Management of Primary Central Nervous System Lymphoma

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  • 1 Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, New York

Primary central nervous system lymphoma (PCNSL) is a unique subtype of non-Hodgkin's lymphoma (NHL). Although PCNSL is both chemosensitive and radiosensitive, it is very difficult to treat and outcomes are substantially inferior when compared with similar extranodal NHL. Furthermore, as a subtype of brain tumors and NHL, the overall incidence has been increasing over the past several decades. This review summarizes the salient clinical features and approach to management of the immunocompetent patient with PCNSL.

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Correspondence: Lauren E. Abrey, MD, Department of Neurology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021. E-mail: abreyl@mskcc.org
  • 1

    Abrey LE, DeAngelis LM, Yahalom J. Long-term survival in primary CNS lymphoma. J Clin Oncol 1998;16:859863.

  • 2

    Paulus W. Classification, pathogenesis and molecular pathology of primary CNS lymphomas. J Neurooncol 1999;43:203208.

  • 3

    Schlegel U, Schmidt-Wolf IG, Deckert M. Primary CNS lymphoma: clinical presentation, pathological classification, molecular pathogenesis and treatment. J Neurol Sci 2000;181:112.

    • Search Google Scholar
    • Export Citation
  • 4

    Bailey P. Intracranial sarcomatous tumours of leptomeningeal origin. Arch Surg 1929;18:13591402.

  • 5

    Olson JE, Janney CA, Rao RD. The continuing increase in the incidence of primary central nervous system non-Hodgkin lymphoma: a surveillance, epidemiology, and end results analysis. Cancer 2002;95:15041510.

    • Search Google Scholar
    • Export Citation
  • 6

    Cote TR, Manns A, Hardy CR. Epidemiology of brain lymphoma among people with or without acquired immunodeficiency syndrome. AIDS/Cancer Study Group. J Natl Cancer Inst 1996;88:675679.

    • Search Google Scholar
    • Export Citation
  • 7

    CBTRUS. Statistical Report: Primary Brain Tumors in the United States, 1995–1999. Central Brain Tumor Registry of the United States, 2002. Available at www.cbtrus.org

    • Search Google Scholar
    • Export Citation
  • 8

    Gurney JG, Kadan-Lottick N. Brain and other central nervous system tumors: rates, trends, and epidemiology. Curr Opin Oncol 2001;13:160166.

    • Search Google Scholar
    • Export Citation
  • 9

    Deangelis LM, Yahalom J, Rosenblum M, Posner JB. Primary CNS lymphoma: managing patients with spontaneous and AIDS-related disease. Oncology (Huntingt) 1987;1:5262.

    • Search Google Scholar
    • Export Citation
  • 10

    Herrlinger U, Schabet M, Bitzer M. Primary central nervous system lymphoma: from clinical presentation to diagnosis. J Neurooncol 1999;43:219226.

    • Search Google Scholar
    • Export Citation
  • 11

    Maher EA, Fine HA. Primary CNS lymphoma. Semin Oncol 1999;26:346356.

  • 12

    Buhring U, Herrlinger U, Krings T. MRI features of primary central nervous system lymphomas at presentation. Neurology 2001;57:393396.

  • 13

    Jenkins CN, Colquhoun IR. Characterization of primary intracranial lymphoma by computed tomography: an analysis of 36 cases and a review of the literature with particular reference to calcification haemorrhage and cyst formation. Clin Radiol 1998;53:428434.

    • Search Google Scholar
    • Export Citation
  • 14

    Roelcke U, Leenders KL. PET in neuro-oncology. J Cancer Res Clin Oncol 2001;127:28.

  • 15

    Roelcke U, Leenders KL. Positron emission tomography in patients with primary CNS lymphomas. J Neurooncol 1999;43:231236.

  • 16

    Taylor CR, Russell R, Lukes RJ, Davis RL. An immunohistological study of immunoglobulin content of primary central nervous system lymphomas. Cancer 1978;41:21972205.

    • Search Google Scholar
    • Export Citation
  • 17

    Tuaillon N, Chan CC. Molecular analysis of primary central nervous system and primary intraocular lymphomas. Curr Mol Med 2001;1:259272.

