Peripheral stem cell apheresis is feasible post 131 iodine-metaiodobenzylguanidine-therapy in high-risk neuroblastoma, but results in delayed platelet reconstitution

Abstract

Purpose: Targeted radiotherapy with 131 iodine-meta-iodobenzylguanidine ( 131 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 131 I-MIBG-therapy. Experimental Design: In two prospective multicenter cohort studies, newly diagnosed patients with HR-NBL were treated with two courses of 131 I-MIBG-therapy, followed by an HR-induction protocol. Hematopoietic stem and progenitor cell (e.g., CD34 þ cell) harvest yield, required number of apheresis sessions, and time to neutrophil (>0.5 10 9 /L) and platelet (>20 10 9 /L) reconstitution after ASCT were analyzed and compared with "chemotherapy-only"-treated patients. Moreover, harvested CD34 þ cells were functionally (viability and clonogenic capacity) and phenotypically (CD33, CD41, and CD62L) tested before cryopreservation (n ¼ 44) and/or after thawing (n ¼ 19). Results: Thirty-eight patients (47%) were treated with 131 I-MIBG-therapy, 43 (53%) only with chemotherapy. Median cumulative 131 I-MIBG dose/kg was 0.81 GBq (22.1 mCi). Median CD34 þ 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 131 I-MIBG- compared with chemotherapy-only-treated patients (29 days vs. 15 days, P ¼ 0.037). Testing of harvested CD34 þ cells revealed a reduced post-thaw viability in the 131 I-MIBG-group. Moreover, the viable CD34 þ population contained fewer cells expressing CD62L (L-selectin), a marker associated with rapid platelet recovery. Conclusions: Harvesting of CD34 þ cells is feasible after 131 I-MIBG. Platelet recovery after ASCT was delayed in 131 I-MIBG-treated patients, possibly due to reinfusion of less viable and CD62L-expressing CD34 þ cells, but without clinical complications. We provide evidence that peripheral stem cell apheresis is feasible after upfront 131 I-MIBG-therapy in newly diagnosed patients with NBL. However, as the harvest of 131 I-MIBG-treated patients contained lower viable CD34 þ cell counts after thawing and platelet recovery after reinfusion was delayed, administration of 131 I-MIBG after apheresis is preferred.