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1.
Correlation of Body Mass Index and Proinflammatory Cytokine Levels with Hematopoietic Stem Cell Mobilization
Wang, T. F., Liou, Y. S., Chang, H. H., Yang, S. H., Li, C. C., Wang, J. H., Sun, D. S.
Journal of clinical medicine. 2022;11(14)
Abstract
This study investigated the correlation of body mass index (BMI) and proinflammatory cytokine levels with hematopoietic stem cell (HSC) mobilization triggered by granulocyte colony-stimulating factor (G-CSF). Stem cell donors (n = 309) were recruited between August 2015 and January 2018 and grouped into four groups according to their BMI: underweight (BMI < 18.5 kg/m(2), n = 10), normal (18.5 kg/m(2) ≦ BMI < 25 kg/m(2), n = 156), overweight (25 kg/m(2) ≦ BMI < 30 kg/m(2), n = 102), and obese (BMI ≧ 30 kg/m(2), n = 41). The participants were then administered with five doses of G-CSF and categorized as good mobilizers (CD34 ≧ 180/μL, n = 15, 4.85%) and poor mobilizers (CD34 ≦ 25/μL, n = 14, 4.53%) according to the number of CD34(+) cells in their peripheral blood after G-CSF administration. The correlation between BMI and HSC mobilization was then analyzed, and the levels of proinflammatory cytokines in the plasma from good and poor mobilizers were examined by ProcartaPlex Immunoassay. Results showed that BMI was highly correlated with G-CSF-triggered HSC mobilization (R(2) = 0.056, p < 0.0001). Compared with poor mobilizers, good mobilizers exhibited higher BMI (p < 0.001) and proinflammatory cytokine [interferon gamma (IFN-γ) (p < 0.05), interleukin-22 (IL-22) (p < 0.05), and tumor necrosis factor alpha (TNF-α) levels (p < 0.05)]. This study indicated that BMI and proinflammatory cytokine levels are positively correlated with G-CSF-triggered HSC mobilization.
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2.
Race/ethnicity and underlying disease influences hematopoietic stem/progenitor cell mobilization response: A single center experience
Uzoka, C., Liu, L. C., Park, Y., Lin, Y., Patel, P., Campbell-Lee, S., Sweiss, K., Wang, X., Tepak, E., Peace, D., et al
Journal of clinical apheresis. 2021
Abstract
BACKGROUND Whether race/ethnicity plays a role in hematopoietic stem/progenitor cells (HSPC) mobilization in autologous donors has not been studied. We hypothesize that donor characteristic including race/ethnicity, age, sex, body mass index, and diagnostic groups influences HSPC mobilization. Diagnostic groups include healthy allogeneic donors, autologous multiple myeloma (MM) and non-MM donors. STUDY DESIGN AND METHODS Here, we conducted a single-center retrospective study in 64 autologous patients and 48 allogeneic donors. Autologous donors were patients diagnosed with MM or non-MM. All donors were grouped as African American (AA), White (W), or "Other"(O). RESULTS Multivariate analysis demonstrated diagnostic group differences for CD34+ cell yields between race/ethnicity. Specifically, non-MM patients had the lowest CD34+ cell yields in AA and O, but not in W. For pre-apheresis peripheral blood (PB) CD34+ cell numbers, race/ethnicity had a significant effect both in bivariate and multivariate analyses. Non-MM patients had the lowest, and AA patients had the highest PB CD34+ cells. The results support the view that past therapies used in MM are likely more conducive of recovery of HSPC. CONCLUSIONS Our study shows that race/ethnicity and diagnostic group differences influenced CD34+ cell mobilization response across donor types. Interestingly, autologous MM donors with the aid of plerixafor displayed comparable CD34 yields to allogeneic donors. Even though both MM and non-MM donors received plerixafor, non-MM donors had significantly lower CD34 yields among AA and O donors but not in W donors. Larger studies would be required to validate the role of diagnostic groups and race/ethnicity interactions.
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3.
Plerixafor-based mobilization in pediatric healthy donors with unfavorable donor/recipient body weight ratio resulted in a better CD34(+) collection yield: A retrospective analysis
Zubicaray, J., Galvez, E., Sebastian, E., Molina, B., González-Vicent, M., Castillo, A., Ramírez, M., Madero, L., Díaz, M. A., Sevilla, J.
