Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Diagnosis and treatment of primary CNS lymphoma

Nature Reviews Neurology volume 9, pages 317–327 (2013)Cite this article

Subjects

Abstract

Primary CNS lymphoma (PCNSL) is a rare lymphoma that is confined to the CNS, with low tendency for systemic dissemination and a relatively aggressive course. Outcome in patients with PCNSL is often poor. Owing to its low incidence, current knowledge about optimal treatment of PCNSL is fragmentary. Chemotherapy regimens based on high-dose methotrexate are currently standard treatment for all patients with PCNSL who can tolerate such drugs. Whole-brain radiotherapy alone can lead to remission in up to 90% of patients, but often results in poor long-term disease control when given alone, and in delayed neurotoxicity when given after high-dose methotrexate. In this Review, we describe current approaches to diagnosis and treatment of PCNSL, and discuss novel therapeutic approaches that are currently in development, such as the use of rituximab and high-dose chemotherapy followed by autologous stem-cell transplantation. The possible use of intrathecal and intraventricular chemotherapy, optimal salvage treatment, and specific treatment approaches in elderly, paediatric and immunocompromised patients, are also considered.

Key Points

  • Primary CNS lymphoma (PCNSL) is a rare aggressive lymphoma, usually of the diffuse large B-cell type, that is confined to the CNS at first diagnosis

  • Diagnosis usually requires stereotactic biopsy from a CNS lesion

  • High-dose methotrexate-based chemotherapy is currently standard treatment for PCNSL

  • Whole-brain radiotherapy should not routinely be used in primary therapy owing to the lack of overall survival prolongation after combined treatment and high risk of delayed CNS toxicity

  • Optimal treatment for elderly patients, immunocompromised patients, children and adolescents, as well as for individuals with relapsed or refractory disease, has not yet been defined

  • Delayed CNS toxicity is a major problem in long-term survivors, and preservation of neurocognitive function is an important treatment goal

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: MRI of a primary CNS lymphoma.
Figure 2: Primary intraocular lymphoma.
Figure 3: Neurotoxicity following treatment for primary CNS lymphoma.
Figure 4: Flow chart of therapy for primary CNS lymphoma in clinical routine.

Similar content being viewed by others

References

  1. Dolecek, T., Propp, J. M., Stroup, N. E. & Kruchko, C. CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2005–2009. Neuro Oncol. 14 (suppl. 5), v1–v49 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  2. Villano J. L., Koshy, M., Shaik, H., Dolecek, T. A. & McCarthy, B. J. Age, gender, and racial differences in incidence and survival in primary CNS lymphoma. Br. J. Cancer 105, 1414–1418 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Deckert, M. et al. Modern concepts in the biology, diagnosis, differential diagnosis and treatment of primary central nervous system lymphoma. Leukemia 25, 1797–1807 (2011).

    Article  CAS  PubMed  Google Scholar 

  4. Thiel, E. et al. High-dose methotrexate with or without whole brain radiotherapy for primarxy CNS lymphoma (G-PCNSL-SG-1): a phase 3, randomised, non-inferiority trial. Lancet Oncol. 11, 1036–1047 (2010).

    Article  CAS  PubMed  Google Scholar 

  5. Batchelor, T. & Loeffler, J. S. Primary CNS Lymphoma. J. Clin. Oncol. 24, 1281–1288 (2006).

    Article  CAS  PubMed  Google Scholar 

  6. Pels, H. & Schlegel, U. Primary central nervous system lymphoma. Curr. Treat. Options Neurol. 8, 346–357 (2006).

    Article  PubMed  Google Scholar 

  7. Küker, W., Nägele, T., Thiel, E., Weller, M. & Herrlinger, U. Primary central nervous system lymphomas (PCNSL): MRI response criteria revised. Neurology 65, 1129–1131 (2005).

    Article  PubMed  Google Scholar 

  8. Toh, C.-H. et al. Primary cerebral lymphoma and glioblastoma: differences in diffusion characteristics evaluated with diffusion tensor imaging. AJNR Am. J. Neuroradiol. 29, 471–475 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  9. Korfel, A. et al. Prognostic impact of meningeal dissemination in primary CNS lymphoma (PCNSL): experience from the G-PCNSL-SG1 trial. Ann. Oncol. 23, 2374–2380 (2012).

