JOURNAL ARTICLE
MULTICENTER STUDY
RESEARCH SUPPORT, NON-U.S. GOV'T
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Peripheral Stem Cell Apheresis is Feasible Post 131 Iodine-Metaiodobenzylguanidine-Therapy in High-Risk Neuroblastoma, but Results in Delayed Platelet Reconstitution.

Clinical Cancer Research 2019 Februrary 2
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+ 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 ( n = 44) and/or after thawing ( n = 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+ 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 = 0.037). Testing of harvested CD34+ cells revealed a reduced post-thaw viability in the 131 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 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+ 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+ cell counts after thawing and platelet recovery after reinfusion was delayed, administration of 131 I-MIBG after apheresis is preferred.

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