Poster Presentation Advances in Neuroblastoma Research Congress 2016

Quantification of bone marrow disease in high risk neuroblastoma patients by anti-GD2 immunocytochemistry – impact on survival. A SIOPEN High Risk Study. (#153)

Klaus Beiske 1 , Angela Sementa 2 , Raffaella Defferrari 2 , Jerzy Klijanienko 3 , Vassilios Papadakis 4 , Katrien Swerts 5 , Tim Lammens 6 , Marta Jeison 7 , Ales Vicha 8 , Yania Yáñez Peralta 9 , Milada Cvancarova 10 , Ulrike Pötschger 11 , Ruth Ladenstein 11
  1. Department of Pathology, Oslo University Hospital Radiumhospitalet, Oslo, Norway
  2. Servizio di Anatomia Patologica, Istituto G.Gaslini, Genova, Italy
  3. Cytopathology, Institut Curie, Paris, France
  4. Dept of Pediatric Hematology-Oncology, Aghia Sophia Children's Hospital, Athens, Greece
  5. VIB, Zwijnaarde, Belgium
  6. Department of Pediatric Hematology-Oncology and Stem Cell Transplantation, Ghent University Hospital, Ghent, Belgium
  7. Pediatric Hematology/Oncology Dept, Cancer Cytogenetics Laboratory, Schneider Children's Medical Center of Israel, Petah-Tikva, Israel
  8. Dept of Pediatric Oncology, 2nd Medical Faculty and Faculty Hospital Motol, Praha, Czech Republic
  9. Oncología Pediátrica, Grupo de Investigación Clínica y Traslacional en Cáncer, Hospital Universitari i Politècnic La Fe, Valencia, Spain
  10. Department of Nursing and Health Promotion, Oslo and Akershus University College of Applied Sciences, Faculty of Health Sciences, Oslo, Norway
  11. CCRI Children's Cancer Research Institute , St. Anna Kinderspital, Vienna, Austria

Background: Bone marrow (BM) infiltration frequently occurs in patients with metastatic neuroblastoma and is routinely analyzed with trephine biopsies and conventional cytomorphology (CCM) on BM smears. The SIOPEN High Risk Study includes a prospective analysis of tumor cell infiltration using anti-GD2 immunocytochemistry (ICC) at diagnosis, after induction chemotherapy, prior to myeloablative therapy and at the end of treatment.

Objective: (1) to evaluate the prognostic impact of the number of infiltrating tumor cells at diagnosis and after induction chemotherapy and (2) to compare the results of anti-GD2 ICC with those of CCM and trephines.

Methods: Mononuclear cells from 878 bilateral BM aspirates pulled from 289 patients were stained with anti-GD2 and evaluated according to international consensus guidelines (Beiske et al, BJC, 2009). Numbers of GD2-positive tumor cells and numbers of investigated BM cells were recorded. Time to progression (EFS) and time to death (overall survival OS) were analyzed using the Kaplan-Meier method. ROC analysis was applied to evaluate possible cut-offs for continuous predictors.

Results: ROC analyses of the sensitivity and specificity of selected cut-off values and various numbers of investigated tumor cells to predict EFS and OS revealed that only BM samples containing >2E+06 BM cells provided prognostic information. At diagnosis, the number of GD2-positive tumor cells was prognostic of EFS (p=0.005) and OS (p=0.003) as it was for BM trephines (EFS p<0.0001, OS p=0.001). In contrast, CCM predicted only EFS (p=0.034) but not OS. After induction, ICC alone was prognostic of EFS (p=0.008) and OS (p=0.007) while cytomorphology and trephines were not.

Conclusion: At diagnosis, both ICC and trephine biopsies were associated with OS and EFS. After induction chemotherapy, only ICC remains informative. It is mandatory to analyze >2E+06 bone marrow cells in order to obtain a prognostically informative result. The ICC assay may contribute to identify patients at ultra-high risk (UHR).