Sevil SADRİ, İpek YÖNAL HİNDİLERDEN, Yaşa Gül MUTLU, Tarık Onur TİRYAKİ, Ali İhsan GEMİCİ, Huseyin Saffet BEKOZ, Ömür GÖKMEN SEVİNDİK, Fehmi HİNDİLERDEN, Sevgi KALAYOĞLU-BEŞIŞIK, Meliha NALÇACI, Deniz SARGIN

Comparison of different plerixafor-based strategies for adequate hematopoietic stem cell collection in poor mobilizers

Objectives: The main objective of the present study was to evaluate whether the use of plerixafor in combination with granulocyte colony-stimulating factor (G-CSF) or subsequent use of isolated G-CSF and then plerixafor following disease-specific chemotherapy, and whether it would allow for adequate peripheral stem cell collection in patients. Methods: The retrospective study evaluated 54 patients with previous mobilization failure who were administered plerixafor in 2 centers. In patients without any side effects, CD 34+ cell counts, the percentage of patients who were found eligible for autologous transplantation, the engraftment kinetics of the patients who underwent transplantation, and their overall survival results were compared between the two groups where G-CSF was used with plerixafor, or where plerixafor was used after isolated G-CSF following chemotherapy. Results: The median age of the patients was 49 years (range: 17-70), and 64.8% (n = 35) were males. It was identified that 31 (57.4%) patients underwent mobilization treatment with isolated G-CSF and plerixafor, and 23 (42.6%) patients underwent mobilization treatment with chemotherapy plus G-CSF and plerixafor. In all patients, mean hemoglobin level (11.3 ± 1.5 g/dL vs. 9.3 ± 1.3 g/dL; p < 0.001) and median platelet level (129.2 ×103/µL vs. 58.4 ×103/µL) were found to be higher, while febrile neutropenia rate (3.3% vs. 60.9%), the percentage of replacement patients (6.7% vs. 65.2%), and median days of G-CSF (6 vs. 9) were found to be lower on the day of plerixafor administration in the isolated G-CSF and plerixafor group compared to the chemotherapy and G-CSF and plerixafor group. Conclusions: In conclusion, our study demonstrated that administration of plerixafor is generally safe and well-tolerated. Regardless of the underlying disease, it offers an effective alternative for patients with previous failed mobilization attempts using conventional regimens, and allows stem cell collection with fewer apheresis sessions.

Keywords:

