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Clinical importance of Bcl-6-positive non-deep-site involvement in non-HIV-related primary central nervous system diffuse large B-cell lymphoma

  • Clinical Study – Patient Study
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

An Erratum to this article was published on 26 March 2011

Abstract

In several studies of primary central nervous system lymphoma (PCNSL), deep-site involvement of the brain, as well as age and performance status (PS), were found to be independent prognostic factors. In immunocompetent patients, most primary central nervous system lymphomas (PCNSL) are diffuse large B-cell lymphomas (DLBCL), and recent studies have shown that Bcl-6 would be a favorable prognostic biomarker in PCNS-DLBCL. The objective of this study is to evaluate the clinical importance of the central nervous system (CNS) involvement pattern combined with Bcl-6 expression in PCNS-DLBCL patients. This study included 65 immunocompetent patients with PCNS-DLBCL who underwent treatment with high-dose methotrexate with whole-brain radiotherapy. Immunochemistry was performed for the Bcl-6 and Ki-67 antigens. Forty-four patients were male and 21 patients were female, with median age of 59 years. During the median follow-up period of 26 months, progression-free survival (PFS) was 25% and overall survival (OS) was 31%. Of 65 cases that could be subclassified, 31 patients were Bcl-6 positive and 34 patients were negative. Deep-site involvement of the brain was observed in 31 patients. The Bcl-6-positive group and the group having non-deep-site involvement of the brain were associated with favorable progression-free survival (PFS) (P < 0.001; P < 0.001) and overall survival (OS) (P = 0.001; P < 0.001). Results of univariate analysis showed that age above 60 years, Eastern Cooperative Oncology Group (ECOG) PS above 2, elevated lactate dehydrogenase (LDH) state, complete response (CR), and Bcl-6-positive and deep-site involvement were prognostic factors associated with PFS and OS. Results of multivariate analysis revealed that age above 60 years, ECOG above 2, elevated LDH state, Bcl-6 positivity, and deep-site involvement were independent prognostic factors for prediction of outcome. According to the combined prognostic value of Bcl-6 expression and the deep-site involvement pattern, the subgroup having Bcl-6-positive non-deep-site involvement of the brain showed more favorable PFS and OS than the other subgroups (P < 0.001, P < 0.001), whereas differences of survival among the other three subgroups were not significant (P = 0.054, P = 0.056). Bcl-6 positivity was found to be an independent prognostic factor for survival. Bcl-6 expression was associated with higher PFS and OS in patients having non-deep-site involvement. However, this was counteracted in the group of patients having deep-site involvement of the brain.

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References

  1. Hochberg FH, Baehring JM, Hochberg EP (2007) Primary CNS lymphoma. Nat Clin Pract Neurol 3(1):24–35

    Article  PubMed  CAS  Google Scholar 

  2. Coté TR, Manns A, Hardy CR, Yellin FJ, Hartge P (1996) Epidemiology of brain lymphoma among people with or without acquired immunodeficiency syndrome. AIDS/Cancer Study Group. J Natl Cancer Inst 88(10):675–679

    Article  PubMed  Google Scholar 

  3. Corry J, Smith JG, Wirth A, Quong G, Liew KH (1998) Primary central nervous system lymphoma: age and performance status are more important than treatment modality. Int J Radiat Oncol Biol Phys 41(3):615–620

    Article  PubMed  CAS  Google Scholar 

  4. Abrey LE, Yahalom J, DeAngelis LM (2000) Treatment for primary CNS lymphoma: the next step. J Clin Oncol 18(17):3144–3150

    PubMed  CAS  Google Scholar 

  5. Reni M, Ferreri AJ, Garancini MP, Villa E (1997) Therapeutic management of primary central nervous system lymphoma in immunocompetent patients: results of a critical review of the literature. Ann Oncol 8(3):227–234

    Article  PubMed  CAS  Google Scholar 

  6. Ferreri AJ, Blay JY, Reni M, Pasini F, Spina M, Ambrosetti A et al (2003) Prognostic scoring system for primary CNS lymphomas: the International Extranodal Lymphoma Study Group experience. J Clin Oncol 21(2):266–272

    Article  PubMed  Google Scholar 

  7. Gabbai AA, Hochberg FH, Linggood RM, Bashir R, Hotleman K. Gabbai AA et al. (1989) Hochberg FH, Linggood RM, Bashir R, Hotleman K. High-dose methotrexate for non-AIDS primary central nervous system lymphoma. Report of 13 cases. J Neurosurg 70(2):190–194

    Google Scholar 

  8. DeAngelis LM, Yahalom J, Thaler HT, Kher U (1992) Combined modality therapy for primary CNS lymphoma. J Clin Oncol 10(4):635–643

    PubMed  CAS  Google Scholar 

  9. DeAngelis LM, Seiferheld W, Schold SC, Fisher B, Schultz CJ (2002) Combination chemotherapy and radiotherapy for primary central nervous system lymphoma: Radiation Therapy Oncology Group Study 93-10. J Clin Oncol 20(24):4643–4648