    Article  CAS  PubMed  Google Scholar 

  10. Schroers, R. et al. Diagnosis of leptomeningeal disease in diffuse large B-cell lymphomas of the central nervous system by flow cytometry and cytopathology. Eur. J. Haematol. 85, 520–528 (2010).

    Article  PubMed  Google Scholar 

  11. Schroers, R. et al. Detection of free immunoglobulin light chains in cerebrospinal fluids of patients with central nervous system lymphomas. Eur. J. Haematol. 85, 236–242 (2010).

    Article  CAS  PubMed  Google Scholar 

  12. Fischer, L. et al. CXCL13 and CXCL12 in central nervous system lymphoma patients. Clin. Cancer Res. 15, 5968–5973 (2009).

    Article  CAS  PubMed  Google Scholar 

  13. Baraniskin, A. et al. Identification of microRNAs in the cerebrospinal fluid as marker for primary diffuse large B-cell lymphoma of the central nervous system. Blood 117, 3140–3146 (2011).

    Article  CAS  PubMed  Google Scholar 

  14. Cinque, P. et al. Epstein-Barr virus DNA in cerebrospinal fluid from patients with AIDS-related primary lymphomas of the central nervous system. Lancet 342, 398–401 (1993).

    Article  CAS  PubMed  Google Scholar 

  15. De Luca, A. et al. Evaluation of cerebrospinal fluid EBV-DNA and IL-10 as markers for in vivo diagnosis of AIDS-related primary central nervous system lymphomas. Br. J. Haematol. 90, 844–849 (1995).

    Article  CAS  PubMed  Google Scholar 

  16. Ambinder, R. F., Bhatia, K., Martinez-Maza, O. & Mitsuyasu, R. Cancer biomarkers in HIV patients. Curr. Opin. HIV AIDS 5, 531–537 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  17. O'Neill, B. P., Vernino, S., Dogan, A. & Giannini, C. EBV-associated lymphoproliferative disorder of CNS associated with the use of mycophenolate mofetil. Neuro Oncol. 9, 364–369 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Grimm, S. A. et al. Primary CNS lymphoma with intraocular involvement: International PCNSL Collaborative Group Report. Neurology 71, 1355–1360 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Chan, C. C. et al. Primary vitreoretinal lymphoma: a report from an International Primary Central Nervous System Lymphoma Collaborative Group symposium. Oncologist 16, 1589–1599 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  20. Pittock, S. J. et al. Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS). Brain 133, 2626–2634 (2010).

    Article  PubMed  Google Scholar 

  21. Preusser, M. et al. Primary central nervous system lymphomas: a clinicopathological study of 75 cases. Pathology 42, 547–552 (2010).

    Article  CAS  PubMed  Google Scholar 

  22. Shenkier, T. N. et al. Primary CNS lymphoma of T-cell origin: a descriptive analysis from the International Primary CNS Lymphoma Collaborative Group. J. Clin. Oncol. 23, 2233–2239 (2005).

    Article  PubMed  Google Scholar 

  23. Jahnke, K. et al. International study on low-grade primary central nervous system lymphoma. Ann. Neurol. 59, 755–762 (2006).

    Article  PubMed  Google Scholar 

  24. Cavaliere, R., Petroni, G., Lopes, M. B. & Schiff, D. Primary central nervous system post-transplantation lymphoproliferative disorder: an International Primary Central Nervous System Lymphomas Collaborative Group report. Cancer 116, 863–870 (2010).

    Article  PubMed  Google Scholar 

  25. Riemersma, S. A. et al. Extensive genetic alterations of the HLA region, including homozygous deletions of HLA class II genes in B-cell lymphomas arising in immune-privileged sites. Blood 96, 3569–3577 (2000).

    CAS  PubMed  Google Scholar 

  26. Abrey, L. E. et al. International Primary CNS Lymphoma Collaborative Group. Report of an international workshop to standardize baseline evaluation and response criteria for primary CNS lymphoma. J. Clin. Oncol. 23, 5034–5043 (2005).

