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Вопросы гематологии/онкологии и иммунопатологии в педиатрии. 2017; 16: 28-39

Результаты мобилизации, афереза и аутореинфузии гемопоэтических стволовых клеток у детей с нейробластомой: роль мониторинга количества CD34+ клеток в периферической крови

Курникова Е. Е., Кумукова И. Б., Гуз И. В., Хисматуллина Р. Д., Шаманская Т. В., Фадеева М. С., Глушкова С. Ю., Бриллиантова В. В., Варфоломеева С. Р., Трахтман П. Е.

https://doi.org/10.24287/1726-1708-2017-16-1-28-39

Аннотация

Миелоаблативная химиотерапия, сопровождающаяся аутологичной трансплантацией гемопоэтических стволовых клеток, способна улучшить результаты долгосрочной выживаемости пациентов с нейробластомой группы высокого риска, но требует достаточного количества аутологичных периферических стволовых клеток крови. Выполнено 118 аферезов для 116 детей с нейробластомой группы высокого риска. Медиана возраста - 2 года 10 мес. (от 6 мес. до 13 лет), медиана массы тела - 13 кг (от 5,8 до 47 кг). Мобилизация гранулоцитарным колониестимулирующим фактором в дозе 10 мкг/кг инициировалась в момент начинающегося восстановления кроветворения после последнего блока химиотерапии; мониторинг CD34+ клеток в периферической крови проводили с 3-го дня дня от начала мобилизации. Аферез выполняли на следующий день после достижения количества CD34+ клеток 15 в мкл после четырех дней мобилизации. Модификация тактики мобилизации, основанная на данных мониторинга числа CD34+ клеток в ПК, позволила достичь ко дню афереза медианы числа CD34+ клеток 105,27 клеток/мкл (от 14,8 до 714,8). В продукте афереза медиана CD34+/кг составила 14,43106/кг (от 2,68 до 74). Были выявлены достоверная корреляция между дозой CD34+/кг в продукте афереза и уровнем CD34+ клеток в ПК в день афереза (R=0,762; р0,0001), снижение результатов мобилизации и аферезов, если проведено более трех блоков ХТ. Благодаря мониторингу количества циркулирующих в ПК CD34+ клеток и модификации тактики мобилизации стала выполнимой задача сбора адекватной дозы CD34+ клеток за одну процедуру афереза: для 88 (75,86%) из 116 пациентов собрано 10106/кг CD34+ клеток и более, для 100% пациентов - более 2,5106/кг CD34+ за один аферез.
Список литературы

1. Caron H.N., Pearson A.D.J. Neuroblastoma. In: Voute P.A., Barrett A., Stevens M.C.G., Caron H.N., еds. Cancer in Сhildren. 5th еd. Oxford: Oxford University Press; 2005:337-352.

2. Brodeur G.M., Maris J.M. Neuroblastoma. In: Pizzo, D.A., Poplack, D.G., еds. Principles and Practice of Pediatric Oncology. 5th ed. Philadelphia, PA, Lippincott: Williams &Wilkins; 2006:933-970.

3. Luksch R., Castellani M. R., Collini P., De Bernardi B., Conte M., Gambini C. еt al. Neuroblastoma (Peripheral neuroblastic tumours). Crit Rev Oncol Hematol. 2016;107:163-181.

4. Seeger R.C., Brodeur G.M., Sather H., Dalton A., Siegel S.E., Wong K.Y. et al. Association of multiple copies of the N-myc oncogene with rapid progression of neuroblastomas. N Engl J Med. 1985;313(18):1111-1116.

5. Shimada H., Stram D.O., Chatten J., Joshi V.V., Hachitanda Y., Brodeur G.M. et al. Identification of subsets of neuroblastomas by combined histopathologic and N-myc analysis. J Natl Cancer Inst. 1995;87(19):1470-1476.

