Skip to main content

Advertisement

SpringerLink
Log in

Treatment of primary central nervous system lymphoma

  • Published:
Current Treatment Options in Neurology Aims and scope Submit manuscript

Opinion statement

Primary central nervous system lymphoma (PCNSL) is a rare form of extranodal non-Hodgkin’s lymphoma that is typically confined to brain, eyes, and cerebrospinal fluid without evidence of systemic spread. The prognosis of patients with PCNSL has improved during the past decade with the introduction of high-dose methotrexate with or without whole brain radiotherapy. However, despite recent progress, results following treatment are durable in few patients, and therapy can be associated with late neurotoxicity. PCNSL is an uncommon tumor, and no phase III trial has been completed so far, leaving many questions about its optimum first-line and salvage treatments unanswered. This review summarizes the literature regarding the treatment of PCNSL in immunocompetent patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Olson JE, Janney CA, Rao RD, et al.: The continuing increase in the incidence of primary central nervous system non-Hodgkin lymphoma: a surveillance, epidemiology, and end results analysis. Cancer 2002, 95:1504–1510.

    Article  PubMed  Google Scholar 

  2. Panageas KS, Elkin EB, DeAngelis LM, et al.: Trends in survival from primary central nervous system lymphoma, 1975–1999. Cancer 2005, 104:2466–2472.

    Article  PubMed  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  4. Nelson DF, Martz KL, Bonner H, 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 Therapy Oncology Group (RTOG): RTOG 83-15. Int J Radiat Oncol Biol Phys 1992, 23:9–17.

    PubMed  CAS  Google Scholar 

  5. Ferreri A, Reni M: Prognostic factors in primary central nervous system lymphomas. Hematol Oncol Clin North Am 2005, 19:629–649.

    Article  PubMed  Google Scholar 

  6. Abrey LE, Ben-Porat L, Panageas KS, et al.: Primary central nervous system lymphoma: the Memorial Sloan-Kettering Cancer Center prognostic model. J Clin Oncol 2006, 24:1–8.

    Article  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  8. Weller M: Glucocorticoid treatment of primary CNS lymphoma. J Neuro-oncol 1999, 43:237–239.

    Article  CAS  Google Scholar 

  9. Pirotte B, Levivier M, Goldman S, et al.: Glucocorticoid induced long term remission in primary cerebral lymphoma: case report and review of literature: J Neuro-oncol 1997, 32:63–69.

    Article  CAS  Google Scholar 

  10. Laack NN, Ballman KV, Brown PB, et al.: Whole-brain radiotherapy and high dose methylprednisolone for elderly patients with primary central nervous system lymphoma: results of North Central Cancer Treatment Group (NCCTG) 96-75-51. Int J Radiat Oncol Biol Phys 2006, 65:1429–1439.

    PubMed  CAS  Google Scholar 

  11. Mathew BS, Carson KA, Grossman SA: Initial response to glucocorticoids. Cancer 2006, 106:383–387.

    Article  PubMed  CAS  Google Scholar 

  12. Shibamoto Y, Ogino H, Hasegawa M, et al.: Results of radiation monotherapy for primary central nervous system lymphoma in the 1990s. Int J Radiat Oncol Biol Phys 2005, 62:809–813.

    PubMed  Google Scholar 

  13. Lai R, Rosenblum MK, DeAngelis LM, et al.: Primary CNS lymphoma: a whole-brain disease? Neurology 2002, 59:1557–1562.

    PubMed  Google Scholar 

  14. Shibamoto Y, Hayabuchi N, Hiratsuka J, et al.: Is whole-brain irradiation necessary for primary central nervous system lymphoma? Patterns of recurrence after partialbrain irradiation. Cancer 2003, 97:128–133.

    Article  PubMed  Google Scholar 

  15. Bessell EM, Lopez-Guillermo A, Villa S, et al.: Importance of radiotherapy in the outcome of patients with primary CNS lymphoma: an analysis of the CHOD/BVAM regimen followed by two different radiotherapy treatments. J Clin Oncol 2002, 20:231–236.

    Article  PubMed  CAS  Google Scholar 

  16. Fisher B, Seiferheld W, Schultz C, et al.: Secondary analysis of Radiation Therapy Oncology Group study (RTOG) 93-10: an intergroup phase II combined modality treatment of primary central nervous system lymphoma. J Neuro-oncol 2005, 74:201–205.

