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Autoimmune disease-related primary CNS lymphoma: systematic review and meta-analysis

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Abstract

Background

Recent studies suggest a relatively high prevalence of autoimmune disorders (AD) among primary CNS lymphoma (PCNSL) patients, however, the literature is limited to case reports. To gain a better understanding of AD-PCNSL we reviewed and analyzed all cases described in the literature.

Methods

We searched the MEDLINE database using the search terms ‘central nervous system lymphoma’ or ‘CNS lymphoma’ along with AD-related terms. We selected 39 records for qualitative synthesis of data and identified 50 AD-PCNSL. Clinical, imaging and outcome data were collected. Overall survival (OS) was analyzed with the Kaplan–Meier method. Univariate and multivariate analyses were performed using log rank test and Cox proportional hazard model.

Results

Most common AD were systemic lupus erythematosus (24%), multiple sclerosis (16%), and myasthenia gravis (14%). All patients had received immunosuppressants for their AD. Median interval from AD until PCNSL diagnosis was 108 months (range: 11–420). Male-to-female ratio was 0.42 and AD-PCNSL was diagnosed at a median age of 57 years (range: 2–88). On imaging lesions typically localized to the hemispheres (65%) and displayed peripheral enhancement (74%). Pathological evaluation revealed diffuse large-B-cell lymphoma (DLBCL) subtype (80%) and Epstein-Barr virus positivity (75%) in most AD-PCNSL. Median OS was 31 months. Age > 60 years (p = 0.014) was identified as a significant prognostic factor.

Conclusions

AD requiring immunosuppression appear over-represented in the population of PCNSL patients. Aggressive polychemotherapy can accomplish long term OS in AD-PCNSL comparable to immunocompetent patients. Age > 60 may serve as a prognostic factor.

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Data availability

Data will be shared by request from investigators.

References

  1. Zintzaras E, Voulgarelis M, Moutsopoulos HM (2005) The risk of lymphoma development in autoimmune diseases: a meta-analysis. Arch Intern Med 165(20):2337–2344

    Article  Google Scholar 

  2. Baecklund E, Ekbom A, Sparen P, Feltelius N, Klareskog L (1998) Disease activity and risk of lymphoma in patients with rheumatoid arthritis: nested case-control study. BMJ 317(7152):180–181

    Article  CAS  Google Scholar 

  3. Ekström Smedby K, Vajdic CM, Falster M, Engels EA, Martínez-Maza O, Turner J et al (2008) Autoimmune disorders and risk of non-Hodgkin lymphoma subtypes: a pooled analysis within the InterLymph Consortium. Blood 111(8):4029–4038

    Article  Google Scholar 

  4. Mahale P, Herr MM, Engels EA, Pfeiffer RM, Shiels MS (2020) Autoimmune conditions and primary central nervous system lymphoma risk among older adults. Br J Haematol 188(4):516–521

    Article  Google Scholar 

  5. Han CH, Batchelor TT (2017) Diagnosis and management of primary central nervous system lymphoma. Cancer 123(22):4314–4324

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  7. Ostrom QT, Gittleman H, Liao P, Vecchione-Koval T, Wolinsky Y, Kruchko C et al (2017) CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States 2010–2014. Neuro Oncol. 19(suppl_5):v1–v88

    Article  Google Scholar 

  8. Kaulen LD, Galluzzo D, Hui P, Barbiero F, Karschnia P, Huttner A et al (2019) Prognostic markers for immunodeficiency-associated primary central nervous system lymphoma. J Neurooncol 144(1):107–115

    Article  CAS  Google Scholar 

  9. Enblad G, Martinsson G, Baecklund E, Hesselager G, Sundstrom C, Amini RM et al (2017) Population-based experience on primary central nervous system lymphoma 2000–2012: the incidence is increasing. Acta Oncol 56(4):599–607

    Article  Google Scholar 

  10. O’Neill BP, Vernino S, Dogan A, Giannini C (2007) EBV-associated lymphoproliferative disorder of CNS associated with the use of mycophenolate mofetil. Neuro-Oncol 9(3):364–369

    Article  Google Scholar 

  11. Kleinschmidt-DeMasters BK, Damek DM, Lillehei KO, Dogan A, Giannini C (2008) Epstein Barr virus-associated primary CNS lymphomas in elderly patients on immunosuppressive medications. J Neuropathol Exp Neurol 67(11):1103–1111

    Article  CAS  Google Scholar 

  12. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP et al (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med 6(7):e1000100

    Article  Google Scholar 

  13. 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  Google Scholar 

  14. Cooper GS, Bynum ML, Somers EC (2009) Recent insights in the epidemiology of autoimmune diseases: improved prevalence estimates and understanding of clustering of diseases. J Autoimmun 33(3–4):197–207

    Article  Google Scholar 

  15. Tran H, Nourse J, Hall S, Green M, Griffiths L, Gandhi MK (2008) Immunodeficiency-associated lymphomas. Blood Rev 22(5):261–281

    Article  Google Scholar 

  16. Cavaliere R, Petroni G, Lopes MB, Schiff D, International Primary Central Nervous System Lymphoma Collaborative G (2010) Primary central nervous system post-transplantation lymphoproliferative disorder: an International Primary Central Nervous System Lymphoma Collaborative Group Report. Cancer 116(4):863–870

    Article  Google Scholar 

  17. Evens AM, Choquet S, Kroll-Desrosiers AR, Jagadeesh D, Smith SM, Morschhauser F et al (2013) Primary CNS posttransplant lymphoproliferative disease (PTLD): an International Report of 84 Cases in the Modern Era. Am J Transplant 13(6):1512–1522