6. Brodeur G.M., Maris J.M., Yamashiro D.J., Hogarty M.D., White P.S. Biology and genetics of human neuroblastomas. J Pediatr Hematol Oncol. 1997;19(2):93-101.

7. NB2004 protocol. Berthold F. (principal investigator) [cited 2016 March 15]. Available at: http://www.kinderkrebsinfo.de/dlja_specialistov/ protokoly_gpoh/pohkinderkrebsinfotherapiestudien/nb2004/index_rus.html.

8. Pearson A.D., Pinkerton C.R., Lewis I.J., Imeson J., Ellershaw C., Machin D.; European Neuroblastoma Study Group; Children’s Cancer and Leukaemia Group (CCLG formerly United Kingdom Children’s Cancer Study Group). High-dose rapid and standard induction chemotherapy for patients aged over 1 year with stage 4 neuroblastoma: a randomised trial. Lancet Oncol. 2008;9(3):247-256.

9. Park J.R., Eggert A., Caron H. Neuroblastoma: biology, prognosis, and treatment. Hematol Оncol Сlin North Am. 2010;24(1):65-86.

10. Matthay K.K., Reynolds C.P., Seeger R.C., Shimada H., Adkins E.S., Haas-Kogan D. E et al. Long-term results for children with high-risk neuroblastoma treated on a randomized trial of myeloablative therapy followed by 13-cis-retinoic acid: a children’s oncology group study. J Clin Oncol. 2009;27(7):1007-1013.

11. Grupp S.A., Cohn S.L., Wall D., Reynolds P.C.; Hematopoietic Stem Cell Transplant Discipline and the Neuroblastoma Disease Committee, Children’s Oncology Group. Collection, storage, and infusion of stem cells in children with high-risk neuroblastoma: saving for a rainy day. Pediatr Blood Cancer. 2006;46(7): 719-722.

12. Cheung N.K., Kushner B.H., La Quaglia M., Kramer K., Gollamudi S., Heller G. et al. N7: а novel multi-modality therapy of high risk neuroblastoma (NB) in children diagnosed over 1 year of age. Med Pediatr Oncol. 2001;36(1):227-230.

13. Donzella G.A., Schols D., Lin S.W., Esté J.A., Nagashima K.A., Maddon P.J. et al. AMD3100, a small molecule inhibitor of HIV-1 entry via the CXCR4 co-receptor. Nat Med 1998;4(1):72-77.

14. Liles W.C., Broxmeyer H.E., Rodger E., Wood B., Hübel K., Cooper S. et al. Mobilization of hematopoietic progenitor cells in healthy volunteers by AMD3100, a CXCR4 antagonist. Blood. 2003;102(8):2728-2730.

15. Flatt T., Lewing K., Gonzalez C., Anthony K., Ryan R., Jones R. et al. Successful mobilization with AMD3100 and filgrastim with engraftment of autologous peripheral blood stem cells in a heavily pretreated pediatric patient with recurrent Burkitt lymphoma. Pediatr Hematol Oncol. 2010;27(2):138-149.

16. Toledano H., Yahel A., Cohen I.J., Yaniv I., Stein J. Successful mobilization, harvest and transplant of peripheral blood stem cells using AMD3100 and G-CSF following high dose craniospinal irradiation for medulloblastoma in a young child. Pediatr Blood Cancer. 2010;54(4):613-615.

17. Sutherland D.R., Anderson L., Keeney M., Nayar R., Chin-Yee I. The ISHAGE guidelines for CD34+ cell determination by flow cytometry. International Society of Hemototherapy and Graft Engineering. J Hematother. 1996;5(3):213-226.

18. Dubrovsky L., Wong E.C., Perez-Albuerne E., Loechelt B., Kamani N., Sande J. et al. CD34+ Collection efficiency as a function of blodd volumes processed in Pediatric autologous peripheral blood stem cell collection. J Clini Apher. 2011;26(3):131-137.

