Advertisement

Primary central nervous system lymphoma in China: a single-center retrospective analysis of 167 cases

  • Xiang-Gui Yuan
  • Yu-Rong Huang
  • Teng Yu
  • Yang Xu
  • Yun Liang
  • Xiao-Hong Zhang
  • Chong-Ran SunEmail author
  • Xiao-Ying ZhaoEmail author
Original Article

Abstract

Primary central nervous system lymphoma (PCNSL) is a rare form of extranodal non-Hodgkin’s lymphoma and a limited number of cases have been reported from China. This study aimed to investigate the clinicopathological features of newly diagnosed PCNSLs from a single center in eastern China and to identify the potential prognostic factors for overall survival (OS) and progression-free survival (PFS). All consecutive patients with histopathologically diagnosed PCNSLs at our center between January 2003 and October 2017 were recruited. Demographic and clinicopathological data were collected and reviewed retrospectively. The potential risk factors for OS and PFS were identified using the log-rank test and Cox regression analysis. A total of 167 immunocompetent cases were enrolled. The median age was 58 years (range 17–96 years), and the male:female ratio was 3:2. Headache (n = 65; 39%) and cerebral hemisphere (n = 96; 57%) were the most common presenting complaint and location, respectively. Out of 167 cases, 150 cases were diffuse large B cell lymphomas. With a median follow-up of 25 months (range 1–152 ), the median OS and PFS were 37 months (95% CI, 25–49) and 17 months (95% CI, 13–20), respectively. Residual tumor after operation, chemotherapy without HD-MTX and palliative treatment was revealed as independent prognostic markers. Moreover, ECOG > 3, multifocal lesions, and palliative treatment were revealed as unfavorable independent prognostic markers for PFS. In conclusion, Chinese patients with PCNSL have distinct characteristics. Further studies are warranted to confirm the prognostic value of these factors and to optimize treatments for these patients.

Keywords

Extranodal non-Hodgkin’s lymphoma Primary central nervous system lymphoma Prognostic factors Multifocal lesions Surgery resection Chinese 

Abbreviations

PCNSL

primary central nervous system lymphoma

NHL

non-Hodgkin’s lymphoma

HIV

human immunodeficiency virus

DLBCL

diffuse large B cell lymphoma

GCB

germinal center B cell

Non-GCB

non-germinal center B cell

IELSG

international Extranodal Lymphoma Study Group

LDH

lactate dehydrogenase

CSF

cerebrospinal fluid

OS

overall survival

KPS

Karnofsky scores

PFS

progression-free survival

ALC

absolute lymphocyte count

MRI

magnetic resonance imaging

HD-MTX

high-dose methotrexate

ASCT

autologous stem cell transplantation

Notes

Authors’ contributions

XG Yuan analyzed the patient data and wrote the manuscript. Yu-Rong Huang, T Yu, Y Liang, and XH Zhang collected clinical data; Y Xu performed the statistical analysis; Xiao-Ying Zhao designed and supervised the research project. CR Sun analyzed and interpreted the patient data regarding the surgery and evaluations of cranial magnetic resonance (MRI). All authors read and approved the final manuscript.

Funding information

This work was supported by Zhejiang Provincial Key Innovation Team (No. 2011R50015), National Natural Science Foundation of China grants (No. 81572920), National Basic Research Program of China (No. 2013CB911303), and Natural Science Foundation of Zhejiang Province of China (No. LY15H160038).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethics approval

This study was approved by the Human Ethics Committee of the Second Affiliated Hospital, School of Medicine, Zhejiang University, China.

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

An informed consent was obtained from all individual participants included in the study.

