. These complications are thought to be driven by a dysfunctional vascular endothelium, but the pathophysiological mechanisms remain incompletely understood, and the diagnoses are challenged by purely clinical diagnostic criteria that are partly overlapping, limiting the possibilities for progress in this field. There is, however, increasing evidence suggesting that these challenges may be met through the development of diagnostic biomarkers to improve diagnostic accuracy of pathogenetically homogenous entities, improved pre-transplant risk assessment and the early identification of patients with increased need for specific treatment. Soluble vascular endothelial growth factor receptor-1 (sVEGF-R1) is emerging as an important biomarker of endothelial damage in patients with trauma and sepsis but has not been studied in HSCT.
Objectives: To investigate sVEGF-R1 as a marker of endothelial damage in pediatric HSCT patients by exploring associations with SOS, CLS, ES, and acute graft-versus-host disease (aGvHD).
Methods: We prospectively included 113 children undergoing myeloablative HSCT and measured sVEGF-R1 in plasma samples obtained weekly during the early period of transplantation and 3 months post-transplant.
Results: All over, sVEGF-R1 levels were significantly increased from day +7 after graft infusion, peaking at day +30, most pronounced in patients receiving busulfan. Patients considered to be at increased risk of SOS and therefore commenced on prophylactic defibrotide had significantly elevated levels of sVEGF-R1 before start of conditioning (446 pg/mL vs. 281 pg/mL, p = 0.0035), and this treatment appeared to stabilize sVEGF-R1 levels compared to patients not treated with defibrotide. Thirteen (11.5%) children meeting the modified Seattle criteria for SOS at median day +8 (1-18), had significantly elevated sVEGF-R1 levels on day +14 (489 pg/mL vs. 327 pg/mL, p = 0.007). In contrast. sVEGF-R1 levels in the much broader group of patients (45.1%) meeting EBMT-SOS criteria, including patients with very mild disease, did not overall differ in sVEGF-R1 levels, but higher sVEGF-R1 levels were seen in EBMT-SOS patients with an increased need for diuretic treatment. Importantly, sVEGF-R1 levels were not associated with ES and CLS but were significantly increased on day +30 in patients with grade III-IV aGvHD (OR = 4.2 pr. quartile, p = 0.023).
Conclusion: VEGF-R1 levels are found to be increased in pediatric patients developing SOS, reflecting the severity of morbidity. sVEGF-R1 were unassociated with both CLS and ES. The potential of sVEGF-R1 as a clinically useful biomarker for SOS should be further explored to improve pre-transplant SOS-risk assessment, SOS-severity grading, and to guide treatment.
Competing Interests: Declaration of Competing Interest There are no conflicts of interests to declare.
(Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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