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Mobilization of allogeneic peripheral blood stem cell donors with intravenous plerixafor mobilizes a unique graft

Mark A. Schroeder, Michael P. Rettig, Sandra Lopez, Stephanie Christ, Mark Fiala, William Eades, Fazia A. Mir, Jin Shao, Kyle McFarland, Kathryn Trinkaus, William Shannon, Elena Deych, Jinsheng Yu, Ravi Vij, Keith Stockerl-Goldstein, Amanda F. Cashen, Geoffery L. Uy, Camille N. Abboud, Peter Westervelt and John F. DiPersio

Key points

  • Plerixafor is a safe, effective, rapid mobilizing agent when administered intravenously.

  • Lower rates of GvHD and CMV viremia with plerixafor-mobilized grafts may be related to a unique cellular composition of the 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 one apheresis. We hypothesized that changing the route of administration of plerixafor from SC to intravenous (IV) may overcome the low stem cell yields and allow collection in one day. A phase I trial followed by a phase II 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 ≥ 2x106 CD34+/Kg recipient weight in one 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 alpha producing ability. The observed CMV viremia rate for patients at risk was low (15%) as was the rates of acute grade II - IV 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.

  • Submitted September 22, 2016.
  • Accepted March 2, 2017.