Journal of clinical apheresis. 2020
Abstract
INTRODUCTION In order to propose risk-adapted mobilization algorithms, several authors have tried to look for predictive factors of the CD34(+) yield in healthy pediatric donors. Donor recipient body weight ratio (D/R ratio) was identified as one of the main variables related with the success to achieve the target cell dose for transplantation. According to this variable we modified the mobilization schedule. MATERIAL AND METHODS We report the results of 46 mobilizations and apheresis procedures performed in our center with unfavorable D/R ratio. Mobilization was attempted by the standard regime of G-CSF (10 mcg/kg/24 hours) in 28 cases (60.9%), with high dose G-CSF (10 mcg/kg/12 hours) in 9 cases (19.6%), and with plerixafor and G-CSF single dose regime in 9 cases (19.6%). RESULTS CD34(+) cell quantification before apheresis is closely related to CD34(+) yield, being the only factor related to collected CD34(+) cells (beta .71; P < .0001). The mobilization efficiency was higher in plerixafor group compared to the other two schedules (P < .0001). By using plerixafor for mobilization, we achieved the target CD34(+) cell dose of ≥2 × 10(6) /kg per recipient body weight in all cases with unfavorable D/R ratio. It was observed that 17.4% of cases that not reached the established target cell dose were located in the standard or high-dose mobilization regimes. This difference is even greater for optimal collections (≥5 × 10(6) /kg), since of the 54.3% cases that did not reach this goal none was mobilized by plerixafor. CONCLUSION Tailoring the mobilization regime we can reach the target cell dose, even in those cases with the worst D/R ratio.
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4.
Old is bad? The effect of age on peripheral stem cell mobilization and transplantation outcomes
Basci, S., Bakirtas, M., Uncu Ulu, B., Yigenoglu, T. N., Yaman, S., Batgi, H., Kilinç, A., Özcan, N., Sahin, D., Darçin, T., et al
Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis. 2020;:103007
Abstract
INTRODUCTION Allogeneic stem cell transplantation (Allo-SCT) is a well-established treatment option for hematological malignancies. With the introduction of reduced-intensity conditioning regimens (RIC) and better supportive measures the elderly are able to receive Allo-SCT. A considerable number of patients are elderly, and often their HLA matched sibling donor is elderly, moreover. Here, we aim to explore the effect of donors' age on stem cell harvesting, engraftment duration after Allo-SCT, and product quality. METHOD Sixty-one healthy allogeneic stem cell donors aged 50 years and older who underwent stem cell mobilization at our center between 2009-2019 were enrolled for the study. All donors received 4-5 days of G-CSF, mostly filgrastim or lenograstim and their biosimilar equivalents were given subcutaneously as a total dose of 10 mcg/kg/day. Groups were separated into three groups as aged 50-54 group A, 55-59 group B, aged 60 and older group C. RESULTS Pre-apheresis peripheral blood CD34+ count was similar all groups (p = 0.2). One day apheresis was sufficient for 72.7 % of group A, 27.3 % for group B and 47.1 % for group C (p = 0.02). Total harvested CD34+ cells were comparable among groups (p = 0.5). CONCLUSION Adequate stem cell harvest in older donors is feasible. Older donors may require more than one apheresis procedure and generally procedure was well tolerated. When assessing donors, age should represent less significance.
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5.
Smoking is an important factor that affects peripheral blood progenitor cells yield in healthy male donors
Zhen, C., Fang, X., Ding, M., Wang, X., Yuan, D., Sui, X., Liu, X., Zhang, L., Xu, H., Li, Y., et al
Journal of clinical apheresis. 2019
Abstract
BACKGROUND Smoking could reduce the CD34+ cells in peripheral blood of healthy individual. This study aimed to investigate the correlation between smoking load and the effect of peripheral blood hematopoietic progenitor cells (PBPCs) mobilization by granulocyte colony-stimulating factor (G-CSF) alone in healthy donors. METHODS Retrospective analysis was performed on 145 healthy adult PBPCs donors who underwent PBPCs mobilization and collection. Smoking factors were evaluated and correlated with mobilization responses, as indicated by the collected CD34+ cells concentration. RESULTS The collected CD34+ cells concentration was closely related to pre-CD34 (P < .001) and CD34+ cells collected per volume blood processed (P < .001) which suggested that collected CD34+ cells concentration was a reliable indicator of PBPCs mobilization efficiency. The heavy smoking donors revealed significantly lower collected CD34+ cells concentration, compared to that of the nonsmoking (P < .001) and light smoking donors (P < .05). The levels of collected CD34+ cells in light smoking were also obviously lower than that in nonsmoking donors (P < .05).There were no obvious differences in the collected CD34+ cells concentration, overall processed blood volume and total collected CD34+ cells between nonsmoking and smoking cessation groups (P = .490; P = .464; P = .819). CONCLUSION Cigarette smoking is an important factor that affects the yield of PBPCs in male donors, especially when the smoking load is more than five pack-years. Mobilization of PBMCs could be restored by smoking cessation in chronic smokers.
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6.
