Poster Presentation Advances in Neuroblastoma Research Congress 2016

Analyzing risk factors for stem-cell collection failure in patients on the High-Risk Neuroblastoma 1 trial (HR-NBL1/SIOPEN) (#152)

Shifra Ash 1 , Daniel Morgenstern 2 , Ulrike Pötschger 3 , Isaac Yaniv 1 , Kate Wheeler 4 , Claudia Pasqualini 5 , Domonique Valteau-Couanet 5 , Alberto Garaventa 6 , Sandro Dallorso 6 , Vassilios Papadakis 7 , Wieczorek Aleksandra 8 , Pablo Berlanga 9 , Ruth Ladenstein 10
  1. Schneider Children's Medical Center of Israel, Rosh Haain, Israel
  2. Paediatric Oncology, Great Ormond Street Hospital, London, United Kingdom
  3. Studies and Statistics on Integrated Research and Projects, St. Anna Kinderkrebsforschung e.v., Vienna, Austria
  4. Paediatric Haematology/Oncology, Oxford University Hospitals NHS Trust, Oxford, United Kingdom
  5. Paediatric and Adolescent Oncology Department, Gustave Roussy, Villejuif, France
  6. Paediatric Haematology/Oncology, Istituto Giannina Gaslini, Genova, Italy
  7. Paediatric Haematology/Oncology, Agia Sofia Children’s Hospital, Athens, Greece
  8. Paediatic/Oncology Hematology, Institute of Pediatrics, Jagiellonian University, Medical College, Krakow, Poland
  9. Paediatric Haematology/Oncology, Hospital La Fe Valencia, Valencia, Spain
  10. Paediatric Haematology/Oncology, St. Anna Kinderspital and St. Anna Kinderkrebsforschung e.v., Vienna, Austria

Background

The current HR-NBL1/SIOPEN strategy permits stem-cell leukopheresis only after completion of induction therapy due to the rapid 10-day schedule of COJEC cycles. Our aim was to define risk factors for insufficient stem cell collection of fewer than 3x106 CD34+ cells/kg body weight (BW) in this population.  

Patients and Methods

Patient eligibility in this analysis was completed induction therapy (COJEC ±TVD), accrual between 2002-2015 and at least one documented peripheral stem cell collection (PSSC) attempt. A total of 1024 patients were included, of which 896 (88%) had stage 4 disease and the remaining 128 MYCN-amplified (MNA) localized or 4S disease.  Median age at diagnosis was 2.7 years (range 22d – 19.8y). Median follow-up time is 5.4yrs. The minimum successful total stem cell yield was 3x106 CD34+ cells/kgBW as mandated by the trial protocol.

Results

689/1024 patients (67.3%) had a successful collection with one collection attempt while in 270 (26.5%) ≥2 collection cycles were undertaken, of whom 46/270 did not achieve the threshold of 3x106 CD34+ cells/kgBW.

In 111/1024 children (11%) ≤3x106/kg CD34+ were collected (range 0.2-2.9x106/kg, median 2.4). Failure of PBSC collection >3x106/kg was more frequent in patients without MNA disease (13.7% vs 8.4%, p=0.01 Fisher exact) and in patients aged ≥5 years at diagnosis (16.3% vs 9.8%, p=0.015). Persistent bone marrow (BM) involvement or other metastatic sites had no apparent impact on collection yield.

35/111 patients underwent additional BM harvest (0.2-14.1x106/kg CD34+ cells, median 2.6). 31/35 reached the threshold and received high-dose chemotherapy; 2/35 were transplanted with <3x106/kg CD34+ cells and 2 patients were not transplanted.

Among patients with <3x106/kg CD34+ cells collected by PSSC 90.8% (n=99) underwent high-dose chemotherapy, compared to 97.4% (n=832) in patients above threshold.  

Conclusion

Unsuccessful PSSC was more common in patients aged >5 years and without MNA disease; there was no statistical correlation with metastatic site involvement at diagnosis. Overall, >3x106/kg CD34+ were collected in 92% of patients.