    Article  PubMed  Google Scholar 

  10. Poortmans PM, Kluin-Nelemans HC, Haaxma-Reiche H, Van’t Veer M, Hansen M, Soubeyran P et al (2003) European Organization for Research and Treatment of Cancer Lymphoma Group. High-dose methotrexate-based chemotherapy followed by consolidating radiotherapy in non-AIDS-related primary central nervous system lymphoma: European Organization for Research and Treatment of Cancer Lymphoma Group Phase II Trial 20962. J Clin Oncol 21(24):4483–4488

    Article  PubMed  CAS  Google Scholar 

  11. Lin CH, Kuo KT, Chuang SS, Kuo SH, Chang JH, Chang KC et al (2006) Comparison of the expression and prognostic significance of differentiation markers between diffuse large B-cell lymphoma of central nervous system origin and peripheral nodal origin. Clin Cancer Res 12(4):1152–1156

    Article  PubMed  CAS  Google Scholar 

  12. Levy O, Deangelis LM, Filippa DA, Panageas KS, Abrey LE (2008) Bcl-6 predicts improved prognosis in primary central nervous system lymphoma. Cancer 112(1):151–156

    Article  PubMed  Google Scholar 

  13. Braaten KM, Betensky RA, de Leval L, Okada Y, Hochberg FH, Louis DN et al (2003) BCL-6 expression predicts improved survival in patients with primary central nervous system lymphoma. Clin Cancer Res 9(3):1063–1069

    PubMed  CAS  Google Scholar 

  14. Bessell EM, Graus F, Lopez-Guillermo A, Lewis SA, Villa S, Verger E et al (2004) Primary non-Hodgkin’s lymphoma of the CNS treated with CHOD/BVAM or BVAM chemotherapy before radiotherapy: long-term survival and prognostic factors. Int J Radiat Oncol Biol Phys 59(2):501–508

    Article  PubMed  Google Scholar 

  15. Abrey LE, Ben-Porat L, Panageas KS, Yahalom J, Berkey B, Curran W et al (2006) Primary central nervous system lymphoma: the Memorial Sloan-Kettering Cancer Center prognostic model. J Clin Oncol 24(36):5711–5715

    Article  PubMed  Google Scholar 

  16. Sugita Y, Tokunaga O, Nakashima A, Shigemori M (2004) SHP-1 expression in primary central nervous system B-cell lymphomas in immunocompetent patients reflects maturation stage of normal B cell counterparts. Pathol Int 54(9):659–666

    Article  PubMed  CAS  Google Scholar 

  17. Camilleri-Broët S, Crinière E, Broët P, Delwail V, Mokhtari K, Moreau A et al (2005) A uniform activated B-cell-like immunophenotype might explain the poor prognosis of primary central nervous system lymphomas: analysis of 83 cases. Blood 107(1):190–196

    Article  PubMed  Google Scholar 

  18. Krogh-Jensen M, Johansen P, D’Amore F (1998) Primary central nervous system lymphomas in immunocompetent individuals: histology, Epstein-Barr virus genome, Ki-67 proliferation index, p53 and bcl-2 gene expression. Leuk Lymphoma 30(12):131–142

    PubMed  CAS  Google Scholar 

  19. Blay JY, Conroy T, Chevreau C, Thyss A, Quesnel N, Eghbali H et al (1998) High-dose methotrexate for the treatment of primary cerebral lymphomas: analysis of survival and late neurologic toxicity in a retrospective series. J Clin Oncol 16(3):864–871

    PubMed  CAS  Google Scholar 

  20. Blay JY, Lasset C, Carrie C, Chauvin F, Coiffier B, Gisselbrecht C et al (1993) Multivariate analysis of prognostic factors in patients with non HIV-related primary cerebral lymphoma. A proposal for a prognostic scoring. Br J Cancer 67(5):1136–1141

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Hematology-Oncology, Busan Cancer Center, Pusan National University Hospital Medical Research Institute, Busan, Korea

    Moo-Kon Song, Joo-Seop Chung, Seung-Geun Kim, Young-Mi Seol, Ho-Jin Shin, Young-Jin Choi & Goon-Jae Cho

  2. Department of Hematology-Oncology, Busan Paik Hospital, Busan, Korea

    Young-Don Joo & Sang-Min Lee

  3. Department of Hematology-Oncology, Dong-A University Medical Center, Busan, Korea

    Sung-Yong Oh

  4. Department of Pathology, Pusan National University Hospital, Busan, Korea

    Dong-Hoon Shin

  5. Department of Statistics, Pusan National University, Busan, Korea

    Eun-Young Yun

  6. Department of Hematology-Oncology, School of Medicine, Pusan National University, 1-10 Ami-dong, Seo-gu, Busan, 602-739, Republic of Korea

    Joo-Seop Chung

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  1. Moo-Kon Song
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Correspondence to Joo-Seop Chung.

Additional information

An erratum to this article can be found at http://dx.doi.org/10.1007/s11060-011-0566-9

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Song, MK., Chung, JS., Joo, YD. et al. Clinical importance of Bcl-6-positive non-deep-site involvement in non-HIV-related primary central nervous system diffuse large B-cell lymphoma. J Neurooncol 104, 825–831 (2011). https://doi.org/10.1007/s11060-011-0555-z

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  • DOI: https://doi.org/10.1007/s11060-011-0555-z

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