Primary Central Nervous System Lymphoma: Systemic Relapse

Chapter
Part of the Tumors of the Central Nervous System book series (TCNS, volume 9)

Abstract

Primary CNS lymphoma (PCNSL) is characterized by the presence of lymphoma cells limited to the CNS, with possible involvement of the eyes or the cerebrospinal fluid. A majority of PCNSL are diffuse large B-cell lymphomas with an aggressive course. Retrospective series show that about 4% of patients (range, 0–24%) may experience a systemic relapse, mainly with unusual extra-nodal involvement. Systemic relapse can occur very early after initial diagnosis of PCNSL, raising the question of the existence of a systemic lymphoma going undetected at the time of conventional PCNSL staging. Late relapse can occur more than 5 years after the diagnosis, suggesting the development of a second lymphoma or the emergence of a systemic lymphoma arising from circulating clones. Globally, the prognosis is poor but seems slightly more favorable than for patients with intra-cerebral relapse. The present chapter reviews the biological implications of systemic relapse in the pathogenesis of PCNSL.

Keywords

Median Overall Survival Autologous Stem Cell Transplantation Primary Central Nervous System Lymphoma Central Nervous System Relapse Systemic Relapse 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Abrey LE, Yahalom J, DeAngelis LM (2000) Treatment for primary CNS lymphoma: the next step. J Clin Oncol 18:3144–3150PubMedGoogle Scholar
  2. Abrey LE, Batchelor TT, Ferreri AJ, Gospodarowicz M, Pulczynski EJ, Zucca E, Smith JR, Korfel A, Soussain C, DeAngelis LM, Neuwelt EA, O’Neill BP, Thiel E, Shenkier T, Graus F, van den Bent M, Seymour JF, Poortmans P, Armitage JO, Cavalli F (2005) Report of an international workshop to standardize baseline evaluation and response criteria for primary CNS lymphoma. J Clin Oncol 23:5034–5043PubMedCrossRefGoogle Scholar
  3. Angelov L, Doolittle ND, Kraemer DF, Siegal T, Barnett GH, Peereboom DM, Stevens G, McGregor J, Jahnke K, Lacy CA, Hedrick NA, Shalom E, Ference S, Bell S, Sorenson L, Tyson RM, Haluska M, Neuwelt EA (2009) Blood–brain barrier disruption and intra-arterial methotrexate-based therapy for newly diagnosed ­primary CNS lymphoma: a multi-institutional experience. J Clin Oncol 27:3503–3509PubMedCrossRefGoogle Scholar
  4. Blay JY, Conroy T, Chevreau C, Thyss A, Quesnel N, Eghbali H, Bouabdallah R, Coiffier B, Wagner JP, Le Mevel A, Dramais-Marcel D, Baumelou E, Chauvin F, Biron P (1998) High-dose methotrexate for the treatment of primary cerebral lymphomas: analysis of survival and late neurologic toxicity in a retrospective series. J Clin Oncol 16:864–871PubMedGoogle Scholar
  5. Chuang SS, Liu H, Huang Y, Chio CC, Lin LC (2009) Primary cerebral diffuse large B-cell lymphoma relapsed solely in the skin with the same clonal origin. Appl Immunohistochem Mol Morphol 17:77–81PubMedCrossRefGoogle Scholar
  6. De Jong D, Glas AM, Boerrigter L, Hermus MC, Dalesio O, Willemse E, Nederlof PM, Kersten MJ (2003) Very late relapse in diffuse large B-cell lymphoma represents clonally related disease and is marked by germinal center cell features. Blood 102:324–327PubMedCrossRefGoogle Scholar