  • 18

    Gijtenbeek JM, Rosenblum MK, DeAngelis LM. Primary central nervous system T-cell lymphoma. Neurology 2001;57:716718.

  • 19

    Camilleri-Broet S, Martin A, Moreau A. Primary central nervous system lymphomas in 72 immunocompetent patients: pathologic findings and clinical correlations. Groupe Ouest Est d'etude des Leucenies et Autres Maladies du Sang (GOELAMS). Am J Clin Pathol 1998;110:607612.

    • Search Google Scholar
    • Export Citation
  • 20

    Bessell EM, Lopez-Guillermo A, Villa S. 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;20:231236.

    • Search Google Scholar
    • Export Citation
  • 21

    Ferreri AJ, Blay JY, Reni M. Prognostic scoring system for primary CNS lymphomas: the International Extranodal Lymphoma Study Group experience. J Clin Oncol 2003;21:266272.

    • Search Google Scholar
    • Export Citation
  • 22

    Fine HA, Mayer RJ. Primary central nervous system lymphoma. Ann Intern Med 1993;119:10931104.

  • 23

    DeAngelis LM, J Y. Primary central nervous lymphoma. In: DeVita VT HS, Rosenberg SA, eds., ed. Cancer: Principles and Practice of Oncology. Philadelphia, PA: Lippincott Williams and Wilkins, 2001:23302339.

    • Search Google Scholar
    • Export Citation
  • 24

    Henry JM, Heffner RR Jr, Dillard SH. Primary malignant lymphomas of the central nervous system. Cancer 1974;34:12931302.

  • 25

    Hochberg FH, Miller DC. Primary central nervous system lymphoma. J Neurosurg 1988;68:835853.

  • 26

    Whitcup SM, Stark-Vancs V, Wittes RE. Association of interleukin 10 in the vitreous and cerebrospinal fluid and primary central nervous system lymphoma. Arch Ophthalmol 1997;115:11571160.

    • Search Google Scholar
    • Export Citation
  • 27

    Miller DC, Hochberg FH, Harris NL. Pathology with clinical correlations of primary central nervous system non-Hodgkin's lymphoma. The Massachusetts General Hospital experience 1958-1989. Cancer 1994;74:13831397.

    • Search Google Scholar
    • Export Citation
  • 28

    Herrlinger U. Primary CNS lymphoma: findings outside the brain. J Neurooncol 1999;43:227230.

  • 29

    DeAngelis LM, Yahalom J, Heinemann MH. Primary CNS lymphoma: combined treatment with chemotherapy and radiotherapy. Neurology 1990;40:8086.

  • 30

    Todd FD 2nd, Miller CA, Yates AJ, Mervis LJ. Steroid-induced remission in primary malignant lymphoma of the central nervous system. Surg Neurol 1986;26:7984.

    • Search Google Scholar
    • Export Citation
  • 31

    Weller M. Glucocorticoid treatment of primary CNS lymphoma. J Neurooncol 1999;43:237239.

  • 32

    Nelson DF, Martz KL, Bonner H. 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;23:917.

    • Search Google Scholar
    • Export Citation
  • 33

    Berry MP, Simpson WJ. Radiation therapy in the management of primary malignant lymphoma of the brain. Int J Radiat Oncol Biol Phys 1981;7:5559.

    • Search Google Scholar
    • Export Citation
  • 34

    Hochberg FH, Loeffler JS, Prados M. The therapy of primary brain lymphoma. J Neurooncol 1991;10:191201.

  • 35

    Hormigo A, DeAngelis LM. Primary ocular lymphoma: clinical features, diagnosis, and treatment. Clin Lymphoma 2003;4:2229.

  • 36

    Chan CC, Buggage RR, Nussenblatt RB. Intraocular lymphoma. Curr Opin Ophthalmol 2002;13:411418.

  • 37

    Ferreri AJ, Reni M, Villa E. Therapeutic management of primary central nervous system lymphoma: lessons from prospective trials. Ann Oncol 2000;11:927937.

    • Search Google Scholar
    • Export Citation
  • 38

    Stewart DJ, Russell N, Atack EA. Cyclophosphamide, doxorubicin, vincristine, and dexamethasone in primary lymphoma of the brain: a case report. Cancer Treat Rep 1983;67:287291.

