Influence of plerixafor on the mobilization of CD34+ cell subpopulations and lymphocyte subtypes

Worel, Nina; Frank, Nelli; Frech, Christian; Fritsch, Gerhard

doi:10.1111/trf.14182

Cited by 16 publications

(18 citation statements)

References 41 publications

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“…Only 0.2–2.8% of CD34 + cells were CD38-negative, but this may be consistent with plerixafor’s effect in normal healthy donors, in that fewer HPC may be mobilized by plerixafor than by G-CSF, where up to 50% of G-CSF-mobilized CD34 + cells are CD38-negative. 13 , 40 …”

Section: Discussionmentioning

confidence: 99%

Safety and efficacy of plerixafor dose escalation for the mobilization of CD34 ⁺ hematopoietic progenitor cells in patients with sickle cell disease: interim results

et al. 2018

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Gene therapy for sickle cell disease is limited by the yield of hematopoietic progenitor cells that can be harvested for transduction or gene editing. We therefore performed a phase I dose-escalation study of the hematopoietic progenitor cell mobilizing agent plerixafor to evaluate the efficacy and safety of standard dosing on peripheral blood CD34+ cell mobilization. Of 15 patients enrolled to date, only one was chronically transfused and ten were on hydroxyurea. Of eight patients who achieved a CD34+ cell concentration >30 cells/μL, six were on hydroxyurea. There was no clear dose response to increasing plerixafor dosage. There was a low rate of serious adverse events; two patients developed vaso-occlusive crises, at the doses of 80 μg/kg and 240 μg/kg. Hydroxyurea may have contributed to the limited CD34+ mobilization by affecting baseline peripheral blood CD34 counts, which correlated strongly with peak peripheral blood CD34 counts. Plerixafor administration did not induce significant increases in the fraction of activated neutrophils, monocytes, or platelets. However, increased neutrophils positive for activated β2 integrin and Mac-1 were associated with serious adverse events. In summary, plerixafor was well tolerated but did not achieve consistent CD34+ cell mobilization in this cohort of patients, most of whom were being actively treated with hydroxyurea and only one was chronically transfused. The study will continue with escalation of the dose of plerixafor and modification of hydroxyurea administration. Clinicaltrials.gov identifier: NCT02193191.

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Section: Discussionmentioning

confidence: 99%

Safety and efficacy of plerixafor dose escalation for the mobilization of CD34 ⁺ hematopoietic progenitor cells in patients with sickle cell disease: interim results

et al. 2018

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“…Based on this observation and previous reports, possibly the peak of CD34+ cells could occur later. A study by Worel et al indicated a high-committed cell population in graft after plerixafor mobilization at 6 -12 hours' time interval (33). On the contrary, Shi et al suggested that despite CD34+ cells peak after 12 hours, CD38-/CD34+ cells, with higher priority, reach their peak between 10 and 18 hours (34).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of CD34+ Cell Count at Different Time Points Following Plerixafor Administration in Autologous Hematopoietic Stem Cell Transplantation

et al. 2022

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Background: In apheresis, collecting an adequate number of CD34+ cells is required for successful autologous hematopoietic stem cell transplantation (auto-HSCT) procedure. It is difficult to harvest a sufficient number of stem cells in certain patients due to their old age and history of intensive chemotherapy. Plerixafor could mobilize stem cells and facilitate peripheral blood hematopoietic stem cell collection. However, not enough information is available on the appropriate time intervals from plerixafor administration to apheresis. Objectives: In this study, we aimed at evaluating the level of peripheral blood CD34+ cells at plerixafor administration time and every three hours to identify the peak time of circulating CD34+ cells. Methods: Circulating CD34+ cells were enumerated by flow cytometry on day 4 post mobilization. Plerixafor was administered to patients with poor mobilization based on the count of peripheral blood hematopoietic stem cells. The number of circulating CD34+ cells was evaluated before and 3, 6, 9, and 12 hours after plerixafor administration to assess the time it takes for stem cells to reach their peak level. Results: The highest level of stem cell concentration was found in 9 hours after plerixafor administration with an increasing trend. A statistically significant relationship was also observed between factors including platelet count on the first day of GCSF injection and the day of stem cell infusion, leukocyte count on admission, and basal levels of CD34+ cells in peripheral blood and the amount of harvested stem cells. Conclusions: We demonstrated that plerixafor causes an incremental trend in CD34+ cells mobilization, reaching its peak after 9 hours. Further research should be performed to provide insights into graft cells’ population and hematologic and immunological recovery.