  7. DeAngelis LM, Seiferheld W, Schold SC, Fisher B, Schultz CJ (2002) Combination chemotherapy and radio­therapy for primary central nervous system lymphoma: Radiation Therapy Oncology Group Study 93–10. J Clin Oncol 20:4643–4648PubMedCrossRefGoogle Scholar
  8. Ferreri AJ, Reni M, Zoldan MC, Terreni MR, Villa E (1996) Importance of complete staging in non-Hodgkin’s lymphoma presenting as a cerebral mass lesion. Cancer 77:827–833PubMedCrossRefGoogle Scholar
  9. Ferreri AJ, Dell’Oro S, Foppoli M, Bernardi M, Brandes AA, Tosoni A, Montanari M, Balzarotti M, Spina M, Ilariucci F, Zaja F, Stelitano C, Bobbio F, Corazzelli G, Baldini L, Ponzoni M, Picozzi P, Caligaris CF, Reni M (2006) MATILDE regimen followed by radiotherapy is an active strategy against primary CNS lymphomas. Neurology 66:1435–1438PubMedCrossRefGoogle Scholar
  10. Ferreri AJ, Reni M, Foppoli M, Martelli M, Pangalis GA, Frezzato M, Cabras MG, Fabbri A, Corazzelli G, Ilariucci F, Rossi G, Soffietti R, Stelitano C, Vallisa D, Zaja F, Zoppegno L, Aondio GM, Avvisati G, Balzarotti M, Brandes AA, Fajardo J, Gomez H, Guarini A, Pinotti G, Rigacci L, Uhlmann C, Picozzi P, Vezzulli P, Ponzoni M, Zucca E, Caligaris-Cappio F, Cavalli F (2009) High-dose cytarabine plus high-dose methotrexate versus high-dose methotrexate alone in patients with primary CNS lymphoma: a randomised phase 2 trial. Lancet 374:1512–1520PubMedCrossRefGoogle Scholar
  11. Gavrilovic IT, Hormigo A, Yahalom J, DeAngelis LM, Abrey LE (2006) 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 24:4570–4574PubMedCrossRefGoogle Scholar
  12. Gerstner ER, Carson KA, Grossman SA, Batchelor TT (2008) Long-term outcome in PCNSL patients treated with high-dose methotrexate and deferred radiation. Neurology 70:401–402PubMedCrossRefGoogle Scholar
  13. Ghesquieres H, Ferlay C, Sebban C, Perol D, Bosly A, Casasnovas O, Reman O, Coiffier B, Tilly H, Morel P, Van den Neste E, Colin P, Haioun C, Biron P, Blay JY (2010) Long-term follow-up of an age-adapted C5R protocol followed by radiotherapy in 99 newly diagnosed primary CNS lymphomas: a prospective multicentric phase II study of the Groupe d’Etude des Lymphomes de l’Adulte (GELA). Ann Oncol 21:842–850PubMedCrossRefGoogle Scholar
  14. Gisselbrecht C, Glass B, Mounier N, Singh GD, Linch DC, Trneny M, Bosly A, Ketterer N, Shpilberg O, Hagberg H, Ma D, Briere J, Moskowitz CH, Schmitz N (2010) Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol 28:4184–4190PubMedCrossRefGoogle Scholar
  15. Herrlinger U, Kuker W, Uhl M, Blaicher HP, Karnath HO, Kanz L, Bamberg M, Weller M (2005) NOA-03 trial of high-dose methotrexate in primary central nervous system lymphoma: final report. Ann Neurol 57:843–847PubMedCrossRefGoogle Scholar
  16. Jahnke K, Hummel M, Korfel A, Burmeister T, Kiewe P, Klasen HA, Muller HH, Stein H, Thiel E (2006a) Detection of subclinical systemic disease in primary CNS lymphoma by polymerase chain reaction of the rearranged immunoglobulin heavy-chain genes. J Clin Oncol 24:4754–4757PubMedCrossRefGoogle Scholar
  17. Jahnke K, Thiel E, Martus P, Herrlinger U, Weller M, Fischer L, Korfel A (2006b) Relapse of primary central nervous system lymphoma: clinical features, outcome and prognostic factors. J Neurooncol 80:159–165PubMedCrossRefGoogle Scholar
