Use of plerixafor to mobilize haematopoietic progenitor cells in healthy donors

Romón, Íñigo; Castillo, Carlos; Cid, Joan; Lozano, Miguel

doi:10.1111/vox.13175

Cited by 7 publications

(2 citation statements)

References 75 publications

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“…Plerixafor is a chemokine receptor antagonist, which acts to prevent the interaction between stromal-derived factor 1 in the bone marrow (BM) niche and C-X-C chemokine receptor type 4 on HPCs, thereby promoting their migration from BM to PB [ 22 ]. Mobilization regimens including plerixafor alone or in combination have been described in autologous and allogeneic transplant settings [ 23 , 24 ]. When used as up-front mobilization, the combination of G-CSF and plerixafor significantly expands the proportion of MM and lymphoma patients achieving a satisfactory cell dose collection [ 25 , 26 ].…”

Section: Introductionmentioning

confidence: 99%

Day -1 CD34+ Cells and Platelet Count Predict the Number of Apheresis in Poor-Mobilizer Patients Rescued by Plerixafor

Valentini

Pellegrino

Putzulu

et al. 2023

JCM

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Plerixafor is widely used as up-front treatment with G-CSF to enhance peripheral blood hematopoietic stem cell output in patients failing previous mobilizations. Less frequently, plerixafor is used to rescue an unsatisfactory mobilization following chemotherapy (CT) and G-CSF. This study investigates if pre-collection factors affect the CD34+ cell harvest in chemotherapy and G-CSF mobilizations rescued by plerixafor. Clinical and hematological data relative to patients, mobilization, and apheresis products were retrospectively examined. The outcome was completing a target cell dose ≥ 2 × 106 CD34+ cells /Kg at first apheresis. The effect exerted on the outcome by patient- and disease-related factors was investigated by univariate and multivariate logistic regression analysis. The analysis included data from 42 patients affected by hematological (39 patients) and non-hematological malignancies (three patients). Twenty-nine patients (69%) attained the target cell dose at first apheresis. Twelve out of the remaining 13 patients received an additional plerixafor administration, and all accomplished the transplant dose at a second apheresis procedure. Day -1 CD34+ PB count (OR1.46, 95% CI 1.1–1.9, p = 0.008) and platelet count (OR1.0, 95% CI 1.0–1.0, p = 0.033) predicted the achievement of the target dose at first apheresis, independently of pre-mobilization CT, radiation therapy, and disease status at mobilization. At ROC curve analysis, the best cut-off value predicting the successful collection at first apheresis was 7.5/µL for Day -1 CD34+ cell count (AUC 0.830, 0.69 sensitivity, and 0.92 specificity) and 75 × 109/L for Day -1 platelet count (AUC = 0.736, 0.65 sensitivity and 0.85 specificity). In conclusion, on-demand plerixafor rescue allows a successful stem cell collection, irrespectively of disease type and status, prior CT lines, and radiation exposure. Pre-apheresis CD34+ cells and platelet count predict the need for one or two aphereses.

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Section: Introductionmentioning

confidence: 99%

Day -1 CD34+ Cells and Platelet Count Predict the Number of Apheresis in Poor-Mobilizer Patients Rescued by Plerixafor

Valentini

Pellegrino

Putzulu

et al. 2023

JCM

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“…However, the efficiency of HSC mobilization by AMD3100 alone is much less than that of G-CSF. Therefore, AMD3100 serves as an accessory treatment in combination with G-CSF to induce a more effective mobilization for clinical use, especially in heavily G-CSF-pretreated patients with lymphoma and myeloma [ 33 – 35 ].…”

Section: Introductionmentioning

confidence: 99%

Platelet-derived circulating soluble P-selectin is sufficient to induce hematopoietic stem cell mobilization

Wang,

Liou,

Yang

et al. 2023

Stem Cell Res Ther

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Background Granulocyte colony-stimulating factor (G-CSF)-mediated mobilization of hematopoietic stem cells (HSCs) is a well-established method to prepare HSCs for transplantation nowadays. A sufficient number of HSCs is critical for successful HSC transplantation. However, approximately 2–6% of healthy stem cell donors are G-CSF-poor mobilizers for unknown reasons; thus increasing the uncertainties of HSC transplantation. The mechanism underlining G-CSF-mediated HSC mobilization remains elusive, so detailed mechanisms and an enhanced HSC mobilization strategy are urgently needed. Evidence suggests that P-selectin and P-selectin glycoprotein ligand-1 (PSGL-1) are one of the cell–cell adhesion ligand–receptor pairs for HSCs to keep contacting bone marrow (BM) stromal cells before being mobilized into circulation. This study hypothesized that blockage of PSGL-1 and P-selectin may disrupt HSC-stromal cell interaction and facilitate HSC mobilization. Methods The plasma levels of soluble P-selectin (sP-sel) before and after G-CSF administration in humans and male C57BL/6J mice were analyzed using enzyme-linked immunosorbent assay. Male mice with P-selectin deficiency (Selp−/−) were further employed to investigate whether P-selectin is essential for G-CSF-induced HSC mobilization and determine which cell lineage is sP-sel derived from. Finally, wild-type mice were injected with either G-CSF or recombinant sP-sel to investigate whether sP-sel alone is sufficient for inducing HSC mobilization and whether it accomplishes this by binding to HSCs and disrupting their interaction with stromal cells in the BM. Results A significant increase in plasma sP-sel levels was observed in humans and mice following G-CSF administration. Treatments of G-CSF induced a decrease in the level of HSC mobilization in Selp−/− mice compared with the wild-type (Selp+/+) controls. Additionally, the transfer of platelets derived from wild-type mice can ameliorate the defected HSC mobilization in the Selp−/− recipients. G-CSF induces the release of sP-sel from platelets, which is sufficient to mobilize BM HSCs into the circulation of mice by disrupting the PSGL-1 and P-selectin interaction between HSCs and stromal cells. These results collectively suggested that P-selectin is a critical factor for G-CSF-induced HSC mobilization. Conclusions sP-sel was identified as a novel endogenous HSC-mobilizing agent. sP-sel injections achieved a relatively faster and more convenient regimen to mobilize HSCs in mice than G-CSF. These findings may serve as a reference for developing and optimizing human HSC mobilization in the future.

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Haemopoietic Stem Cell Processing and Storage

Gupta

Foley

2022

Practical Transfusion Medicine

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Use of plerixafor to mobilize haematopoietic progenitor cells in healthy donors

Cited by 7 publications

References 75 publications

Day -1 CD34+ Cells and Platelet Count Predict the Number of Apheresis in Poor-Mobilizer Patients Rescued by Plerixafor

Day -1 CD34+ Cells and Platelet Count Predict the Number of Apheresis in Poor-Mobilizer Patients Rescued by Plerixafor

Platelet-derived circulating soluble P-selectin is sufficient to induce hematopoietic stem cell mobilization

Haemopoietic Stem Cell Processing and Storage

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