    Article  PubMed  Google Scholar 

  27. Ferreri, A. J. et al. Prognostic scoring system for primary CNS lymphomas: the International Extranodal Lymphoma Study Group experience. J. Clin. Oncol. 21, 266–272 (2003).

    Article  PubMed  Google Scholar 

  28. Abrey, L. E. et al. Primary central nervous system lymphoma: the Memorial Sloan-Kettering Cancer Center prognostic model. J. Clin. Oncol. 24, 5711–5715 (2006).

    Article  PubMed  Google Scholar 

  29. Pels, H. et al. Early complete response during chemotherapy predicts favorable outcome in patients with primary CNS lymphoma. Neuro Oncol. 12, 720–724 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  30. Mead, G. M. et al. A medical research council randomized trial in patients with primary cerebral non-Hodgkin lymphoma: cerebral radiotherapy with and without cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy. Cancer 89, 1359–1370 (2000).

    Article  CAS  PubMed  Google Scholar 

  31. Borsi, J. D. & Moe, P. J. A comparative study on the pharmacokinetics of methotrexate in a dose range of 0.5 g to 33.6 g/m2 in children with acute lymphoblastic leukemia. Cancer 60, 5–13 (1987).

    Article  CAS  PubMed  Google Scholar 

  32. Shapiro, W. R., Young, D. F. & Mehta, B. M. Methotrexate: distribution in cerebrospinal fluid after intravenous, ventricular and lumbar injections. N. Engl. J. Med. 293, 161–166 (1975).

    Article  CAS  PubMed  Google Scholar 

  33. Herrlinger, U. et al. NOA-03 trial of high-dose methotrexate in primary central nervous system lymphoma: final report. Ann. Neurol. 57, 843–847 (2005).

    Article  CAS  PubMed  Google Scholar 

  34. Batchelor, T. et al. Treatment of primary CNS lymphoma with methotrexate and deferred radiotherapy: a report of NABTT 96–07. J. Clin. Oncol. 21, 1044–1049 (2003).

    Article  CAS  PubMed  Google Scholar 

  35. Ferreri, A. J. et al. 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, 1512–1520 (2009).

    Article  CAS  PubMed  Google Scholar 

  36. Abrey, L. E., Yahalom, J. & DeAngelis, L. M. Treatment for primary CNS lymphoma: the next step. J. Clin. Oncol. 18, 3144–3150 (2000).

    Article  CAS  PubMed  Google Scholar 

  37. DeAngelis, L. M., Seiferheld, W., Schold, S. C., Fisher, B. & Schultz, C. J. Combination chemotherapy radiotherapy for primary central nervous system lymphoma: Radiation Therapy Oncology Group study 93–10. J. Clin. Oncol. 20, 4643–4648 (2002).

    Article  PubMed  Google Scholar 

  38. O'Brien, P. C. et al. Combined modality therapy for primary central nervous system lymphoma: long-term data from a phase II multicenter study (Trans-Tasman Radiation Oncology Group). Int. J. Radiat. Oncol. Biol. Phys. 64, 408–413 (2006).

    Article  PubMed  Google Scholar 

  39. Poortmans, P. M. et al. 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, 4483–4488 (2003).

    Article  CAS  PubMed  Google Scholar 

  40. Korfel, A. et al. German Primary Central Nervous System Lymphoma Study Group (G-PCNSL-SG). Response to chemotherapy and treating institution predict survival in primary central nervous system lymphoma. Br. J. Haematol. 128, 177–183 (2005).

    Article  PubMed  Google Scholar 

  41. Ferreri, A. J. et al. MATILDE regimen followed by radiotherapy is an active strategy against primary CNS lymphomas. Neurology 66, 1435–1438 (2006).

    Article  CAS  PubMed  Google Scholar 

  42. Pels, H. et al. Primary central nervous system lymphoma: results of a pilot and phase II study of systemic and intraventricular chemotherapy with deferred radiotherapy. J. Clin. Oncol. 21, 4489–4495 (2003).

    Article  CAS  PubMed  Google Scholar 

  43. Juergens, A. et al. Long-term survival with favorable cognitive outcome after chemotherapy in primary central nervous system lymphoma. Ann. Neurol. 67, 182–189 (2010).