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“…Different administration schedules could advantageously be studied in order to perhaps optimize mobilization of TCR γδ and NK cells. Moreover, the effects on TCR γδ and NK cell of another mobilizing agent, Plerixafor, are unknown and as this information could also help guide decisions on different mobilization strategies ( 41 , 42 ).…”

Section: Discussionmentioning

confidence: 99%

Granulocyte Colony-Stimulating Factor Effectively Mobilizes TCR γδ and NK Cells Providing an Allograft Potentially Enhanced for the Graft-Versus-Leukemia Effect for Allogeneic Stem Cell Transplantation

et al. 2021

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Allogeneic hematopoietic stem cell transplantation (HSCT) is a potential cure for patients with hematological malignancies but substantial risks of recurrence of the malignant disease remain. TCR γδ and NK cells are perceived as potent innate effector cells in HSCT and have been associated with post-transplant protection from relapse in clinical studies. Immunocompetent cells from the donor are crucial for patient outcomes and peripheral blood stem cells (PBSC) are being increasingly applied as graft source. G-CSF is the preferential mobilizing agent in healthy donors for PBSC grafts, yet effects of G-CSF on TCR γδ and NK cells are scarcely uncovered and could influence the graft composition and potency of these cells. Therefore, we analyzed T and NK cell subsets and activation markers in peripheral blood samples of 49 donors before and after G-CSF mobilization and—for a subset of donors—also in the corresponding graft samples using multicolor flowcytometry with staining for CD3, CD4, CD8, TCRαβ, TCRγδ, Vδ1, Vδ2, HLA-DR, CD45RA, CD197, CD45RO, HLA-DR, CD16, CD56, and CD314. We found that TCR γδ cells were mobilized and harvested with an efficiency corresponding that of TCR αβ cells. For TCR γδ as well as for TCR αβ cells, G-CSF preferentially mobilized naïve and terminally differentiated effector (TEMRA) cells over memory cells. In the TCR γδ cell compartment, G-CSF preferentially mobilized cells of the nonVδ2 types and increased the fraction of HLA-DR positive TCR γδ cells. For NK cells, mobilization by G-CSF was increased compared to that of T cells, yet NK cells appeared to be less efficiently harvested than T cells. In the NK cell compartment, G-CSF-stimulation preserved the proportion of CD56dim NK effector cells which have been associated with relapse protection. The expression of the activating receptor NKG2D implied in anti-leukemic responses, was significantly increased in both CD56dim and CD56bright NK cells after G-CSF stimulation. These results indicate differentiated mobilization and altering properties of G-CSF which could improve the effects of donor TCR γδ and NK cells in the processes of graft-versus-leukemia for relapse prevention after HSCT.

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Influence of plerixafor on the mobilization of CD34+ cell subpopulations and lymphocyte subtypes

Cited by 16 publications

References 41 publications

Safety and efficacy of plerixafor dose escalation for the mobilization of CD34 ⁺ hematopoietic progenitor cells in patients with sickle cell disease: interim results

Safety and efficacy of plerixafor dose escalation for the mobilization of CD34 ⁺ hematopoietic progenitor cells in patients with sickle cell disease: interim results

Evaluation of CD34+ Cell Count at Different Time Points Following Plerixafor Administration in Autologous Hematopoietic Stem Cell Transplantation

Granulocyte Colony-Stimulating Factor Effectively Mobilizes TCR γδ and NK Cells Providing an Allograft Potentially Enhanced for the Graft-Versus-Leukemia Effect for Allogeneic Stem Cell Transplantation

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Influence of plerixafor on the mobilization of CD34+ cell subpopulations and lymphocyte subtypes

Cited by 16 publications

References 41 publications

Safety and efficacy of plerixafor dose escalation for the mobilization of CD34 + hematopoietic progenitor cells in patients with sickle cell disease: interim results

Safety and efficacy of plerixafor dose escalation for the mobilization of CD34 + hematopoietic progenitor cells in patients with sickle cell disease: interim results

Evaluation of CD34+ Cell Count at Different Time Points Following Plerixafor Administration in Autologous Hematopoietic Stem Cell Transplantation

Granulocyte Colony-Stimulating Factor Effectively Mobilizes TCR γδ and NK Cells Providing an Allograft Potentially Enhanced for the Graft-Versus-Leukemia Effect for Allogeneic Stem Cell Transplantation

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Safety and efficacy of plerixafor dose escalation for the mobilization of CD34 ⁺ hematopoietic progenitor cells in patients with sickle cell disease: interim results

Safety and efficacy of plerixafor dose escalation for the mobilization of CD34 ⁺ hematopoietic progenitor cells in patients with sickle cell disease: interim results