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Phase 1 Study of Maraviroc As Acute Graft-Versus-Host Disease Prophylaxis in Pediatrics
Pooja Khandelwal, MD, Tsuyoshi Fukuda, PhD, Ashley Teusink, PharmD, MBA, BCPS, Rebecca A. Marsh, MD, Jack Bleesing, MD, PhD, Alexander Vinks, PharmD, PhD, FCP, Kana Mizuno, PhD, Angela D.M. Kashuba, BScPhm, PharmD, DABCP, Stella M. Davies, MBBS, PhD Biology of Blood and Marrow Transplantation Volume 22, Issue 3, Pages S96-S97 (March 2016) DOI: /j.bbmt Copyright © Terms and Conditions
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Figure 1 PK profiles on day zero and day+10 ( Mean ± SD , n=9).
Biology of Blood and Marrow Transplantation , S96-S97DOI: ( /j.bbmt ) Copyright © Terms and Conditions
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Figure 2 Normalized maraviroc clearance.
Biology of Blood and Marrow Transplantation , S96-S97DOI: ( /j.bbmt ) Copyright © Terms and Conditions
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Figure 3 Pharmacodynamic assay showing functional blockade of CCR5 in patients enrolled on study. MVC= Maraviroc . CB= Control blood. When CCL5 binds to CCR5 on lymphocytes, it leads to CCR5 internalization and lack of CCR5 detection on surface flowcytometry. In healthy controls, it is expected to observe CCR5 internalization with addition of CCL5. This internalization does not occur when maraviroc is added to the sample, since it blocks CCR5 and prevents binding of CCL5. In patients on study, their pre BMT plasma was incubated with healthy control blood in the presence of CCL5 and CCR5 expression was not detected on flowcytometry due to expected internalization of CCR5. Day zero and day+14 plasma was incubated with healthy control blood in the presence of CCL5 (maraviroc starts on day - 3). No internalization of CCR5 was observed at day zero and day+14 since maraviroc in patients' plasma inhibited CCR5 on healthy control lymphocytes and prevented binding of CCL5 to CCR5. Biology of Blood and Marrow Transplantation , S96-S97DOI: ( /j.bbmt ) Copyright © Terms and Conditions
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