    Article  CAS  PubMed  Google Scholar 

  44. Angelov, L. et al. Blood–brain barrier disruption and intraarterial methotrexate-based therapy for newly diagnosed primary CNS lymphoma: a multi-institutional experience. J. Clin. Oncol. 27, 3503–3509 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Bleyer, W. A., Poplack, D. G. & Simon, R. M. “Concentration x time” methotrexate via a subcutaneous reservoir: a less toxic regimen for intraventricular chemotherapy of central nervous system neoplasms. Blood 51, 835–842 (1978).

    CAS  PubMed  Google Scholar 

  46. Hoang-Xuan, K. et al. European Organization for Research and Treatment of Cancer Brain Tumor Group. Chemotherapy alone as initial treatment for primary CNS lymphoma in patients older than 60 years: a multicenter phase II study (26952) of the European Organization for Research and Treatment of Cancer Brain Tumor Group. J. Clin. Oncol. 21, 2726–2731 (2003).

    Article  CAS  PubMed  Google Scholar 

  47. Pels, H. et al. Early relapses in primary CNS lymphoma after response to polychemotherapy without intraventricular treatment: results of a phase II study. J. Neurooncol. 91, 299–305 (2009).

    Article  CAS  PubMed  Google Scholar 

  48. Ferreri, A. J. et al. A multicenter study of treatment of primary CNS lymphoma. Neurology 58, 1513–1520 (2002).

    Article  CAS  PubMed  Google Scholar 

  49. Khan, R. B., Shi, W., Thaler, H. T., DeAngelis, L. M. & Abrey. L. E. Is intrathecal methotrexate necessary in the treatment of primary CNS lymphoma? J. Neurooncol. 58, 175–178 (2002).

    Article  PubMed  Google Scholar 

  50. Sierra Del Rio, M. et al. Prophylactic intrathecal chemotherapy in primary CNS lymphoma. J. Neurooncol. 106, 143–146 (2012).

    Article  CAS  PubMed  Google Scholar 

  51. Rubenstein, J. L. et al. Phase I study of intraventricular administration of rituximab in patients with recurrent CNS and intraocular lymphoma. J. Clin. Oncol. 25, 1350–1356 (2007).

    Article  CAS  PubMed  Google Scholar 

  52. Rubenstein, J. L. et al. Multicenter phase 1 trial of intraventricular immuno-chemotherapy in recurrent CNS lymphoma. Blood 121, 745–751 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Abrey, L. E. et al. Intensive methotrexate and cytarabine followed by high-dose chemotherapy with autologous stem-cell rescue in patients with newly diagnosed primary CNS lymphoma: an intent-to-treat analysis. J. Clin. Oncol. 21, 4151–4156 (2003).

    Article  CAS  PubMed  Google Scholar 

  54. Cheng, T. et al. High-dose thiotepa, busulfan, cyclophosphamide and ASCT without whole-brain radiotherapy for poor prognosis primary CNS lymphoma. Bone Marrow Transplant. 31, 679–685 (2003).

    Article  CAS  PubMed  Google Scholar 

  55. Brevet, M. et al. First-line autologous stem cell transplantation in primary CNS lymphoma. Eur. J. Haematol. 75, 288–292 (2005).

    Article  CAS  PubMed  Google Scholar 

  56. Illerhaus, G. et al. High dose chemotherapy with autologous stem-cell transplantation and hyperfractionated radiotherapy as first-line treatment of primary CNS lymphoma. J. Clin. Oncol. 24, 3865–3870 (2006).

    Article  CAS  PubMed  Google Scholar 

  57. Colombat, P. et al. High-dose chemotherapy with autologous stem cell transplantation as first-line therapy for primary CNS lymphoma in patients younger than 60 years: a multicenter phase II study of the GOELAMS group. Bone Marrow Transplant. 38, 417–420 (2006).

    Article  CAS  PubMed  Google Scholar 

  58. Montemurro, M. et al. Primary central nervous system lymphoma treated with high-dose methotrexate, high-dose busulfan/thiotepa, autologous stem-cell transplantation and response-adapted whole-brain radiotherapy: results of the multicenter Ostdeutsche Studiengruppe Hamato-Onkologie OSHO-53 phase II study. Ann. Oncol. 18, 665–671 (2007).

