rhTPO combined with chemotherapy and G-CSF for autologous peripheral blood stem cells in patients with refractory/relapsed non-Hodgkin's lymphoma

Jun Zhu, Si-Guo Hao, Jiong Hu, Jing-Li Zhuang, Chun Wang, Hai-Tao Bai, Jun Zhu, Si-Guo Hao, Jiong Hu, Jing-Li Zhuang, Chun Wang, Hai-Tao Bai

Abstract

Objective: The mobilization and collection of sufficient autologous peripheral blood stem cells (APBSCs) are important for the fast and sustained reconstruction of hematopoietic function after autologous transplantation. This study aims to evaluate the mobilization effect and safety of thrombopoietin (TPO) combined with chemotherapy + G-CSF for APBSCs in patients with refractory/relapsed non-Hodgkin's lymphoma.

Methods: A total of 78 patients were included in the present study. After receiving mobilization chemotherapy, all patients were randomly divided into two groups: TPO group (n=40), patients were given subcutaneous injection of rhTPO + G-CSF, and control group (n=38), patients were given subcutaneous injection of G-CSF. The primary endpoint was the total number of obtained CD34+ cells. The secondary endpoints were the mononuclear cell count, the proportion of target and minimum mobilization, the engraftment time of neutrophils and platelets after APBSCT, the number of platelet and red blood cell infusions, the incidence of infectious fever and fever duration, and TPO-related side effects in patients.

Results: TPO participation significantly increased the total CD34+ cell count. A higher proportion of patients in the TPO group achieved the minimum and target CD34+ cells, when compared to the control group. TPO-related adverse events were not observed in either of these groups. In addition, there were no significant differences in engraftment time, the number of platelet and red blood cell transfusions, the incidence of infectious fever, and fever duration between these two groups.

Conclusion: TPO combined with chemotherapy + G-CSF can safely and effectively enhance the mobilization effect for APBSCs in patients with refractory/relapsed non-Hodgkin's lymphoma.

Keywords: mobilization; non-Hodgkin’s; recombinant human thrombopoietin.

Conflict of interest statement

The authors declare that they have no conflicts of interest in this work.

© 2019 Zhu et al.