19. Reinhardt P., Brauninger S., Bialleck H., Thorausch K., Smith R., Schrezenmeier H. et al. Automatic interface-controlled apheresis collection of stem/progenitor cells: results from an autologus donor validation trial of a novel stem cell apheresis device. Transfusion. 2010;51(6):1321-1330.

20. Lie A.K., To L.B. Peripheral Blood Stem Cells: Transplantation and Beyond. Oncologist. 1997;2(1):40-49.

21. Modak S., Cheung I.Y., Kushner B.H., Kramer K., Reich L., Cheung N.K. Plerixafor plus granulocyte-colony stimulating factor for autologous hematopoietic stem cell mobilization in patients with metastatic neuroblastoma. Pediatr Blood Cancer. 2012;58(3):469-471.

22. Maschan A.A., Balashov D.N., Kurnikova E.E., Trakhtman P.E., Boyakova E.V., еt al. Efficacy of plerixafor in children with malignant tumors failing to mobilize a sufficient number of hematopoietic progenitors with G-CSF. Bone Marrow Transplant. 2015;50(8):1089-1091.

23. Sevilla J., Gonzalez-Vicent M., Madero L., Garcia-Sanchez F., Diaz M.A. Granulocytecolony stimulating factor alone at 12 microg/kg twice a day for 4 days for peripheral blood progenitor cell priming in pediatric patients. Bone Marrow Transplant. 2002;30(7):417-420.

24. Bensinger W., Appelbaum F., Rowley S., Storb R., Sanders J., Lilleby K. et al. Factors that influence collection and engraftment of autologous peripheral blood stem cells. J Clin Oncol. 1995;13(10):2547-2555.

25. Giralt S., Costa L., Schriber J., Dipersio J., Maziarz R., McCarty J. et al. Optimizing autologous stem cell mobilization strategies to improve patient outcomes: consensus guidelines and recommendations. Biol Blood Marrow Transplant. 2014;20(3):295-308.

26. Kroger N., Renges H., Kruger W., Gutensohn K., Löliger C., Carrero I. et al. A randomized comparison of once versus twice daily recombinant human granulocyte colony stimulating factor (filgrastim) for stem cell mobilization in healthy donors for allogeneic transplantation. Br J Haematol. 2000;111(3):761-765.

27. Meier R., Mühlethaler-Mottet A., Flahaut М., Coulon A., Fusco C., Louache F. et al. The chemokine receptor CXCR4 strongly promotes neuroblastoma primary tumour, metastatic growth, but not invasion. PLoS One. 2007;2(10):e1016.

28. Geminder H., Sagi-Assif O., Goldberg L., Meshel T., Rechavi G., Witz I.P. et al. A possible role for CXCR4 and its ligand, the CXC chemokine stromal cell-derived factor-1, in the development of bone marrow metastases in neuroblastoma. J Immunol. 2001;167(8):4747-4757.

29. Airoldi I., Raffaghello L., Piovan E., Cocco C., Carlini B., Amadori A. CXCL12 does not attract CXCR4þ human metastatic neuroblastoma cells: clinical implications. Clin Cancer Res. 2006;12(1):77-82.

30. Carlisle A.J., Lyttle C.A., Carlisle R.Y., Maris J.M. CXCR4 expression heterogeneity in neuroblastoma cells due to ligand-independent regulation. Mol Cancer. 2009;8:126.

31. Bensimhon P., Villablanca J.G., Sender L.S., Matthay K.K., Park J.R., Seeger R. et al. Peripheral blood stem cell support for multiple cycles of dose intensive induction therapy is feasible with little risk of tumor contamination in advanced stage neuroblastoma: a report from the Children’s Oncology Group. Pediatr Blood Cancer. 2010;54(4):596-602.

32. Kreissman S.G., Seeger R.C., Matthay K.K., London W.B., Sposto R., Grupp S.A. Purged versus non-purged peripheral blood stem-cell transplantation for high-risk neuroblastoma (COG A3973): a randomised phase 3 trial. Lancet Oncol. 2013;14(10):999-1008.

