Plerixafor added to G‐CSF allows mobilization of a sufficient number of hematopoietic progenitors without impacting the efficacy of TCR‐alpha/beta depletion in pediatric haploidentical and genoidentical donors failing to mobilize with G‐CSF alone

Abstract

Background Collection of a large number of early hematopoietic progenitors is essential for allogeneic apheresis products intended for TCR‐alpha/beta depletion. Materials and Methods We added plerixafor 0.24 mg/kg body weight (bw) on day 4 of high‐dose filgrastim mobilization 10 hours prior to apheresis in 16 (30.5%) pediatric allogeneic donors who failed to recover a sufficient number of CD34+ cells. Results On day 4 of G‐CSF, the median CD34+ cell count in peripheral blood was 6 per μL (range 4‐9 per μL) in 6 poor mobilizers and 16 per μL (range 12‐19 per μL) in insufficient mobilizers. In all donors, the threshold of 50 CD34+ cells/μL was achieved, and the median increase was 14.8‐fold in poor mobilizers and 6.5‐fold in insufficient mobilizers, whereas it was 3.45‐fold increase in those mobilized with G‐CSF alone. Discussion In all donors, a predefined number of >10 × 106 CD34+ cells/kg of recipient bw before depletion was reached in the apheresis product. The use of plerixafor did not affect the purity of further TCR‐alpha/beta depletion. Side effects were mild to moderate and consisted of nausea and vomiting. Conclusion Thus, the safety and high efficacy of plerixafor was proven in healthy pediatric allogeneic hematopoietic cell donors.

Addition of plerixafor in poorly mobilized allogeneic stem cell donors

“…Plerixafor has also been shown effective as a rescue agent in allogeneic donors initially mobilized with G‐CSF 2,15,20‐22,26,29,32‐36 . Most of these studies were either small case series with ≤10 subjects, 15,26 or single case reports 20‐22,29,36 which showed G‐CSF mobilization and rescue plerixafor resulted in increased CD34+ cell yield with successful collections.…”

“…Plerixafor has also been shown effective as a rescue agent in allogeneic donors initially mobilized with G-CSF. 2,15,[20][21][22]26,29,[32][33][34][35][36] Most of these studies were either small case series with ≤10 subjects, 15,26 or single case reports [20][21][22]29,36 which showed G-CSF mobilization and rescue plerixafor resulted in increased CD34+ cell yield with successful collections. A couple of studies, 32,33 one with pediatric donors only, 32 with plerixafor use in evening of day 4 in donors with low peripheral blood CD34+ after 4 days of G-CSF and first-day collection on day 5, showed a significantly increased peripheral CD34+ on day 5.…”

“…In addition, plerixafor has crossed over for use in allogeneic collections. This has been documented in literature for more than a decade where it has been used as the single mobilization agent or as a rescue agent in donors with suboptimal mobilization with G‐CSF 2,3,15‐35 …”

“…In allogeneic donors there is a 2% to 4.6% collection failure rate (<2.0 × 10 6 CD34+ cells/kg recipient weight collected) using G‐CSF alone. Due to the small numbers of allogeneic donors who mobilize poorly, there are only case reports and small studies to support using plerixafor only 3,19,30,31 or in combination with G‐CSF 2,15,20‐22,26,29,32‐36 . All literature so far on low‐yield CD34+ donors mobilized with G‐CSF and plerixafor rescue in allogeneic donors have demonstrated increased CD34+ collection yield with plerixafor use 2,15,21,22,26,29,34‐36 .…”

“…Due to the small numbers of allogeneic donors who mobilize poorly, there are only case reports and small studies to support using plerixafor only 3,19,30,31 or in combination with G-CSF. 2,15,[20][21][22]26,29,[32][33][34][35][36] All literature so far on low-yield CD34+ donors mobilized with G-CSF and plerixafor rescue in allogeneic donors have demonstrated increased CD34+ collection yield with plerixafor use. 2,15,21,22,26,29,[34][35][36] At our medical center plerixafor has been used as a rescue agent for the past 8 years in allogeneic donors, with increased use in recent years.…”