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Standard chemotherapy is superior to high-dose chemotherapy with autologous stem cell transplantation on overall survival as the first-line therapy for patients with aggressive non-Hodgkin lymphoma: a meta-analysis

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Abstract

Randomized controlled trials (RCTs) have reported conflicting results on the impact of high-dose chemotherapy with autologous hematopoietic stem cell transplantation (HDCT) as the first-line treatment for patients with aggressive non-Hodgkin lymphoma (NHL). We performed a systematic meta-analysis to assess the efficacy of HDCT compared to conventional chemotherapy in patients with aggressive NHL with regard to overall survival (OS) at 3 years. We gathered the data for our analysis from MEDLINE, EMBASE, Cochrane controlled trials register, Cochrane Library, and Science Citation Index (1/1990 to 11/2008) searches. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using the random effect model. Fourteen RCTs were identified that were published in full text and included a total of 2,413 patients. There was evidence that HDCT showed decreased OS (HR 1.20, 95% CI 1.05–1.37, P = 0.006) at 3 years when compared with conventional chemotherapy. The variation in OS probabilities between studies was not statistically significant (test for heterogeneity, Q = 10.14, df = 13, P = 0.683). Thus, our meta-analysis showed that HDCT in aggressive non-Hodgkin lymphoma had decreased overall survival outcome compared with conventional chemotherapy.

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References

  1. Villanueva ML, Vose JM. The role of haematopoietic stem cell transplantation in non-Hodgkin lymphoma. Clin Adv Hematol Oncol. 2006;4:521–30.

    PubMed  Google Scholar 

  2. Kim SW, Tanimoto TE, Hirabayashi N, et al. Myeloablative allogeneic haematopoietic stem cell transplantation for non-Hodgkin lymphoma: a nationwide survey in Japan. Blood. 2006;108:382–9.

    Article  PubMed  CAS  Google Scholar 

  3. Philip T, Guglielmi C, Hagenbeek A, et al. Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin’s lymphoma. N Engl J Med. 1995;333(23):1540–5.

    Article  PubMed  CAS  Google Scholar 

  4. Greb A, Bohlius J, Trelle S, et al. High-dose chemotherapy with autologous stem cell support in first-line treatment of aggressive non-Hodgkin lymphoma–Results of a comprehensive meta-analysis. Cancer Treat Rev. 2007;33:338–46.

    Article  PubMed  CAS  Google Scholar 

  5. Peter JV, John P, Graham PL, et al. Corticosteroids in the prevention and treatment of acute respiratory distress syndrome (ARDS) in adults: meta-analysis. BMJ. 2008;336:1006–9.

    Article  PubMed  Google Scholar 

  6. Parmar MK, Torri V, Stewart L. Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Stat Med. 1998;17:2815–34.

    Article  PubMed  CAS  Google Scholar 

  7. Berlin JA, Laird NM, Sacks HS, et al. A comparison of statistical methods for combining event rates from clinical trials. Stat Med. 1989;8:141–51.

    Article  PubMed  CAS  Google Scholar 

  8. Linch D, Yung L, Smith P, et al. A randomised trial of CHOP × 6–8 vs HOP × 3 + BEAM + ASCT in 457 patients with poor prognosis histologically aggressive non-Hodgkins lymphoma. Ann Oncol. 2002;13:28.

    Google Scholar 

  9. De Souza C, Baldissera R, Simoes B, et al. Unselected High-Risk IPI NHL presented a high early mortality rate in a prospective randomized study comparing conventional chemotherapy and high-dose escalation followed by autologous bone marrow transplantation. Blood. 2001;98:391B.

    Google Scholar 

  10. Rodriguez MA, van Besien K, Hagemeister FB, et al. Randomized comparison of frontline alternating chemotherapy (ATT) versus brief induction followed by autologous stem cell transplantation (ASCT) for aggressive lymphomas. Blood. 2003;102:402A.

    Article  Google Scholar 

  11. Santini G, Olivieri A, Congiu M, et al. VACOP-B vs VACOP-B High-dose sequential therapy (HDS) for aggressive non-Hodgkin’s lymphoma (NHL). Final analysis of the NHLCSG. ASCO Annual Meeting; 2003.

  12. Milpied N, Deconinck E, Gaillard F, et al. Initial treatment of aggressive lymphoma with high-dose chemotherapy and autologous stem-cell support. N Engl J Med. 2004;350(13):1287–95.

    Article  PubMed  CAS  Google Scholar 

  13. Gianni AM, Bregni M, Siena S, et al. High-dose chemotherapy and autologous bone marrow transplantation compared with MACOP-B in aggressive B-cell lymphoma. N Engl J Med. 1997;336:1290–7.

    Article  PubMed  CAS  Google Scholar 

  14. Gisselbrecht C, Lepage E, Molina T, et al. Shortened first-line high-dose chemotherapy for patients with poor-prognosis aggressive lymphoma. J Clin Oncol. 2002;20:2472–9.

    Article  PubMed  CAS  Google Scholar 

  15. Haioun C, Lepage E, Gisselbrecht C, et al. Comparison of autologous bone marrow transplantation with sequential chemotherapy for intermediate-grade and high-grade non-Hodgkin’s lymphoma in first complete remission: a study of 464 patients. Groupe d’Etude des Lymphomes de l’Adulte. J Clin Oncol. 1994;12:2543–51.

    PubMed  CAS  Google Scholar 

  16. Intragumtornchai T, Prayoonwiwat W, Numbenjapon T, et al. CHOP versus CHOP plus ESHAP and high-dose therapy with autologous peripheral blood progenitor cell transplantation for high-intermediate-risk and high-risk aggressive non-Hodgkin’s lymphoma. Clin Lymphoma. 2000;1:219–25.

