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administration and HSPC mobilization. Furthermore, Plerixafor synergistically augments Filgrastim-induced mobilization of HSPC,17 and so has been widely combined with Filgrastim (i) in Filgrastim-non-responsive patients, (ii) as an adjunct to increase the overall recovery of CD34+ cells for autologous or allogenic HSCT, and (iii) in gene therapy trials for β-thalassemia and Wiskott-Aldrich syn- drome.18-20 In view of all the above data, we initiated a phase I/II clinical trial of Plerixafor as a single mobilizing agent (NCT02212535). Our objective was to demonstrate that SCD patients can be safely mobilized under well- defined, controlled clinical and biological conditions. Moreover, this clinical trial provided an estimate of the overall recovery of CD34+ HSPC after apheresis in adult Plerixafor-mobilized SCD patients – thus providing a basis for the wider use of this protocol for gene-addition or genome-editing approaches.
Methods
Study design and human samples
This open-label phase I/II trial (ClinicalTrials.gov number, NCT02212535) was sponsored by the Assistance Publique Hôpitaux de Paris. The protocol was reviewed and approved by the French Drug Agency (Agence Nationale de Sécurité du Médicament) and the local independent ethics committee (Comité de Protection des Personnes Ile-de-France II, Paris, France). The trial was performed in accordance with the Declaration of Helsinki. Adult SCD patients and healthy donors (for control samples) provided their written, informed consent (Online Supplementary Table S1). The study was designed to demonstrate the safety and efficacy of the mobilization and harvesting of peripheral HSPC following a single injection of 0.24 mg/kg Plerixafor in adult SCD patients, with the inclusion criteria described in the Online Supplementary Methods.
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B
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Figure 1. Plerixafor is highly efficient at mobilizing hematopoietic stem and progenitor cells from sick- le cell disease patients. (A) Changes in white blood cell (WBC) and (B) CD34+ hematopoietic stem/prog- enitor cell (HSPC) counts over the 66 h following Plerixafor administration in SCD Pler 1 (red squares), SCD Pler 2 (blue circles) and SCD Pler 3 (green triangles). Arrows indicate time and duration of apheresis. (C) Number of hematopoietic stem cells (HSC, black bars) and multipotent progenitors (MPP, dotted bars) per 1,000 CD34+ cells in sam- ples of various origins. HD: healthy donor, BM: bone marrow, SCD: sickle cell disease, Pler: Plerixafor, Filg: Filgrastim.
haematologica | 2018; 103(5)