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Phase I/II Study of Intravenous Plerixafor Added to a Mobilization Regimen of Granulocyte Colony–Stimulating Factor in Lymphoma Patients Undergoing Autologous.

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Presentation on theme: "Phase I/II Study of Intravenous Plerixafor Added to a Mobilization Regimen of Granulocyte Colony–Stimulating Factor in Lymphoma Patients Undergoing Autologous."— Presentation transcript:

1 Phase I/II Study of Intravenous Plerixafor Added to a Mobilization Regimen of Granulocyte Colony–Stimulating Factor in Lymphoma Patients Undergoing Autologous Stem Cell Collection  Amanda F. Cashen, Michael Rettig, Feng Gao, Angela Smith, Camille Abboud, Keith Stockerl-Goldstein, Ravi Vij, Geoffrey Uy, Peter Westervelt, John DiPersio  Biology of Blood and Marrow Transplantation  Volume 23, Issue 8, Pages (August 2017) DOI: /j.bbmt Copyright © 2017 The American Society for Blood and Marrow Transplantation Terms and Conditions

2 Figure 1 Treatment schema and CD34+ stem cell mobilization. (A) Treatment schema. Lymphoma patients were mobilized sequentially with s.c. plerixafor (P) alone, G-CSF (G) alone, and G-CSF combined with i.v. plerixafor. These patients received a single s.c. injection of .24 mg/kg plerixafor on day −5. Twenty-four hours later, patients were treated with G-CSF for 4 days. On the fifth day, patients received a dose of G-CSF and a dose of i.v. plerixafor followed 4 hours later by pheresis. These procedures were repeated for up to 3 additional consecutive days of pheresis or until ≥ 5 × 106 CD34+ cells/kg cumulatively were collected, whichever occurred first. Mobilization study samples were collected before and after treatment with s.c. plerixafor on day −5 as well as immediately before and 2, 4 (immediately before initiation of pheresis), and 8 hours after plerixafor administration on day 0. (B) Mobilization of CD34+ cells to the peripheral blood over time from patients in phase I portion of the trial. Statistical comparisons were performed using a 2-way ANOVA. ****P <  (C) Comparison of CD34+ stem cell mobilization in healthy and lymphoma donors. Healthy (n = 45) or lymphoma (n = 25) patients were treated with .24 mg/kg s.c. plerixafor and the number of circulating CD34+/µL cells in the peripheral blood was determined 6 hours after plerixafor administration. Data from healthy donors was obtained from previous studies by Devine et al. [7] and Schroeder et al [6]. Statistical comparison was performed using a 2-sample Student t-test. ***P < .001. Data are presented in box and whiskers plots with 5% to 95% confidence intervals. (D) Intravenous plerixafor augments the mobilization of CD34+ cells by G-CSF. Mobilization of total CD34+ cells to the peripheral blood before and 4 hours after administration of a single dose of i.v. plerixafor at .16 mg/kg (n = 10), .24 mg/kg (n = 3), .32 mg/kg (n = 6), or .40 mg/kg (n = 6). Statistical comparisons were performed using a 2-way ANOVA. *P < .05, **P < .01. Biology of Blood and Marrow Transplantation  , DOI: ( /j.bbmt ) Copyright © 2017 The American Society for Blood and Marrow Transplantation Terms and Conditions

3 Figure 2 Relationships between peripheral blood CD34 counts after s.c. plerixafor, age, and CD34+ stem cell mobilization after G-CSF and G-CSF + i.v. plerixafor. (A-C) Relationships between peripheral blood CD34/µL counts after .24 mg/kg s.c. plerixafor and 5 days of G-CSF (A), G-CSF and i.v. plerixafor (B) and total CD34+ stem cell yield after the first day of pheresis (C). (D-F) Relationships between age and s.c. plerixafor (D), 5 days of G-CSF (E), and G-CSF and i.v. plerixafor (F). Biology of Blood and Marrow Transplantation  , DOI: ( /j.bbmt ) Copyright © 2017 The American Society for Blood and Marrow Transplantation Terms and Conditions

4 Figure 3 Preferential mobilization of CD34+CD45RA+CD123++ cells by plerixafor. (A) CD34+ HSPCs from a patient mobilized sequentially with plerixafor (P) alone, G-CSF (G) alone, and G-CSF combined with plerixafor were purified by immunomagnetic selection and evaluated by flow cytometry. The percentages of CD34+CD45RA-CD123+/- common myeloid progenitors (CMPs) and HSCs, CD34+CD45RA+CD123+/- granulocyte/macrophage and lymphoid progenitors (GMPs) + CLPs, and CD34+CD45RA+CD123++ pro-DC2s cells are shown. (B) Relative contribution of each CD34+ subset. CD34+ HSPCs from patients at baseline (day −5 pre-P, n = 6) or after treatment with plerixafor (P) alone (n = 25), G-CSF (G) alone (n = 23), or G-CSF combined with plerixafor (n = 31) were purified by immunomagnetic selection and evaluated by flow cytometry. The percentages of CD34+CD45RA-CD123+/- CMPs and HSCs, CD34+CD45RA+CD123+/- GMPs + CLPs, and CD34+CD45RA+CD123++ pro-DC2s cells are shown. Statistical comparisons were performed using 1-way ANOVA. *P < .05, **P < .01, ***P < .001, ****P <  Data are presented in box and whiskers plots where the whiskers represent minimum and maximum values. Biology of Blood and Marrow Transplantation  , DOI: ( /j.bbmt ) Copyright © 2017 The American Society for Blood and Marrow Transplantation Terms and Conditions

5 Figure 4 CXCR4 expression on CD34+ HSPCs. (A) CD34+ HSPCs isolated from 5 patients at baseline (day −5: pre-P) and following treatment with plerixafor (P) alone, G-CSF (G) alone, and G-CSF combined with plerixafor were evaluated by flow cytometry. A representative histogram of CXCR4 expression on total CD34+ HSPCs isolated from a single patient as well as a plot of the relative mean fluorescence intensity ratio of CXCR4 for all 5 patients are shown. (B) Expression of CXCR4 on CD34+CD45RA-CD123+/- CMPs and HSCs, CD34+CD45RA+CD123+/- GMPs + CLPs, and CD34+CD45RA+CD123++ pro-DC2s cells. CD34+ HSPC subsets isolated from patients at baseline (day −5 pre-P, n = 5) or after treatment with plerixafor (P) alone (n = 5), G-CSF (G) alone (n = 7), or G-CSF combined with plerixafor (n = 9) were evaluated by flow cytometry. A representative histogram of CXCR4 expression on the different CD34+ HSPC subsets in a single patient mobilized with plerixafor alone is shown as well as a plot of the relative mean fluorescence intensity ratio of CXCR4 for the different HSPCs subsets. Statistical comparisons were performed using 2-sample Student t-test or 1-way ANOVA. *P < .05, **P < .01. Biology of Blood and Marrow Transplantation  , DOI: ( /j.bbmt ) Copyright © 2017 The American Society for Blood and Marrow Transplantation Terms and Conditions


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