Combined plerixafor and granulocyte colony‐stimulating factor for harvesting high‐dose hematopoietic stem cells: Possible niche for plerixafor use in pediatric patients

Abstract

PB is a source of HSC, especially for autologous HCT in solid tumors. However, there is a risk of failing to achieve the target number of SC after mobilization with growth factors alone in patients who were heavily pretreated with chemotherapy or those in need for tandem transplants. SC were harvested from seven pediatric patients with solid tumors who were in need of autologous HCT following combination GCSF and plerixafor. Six of them received plerixafor after failing to achieve enough SC with GCSF only, while the seventh patient received the combined protocol upfront. All seven patients achieved the target number of SC according to their treatment protocol. There were no adverse events. All patients underwent autologous HCT using the harvested HSC and achieved full engraftment. A protocol for harvesting autologous HCT using GCSF and plerixafor is feasible and safe in children with solid tumors who had been heavily pretreated with chemotherapy or needed tandem transplants.

A multicenter report on the safety and efficacy of plerixafor based stem cell mobilization in children with malignant disorders

“…As in other pediatric studies that have shown the utility of plerixafor to facilitate PBSC mobilization with success rates ranging from 57%‐100%, 2,3,5–7,15–20,23–27 we observed adequate CD34+ yield in 87.2% of recipients, with no difference between Group A or B patients (84.2% vs 89.2%) groups. In the phase I part of their study (n = 27), Morland et al determined the dose of plerixafor in children to be 240 μg/kg which was the dose received by majority of patients in our cohort.…”

“…4 Risk factors for poor mobilization include multiple prior chemotherapy cycles, exposure to platinum or alkylating agents, and prior radiation therapy or a primary diagnosis of neuroblastoma, medulloblastoma or relapsed/refractory Hodgkin lymphoma (HL). [4][5][6] Plerixafor, a bicyclam derivative and a reversible CXCR4 receptor antagonist, disrupts the interaction of SDF-1 with its receptor CXCR4 on the surface of stem cells, causing release of stem cells from the marrow. 1 Plerixafor along with GCSF has been successfully used in adults either after failure of chemotherapy and cytokinebased mobilization, or as a preemptive agent if peripheral blood (PB) CD34+ cell counts are inadequate.…”

“…However, this standard mobilization (SM) approach (GCSF ± chemotherapy) has been associated with inadequate collection in 11%‐13% of children 2,3 and 30%‐40% of adults with malignant disorders 4 . Risk factors for poor mobilization include multiple prior chemotherapy cycles, exposure to platinum or alkylating agents, and prior radiation therapy or a primary diagnosis of neuroblastoma, medulloblastoma or relapsed/refractory Hodgkin lymphoma (HL) 4–6 …”

“…4,12,13 Prior reports on the off-label use showing safety and efficacy of plerixafor for stem cell mobilization in children are limited by small numbers or to single centers. 5,[14][15][16][17][18][19][20] A phase I/II randomized study showed improved outcomes in children who received plerixafor upfront along with SM compared to children who received SM alone. 21,22 Based on these findings, plerixafor is now approved for use in children in Europe.…”

The Biological and Clinical Relevance of G Protein-Coupled Receptors to the Outcomes of Hematopoietic Stem Cell Transplantation: A Systematized Review

“…Interestingly, in patients responding poorly to G-CSF (< 20 × 10 6 /L CD34+ cells in PB), pre-emptive plerixafor treatment led to a final yield equivalent to a rescue strategy administered to patients with insufficient leukapheresis [50]. Several additional studies have endorsed the use of plerixafor in autologous transplantation for diabetic patients [51] and pediatric patients [52,53,54], whereas other articles have supported its use in elderly patients and those with renal insufficiency [55,56]#.…”