TY - JOUR
T1 - Peripheral stem cell apheresis is feasible post 131iodine-metaiodobenzylguanidine-therapy in high-risk neuroblastoma, but results in delayed platelet reconstitution
AU - Kraal, Kathelijne C. J. M.
AU - Timmerman, Ilse
AU - Kansen, Hannah M.
AU - van den Bos, Cor
AU - Zsiros, Jozsef
AU - van den Berg, Henk
AU - Somers, Sebastiaan
AU - Braakman, Eric
AU - Peek, Annemarie M. L.
AU - van Noesel, Max M.
AU - van der Schoot, C. Ellen
AU - Fiocco, Marta
AU - Caron, Huib N.
AU - Voermans, Carlijn
AU - Tytgat, Godelieve A. M.
PY - 2019
Y1 - 2019
N2 - 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 hematologic reconstitution after autologous stem cell transplantation (ASCT) in patients with HR-NBL treated with upfront 131I-MIBG-therapy. Experimental Design: In two prospective multicenter cohort studies, newly diagnosed patients with HR-NBL were treated with two courses of131I-MIBG-therapy, followed by an HR-induction protocol. Hematopoietic stem and progenitor cell (e.g., CD34þ 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 CD34þ 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 with131I-MIBG-therapy, 43 (53%) only with chemotherapy. Median cumulative131I-MIBG dose/kg was 0.81 GBq (22.1 mCi). Median CD34þ 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 in131I-MIBG- compared with chemotherapy-only-treated patients (29 days vs. 15 days, P ¼ 0.037). Testing of harvested CD34þ cells revealed a reduced post-thaw viability in the131I-MIBG-group. Moreover, the viable CD34þ population contained fewer cells expressing CD62L (L-selectin), a marker associated with rapid platelet recovery. Conclusions: Harvesting of CD34þ cells is feasible after131I-MIBG. Platelet recovery after ASCT was delayed in131I-MIBG-treated patients, possibly due to reinfusion of less viable and CD62L-expressing CD34þ cells, but without clinical complications. We provide evidence that peripheral stem cell apheresis is feasible after upfront131I-MIBG-therapy in newly diagnosed patients with NBL. However, as the harvest of131I-MIBG-treated patients contained lower viable CD34þ cell counts after thawing and platelet recovery after reinfusion was delayed, administration of131I-MIBG after apheresis is preferred.
AB - 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 hematologic reconstitution after autologous stem cell transplantation (ASCT) in patients with HR-NBL treated with upfront 131I-MIBG-therapy. Experimental Design: In two prospective multicenter cohort studies, newly diagnosed patients with HR-NBL were treated with two courses of131I-MIBG-therapy, followed by an HR-induction protocol. Hematopoietic stem and progenitor cell (e.g., CD34þ 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 CD34þ 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 with131I-MIBG-therapy, 43 (53%) only with chemotherapy. Median cumulative131I-MIBG dose/kg was 0.81 GBq (22.1 mCi). Median CD34þ 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 in131I-MIBG- compared with chemotherapy-only-treated patients (29 days vs. 15 days, P ¼ 0.037). Testing of harvested CD34þ cells revealed a reduced post-thaw viability in the131I-MIBG-group. Moreover, the viable CD34þ population contained fewer cells expressing CD62L (L-selectin), a marker associated with rapid platelet recovery. Conclusions: Harvesting of CD34þ cells is feasible after131I-MIBG. Platelet recovery after ASCT was delayed in131I-MIBG-treated patients, possibly due to reinfusion of less viable and CD62L-expressing CD34þ cells, but without clinical complications. We provide evidence that peripheral stem cell apheresis is feasible after upfront131I-MIBG-therapy in newly diagnosed patients with NBL. However, as the harvest of131I-MIBG-treated patients contained lower viable CD34þ cell counts after thawing and platelet recovery after reinfusion was delayed, administration of131I-MIBG after apheresis is preferred.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85060910029&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/30314967
U2 - https://doi.org/10.1158/1078-0432.CCR-18-1904
DO - https://doi.org/10.1158/1078-0432.CCR-18-1904
M3 - Article
C2 - 30314967
SN - 1078-0432
VL - 25
SP - 1012
EP - 1021
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 3
ER -