    Article  CAS  Google Scholar 

  18. Kandiel A, Fraser AG, Korelitz BI, Brensinger C, Lewis JD (2005) Increased risk of lymphoma among inflammatory bowel disease patients treated with azathioprine and 6-mercaptopurine. Gut 54(8):1121–1125

    Article  CAS  Google Scholar 

  19. Crane GM, Powell H, Kostadinov R, Rocafort PT, Rifkin DE, Burger PC et al (2015) Primary CNS lymphoproliferative disease, mycophenolate and calcineurin inhibitor usage. Oncotarget 6(32):33849–33866

    Article  Google Scholar 

  20. Leray E, Yaouanq J, Le Page E, Coustans M, Laplaud D, Oger J et al (2010) Evidence for a two-stage disability progression in multiple sclerosis. Brain 133(Pt 7):1900–1913

    Article  Google Scholar 

  21. Sharma MC, Gupta RK, Kaushal S, Suri V, Sarkar C, Singh M et al (2016) A clinicopathological study of primary central nervous system lymphomas & their association with Epstein-Barr virus. Indian J Med Res 143(5):605–615

    Article  CAS  Google Scholar 

  22. Ambinder RF (2000) Gammaherpesviruses and “Hit-and-Run” oncogenesis. Am J Pathol 156(1):1–3

    Article  CAS  Google Scholar 

  23. Thériault C, Galoin S, Valmary S, Selves J, Lamant L, Roda D et al (2000) PCR analysis of immunoglobulin heavy chain (IgH) and TcR-γ Chain gene rearrangements in the diagnosis of lymphoproliferative disorders: results of a study of 525 cases. Mod Pathol 13(12):1269–1279

    Article  Google Scholar 

  24. Thiel E, Korfel A, Martus P, Kanz L, Griesinger F, Rauch M et al (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

    Article  CAS  Google Scholar 

  25. Kwong YL, Chan TSY, Tan D, Kim SJ, Poon LM, Mow B et al (2017) PD1 blockade with pembrolizumab is highly effective in relapsed or refractory NK/T-cell lymphoma failing l-asparaginase. Blood 129(17):2437–2442

    Article  CAS  Google Scholar 

  26. Kim SJ, Hyeon J, Cho I, Ko YH, Kim WS (2019) Comparison of efficacy of pembrolizumab between Epstein-Barr virus positive and negative relapsed or refractory non-Hodgkin lymphomas. Cancer Res Treat Off J. Korean Cancer Assoc 51(2):611–622

    CAS  Google Scholar 

  27. Nayyar N, White MD, Gill CM, Lastrapes M, Bertalan M, Kaplan A et al (2019) MYD88 L265P mutation and CDKN2A loss are early mutational events in primary central nervous system diffuse large B-cell lymphomas. Blood Adv 3(3):375–383

    Article  CAS  Google Scholar 

  28. Johnson DB, Sullivan RJ, Ott PA, Carlino MS, Khushalani NI, Ye F et al (2016) Ipilimumab therapy in patients with advanced melanoma and preexisting autoimmune disorders. JAMA Oncol 2(2):234–240

    Article  Google Scholar 

  29. Arbour KC, Mezquita L, Long N (2018) Impact of baseline steroids on efficacy of programmed cell death-1 and programmed death-ligand 1 blockade in patients with non-small-cell lung cancer. J Clin Oncol 36:2872–2878

    Article  CAS  Google Scholar 

  30. Shiels MS, Pfeiffer RM, Besson C, Clarke CA, Morton LM, Nogueira L et al (2016) Trends in primary central nervous system lymphoma incidence and survival in the U.S. Br J Haematol. 174(3):417–424

    Article  Google Scholar 

  31. Korfel A, Schlegel U (2013) Diagnosis and treatment of primary CNS lymphoma. Nat Rev Neurol 9(6):317–327

    Article  CAS  Google Scholar 

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Acknowledgements

The abstract was previously presented at the 2019 annual meeting of the European Association of Neuro-Oncology (EANO) and was published in Neuro-Oncology, Volume 21, Issue suppl_3, Pages iii72.

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No targeted funding.

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Authors and Affiliations

  1. Department of Neurology, Yale School of Medicine, 15 York Street, New Haven, CT, 06510, USA

    Leon D. Kaulen, Philipp Karschnia & Joachim M. Baehring

  2. Department of Neurology, Heidelberg University, Heidelberg, Germany

    Leon D. Kaulen

  3. Department of Neurosurgery, Ludwig Maximilian University (LMU), Munich, Germany

    Philipp Karschnia

  4. Division of Neuro-Oncology, Department of Neurology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, USA

    Jorg Dietrich

  5. Department of Neurosurgery, Yale School of Medicine, New Haven, USA

    Joachim M. Baehring

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  1. Leon D. Kaulen
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  4. Joachim M. Baehring
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Contributions

LDK and JMB designed the study, analyzed and interpreted data, and drafted the manuscript. LDK conducted the review of literature. LDK, PK, JD and JMB critically revised, read and approved the final manuscript.

Corresponding author

Correspondence to Joachim M. Baehring.

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This study was approved by the institutional review board (IRB).

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Kaulen, L.D., Karschnia, P., Dietrich, J. et al. Autoimmune disease-related primary CNS lymphoma: systematic review and meta-analysis. J Neurooncol 149, 153–159 (2020). https://doi.org/10.1007/s11060-020-03583-9

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  • DOI: https://doi.org/10.1007/s11060-020-03583-9

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