Optimization of methods for collecting peripheral hematopoietic stem cells in children with cancer: literature review

Autologous hematopoietic stem cell transplantation (auto-HSCT) is a standard for the treatment of oncological, hematologic, and also some immune diseases, ensuring the restoration of blood counts after high-dose chemotherapy. In children, the success of mobilization and collection of hematopoietic stem cells (HSCs) is especially important. Mobilization schemes for children are decided on an individual basis, which requires the development and implementation of recommendations for improving the efficiency of mobilization and collection of HSCs. Mobilization schemes include the use of granulocyte colony-stimulating factor in the form of monotherapy or in combination with CXCR4 antagonists. These schemes are ineffective in some children, which requires re-mobilization or rejection of transplantation, which negatively affects the prognosis. When preparing a patient for HSCs collection, it is necessary to take into account all previous therapy, the patient’s age, weight and height indicators, and general somatic state. Harvesting the required amount of HSCs will allow for high-dose therapy followed by auto-HSCT, and thereby increase the effectiveness of treatment. It is necessary to optimize the protocol for mobilization of HSCs with a large bias for pediatric patients, which will clearly define the criteria for mobilization, give indications for this procedure and determine the criteria for technical collection, which will allow to obtain the optimal number of CD34+ cells, which will ensure the success of the treatment.

1. Vladimirskaya E.B. Normal blood formation and its regulation. Klinicheskaya onkogematologiya = Clinical Oncohematology 2015;8(2):109–19. (In Russ.)

2. Orkin S.H. Hematopoiesis: how does it happen? Curr Opin Cell Biol 1995;7(6):870–7. doi: 10.1016/0955-0674(95)80072-7.

3. Bennett C.L., Smith T.J., Weeks J.C., Bredt A.B., Feinglass J., Fetting J.H., Hillner B.E., Somerfi eld M.R., Winn R.J. Use of hematopoietic colony stimulating factors: the American society of clinical oncology survey. J Clin Oncol 1996;14(9):2511–20. doi: 10.1200/JCO.1996.14.9.2511.

4. Kiel M.J., Yilmaz O.H., Iwashita T., Yilmaz O.H., Terhorst C., Morrison S.J. SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells. Cell 2005;121(7):1109–21. doi: 10.1016/j.cell.2005.05.026.

5. Barrett D., Fish J.D., Grupp S.A. Autologous and allogeneic cellular therapies for high-risk pediatric solid tumors. Pediatr Clin North Am 2010;57(1):47–66. doi: 10.1016/j.pcl.2010.01.001.

6. Civriz Bozdag S., Tekgunduz E., Altuntas F. The current status in hematopoietic stem cell mobilization. J Clin Apher 2015;30(5):273–80. doi: 10.1002/jca.21374.

7. Dreger P., Kloss M., Petersen B., Haferlach T., Loffl er H., Schmitz N. Autologous progenitor cell transplantation: prior exposure to stem cell-toxic drugs determines yield and engraftment of peripheral blood progenitor cell but not of bone marrow grafts. Blood 1995;86(10):3970–8. PMID: 7579368.

8. Sugrue M.W., Williams K., Pollock B.H., Khan S., Peracha S., Wingard J.R., Moreb J.S. Characterization and outcome of ‘hard to mobilize’ lymphoma patients undergoing autologous stem cell transplantation. Leuk Lymphoma 2000;39(5–6):509–19. doi: 10.3109/10428190009113381.

9. Schmitz N., Linch D.C., Dreger P., Goldstone A.H., Boogaerts M.A., Ferrant A., Demuynck H.M., Link H., Zander A., Barge A. 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. doi: 10.1016/s0140-6736(96)90536-x.

10. Copland M., Alcorn M., Patton D., Doig A., Farrell E., Currie C., Sinclair J.E., Parker A., Douglas K.W. Signifi cantly lower cryopreservation volumes for PBSC collections using Spectra Optia(R) version 5 software compared with the MNC setting on COBE(R) Spectra, particularly when using plerixafor for mobilization. Blood 2010;116(21):825. doi: 10.1182/blood.V116.21.825.825.

11. Mendez-Ferrer S., Lucas D., Battista M., Frenette P.S. Haematopoietic stem cell release is regulated by circadian ascillatins. Nature 2008;452(7186):442–7. doi: 10.1038/nature06685.

12. Katayama Y., Battista M., Kao W.M., Hidalgo A., Peired J.A., Thomas S.A., Frennete P.S. Signals from the sympathetic nervous system regulate hematopoietic stem cell egress from bone marrow. Cell 2006;124(2):407–21. doi: 10.1016/j.cell.2005.10.041.

13. Sugiyama T., Kohara H., Noda M., Takashi N. Maintenance of the hematopoietic stem cell pool by CXCL12-CXCR4 chemokine signaling in bone marrow stromal cell niches. Immunity 2006;25(6):977–88. doi: 10.1016/j.immuni.2006.10.016.

