A novel preemptive approach to plerixafor use in mobilization failure

Abstract

Objective: Plerixafor is a highly effective mobilization agent in cases of mobilization failure. We aimed to clarify whether early administration of plerixafor after stem cell collection failure results in outcomes similar to those achieved with later administration. Patients and Methods: Sixty-six autologous stem cell transplantation patients who received plerixafor for mobilization failure were included in the study. Patients were divided into two groups; patients receiving early plerixafor [receiving granulocyte-colony stimulation factor (G-CSF) for 2 or 3 days] and standard plerixafor (receiving G-CSF for 4 days). Both groups were evaluated in terms of neutrophil and platelet engraftment time, CD34 stem cell levels, and side effects. Results: There was no significant difference between the two groups—early plerixafor and standard plerixafor—in terms of neutrophil and platelet engraftment times, CD34⁺ stem cell counts, and adverse effects (CD34/p = 0.201; neutrophil/p = 0.415; platelet/p = 0.077; adverse effects/p = 0.439). No differences were observed between the groups regarding age, gender, transplant type, plerixafor preparation, adverse effects, or transplant conditioning regimen. Additionally, there was no difference in transplant conditioning regimen between surviving and deceased patients. Conclusion: While the use of G-CSF alone is routine in stem cell mobilization, the addition of plerixafor is preferred in cases of mobilization failure. Although chemotherapy-based mobilization is included in mobilization schemes, its use is very limited today. It was concluded that plerixafor is a highly effective agent for mobilization, can be used safely in cases of failure in stem cell collection, and that its early use in patients with insufficient reserve may be more cost-effective.

Keywords

• Autologous stem cell transplantation
• Mobilization
• Plerixafor

References

1. Morrison SJ, Uchida N, Weissman IL. The biology of hematopoietic stem cells. Annu Rev Cell Dev Biol 1995;11:35- 71. doi: 10.1146/annurev.cb.11.110.195.000343.
2. Saad A, Loren A, Bolaños-Meade J, et al. NCCN guidelines® insights: hematopoietic cell transplantation, version 3.2022. J Natl Compr Canc Netw 2023;21:108-15. doi: 10.6004/ jnccn.2023.0007.
3. de Kruijf EFM, Fibbe WE, van Pel M. Cytokine-induced hematopoietic stem and progenitor cell mobilization: unraveling interactions between stem cells and their niche. Ann N Y Acad Sci 2020;1466:24-38. doi: 10.1111/nyas.14059.
4. Miyazaki K, Suzuki K. Poor mobilizer and its countermeasures. Transfus Apher Sci 2018 ;57:623-7. doi: 10.1016/j. transci.2018.09.007.
5. Duong HK, Savani BN, Copelan E, et al. Peripheral blood progenitor cell mobilization for autologous and allogeneic hematopoietic cell transplantation: guidelines from the American Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant 2014 ;20:1262-73. doi: 10.1016/j. bbmt.2014.05.003.
6. Altuntaş F, Korkmaz S. Hematopoietic progenitor cell mobilization. Transfus Apher Sci 2017;56:787. doi: 10.1016/j. transci.2017.11.024.
7. Fadini GP, Ciciliot S and Albiero M. Concise review: perspectives and clinical implications of bone marrow and circulating stem cell defects in diabetes. Stem Cells 2017;35: 106-16. doi: 10.1002/stem.2445.
8. Pidala J, Anasetti C, Kharfan-Dabaja MA, et al. Decision analysis of peripheral blood versus bone marrow hematopoietic stem cells for allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant 2009;15:1415- 21. doi: 10.1016/j.bbmt.2009.07.009.

9. Majolino I, Pearce R, Taghipour G, Goldstone AH. Peripheralblood stem-cell transplantation versus autologous bone marrow transplantation in Hodgkin’s and non-Hodgkin’s lymphomas: a new matched-pair analysis of the European Group for Blood and Marrow Transplantation Registry Data. Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. J Clin Oncol 1997;15:509-17. doi: 10.1200/JCO.1997.15.2.509.
10. Remberger M, Ringdén O. Similar outcome after unrelated allogeneic peripheral blood stem cell transplantation compared with bone marrow in children and adolescents. Transplantation 2007;84:551-4. doi: 10.1097/01.tp.000027.5184.41831.6d.
11. Gertz MA. Current status of stem cell mobilization. Br J Haematol 2010;150:647-62. doi: 10.1111/j.1365- 2141.2010.08313.x.
12. Pelus LM, Fukuda S. Chemokine-mobilized adult stem cells; defining a better hematopoietic graft. Leukemia 2008;22:466- 73. doi: 10.1038/sj.leu.2405021.
13. Pusic I, Jiang SY, Landua S, et al. Impact of mobilization and remobilization strategies on achieving sufficient stem cell yields for autologous transplantation. Biol Blood Marrow Transplant 2008;14:1045-56. doi: 10.1016/j.bbmt.2008.07.004.
14. Micallef IN, Stiff PJ, Nademanee AP, et al. Plerixafor plus granulocyte colony-stimulating factor for patients with non- Hodgkin lymphoma and multiple myeloma: long-term follow-up report. Biol Blood Marrow Transplant 2018;24:1187- 95. doi: 10.1016/j.bbmt.2018.01.039.
15. Crees ZD, Rettig MP, Jayasinghe RG, et al. Motixafortide and G-CSF to mobilize hematopoietic stem cells for autologous transplantation in multiple myeloma: a randomized phase 3 trial. Nat Med 2023; 29:869-79. ddoi: 10.1038/s41591-023- 02273-z.
16. Gertz MA, Kumar SK, Lacy MQ, et al. Comparison of highdose CY and growth factor with growth factor alone for mobilization of stem cells for transplantation in patients with multiple myeloma. Bone Marrow Transplant 2009;43:619-25. doi: 10.1038/bmt.2008.369. Epub 2008 Nov 10.
17. Shpall EJ, Wheeler CA, Turner SA, et al. A randomized phase 3 study of peripheral blood progenitor cell mobilization with stem cell factor and filgrastim in high-risk breast cancer patients. Blood 1999; 15;93:2491-501.
18. Cohen J. Statistical Power Analysis for the Nehavioral Sciences. Canbridge: Academic Pres, 2013.
19. De Clercq E. Mozobil® (Plerixafor, AMD3100), 10 years after its approval by the US Food and Drug Administration. Antivir Chem Chemother 2019;27:204.020.6619829382. doi: 10.1177/2040206619829382.
20. Lanza F, Gardellini A, Laszlo D, Martino M. Plerixafor: what we still have to learn. Expert Opin Biol Ther 2015;15:143-7. doi: 10.1517/14712598.2015.971750.
21. Pierelli L, Perseghin P. Plerixafor (Mozobil) and other mobilizing agents. Transfus Apher Sci 2013;48:133-5.
22. antunen E, Lemoli RM. Preemptive use of plerixafor in difficultto- mobilize patients: an emerging concept. Transfusion 2012;52:906-14. doi: 10.1111/j.1537-2995.2011.03349.x.
23. Stewart DA, Smith C, MacFarland R, Calandra G. Pharmacokinetics and pharmacodynamics of plerixafor in patients with non-Hodgkin lymphoma and multiple myeloma. Biol Blood Marrow Transplant 2009;15:39-46. doi: 10.1016/j. bbmt.2008.10.018.
24. Romon I, Castillo C, Cid J, Lozano M. Use of plerixafor to mobilize haematopoietic progenitor cells in healthy donors. Vox Sang 2022;117:6-16. doi: 10.1111/vox.13175.