ISSN 1866-8836
Клеточная терапия и трансплантация

PO-05. Experience with CXCR4 antagonist (Plerixafor) in pediatric clinic at the R. Gorbacheva Memorial Instotute of Pediatric Oncology, Hematology and Transplantation

Margarita S. Khalipskaya, Polina S. Kuga, Ilya V. Kazantsev, Maria A. Estrina, Elena V. Babenko, Alexander N. Galimov, Daria A. Drozdovskaya, Olesya S. Yudintseva, Tatiana V. Grishchenko, Polina S. Tolkunova, Olga I. Bogdanova, Andrei V. Kozlov, Svetlana A. Safonova, Yuri A. Punanov, Ludmila S. Zubarovskaya

RM Gorbacheva Research Institute, Pavlov University, St. Petersburg, Russia


Contact: Dr. Margarita S. Khalipskaya, e-mail: msgolenkova24@gmail.com

doi 10.18620/ctt-1866-8836-2023-12-3-1-176

Summary

High-dose chemotherapy with autologous hemopoietic stem cell transplantation (auto-HSCT) is a relatively common therapeutic modality for pediatric patients with high-risk solid tumors. The lower threshold for hemopoietic stem cells count in autologous transplant is usually set at 2×106 CD34+/kg. The lack of response to G-CSF administration during hemopoietic stem cells mobilization prevents adequate high-dose therapy and lowers the chances for subsequent long-term disease-free survival. Since plerixafor, a CXCR4 chemokine receptors inhibitor, may greatly enhance G-CSF effectiveness and enable sufficient stem cell harvest, this therapeutic agent is still not included into standard options for the mobilized patients under 18 years old. Our aim was to evaluate effectiveness of CXCR4 chemokine receptor inhibitor (plerixafor) in combination with G-CSF for the patients younger than 18 years old subjected to harvesting of autologous hematopoietic stem cells.

Materials and methods

This retrospective study enrolled a cohort of 249 pediatric patients aged 6 months to 18 years (median, 7.8 years) attempting peripheral blood stem cells (PBSCs) mobilization at the R. M.Gorbacheva Research Institute from January 2017 till August 2023. We performed a total of 256 mobilization procedures at stable hemopoiesis, or upon recovery after chemotherapy. The underlying conditions were as follows: neuroblastoma in 40% (n=100), central nervous system tumors in 25.2% (n=63), Hodgkin lymphoma in 13.2% (n=33), non-Hodgkin lymphoma in 8.4% (n=21), Ewing sarcoma in 10% (n=24), germ-cell tumor in 2.4% (n=6), and nephroblastoma in 0.8% (n=2) of cases. The CD34+ cells counts were performed by flow cytometry on D+4 after G-SCF initiation under stable hemopoiesis, or on first day of blood recovery (WBC >1×109/L) after preceding chemotherapy course with G-SCF started on D+5 after chemotherapy regimen (D+10 or more from the last day of chemotherapy regimen). The patient was given plerixafor, if the HSC mobilization deemed to be ineffective (CD34+ <10 cells/µL) or suboptimal (CD34+ of 10-20 cells/µL).

Results

The harvest was successful (≥2×106 CD34+ cells/kg) in 237 of 242 cases (99%). In 14 of 256 cases (5.4%), the patient was ineligible for leukapheresis due to different reasons. A total of 101 (39%) mobilization regimens, performed at stable hemopoiesis (n=95), and 6 procedures upon recovery after chemotherapy, included CXCR4 chemokine receptors antagonist given 10-12 hours prior to leukapheresis procedure. Only 2 patients (2%) did not respond to mobilization and underwent apheresis. Plerixafor usage allowed harvesting an adequate amount of CD34+ cells in 51 of 55 (92.7%) patients with CD34+ cells counts of <10 per µL, and in 30 of 31 patients with CD34+ cells counts of 10 to 20 cells per µL. In 3 of 5 latter cases, an adequate transplant was obtained by second harvest procedure.

Conclusions

The use of CXCR4 chemokine receptor antagonist allows harvesting autologous stem cells in most patients with ineffective or low-effective mobilization in order to make them candidates for dose-intensive consolidation. Although plerixafor is not yet included in clinical guidelines, it should nevertheless be used on individual basis.

Keywords

Autologous hemopoietic stem cell transplantation, plerixafor, peripheral blood stem cells, mobilization.


Supplement 12-3
09/30/2023

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doi 10.18620/ctt-1866-8836-2023-12-3-1-176

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