References

  1. 1.
    Dolecek TA, Propp JM, Stroup NE, Kruchko C (2012) CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2005-2009. Neuro-Oncology 14(Suppl 5):v1–v49.  https://doi.org/10.1093/neuonc/nos218 CrossRefGoogle Scholar
  2. 2.
    Patrick LB, Mohile NA (2015) Advances in primary central nervous system lymphoma. Curr Oncol Rep 17(12):60.  https://doi.org/10.1007/s11912-015-0483-8 CrossRefPubMedGoogle Scholar
  3. 3.
    Ruiz A, Post JD, Bundschu C, Ganz WI, Georgiou M (1997) Primary central nervous system lymphoma in patients with AIDS. Neuroimaging Clin N Am 7(2):281PubMedGoogle Scholar
  4. 4.
    Phan TG, O’Neill BP, Habermann TM (1999) Post-transplant primary central nervous system lymphoma. Ann Neurol 46(3):463–463Google Scholar
  5. 5.
    Bataille B, Delwail V, Menet E, Vandermarcq P, Ingrand P, Wager M, Guy G, Lapierre F (2000) Primary intracerebral malignant lymphoma: report of 248 cases. J Neurosurg 92(2):261–266.  https://doi.org/10.3171/jns.2000.92.2.0261 CrossRefPubMedGoogle Scholar
  6. 6.
    Raoux D, Duband S, Forest F, Trombert B, Chambonniere ML, Dumollard JM, Khaddage A, Gentil-Perret A, Peoc’h M (2010) Primary central nervous system lymphoma: immunohistochemical profile and prognostic significance. Neuropathology 30(3):232–240.  https://doi.org/10.1111/j.1440-1789.2009.01074.x CrossRefPubMedGoogle Scholar
  7. 7.
    Sierra del Rio M, Rousseau A, Soussain C, Ricard D, Hoang-Xuan K (2009) Primary CNS lymphoma in immunocompetent patients. Oncologist 14(5):526–539.  https://doi.org/10.1634/theoncologist.2008-0236 CrossRefPubMedGoogle Scholar
  8. 8.
    Hans CP, Weisenburger DD, Greiner TC, Gascoyne RD, Delabie J, Ott G, Muller-Hermelink HK, Campo E, Braziel RM, Jaffe ES, Pan ZG, Farinha P, Smith LM, Falini B, Banham AH, Rosenwald A, Staudt LM, Connors JM, Armitage JO, Chan WC (2004) Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood 103(1):275–282.  https://doi.org/10.1182/blood-2003-05-1545 CrossRefPubMedGoogle Scholar
  9. 9.
    Norden AD, Drappatz J, Wen PY, Claus EB (2011) Survival among patients with primary central nervous system lymphoma, 1973-2004. J Neuro-Oncol 101(3):487–493.  https://doi.org/10.1007/s11060-010-0269-7 CrossRefGoogle Scholar
  10. 10.
    Ferreri AJ, Blay JY, Reni M, Pasini F, Spina M, Ambrosetti A, Calderoni A, Rossi A, Vavassori V, Conconi A, Devizzi L, Berger F, Ponzoni M, Borisch B, Tinguely M, Cerati M, Milani M, Orvieto E, Sanchez J, Chevreau C, Dell’Oro S, Zucca E, Cavalli F (2003) Prognostic scoring system for primary CNS lymphomas: the International Extranodal Lymphoma Study Group experience. J Clin Oncol 21(2):266–272.  https://doi.org/10.1200/JCO.2003.09.139 CrossRefPubMedGoogle Scholar
  11. 11.
    Bessell EM, Graus F, Lopez-Guillermo A, Lewis SA, Villa S, Verger E, Petit J (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.  https://doi.org/10.1016/j.ijrobp.2003.11.001 CrossRefPubMedGoogle Scholar
  12. 12.
    Abrey LE, Ben-Porat L, Panageas KS, Yahalom J, Berkey B, Curran W, Schultz C, Leibel S, Nelson D, Mehta M, DeAngelis LM (2006) Primary central nervous system lymphoma: the Memorial Sloan-Kettering Cancer Center prognostic model. J Clin Oncol 24(36):5711–5715.  https://doi.org/10.1200/JCO.2006.08.2941 CrossRefPubMedGoogle Scholar
  13. 13.
    Jang JE, Kim YR, Kim SJ, Cho H, Chung H, Lee JY, Park H, Kim Y, Cheong JW, Min YH, Kim JS (2016) A new prognostic model using absolute lymphocyte count in patients with primary central nervous system lymphoma. Eur J Cancer 57:127–135.  https://doi.org/10.1016/j.ejca.2016.01.016 CrossRefPubMedGoogle Scholar
  14. 14.
    Preusser M, Woehrer A, Koperek O, Rottenfusser A, Dieckmann K, Gatterbauer B, Roessler K, Slavc I, Jaeger U, Streubel B, Hainfellner JA, Chott A (2010) Primary central nervous system lymphoma: a clinicopathological study of 75 cases. Pathology 42(6):547–552.  https://doi.org/10.3109/00313025.2010.508786 CrossRefPubMedGoogle Scholar
