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Vol 11, No 6 (2015)
Review paper
Published online: 2016-03-08
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Primary central nervous system lymphoma — a review of current therapeutic strategies

Michał Osowiecki, Beata Ostrowska, Jan Walewski
Oncol Clin Pract 2015;11(6):310-316.

open access

Vol 11, No 6 (2015)
REVIEW ARTICLES
Published online: 2016-03-08

Abstract

Primary central nervous system lymphoma (PCNSL) is a highly aggressive extranodal lymphoma subtype arising in the brain parenchyma, spinal cord, meninges, cranial nerves, and/or intraocularly. PCNSL accounts for 3% of brain tumours and 2–3% cases of non-Hodgkin’s lymphoma. Diffuse large B-cell lymphoma (DLBCL) is a primary diagnosis in 95% of all PCNSL, with highly aggressive lymphomas (Burkitt’s lymphoma, lymphoblastic lymphoma) and marginal zone lymphoma (MZL) or T-cell lymphomas accounting for the other 5%. Over the last 40 years, PCNSL rates have been increasing. Although PCNSL shares many histopathological features with DLBCL (not otherwise specified; NOS), its prognosis is generally far worse. The current WHO 2008 classification for cancers of the haematopoietic system and lymphomas assigns DLBCL CNS into a distinct diagnostic entity of lymphoma.

Abstract

Primary central nervous system lymphoma (PCNSL) is a highly aggressive extranodal lymphoma subtype arising in the brain parenchyma, spinal cord, meninges, cranial nerves, and/or intraocularly. PCNSL accounts for 3% of brain tumours and 2–3% cases of non-Hodgkin’s lymphoma. Diffuse large B-cell lymphoma (DLBCL) is a primary diagnosis in 95% of all PCNSL, with highly aggressive lymphomas (Burkitt’s lymphoma, lymphoblastic lymphoma) and marginal zone lymphoma (MZL) or T-cell lymphomas accounting for the other 5%. Over the last 40 years, PCNSL rates have been increasing. Although PCNSL shares many histopathological features with DLBCL (not otherwise specified; NOS), its prognosis is generally far worse. The current WHO 2008 classification for cancers of the haematopoietic system and lymphomas assigns DLBCL CNS into a distinct diagnostic entity of lymphoma.

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Keywords

llymphoma, central nervous system, methotrexate

About this article
Title

Primary central nervous system lymphoma — a review of current therapeutic strategies

Journal

Oncology in Clinical Practice

Issue

Vol 11, No 6 (2015)

Article type

Review paper

Pages

310-316

Published online

2016-03-08

Bibliographic record

Oncol Clin Pract 2015;11(6):310-316.