    • Search Google Scholar
    • Export Citation
  • 39

    Shibamoto Y, Tsutsui K, Dodo Y. Improved survival rate in primary intracranial lymphoma treated by high-dose radiation and systemic vincristine-doxorubicin-cyclophosphamide-prednisolone chemotherapy. Cancer 1990;65:19071912.

    • Search Google Scholar
    • Export Citation
  • 40

    Lachance DH, Brizel DM, Gockerman JP. Cyclophosphamide, doxorubicin, vincristine, and prednisone for primary central nervous system lymphoma: short-duration response and multifocal intracerebral recurrence preceding radiotherapy. Neurology 1994;44:17211727.

    • Search Google Scholar
    • Export Citation
  • 41

    Mead GM, Bleehen NM, Gregor A. 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 2000;89:13591370.

    • Search Google Scholar
    • Export Citation
  • 42

    Schultz C, Scott C, Sherman W. 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;14:556564.

    • Search Google Scholar
    • Export Citation
  • 43

    Brada M, Hjiyiannakis D, Hines F. Short intensive primary chemotherapy and radiotherapy in sporadic primary CNS lymphoma (PCL). Int J Radiat Oncol Biol Phys 1998;40:11571162.

    • Search Google Scholar
    • Export Citation
  • 44

    Reni M, Ferreri AJ, Garancini MP, Villa E. Therapeutic management of primary central nervous system lymphoma in immunocompetent patients: results of a critical review of the literature. Ann Oncol 1997;8:227234.

    • Search Google Scholar
    • Export Citation
  • 45

    Blay JY, Conroy T, Chevreau C. 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;16:864871.

    • Search Google Scholar
    • Export Citation
  • 46

    Loeffler JS, Ervin TJ, Mauch P. Primary lymphomas of the central nervous system: patterns of failure and factors that influence survival. J Clin Oncol 1985;3:490494.

    • Search Google Scholar
    • Export Citation
  • 47

    Gabbai AA, Hochberg FH, Linggood RM. High-dose methotrexate for non-AIDS primary central nervous system lymphoma. Report of 13 cases. J Neurosurg 1989;70:190194.

    • Search Google Scholar
    • Export Citation
  • 48

    Glass J, Gruber ML, Cher L, Hochberg FH. Preirradiation methotrexate chemotherapy of primary central nervous system lymphoma: long-term outcome. J Neurosurg 1994;81:188195.

    • Search Google Scholar
    • Export Citation
  • 49

    DeAngelis LM, Yahalom J, Thaler HT, Kher U. Combined modality therapy for primary CNS lymphoma. J Clin Oncol 1992;10:635643.

  • 50

    Sandor V, Stark-Vancs V, Pearson D. Phase II trial of chemotherapy alone for primary CNS and intraocular lymphoma. J Clin Oncol 1998;16:30003006.

    • Search Google Scholar
    • Export Citation
  • 51

    Cheng AL, Yeh KH, Uen WC. Systemic chemotherapy alone for patients with non-acquired immunodeficiency syndrome-related central nervous system lymphoma: a pilot study of the BOMES protocol. Cancer 1998;82:19461951.

    • Search Google Scholar
    • Export Citation
  • 52

    Guha-Thakurta N, Damek D, Pollack C, Hochberg FH. Intravenous methotrexate as initial treatment for primary central nervous system lymphoma: response to therapy and quality of life of patients. J Neurooncol 1999;43:259268.

    • Search Google Scholar
    • Export Citation
  • 53

    Abrey LE, Yahalom J, DeAngelis LM. Treatment for primary CNS lymphoma: the next step. J Clin Oncol 2000;18:31443150.

  • 54

    McAllister LD, Doolittle ND, Guastadisegni PE. Cognitive outcomes and long-term follow-up results after enhanced chemotherapy delivery for primary central nervous system lymphoma. Neurosurgery 2000;46:5160; discussion 60–61.

    • Search Google Scholar
    • Export Citation
  • 55

    Ferreri AJ, Reni M, Dell'Oro S. 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;60:134140.

