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Prognostic value of ferritin, neuron-specific enolase, lactate dehydrogenase, and urinary and plasmatic catecholamine metabolites in children with neuroblastoma

Authors Cangemi, Reggiardo, Barco, Barbagallo, Conte, D'Angelo, Bianchi, Favre, Galleni, Melioli, Haupt R, Garaventa, Corrias MV

Received 26 July 2012

Accepted for publication 4 September 2012

Published 30 November 2012 Volume 2012:5 Pages 417—423


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Giuliana Cangemi,1 Giorgio Reggiardo,2 Sebastiano Barco,1 Laura Barbagallo,1 Massimo Conte,3 Paolo D'Angelo,4,# Maurizio Bianchi,5,# Claudio Favre,6,# Barbara Galleni,3 Giovanni Melioli,1 Riccardo Haupt,7 Alberto Garaventa,3 Maria V Corrias8

1Clinical Pathology Laboratory Unit, Giannina Gaslini Institute, Genoa, Italy; 2Data Management and Biostatistics Unit, Medi Service, Genoa, Italy; 3Department of Hematology-Oncology, Giannina Gaslini Institute, Genoa, Italy; 4Pediatric Oncology Unit, Azienda Civico, Di Cristina e Benfratelli, Palermo, Italy; 5Pediatric Onco-Hematology, Stem Cell Transplantation and Cellular Therapy Division, Regina Margherita Children's Hospital, Turin, Italy; 6Department of Hematology-Oncology, Pisana University Hospital, Pisa, Italy; 7Epidemiology and Biostatistics Unit, Giannina Gaslini Institute, Genoa, Italy; 8Laboratory of Oncology, Giannina Gaslini Institute, Genoa, Italy

#On behalf of the Italian Association of Pediatric Hematology and Oncology (AIEOP)

Abstract: Different plasma and urinary parameters have been tested as valuable prognostic markers for children with neuroblastoma (NB), but conclusive results from multivariate analyses are still lacking. Samples collected at diagnosis from 505 patients diagnosed in Italy between June 1994 and November 2010 were analyzed at the Italian reference laboratory according to standard methodologies. Patient clinical data were retrieved from the Italian NB Registry. For statistical analysis, patients were grouped according to stage, age, MYCN status, and outcome. Cumulative survival was calculated by the Kaplan–Meier procedure using the first quartile of the marker distribution as a cut-off value to stratify the patients. Multivariate analysis was performed by the Cox regression model by considering only the significant variables. When the entire cohort of patients was considered, none of the different parameters had an independent prognostic value. However, in patients with localized disease without MYCN amplification the significant positive associations between urinary and plasmatic vanillylmandelic acid (VMA)/homovanillic acid (HVA) ratio and a better prognosis remained significant (P < 0.05 and P < 0.01, respectively), as well as, the positive association between high lactate dehydrogenase (LDH) values and a worse prognosis (P < 0.001). Moreover, in stage 4 patients without MYCN amplification, neuron-specific enolase levels above 200 ng/mL and LDH levels above 2500 IU/mL maintained their significant association with a worse outcome (P = 0.01 and P = 0.0001, respectively). In conclusion, LDH had an independent prognostic value in patients of all stages without MYCN amplification. Moreover, the urinary and plasmatic VMA/HVA ratio was an independent predictor of prognosis in patients with localized disease without MYCN amplification. Since LDH and catecholamine metabolites are measured in all patients at diagnosis, these findings may be helpful for an easy, cost-effective, patient risk stratification.

Keywords: neuroblastoma, markers, prognosis

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