Plerixafor on demand in ten healthy family donors as a rescue strategy to achieve an adequate graft for stem cell transplantation

Gattillo, Salvatore; Marktel, Sarah; Rizzo, Lorenzo; Malato, Simona; Malabarba, Lucia; Coppola, M.; Assanelli, Andrea; Milani, Raffaella; Freitas, Tiago; Corti, Consuelo; Bellio, Laura; Ciceri, Fabio

doi:10.1111/trf.13059

Cited by 28 publications

(27 citation statements)

References 26 publications

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“…These doses of both G‐CSF and Mozobil (1 mg/kg) are higher than typically administered to human subjects, but are typical of what has been used in nonhuman primate studies in the last two decades . There was an animal that was mobilized twice but had poor mobilization on both occasions, consistent with individual variability, a phenomenon that is also seen in normal healthy human volunteer donors . Like humans we also observed the common side effect of thrombocytopenia in the nonhuman primate model.…”

Section: Discussionsupporting

confidence: 73%

Collection of hematopoietic CD34 stem cells in rhesus macaques using Spectra Optia

Haynes

Coonen

Post

et al. 2016

J of Clinical Apheresis

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Background Non-human primates, particularly rhesus macaques, are ideal pre-clinical large animal models to investigate organ tolerance induction protocols using donor hematopoietic stem cells (HSCs) to induce microchimerism. Their relatively small size poses some challenges for the safe and effective collection of peripheral blood HSCs through apheresis procedures. We describe our experiences using the Spectra Optia apheresis unit to successfully obtain HSCs from mobilized peripheral blood of rhesus macaques. Method Mobilization of peripheral blood HSCs was induced using granulocyte stimulating factor (G-CSF) and Mozobil. The Spectra Optia unit was used in 18 apheresis procedures in 13 animals (4.9–10 kg). Animal health was carefully monitored during and after the procedure. Changes in peripheral blood cells before, during and after procedure were determined by complete blood count and flow cytometry. Results The automatic settings of the Spectra Optia unit were applied successfully to the procedures on the rhesus macaque. All animals tolerated the procedure well with no mortality. Mobilization of HSCs were most consistently achieved using 50μg/kg of G-CSF for 5 days and a single dose of Mozobil on the 5th day, followed by collection of cells 3 hours after Mozobil injection. The final apheresis product contained an average of 23 billion total nucleated cells with 47% granulocytes, 3,871 million total CD3 cells and 77 million CD34 cells which resulted in an average of 10 million CD34+ cells/kg of donor weight. Conclusion Apheresis of peripheral blood mobilized HSCs in rhesus macaques using Spectra Optia is a safe and effective procedure.

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Section: Discussionsupporting

confidence: 73%

Collection of hematopoietic CD34 stem cells in rhesus macaques using Spectra Optia

Haynes

Coonen

Post

et al. 2016

J of Clinical Apheresis

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“…Notably, in cases in which a single donor exists, the prediction of being a "poor mobilizer" could also be of interest. In this regard, plerixafor, a drug approved in the autologous setting [37] to improve the number of circulating CD34 + cells, has also been successfully employed in HDs when G-CSF has failed [38,39]. If the only available donor is considered a poor mobilizer, the clinician may decide to administer plerixafor as the preferred approach for stem cell mobilization.…”

Section: Discussionmentioning

confidence: 99%

Basal CD34 + Cell Count Predicts Peripheral Blood Stem Cell Mobilization in Healthy Donors after Administration of Granulocyte Colony–Stimulating Factor: A Longitudinal, Prospective, Observational, Single-Center, Cohort Study