References

    1. Zahid U, Akbar F, Amaraneni A, et al. A review of autologous stem cell transplantation in lymphoma. Curr Hematol Malig Rep. 2017;12(3):217–226. doi:10.1007/s11899-017-0382-1
    1. Sheppard D, Bredeson C, Allan D, Tay J. Systematic review of randomized controlled trials of hematopoietic stem cell mobilization strategies for autologous transplantation for hematologic malignancies. Biol Blood Marrow Transplant. 2012;18(8):1191–1203. doi:10.1016/j.bbmt.2012.01.008
    1. Moskowitz CH, Glassman JR, Wuest D, et al. Factors affecting mobilization of peripheral blood progenitor cells in patients with lymphoma. Clin Cancer Res. 1998;4(2):311–316. PMID: 9516916.
    1. Devine SM, Flomenberg N, Vesole DH, et al. Rapid mobilization of CD34+ cells following administration of the CXCR4 antagonist AMD3100 to patients with multiple myeloma and non-Hodgkin’s lymphoma. J Clin Oncol. 2004;22(6):1095–1102. doi:10.1200/JCO.2004.07.131
    1. To LB, Levesque JP, Herbert KE. How I treat patients who mobilize hematopoietic stem cells poorly. Blood. 2011;118(17):4530–4540. doi:10.1182/blood-2011-06-318220
    1. Gisselbrecht C, Glass B, Mounier N, et al. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol. 2010;28(27):4184–4190. doi:10.1200/JCO.2010.28.1618
    1. van Gorkom G, Finel H, Giebel S, et al. Prospective noninterventional study on peripheral blood stem cell mobilization in patients with relapsed lymphomas. J Clin Apher. 2017;32(5):295–301. doi:10.1002/jca.21506
    1. Kaushansky K. Thrombopoietin: understanding and manipulating platelet production. Annu Rev Med. 1997;48:1–11. doi:10.1146/annurev.med.48.1.1
    1. Linker C, Anderlini P, Herzig R, et al. Recombinant human thrombopoietin augments mobilization of peripheral blood progenitor cells for autologous transplantation. Biol Blood Marrow Transplant. 2003;9(6):405–413. PMID: 12813449.
    1. Wang G, Chen W, Wu Y, Li Y, Leng Y, Liu A. Recombinant human thrombopoietin improves the efficacy of intermediate-dose cyclophosphamide plus granulocyte colony-stimulating factor in mobilizing peripheral blood stem cells in patients with multiple myeloma: a cohort study. Medicine (Baltimore). 2017;96(50):e9302. doi:10.1097/MD.0000000000009302
    1. Somlo G, Sniecinski I, Ter Veer A, et al. Recombinant human thrombopoietin in combination with granulocyte colony-stimulating factor enhances mobilization of peripheral blood progenitor cells, increases peripheral blood platelet concentration, and accelerates hematopoietic recovery following high-dose chemotherapy. Blood. 1999;93(9):2798–2806. PMID: 10216073.
    1. Haverkos B, Geyer S, McBride A, et al. Mobilization for autologous stem cell transplantation in Hodgkin’s lymphoma (HL) and non-Hodgkin lymphoma: a single institution experience. Biol Blood Marrow Transplant. 2014;20(2):S111–S112. doi:10.1016/j.bbmt.2013.12.160
    1. Tomblyn M, Burns LJ, Blazar B, et al. Difficult stem cell mobilization despite adequate CD34+ cell dose predicts shortened progression free and overall survival after autologous HSCT for lymphoma. Bone Marrow Transplant. 2007;40(2):111–118. doi:10.1038/sj.bmt.1705708
    1. Canales M, Fernández-Jiménez MC, Martín A, et al. Identification of factors associated with poor peripheral blood progenitor cell mobilization in Hodgkin’s disease. Haematologica. 2001;86(5):494–498. PMID: 11410412.
    1. Yoon DH, Sohn BS, Jang G, et al. Higher infused CD34+ hematopoietic stem cell dose correlates with earlier lymphocyte recovery and better clinical outcome after autologous stem cell transplantation in non-Hodgkin’s lymphoma. Transfusion. 2009;49(9):1890–1900. doi:10.1111/j.1537-2995.2009.02202.x
    1. Ataca Atilla P, Bakanay Ozturk SM, Demirer T. How to manage poor mobilizers for high dose chemotherapy and autologous stem cell transplantation? Transfus Apher Sci. 2017;56(2):190–198. doi:10.1016/j.transci.2016.11.005
    1. Herbert KE, Levesque JP, Mills AK, et al. How we mobilize haemopoietic stem cells. Intern Med J. 2011;41(8):588–594. doi:10.1111/j.1445-5994.2011.02544.x
    1. Bensinger W, DiPersio JF, McCarty JM. Improving stem cell mobilization strategies: future directions. Bone Marrow Transplant. 2009;43(3):181–195. doi:10.1038/bmt.2008.410
    1. Jantunen E, Varmavuo V, Valtola J. Plerixafor injection: a hematopoietic stem cell mobilizer in non-Hodgkin lymphoma and multiple myeloma. Expert Rev Hematol. 2016;9(8):723–732. doi:10.1080/17474086.2016.1208082
    1. Salvino MA, Ruiz J. Hematopoietic progenitor cell mobilization for autologous transplantation-a literature review. Rev Bras Hematol Hemoter. 2016;38(1):28–36. doi:10.1016/j.bjhh.2015.07.011
    1. Bilgin YM, de Greef GE. Plerixafor for stem cell mobilization: the current status. Curr Opin Hematol. 2016;23(1):67–71. doi:10.1097/MOH.0000000000000200
    1. Wagemaker G, Hartong SC, Neelis KJ, Egeland T, Wognum AW. In vivo expansion of hemopoietic stem cells. Stem Cells. 1998;16:185–191. doi:10.1002/stem.5530160822
    1. Wagemaker G, Neelis KJ, Hartong SC, et al. The efficacy of recombinant thrombopoietin in murine and nonhuman primate models for radiation-induced myelosuppression and stem cell transplantation. Stem Cells. 1998;16(6):375–386. doi:10.1002/stem.160375

Source: PubMed

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