    Article  CAS  PubMed  Google Scholar 

  59. Illerhaus, G. et al. High-dose chemotherapy and autologous stem-cell transplantation without consolidating radiotherapy as first-line treatment for primary lymphoma of the central nervous system. Haematologica 93, 147–148 (2008).

    Article  CAS  PubMed  Google Scholar 

  60. Yoon, D. H. et al. Feasibility of BU, CY and etoposide (BUCYE), and auto-SCT in patients with newly diagnosed primary CNS lymphoma: a single-center experience. Bone Marrow Transplant. 46, 105–109 (2011).

    Article  CAS  PubMed  Google Scholar 

  61. Kasenda, B., Schorb, E., Fritsch, K., Finke, J. & Illerhaus, G. Prognosis after high-dose chemotherapy followed by autologous stem-cell transplantation as first-line treatment in primary CNS lymphoma—a long-term follow-up study. Ann. Oncol. 23, 2670–2673 (2012).

    Article  CAS  PubMed  Google Scholar 

  62. Rubenstein, J. L. et al. Rituximab therapy for CNS lymphomas: targeting the leptomeningeal compartment. Blood 101, 466–468 (2003).

    Article  CAS  PubMed  Google Scholar 

  63. Batchelor, T. T. et al. Rituximab monotherapy for patients with primary CNS lymphoma. Neurology 76, 929–930 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Jahnke, K. et al. Detection of subclinical systemic disease in primary CNS lymphoma by polymerase chain reaction of the rearranged immunoglobulin heavy-chain genes. J. Clin. Oncol. 24, 4754–4757 (2006).

    Article  CAS  PubMed  Google Scholar 

  65. McCann, K. J., Ashton-Key, M., Smith, K., Stevenson, F. K, & Ottensmeier, C. H. Primary central nervous system lymphoma: tumor-related clones exist in the blood and bone marrow with evidence for separate development. Blood 113, 4677–4680 (2009).

    Article  CAS  PubMed  Google Scholar 

  66. Shah, G. D. et al. Combined immunochemotherapy with reduced whole-brain radiotherapy for newly diagnosed CNS lymphoma. J. Clin. Oncol. 25, 4730–4735 (2007).

    Article  CAS  PubMed  Google Scholar 

  67. Chamberlain, M. C. & Johnston, S. K. High-dose methotrexate and rituximab with deferred radiotherapy for newly diagnoses primary B-cell CNS lymphoma. Neuro Oncol. 12, 736–744 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Wieduwilt, M. J. et al. Immunochemotherapy with intensive consolidation for primary CNS lymphoma: a pilot study and prognostic assessment by diffusion-weighted MRI. Clin. Cancer Res. 18, 1146–1155 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Nelson, D. F. et al. Non-Hodgkin's lymphoma of the brain: can high dose, large volume radiation therapy improve survival? Report on a prospective trial by the radiation oncology group (RTOG): RTOG 8315. Int. J. Radiat. Oncol. Biol. Phys. 23, 9–17 (1992).

    Article  CAS  PubMed  Google Scholar 

  70. Laperriere, H. J. et al. Primary lymphoma of brain: results of management of a modern cohort with radiation therapy. Radiother. Oncol. 43, 247–252 (1997).

    Article  CAS  PubMed  Google Scholar 

  71. Abrey, L. E., DeAngelis, L. M. & Yahalom, J. Long-term survival in primary CNS lymphoma. J. Clin. Oncol. 16, 859–863 (1998).

    Article  CAS  PubMed  Google Scholar 

  72. Ferreri, A. J. et al. Whole-brain radiotherapy in primary CNS lymphoma. Lancet Oncol. 12, 118–119 (2011).

    Article  PubMed  Google Scholar 

  73. Omuro, A. et al. Primary CNS lymphoma in patients younger than 60: can whole-brain radiotherapy be deferred? J. Neurooncol. 104, 323–330 (2011).

    Article  PubMed  Google Scholar 

  74. Ekenel, M. et al. Primary central nervous system lymphoma: the role of consolidation treatment after a complete response to high-dose methotrexate-based chemotherapy. Cancer 113, 1025–1031 (2008).

