Successful hematopoietic stem cell mobilization and apheresis collection using plerixafor alone in sickle cell patients

Author:

Esrick Erica B.1ORCID,Manis John P.2ORCID,Daley Heather3,Baricordi Cristina45,Trébéden-Negre Hélène3,Pierciey Francis J.6,Armant Myriam7,Nikiforow Sarah3,Heeney Matthew M.1,London Wendy B.1,Biasco Luca45,Asmal Mohammed6,Williams David A.1458,Biffi Alessandra1458

Affiliation:

1. Division of Hematology/Oncology, Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, Boston, MA;

2. Department of Laboratory Medicine, Boston Children’s Hospital, Boston, MA;

3. Connell & O’Reilly Families Cell Manipulation Core Facility, Dana-Farber Cancer Institute, Boston, MA;

4. Gene Therapy Program, Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, Boston, MA;

5. Gene Therapy Program for Rare Diseases, Department of Medicine, Boston Children’s Hospital, Boston, MA;

6. Bluebird bio, Cambridge, MA;

7. TransLab, Translational Research Program, Boston Children’s Hospital, Boston, MA; and

8. Harvard Stem Cell Institute, Boston, MA

Abstract

Abstract 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 × 106 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.

Publisher

American Society of Hematology

Subject

Hematology

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