Evidence for continued dose escalation of plerixafor for hematopoietic progenitor cell collections in sickle cell disease

Boulad, Farid; Zhang, Jiahao; Yazdanbakhsh, Karina; Sadelain, Michel; Shi, Patricia A.

doi:10.1016/j.bcmd.2021.102588

Cited by 3 publications

(2 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Increased plerixafor dosing beyond the standard of 240 mg/kg resulted in a higher fold increase in PB CD34 þ counts in two individuals with SCD [65], consistent with observations in healthy individuals [50]. Hence, higher plerixafor doses may improve HSC yield in some poorly mobilizing SCD patients.…”

Section: Changes To Plerixafor Administrationsupporting

confidence: 76%

“…Changing the route of plerixafor administration from subcutaneous to intravenous did not increase CD34 + mobilization in healthy donors [52]. Increased plerixafor dosing beyond the standard of 240 μg/kg resulted in a higher fold increase in PB CD34 + counts in two individuals with SCD [65], consistent with observations in healthy individuals [50]. Hence, higher plerixafor doses may improve HSC yield in some poorly mobilizing SCD patients.…”

Section: Novel Strategies For Mobilization Of Sickle Cell Disease Hem...supporting

confidence: 70%

See 1 more Smart Citation

Hematopoietic stem cell collection for sickle cell disease gene therapy

Leonard,

Weiss

2024

Current Opinion in Hematology

View full text Add to dashboard Cite

Purpose of review Gene therapy for sickle cell disease (SCD) is advancing rapidly, with two transformative products recently approved by the US Food and Drug Administration and numerous others under study. All current gene therapy protocols require ex vivo modification of autologous hematopoietic stem cells (HSCs). However, several SCD-related problems impair HSC collection, including a stressed and damaged bone marrow, potential cytotoxicity by the major therapeutic drug hydroxyurea, and inability to use granulocyte colony stimulating factor, which can precipitate severe vaso-occlusive events. Recent findings Peripheral blood mobilization of HSCs using the CXCR4 antagonist plerixafor followed by apheresis collection was recently shown to be safe and effective for most SCD patients and is the current strategy for mobilizing HSCs. However, exceptionally large numbers of HSCs are required to manufacture an adequate cellular product, responses to plerixafor are variable, and most patients require multiple mobilization cycles, increasing the risk for adverse events. For some, gene therapy is prohibited by the failure to obtain adequate numbers of HSCs. Summary Here we review the current knowledge on HSC collection from individuals with SCD and potential improvements that may enhance the safety, efficacy, and availability of gene therapy for this disorder.

show abstract

Section: Changes To Plerixafor Administrationsupporting

confidence: 76%