Effectiveness and challenges of apheresis of peripheral blood stem cells in children with malignant neoplasms: results of a single-center study

Peripheral blood stem cell apheresis (PBSC) is an effective and safe method of collecting hematopoietic stem cells (HSC) in patients with malignant neoplasms (MN) for subsequent high-dose chemotherapy (HDCT) with autologous hematopoietic stem cell transplantation (auto-HSCT) compared to myeloexfusion. Optimization of the method for young children in terms of increasing efficiency and reducing the risks of associated complications remains a challenge. The article presents a single-center retrospective analysis of PBSC apheresis in children with cancer. The study included 97 patients who underwent 138 PBSC apheresis. The median age was 2 years 11 months, the median body weight was 16.05 kg. Mobilization of CD34+ cells was performed with filgrastim, in 2 cases with plerixafor. By the day of apheresis, the median CD34+ cell count was 100.5 (10.5–1032) cells/µl. The absolute CD34+ cell count as a result of 1 session ranged from 0.38 to 71.91, the median was 4.8·106/kg. Factors influencing the efficiency of PBSC apheresis were lower body weight (p=0.039), fewer courses of previous antitumor therapy (p=0.002), and a higher number of HSCs (CD34+/45+) in 1 µl of peripheral blood based on the mobilization results (p=0.001). There were no complications associated with the apheresis procedure. Adequate preparation and the proper concomitant therapy, taking into account the prediction of all risks, allow preventing complications and performing PBSC apheresis with a satisfactory result.

1. Sergeenko K. A., Dokuchaeva Y. Y., Kostareva I. O. et al. High-dose chemotherapy with autologous hemopoietic stem cell transplantation in children with retinoblastoma. Literature review and case series // Cellular Therapy and Transplantation. 2022;11(1):6–12. http://doi.org/10.18620/ctt-1866-8836-2022-11-1-6-12.

2. Ussowicz M., Mielcarek-Siedziuk M., Musiał J. et al. Melphalan, Etoposide, and Carboplatin Megatherapy with Autologous Stem Cell Transplantation in Children with Relapsing or Therapy-Resistant Extracranial Germ-Cell Tumors – A Retrospective Analysis // Cancers. 2020;12(12):3841. https://doi.org/10.3390/cancers12123841.

3. Dinikina Yu. V., Morgacheva D. A., Smirnova A. Yu. et al. Experience in using intensive chemotherapy regimens with autologous stem cell transplantation in children with high-risk malignant tumors // Russian Journal of Personalized Medicine. 2022;2(1):104–116. (In Russ.). https://doi.org/10.18705/2782-3806-2022-2-1-104-116.

4. Stepanyan N. G., Sidorova N. V., Rubanskaya M. V. et al. Optimization of methods for collecting peripheral hematopoietic stem cells in children with cancer: a literature review // Russian Journal of Pediatric Hematology and Oncology. 2020;7(2):78–85. (In Russ.). https://doi.org/10.21682/2311-1267-2020-7-2-78-85.

5. Motalkina M. S., Kuleva S. A., Alekseev S. M. et al. Mobilization of hematopoietic stem cells: past, present and future // Pediatr. 2016;7(2):96–0103. (In Russ.). http://doi.org/10.17816/PED7296-103.

6. Porfyriou E., Letsa S., Kosmas C. Hematopoietic stem cell mobilization strategies to support high-dose chemotherapy: A focus on relapsed/refractory germ cell tumors // World J Clin Oncol. 2021;12(9):746–766. (In Russ.). http://doi.org/10.5306/wjco.v12.i9.746.

7. Sevilla J., González-Vicent M., Madero L., Díaz M. A. Peripheral blood progenitor cell collection in low-weight children // J Hematother Stem Cell Res. 2002;11(4):633–42. (In Russ.). http://doi.org/10.1089/15258160260194776.

8. Schmitz N., Linch D. C., Dreger P. et al. Randomised trial of fi lgrastim- mobilised peripheral blood progenitor cell transplantation versus autologous bone-marrow transplantation in lymphoma patients // Lancet. 1996;347(8998):353–7. http://doi.org/10.1016/s0140-6736(96)90536-x.

9. Kournikova E. E., Khamin I. G., Shchukin V. V., et al. Apheresis of hematopoietic stem cells in children with extremely low body weight, as we do: the experience of the Dmitry Rogachev National Medical Research Center for Pediatric Hematology and Oncology // Issues of Hematology/Oncology and Immunopathology in Pediatrics. 2020;19(2):152–159. (In Russ.). https://doi.org/10.24287/1726-1708-2020-19-2-152-159.

10. Ospanova M. E., Ramil’eva I. R., Turganbekova A. A. Hematopoietic stem cells // Clinical Medicine of Kazakhstan. 2011;1(20):78–82. (In Russ.).

11. Michon B., Moghrabi A., Winikoff R. et al. Complications of apheresis in children // Transfusion. 2007;47(10):1837– 42. http://doi.org/10.1111/j.1537-2995.2007.01405.x.

12. Kournikova E. E., Kumukova I. B., Guz I. V., et al. Results of mobilization, apheresis and autoreinfusion of hematopoietic stem cells in children with neuroblastoma: the role of monitoring the number of CD34+ cells in peripheral blood // Issues of hematology/oncology and immunopathology in pediatrics. 2017;16(1):28–39. (In Russ.). https://doi.org/10.24287/1726-1708-2017-16-1-28-39.

13. Cesaro S., Tintori V., Nesi F. et al. A prospective study on the effi-cacy of mobilization of autologous peripheral stem cells in pediatric oncohematology patients // Transfusion. 2013;53(7):1501–1509. http://doi.org/10.1111/j.1537-2995.2012.03911.x.

14. Kim H. C. Therapeutic pediatric apheresis // J Clin Apher. 2000;15(1–2):129–57. http://doi.org/10.1002/(sici)1098-1101(2000)15:1/2<129::aid-jca7>3.0.co;2-h.

15. Salazar-Riojas R., García-Lozano J. A., Valdés-Galván M. et al. Effective collection of peripheral blood stem cells in children weighing 20 kilogram or less in a single large-volume apheresis procedure // J Clin Apher. 2015;30(5):281–7. http://doi.org/10.1002/jca.21375.

16. Even-Or E., Grunspan A., Swerdlow Y. et al. Peripheral blood stem-cell harvest using percutaneous arterial lines in children // Pediatr Blood Cancer. 2013;60(6):946–8. http://doi.org/10.1002/pbc.24369. PMID: 23109232.

17. Truong T. H., Prokopishyn N. L., Luu H. et al. Predictive factors for successful peripheral blood stem cell mobilization and collection in children // J Clin Apher. 2019;34(5):598–606. http://doi.org/10.1002/jca.21738. PMID: 31390093.

18. Takaue Y., Kawano Y., Abe T. et al. Collection and transplantation of peripheral blood stem cells in very small children weighing 20 kg or less // Blood. 1995; 86(l): 372–80.

19. Delaney M., Capocelli K. E., Eder A. F. et al. An international survey of pediatric apheresis practice // J Clin Apher. 2014;29(2):120–6. http://doi.org/10.1002/jca.21301. PMID: 24105856.

20. Delgado J., Fernandez-Jimenez M. C., Martinez A. et al. Analysis of factors affecting PBPC collection in lowweight children with malignant disorders // Cytotherapy. 2004;6(1):43–9. http://doi.org/10.1080/14653240310004566. PMID: 14985166.