  18. McAllister LD, Doolittle ND, Guastadisegni PE, Kraemer DF, Lacy CA, Crossen JR, Neuwelt EA (2000) Cogni­tive outcomes and long-term follow-up results after enhanced chemotherapy delivery for primary central nervous system lymphoma. Neurosurgery 46:51–60PubMedCrossRefGoogle Scholar
  19. McCann KJ, Ashton-Key M, Smith K, Stevenson FK, Ottensmeier CH (2009) Primary CNS lymphoma: tumor-related clones exist in the blood and bone marrow with evidence for separate development. Blood 113:4677–4680PubMedCrossRefGoogle Scholar
  20. Mohile NA, DeAngelis LM, Abrey LE (2008) The utility of body FDG PET in staging primary central nervous system lymphoma. Neuro Oncol 10:223–228PubMedCrossRefGoogle Scholar
  21. Nayak L, Hedvat C, Rosenblum MK, Abrey LE, DeAngelis LM (2011) Late relapse in primary central nervous system lymphoma: clonal persistence. Neuro Oncol 13:525–529PubMedCrossRefGoogle Scholar
  22. O’Brien P, Roos D, Pratt G, Liew K, Barton M, Poulsen M, Olver I, Trotter G (2000) Phase II multicenter study of brief single-agent methotrexate followed by irradiation in primary CNS lymphoma. J Clin Oncol 18:519–526PubMedGoogle Scholar
  23. Omuro AM, DeAngelis LM, Yahalom J, Abrey LE (2005) Chemoradiotherapy for primary CNS lymphoma: an intent-to-treat analysis with complete follow-up. Neurology 64:69–74PubMedCrossRefGoogle Scholar
  24. Omuro AM, Taillandier L, Chinot O, Carnin C, Barrie M, Hoang-Xuan K (2007) Temozolomide and methotrexate for primary central nervous system lymphoma in the elderly. J Neurooncol 85:207–211PubMedCrossRefGoogle Scholar
  25. O’Neill BP, Dinapoli RP, Kurtin PJ, Habermann TM (1995) Occult systemic non-Hodgkin’s lymphoma (NHL) in patients initially diagnosed as primary central nervous system lymphoma (PCNSL): how much staging is enough? J Neurooncol 25:67–71PubMedCrossRefGoogle Scholar
  26. Pels H, Schmidt-Wolf IG, Glasmacher A, Schulz H, Engert A, Diehl V, Zellner A, Schackert G, Reichmann H, Kroschinsky F, Vogt-Schaden M, Egerer G, Bode U, Schaller C, Deckert M, Fimmers R, Helmstaedter C, Atasoy A, Klockgether T, Schlegel U (2003) Primary central nervous system lymphoma: results of a pilot and phase II study of systemic and intraventricular chemotherapy with deferred radiotherapy. J Clin Oncol 21:4489–4495PubMedCrossRefGoogle Scholar
  27. Provencher S, Ferlay C, Alaoui-Slimani K, Devidas A, Lepretre S, de Prijck B, Sebban C, de la Fouchardiere A, Chassagne-Clement C, Ketterer N, Thyss A, Delannoy A, Tilly H, Biron P, Blay JY, Ghesquieres H (2011) Clinical characteristics and outcome of isolated extracerebral relapses of primary central nervous system lymphoma: a case series. Hematol Oncol 29:10–16PubMedCrossRefGoogle Scholar
  28. Thiel E, Korfel A, Martus P, Kanz L, Griesinger F, Rauch M, Roth A, Hertenstein B, von Toll T, Hundsberger T, Mergenthaler HG, Leithauser M, Birnbaum T, Fischer L, Jahnke K, Herrlinger U, Plasswilm L, Nagele T, Pietsch T, Bamberg M, Weller M (2010) 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 11:1036–1047PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  1. 1.Department of Medical Oncology, Centre Léon BérardUniversité de LyonLyonFrance

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