    Article  Google Scholar 

  17. Schultz C, Scott C, Sherman W, et al.: Preirradiation chemotherapy with cyclophosphamide, doxorubicin, vincristine, and dexamethasone for primary CNS lymphomas: initial report of Radiation Therapy Oncology Group protocol 88-06. J Clin Oncol 1996, 14:556–564.

    PubMed  CAS  Google Scholar 

  18. Lachance DH, Brizel DM, Gockerman JP, et al.: Cyclophosphamide, doxorubicin, vincristine, and prednisone for primary central nervous system lymphoma. Neurology 1994, 44:1721–1727.

    PubMed  CAS  Google Scholar 

  19. DeAngelis LM, Yahalom J, Thaler HT, et al.: Combined modality therapy for primary CNS lymphoma. J Clin Oncol 1992, 10:635–643.

    PubMed  CAS  Google Scholar 

  20. O’Brien P, Roos D, Pratt G, et al.: Phase II multicenter study of brief single-agent methotrexate followed by irradiation in primary CNS lymphoma. J Clin Oncol 2000, 18:519–526.

    PubMed  CAS  Google Scholar 

  21. O’Brien PC, Roos DE, Pratt G, 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 2006, 64:408–413.

    PubMed  Google Scholar 

  22. Omuro AM, DeAngelis LM, Yahalom J, et al.: Chemoradiotherapy for primary CNS lymphoma: an intent-to-treat analysis with complete follow-up. Neurology 2005, 64:69–74.

    Article  PubMed  CAS  Google Scholar 

  23. Korfel A, Martus P, Nowrousian MR, et al.: Response to chemotherapy and treating institution predict survival in primary central nervous system lymphoma. Br J Hematol 2004, 128:177–183.

    Article  Google Scholar 

  24. Gavrilovic IT, Hormigo A, Yahalom J, et al.: Long term follow up of high dose methotrexate based therapy with and without whole brain irradiation for newly diagnosed primary CNS lymphoma. J Clin Oncol 2006, 24:4570–4574.

    Article  PubMed  CAS  Google Scholar 

  25. DeAngelis LM, Seiferheld W, Schold SC, et al.: Combination chemotherapy and radiotherapy for primary central nervous system lymphoma: Radiation Therapy Oncology Group Study 93-10. J Clin Oncol 2002, 20:4643–4648.

    Article  PubMed  Google Scholar 

  26. Ferreri AJ, Reni M, Dell’Oro S, et al.: Combined treatment with high-dose methotrexate, vincristine and procarbazine, without intrathecal chemotherapy, followed by consolidation radiotherapy for primary central nervous system lymphoma in immunocompetent patients. Oncology 2001, 60:134–140.

    Article  PubMed  CAS  Google Scholar 

  27. Glass J, Gruber ML, Cher L, et al.: Preirradiation methotrexate chemotherapy of primary central nervous system lymphoma: long-term outcome. J Neurosurg 1994, 81:188–195.

    Article  PubMed  CAS  Google Scholar 

  28. Poortmans PM, Kluin-Nelemans HC, Haaxma-Reiche H, 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 2003, 21:4483–4488.

    Article  PubMed  CAS  Google Scholar 

  29. Ferreri AJ, Dell’Oro S, Foppoli M, et al.: MATILDE regimen followed by radiotherapy is an active strategy against primary CNS lymphomas. Neurology 2006, 66:1435–1438.

    Article  PubMed  CAS  Google Scholar 

  30. Hoang-Xuan K, Taillandier L, Chinot O, et al.: 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 2003, 21:2726–2731.

    Article  PubMed  CAS  Google Scholar 

  31. Pels H, Schmidt-Wolf IG, Glasmacher A, 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 2003, 21:4489–4495.

    Article  PubMed  CAS  Google Scholar 

  32. Sandor V, Stark-Vancs V, Pearson D, et al.: Phase II trial of chemotherapy alone for primary CNS and intraocular lymphoma. J Clin Oncol 1998, 16:3000–3006.

    PubMed  CAS  Google Scholar 

  33. Cheng AL, Yeh KH, Uen WC, et al.: Systemic chemotherapy alone for patients with non-acquired immunodeficiency syndrome-related central nervous system lymphoma: a pilot study of the BOMES protocol. Cancer 1998, 82:1946–1951.

    Article  PubMed  CAS  Google Scholar 

  34. Herrlinger U, Schabet M, Brugger W, et al.: German Cancer Society Neuro-oncology Working Group NOA-03 multicenter trial of single-agent high-dose methotrexate for primary central nervous system lymphoma. Ann Neurol 2002, 51:247–252.