    Article  CAS  PubMed  Google Scholar 

  75. Correa, D. D. et al. Prospective cognitive follow-up in primary CNS lymphoma patients treated with chemotherapy and reduced-dose radiotherapy. J. Neurooncol. 91, 315–321 (2009).

    Article  CAS  PubMed  Google Scholar 

  76. Ferreri, A. How I treat primary CNS lymphoma. Blood 118, 510–522 (2011).

    Article  CAS  PubMed  Google Scholar 

  77. Bellinzona, M., Roser, F., Ostertag, H., Gaab, R. M. & Saini, M. Surgical removal of primary central nervous system lymphomas (PCNSL) presenting as space occupying lesions: a series of 33 cases. Eur. J. Surg. Oncol. 31, 100–105 (2005).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  79. Weller, M., Martus, P., Roth, P., Thiel, E. & Korfel, A. Surgery for primary CNS lymphoma? Challenging a paradigm. Neuro Oncol. 14, 1481–1484 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  80. Reni, M. et al. Primary central nervous system lymphomas: salvage treatment after failure to high-dose methotrexate. Cancer Lett. 258, 165–170 (2007).

    Article  CAS  PubMed  Google Scholar 

  81. Hottinger, A. F., DeAngelis, L. M., Yahalom, J. & Abrey, L. E. Salvage whole brain radiotherapy for recurrent or refractory primary CNS lymphoma. Neurology 69, 1178–1182 (2007).

    Article  PubMed  Google Scholar 

  82. Nguyen, P. L. et al. Results of whole brain radiation as salvage of methotrexate failure for immunocompetent patients with primary central nervous system lymphoma. J. Clin. Oncol. 23, 1507–1513 (2003).

    Article  Google Scholar 

  83. Omuro, A. M. et al. Delayed neurotoxicity in primary central nervous system lymphoma. Arch. Neurol. 62, 1595–1600 (2005).

    Article  PubMed  Google Scholar 

  84. Fischer, L. et al. Prospective trial on topotecan salvage therapy in primary CNS lymphoma. Ann. Oncol. 17, 1141–1145 (2006).

    Article  CAS  PubMed  Google Scholar 

  85. Voloschin, A. D., Betensky, R., Wen, P. Y., Hochberg, F. & Batchelor, T. Topotecan as salvage therapy for relapsed or refractory primary central nervous system lymphoma. J. Neurooncol. 86, 211–215 (2008).

    Article  CAS  PubMed  Google Scholar 

  86. Reni, M. et al. Temozolomide as salvage treatment in primary brain lymphomas. Br. J. Cancer. 96, 864–867 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Enting, R. H., Demopoulos, A., DeAngelis, L. M. & Abrey, L. E. Salvage therapy for primary CNS lymphoma with a combination of rituximab and temozolomide. Neurology 63, 901–903 (2004).

    Article  CAS  PubMed  Google Scholar 

  88. Arellano-Rodrigo, E. et al. Salvage treatment with etoposide (VP-16), ifosfamide and cytarabine (Ara-C) for patients with recurrent primary central nervous system lymphoma. Eur. J. Haematol. 70, 219–224 (2003).

    Article  CAS  PubMed  Google Scholar 

  89. Tyson, R. M. et al. Current status and future of relapsed primary central nervous system lymphoma (PCNSL). Leuk. Lymphoma 44, 627–633 (2003).

    Article  CAS  PubMed  Google Scholar 

  90. Mappa, S. et al. Salvage chemoimmunotherapy with rituximab, ifosfamide and etoposide (R-IE regimen) in patients with primary CNS lymphoma relapsed or refractory to high-dose methotrexate-based chemotherapy. Hematol. Oncol. http://dx.doi.org/10.1002/hon.2037.

  91. Plotkin, S. R. et al. Treatment of relapsed central nervous system lymphoma with high-dose methotrexate. Clin. Cancer Res. 10, 5643–5646 (2004).

    Article  CAS  PubMed  Google Scholar 

  92. Soussain, C. et al. Intensive chemotherapy followed by hematopoietic stem-cell rescue for refractory and recurrent primary CNS and intraocular lymphoma: Société Française de Greffe de Moelle Osseuse-Thérapie Cellulaire. J. Clin. Oncol. 26, 2512–2518 (2008).

