Poster Presentation Advances in Neuroblastoma Research Congress 2016

131Iodine-metaiodobenzylguanidine (131I -MIBG) and autologous stem cell transplantation harvesting and hematological reconstitution in high-risk neuroblastoma patients. (#335)

Kathelijne Kraal 1 , Hannah Kansen 1 , Carlijn Voermans 2 , Cor van den Bos 3 , Jozsef Zsiros 1 3 , Henk van den Berg 3 , Sebastiaan Somers 3 , Max van Noesel 1 , Ellen van der Schoot 2 , Marta Fiocco 4 5 , Hubert Caron 3 , Godelieve Tytgat 1 3
  1. Princess Máxima centre for Pediatric Oncology (PMC), Utrecht, the Netherlands
  2. Department of Experimental Immunohematology, Sanquin Research, and Landsteiner Laboratory of the AMC, Amsterdam, the Netherlands
  3. Department of Pediatric Oncology, Emma Children’s Hospital, Academical Medical Center, Amsterdam, the Netherlands
  4. Mathematical institute, Leiden University, Leiden, the Netherlands
  5. Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, the Netherlands

Aim: To evaluate feasibility of stem cell (SC) apheresis and hematological reconstitution after autologous stem cell transplantation (ASCT) in high-risk neuroblastoma (HR NBL) patients treated with upfront 131Iodine- metaiodobenzylguanidine (131I-MIBG) therapy.

Methods: In two prospective, multi-centre (AMC, Erasmus Medical Centre, University Medical Centre of Groningen, PMC) cohort studies (January 2005-2011 and 2011-October 2015), newly diagnosed HR NBL patients, 0-19 years, were treated with 2 courses of upfront 131I-MIBG therapy (fixed dose GBq (mCi): 1st 7.4 (200), 2nd 5.5 (150)), followed by HR GPOH NBL protocol. Harvest SC yield, number of sessions needed and time to neutrophil (0.5x109/L) and platelet reconstitution (>20x109/L) after ASCT were analysed (Kaplan Meier methodology).

Results: Eighty-two children were included (median age 3.2 years): thirty-eight (46.3%) treated with 131I-MIBG therapy, forty-four (53.7%) received only chemotherapy, because of poor clinical condition(n=27), MIBG non-avid tumors(n=11) and logistic failure(n=6). Median cumulative 131I-MIBG dose/kg was 0.76 gBQ (20.6 mCi). Median SC-apheresis yield (range): 5.4 x106/kg CD34+ cells (0.9-32.3) in 131I-MIBG+ patients(n=35) and 5.6 x106/kg (0.5-44.5) in chemotherapy-only patients(n=36). Median cumulative apheresis days: 2 days (range 1-8). One apheresis day was sufficient in 44.1% of 131I-MIBG+ and 62.2% of chemotherapy-only patients, two days in respectively 75.5% and 75.7%. Total number of apheresis sessions and -days were comparable between groups. Failure to harvest PB (peripheral blood) SC: 131I-MIBG therapy one patient and chemotherapy group two patients. A multivariate regression model for SC harvest yield showed, after adjusting for age/ gender/ MycN amplification/ LOH1p /Cisplatin dose, a significant association with bone marrow infiltration at diagnosis, (p=0.002). Median time to platelet reconstitution (95% CI) was 29 (11-47) and 15 days (12-18) (p=0.037) respectively for I-MIBG+ and chemotherapy-only group, neutrophil reconstitution (95% CI) respectively 11 (10-12) and 10 (9-11) days.

Conclusion: Stem cell harvesting is feasible after upfront 131I-MIBG in HR NBL patients with comparable neutrophil, but delayed platelets reconstitution compared with chemotherapy-only patients.