Esther M van Wezel1, Boris Decarolis2, Janine Stutterheim1, Lily Zappeij-Kannegieter3, Frank Berthold2, Roswitha Schumacher-Kuckelkorn2, Thorsten Simon2, Marta Fiocco4, Max M van Noesel5, Huib N Caron6, C Ellen van der Schoot3, Barbara Hero2, Godelieve A M Tytgat7. 1. Department of Experimental Immunohematology, Sanquin Research and Landsteiner Laboratory of the AMC, University of Amsterdam, Amsterdam, The Netherlands; Department of Pediatric Oncology, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, The Netherlands. 2. Children's Hospital, University of Cologne, Pediatric Hematology and Oncology, Germany. 3. Department of Experimental Immunohematology, Sanquin Research and Landsteiner Laboratory of the AMC, University of Amsterdam, Amsterdam, The Netherlands. 4. Department of Biostatistics, Leiden University Medical Center and Dutch Childhood Oncology Group, The Hague, The Netherlands. 5. Department of Pediatric Oncology, Sophia Children's Hospital, Erasmus Medical Center, Rotterdam, The Netherlands; Prinses Máxima Centrum, Utrecht, The Netherlands. 6. Department of Pediatric Oncology, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, The Netherlands. 7. Department of Pediatric Oncology, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, The Netherlands; Prinses Máxima Centrum, Utrecht, The Netherlands. Electronic address: g.a.tytgat@amc.uva.nl.
Abstract
INTRODUCTION: The clinical importance of the detection of neuroblastoma messenger RNA (mRNA) in bone marrow (BM) of localised neuroblastoma patients at diagnosis remains unclear. In this prospective multicentre study, BM samples of a large cohort, were studied using real-time quantitative polymerase chain reaction (qPCR). METHODS: BM samples at diagnosis from 160 patients with localised neuroblastoma were prospectively collected at Dutch and German centres between 2009 and 2013. qPCR was performed using five neuroblastoma specific markers. The association with other biological factors and the prognostic impact of BM positivity and clinical response was assessed. RESULTS: In 58 out of 160 patients neuroblastoma mRNA was detected in BM. In 47 of the 58 positive samples only one marker was found positive. BM positivity was significantly associated with MYCN amplification (p = 0.02) and deletion of chromosome 1p (p = 0.04). In total 31 patients had an event, of which only five patients had progression to stage IV. BM positivity was not associated with an unfavourable outcome. However, the detection of more than one marker was associated with an unfavourable outcome (systemic or local relapse) (event free survival 48% versus 85%; p = 0.03) in the whole cohort and in the observation group. CONCLUSIONS: BM positivity was associated with unfavourable biological factors and might represent more aggressive tumours. Patients with qPCR positive BM should not be upstaged, because of very few systemic events in the cohort. However, for patients with more than one marker positive a more careful follow-up is advisable. These results need to be verified in a very large cohort of localised patients.
INTRODUCTION: The clinical importance of the detection of neuroblastoma messenger RNA (mRNA) in bone marrow (BM) of localised neuroblastomapatients at diagnosis remains unclear. In this prospective multicentre study, BM samples of a large cohort, were studied using real-time quantitative polymerase chain reaction (qPCR). METHODS: BM samples at diagnosis from 160 patients with localised neuroblastoma were prospectively collected at Dutch and German centres between 2009 and 2013. qPCR was performed using five neuroblastoma specific markers. The association with other biological factors and the prognostic impact of BM positivity and clinical response was assessed. RESULTS: In 58 out of 160 patientsneuroblastoma mRNA was detected in BM. In 47 of the 58 positive samples only one marker was found positive. BM positivity was significantly associated with MYCN amplification (p = 0.02) and deletion of chromosome 1p (p = 0.04). In total 31 patients had an event, of which only five patients had progression to stage IV. BM positivity was not associated with an unfavourable outcome. However, the detection of more than one marker was associated with an unfavourable outcome (systemic or local relapse) (event free survival 48% versus 85%; p = 0.03) in the whole cohort and in the observation group. CONCLUSIONS: BM positivity was associated with unfavourable biological factors and might represent more aggressive tumours. Patients with qPCR positive BM should not be upstaged, because of very few systemic events in the cohort. However, for patients with more than one marker positive a more careful follow-up is advisable. These results need to be verified in a very large cohort of localised patients.
Authors: Neha Jain; Shaista Sattar; Sarah Inglott; Susan Burchill; Jonathan Fisher; Andreea-Madalina Serban; Rebecca Thomas; Chris Connor; Niharendu Ghara; Tanzina Chowdhury; Catriona Duncan; Giuseppe Barone; John Anderson Journal: F1000Res Date: 2021-09-21
Authors: Ruben Van Paemel; Roos Vlug; Katleen De Preter; Nadine Van Roy; Frank Speleman; Leen Willems; Tim Lammens; Geneviève Laureys; Gudrun Schleiermacher; Godelieve A M Tytgat; Kathy Astrahantseff; Hedwig Deubzer; Bram De Wilde Journal: Eur J Pediatr Date: 2020-01-03 Impact factor: 3.183