Gender, cholinesterase, platelet count and red cell count are main predictors of peripheral blood stem cell mobilization in healthy donors
Furst, D., Hauber, D., Reinhardt, P., Schauwecker, P., Bunjes, D., Schulz, A., Mytilineos, J., Wiesneth, M., Schrezenmeier, H., Korper, S.
Vox sanguinis. 2019
Abstract
BACKGROUND AND OBJECTIVES Mobilization of CD34(+) cells by stimulation with G-CSF shows considerable variation across stem cell donors. Upfront prediction of CD34(+) cell counts in peripheral blood based on easily available steady-state parameters would be helpful for the planning of apheresis and stem cell transplantation. Commonly accepted steady-state predictors for the mobilization are gender, body mass index and platelet count. The aim of the study was the identification of novel predictors that might influence mobilization efficacy and to create a model for the prediction of stem cell mobilization. METHODS A total of 333 healthy stem cell donors who donated peripheral stem cells in our institution were retrospectively analysed. All available data before stem cell mobilization with G-CSF were included in the database. Primary end-point was CD34(+) cell count before the first apheresis. RESULTS In this cohort cholinesterase, differential blood cell counts including platelets, gender and body mass index were significantly correlated with CD34(+) cell count. G-CSF dose per lean body weight showed a significant correlation with mobilization efficacy in women but not in men. A multivariate analysis identified gender, cholinesterase and platelet and red cell count as main predictors of mobilization. Red cell count showed a strong gender dependence, with higher predictive value in females. CONCLUSION The counts of eosinophils, platelets, red cells, cholinesterase and gender are the most important predictors of CD34(+) cell mobilization in our deduced models. The red cell count as a predictor for mobilization showed a differential gender dependence.
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7.
Factors associated with bone marrow stem cell yield for pediatric allogeneic stem cell transplantation: The impact of donor characteristics
Fettah, A., Ozbek, N., Ozguner, M., Azik, F., Isik, P., Avci, Z., Yarali, N., Uckan, D., Tunc, B.
Pediatric Transplantation. 2017;21(1)
Abstract
The aim of this study was to investigate the effects of donor characteristics on CD34+cell yield in BM harvest. Between April 2010 and November 2013, consecutive donors who underwent BM harvesting in our BM transplantation unit were retrospectively investigated. Donors were classified into two groups: those who donated BM without mobilization (steady-state BM donors) and those who received G-CSF for stem cell mobilization (G-CSF-primed BM donors). Donor characteristics (age, gender, race, body weight, BMI, and laboratory factors including donor's leukocyte, platelet, and monocyte) and their relationship with total nuclear cell and CD34+cell numbers has been evaluated. A total of 64 healthy related donors (29 males/35 females, median age 11.2 years; 49 [76.6%] younger than 18 and 36 [56.3%] younger than 12 years) were included in the study. The median CD34+cell yield in the harvest was 0.12x106/L (0.02-0.21) in SS-BM donors and 0.18x106/L (0.09-0.67) in GP-BM donors (P=.03). Median of CD34+cell count given to recipients was 2.6x106/recipient body weight (1.3-19.3) in SS-BM yields and 3.8x106/recipient body weight (1.1-10.2) in GP-BM yields, respectively. Multiple regression analysis showed that donor height and pre-G-CSF platelet were the most important parameters to obtain a sufficient BM harvest. Our data suggest that the shorter donors and the donors with higher thrombocyte counts may offer more hematopoietic stem cell. The height and thrombocyte count of the donors should be taken into consideration before planning the targeted CD34+cell count especially for pediatric donors.
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8.
Alterations of CCR5 and CCR7 expression on donor peripheral blood T cell subsets after mobilization with rhG-CSF correlate with acute graft-versus-host disease
Wang, M., Hu, J., Qiu, Z. X., Liu, W., Wang, M. J., Li, Y., Sun, Y. H., Zhu, S. N., Ren, H. Y., Dong, Y. J.
Clinical Immunology. 2017
Abstract
To investigate the effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on chemokine receptors and explore the potential mechanism of rhG-CSF inducing immune tolerance, ninety-seven donor and recipient pairs undergoing family-donor allogeneic hematopoietic stem cell transplantation were studied. The results indicated that different donors showed great disparities in expression changes after mobilization. Multivariate analysis revealed that both HLA mismatching and CCR7 downregulation on donors' CD4+ T cells after mobilization were independent risk factors for acute graft-versus-host disease (GVHD). In contrast, CCR5 downregulation on CD4+ T cells was associated with reduced incidence of acute GVHD. In conclusion, rhG-CSF mobilization could lead to differential regulation of chemokine receptors expression on T cell subsets in different donors. Downregulation of CCR5 and upregulation of CCR7 expression on donor CD4+ T cells might protect recipients from acute GVHD. This finding may provide a promising new strategy for the prevention and treatment of acute GVHD. Copyright © 2017. Published by Elsevier Inc.