  15. 15.
    Dalia S, Forsyth P, Chavez J, Price S, Shah B, Bello C, Sokol L, Pan E, Sotomayor E, Lee JH, Fisher K, Jaglal M (2014) Primary B-cell CNS lymphoma clinicopathologic and treatment outcomes in 89 patients from a single tertiary care center. Int J Hematol 99(4):450–456.  https://doi.org/10.1007/s12185-014-1540-z CrossRefPubMedGoogle Scholar
  16. 16.
    Lai R, Rosenblum MK, DeAngelis LM (2002) Primary CNS lymphoma: a whole-brain disease? Neurology 59(10):1557–1562CrossRefGoogle Scholar
  17. 17.
    Bellinzona M, Roser F, Ostertag H, Gaab RM, Saini M (2005) Surgical removal of primary central nervous system lymphomas (PCNSL) presenting as space occupying lesions: a series of 33 cases. Ejso 31(1):100–105.  https://doi.org/10.1016/j.ejso.2004.10.002 CrossRefPubMedGoogle Scholar
  18. 18.
    Weller M, Martus P, Roth P, Thiel E, Korfel A (2012) Surgery for primary CNS lymphoma? Challenging a paradigm. Neuro-Oncology 14(12):1481–1484.  https://doi.org/10.1093/neuonc/nos159 CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Labak CM, Holdhoff M, Bettegowda C, Gallia GL, Lim M, Weingart JD, Mukherjee D (2019) Surgical resection for primary central nervous system lymphoma: a systematic review. World Neurosurg.  https://doi.org/10.1016/j.wneu.2019.02.252 CrossRefGoogle Scholar
  20. 20.
    Cloney MB, Sonabend AM, Yun J, Yang J, Iwamoto F, Singh S, Bhagat G, Canoll P, Zanazzi G, Bruce JN, Sisti M, Sheth S, Connolly ES, McKhann G (2017) The safety of resection for primary central nervous system lymphoma: a single institution retrospective analysis. J Neuro-Oncol 132(1):189–197.  https://doi.org/10.1007/s11060-016-2358-8 CrossRefGoogle Scholar
  21. 21.
    Yun J, Yang JY, Cloney M, Mehta A, Singh S, Iwamoto FM, Neugut AI, Sonabend AM (2017) Assessing the safety of craniotomy for resection of primary central nervous system lymphoma: a nationwide inpatient sample analysis. Front Neurol 8:478.  https://doi.org/10.3389/Fneur.2017.00478 CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Lin CH, Ku KT, Chuang SS, Kuo SH, Chang JH, Chang KC, Hsu HC, Tien HF, Cheng 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.  https://doi.org/10.1158/1078-0432.CCR-05-1699 CrossRefPubMedGoogle Scholar
  23. 23.
    Pasqualucci L, Dalla-Favera R (2015) The genetic landscape of diffuse large B-cell lymphoma. Semin Hematol 52(2):67–76.  https://doi.org/10.1053/j.seminhematol.2015.01.005 CrossRefGoogle Scholar
  24. 24.
    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.  https://doi.org/10.1002/cncr.23149 CrossRefPubMedGoogle Scholar
  25. 25.
    Liu J, Wang YM, Liu YT, Liu Z, Cui Q, Ji N, Sun SJ, Wang BX, Wang YJ, Sun XF, Liu YB (2017) Immunohistochemical profile and prognostic significance in primary central nervous system lymphoma: analysis of 89 cases. Oncol Lett 14(5):5505–5512.  https://doi.org/10.3892/ol.2017.6893 CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Ferreri AJM, Reni M, Foppoli M, Martelli M, Pangalis GA, Frezzato M, Cabras MG, Fabbri A, Corazzelli G, Ilariucci F, Rossi G, Soffietti R, Stelitano C, Vallisa D, Zaja F, Zoppegno L, Aondio GM, Avvisati G, Balzarotti M, Brandes AA, Fajardo J, Gomez H, Guarini A, Pinotti G, Rigacci L, Uhlmann C, Picozzi P, Vezzulli P, Ponzoni M, Zucca E, Caligaris-Cappio F, Cavalli F, Ielsg (2009) High-dose cytarabine plus high-dose methotrexate versus high-dose methotrexate alone in patients with primary CNS lymphoma: a randomised phase 2 trial. Lancet 374(9700):1512–1520.  https://doi.org/10.1016/S0140-6736(09)61416-1 CrossRefPubMedGoogle Scholar
  27. 27.
