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Neurotherapeutics. 2009 July; 6(3): 587–597.
PMCID: PMC4942275
NIHMSID: NIHMS130545

Biology and treatment of primary central nervous system lymphoma

Summary

Primary central nervous system lymphoma (PCNSL) is a rare variant of extranodal non-Hodgkin lymphoma that is restricted in distribution to the brain, leptomeninges, spinal cord, and intraocular compartments. Although PCNSL shares overlapping features with systemic lymphoma, recent studies also reveal a unique pattern of gene and protein expression in PCNSL. These findings have yielded new insights into the pathophysiology of the disease, as well as the identification of novel prognostic biomarkers. Immune system compromise, such as is seen in acquired immune deficiency syndrome (AIDS), is the best established known risk factor for PCNSL. Like other lesions of the brain, meninges, and eye, the presenting symptoms associated with PCNSL typically include focal neurological deficits related to the site of disease or more global consequences of increased intracranial pressure. Diagnosis of PCNSL typically includes gadolinium-enhanced MRI and pathologic tissue analysis, as well as additional studies aimed at excluding concurrent systemic disease. PCNSL typically has a worse overall prognosis than systemic lymphoma. High-dose chemotherapy, particularly with methotrexate-based regimens, is the backbone of therapy for most patients, and chemotherapy is associated with much lower rates of treatment-related morbidity and mortality than whole-brain irradiation. Autologous stem cell transplantation is an emerging treatment modality, particularly in younger patients with relapsed disease, but high rates of treatment-related mortality are observed in older patients. Immunotherapy, including treatment with intrathecal rituximab, is another area of active research that may have promise in refractory or relapsed disease. Treatment options for intraocular lymphoma parallel those for PCNSL elsewhere in the brain: systemic chemotherapy, radiation, and local delivery of cytotoxic and immunologically active agents such as anti-CD20 antibody.

Key Words: Brain tumor treatment, gene expression, pathobiology, immunotherapy

References

1. Hochberg FH, Baehring JM, Hochberg EP. Primary CNS lymphoma. Nat Clin Pract Neurol. 2007;3:24–35. doi: 10.1038/ncpneuro0395. [PubMed] [Cross Ref]
2. Fine HA, Mayer RJ. Primary central nervous system lymphoma. Ann Intern Med. 1993;119:1093–1104. [PubMed]
3. Cote TR, Manns A, Hardy CR, Yellin FJ, Hartge P, AIDS/Cancer Study Group Epidemiology of brain lymphoma among people with or without acquired immunodeficiency syndrome. J Natl Cancer Inst. 1996;88:675–679. doi: 10.1093/jnci/88.10.675. [PubMed] [Cross Ref]
4. Diamond C, Taylor TH, Aboumrad T, Anton-Culver H. Changes in acquired immunodeficiency syndrome-related non-Hodgkin lymphoma in the era of highly active antiretroviral therapy: incidence, presentation, treatment, and survival. Cancer. 2006;106:128–135. doi: 10.1002/cncr.21562. [PubMed] [Cross Ref]
5. Kadoch C, Treseler P, Rubenstein JL. Molecular pathogenesis of primary central nervous system lymphoma. Neurosurg Focus. 2006;21(5):E1–E1. doi: 10.3171/foc.2006.21.5.2. [PubMed] [Cross Ref]
6. Montesinos-Rongen M, Kuppers R, Schluter D, et al. Primary central nervous system lymphomas are derived from germinal-center B cells and show a preferential usage of the V4-34 gene segment. Am J Pathol. 1999;155:2077–2086. doi: 10.1016/S0002-9440(10)65526-5. [PubMed] [Cross Ref]
7. 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;107:190–196. doi: 10.1182/blood-2005-03-1024. [PubMed] [Cross Ref]
8. Lin CH, Kuo KT, Chuang SS, et al. Comparison of the expression and prognostic significance of differentiation markers between diffuse large B-cell lymphoma of central nervous system origin and peripheral nodal origin. Clin Cancer Res. 2006;12:1152–1156. doi: 10.1158/1078-0432.CCR-05-1699. [PubMed] [Cross Ref]
9. Rubenstein JL, Fridlyand J, Shen A, et al. Gene expression and angiotropism in primary CNS lymphoma. Blood. 2006;107:3716–3723. doi: 10.1182/blood-2005-03-0897. [PubMed] [Cross Ref]
10. Montesinos-Rongen M, Van Roost D, Schaller C, Wiestler OD, Deckert M. Primary diffuse large B-cell lymphomas of the central nervous system are targeted by aberrant somatic hypermutation. Blood. 2004;103:1869–1875. doi: 10.1182/blood-2003-05-1465. [PubMed] [Cross Ref]
11. Rubenstein JL, Shen A, Fridlyand J, et al. Gene expression profile analysis of primary CNS lymphoma: class distinction and outcome prediction. Proc Am Assoc Cancer Res 2004;45:abstract 4433.