14. Ulyanova T., Scott L.M., Priestley G.V., Jiang Y, Nakamoto B., Koni P.A., Papayannopoulou T. VCAM-1 expression in adult hematopoietic and nonhematopoietic cells is controlled by tissueinductive signals and refl ects their developmental origin. Blood 2015;106(1):86–94. doi: 10.1182/blood-2004-09-3417.

15. Winkler I.G., Sims N.A., Pettit A.R., Barbier V., Nowlan B., Helwani F., Poulton I.J., van Rooijen N., Alexander K.A., Raggatt L.J., Levesque J.P. Bone marrow macrophages maintain hematopoietic stem cell (HSC) niches and their depletion mobilizes HSCs. Blood 2010;116(23):4815–28. doi: 10.1182/blood-2009-11-253534.

16. Haas R., Mohle R., Fruhauf S., Goldschmidt H., Witt B., Flentje M., Wannenmacher M., Hunstein W. Patient characteristics associated with successful mobilizing and autografting of peripheral blood progenitor cells in malignant lymphoma. Blood 1994;83(12):3787–94. PMID: 751521.

17. Dingli D., Nowakowski G.S., Dispenzieri A., Lacy M.Q., Hayman S., Litzow M.R., Gastineau D.A., Gertz M.A. Cyclophosphamide mobilization does not improve outcome in patients receiving stem cell trans- plantation for multiple myeloma. Clin Lymphoma Myeloma 2006;6(5):384–8. doi:10.3816/CLM.2006.n.014.

18. Desikan K.R., Barlogie B., Jagannath S., Vesole D.H., Siegel D., Fassas A., Munshi N., Singhal S., Mehta J., Tindle S., Nelson J., Bracy D., Mattox S., Tricot G. Comparable engraftment kinetics following peripheral-blood stem-cell infusion mobilized with granulocyte colony-stimulating factor with or without cyclophosphamide in multiple myeloma. J Clin Oncol 1998;16(4):1547–53. doi: 10.1200/JCO.1998.16.4.1547.

19. Truong T.H., Prokopishyn N.L., Luu H., Guilcher GM.T., Lewis V.A. Predictive factors for successful peripheral blood stem cell mobilization and collection in children. J Clin Apher 2019;34(5):598–606. doi: 10.1002/jca.21738.

20. De Clercq E. Mozobil® (Plerixafor, AMD3100), 10 years after its approval by the US Food and Drug Administration. Antivir Chem Chemother 2019;27:2040206619829382. doi: 10.1177/2040206619829382.

21. Lee H.M., Wu W., Wysoczynski M., Liu R., Zuba-Surma E.K., Kucia M., Ratajczak J., Ratajczak M.Z. Impaired mobilization of hematopoietic stem/progenitor cells in C5-defi cient mice supports the pivotal involvement of innate immunity in this process and reveals novel promobilization eff ects of granulocytes. Leukemia 2009;23(11):2052–62. doi: 10.1038/leu.2009.158.

22. Levesque J.P., Liu F., Simmons P.J., Betsuyaku T., Senior R.M., Pham C., Link D.C. Characterization of hematopoietic progenitor mobilization in protease-defi cient mice. Blood 2014;104(1):65–72. doi: 10.1182/blood-2003-05-1589.

23. Dar A., Schajnovitz A., Lapid K., Kalinkovich A., Itkin T., Ludin A., Kao W.M., Battista M., Tesio M., Kollet O., Cohen N.N., Margalit R., Buss E.C., Baleux F., Oishi S., Fujii N., Larochelle A., Dunbar C.E., Broxmeyer H.E., Frenette P.S., Lapidot T. Rapid mobilization of hematopoietic progenitors by AMD3100 and catecholamines is mediated by CXCR4-depen- dent SDF-1 release from bone marrow stromal cells. Leukemia 2011;25(8):1286–96. doi: 10.1038/leu.2011.62.

24. Christopher M.J., Liu F., Hilton M.J., Long F., Link D.C. Suppression of CXCL12 production by bone marrow osteoblasts is a common and critical pathway for cytokine-induced mobilization. Blood 2009;114(7):1331–9. doi: 10.1182/blood-2008-10-184754.

25. Calandra G., McCarty J., McGuirk J., Tricot G., Crocker S.A., Badel K., Grove B., Dye A., Bridger G. AMD3100 plus G-CSF can successfully mobilize CD34+ cells from non-Hodgkin’s lymphoma, Hodgkin’s disease and multiple myeloma patients previously failing mobilization with chemotherapy and/or cytokine treatment: compassionate use data. Bone Marrow Transplant 2008;41(4):331–8. doi: 10.1038/sj.bmt.1705908.

