@article{0a5a4ed42f974056bbd2c900925e2c06,
title = "Mobilization of allogeneic peripheral blood stem cell donors with intravenous plerixafor mobilizes a unique graft",
abstract = "A single subcutaneous (SC) injection of plerixafor results in rapid mobilization of hematopoietic progenitors, but fails to mobilize 33% of normal allogeneic sibling donors in 1 apheresis. We hypothesized that changing the route of administration of plerixafor fromSCto IV may overcome the low stem cell yields and allow collection in 1 day.Aphase 1 trial followed by a phase 2 efficacy trial was conducted in allogeneic sibling donors. The optimal dose of IV plerixafor was determined to be 0.32 mg/kg. The primary outcome of reducing the failure to collect≥2×106 CD34+/kg recipient weight in 1 apheresis collection to ≤10% was not reached. The failure rate was 34%. Studies evaluating the stem cell phenotype and gene expression revealed a novel plasmacytoid dendritic cell precursor preferentially mobilized by plerixafor with high interferon-α producing ability. The observed cytomegalovirus (CMV) viremia rate for patients at risk was low (15%), as were the rates of acute grade 2-4 graft-versus-host disease (GVHD) (21%). Day 100 treatment related mortality was low (3%). In conclusion, plerixafor results in rapid stem cell mobilization regardless of route of administration and resulted in novel cellular composition of the graft and favorable recipient outcomes. These trials were registered at clinicaltrials. gov as #NCT00241358 and #NCT00914849.",
author = "Schroeder, {Mark A.} and Rettig, {Michael P.} and Sandra Lopez and Stephanie Christ and Mark Fiala and William Eades and Mir, {Fazia A.} and Jin Shao and Kyle McFarland and Kathryn Trinkaus and William Shannon and Elena Deych and Jinsheng Yu and Ravi Vij and Keith Stockerl-Goldstein and Cashen, {Amanda F.} and Uy, {Geoffrey L.} and Abboud, {Camille N.} and Peter Westervelt and DiPersio, {John F.}",
note = "Funding Information: The authors thank the Alvin J. Siteman Cancer Center at Washington University School of Medicine and Barnes-Jewish Hospital in St. Louis, MO, for the use of their core facilities. The Siteman Cancer Center is supported in part by the National Cancer Institute at the National Institutes of Health (Cancer Center Support Grant P30 CA91842). The authors also thank J. Evan Sadler,Monica Bessler, and Matthew Walter for critical feedback and mentoring; Timothy A. Graubert for CXCL12 single-nucleotide polymorphism analysis, critical feedback, and mentoring; Darja Karpova for critical review of the manuscript and feedback; and Jackie Wu (Sanofi Genzyme) and Yaming Su (Sanofi Genzyme) for their statistical review/contributions to this publication surround pharmacokinetic data analysis (both are supported by funding from Sanofi Genzyme). This research was supported Genzyme (J.F.D.); the National Institutes of Health (NIH) National Cancer Institute (grants R01 CA152329, R21 CA141523, and R21 CA132269) (J.F.D.); NIH, National Heart, Lung, and Blood Institute (grant 5K12HL08710703) (M.A.S.); the Washington University Institute of Clinical and Translational Sciences from the NIHNational Center for Advancing Translational Sciences (grant UL1 TR000448); and the Cancer and Leukemia Group B and Alliance (M.A.S.). Publisher Copyright: {\textcopyright} 2017 by The American Society of Hematology.",
year = "2017",
month = may,
day = "11",
doi = "10.1182/blood-2016-09-739722",
language = "English",
volume = "129",
pages = "2680--2692",
journal = "Blood",
issn = "0006-4971",
number = "19",
}