Salvage treatment with plerixafor in poor mobilizing allogeneic stem cell donors: results of a prospective phase II-trial

Abstract

We conducted a prospective clinical trial to investigate the safety and efficacy of plerixafor (P) in allogeneic peripheral blood stem cells (PBSC) donors with poor mobilization response to standard-dose granulocyte colony-stimulating factor (G-CSF), defined by <2 × 10 6 CD34 + cells/kg recipient body-weight (CD34+/kg RBW) after 1st apheresis. A single dose of 240 µg/kg P was injected subcutaneously at 10 p.m. on the day of the 1st apheresis. Thirty-seven allogeneic PBSC donors underwent study treatment. The median CD34+ count in peripheral blood was 15/µl on Day 1 after G-CSF alone, versus 44/µl on Day 2 after G-CSF plus P ( p < 0.001). The median yield of CD34+ cells was 1.1 × 10 8 on Day 1 and 2.8 × 10 8 on Day 2. In contrast to a median yield of only 1.31 × 10 6 CD CD34+/kg RBW on Day 1, triggering study inclusion, a median of 3.74 × 10 6 CD CD34+/kg RBW were collected with G-CSF plus P on Day 2. Of 37 donors, 21 reached the target cell count of >4.5 × 10 6 CD34+/kg RBW (57%, 95%CI 40–73%). No donor experienced a severe adverse event requiring treatment. In conclusion, P might be considered on a case-by-case basis for healthy allogeneic donors with very poor stem cell mobilization success after G-CSF.

Use of Plerixafor for Stem Cell Mobilization in the Setting of Autologous and Allogeneic Stem Cell Transplantations: An Update

“…In two studies published in 2021 plerixafor was added pre-emptively to the mobilization with G-CSF. 68,69 The peripheral CD34+ cell count showed 2.9-fold and 3.4-fold increases after adding a single injection of plerixafor. In these two studies, the collected CD34+ cells was 1.1×10 6 /kg and 1.6×10 6 /kg with G-CSF alone and it was raised to 2.8×10 6 /kg and 4.9 x 10 6 /kg with the combination G-CSF and plerixafor.…”

“…The most common events were tingling, pain, fatigue, nausea, diarrhea, abdominal bloating and injection site reactions. 66,68 All events resolved immediately, in contrast with G-CSF no bone pain was observed after administration of plerixafor. 67 This suggests that the adverse events of administration of G-CSF for multiple days can overcome with one or two injections of plerixafor.…”

“…In human leukocyte antigen (HLA)-identical and haplo-identical donors plerixafor was administered using several approaches: upfront, 60 , 64 , 66 , 67 pre-emptive after failure with G-CSF, 61 , 62 , 65 , 68 , 69 or remobilization after mobilization failure with G-CSF. 63 Moreover plerixafor was used successfully for haplo-identical SCT requiring a higher number of CD34+ cells.…”

Use of plerixafor to mobilize haematopoietic progenitor cells in healthy donors

“…When published, the median increase of CD34+ cells in PB before and after plerixafor administration ranged from 2 to 3, but there was a significant donor-to-donor variability (Table 1). Recently, Hölig et al found that CD34+ yield increased up to five times, especially in donors with poor mobilization [30]. Apheresis is usually performed on day +5 of mobilization with G-CSF.…”

“…Use of plerixafor in this setting is considered off-label, as plerixafor is licensed by European Medicines Agency in Europe [20] and by the Food and Drug Administration (FDA) in the United States [21] only in combination with G-CSF for CD34+ cell mobilization failures for autologous HCT in lymphoma and myeloma patients. As a result, evidence on the use of plerixafor as a mobilization agent in HDs for allogeneic HCT is scarce [22][23][24][25][26][27][28][29][30][31][32].…”