Keywords

llymphoma
central nervous system
methotrexate

Authors

Michał Osowiecki
Beata Ostrowska
Jan Walewski

References (53)
  1. Batchelor T, Loeffler JS. Primary CNS lymphoma. J Clin Oncol. 2006; 24(8): 1281–1288.
  2. 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(7): 1504–1510.
  3. Kurzwelly D, Glas M, Roth P, et al. Clinical presentation and therapeutic outcome in 26 patients with primary CNS lymphoma. Acta Neurol Scand. 1998; 97(4): 257–264.
  4. Camilleri-Broët S, Crinière E, Broët P, et al. A uniform activated B-cell-like immunophenotype might explain the poor prognosis of primary central nervous system lymphomas: analysis of 83 cases. Blood. 2006; 107(1): 190–196.
  5. Ponzoni M, Issa S, Batchelor TT, et al. Beyond high-dose methotrexate and brain radiotherapy: novel targets and agents for primary CNS lymphoma. Ann Oncol. 2014; 25(2): 316–322.
  6. Campo E, Swerdlow SH, Harris NL, et al. The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications. Blood. 2011; 117(19): 5019–5032.
  7. Rubenstein JL, Gupta NK, Mannis GN, et al. How I treat CNS lymphomas. Blood. 2013; 122(14): 2318–2330.
  8. Pirotte B, Levivier M, Goldman S, et al. Glucocorticoid-induced long-term remission in primary cerebral lymphoma: case report and review of the literature. J Neurooncol. 1997; 32(1): 63–69.
  9. Benevolo G, Stacchini A, Spina M, et al. Fondazione Italiana Linfomi. Final results of a multicenter trial addressing role of CSF flow cytometric analysis in NHL patients at high risk for CNS dissemination. Blood. 2012; 120(16): 3222–3228.
  10. Hegde U, Filie A, Little RF, et al. High incidence of occult leptomeningeal disease detected by flow cytometry in newly diagnosed aggressive B-cell lymphomas at risk for central nervous system involvement: the role of flow cytometry versus cytology. Blood. 2005; 105(2): 496–502.
  11. Baraniskin A, Kuhnhenn J, Schlegel U, et al. Identification of microRNAs in the cerebrospinal fluid as marker for primary diffuse large B-cell lymphoma of the central nervous system. Blood. 2011; 117(11): 3140–3146.
  12. Abrey LE, Batchelor TT, Ferreri AJM, 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. 2005; 23(22): 5034–5043.
  13. Cheson BD, Fisher RI, Barrington SF, et al. Alliance, Australasian Leukaemia and Lymphoma Group, Eastern Cooperative Oncology Group, European Mantle Cell Lymphoma Consortium, Italian Lymphoma Foundation, European Organisation for Research, Treatment of Cancer/Dutch Hemato-Oncology Group, Grupo Español de Médula Ósea, German High-Grade Lymphoma Study Group, German Hodgkin's Study Group, Japanese Lymphorra Study Group, Lymphoma Study Association, NCIC Clinical Trials Group, Nordic Lymphoma Study Group, Southwest Oncology Group, United Kingdom National Cancer Research Institute. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014; 32(27): 3059–3068.
  14. Ferreri AJM, Blay JY, Reni M, et al. Prognostic scoring system for primary CNS lymphomas: the International Extranodal Lymphoma Study Group experience. J Clin Oncol. 2003; 21(2): 266–272.
  15. 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(36): 5711–5715.
  16. Henry JM, Heffner RR, Dillard SH, et al. Primary malignant lymphomas of the central nervous system. Cancer. 1974; 34(4): 1293–1302.
  17. 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 8315. Int J Radiat Oncol Biol Phys. 1992; 23(1): 9–17.
  18. Morris PG, Correa DD, Yahalom J, et al. Long-term survival in primary CNS lymphoma. J Clin Oncol. 1998; 16(3): 859–863.
  19. Ervin T, Canellos GP. Successful treatment of recurrent primary central nervous system lymphoma with high-dose methotrexate. Cancer. 1980; 45(7): 1556–1557.
  20. DeAngelis LM, Yahalom J, Thaler HT, et al. Combined modality therapy for primary CNS lymphoma. Journal of Clinical Oncology. 1992; 10(4): 635–643.
  21. DeAngelis LM. Primary CNS lymphoma: treatment with combined chemotherapy and radiotherapy. J Neurooncol. 1999; 43(3): 249–257.
  22. Doolittle ND, Dósa E, Fu R, et al. Preservation of cognitive function in primary CNS lymphoma survivors a median of 12 years after enhanced chemotherapy delivery. J Clin Oncol. 2013; 31(31): 4026–4027.
  23. Shah GD, Yahalom J, Correa DD, et al. Combined immunochemotherapy with reduced whole-brain radiotherapy for newly diagnosed primary CNS lymphoma. J Clin Oncol. 2007; 25(30): 4730–4735.
  24. Korfel A, Thiel E, Martus P, et al. Randomized phase III study of whole-brain radiotherapy for primary CNS lymphoma. Neurology. 2015; 84(12): 1242–1248.
  25. Thiel E, Korfel A, Martus P, et al. 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. 2010; 11(11): 1036–1047.
  26. Morris PG, Correa DD, Yahalom J, et al. Rituximab, methotrexate, procarbazine, and vincristine followed by consolidation reduced-dose whole-brain radiotherapy and cytarabine in newly diagnosed primary CNS lymphoma: final results and long-term outcome. J Clin Oncol. 2013; 31(31): 3971–3979.
  27. Bataille B, Delwail V, Menet E, et al. Primary intracerebral malignant lymphoma: report of 248 cases. J Neurosurg. 2000; 92(2): 261–266.
