Data from Peripheral Stem Cell Apheresis is Feasible Post <sup>131</sup>Iodine-Metaiodobenzylguanidine-Therapy in High-Risk Neuroblastoma, but Results in Delayed Platelet Reconstitution
Authors: Kraal Kathelijne C.J.M. , Timmerman Ilse , Kansen Hannah M. , van den Bos Cor , Zsiros Jozsef , van den Berg Henk , Somers Sebastiaan , Braakman Eric , Peek Annemarie M.L. , van Noesel Max M. , van der Schoot C. Ellen , Fiocco Marta , Caron Huib N. , Voermans Carlijn , Tytgat Godelieve A.M. 
Published: April 2023

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