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

Purpose: 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 hematological reconstitution after autologous stem cell transplantation (ASCT) in HR-NBL patients treated with upfront ¹³¹I-MIBG-therapy. Experimental Design: In two prospective multi-center cohort studies, newly diagnosed HR-NBL patients were treated with two courses of ¹³¹I-MIBG-therapy, followed by a HR-induction protocol. Hematopoietic stem- and progenitor cell (e.g. CD34+cell) harvest yield, required number of apheresis sessions, and time to neutrophil (>0.5x10⁹/L) and platelet (>20x10⁹/L) reconstitution after ASCT, were analyzed and compared to 'chemotherapy-only' -treated patients. Moreover, harvested CD34⁺cells were functionally (viability and clonogenic capacity) and phenotypically (CD33, CD41 and CD62L) tested, prior to cryopreservation (n=44) and/or post-thawing (n=19). Results: Thirty-eight (47%) patients 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 versus 10 days), while platelet recovery was delayed in ¹³¹I-MIBG- compared to chemotherapy-only-treated patients (29 versus 15 days, p=0.037). Testing of harvested CD34+cells revealed a reduced post-thaw viability in the ¹³¹I-MIBG-group. Moreover, the viable CD34+ population contained less cells expressing CD62L (L-selectin), a marker associated with rapid platelet recovery. Conclusions: Harvesting of CD34+cells is feasible post ¹³¹I-MIBG. Platelet recovery after ASCT was delayed in ¹³¹I-MIBG-treated patients, possibly due to re-infusion of less viable and CD62L-expressing CD34+cells, but without clinical complications.

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