33. Chambon F., Tchirkov A., Pereira B., Rochette E., Demeocq F., Kanold J. Molecular assessment of minimal residual disease in PBSC harvests provides prognostic information in neuroblastoma. Pediatr Blood Cancer. 2013; published online March 21.

34. Burchill S.A., Kinsey S.E., Picton S., Roberts P., Pinkerton C.R., Selby P. et al. Minimal residual disease at the time of peripheral blood stem cell harvest in patients with advanced neuroblastoma. Med Pediatr Oncol. 2001;36(1):213-219.

35. Corrias M.V., Haupt R., Carlini B., Parodi S., Rivabella L., Garaventa A. et al. Peripheral blood stem cell tumor cell contamination and survival of neuroblastoma patients. Clin Cancer Res. 2006;12(19):5680-5685.

36. Reynolds C.P., Seeger R.C., Vo D.D., Black A.T., Wells J., Ugelstad J. Model system for removing neuroblastoma cells from bone marrow using monoclonal antibodies and magnetic immunobeads. Cancer Res. 1986;46(11):5882-5886.

37. Cherqaoui B., Rouel N., Defachelles A.S., Auvrignon A., Demeocq F., Merlin E. Peripheral blood stem cell collection in low-weight children: retrospective comparison of two apheresis devices. Transfusion. 2014;54(5):1371-1378.

38. Ravagnani F., Coluccia P., Notti P., Arienti F., Bompadre A., Avella M. et al. Peripheral blood stem cell collection in pediatric patients: feasibility of leukapheresis under anesthesia in uncompliant small children with solid tumors. J Clin Apher. 2006;21(2):85-91.

39. Delgado J., Fernandez-Jimenez M.C., Martinez A., Sastre A., Garcia-Miguel P., Hernandez-Navarro F., et al. Analysis of factors affecting PBPC collection in low-weight children with malignant disorders. Cytotherapy. 2004;6(1):43-49

Pediatric Hematology/Oncology and Immunopathology. 2017; 16: 28-39

Results of mobilization, apheresis and autoreinfusion of hematopoietic stem cells in children with neuroblastoma: role of monitoring the count of CD34+ cells in peripheral blood

Kurnikova E. E., Kumukova I. B., Guz I. V., Chismatullina R. D., Shamanskaya T. V., Fadeeva M. S., Glushkova S. Y., Brilliantova V. V., Varfolomeyeva S. R., Trakhtman P. E.

https://doi.org/10.24287/1726-1708-2017-16-1-28-39

Abstract

Myeloablative chemotherapy with autologous hematopoietic stem cells transplantation, can improve the results of long-term survival in patients with high-risk neuroblastoma. This treatment requires a sufficient number of autologous peripheral blood stem cells. Methods: 118 apheresis procedures was completed for 116 children with high-risk neuroblastoma, the median age was 2 years and 10 months (range, 6 months to 13 years), median body weight of 13 kg (range, 5.8 to 47 kg). Mobilization with G-CSF at a dose of 10 mg/kg was initiated at the time of incipient recovery of hematopoiesis after the last cycle of chemotherapy, monitoring of CD34+ cells in peripheral blood were started on 3rd day from the beginning of mobilization. Apheresis was performed the following day after reaching the number of CD34+ cells >15 cells/μl after 4 consequent days of mobilization. Results: Modification of mobilization, based on CD34+ cells monitoring data, allowed us to reach the median number of CD34+ cells of 105,27 cells/μl (range, 14.8–714.8) at the day of apheresis. The median number of collected CD34+/kg was 14,43×106/kg b.w. (range, 2.68–74). Was revealed a significant correlation between the dose of CD34+/kg b.w in the apheresis product and the level of CD34+ cells in peripheral blood at the day of apheresis (R=0.762; р<0.0001) and decrease of the results of mobilizing results and apheresis efficiency if mobilization was initiated later than after the 3rd course of chemotherapy. Conclusion: By monitoring the number of circulating CD34+ cells in peripheral blood and modification of mobilization tactic, the task to collect an adequate dose of CD34+ cells for autoSCT with one apheresis procedure was feasible. In 88 (75.86%) of the 116 patients we were able to collect 10×106/kg CD34+ cells and more, and 100% of patients collected > 2.5×106/kg CD34+ cells with 1 apheresis.