    • Search Google Scholar
    • Export Citation
  • 56

    DeAngelis LM, Seiferheld W, Schold SC. Combination chemotherapy and radiotherapy for primary central nervous system lymphoma: Radiation Therapy Oncology Group Study 93-10. J Clin Oncol 2002;20:46434648.

    • Search Google Scholar
    • Export Citation
  • 57

    Batchelor T, Carson K, O'Neill A. Treatment of primary CNS lymphoma with methotrexate and deferred radiotherapy: a report of NABTT 96-07. J Clin Oncol 2003;21:10441049.

    • Search Google Scholar
    • Export Citation
  • 58

    Poortmans PM, Kluin-Nelemans HC, Haaxma-Reiche H. 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;21:44834488.

    • Search Google Scholar
    • Export Citation
  • 59

    Pels H, Schmidt-Wolf IG, Glasmacher A. 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;21:44894495.

    • Search Google Scholar
    • Export Citation
  • 60

    Hiraga S, Arita N, Ohnishi T. Rapid infusion of high-dose methotrexate resulting in enhanced penetration into cerebrospinal fluid and intensified tumor response in primary central nervous system lymphomas. J Neurosurg 1999;91:221230.

    • Search Google Scholar
    • Export Citation
  • 61

    Khan RB, Shi W, Thaler HT. Is intrathecal methotrexate necessary in the treatment of primary CNS lymphoma? J Neurooncol 2002;58:175178.

  • 62

    Ferreri AJ, Guerra E, Regazzi M. Area under the curve of methotrexate and creatinine clearance are outcome-determining factors in primary CNS lymphomas. Br J Cancer 2004;90:353358.

    • Search Google Scholar
    • Export Citation
  • 63

    Abrey LE, Moskowitz CH, Mason WP. 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;21:41514156.

    • Search Google Scholar
    • Export Citation
  • 64

    Reni M, Ferreri AJ, Landoni C, Villa E. Salvage therapy with temozolomide in an immunocompetent patient with primary brain lymphoma. J Natl Cancer Inst 2000;92:575576.

    • Search Google Scholar
    • Export Citation
  • 65

    Pels H, Schulz H, Schlegel U, Engert A. Treatment of CNS lymphoma with the anti-CD20 antibody rituximab: experience with two cases and review of the literature. Onkologie 2003;26:351354.

    • Search Google Scholar
    • Export Citation
  • 66

    Ciordia R, Hochberg F, Batchelor T. Topotecan as salvage therapy for refractory or relapsed primary central nervous system lymphoma. Proc Am Soc Clin Oncol 2000:165a, Abstract 639.

    • Search Google Scholar
    • Export Citation
  • 67

    Peterson K, Gordon KB, Heinemann MH, DeAngelis LM. The clinical spectrum of ocular lymphoma. Cancer 1993;72:843849.

  • 68

    Kessler LS, Ruiz A, Donovan Post MJ. Thallium-201 brain SPECT of lymphoma in AIDS patients: pitfalls and technique optimization. AJNR Am J Neuroradiol 1998;19:11051109.

    • Search Google Scholar
    • Export Citation
  • 69

    Lorberboym M, Wallach F, Estok L. Thallium-201 retention in focal intracranial lesions for differential diagnosis of primary lymphoma and nonmalignant lesions in AIDS patients. J Nucl Med 1998;39:13661369.

    • Search Google Scholar
    • Export Citation
  • 70

    Antinori A, De Rossi G, Ammassari A. Value of combined approach with thallium-201 single-photon emission computed tomography and Epstein-Barr virus DNA polymerase chain reaction in CSF for the diagnosis of AIDS-related primary CNS lymphoma. J Clin Oncol 1999;17:554560.

    • Search Google Scholar
    • Export Citation
  • 71

    Tosi P, Gherlinzoni F, Visani G. AZT plus methotrexate in HIV-related non-Hodgkin's lymphomas. Leuk Lymphoma 1998;30:175179.

  • 72

    Jacomet C, Girard PM, Lebrette MG. Intravenous methotrexate for primary central nervous system non-Hodgkin's lymphoma in AIDS. Aids 1997;11:17251730.

    • Search Google Scholar
    • Export Citation
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