    Article  PubMed  CAS  Google Scholar 

  17. Kaiser U, Uebelacker I, Abel U, et al. Randomized study to evaluate the use of high-dose therapy as part of primary treatment for “aggressive” lymphoma. J Clin Oncol. 2002;20:4413–9.

    Article  PubMed  CAS  Google Scholar 

  18. Kluin-Nelemans HC, Zagonel V, Anastasopoulou A, et al. Standard chemotherapy with or without high-dose chemotherapy for aggressive non-Hodgkin’s lymphoma: randomized phase III EORTC study. J Natl Cancer Inst. 2001;93:22–30.

    Article  PubMed  CAS  Google Scholar 

  19. Martelli M, Vignetti M, Zinzani PL, et al. High-dose chemotherapy followed by autologous bone marrow transplantation versus dexamethasone, cisplatin, and cytarabine in aggressive non-Hodgkin’s lymphoma with partial response to front-line chemotherapy: a prospective randomized italian multicenter study. J Clin Oncol. 1996;14:534–42.

    PubMed  CAS  Google Scholar 

  20. Martelli M, Gherlinzoni F, De Renzo A, et al. Early autologous stem-cell transplantation versus conventional chemotherapy as front-line therapy in high-risk, aggressive non-Hodgkin’s lymphoma: an Italian multicenter randomized trial. J Clin Oncol. 2003;21:1255–62.

    Article  PubMed  Google Scholar 

  21. Santini G, Salvagno L, Leoni P, et al. VACOP-B versus VACOP-B plus autologous bone marrow transplantation for advanced diffuse non-Hodgkin’s lymphoma: results of a prospective randomized trial by the non-Hodgkin’s Lymphoma Cooperative Study Group. J Clin Oncol. 1998;16:2796–802.

    PubMed  CAS  Google Scholar 

  22. Verdonck LF, van Putten WL, Hagenbeek A, et al. Comparison of CHOP chemotherapy with autologous bone marrow transplantation for slowly responding patients with aggressive non-Hodgkin’s lymphoma. N Engl J Med. 1995;332:1045–51.

    Article  PubMed  CAS  Google Scholar 

  23. Baldissera RC, Nucci M, Vigorito AC, et al. Frontline therapy with early intensification and autologous stem cell transplantation versus conventional chemotherapy in unselected high-risk, aggressive non-Hodgkin’s lymphoma patients: a prospective randomized GEMOH report. Acta Haematol. 2006;115:15–21.

    Article  PubMed  CAS  Google Scholar 

  24. Betticher DC, Martinelli G, Radford JA, et al. Sequential high dose chemotherapy as initial treatment for aggressive sub-types of non-Hodgkin lymphoma: results of the international randomized phase III trial (MISTRAL). Ann Oncol. 2006;17:1546–52.

    Article  PubMed  CAS  Google Scholar 

  25. Olivieri A, Santini G, Patti C, et al. Upfront high-dose sequential therapy (HDS) versus VACOP-B with or without HDS in aggressive non-Hodgkin’s lymphoma: long-term results by the NHLCSG. Ann Onco. 2005;l16:1941–8.

    Article  Google Scholar 

  26. Vitolo U, Liberati AM, Cabras MG, et al. High dose sequential chemotherapy with autologous transplantation versus dose-dense chemotherapy MegaCEOP as first line treatment in poor-prognosis diffuse large cell lymphoma: an “Intergruppo Italiano Linfomi” randomized trial. Haematologica. 2005;90:793–801.

    PubMed  CAS  Google Scholar 

  27. Freedman AS, Takvorian T, Neuberg D, et al. Autologous bone marrow transplantation in poor-prognosis intermediate-grade and high-grade B-cell non-Hodgkin’s lymphoma in first remission: a pilot study. J Clin Oncol. 1993;11:931–6.

    PubMed  CAS  Google Scholar 

  28. Nademanee A, Molina A, O’Donnell MR, et al. Results of highdose therapy and autologous bone marrow/stem cell transplantation during remission in poor-risk intermediate- and high-grade lymphoma: international index high and high-intermediate risk group. Blood. 1997;90:3844–52.

    PubMed  CAS  Google Scholar 

  29. Fanin R, Silvestri F, Geromin A. Autologous stem cell transplantation for aggressive non-Hodgkin’s lymphomas in first complete or partial remission: a retrospective analysis of the outcome of 52 patients according to the age-adjusted International Prognostic Index. Bone Marrow Transpl. 1998;21:263–71.

    Article  CAS  Google Scholar 

  30. Cortelazzo S, Rossi A, Bellavita P, et al. Clinical outcome after autologous transplantation in non-Hodgkin’s lymphoma patients with high international prognostic index (IPI). Ann Oncol. 1999;10:427–32.

    Article  PubMed  CAS  Google Scholar 

  31. Strehi J, Mey U, Glasmacher A, et al. High-dose chemotherapy followed by autologous stem cell transplantation as first-line therapy in aggressive non-Hodgkin’s lymphoma: a meta-analysis. Haematologica. 2003;88:1304–15.

    Google Scholar 

  32. Wheatley K. Current controversies: which patients with acute myeloid leukaemia should receive a bone marrow transplantation?–a statistician’s view. Br J Haematol. 2002;118:351–6.

    Article  PubMed  Google Scholar 

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Conflict of Interest

We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service, and company that could be construed as influencing the position presented in, or the review of, the manuscript.

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Correspondence to Jian Ouyang.

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Wang, J., Zhan, P., Ouyang, J. et al. Standard chemotherapy is superior to high-dose chemotherapy with autologous stem cell transplantation on overall survival as the first-line therapy for patients with aggressive non-Hodgkin lymphoma: a meta-analysis. Med Oncol 28, 822–828 (2011). https://doi.org/10.1007/s12032-010-9517-0

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