References

1. Caron H.N., Pearson A.D.J. Neuroblastoma. In: Voute P.A., Barrett A., Stevens M.C.G., Caron H.N., eds. Cancer in Shildren. 5th ed. Oxford: Oxford University Press; 2005:337-352.

2. Brodeur G.M., Maris J.M. Neuroblastoma. In: Pizzo, D.A., Poplack, D.G., eds. Principles and Practice of Pediatric Oncology. 5th ed. Philadelphia, PA, Lippincott: Williams &Wilkins; 2006:933-970.

3. Luksch R., Castellani M. R., Collini P., De Bernardi B., Conte M., Gambini C. et al. Neuroblastoma (Peripheral neuroblastic tumours). Crit Rev Oncol Hematol. 2016;107:163-181.

4. Seeger R.C., Brodeur G.M., Sather H., Dalton A., Siegel S.E., Wong K.Y. et al. Association of multiple copies of the N-myc oncogene with rapid progression of neuroblastomas. N Engl J Med. 1985;313(18):1111-1116.

5. Shimada H., Stram D.O., Chatten J., Joshi V.V., Hachitanda Y., Brodeur G.M. et al. Identification of subsets of neuroblastomas by combined histopathologic and N-myc analysis. J Natl Cancer Inst. 1995;87(19):1470-1476.

6. Brodeur G.M., Maris J.M., Yamashiro D.J., Hogarty M.D., White P.S. Biology and genetics of human neuroblastomas. J Pediatr Hematol Oncol. 1997;19(2):93-101.

7. NB2004 protocol. Berthold F. (principal investigator) [cited 2016 March 15]. Available at: http://www.kinderkrebsinfo.de/dlja_specialistov/ protokoly_gpoh/pohkinderkrebsinfotherapiestudien/nb2004/index_rus.html.

8. Pearson A.D., Pinkerton C.R., Lewis I.J., Imeson J., Ellershaw C., Machin D.; European Neuroblastoma Study Group; Children’s Cancer and Leukaemia Group (CCLG formerly United Kingdom Children’s Cancer Study Group). High-dose rapid and standard induction chemotherapy for patients aged over 1 year with stage 4 neuroblastoma: a randomised trial. Lancet Oncol. 2008;9(3):247-256.

9. Park J.R., Eggert A., Caron H. Neuroblastoma: biology, prognosis, and treatment. Hematol Oncol Slin North Am. 2010;24(1):65-86.

10. Matthay K.K., Reynolds C.P., Seeger R.C., Shimada H., Adkins E.S., Haas-Kogan D. E et al. Long-term results for children with high-risk neuroblastoma treated on a randomized trial of myeloablative therapy followed by 13-cis-retinoic acid: a children’s oncology group study. J Clin Oncol. 2009;27(7):1007-1013.

11. Grupp S.A., Cohn S.L., Wall D., Reynolds P.C.; Hematopoietic Stem Cell Transplant Discipline and the Neuroblastoma Disease Committee, Children’s Oncology Group. Collection, storage, and infusion of stem cells in children with high-risk neuroblastoma: saving for a rainy day. Pediatr Blood Cancer. 2006;46(7): 719-722.

12. Cheung N.K., Kushner B.H., La Quaglia M., Kramer K., Gollamudi S., Heller G. et al. N7: a novel multi-modality therapy of high risk neuroblastoma (NB) in children diagnosed over 1 year of age. Med Pediatr Oncol. 2001;36(1):227-230.

