Canarutto Daniele, Tucci Francesca, Gattillo Salvatore, Zambelli Matilde, Calbi Valeria, Gentner Bernhard, Ferrua Francesca, Marktel Sarah, Migliavacca Maddalena, Barzaghi Federica, Consiglieri Giulia, Gallo Vera, Fumagalli Francesca, Massariello Paola, Parisi Cristina, Viarengo Gianluca, Albertazzi Elena, Silvani Paolo, Milani Raffaella, Santoleri Luca, Ciceri Fabio, Cicalese Maria Pia, Bernardo Maria Ester, Aiuti Alessandro
Vita-Salute San Raffaele University, Via Olgettina, 58, 20132 Milan, Italy.
San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS San Raffaele Scientific Institute, Via Olgettina, 60, 20132 Milan, Italy.
Mol Ther Methods Clin Dev. 2021 Jun 1;22:76-83. doi: 10.1016/j.omtm.2021.05.013. eCollection 2021 Sep 10.
Hematopoietic stem and progenitor cell (HSPC)-based gene therapy (GT) requires the collection of a large number of cells. While bone marrow (BM) is the most common source of HSPCs in pediatric donors, the collection of autologous peripheral blood stem cells (PBSCs) is an attractive alternative for GT. We present safety and efficacy data of a 10-year cohort of 45 pediatric patients who underwent PBSC collection for backup and/or purification of CD34 cells for gene transfer. Median age was 3.7 years and median weight 15.8 kg. After mobilization with lenograstim/plerixafor (n = 41) or lenograstim alone (n = 4) and 1-3 cycles of leukapheresis, median collection was 37 × 10 CD34 cells/kg. The procedures were well tolerated. Patients who collected ≥7 and ≥13 × 10 CD34 cells/kg in the first cycle had pre-apheresis circulating counts of at ≥42 and ≥86 CD34 cells/μL, respectively. Weight-adjusted CD34 cell yield was positively correlated with peripheral CD34 cell counts and influenced by female gender, disease, and drug dosage. All patients received a GT product above the minimum target, ranging from 4 to 30.9 × 10 CD34 cells/kg. Pediatric PBSC collection compares well to BM harvest in terms of CD34 cell yields for the purpose of GT, with a favorable safety profile.
基于造血干细胞和祖细胞（HSPC）的基因治疗（GT）需要采集大量细胞。虽然骨髓（BM）是儿科供体中最常见的HSPC来源，但采集自体外周血干细胞（PBSC）是GT的一种有吸引力的替代方法。我们展示了45名儿科患者的10年队列的安全性和有效性数据，这些患者接受了PBSC采集，用于备份和/或纯化CD34细胞以进行基因转移。中位年龄为3.7岁，中位体重为15.8千克。在用来那度胺/普乐沙福（n = 41）或仅用来那度胺（n = 4）动员并进行1 - 3个周期的白细胞分离术后，中位采集量为37×10⁶个CD34细胞/千克。这些操作耐受性良好。在第一个周期中采集≥7×10⁶和≥13×10⁶个CD34细胞/千克的患者，采集前循环计数分别≥42和≥86个CD34细胞/微升。体重调整后的CD34细胞产量与外周CD34细胞计数呈正相关，并受女性性别、疾病和药物剂量影响。所有患者接受的GT产品均高于最低目标，范围为4至30.9×10⁶个CD34细胞/千克。就GT目的而言，儿科PBSC采集在CD34细胞产量方面与BM采集相当，且安全性良好。
