Peripheral Stem Cell Apheresis is Feasible Post ¹³¹Iodine-Metaiodobenzylguanidine-Therapy in High-Risk Neuroblastoma, but Results in Delayed Platelet Reconstitution.

Abstract

Targeted radiotherapy with ¹³¹iodine-meta-iodobenzylguanidine (¹³¹I-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 ¹³¹I-MIBG-therapy. In two prospective multicenter cohort studies, newly diagnosed patients with HR-NBL were treated with two courses of ¹³¹I-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 × 10⁹/L) and platelet (>20 × 10⁹/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 (<i>n</i> = 44) and/or after thawing (<i>n</i> = 19). Thirty-eight patients (47%) were treated with ¹³¹I-MIBG-therapy, 43 (53%) only with chemotherapy. Median cumulative ¹³¹I-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 ¹³¹I-MIBG- compared with chemotherapy-only-treated patients (29 days vs. 15 days, <i>P</i> = 0.037). Testing of harvested CD34⁺ cells revealed a reduced post-thaw viability in the ¹³¹I-MIBG-group. Moreover, the viable CD34⁺ population contained fewer cells expressing CD62L (L-selectin), a marker associated with rapid platelet recovery. Harvesting of CD34⁺ cells is feasible after ¹³¹I-MIBG. Platelet recovery after ASCT was delayed in ¹³¹I-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 ¹³¹I-MIBG-therapy in newly diagnosed patients with NBL. However, as the harvest of ¹³¹I-MIBG-treated patients contained lower viable CD34⁺ cell counts after thawing and platelet recovery after reinfusion was delayed, administration of ¹³¹I-MIBG after apheresis is preferred.