13. Donzella G.A., Schols D., Lin S.W., Esté J.A., Nagashima K.A., Maddon P.J. et al. AMD3100, a small molecule inhibitor of HIV-1 entry via the CXCR4 co-receptor. Nat Med 1998;4(1):72-77.

14. Liles W.C., Broxmeyer H.E., Rodger E., Wood B., Hübel K., Cooper S. et al. Mobilization of hematopoietic progenitor cells in healthy volunteers by AMD3100, a CXCR4 antagonist. Blood. 2003;102(8):2728-2730.

15. Flatt T., Lewing K., Gonzalez C., Anthony K., Ryan R., Jones R. et al. Successful mobilization with AMD3100 and filgrastim with engraftment of autologous peripheral blood stem cells in a heavily pretreated pediatric patient with recurrent Burkitt lymphoma. Pediatr Hematol Oncol. 2010;27(2):138-149.

16. Toledano H., Yahel A., Cohen I.J., Yaniv I., Stein J. Successful mobilization, harvest and transplant of peripheral blood stem cells using AMD3100 and G-CSF following high dose craniospinal irradiation for medulloblastoma in a young child. Pediatr Blood Cancer. 2010;54(4):613-615.

17. Sutherland D.R., Anderson L., Keeney M., Nayar R., Chin-Yee I. The ISHAGE guidelines for CD34+ cell determination by flow cytometry. International Society of Hemototherapy and Graft Engineering. J Hematother. 1996;5(3):213-226.

18. Dubrovsky L., Wong E.C., Perez-Albuerne E., Loechelt B., Kamani N., Sande J. et al. CD34+ Collection efficiency as a function of blodd volumes processed in Pediatric autologous peripheral blood stem cell collection. J Clini Apher. 2011;26(3):131-137.

19. Reinhardt P., Brauninger S., Bialleck H., Thorausch K., Smith R., Schrezenmeier H. et al. Automatic interface-controlled apheresis collection of stem/progenitor cells: results from an autologus donor validation trial of a novel stem cell apheresis device. Transfusion. 2010;51(6):1321-1330.

20. Lie A.K., To L.B. Peripheral Blood Stem Cells: Transplantation and Beyond. Oncologist. 1997;2(1):40-49.

21. Modak S., Cheung I.Y., Kushner B.H., Kramer K., Reich L., Cheung N.K. Plerixafor plus granulocyte-colony stimulating factor for autologous hematopoietic stem cell mobilization in patients with metastatic neuroblastoma. Pediatr Blood Cancer. 2012;58(3):469-471.

22. Maschan A.A., Balashov D.N., Kurnikova E.E., Trakhtman P.E., Boyakova E.V., et al. Efficacy of plerixafor in children with malignant tumors failing to mobilize a sufficient number of hematopoietic progenitors with G-CSF. Bone Marrow Transplant. 2015;50(8):1089-1091.

23. Sevilla J., Gonzalez-Vicent M., Madero L., Garcia-Sanchez F., Diaz M.A. Granulocytecolony stimulating factor alone at 12 microg/kg twice a day for 4 days for peripheral blood progenitor cell priming in pediatric patients. Bone Marrow Transplant. 2002;30(7):417-420.

24. Bensinger W., Appelbaum F., Rowley S., Storb R., Sanders J., Lilleby K. et al. Factors that influence collection and engraftment of autologous peripheral blood stem cells. J Clin Oncol. 1995;13(10):2547-2555.

25. Giralt S., Costa L., Schriber J., Dipersio J., Maziarz R., McCarty J. et al. Optimizing autologous stem cell mobilization strategies to improve patient outcomes: consensus guidelines and recommendations. Biol Blood Marrow Transplant. 2014;20(3):295-308.