    Article  PubMed  Google Scholar 

  93. Berenbom, A., Davila, R. M., Lin, H. S. & Harbour, J. W. Treatment outcomes for primary intraocular lymphoma: implications for external beam radiotherapy. Eye 21, 1198–1201 (2007).

    Article  CAS  PubMed  Google Scholar 

  94. Giuliari, G. P., Hinkle, D. M. & Foster, C. S. Local treatment for lymphoid malignancies of the eye. Anticancer Agents Med. Chem. 9, 1123–1128 (2009).

    Article  CAS  PubMed  Google Scholar 

  95. Grimm, S. A. et al. Primary intraocular lymphoma: an International Primary Central Nervous System Lymphoma Collaborative Group report. Ann. Oncol. 18, 1851–1855 (2007).

    Article  CAS  PubMed  Google Scholar 

  96. Jahnke, K. et al. Pharmacokinetics and efficacy of ifosfamide or trofosfamide in patients with intraocular lymphoma. Ann. Oncol. 16, 1974–1978 (2005).

    Article  CAS  PubMed  Google Scholar 

  97. Panageas, K. S., Elkin, E. B., Ben-Porat, L., DeAngelis, L. M. & Abrey, L. E. Patterns of treatment in older adults with primary central nervous system lymphoma. Cancer 110, 1338–1344 (2007).

    Article  PubMed  Google Scholar 

  98. Roth, P. et al. Outcome of elderly patients with primary CNS lymphoma in the G-PCNSL-SG-1 trial. Neurology 79, 890–896 (2012).

    Article  PubMed  Google Scholar 

  99. Ng, S., Rosenthal, M. A., Ashley, D. & Cher, L. High-dose methotrexate for primary CNS lymphoma in the elderly. Neuro Oncol. 2, 40–44 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Omuro, A. M. et al. Temozolomide and methotrexate for primary central nervous system lymphoma in the elderly. J. Neurooncol. 85, 207–211 (2007).

    Article  CAS  PubMed  Google Scholar 

  101. Illerhaus, G. et al. High-dose methotrexate combined with procarbazine and CCNU for primary CNS lymphoma in the elderly: results of a prospective pilot and phase II study. Ann. Oncol. 20, 319–325 (2009).

    Article  CAS  PubMed  Google Scholar 

  102. Zhu, J. J. et al. High-dose methotrexate for elderly patients with primary CNS lymphoma. Neuro Oncol. 11, 211–215 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Fritsch, K. et al. Immunochemotherapy with rituximab, methotrexate, procarbazine, and lomustine for primary CNS lymphoma (PCNSL) in the elderly. Ann. Oncol. 22, 2080–2085 (2011).

    Article  CAS  PubMed  Google Scholar 

  104. Kurzwelly, D. et al. Primary CNS lymphoma in the elderly: temozolomide therapy and MGMT status. J. Neurooncol. 97, 389–392 (2010).

    Article  CAS  PubMed  Google Scholar 

  105. Jahnke, K. et al. High-dose methotrexate toxicity in elderly patients with primary central nervous system lymphoma. Ann. Oncol. 16, 445–449 (2005).

    Article  CAS  PubMed  Google Scholar 

  106. Abla, O. et al. Primary CNS lymphoma in children and adolescents: a descriptive analysis from the International Primary CNS Lymphoma Collaborative Group (IPCG). Clin. Cancer Res. 17, 346–352 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Taylor, A. L., Marcus, R. & Bradley, J. A. Post-transplant lymphoproliferative disorders (PTLD) after solid organ transplantation. Crit. Rev. Oncol. Hematol. 56, 155–167 (2005).

    Article  PubMed  Google Scholar 

  108. Diamond, C. et al. Highly active antiretroviral therapy is associated with improved survival among patients with AIDS related primary central nervous system non-Hodgkin's lymphoma. Curr. HIV Res. 4, 375–378 (2006).

    Article  CAS  PubMed  Google Scholar 

  109. Skiest, D. J. & Crosby, C. Survival is prolonged by highly active antiretroviral therapy in AIDS patients with primary central nervous system lymphoma. AIDS 17, 1787–1793 (2003).