26. Lie A.K., To L.B. Peripheral blood stem cells: transplantation and beyond. Oncologist 1997;2(1):40–9. PMID: 10388028. 27. Maschan A.A., Balashov D.N., Kurnikova E.E., Trakhtman P.E., Boyakova E.V., Skorobogatova E.V., Novichkova G.A., Maschan M.A. Effi cacy of plerixafor in children with malignant tumors failing to mobilize a suffi cient number of hematopoietic progenitors with G-CSF. Bone Marrow Transplant 2015;50(8):1089–91. doi: 10.1038/bmt.2015.71.

27. 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):469–71. doi: https:10.1002/pbc.23132.

28. Morland B., Kepak T., Dallorso S., Sevilla J., Murphy D., Luksch R., Yaniv I., Bader P., Rößler J., Bisogno G., Maecker-Kolhoff B., Lang P., Zwaan C.M., Sumerauer D., Kriván G., Bernard J., Liu Q., Doyle E., Locatelli F. Plerixafor combined with standard regimens for hematopoietic stem cell mobilization in pediatric patients with solid tumors eligible for autologous transplants: two-arm phase I/II study (MOZAIC). Bone Marrow Transplant 2020. [Epub ahead of print]. doi: 10.1038/s41409-020-0836-2.

29. Kawano Y., Takaue Y., Watanabe T., Abe T., Okamoto Y., Iwai A., Iwai T., Watanabe A., Ito E., Makimoto A., Nakagawa R., Watanabe H., Sato J., Suenaga K., Suzuya H., Ohnishi T., Kanamaru S., Kaneko M., Kuroda Y. Effi cacy of the mobilization of peripheral blood stem cells by granulocyte colony-stimulating factor in pediatric donors. Cancer Res 1999;59:3321–4. PMID: 10416586.

30. Fu P., Bagai R.K., Meyerson H., Kane D., Fox R.M., Creger R.J., Cooper B.W., Gerson S.L., Laughlin M.J., Koc O.N., Lazarus H.M. Pre-mobilization therapy blood CD34+ cell count predicts the likelihood of successful hematopoietic stem cell mobilization. Bone Marrow Transplant 2006;38(3):189–96. doi: 10.1038/sj.bmt.1705431.

31. Empringham B., Chiang K.Y., Krueger J. Collection of hematopoietic stem cells and immune eff ector cells in small children. Transfus Apher Sci 2018;57(5):614–8. doi: 10.1016/j.transci.2018.10.004.

32. 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. Результаты мобилизации, афереза и аутореинфузии гемопоэтических стволовых клеток у детей с нейробластомой: роль мониторинга количества CD34+ клеток в периферической крови. Вопросы гематологии/онкологии и иммунопатологии в педиатрии 2017;16(1):28–39. doi: 10.24286/1726-1708. [Kurnikova E.E., Kumukova I.B., Guz I.V., Chismatullina R.D., Shamanskaya T.V., Fadeeva M.S., Glushkova S.Yu., Brilliantova V.V., Varfolomeyeva S.R., Trakhtman P.E. 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. Voprosy gematologii/onkologii i immunopatologii v pediatrii = Pediatric Hematology/Oncology and Immunopathology 2017;16(1):28–39. (In Russ.)].

33. Xie Y., Yin T., Wiegraebe W., He X.C., Miller D., Stark D., Perko K., Alexander R., Schwartz J., Grindley J.C., Park J., Haug J.S., Wunderlich J.P., Li H., Zhang S., Johnson T., Feldman R.A. Detection of functional haematopoietic stem cell niche using real-time imaging. Nature 2009;457(7225):97–101. doi: 10.1038/nature07639.

34. 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):719–22. PMID: 16429413.

35. Koc O.N., Gerson S.L., Cooper B.W., Laughlin M., Meyerson H., Kutteh L., Fox R.M., Szekely E.M., Tainer N., Lazarus H.M. Randomized cross-over trial of progenitor-cell mobilization: high-dose cyclophosphamide plus granulocyte colony-stimulating factor (G-CSF) versus granulocytemacrophage colony-stimulating factor plus G-CSF. J Clin Oncol 2000;18(9):1824–30. doi: 10.1200/JCO.2000.18.9.1824.

36. Flomenberg N., Devine S.M., Dipersio J.F., Liesveld J.L., Rowley S.D., Vesole D.H., Badel K., Calandra G. The use of AMD3100 plus G-CSF for autologous hematopoietic progenitor cell mobilization is superior to G-CSF alone. Blood 2005;106(5):1867–74. doi: 10.1182/blood-2005-02-0468.

37. Miano M., Labopin M., Hartmann O., Angelucci E., Cornish J., Gluckman E., Locatelli F., Fischer A., Egeler R.M., Or R., Peters C., Ortega J., Veys P., Bordigoni P., Iori A.P., Niethammer D., Rocha V., Dini G.; Paediatric Diseases Working Party of the European Group for Blood and Marrow Transplantation. Haematopoietic stem cell transplantation trends in children over the last three decades: a survey by the paediatric diseases working party of the European Group for Blood and Marrow Transplantation. Bone Marrow Transplant 2007;39(2):89–99. doi: 10.1038/bmt.