Successful Hematopoietic Stem Cell Mobilization and Apheresis Collection Using Plerixafor Alone in Sickle Cell Patients
Overview
Authors
Affiliations
Novel therapies for sickle cell disease (SCD) based on genetically engineered autologous hematopoietic stem and progenitor cells (HSPCs) are critically dependent on a safe and effective strategy for cell procurement. We sought to assess the safety and efficacy of plerixafor when used in transfused patients with SCD for HSC mobilization. Six adult patients with SCD were recruited to receive a single dose of plerixafor, tested at lower than standard (180 µg/kg) and standard (240 µg/kg) doses, followed by CD34 cell monitoring in peripheral blood and apheresis collection. The procedures were safe and well-tolerated. Mobilization was successful, with higher peripheral CD34 cell counts in the standard vs the low-dose group. Among our 6 donors, we improved apheresis cell collection results by using a deep collection interface and starting apheresis within 4 hours after plerixafor administration. In the subjects who received a single standard dose of plerixafor and followed the optimized collection protocol, yields of up to 24.5 × 10 CD34 cells/kg were achieved. Interestingly, the collected CD34 cells were enriched in immunophenotypically defined long-term HSCs and early progenitors. Thus, we demonstrate that plerixafor can be employed safely in patients with SCD to obtain sufficient HSCs for potential use in gene therapy.
How I treat sickle cell disease with gene therapy.
Sharma A Blood. 2024; 144(26):2693-2705.
PMID: 39356871 PMC: 11830977. DOI: 10.1182/blood.2024024519.
Frati G, Brusson M, Sartre G, Mlayah B, Felix T, Chalumeau A Mol Ther. 2024; 32(12):4337-4352.
PMID: 39044427 PMC: 11638826. DOI: 10.1016/j.ymthe.2024.07.015.
Hematopoietic stem cell collection for sickle cell disease gene therapy.
Leonard A, Weiss M Curr Opin Hematol. 2024; 31(3):104-114.
PMID: 38359264 PMC: 11414477. DOI: 10.1097/MOH.0000000000000807.
Gene therapy for sickle cell disease.
Leonard A, Tisdale J Hematology Am Soc Hematol Educ Program. 2023; 2023(1):542-547.
PMID: 38066927 PMC: 10727030. DOI: 10.1182/hematology.2023000487.
Piel F, Rees D, DeBaun M, Nnodu O, Ranque B, Thompson A Lancet Haematol. 2023; 10(8):e633-e686.
PMID: 37451304 PMC: 11459696. DOI: 10.1016/S2352-3026(23)00096-0.