    Article  PubMed  CAS  Google Scholar 

  35. Herrlinger U, Kuker W, Uhl M, et al.: NOA-03 trial of high-dose methotrexate in primary central nervous system lymphoma: final report. Ann Neurol 2005, 57:843–847.

    Article  PubMed  CAS  Google Scholar 

  36. Batchelor T, Carson K, O’Neill A, et al.: Treatment of primary CNS lymphoma with methotrexate and deferred radiotherapy: a report of NABTT 96-07. J Clin Oncol 2003, 21:1044–1049.

    Article  PubMed  CAS  Google Scholar 

  37. Kraemer DF, Fortin D, Doolittle ND, et al.: Association of total dose intensity of chemotherapy in primary central nervous system lymphoma (human non-acquired immunodeficiency syndrome) and survival. Neurosurgery 2001, 48:1033–1040.

    Article  PubMed  CAS  Google Scholar 

  38. Soussain C, Suzan F, Hoang-Xuan K, et al.: Results of intensive chemotherapy followed by hematopoietic stem-cell rescue in 22 patients with refractory or recurrent primary CNS lymphoma or intraocular lymphoma. J Clin Oncol 2001, 19:742–749.

    PubMed  CAS  Google Scholar 

  39. Abrey LE, Moskowitz CH, Mason WP, 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 2003, 21:4151–4156.

    Article  PubMed  CAS  Google Scholar 

  40. Cheng T, Forsyth P, Chaudhry A, et al.: High-dose thiotepa, busulfan, cyclophosphamide and ASCT without whole-brain radiotherapy for poor prognosis primary CNS lymphoma. Bone Marrow Transplant 2003, 31:679–685.

    Article  PubMed  CAS  Google Scholar 

  41. Brevet M, Garidi R, Gruson B, et al.: First-line autologous stem cell transplantation in primary CNS lymphoma. Eur J Haematol 2005, 75:288–292.

    Article  PubMed  CAS  Google Scholar 

  42. Illerhaus G, Marks R, Ihorst 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 2006, 24:3865–3870.

    Article  PubMed  CAS  Google Scholar 

  43. Colombat PH, Lemevel A, Bertrand 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 2006, 38:417–420.

    Article  PubMed  CAS  Google Scholar 

  44. Herrlinger U, Brugger W, Bamberg M, et al.: PCV salvage chemotherapy for recurrent primary CNS lymphoma. Neurology 2000, 54:1707–1708.

    PubMed  CAS  Google Scholar 

  45. Reni M, Mason W, Zaja F, et al.: Salvage chemotherapy with temozolomide in primary CNS lymphomas: preliminary results of a phase II trial. Eur J Cancer 2004, 40:1682–1688.

    Article  PubMed  CAS  Google Scholar 

  46. Enting RH, Demopoulos A, DeAngelis LM, et al.: Salvage therapy for primary CNS lymphoma with a combination of rituximab and temozolomide. Neurology 2004, 63:901–903.

    PubMed  CAS  Google Scholar 

  47. Arellano-Rodrigo E, Lopez-Guillermo A, Bessell EM, 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 2003, 70:219–224.

    Article  PubMed  CAS  Google Scholar 

  48. Fischer L, Thiel E, Klasen HA, et al.: Prospective trial on topotecan salvage therapy in primary CNS lymphoma. Ann Oncol 2006, 17:1141–1145.

    Article  PubMed  CAS  Google Scholar 

  49. Nguyen PL, Chakravarti A, Finkelstein DM, et al.: Results of whole-brain radiation as salvage of methotrexate failure for immunocompetent patients with primary CNS lymphoma. J Clin Oncol 2005, 23:1507–1513.

    Article  PubMed  Google Scholar 

  50. Plotkin SR, Betensky RA, Hochberg FH, et al.: Treatment of relapsed central nervous system lymphoma with high-dose methotrexate. Clin Cancer Res 2004, 10:5643–5646.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY, 10021, USA

    Lisa M. DeAngelis MD

Authors
  1. Meltem Ekenel MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lisa M. DeAngelis MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lisa M. DeAngelis MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ekenel, M., DeAngelis, L.M. Treatment of primary central nervous system lymphoma. Curr Treat Options Neurol 9, 271–282 (2007). https://doi.org/10.1007/s11940-007-0013-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11940-007-0013-6

Keywords

Search

Navigation