  28. Weller M, Martus P, Roth P, et al. German PCNSL Study Group. Surgery for primary CNS lymphoma? Challenging a paradigm. Neuro Oncol. 2012; 14(12): 1481–1484.
  29. Ostrowska B, Osowiecki M, Domanska-Czyz K, et al. CHOP-R and high-dose methotrexete in the primary CNS lymphoma revisited: 10-year experience and 92 patients from single institution. Blood. 2013; 122: 3051.
  30. Blay JY, Conroy T, Chevreau C, et al. High-dose methotrexate for the treatment of primary cerebral lymphomas: analysis of survival and late neurologic toxicity in a retrospective series. J Clin Oncol. 1998; 16(3): 864–871.
  31. Khan RB, Shi W, Thaler HT, et al. Is intrathecal methotrexate necessary in the treatment of primary CNS lymphoma? J Neurooncol. 2002; 58(2): 175–178.
  32. 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(6): 1044–1049.
  33. DeAngelis LM, Seiferheld W, Schold SC, Fisher B, Schultz CJ. Combination chemotherapy and radiotherapy for primary central nervous system lymphoma: Radiation Therapy Oncology Group Study 93-10.
  34. Alvarnas JC, Negrin RS, Horning SJ, et al. High-dose therapy with hematopoietic cell transplantation for patients with central nervous system involvement by non-Hodgkin's lymphoma. Biol Blood Marrow Transplant. 2000; 6(3A): 352–358.
  35. Illerhaus G, Müller F, Feuerhake F, 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. 2008; 93(1): 147–148.
  36. Ferreri AJM, Reni M, Foppoli M, et al. International Extranodal Lymphoma Study Group (IELSG). High-dose cytarabine plus high-dose methotrexate versus high-dose methotrexate alone in patients with primary CNS lymphoma: a randomised phase 2 trial. Lancet. 2009; 374(9700): 1512–1520.
  37. Rubenstein JL, Hsi ED, Johnson JL, et al. Intensive chemotherapy and immunotherapy in patients with newly diagnosed primary CNS lymphoma: CALGB 50202 (Alliance 50202). J Clin Oncol. 2013; 31(25): 3061–3068.
  38. 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(6): 417–420.
  39. Chen YB, Batchelor T, Li S, et al. Phase 2 trial of high-dose rituximab with high-dose cytarabine mobilization therapy and high-dose thiotepa, busulfan, and cyclophosphamide autologous stem cell transplantation in patients with central nervous system involvement by non-Hodgkin lymphoma. Cancer. 2015; 121(2): 226–233.
  40. Omuro A, Correa DD, DeAngelis LM, et al. R-MPV followed by high-dose chemotherapy with TBC and autologous stem-cell transplant for newly diagnosed primary CNS lymphoma. Blood. 2015; 125(9): 1403–1410.
  41. Ferreri AJ, Cwynarski K, Pulczynski E, et al. Addition of thiotepa and rituximab to antimetabolites significantly improves outcomes in primary CNS lymphoma: first randomization of the IELSG32 trial. Hematol Oncol . 2015; 33: 103–104, 109.
  42. Schorb E, Kasenda B, Atta J, et al. Prognosis of patients with primary central nervous system lymphoma after high-dose chemotherapy followed by autologous stem cell transplantation. Haematologica. 2013; 98: 765–770.
  43. Batchelor TT, Grossman SA, Mikkelsen T, et al. Rituximab monotherapy for patients with recurrent primary CNS lymphoma. Neurology. 2011; 76(10): 929–930.
  44. Tomita N, Yokoyama M, Yamamoto W, et al. Central nervous system involvement in diffuse large B-cell lymphoma. Eur J Haematol. 2010; 85(1): 6–10.
  45. Ambady P, Holdhoff M, Bonekamp D, et al. High-dose methotrexate with or without rituximab in newly diagnosed primary CNS lymphoma. Neurology. 2014; 83(3): 235–239.
  46. Rubenstein JL, Fridlyand J, Abrey L, et al. Phase I study of intraventricular administration of rituximab in patients with recurrent CNS and intraocular lymphoma. J Clin Oncol. 2007; 25(11): 1350–1356.
  47. Plotkin SR, Betensky RA, Hochberg FH, et al. Treatment of relapsed central nervous system lymphoma with high-dose methotrexate. Clin Cancer Res. 2004; 10(17): 5643–5646.
  48. 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(7): 1507–1513.
  49. Soussain C, Hoang-Xuan K, Taillandier L, et al. Société Française de Greffe de Moëlle Osseuse-Thérapie Cellulaire. Intensive chemotherapy followed by hematopoietic stem-cell rescue for refractory and recurrent primary CNS and intraocular lymphoma: Société Française de Greffe de Moëlle Osseuse-Thérapie Cellulaire. J Clin Oncol. 2008; 26(15): 2512–2518.
  50. Soussain C, Choquet S, Fourme E, et al. Platine and cytarabine-based salvage treatment for primary central nervous system lymphoma. J Neurooncol. 2011; 105(2): 409–414.
  51. Korfel A, Elter T, Thiel E, et al. Phase II study of central nervous system (CNS)-directed chemotherapy including high-dose chemotherapy with autologous stem cell transplantation for CNS relapse of aggressive lymphomas. Haematologica. 2013; 98(3): 364–370.
  52. Illerhaus G, Fritsch K, Schmidt-Wolf I, et al. High dose-chemotherapy followed by autologous peripheral blood stem cell transplantation for patients with refractory or recurrent primary central nervous system lymphoma — results of a multicenter study by the Germany Collaborative PCNSL Study Group. Blood. 2014; 124: 2527.
  53. Wang CC, Carnevale J, Rubenstein JL. Progress in central nervous system lymphomas. Br J Haematol. 2014; 166(3): 311–325.

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