Autologous stem cell transplantation, mobilization, plerixafor,

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1. Gratwohl A, Baldomero H. Trends of hematopoietic stem cell transplantation in the third millennium. Curr Opin Hematol 2009;16: 420-6.
2. Child JA, Morgan GJ, Davies FE, Owen RG, Bell SE, Hawkins K, et al. High dose chemotherapy with hematopoietic stem cell rescue for multiple myeloma. N Engl J Med 2003;348:1875-83.
3. Villanueva ML, Vose JM. The role of hematopoietic stem cell transplantation in non-Hodgkin lymphoma. Clin Adv Hematol Oncol 2006;4:521-30.
4. Baldomero H, Grathwohl M, Gratwhol A, Tichelli A, Niederwiser D, Madrigal, A, et al. European group for blood and Marrow transplantation EBMT. The EBMT activity survey 2009:trends over the past 5 years. Bone Marrow Transplant 2011;46:485-501.
5. Wuchter P, Ran D, Bruckner T, Schmit T, Witzens-Harig M, Neben K, et al. Poor mobolization of hematopoietic stem cells-definitions, incidence, risk factors, and impact on outcome of autologous transplantation. Biol Blood Marrow Transplant 2010;16:490-9.
6. Bender JG, To LB , William S, Schwartzberg LS. Defining a therapeutic dose of peripheral blood stem cells . Hematother1992;1:329-41.
7. Passos-Coelho JL, Braine HG, Davis JM, Huelskamp AM, Schepers KG, Ohly K, et al. Predictive factors for peripheral blood progenitor cell collections using a single large volume leukopheresis after cyclophosphamide and granulocyte macrophage colony stimulating factor mobilization. J Clin Oncol 1995;13:705-14.
8. Gandhi MK, Jestice K, Scott MA, Bloxham D, Bass G, Marcus RE. The minimum CD34 threshold depends on prior chemotherapy in autologous peripheral blood stem cell recipient. Bone Marrow Transplant1999;23:9-13.
9. Montgomery M, Cottler-Fox M. Mobolization and collection autologous hematopoietic progenitor/stem cells. Clin Adv Hematol Oncol 2007;5:127-36.
10. Limat S, Woronoff-Lemsi MC, Milpied N, Chartrin I, Ifrah N, Deconinck E, et al Groupe Ouest Est d’etude des Leucemies et Autres Maladies du Sang(GOELAMS). Effect of cell cell determinant CD34+ cell dose on the cost and consequences of peripheral blood stem cell transplantation for non-Hodgkin’s lymphoma patients in front line therapy. Eur J Cancer 2000;36:2360-7.
11. Morris CL, Siegel E, Barlogie B, Cottler Fox M, Lin P, Fassas A, et al. Mobolization of CD34+ cells in eldely patients (>70 years) with multiple myeloma: influence of age, prior therapy , platelet count and mobilization regimen. Br J Haematol 2003;120:413-23.
12. Lee JL, Kim SB, Lee GW, Ryu MH, Kim EK, KİM S, et al. Collection of peripheral blood progenitor cells: analysis of factors predicting the yields. Transfus Apher Sci 2003;29:29-37.
13. Paripati H, Stewart AK, Cabou S, Dueck A, Zepeda VJ, Pirooz N, et al . Compromised stem cell moblizaiton following induction therapy with lenalidomid in myeloma. Leukemia 2008;22:1282-4.
14. Bensinger W, DiPersio JF, McCarty JM. Improving stem cell mobolization strategies: future directions. Bone Marrow Transplant 2009;43:181-95.
15. Majado MJ, Minguela A, Gonzalez-Garcia C, Salido E, Blanquer M, Funes C, et al. Large volume apheresis facilitates autologous transplantation of hematopoietic progenitors in poor mobilizer patients. J Clin Apher 2009;24:12-7.
16. Lie AK, Hui CH, Rawling T, Dyson PG, Thorp D, Benic J, et al. Granulocyte stimulating factor(G-CSF) dose dependent efficacy in peripheral blood stem cell mobolization in patients who had failed initial mobolization with chemotherapy and G-CSF. Bone Marrow Transplant 1998;22:853-7.
17. Worth N. Plerixafor –the magic bullet in stem cell moblilzation failure? Leuk Res 2011;35:701-2.
18. DiPersio JF, Stadtmauer EA, Nademanee A, Micallef INM, Stiff PJ, Kaufman JI, et al. Plerixafor and G-CSF versus placebo and G-CSF to mobolize hematopoetic stem cells for autologous stem cell transplantation in patients with multiple myeloma. Blood 2009;113:5720-6.
19. DiPersio JF, Micallef IN, Stiff PJ, Bolwell BJ, Maziarz RT, Jacobsen E, et al. Phase III prospective randomized double-blind placebo-controlled trial of plerixafor plus granulocyte colony-stimulating factor for autologous stem cell mobilization and transplantation for patients with non-Hodgkin’s lymphoma. J Clin Oncol 2009;27:4746-73.
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.
21. Hübel K, Fresen MM, Salwender H, Basara N, Beier R, Theurich S, et al. Plerixafor with and without chemotherapy in poor mobilizers: results from the German compassionate use program. Bone marrow Transplant 2011;46:1045-52.