    Article  PubMed  Google Scholar 

  110. Jacomet, C. et al. Intravenous methotrexate for primary central nervous system non-Hodgkin's lymphoma in AIDS. AIDS 11, 1725–1730 (1997).

    Article  CAS  PubMed  Google Scholar 

  111. Faller, D. V., Mentzer, S. J. & Perrine, S. P. Induction of the Epstein- Barr virus thymidine kinase gene with concomitant nucleoside antivirals as a therapeutic strategy for Epstein-Barr virus-associated malignancies. Curr. Opin. Oncol. 13, 360–367 (2011).

    Article  Google Scholar 

  112. Roychowdhury, S. et al. Experimental treatment of Epstein-Barr virus-associated primary central nervous system lymphoma. Cancer Res. 63, 965–971 (2003).

    CAS  PubMed  Google Scholar 

  113. Lai, R., Abrey, L. E., Rosenblum, M. K. & DeAngelis, L. M. Treatment-induced leukoencephalopathy in primary CNS lymphoma. Neurology 62, 451–456 (2004).

    Article  PubMed  Google Scholar 

  114. Correa, D. D. et al. Cognitive functions in primary central nervous system lymphoma: literature review and assessment guidelines. Ann. Oncol. 18, 1145–1151 (2007).

    Article  CAS  PubMed  Google Scholar 

  115. Harder, H. et al. Cognitive status and quality of life after treatment for primary CNS lymphoma. Neurology 62, 544–547 (2004).

    Article  CAS  PubMed  Google Scholar 

  116. Correa, D. D. et al. Cognitive functions in survivors of primary central nervous system lymphoma. Neurology 62, 548–555 (2004).

    Article  CAS  PubMed  Google Scholar 

  117. Correa, D. D. et al. Cognitive functions in primary CNS lymphoma after single or combined modality treatments. Neuro Oncol. 14, 101–108 (2012).

    Article  CAS  PubMed  Google Scholar 

  118. Dietrich, J., Monje, M., Wefel, J. & Meyers, C. Clinical patterns and biological correlates of cognitive dysfunction associated with cancer therapy. Oncologist 13, 1285–1295 (2008).

    Article  PubMed  Google Scholar 

  119. Doolittle, N. D. et al. Long-term assessment and correlation of neuropsychological, neuroimaging and quality of life outcomes in primary CNS lymphoma survivor. Presented at the 2012 American Society of Clinical Oncology Annual Meeting (abstract 2040).

  120. Morton, L. M. et al. Lymphoma incidence patterns by WHO subtypes in the United States, 1992–2001. Blood 107, 265–276 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Sant, M. et al. Incidence of hematologic malignancies in Europe by morphologic subtype: results of the HAEMCARE project. Blood 116, 3724–3734 (2010).

    Article  CAS  PubMed  Google Scholar 

  122. Smith, A. et al. Incidence of haematological malignancy by subtype a report from the Hematological Malignancy Research Network. Brit. J. Cancer 105, 1684–1692 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Shenoy, P. J. et al. Racial differences in the presentation and outcome of diffuse large B-cell lymphoma in the United States. Cancer 117, 2530–2540 (2011).

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Haematology and Oncology, Charité—Campus Benjamin Franklin, University Medicine Berlin, Hindenburgdamm 30, Berlin, 12200, Germany

    Agnieszka Korfel

  2. Department of Neurology, Knappschaftskrankenhaus, Ruhr-University of Bochum, In der Schornau 23-25, Bochum, 44892, Germany

    Uwe Schlegel

Authors
  1. Agnieszka Korfel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Uwe Schlegel
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Both authors contributed to researching data for the article, discussion of the content, writing of the article, and to review and/or editing of the manuscript before submission.

Corresponding author

Correspondence to Agnieszka Korfel.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Korfel, A., Schlegel, U. Diagnosis and treatment of primary CNS lymphoma. Nat Rev Neurol 9, 317–327 (2013). https://doi.org/10.1038/nrneurol.2013.83

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrneurol.2013.83

This article is cited by

Search

Advanced search

Quick links

Nature Briefing: Cancer

Sign up for the Nature Briefing: Cancer newsletter — what matters in cancer research, free to your inbox weekly.

Get what matters in cancer research, free to your inbox weekly. Sign up for Nature Briefing: Cancer