12. Tun HW, Personett D, Baskerville KA, et al. Pathway analysis of primary central nervous system lymphoma. Blood. 2008;111:3200–3210. doi: 10.1182/blood-2007-10-119099. [PubMed] [Cross Ref]
13. Han JI, Huang NN, Kim DU, Kehrl JH. RGS1 and RGS13 mRNA silencing in a human B lymphoma line enhances responsiveness to chemoattractants and impairs desensitization. J Leukoc Biol. 2006;79:1357–1368. doi: 10.1189/jlb.1105693. [PubMed] [Cross Ref]
14. Cobbers JM, Wolter M, Reifenberger J, et al. Frequent inactivation of CDKN2A and rare mutation of TP53 in PCNSL. Brain Pathol. 1998;8:263–276. doi: 10.1111/j.1750-3639.1998.tb00152.x. [PubMed] [Cross Ref]
15. Rubenstein JL, Treseler P, O’Brien JM. Pathology and genetics of primary central nervous system and intraocular lymphoma. Hematol Oncol Clin North Am. 2005;19:705–717. doi: 10.1016/j.hoc.2005.05.012. [PubMed] [Cross Ref]
16. Harada K, Nishizaki T, Kubota H, et al. Distinct primary central nervous system lymphoma defined by comparative genomic hybridization and laser scanning cytometry. Cancer Genet Cytogenet. 2001;125:147–150. doi: 10.1016/S0165-4608(00)00377-0. [PubMed] [Cross Ref]
17. Nakamura M, Kishi M, Sakaki T, et al. Novel tumor suppressor loci on 6q22–23 in primary central nervous system lymphomas. Cancer Res. 2003;63:737–741. [PubMed]
18. Mazzucchelli L, Blaser A, Rappeler A, et al. BCA-1 is highly expressed in Helicobacter prylori-induced mucosa-associated lymphoid tissue and gastric lymphoma. J Clin Invest. 1999;104:R49–R54. doi: 10.1172/JCI7830. [PMC free article] [PubMed] [Cross Ref]
19. Smith JR, Braziel RM, Paoletti S, et al. Expression of B-cell-attracting chemokine 1 (CXCL13) by malignant lymphocytes and vascular endothelium in primary central nervous system lymphoma. Blood. 2003;101:815–821. doi: 10.1182/blood-2002-05-1576. [PubMed] [Cross Ref]
20. Antinori A, De Rossi G, Ammassari A, et al. Value of combined approach with thallium-201 single-photon emission computed tomography and Epstein-Barr viras DNA polymerase chain reaction in CSF for the diagnosis of AIDS-related primary CNS lymphoma. J Clin Oncol. 1999;17:554–560. [PubMed]
21. Bossolasco S, Cinque P, Ponzoni M, et al. Epstein-Barr virus DNA load in cerebrospinal fluid and plasma of patients with AIDS-related lymphoma. J Neurovirol. 2002;8:432–438. doi: 10.1080/13550280260422730. [PubMed] [Cross Ref]
22. Klemschmidt-DeMasters BK, Damek DM, Lillehei KO, Dogan A, Giannini C. Epstein Barr virus-associated primary CNS lymphomas in elderly patients on immunosuppressive medications. J Neuropathol Exp Neurol. 2008;67:1103–111. doi: 10.1097/NEN.0b013e31818beaea. [PubMed] [Cross Ref]
23. Penn I. The role of immunosuppression in lymphoma formation. Springer Semin Immunopathol. 1998;20:343–355. doi: 10.1007/BF00838048. [PubMed] [Cross Ref]
24. Cingolani A, Gastaldi R, Fassone L, et al. Epsteiu-Barr virus infection is predictive of CNS involvement in systemic AIDS-related non-Hodgkin’s lymphomas. J Clin Oncol. 2000;18:3325–3330. [PubMed]
25. Roy S, Josephson SA, Fridlyand J, et al. Protein biomarker identification in the CSF of patients with CNS lymphoma. J Clin Oncol. 2008;26:96–105. doi: 10.1200/JCO.2007.12.1053. [PMC free article] [PubMed] [Cross Ref]
26. Kadan-Lottick NS, Skluzacek MC, Gurney JG. Decreasing incidence rates of primary central nervous system lymphoma. Cancer. 2002;95:193–202. doi: 10.1002/cncr.10643. [PubMed] [Cross Ref]
27. Schabet M. Epidemiology of primary CNS lymphoma. J Neurooncol. 1999;43:199–201. doi: 10.1023/A:1006290032052. [PubMed] [Cross Ref]
28. Penu I, Porat G. Central nervous system lymphomas in organ allograft recipients. Transplantation. 1995;59:240–244. [PubMed]
29. 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. doi: 10.1002/cncr.10851. [PubMed] [Cross Ref]
30. Hochberg FH, Batchelor T, Loeffler JS. Clinical presentation, pathologic features, and diagnosis of primary central nervous system lymphoma. Available at: http://www.uptodate.com. Last updated: Nov. 13, 2008; last literature review version 17.1: January 2009. Accessed April 24, 2009.
