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Autografting

Etoposide plus G-CSF priming compared with G-CSF alone in patients with lymphoma improves mobilization without an increased risk of secondary myelodysplasia and leukemia

Abstract

The use of etoposide (VP-16) for stem cell mobilization has been reported as a significant risk factor for the development of therapy-related myelodysplasia/therapy-related AML (tMDS/tAML) after transplantation. We compared the safety and effectiveness of VP-16+G-CSF (VP+G) to G-CSF alone for PBPC mobilization in patients with non-Hodgkin's lymphoma and Hodgkin's lymphoma who underwent autologous transplantation at the Cleveland Clinic and Ohio State University. In the VP+G group, median total CD34+ cells collected were 9.34 × 106 per kg (range 0.97–180.89), with 42% of all patients having adequate (2 × 106 cells per kg) CD 34+ collection after 2 days of apheresis compared with a median in the G-CSF group of 3.83 × 106 per kg (range, 0.72–50.38), with only 16% patients having adequate collection after 2 days (P<0.001). tMDS/tAML occurred in 15 patients (2.3%) in the VP+G and in 12 patients (3.8%) receiving G-CSF alone. (P=0.62). Increased number of days of apheresis was associated with the risk of tMDS/tAML (hazard ratio (HR) 1.19, 95% confidence interval (CI) 1.08–1.30, P<0.001). Priming regimen was not a significant variable for relapse-free survival or OS. The addition of etoposide significantly improves the effectiveness of mobilization at the cost of an increased incidence of neutropenic fever though with no mortalities. There is no evidence of increased incidence of tMDS/tAML in patients receiving VP+G compared with those mobilized with G-CSF alone.

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References

  1. Shipp MA, Abeloff MD, Antman KH, Carroll G, Hagenbeek A, Loeffler M et al. International Consensus Conference on High-Dose Therapy with Hematopoietic Stem Cell Transplantation in Aggressive Non-Hodgkin's Lymphomas: report of the jury. J Clin Oncol 1999; 17: 423–429.

    Article  CAS  PubMed  Google Scholar 

  2. Majhail NS, Weisdorf DJ, Defor TE, Miller JS, McGlave PB, Slungaard A et al. Long-term results of autologous stem cell transplantation for primary refractory or relapsed Hodgkin's lymphoma. Biol Blood Marrow Transplant 2006; 12: 1065–1072.

    Article  PubMed  Google Scholar 

  3. Wadehra N, Farag S, Bolwell B, Elder P, Penza S, Kalaycio M et al. Long-term outcome of Hodgkin disease patients following high-dose busulfan, etoposide, cyclophosphamide, and autologous stem cell transplantation. Biol Blood Marrow Transplant 2006; 12: 1343–1349.

    Article  CAS  PubMed  Google Scholar 

  4. Copelan EA, Ceselski SK, Ezzone SA, Lasky LC, Penza SL, Bechtel TP et al. Mobilization of peripheral-blood progenitor cells with high-dose etoposide and granulocyte colony-stimulating factor in patients with breast cancer, non-Hodgkin's lymphoma, and Hodgkin's disease. J Clin Oncol 1997; 15: 759–765.

    Article  CAS  PubMed  Google Scholar 

  5. Krishnan A, Bhatia S, Slovak ML, 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: 1588–1593.

    CAS  PubMed  Google Scholar 

  6. Metayer C, Curtis RE, Vose J, Sobocinski KA, Horowitz MM, Bhatia S et al. Myelodysplastic syndrome and acute myeloid leukemia after autotransplantation for lymphoma: a multicenter case-control study. Blood 2003; 101: 2015–2023.

    Article  CAS  PubMed  Google Scholar 

  7. Micallef IN, Lillington DM, Apostolidis J, Amess JA, Neat M, Matthews J et al. Therapy-related myelodysplasia and secondary acute myelogenous leukemia after high-dose therapy with autologous hematopoietic progenitor-cell support for lymphoid malignancies. J Clin Oncol 2000; 18: 947–955.

    Article  CAS  PubMed  Google Scholar 

  8. Darrington DL, Vose JM, Anderson JR, Bierman PJ, Bishop MR, Chan WC et al. Incidence and characterization of secondary myelodysplastic syndrome and acute myelogenous leukemia following high-dose chemoradiotherapy and autologous stem-cell transplantation for lymphoid malignancies. J Clin Oncol 1994; 12: 2527–2534.

    Article  CAS  PubMed  Google Scholar 

  9. Hosing C, Munsell M, Yazji S, Andersson B, Couriel D, de Lima M et al. Risk of therapy-related myelodysplastic syndrome/acute leukemia following high-dose therapy and autologous bone marrow transplantation for non-Hodgkin's lymphoma. Ann Oncol 2002; 13: 450–459.

    Article  CAS  PubMed  Google Scholar 

  10. Stone RM, Neuberg D, Soiffer R, Takvorian T, Whelan M, Rabinowe SN et al. Myelodysplastic syndrome as a late complication following autologous bone marrow transplantation for non-Hodgkin's lymphoma. J Clin Oncol 1994; 12: 2535–2542.

    Article  CAS  PubMed  Google Scholar 

  11. Copelan E, Hoshaw-Woodard S, Elder P, Penza S, Farag S, Marcucci G et al. Therapy-related myelodysplasia and leukemia occur infrequently following VP-16 priming and autotransplantation without total body irradiation. Bone Marrow Transplant 2004; 34: 85–87.

    Article  CAS  PubMed  Google Scholar 

  12. Thirman MJ, Larson RA . Therapy-related myeloid leukemia. Hematol Oncol Clin North Am 1996; 10: 293–320.

    Article  CAS  PubMed  Google Scholar 

  13. Kalaycio M, Rybicki L, Pohlman B, Sobecks R, Andresen S, Kuczkowski E et al. Risk factors before autologous stem-cell transplantation for lymphoma predict for secondary myelodysplasia and acute myelogenous leukemia. J Clin Oncol 2006; 24: 3604–3610.

    Article  PubMed  Google Scholar 

  14. Gordan LN, Sugrue MW, Lynch JW, Williams KD, Khan SA, Wingard JR et al. Poor mobilization of peripheral blood stem cells is a risk factor for worse outcome in lymphoma patients undergoing autologous stem cell transplantation. Leuk Lymphoma 2003; 44: 815–820.

    Article  CAS  PubMed  Google Scholar 

  15. Bolwell BJ, Pohlman B, Rybicki L, Sobecks R, Dean R, Curtis J et al. Patients mobilizing large numbers of CD34+ cells (‘super mobilizers’) have improved survival in autologous stem cell transplantation for lymphoid malignancies. Bone Marrow Transplant 2007; 40: 437–441.

    Article  CAS  PubMed  Google Scholar 

  16. Yoon DH, Sohn BS, Jang G, Kim EK, Kang BW, Kim C 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: 1890–1900.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to A Mahindra.

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Mahindra, A., Bolwell, B., Rybicki, L. et al. Etoposide plus G-CSF priming compared with G-CSF alone in patients with lymphoma improves mobilization without an increased risk of secondary myelodysplasia and leukemia. Bone Marrow Transplant 47, 231–235 (2012). https://doi.org/10.1038/bmt.2011.73

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