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A systematic review and meta-analysis of rituximab-based immunochemotherapy for subtypes of diffuse large B cell lymphoma

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Abstract

Addition of rituximab to chemotherapy (R-chemo) has been shown to improve overall survival (OS) in patients with diffuse large B cell lymphoma (DLBCL). Germinal center B cell-like (GCB) subtype of DLBCL has a significantly better clinical outcome than those with non-germinal center B cell-like (non-GCB) subtype. Further research is needed to confirm this difference between those two subtypes treated with R-chemo. We searched for randomized controlled trials that compared R-chemo with identical chemotherapy alone in patients with newly diagnosed or relapsed DLBCL. A random versus fixed effects model was selected according to heterogeneity. Six eligible trials involving 748 adult patients were included in this meta-analysis. Fixed-effects analysis showed OS to be superior for the GCB patients treated with R-chemo (relative risk (RR) = 1.16, 95% confidence interval (CI) = 1.03–1.31, P = 0.02). Superiority was also observed for the GCB subtype under R-chemo with respect to disease control (RR = 1.16, 95% CI = 0.99–1.36) and overall response (RR = 1.19, 95% CI = 0.99–1.99). Both subtypes showed an increased OS (RR = 1.30, 95% CI = 1.11–1.51; RR = 1.89, 95% CI = 1.52–2.35, respectively) and disease control rate (RR = 1.27, 95% CI = 1.05–1.54, P = 0.01; RR = 2.21, 95% CI = 1.68–2.90, respectively) following R-chemo. Therefore, treated with R-chemo, GCB patients still has a significantly better clinical outcome than those with non-GCB subtype.

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References

  1. Morton LM, Wang SS, Devesa SS, Hartge P, Weisenburger DD, Linet MS (2006) Lymphoma incidence patterns by WHO subtype in the United States, 1992–2001. Blood 107:265–276

    Article  CAS  PubMed  Google Scholar 

  2. Anonymous (1997) A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin's lymphoma. The Non-Hodgkin's Lymphoma Classification Project. Blood 89:3909–3918

  3. Coiffier B (2001) Diffuse large cell lymphoma. Curr Opin Oncol 13:325–334

    Article  CAS  PubMed  Google Scholar 

  4. Coiffier B (2007) Rituximab therapy in malignant lymphoma. Oncogene 26:3603–3613

    Article  CAS  PubMed  Google Scholar 

  5. Alizadeh AA, Eisen MB, Davis RE et al (2000) Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature 403:503–511

    Article  CAS  PubMed  Google Scholar 

  6. Hans CP, Weisenburger DD, Greiner TC et al (2004) Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood 103:275–282

    Article  CAS  PubMed  Google Scholar 

  7. Gao G, Liang X, Jiang J et al (2009) A systematic review and meta-analysis of immunochemotherapy with rituximab for B-cell non-Hodgkin's lymphoma. Acta Oncol 49:1–11

    Article  CAS  Google Scholar 

  8. Lenz G, Wright G, Dave S et al (2007) Gene expression signatures predict overall survial in diffuse large B cell lymphoma treated with rituximab and chop-like chemotherapy. Blood 110:209a, ASH Annual Meeting Abstracts 348

    Google Scholar 

  9. Xia Y, Li ZM, Shi YX, Xia ZJ, Jiang WQ, Huang HQ (2009) Short-term efficacy of rituximab-CHOP and CHOP regimens on two subtypes of diffuse large B-cell lymphoma. Chin J Cancer 28:146–149

    Google Scholar 

  10. Wilson WH, Dunleavy K, Pittaluga S et al (2008) Phase II study of dose-adjusted EPOCH and rituximab in untreated diffuse large B-cell lymphoma with analysis of germinal center and post-germinal center biomarkers. J Clin Oncol 26:2717–2724

    Article  CAS  PubMed  Google Scholar 

  11. Xia ZG, Xu ZZ, Zhao WL et al (2010) The prognostic value of immunohistochemical subtyping in Chinese patients with de novo diffuse large B-cell lymphoma undergoing CHOP or R-CHOP treatment. Ann Hematol 89:171–177

    Article  CAS  PubMed  Google Scholar 

  12. Nyman H, Adde M, Karjalainen-Lindsberg ML et al (2007) Prognostic impact of immunohistochemically defined germinal center phenotype in diffuse large B-cell lymphoma patients treated with immunochemotherapy. Blood 109:4930–4935

    Article  CAS  PubMed  Google Scholar 

  13. Falagas ME, Matthaiou DK, Bliziotis IA (2006) The role of aminoglycosides in combination with a beta-lactam for the treatment of bacterial endocarditis: a meta-analysis of comparative trials. J Antimicrob Chemother 57:639–647

