Peripheral Stem Cell Apheresis is Feasible Post Iodine-Metaiodobenzylguanidine-Therapy in High-Risk Neuroblastoma, but Results in Delayed Platelet Reconstitution.

PURPOSE

Targeted radiotherapy with iodine-meta-iodobenzylguanidine (I-MIBG) is effective for neuroblastoma (NBL), although optimal scheduling during high-risk (HR) treatment is being investigated. We aimed to evaluate the feasibility of stem cell apheresis and study hematologic reconstitution after autologous stem cell transplantation (ASCT) in patients with HR-NBL treated with upfront I-MIBG-therapy.

EXPERIMENTAL DESIGN

In two prospective multicenter cohort studies, newly diagnosed patients with HR-NBL were treated with two courses of I-MIBG-therapy, followed by an HR-induction protocol. Hematopoietic stem and progenitor cell (e.g., CD34 cell) harvest yield, required number of apheresis sessions, and time to neutrophil (>0.5 × 10/L) and platelet (>20 × 10/L) reconstitution after ASCT were analyzed and compared with "chemotherapy-only"-treated patients. Moreover, harvested CD34 cells were functionally (viability and clonogenic capacity) and phenotypically (CD33, CD41, and CD62L) tested before cryopreservation ( = 44) and/or after thawing ( = 19).

RESULTS

Thirty-eight patients (47%) were treated with I-MIBG-therapy, 43 (53%) only with chemotherapy. Median cumulative I-MIBG dose/kg was 0.81 GBq (22.1 mCi). Median CD34 cell harvest yield and apheresis days were comparable in both groups. Post ASCT, neutrophil recovery was similar (11 days vs. 10 days), whereas platelet recovery was delayed in I-MIBG- compared with chemotherapy-only-treated patients (29 days vs. 15 days, = 0.037). Testing of harvested CD34 cells revealed a reduced post-thaw viability in the I-MIBG-group. Moreover, the viable CD34 population contained fewer cells expressing CD62L (L-selectin), a marker associated with rapid platelet recovery.

CONCLUSIONS

Harvesting of CD34 cells is feasible after I-MIBG. Platelet recovery after ASCT was delayed in I-MIBG-treated patients, possibly due to reinfusion of less viable and CD62L-expressing CD34 cells, but without clinical complications. We provide evidence that peripheral stem cell apheresis is feasible after upfront I-MIBG-therapy in newly diagnosed patients with NBL. However, as the harvest of I-MIBG-treated patients contained lower viable CD34 cell counts after thawing and platelet recovery after reinfusion was delayed, administration of I-MIBG after apheresis is preferred.

©2018 American Association for Cancer Research.