PAI-1 and protein C as early markers of veno-occlusive disease in patients treated for Wilms tumor.
Adolescent
Antineoplastic Combined Chemotherapy Protocols
/ administration & dosage
Child
Child, Preschool
Female
Hepatic Veno-Occlusive Disease
/ blood
Humans
Incidence
Infant
Male
Neoplasm Proteins
/ blood
Plasminogen Activator Inhibitor 1
/ blood
Prospective Studies
Protein C
/ metabolism
Retrospective Studies
Wilms Tumor
/ blood
PAI-1
Wilms tumor
liver toxicity
protein C
veno-occlusive disease
Journal
Pediatric blood & cancer
ISSN: 1545-5017
Titre abrégé: Pediatr Blood Cancer
Pays: United States
ID NLM: 101186624
Informations de publication
Date de publication:
07 2019
07 2019
Historique:
received:
03
12
2018
revised:
31
01
2019
accepted:
21
02
2019
pubmed:
14
3
2019
medline:
18
12
2019
entrez:
14
3
2019
Statut:
ppublish
Résumé
Hepatic veno-occlusive (VOD) disease has been described in hematopoietic stem cell transplantation (HSCT), solid tumors, and acute lymphoblastic leukemia. The incidence of VOD in Wilms tumor (WT) ranges from 1.2% to 8%. The diagnosis of VOD is clinical, and there are no validated laboratory biomarkers. We prospectively evaluated the specificity and sensitivity of plasminogen-activator inhibitor-1 (PAI-1) and protein C as diagnostic markers of VOD in WT patients. Fifty patients treated from 2008 to 2016 for WT were eligible. VOD was diagnosed according to modified Seattle criteria and retrospectively reclassified according to the recently published criteria for VOD in pediatric HSCT patients. VOD occurred in 6 of 50 patients (12%) after 20 to 97 days from starting chemotherapy. The average duration of VOD was 10 days (range, 4-13 days). PAI-1 levels were elevated in all VOD patients, while a decrease in protein C levels was observed in 33% of patients with VOD. PAI-1 antigen (Ag) values ≥ 26.4 ng/mL demonstrated high sensitivity and specificity for the clinical diagnosis of VOD with sensitivity 100%, specificity 93%; whereas protein C levels below 34.5% had sensitivity 67%, specificity 100%. Both PAI-1 and protein C had an high negative predictive value: PAI-1 Ag 100%; protein C 95%. PAI-1 Ag and protein C have good sensitivity and specificity for the diagnosis of VOD in WT patients. Their high negative predictive value can be used in the differential diagnosis of liver toxicity, especially in VOD episodes with absent or delayed hyperbilirubinemia.
Sections du résumé
BACKGROUND
Hepatic veno-occlusive (VOD) disease has been described in hematopoietic stem cell transplantation (HSCT), solid tumors, and acute lymphoblastic leukemia. The incidence of VOD in Wilms tumor (WT) ranges from 1.2% to 8%. The diagnosis of VOD is clinical, and there are no validated laboratory biomarkers.
PROCEDURE
We prospectively evaluated the specificity and sensitivity of plasminogen-activator inhibitor-1 (PAI-1) and protein C as diagnostic markers of VOD in WT patients. Fifty patients treated from 2008 to 2016 for WT were eligible. VOD was diagnosed according to modified Seattle criteria and retrospectively reclassified according to the recently published criteria for VOD in pediatric HSCT patients.
RESULTS
VOD occurred in 6 of 50 patients (12%) after 20 to 97 days from starting chemotherapy. The average duration of VOD was 10 days (range, 4-13 days). PAI-1 levels were elevated in all VOD patients, while a decrease in protein C levels was observed in 33% of patients with VOD. PAI-1 antigen (Ag) values ≥ 26.4 ng/mL demonstrated high sensitivity and specificity for the clinical diagnosis of VOD with sensitivity 100%, specificity 93%; whereas protein C levels below 34.5% had sensitivity 67%, specificity 100%. Both PAI-1 and protein C had an high negative predictive value: PAI-1 Ag 100%; protein C 95%.
CONCLUSIONS
PAI-1 Ag and protein C have good sensitivity and specificity for the diagnosis of VOD in WT patients. Their high negative predictive value can be used in the differential diagnosis of liver toxicity, especially in VOD episodes with absent or delayed hyperbilirubinemia.
Substances chimiques
Neoplasm Proteins
0
Plasminogen Activator Inhibitor 1
0
Protein C
0
SERPINE1 protein, human
0
Types de publication
Clinical Trial
Journal Article
Multicenter Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
e27695Informations de copyright
© 2019 Wiley Periodicals, Inc.