31. Hormigo A, Abrey L, Heinemann MH, DeAngelis LM. Ocular presentation of primary central nervous system lymphoma: diagnosis and treatment. Br J Haematol. 2004;126:202–208. doi: 10.1111/j.1365-2141.2004.05028.x. [PubMed] [Cross Ref]
32. Park S, Abad S, Tulliez M, et al. Pseudouveitis: a clue to the diagnosis of primary central nervous system lymphoma in immunocompetent patients. Medicine (Baltimore) 2004;83:223–232. doi: 10.1097/01.md.0000134850.35118.46. [PubMed] [Cross Ref]
33. Buhring U, Herrlinger U, Krings T, Thiex R, Weller M, Küker W. MRI features of primary central nervous system lymphomas at presentation. Neurology. 2001;57:393–396. [PubMed]
34. Cha S, Knopp EA, Johnson G, et al. Intracranial mass lesions: dynamic contrast-enhanced susceptibility-weighted echo-planar perfusion MR imaging. Radiology. 2002;223:11–29. doi: 10.1148/radiol.2231010594. [PubMed] [Cross Ref]
35. Guo AC, Cummings TJ, Dash RC, Provenzale JM. Lymphomas and high-grade astrocytomas: comparison of water diffusibility and histologic characteristics. Radiology. 2002;224:177–183. doi: 10.1148/radiol.2241010637. [PubMed] [Cross Ref]
36. Huang MQ, Pickup S, Nelson DS, et al. Monitoring response to chemotherapy of non-Hodgkin’s lymphoma xenografts by T2-weighted and diffusion-weighted MRI. NMR Biomed. 2008;21:1021–1029. doi: 10.1002/nbm.1261. [PubMed] [Cross Ref]
37. Balmaceda C, Gaynor JJ, Sun M, Gluck JT, DeAngelis LM. Leptomeningeal tumor in primary central nervous system lymphoma: recognition, significance, and implications. Ann Neurol. 1995;38:202–209. doi: 10.1002/ana.410380212. [PubMed] [Cross Ref]
38. Batchelor T, Loeffler JS. Primary CNS lymphoma. J Clin Oncol. 2006;24:1281–1288. doi: 10.1200/JCO.2005.04.8819. [PubMed] [Cross Ref]
39. Fitzsimmons A, Upchurch K, Batchelor T. Clinical features and diagnosis of primary central nervous system lymphoma. Hematol Oncol Clin North Am. 2005;19:689–703. doi: 10.1016/j.hoc.2005.05.009. [PubMed] [Cross Ref]
40. Pierce MA, Johnson MD, Maciunas RJ, et al. Evaluating contrast-enhancing brain lesions in patients with AIDS by using positron emission tomography. Ann Intern Med. 1995;123:594–598. [PubMed]
41. Kulkarni AV, Guha A, Lozano A, Bernstein M. Incidence of silent hemorrhage and delayed deterioration after stereotactic brain biopsy. J Neurosurg. 1998;89:31–35. doi: 10.3171/jns.1998.89.1.0031. [PubMed] [Cross Ref]
42. Boviatsis EJ, Kouyialis AT, Stranjalis G, Korfias S, Sakas DE. CT-guided stereotactic biopsies of brain stem lesions: personal experience and literature review. Neurol Sci. 2003;24:97–102. doi: 10.1007/s10072-003-0093-3. [PubMed] [Cross Ref]
43. Soo TM, Bernstein M, Provias J, et al. Failed stereotactic biopsy in a series of 518 cases. Stereotact Funct Neurosurg. 1995;64:183–196. [PubMed]
44. Weller M. Glucocorticoid treatment of primary CNS lymphoma. J Neurooncol. 1999;43:237–239. doi: 10.1023/A:1006254518848. [PubMed] [Cross Ref]
45. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: central nervous system cancers. Available at: http://www.nccn.org/professionals/physician_gls/f_guidelines. asp. Accessed April 24, 2009.
