Plerixafor‐based mobilization in pediatric healthy donors with unfavorable donor/recipient body weight ratio resulted in a better CD34⁺ collection yield: A retrospective analysis

Abstract

Introduction: In order to propose risk-adapted mobilization algorithms, several authors have tried to look for predictive factors of the CD34 + yield in healthy pediatric donors. Donor recipient body weight ratio (D/R ratio) was identified as one of the main variables related with the success to achieve the target cell dose for transplantation. According to this variable we modified the mobilization schedule. Material and methods: We report the results of 46 mobilizations and apheresis procedures performed in our center with unfavorable D/R ratio. Mobilization was attempted by the standard regime of G-CSF (10 mcg/kg/24 hours) in 28 cases (60.9%), with high dose G-CSF (10 mcg/kg/12 hours) in 9 cases (19.6%), and with plerixafor and G-CSF single dose regime in 9 cases (19.6%). Results: CD34 + cell quantification before apheresis is closely related to CD34 + yield, being the only factor related to collected CD34 + cells (beta .71; P < .0001). The mobilization efficiency was higher in plerixafor group compared to the other two schedules (P < .0001). By using plerixafor for mobilization, we achieved the target CD34 + cell dose of ≥2 × 10 6 /kg per recipient body weight in all cases with unfavorable D/R ratio. It was observed that 17.4% of cases that not reached the established target cell dose were located in the standard or high-dose mobilization regimes. This difference is even greater for optimal collections (≥5 × 10 6 /kg), since of the 54.3% cases that did not reach this goal none was mobilized by plerixafor. Conclusion: Tailoring the mobilization regime we can reach the target cell dose, even in those cases with the worst D/R ratio.

Use of plerixafor to mobilize haematopoietic progenitor cells in healthy donors

“…In healthy children, adverse effects were similar to those found in adults and were difficult to separate from those induced by G-CSF [64]. Among nine cases reported by Zubicaray et al receiving plerixafor and G-CSF, adverse events related to the mobilization regime were found in five of nine donors (55.5%), each of them presenting one or several simultaneous adverse events: three of them reported nausea, two reported bone pain, one case of a low-grade fever, another of myalgia and another one suffered abdominal discomfort [29].…”

“…In paediatric transplantation, an adverse donor/recipient weight ratio (<0.75) can appear in 33% donor/recipient pairs and is usually a source of special concern [29]. Other authors analysed 29 HDs weighing ≤20 kg, where a third of subjects had a donor/recipient weigh ratio ≤ 1.…”

“…Plerixafor was used 'upfront', not waiting for CD34+ cell count. This strategy was more successful when compared with normal (10 μg/ kg/24 h) or high (10 μg/kg/12 h) doses of G-CSF, especially when ≥5 Â 10 6 CD 34+ cells/kg of recipient weight were collected [29].…”

“…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].…”

Single‐center results reporting improved hematopoietic stem cell mobilization success in pediatric and young adult patients with solid tumors and lymphoma

“…Plerixafor (Mozobil) is a selective, reversible CXC chemokine receptor type 4 (CXCR4) antagonist that disrupts stromal cell‐derived factor‐1α (SDF‐1α) interaction with CXCR4, which results in prompt mobilization of bone marrow stem cells into the peripheral blood 10,14 . Plerixafor is used as the standard second‐line agent for stem cell mobilization in adults, 14,15 and has been used successfully in many pediatric patients 11,16–25 . Currently, there are no published guidelines for the use of stem cell mobilization agents such as G‐CSF and plerixafor in pediatric patients who are considered to be poor mobilizers.…”