Poster Presentation Advances in Neuroblastoma Research Congress 2016

Detection of PHOX2B and TH mRNA by RTqPCR in peripheral blood stem cell harvests may identify children with stage 4 neuroblastoma that have an increased risk of an event post reinfusion: a SIOPEN study (#156)

Sue A Burchill 1 , Maria V Corrias 2 , Sandro Dallorso 2 , Andrei Tchirkov 3 , Tim Lammens 4 , Ales Vicha 5 , Aimee Houlton 6 , Keith Wheatley 6 , Walter M Gregory 7 , Ulrike Poetschger 8 , Martin Elliott 9 , Roberto Luksch 10 , Domonique Valteau-Couanet 11 , Genevieve Laureys 4 , Ruth Ladenstein 8
  1. Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, United Kingdom
  2. Gaslini Institute, Genoa, Italy
  3. CHU Clermont-Ferrand, Service de Cytogenetique Medicale and Clermont University, University of Auvergne, Clermont-Ferrand, France
  4. University Hospital Ghent, Ghent, Belgium
  5. 2nd Faculty of Medicine Charles University and University Hospital Motel, Prague, Czech Republic
  6. Clinical Trials Research Unit, Birmingham, United Kingdom
  7. Leeds Institute of Clinical Trials Research, Leeds, United Kingdom
  8. St Anna Children's Hospital, Vienna, Austria
  9. Paediatric Oncology and Haematology Leeds General Infirmary, Leeds, United Kingdom
  10. Fondazione IRCCS Instituto Nazionale dei Tumori, Milano, Italy
  11. Institut Gustave Roussy, Villejuif, France

Purpose: To evaluate the prognostic power of paired-like homeobox 2b (PHOX2B) and tyrosine hydroxylase (TH) mRNAs detected by reverse transcriptase quantitative polymerase chain reaction (RTqPCR) in peripheral blood stem cell (PBSC) harvests from stage 4 children entered into the European trial HR-NBL-1/SIOPEN.

 

Methods: Samples were collected and RTqPCR performed for PHOX2B and TH mRNA in PBSC (n=189) and paired blood taken at diagnosis (n=166) as previously described (Viprey et al, 2007,EJC,43;341-50; Viprey et al, 2014,JCO,32;1074-83).

 

Results: When considered as binary or continuous variables there was no significant relationship between TH or PHOX2B mRNAs in PBSC harvests, the time of reinfusion and event-free survival (EFS). Additionally no prognostic cut-point could be identified. Consistent with previous observations, high levels of TH (log10 >0.8) or PHOX2B (log10>0.28) mRNA in blood at diagnosis identified a group of children with an increased risk of an event, with 5 year EFS of 16% compared to 43% ((HR (95% CI) =2.44 (1.58, 3.75), p<0.0001). In the children with a more favourable outcome (n=117), the presence of TH or PHOX2B mRNAs in PBSC harvest predicted an increased risk of an event post reinfusion. This effect appeared greatest when both TH and PHOX2B mRNA were detected (HR (95% CI) =3.55 (1.30, 9.73), p=0.01); this requires validation. There was no correlation between the level of PHOX2B or TH mRNA in PBSC harvest and the time of harvest or surgery.

 

Conclusion: PHOX2B and TH mRNAs in PBSC harvests do not predict EFS from the time of reinfusion in all children with stage 4 neuroblastoma. However, they may identify a sub-group of children who have an increased risk of an event post reinfusion of the PBSC harvest.