    Article  CAS  PubMed  Google Scholar 

  14. Cheson BD, Pfistner B, Juweid ME et al (2007) Revised response criteria for malignant lymphoma. J Clin Oncol 25:579–586

    Article  PubMed  Google Scholar 

  15. Saito B, Shiozawa E, Usui T et al (2007) Rituximab with chemotherapy improves survival of non-germinal center type untreated diffuse large B-cell lymphoma. Leukemia 21:2563–2566

    Article  CAS  PubMed  Google Scholar 

  16. Fu K, Weisenburger DD, Choi WWL et al (2008) Addition of rituximab to standard chemotherapy improves the survival of both the germinal center B-cell-like and non-germinal center B-cell-like subtypes of diffuse large B-cell lymphoma. J Clin Oncol 26:4587–4594

    Article  CAS  PubMed  Google Scholar 

  17. Rosenwald A, Wright G, Chan WC et al (2002) The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N Engl J Med 346:1937–1947

    Article  PubMed  Google Scholar 

  18. Cheson BD (2006) Monoclonal antibody therapy for B-cell malignancies. Semin Oncol 33:S2–S14

    Article  CAS  PubMed  Google Scholar 

  19. Stolz C, Schuler M (2009) Molecular mechanisms of resistance to rituximab and pharmacologic strategies for its circumvention. Leuk Lymphoma 50:873–885

    Article  CAS  PubMed  Google Scholar 

  20. Hilchey SP, Hyrien O, Mosmann TR et al (2009) Rituximab immunotherapy results in the induction of a lymphoma idiotype-specific T-cell response in patients with follicular lymphoma: support for a “vaccinal effect” of rituximab. Blood 113:3809–3812

    Article  CAS  PubMed  Google Scholar 

  21. Jazirehi AR, Huerta-Yepez S, Cheng G, Bonavida B (2005) Rituximab (chimeric anti-CD20 monoclonal antibody) inhibits the constitutive nuclear factor-{kappa}B signaling pathway in non-Hodgkin's lymphoma B-cell lines: role in sensitization to chemotherapeutic drug-induced apoptosis. Cancer Res 65:264–276

    CAS  PubMed  Google Scholar 

  22. Davis RE, Brown KD, Siebenlist U, Staudt LM (2001) Constitutive nuclear factor kappaB activity is required for survival of activated B cell-like diffuse large B cell lymphoma cells. J Exp Med 194:1861–1874

    Article  CAS  PubMed  Google Scholar 

  23. Iqbal J, Neppalli VT, Wright G et al (2006) BCL2 expression is a prognostic marker for the activated B-cell-like type of diffuse large B-cell lymphoma. J Clin Oncol 24:961–968

    Article  CAS  PubMed  Google Scholar 

  24. He L, Thomson J, Hemann M et al (2005) A microRNA polycistron as a potential human oncogene. Nature 435:828–833

    Article  CAS  PubMed  Google Scholar 

  25. Chen CZ (2005) MicroRNAs as oncogenes and tumor suppressors. N Engl J Med 353:1768–1771

    Article  CAS  PubMed  Google Scholar 

  26. Lawrie CH, Soneji S, Marafioti T et al (2007) MicroRNA expression distinguishes between germinal center B cell-like and activated B cell-like subtypes of diffuse large B cell lymphoma. Int J Cancer 121:1156–1161

    Article  CAS  PubMed  Google Scholar 

  27. Lawrie CH, Gal S, Dunlop HM et al (2008) Detection of elevated levels of tumour-associated microRNAs in serum of patients with diffuse large B-cell lymphoma. Br J Haematol 141:672–675

    Article  PubMed  Google Scholar 

  28. Lawrie CH, Chi J, Taylor S et al (2009) Expression of microRNAs in diffuse large B cell lymphoma is associated with immunophenotype, survival and transformation from follicular lymphoma. J Cell Mol Med 13:1248–1260

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This study was supported by National Natural Science Foundation of China (30871104, 30971296, 30971295).

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Authors and Affiliations

  1. Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, 210029, China

    Cheng Fang, Wei Xu & Jian-Yong Li

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  1. Cheng Fang
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  2. Wei Xu
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Correspondence to Wei Xu.

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Fang, C., Xu, W. & Li, JY. A systematic review and meta-analysis of rituximab-based immunochemotherapy for subtypes of diffuse large B cell lymphoma. Ann Hematol 89, 1107–1113 (2010). https://doi.org/10.1007/s00277-010-0990-5

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  • DOI: https://doi.org/10.1007/s00277-010-0990-5

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