22. Duarte RF, Shaw Be, Marin P, Kottaridis P, Ortiz M, Morante C, et al. Pleraxifor plus granulocyte CSF can mobolize hematopoetic stem cells from multiple myeloma and lymphoma patients failing previous mobolization attempts: EU compassionate use data. Bone marrow Transplant 2011;46:52-8.
23. Calandra G, McCarty J, McGuirk J, Tricot G, Crocker S-A, Badel K, et al. 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;41:331-8.
24. Tricot G, Cottler-Fox MH, Calandra G. Saftey and efficacy assesment of plerixafor to be poor moblizers, including assessment of tumor cell mobilization. Bone Marrow Transplant 2010;45:63-8.
25. Micallef IN, Stiff PJ, DiPersio JF, Maziarz RT, McCarty JM, Bridger G, et al. Successful stem cell remobilization using plerixafor(mozobil) plus granulocyte colony stimulating factor in patients with non-Hodgkin lymphoma:results from plerixafor NHL phase 3 study rescue protocol. Biol Blood Marrow Transplant 2009;15:1578-86.
26. Fowler CJ, Dunn A, Hayes-Lattin B, Hansen K, Hansen L, Lanier K, et al. Rescue from failed growht factor and/or chemotherapy HSC mobilizationwith G-CSF and plerixafor (AMD3100): an institutional experience. Bone Marrow Transplant 2009;43:909-17.
27. Dipersio JF, Stadtmatuer EA, Nademanee A, Micallef INM, Stiff PJ, Kaufman JL, et al. Plerixafor and G-CSF versus placebo and G-CSF to mobilize hematopoetic stem cells for autologous stem cell transplantation in patients with multiple myeloma. Blood 2009;113:5720-6.
28. Flomenberg N, Comenzp RL, Badel K, Calandra G. Plerixafor (Mozobil) alone to mobilize hematopoietic stem cells from multiple myeloma patients for autologous transplantation. Biol Blood Marrow Transplant 2010;16:695-700.
29. Maschan AA, Balashov DN, Kurnikova EE, Trakhtman PE, Boyakova EV, Skorobogatova EV, 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;50:1089-91.
30. Krishnan A, Bhatia S,Slovak M. L, Arber DA, Niland JC, Nademanee A, et al. Predictors of therapy-related leukemia and myelodysplasia following autologous transplantation for lymphoma: an assessment of risk factors. Blood 2000;95:1588-93.
31. Desikan KR, Barlogie B, Jagannath S, Vesole DH, Siegel D, Fassas A, et al. 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;16:1547-53.
32. Koc ON, Gerson SL, Cooper BW, L, Laughlin M, Meyerson H, Kutteh L, et al. Randomized cross-over trial of progenitor-cell mobilization: high-dose cyclophosphamide plus granulocyte colony-stimulating factor (G-CSF) versus granulocyte-macrophage colony-stimulating factor plus G-CSFJ. Clin Oncol 2000;18:1824-30.
33. Gupta S, Zhou P, Hassoun H, Kewalramani T, Reich L, Costello S, et al. Hematopoietic stem cell mobilization with intravenous melphalan and G-CSF in patients with chemoresponsive multiple myeloma: report of a phase I trial. Bone Marrow Transplant 2005;35:441-7.
34. Perea G, Sureda A, Martino R, Altes A, Martinez C, Cabezudo E, et al. Predictive factors for a successful mobilization of peripheral blood CD34+ cells in multiple myeloma. Ann Hematol 2001;80:592-7.
35. To LB, Haylock DN, Simmons PJ, Juttner CA. The biology and clinical uses of blood stem cells. Blood 1997;89:2233-58.
36. Weaver CH, Tauer K, Zhen B, Schwartzberg LS, Hazelton B, Weaver Z, et al. Second attempts at mobilization of peripheral blood stem cells in patients with initial low CD34+ cell yields. J Hematother 1998;7:241-9.
37. Desikan KR, Tricot G, Munshi NC, Anaissie E, Spoon D, Fassas A, et al. Preceding chemotherapy, tumour load and age influence engraftment in multiple myeloma patients mobilized with granulocyte colony-stimulating factor alone. Br J Haematol 2001;112:242-7.
38. Kuittinen T, Nousiainen T, Halonen P, Mahlamäki E, Jantunen E. Prediction of mobilisation failure in patients with non-Hodgkin’s lymphoma. Bone Marrow Transplant 2004;33:907-12.
39. Paripati H, Stewart AK, Cabou S, Dueck A, Zepeda VJ, Pirooz N, et al. Compromised stem cell mobilization following induction therapy with lenalidomide in myeloma. Leukemia 2008;22:1282-4.
40. Lacy MQ, Gertz MA, Dispenzieri A, Hayman SR, Geyer S, Kabat B, et al. Long-term results of response to therapy, time to progression, and survival with lenalidomide plus dexamethasone in newly diagnosed myeloma. Mayo Clin Proc 2007;82:1179-84.
41. Kumar S, Dispenzieri A, Lacy MQ, Hayman SR, Buadi FK, Gastineau DA, et al. Impact of lenalidomide therapy on stem cell mobilization and engraftment post-peripheral blood stem cell transplantation in patients with newly diagnosed myeloma. Leukemia 2007;21:2035-42.
42. Olivieri J, Attolico I, Nuccorini R, Pascale SP, Chiarucci M, Poiani M, et al. Predicting failure of hematopoietic stem cell mobilization before it starts: the predicted poor mobilizer (pPM) score. Bone Marrow Transplant 2018;53:461-73.