Plerixafor, Breaking Barriers and Moving the World of Bone Marrow Transplant

Introduction

Plerixafor is an up-and-coming medication in stem cell transplant. Initially discovered for the treatment of HIV, it was later found to aid in hematopoietic stem cell (HSC) mobilization by inhibiting the binding of stromal cell-derived factor-1α (SDF-1α) to its receptor CXCR4 on HSCs. Although approved in adults to assist in mobilization, it is not yet standard of care in the adult or pediatric population due to various issues such as cost and undetermined dosage in pediatric patients.

Method

Retrospective chart review examined 6 pediatric patients at a single pediatric center between 2023-2024.

Case Series

The chart review included 6 patients who received Plerixafor during 2023-2024. These patients were admitted to the pediatric ICU, received G-CSF 4-6 days outpatient prior to admission (doses ranging from 6-15 mcg/kg subcutaneous), and continued daily in-patient during collection. They received Plerixafor 10-12 hours before each collection at a dosage of 250 μg/kg. The goal collection was between 4-6x10^6 cells/kg. Two of these patients were readmitted after a failed HSC collection with G-CSF alone. Among the 6 patients, two were male and four were female. The readmission patients had relapsed Hodgkin's lymphoma (HL) and metastatic high-risk neuroblastoma. The patient with relapsed (HL) had their first mobilization in April 2023, achieving 3.19x10^6 cells/kg after three days with G-CSF alone. Their second mobilization, a month later using the combination of Plerixafor and G-CSF, yielded 5.78x10^6 cells/kg in one day. The high-risk neuroblastoma patient's first harvest yielded 3.19x10^6 cells/kg in three days. During the readmission, they collected 2.4x10^6 cells/kg on the first day and 28.9x10^6 cells/kg the second day.

First-time admission patients, one patient had refractory (HL), two patients had relapsed (HL), and the last patient had a brain pineal nongerminomatous germ cell tumor. Except for the refractory Hodgkin's lymphoma (HL) patient, who required 4 days to reach their goal, the others reached their goals within 1-2 days. There were no significant side effects reported, except for nausea and pain at the injection site.

Patient Data:

1. Female, 16 years, 63 kg, refractory (HL), first collection, 15 mcg/kg G-CSF, 4 doses of Plerixafor, 4.63x10^6 cells/kg collected.

2. Female, 4 years, 21.8 kg, relapsed (HL), first collection, 15 mcg/kg G-CSF, 1 dose of Plerixafor, 6.22x10^6 cells/kg collected.

3. Female, 16 years, 48.45 kg, relapsed (HL), first collection, 15 mcg/kg G-CSF, 1 dose of Plerixafor, 5.60x10^6 cells/kg collected.

4. Male, 14 years, 63.9 kg, pineal pineal nongerminomatous germ cell tumor, first collection, 10 mcg/kg G-CSF, 1 dose of Plerixafor, 23.6x10^6 cells/kg collected

5. Male, 18 years, 70.9 kg, relapsed (HL), second collection, 6 mcg/kg G-CSF, 1 dose of Plerixafor, 5.78x10^6 cells/kg collected.

6. Female, 3 years, 16.3 kg, metastatic high-risk neuroblastoma, second collection, 15 mcg/kg G-CSF, 2 doses of Plerixafor, 31.3x10^6 cells/kg collected.

Discussion

In patients receiving chemotherapy, their immature HSC count could be affected during stem cell collection. While G-CSF alone has been effective, it often necessitates multiple days inpatient or repeated admissions to achieve adequate collection. In our patient population, especially those who previously used G-CSF alone, the number of CD34+ cells collected increased fivefold with the combination of Plerixafor and G-CSF. This finding corroborates previous studies demonstrating increased mobilization of CD34+ cells with Plerixafor, thereby enhancing the probability of collecting the target number of cells in a shorter timeframe and without major side effects.

Conclusion

Combining Plerixafor with G-CSF could become the new regimen for peripheral stem cell collection (PSCC), reducing hospital stays and improving the chances of adequate collection for autologous stem cell transplantation (SCT) on the first attempt. Although Plerixafor is expensive, the reduced duration of hospital stay could offset the cost by decreasing the need for multiple sessions. Further investigation into Plerixafor's role in treatment and preparation is necessary, especially in pediatrics. A large randomized multicenter study would be instrumental in establishing Plerixafor as a mainstream method for PSCC.

No relevant conflicts of interest to declare.