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. 2021 Jun 1:22:76-83.
doi: 10.1016/j.omtm.2021.05.013. eCollection 2021 Sep 10.

Peripheral blood stem and progenitor cell collection in pediatric candidates for ex vivo gene therapy: a 10-year series

Daniele Canarutto  1   2   3 , Francesca Tucci  2   3 , Salvatore Gattillo  4 , Matilde Zambelli  4 , Valeria Calbi  2   3 , Bernhard Gentner  2   5 , Francesca Ferrua  2   3 , Sarah Marktel  5 , Maddalena Migliavacca  2   3 , Federica Barzaghi  2   3 , Giulia Consiglieri  2   3 , Vera Gallo  2   3 , Francesca Fumagalli  2   3 , Paola Massariello  6 , Cristina Parisi  4 , Gianluca Viarengo  7 , Elena Albertazzi  2 , Paolo Silvani  8 , Raffaella Milani  4 , Luca Santoleri  4 , Fabio Ciceri  1   5 , Maria Pia Cicalese  2   3 , Maria Ester Bernardo  1   2   3 , Alessandro Aiuti  1   2   3
Affiliations

Peripheral blood stem and progenitor cell collection in pediatric candidates for ex vivo gene therapy: a 10-year series

Daniele Canarutto et al. Mol Ther Methods Clin Dev. .

Abstract

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 ex vivo 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 × 106 CD34+ cells/kg. The procedures were well tolerated. Patients who collected ≥7 and ≥13 × 106 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 × 106 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.

Keywords: apheresis; congenital; harvest; hematopoietic stem and progenitor cells; lenograstim; mobilization; plerixafor; rare disease.

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Conflict of interest statement

SR-TIGET is a joint venture between Fondazione Telethon and OSR. Gene therapies for ADA-SCID, WAS, MLD, β-thalassemia, and MPSIH developed at SR-TIGET were licensed to Orchard Therapeutics (OTL) in 2018 and 2019. A.A. is the principal investigator (PI) of the above clinical trials. M.E.B. is the current PI of the MPSIH clinical trial.

Figures

None
Graphical abstract
Figure 1
Figure 1
CD34+ cell counts in peripheral blood, apheresis bags, and collection yield Box and whiskers plots illustrating the absolute number of CD34+ cells in peripheral blood before the apheresis (A) and the corresponding relative CD34+ content in the apheresis bag (B) and absolute CD34+ cell yield averaged by weight (C). Whiskers range from minimum to maximum.
Figure 2
Figure 2
Comparison of CD34+ cell yield of mobilization and leukapheresis versus bone marrow harvest (A) MLD patients. (B) WAS patients. Whiskers range from minimum to maximum. ∗ p<0.05 ∗∗∗∗ p <0.0001.
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