    Ferreri AJM, Cwynarski K, Pulczynski E, Ponzoni M, Deckert M, Politi LS, Torri V, Fox CP, La Rosee P, Schorb E, Ambrosetti A, Roth A, Hemmoway C, Ferrari A, Linton KM, Ruda R, Binder M, Pukrop T, Balzarotti M, Fabbri A, Johnson P, Gorlov JS, Hess G, Panse J, Pisani F, Tucci A, Stilgenbauer S, Hertenstein B, Keller U, Krause SW, Levis A, Schmoll HJ, Covalli F, Finke J, Reni M, Zucca E, Illerhaus G, Ielsg (2016) Chemoimmunotherapy with methotrexate, cytarabine, thiotepa, and rituximab (MATRix regimen) in patients with primary CNS lymphoma: results of the first randomisation of the International Extranodal Lymphoma Study Group-32 (IELSG32) phase 2 trial. Lancet Haematol 3(5):E217–E227.  https://doi.org/10.1016/S2352-3026(16)00036-3 CrossRefGoogle Scholar
  28. 28.
    Ferreri AJM, Cwynarski K, Pulczynski E, Fox CP, Schorb E, La Rosee P, Binder M, Fabbri A, Torri V, Minacapelli E, Falautano M, Ilariucci F, Ambrosetti A, Roth A, Hemmaway C, Johnson P, Linton KM, Pukrop T, Gorlov JS, Balzarotti M, Hess G, Keller U, Stilgenbauer S, Panse J, Tucci A, Orsucci L, Pisani F, Levis A, Krause SW, Schmoll HJ, Hertenstein B, Rummel M, Smith J, Pfreundschuh M, Cabras G, Angrilli F, Ponzoni M, Deckert M, Politi LS, Finke J, Reni M, Cavalli F, Zucca E, Illerhaus G, Ielsg (2017) Whole-brain radiotherapy or autologous stem-cell transplantation as consolidation strategies after high-dose methotrexate-based chemoimmunotherapy in patients with primary CNS lymphoma: results of the second randomisation of the International Extranodal Lymphoma Study Group-32 phase 2 trial. Lancet Haematol 4(11):E510–E523.  https://doi.org/10.1016/S2352-3026(17)30174-6 CrossRefPubMedGoogle Scholar
  29. 29.
    Nelson DF, Martz KL, Bonner H, Nelson JS, Newall J, Kerman HD, Thomson JW, Murray KJ (1992) Non-Hodgkin’s lymphoma of the brain: can high-dose, large volume radiation therapy improve survival? Report on a prospective trial by the Radiation. Therapy Oncology Group (RTOG): RTOG 8315 Int J Radiat Oncol 23(1):9–17.  https://doi.org/10.1016/0360-3016(92)90538-S CrossRefGoogle Scholar
  30. 30.
    Shibamoto Y, Ogino H, Hasegawa M, Suzuki K, Nishio M, Fujii T, Kato E, Ishihara SI, Sougawa M, Kenjo M, Kawamura T, Hayabuchi N (2005) Results of radiation monotherapy for primary central nervous system lymphoma in the 1990s. Int J Radiat Oncol 62(3):809–813.  https://doi.org/10.1016/j.ijrpbp.2004.12.043 CrossRefGoogle Scholar
  31. 31.
    Thiel E, Korfel A, Martus P, Kanz L, Griesinger F, Rauch M, Roth A, Hertenstein B, von Toll T, Hundsberger T, Mergenthaler HG, Leithauser M, Birnbaum T, Fischer L, Jahnke K, Herrlinger U, Plasswilm L, Nagele T, Pietsch T, Bamberg M, Weller M (2010) High-dose methotrexate with or without whole brain radiotherapy for primary CNS lymphoma (G-PCNSL-SG-1): a phase 3, randomised, non-inferiority trial. Lancet Oncol 11(11):1036–1047.  https://doi.org/10.1016/S1470-2045(10)70229-1 CrossRefGoogle Scholar
  32. 32.
    Benekou K, Montoto S (2017) Role of stem cell transplant in lymphoma in the era of new drugs. Curr Opin Oncol 29(6):455–459.  https://doi.org/10.1097/Cco.0000000000000403 CrossRefPubMedGoogle Scholar
  33. 33.
    Ghesquieres H, Drouet Y, Sunyach MP, Sebban C, Chassagne-Clement C, Jouanneau E, Honnorat J, Biron P, Blay JY (2013) Evidence of time-dependent prognostic factors predicting early death but not long-term outcome in primary CNS lymphoma: a study of 91 patients. Hematol Oncol 31(2):57–64.  https://doi.org/10.1002/hon.2021 CrossRefGoogle Scholar
  34. 34.
    Kiewe P, Fischer L, Martus P, Thiel E, Korfel A (2010) Meningeal dissemination in primary CNS lymphoma: diagnosis, treatment, and survival in a large monocenter cohort. Neuro-Oncology 12(4):409–417.  https://doi.org/10.1093/neuonc/nop053 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Hematology, the Second Affiliated HospitalZhejiang University School of MedicineHangzhouChina
  2. 2.Department of Neurosurgery, the Second Affiliated HospitalZhejiang University School of MedicineHangzhouChina

Personalised recommendations