46. Jahnke K, Hummel M, Korfel A, 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. 2006;24:4754–4757. doi: 10.1200/JCO.2006.06.7165. [PubMed] [Cross Ref]
47. Ferreri AJ, Blay JY, Reni M, et al. Prognostic scoring system for primary CNS lymphomas: the International Extranodal Lymphoma Study Group experience. J Clin Oncol. 2003;21:266–272. doi: 10.1200/JCO.2003.09.139. [PubMed] [Cross Ref]
48. Abrey LE, DeAngelis LM, Yahalom J. Long-term survival in primary CNS lymphoma. J Clin Oncol. 1998;16:859–863. [PubMed]
49. Bellinzona M, Roser F, Ostertag H, Gaab RM, Saint M. 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. doi: 10.1016/j.ejso.2004.10.002. [PubMed] [Cross Ref]
50. Henry JM, Heffner RR, Dillard SH, Earle KM, Davis RL. Primary malignant lymphomas of the central nervous system. Cancer. 1974;34:1293–1302. doi: 10.1002/1097-0142(197410)34:4<1293::AID-CNCR2820340441>3.0.CO;2-P. [PubMed] [Cross Ref]
51. Murray K, Kun L, Cox J. Primary malignant lymphoma of the central nervous system: results of treatment of 11 cases and review of the literature. J Neurosurg. 1986;65:600–607. doi: 10.3171/jns.1986.65.5.0600. [PubMed] [Cross Ref]
52. DeAngelis LM. Current management of primary central nervous system lymphoma. Oncology (Williston Park) 1995;9:63–71. [PubMed]
53. 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;23:9–17. doi: 10.1016/0360-3016(92)90538-S. [PubMed] [Cross Ref]
54. Harder H, Holtel H, Bromberg JE, et al. Cognitive status and quality of life after treatment for primary CNS lymphoma. Neurology. 2004;62:544–547. [PubMed]
55. Bessell EM, López-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. doi: 10.1200/JCO.20.1.231. [PubMed] [Cross Ref]
56. DeAngelis LM, Yahalom J, Thaler HT, Kher U. Combined modality therapy for primary CNS lymphoma. J Clin Oncol. 1992;10:635–643. [PubMed]
57. Omuro AM, Ben-Porat LS, Panageas KS, et al. Delayed neurotoxicity in primary central nervous system lymphoma. Arch Neurol. 2005;62:1595–1600. doi: 10.1001/archneur.62.10.1595. [PubMed] [Cross Ref]
58. DeAngelis LM, Sciferheld W, Schold SC, Fisher B, Schultz CJ, Radiation Therapy Oncology Group Study 93-10 Combination chemotherapy and radiotherapy for primary central nervous system lymphoma: Radiation Therapy Oncology Group Study 93-10. J Clin Oncol. 2002;20:4643–4648. doi: 10.1200/JCO.2002.11.013. [PubMed] [Cross Ref]
59. 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;25:4730–4735. doi: 10.1200/JCO.2007.12.5062. [PubMed] [Cross Ref]
60. Correa DD, Rocco-Donovan M, DeAngelis LM, et al. Prospective cognitive follow-up in primary CNS lymphoma patients treated with chemotherapy and reduced-dose radiotherapy. J Neurooncol. 2009;91:315–321. doi: 10.1007/s11060-008-9716-0. [PubMed] [Cross Ref]
61. 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. doi: 10.1200/JCO.2003.03.108. [PubMed] [Cross Ref]
62. Ervin T, Canellos GP. Successful treatment of recurrent primary central nervous system lymphoma with high-dose methotrexate. Cancer. 1980;45:1556–1557. doi: 10.1002/1097-0142(19800401)45:7<1556::AID-CNCR2820450707>3.0.CO;2-B. [PubMed] [Cross Ref]
63. Herbst KD, Corder MP, Justice GR. Successful therapy with methotrexate of a multicentric mixed lymphoma of the central nervous system. Cancer. 1976;38:1476–1478. doi: 10.1002/1097-0142(197610)38:4<1476::AID-CNCR2820380405>3.0.CO;2-J. [PubMed] [Cross Ref]