Martino

Gori

Pitino

et al. 2017

Biology of Blood and Marrow Transplantation

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A longitudinal, prospective, observational, single-center, cohort study on healthy donors (HDs) was designed to identify predictors of CD34 + cells on day 5 with emphasis on the predictive value of the basal CD34 + cell count. As potential predictors of mobilization, age, sex, body weight, height, blood volume as well as white blood cell count, peripheral blood (PB) mononuclear cells, platelet count, hematocrit, and hemoglobin levels were considered. Two different evaluations of CD34 + cell counts were determined for each donor: baseline (before granulocyte colony-stimulating factor [G-CSF] administration) and in PB after G-CSF administration on the morning of the fifth day (day 5). A total of 128 consecutive HDs (66 males) with a median age of 43 years were enrolled. CD34 + levels on day 5 displayed a non-normal distribution, with a median value of 75.5 cells/ μL. To account for the non-normal distribution of the dependent variable, a quantile regression analysis to predict CD34 + on day 5 using the baseline value of CD34 + as the key predictor was performed. On crude analysis, a baseline value of CD34 + ranging from .5 cells/μL to 1 cells/μL predicts a median value of 50 cells/μL on day 5; a value of 2 cells/μL predicts a median value of 70.7 cells/μL; a value of 3 cells/μL to 4 cells/μL predicts a median value of 91.3 cells/μL, and a value ≥ 5 predicts a median value of 112 cells/μL. In conclusion, the baseline PB CD34 + cell count correlates with the effectiveness of allogeneic PB stem cell mobilization and could be useful to plan the collection.

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“…Px can safely be used in combination with granulocyte colony-stimulating factor (G-CSF) to increase the mobilization of autologous CD34 + HSCs in patients with myeloma and lymphoma [7]. However, data on safety and efficacy in normal healthy donors are scant [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Impact of Single-Dose Plerixafor as an Adjunct to Granulocyte Colony-Stimulating Factor–Based Peripheral Blood Stem Cell Mobilization on the Graft Composition and Outcome for T Cell–Replete Haploidentical Peripheral Blood Stem Cell Transplantation with Post-Transplantation Cyclophosphamide: A Comparative Study

Jaiswal¹,

Bhakuni²,

Joy³

et al. 2018

Biology of Blood and Marrow Transplantation

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We conducted a prospective study on T and natural killer (NK) cell subset composition of graft and transplant outcomes in T cell-replete haploidentical transplantation with a single dose of subcutaneous plerixafor (Px) added to granulocyte colony-stimulating factor (G-CSF)-based mobilization in allogeneic donors to collect 10 × 10/kg CD34 hematopoietic stem cells (HSCs) at single apheresis. Twnety-six donors received G-CSF + Px and 25 G-CSF alone for mobilization. Despite significantly lower peripheral blood (PB) CD34 HSCs on day 4 in the G-CSF + Px group (33 [range, 6-47] cells/µL versus 81 [range, 50-168] cells/µL in the G-CSF group; P = .0001), PB CD34 HSC count (median 136 versus 139 cells/µL) on day 5 as well as that in the graft (2.7 versus 2.3 × 10/mL, P = .1) were comparable between the 2 groups. The total nucleated cell count was higher (3.4 versus 3.1 × 10/mL, P = .05), but CD4 T cells (2.3 versus 2.7 × 10/mL, P = .09) were lower in the G-CSF group with mobilization of regulatory T cells being similar. NK cells were skewed toward the CD56/16 subset in both groups, varying significantly from the steady-state NK subset ratio in PB. The time to engraftment, incidences of acute and chronic graft-versus-host disease, nonrelapse mortality, and overall survival were also similar. Addition of single-dose Px to G-CSF mobilization improves CD34 recovery and does not significantly alter the T and NK cell composition of the graft, including regulatory T cells, with no adverse impact on transplant outcomes.

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Plerixafor on demand in ten healthy family donors as a rescue strategy to achieve an adequate graft for stem cell transplantation

Abstract: We exposed 10 allogeneic donors to mobilization with PL. PL was well tolerated in all cases and ensured procurement of an adequate graft for transplantation resulting in a normal hematopoietic engraftment.

Cited by 28 publications

References 26 publications

Collection of hematopoietic CD34 stem cells in rhesus macaques using Spectra Optia

Collection of hematopoietic CD34 stem cells in rhesus macaques using Spectra Optia

Basal CD34 + Cell Count Predicts Peripheral Blood Stem Cell Mobilization in Healthy Donors after Administration of Granulocyte Colony–Stimulating Factor: A Longitudinal, Prospective, Observational, Single-Center, Cohort Study

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