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.