64. O’Neill BP, O’Fallon JR, Earle JD, et al. Primary central nervous system non-Hodgkin’s lymphoma: survival advantages with combined initial therapy? Int J Radiat Oncol Biol Phys. 1995;33:663–673. doi: 10.1016/0360-3016(95)00207-F. [PubMed] [Cross Ref]
65. 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]
66. Shapiro WR, Young DF, Mehta BM. Methotrexate: distribution in cerebrospinal fluid after intravenous, ventricular and lumbar injections. N Engl J Med. 1975;293:161–166. doi: 10.1056/NEJM197507242930402. [PubMed] [Cross Ref]
67. Glantz MJ, Cole BF, Recht L, et al. High-dose intravenous methotrexate for patients with nonleukemic leptomeningeal cancer: is intrathecal chemotherapy necessary? J Clin Oncol. 1998;16:1561–1567. [PubMed]
68. Khan RB, Shi W, Thaler HT, DeAngelis LM, Abrey LE. Is intrathecal methotrexate necessary in the treatment of primary CNS lymphoma? J Neurooncol. 2002;58:175–178. doi: 10.1023/A:1016077907952. [PubMed] [Cross Ref]
69. Doolittle ND, Miner ME, Hall WA, et al. Safety and efficacy of a multicenter study using intraarterial chemotherapy in conjunction with osmotic opening of the blood-brain barrier for the treatment of patients with malignant brain tumors. Cancer. 2000;88:637–647. doi: 10.1002/(SICI)1097-0142(20000201)88:3<637::AID-CNCR22>3.0.CO;2-Y. [PubMed] [Cross Ref]
70. McAllister LD, Doolittle ND, Guastadisegni PE, et al. Cognitive outcomes and long-term follow-up results after enhanced chemotherapy delivery for primary central nervous system lymphoma. Neurosurgery. 2000;46:51–60. doi: 10.1097/00006123-200001000-00010. [PubMed] [Cross Ref]
71. Cher L, Glass J, Harsh GR, Hochberg FH. Therapy of primary CNS lymphoma with methotrexate-based chemotherapy and deferred radiotherapy: preliminary results. Neurology. 1996;46:1757–1759. [PubMed]
72. 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;43:259–268. doi: 10.1023/A:1006210703827. [PubMed] [Cross Ref]
73. 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. doi: 10.1200/JCO.2003.03.036. [PubMed] [Cross Ref]
74. Herrlinger U, Küker 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. doi: 10.1002/ana.20495. [PubMed] [Cross Ref]
75. 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. doi: 10.1016/j.ejca.2004.03.008. [PubMed] [Cross Ref]
76. Reni M, Zaja F, Mason W, et al. Temozolomide as salvage treatment in primary brain lymphomas. Br J Cancer. 2007;96:864–867. doi: 10.1038/sj.bjc.6603660. [PMC free article] [PubMed] [Cross Ref]
77. Coiffier B, Lepage E, Briere J, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002;346:235–242. doi: 10.1056/NEJMoa011795. [PubMed] [Cross Ref]
78. Rubenstein JL, Combs D, Rosenberg J, et al. Rituximab therapy for CNS lymphomas: targeting the leptomeningeal compartment. Blood. 2003;101:466–468. doi: 10.1182/blood-2002-06-1636. [PubMed] [Cross Ref]
79. Stemmler HJ, Schmitt M, Willems A, et al. Ratio of trastuzumab levels in serum and cerebrospinal fluid is altered in HER2-positive breast cancer patients with brain metastases and impairment of blood-brain barrier. Anticancer Drugs. 2007;18:23–28. doi: 10.1097/01.cad.0000236313.50833.ee. [PubMed] [Cross Ref]
80. Issa S, Shen A, Karch J, et al. Treatment of primary CNS lymphoma with induction high-dose methotrexate, temozolomide, rituximab followed by consolidation cytarabine/etoposide: a pilot study with biomarker analysis. Presented at the American Society of Hematology 2008 Annual Meeting; December 8, 2008; Atlanta, GA. Abstract 1364.
