Effect of high-dose plerixafor on CD34+ cell mobilization in healthy stem cell donors

Results of a randomized crossover trial

Jeremy Mark Pantin, Enkhtsetseg Purev, Xin Tian, Lisa Cook, Theresa Donohue-Jerussi, Elena Cho, Robert Reger, Matthew Hsieh, Hanh Khuu, Gary Calandra, Nancy L. Geller, Richard W. Childs

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

CSFH ematopoietic stem cells can be mobilized from healthy donors using single-agent plerixafor without granulocyte colony-stimulating factor and, following allogeneic transplantation, can result in sustained donor-derived hematopoiesis. However, when a single dose of plerixafor is administered at a conventional 240 μg/kg dose, approximately one-third of donors will fail to mobilize the minimally acceptable dose of CD34+ cells needed for allogeneic transplantation. We conducted an open-label, randomized trial to assess the safety and activity of highdose (480 μg/kg) plerixafor in CD34+ cell mobilization in healthy donors. Subjects were randomly assigned to receive either a high dose or a conventional dose (240 μg/kg) of plerixafor, given as a single subcutaneous injection, in a two-sequence, two-period, crossover design. Each treatment period was separated by a 2-week minimum washout period. The primary endpoint was the peak CD34+ count in the blood, with secondary endpoints of CD34+ cell area under the curve (AUC), CD34+ count at 24 hours, and time to peak CD34+ following the administration of plerixafor. We randomized 23 subjects to the two treatment sequences and 20 subjects received both doses of plerixafor. Peak CD34+ count in the blood was significantly increased (mean 32.2 versus 27.8 cells/μL, P=0.0009) and CD34+ cell AUC over 24 hours was significantly increased (mean 553 versus 446 h cells/mL, P<0.0001) following the administration of the 480 μg/kg dose of plerixafor compared with the 240 μg/kg dose. Remarkably, of seven subjects who mobilized poorly (peak CD34+ ≤20 cells/mL) after the 240 mg/kg dose of plerixafor, six achieved higher peak CD34+ cell numbers and all achieved higher CD34+ AUC over 24 hours after the 480 μg/kg dose. No grade 3 or worse drug-related adverse events were observed. This study establishes that high-dose plerixafor can be safely administered in healthy donors and mobilizes greater numbers of CD34+ cells than conventional-dose plerixafor, which may improve CD34+ graft yields and reduce the number of apheresis procedures needed to collect sufficient stem cells for allogeneic transplantation.

Original languageEnglish (US)
Pages (from-to)600-609
Number of pages10
JournalHaematologica
Volume102
Issue number3
DOIs
StatePublished - Feb 28 2017

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Cross-Over Studies
Stem Cells
Homologous Transplantation
Area Under Curve
Cell Count
JM 3100
Blood Component Removal
Hematopoiesis
Stem Cell Transplantation
Granulocyte Colony-Stimulating Factor
Subcutaneous Injections
Drug-Related Side Effects and Adverse Reactions
Transplants
Safety
Therapeutics

ASJC Scopus subject areas

  • Hematology

Cite this

Pantin, J. M., Purev, E., Tian, X., Cook, L., Donohue-Jerussi, T., Cho, E., ... Childs, R. W. (2017). Effect of high-dose plerixafor on CD34+ cell mobilization in healthy stem cell donors: Results of a randomized crossover trial. Haematologica, 102(3), 600-609. https://doi.org/10.3324/haematol.2016.147132

Effect of high-dose plerixafor on CD34+ cell mobilization in healthy stem cell donors : Results of a randomized crossover trial. / Pantin, Jeremy Mark; Purev, Enkhtsetseg; Tian, Xin; Cook, Lisa; Donohue-Jerussi, Theresa; Cho, Elena; Reger, Robert; Hsieh, Matthew; Khuu, Hanh; Calandra, Gary; Geller, Nancy L.; Childs, Richard W.

In: Haematologica, Vol. 102, No. 3, 28.02.2017, p. 600-609.

Research output: Contribution to journalArticle

Pantin, JM, Purev, E, Tian, X, Cook, L, Donohue-Jerussi, T, Cho, E, Reger, R, Hsieh, M, Khuu, H, Calandra, G, Geller, NL & Childs, RW 2017, 'Effect of high-dose plerixafor on CD34+ cell mobilization in healthy stem cell donors: Results of a randomized crossover trial', Haematologica, vol. 102, no. 3, pp. 600-609. https://doi.org/10.3324/haematol.2016.147132
Pantin, Jeremy Mark ; Purev, Enkhtsetseg ; Tian, Xin ; Cook, Lisa ; Donohue-Jerussi, Theresa ; Cho, Elena ; Reger, Robert ; Hsieh, Matthew ; Khuu, Hanh ; Calandra, Gary ; Geller, Nancy L. ; Childs, Richard W. / Effect of high-dose plerixafor on CD34+ cell mobilization in healthy stem cell donors : Results of a randomized crossover trial. In: Haematologica. 2017 ; Vol. 102, No. 3. pp. 600-609.
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