26. Kroger N., Renges H., Kruger W., Gutensohn K., Löliger C., Carrero I. et al. A randomized comparison of once versus twice daily recombinant human granulocyte colony stimulating factor (filgrastim) for stem cell mobilization in healthy donors for allogeneic transplantation. Br J Haematol. 2000;111(3):761-765.

27. Meier R., Mühlethaler-Mottet A., Flahaut M., Coulon A., Fusco C., Louache F. et al. The chemokine receptor CXCR4 strongly promotes neuroblastoma primary tumour, metastatic growth, but not invasion. PLoS One. 2007;2(10):e1016.

28. Geminder H., Sagi-Assif O., Goldberg L., Meshel T., Rechavi G., Witz I.P. et al. A possible role for CXCR4 and its ligand, the CXC chemokine stromal cell-derived factor-1, in the development of bone marrow metastases in neuroblastoma. J Immunol. 2001;167(8):4747-4757.

29. Airoldi I., Raffaghello L., Piovan E., Cocco C., Carlini B., Amadori A. CXCL12 does not attract CXCR4þ human metastatic neuroblastoma cells: clinical implications. Clin Cancer Res. 2006;12(1):77-82.

30. Carlisle A.J., Lyttle C.A., Carlisle R.Y., Maris J.M. CXCR4 expression heterogeneity in neuroblastoma cells due to ligand-independent regulation. Mol Cancer. 2009;8:126.

31. Bensimhon P., Villablanca J.G., Sender L.S., Matthay K.K., Park J.R., Seeger R. et al. Peripheral blood stem cell support for multiple cycles of dose intensive induction therapy is feasible with little risk of tumor contamination in advanced stage neuroblastoma: a report from the Children’s Oncology Group. Pediatr Blood Cancer. 2010;54(4):596-602.

32. Kreissman S.G., Seeger R.C., Matthay K.K., London W.B., Sposto R., Grupp S.A. Purged versus non-purged peripheral blood stem-cell transplantation for high-risk neuroblastoma (COG A3973): a randomised phase 3 trial. Lancet Oncol. 2013;14(10):999-1008.

33. Chambon F., Tchirkov A., Pereira B., Rochette E., Demeocq F., Kanold J. Molecular assessment of minimal residual disease in PBSC harvests provides prognostic information in neuroblastoma. Pediatr Blood Cancer. 2013; published online March 21.

34. Burchill S.A., Kinsey S.E., Picton S., Roberts P., Pinkerton C.R., Selby P. et al. Minimal residual disease at the time of peripheral blood stem cell harvest in patients with advanced neuroblastoma. Med Pediatr Oncol. 2001;36(1):213-219.

35. Corrias M.V., Haupt R., Carlini B., Parodi S., Rivabella L., Garaventa A. et al. Peripheral blood stem cell tumor cell contamination and survival of neuroblastoma patients. Clin Cancer Res. 2006;12(19):5680-5685.

36. Reynolds C.P., Seeger R.C., Vo D.D., Black A.T., Wells J., Ugelstad J. Model system for removing neuroblastoma cells from bone marrow using monoclonal antibodies and magnetic immunobeads. Cancer Res. 1986;46(11):5882-5886.

37. Cherqaoui B., Rouel N., Defachelles A.S., Auvrignon A., Demeocq F., Merlin E. Peripheral blood stem cell collection in low-weight children: retrospective comparison of two apheresis devices. Transfusion. 2014;54(5):1371-1378.

38. Ravagnani F., Coluccia P., Notti P., Arienti F., Bompadre A., Avella M. et al. Peripheral blood stem cell collection in pediatric patients: feasibility of leukapheresis under anesthesia in uncompliant small children with solid tumors. J Clin Apher. 2006;21(2):85-91.

39. Delgado J., Fernandez-Jimenez M.C., Martinez A., Sastre A., Garcia-Miguel P., Hernandez-Navarro F., et al. Analysis of factors affecting PBPC collection in low-weight children with malignant disorders. Cytotherapy. 2004;6(1):43-49