81. 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. doi: 10.1200/JCO.2003.04.056. [PubMed] [Cross Ref]
82. Pels H, Juergens A, Glasmacher A, et al. Early relapses in primary CNS lymphoma after response to polychemotherapy without intraventricular treatment: results of a phase II study. J Neurooncol. 2009;91:299–305. doi: 10.1007/s11060-008-9712-4. [PubMed] [Cross Ref]
83. 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. doi: 10.1200/JCO.2003.05.024. [PubMed] [Cross Ref]
84. Montemurro M, Kiefer T, Schüler F, 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 multi-center Ostdeutsche Studiengruppe Hämato-Onkologie OSHO-53 phase II study. Ann Oncol. 2007;18:665–671. doi: 10.1093/annonc/mdl458. [PubMed] [Cross Ref]
85. 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 Moelle Osseuse-Thérapie Cellulaire. J Clin Oncol. 2008;26:2512–2518. doi: 10.1200/JCO.2007.13.5533. [PubMed] [Cross Ref]
86. 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. doi: 10.1158/1078-0432.CCR-04-0159. [PubMed] [Cross Ref]
87. Herrlinger U, Brugger W, Bamberg M, Küker W, Dichgans J, Weller M. PCV salvage chemotherapy for recurrent primary CNS lymphoma. Neurology. 2000;54:1707–1708. [PubMed]
88. 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. doi: 10.1200/JCO.2005.01.161. [PubMed] [Cross Ref]
89. Sakamoto M, Oya N, Mizowaki T, et al. Initial experiences of palliative stereotactic radiosurgery for recurrent brain lymphomas. J Neurooncol. 2006;77:53–58. doi: 10.1007/s11060-005-7698-8. [PubMed] [Cross Ref]
90. 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;25:1350–1356. doi: 10.1200/JCO.2006.09.7311. [PubMed] [Cross Ref]
91. Chamberlain MC, Johnston SK, Van Horn A, Glantz MJ. Recurrent lymphomatous meningitis treated with intra-CSF rituximab and liposomal ara-C. J Neurooncol. 2009;91:271–277. doi: 10.1007/s11060-008-9707-1. [PubMed] [Cross Ref]
92. de Smet MD, Stark-Vancs V, Kohler DR, Smith J, Wittes R, Nussenblatt RB. Intraocular levels of methotrexate after intravenous administration. Am J Ophthalmol. 1996;121:442–444. [PubMed]
93. Batchelor TT, Kolak G, Ciordia R, Foster CS, Henson JW. High-dose methotrexate for intraocular lymphoma. Clin Cancer Res. 2003;9:711–715. [PubMed]
94. Baumann MA, Ritch PS, Hande KR, et al. Treatment of intraocular lymphoma with high-dose Ara-C. Cancer. 1986;57:1273–1275. doi: 10.1002/1097-0142(19860401)57:7<1273::AID-CNCR2820570702>3.0.CO;2-C. [PubMed] [Cross Ref]
95. Grimm SA, McCannel CA, Omuro AM, et al. Primary CNS lymphoma with intraocular involvement: International PCNSL Collaborative Group Report. Neurology. 2008;71:1355–1360. doi: 10.1212/01.wnl.0000327672.04729.8c. [PMC free article] [PubMed] [Cross Ref]
96. Itty S, Pulido JS. Rituximab for intraocular lymphoma. Retina. 2009;29:129–132. doi: 10.1097/IAE.0b013e318192f574. [PubMed] [Cross Ref]
97. Kim H, Csaky KG, Chan CC, et al. The pharmacokinetics of rituximab following an intravitreal injection. Exp Eye Res. 2006;82:760–766. doi: 10.1016/j.exer.2005.09.018. [PubMed] [Cross Ref]
98. Ohguro N, Hashida N, Tano Y. Effect of intravitreous rituximab injections in patients with recurrent ocular lesions associated with central nervous system lymphoma. Arch Ophthalmol. 2008;126:1002–1003. doi: 10.1001/archopht.126.7.1002. [PubMed] [Cross Ref]
99. Rubenstein JL, Shen A, Batchelor TT, Kadoch C, Treseler P, Shuman MA. Differential gene expression in central nervous system lymphoma. Blood. 2009;113:266–267. doi: 10.1182/blood-2008-04-152835. [PubMed] [Cross Ref]

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