Haematopoietic stem cell transplantation (HCT) is a critical treatment for various blood-related disorders, such as leukemia. Mobilizing sufficient hematopoietic progenitor cells (HPCs) from healthy donors is a key factor for successful transplantation. To address this challenge, plerixafor, a selective CXCR4 antagonist, has been developed as an effective mobilization agent.
Plerixafor: a Selective CXCR4 Antagonist Used for Haematopoietic Cell Transplantation Research
Plerixafor is a selective CXCR4 antagonist that has emerged as an effective mobilization agent. It works by disrupting the CXCR4-CXCL12 axis, which normally retains HPCs within the bone marrow niche. By blocking this pathway, plerixafor promotes the migration of HPCs into peripheral blood, facilitating their collection for transplantation.
The Effect of Plerixafor
Devine et al. studied 25 healthy related donors in 2008. They used plerixafor at 0.24 mg/kg without G-CSF. The median CD34+ cell count was 2.9 × 10⁶/kg. Hauge et al. in 2014 gave plerixafor at 0.24 mg/kg to six healthy stem cell donors. They achieved a median CD34+ cell count of 10.2 × 10⁶/kg. Gattillo et al. in 2015 used plerixafor at 0.35 mg/kg in ten healthy family donors. They obtained a median CD34+ cell count of 5.9 × 10⁶/kg.
Schroeder et al. in 2017 administered intravenous plerixafor at 0.08–0.48 mg/kg to 50 donors. They found the maximally effective dose was 0.32 mg/kg. Teipel et al. in 2018 compared cellular products in G-CSF mobilized HDs before and after additional plerixafor. They found plerixafor increased total nucleated cells, including CD19+ B cells, CD4+ and CD8+ T cells, and CD34+ haematopoietic stem and progenitor cells.
In summary, plerixafor is a selective CXCR4 antagonist which has proven effective in HCT research. It boosts HPC yield in healthy donors, whether used alone or with G-CSF. Moreover, it is generally well tolerated. Additionally, Plerixafor shows promise for enhancing transplant outcomes, particularly in addressing mobilization failure.
