Download PDF
Onkologie up2date 2021; 03(03): 253-265
DOI: 10.1055/a-1510-5709
Onkologische Hämatologie

Primäre Lymphome des zentralen Nervensystems

Uwe Schlegel
1   Mund-, Kiefer- u. Gesichtschirurgie, Knappschaftskrankenhaus, Bochum, Deutschland
,
Sabine Seidel
1   Mund-, Kiefer- u. Gesichtschirurgie, Knappschaftskrankenhaus, Bochum, Deutschland
› Author Affiliations
› Further Information
    Permissions and Reprints All articles of this category

Primäre ZNS-Lymphome sind Non-Hodgkin Lymphome des Gehirnparenchyms, der Meningen, und/oder des Rückenmarks mit fakultativer Beteiligung der Augen. Durch die Verfügbarkeit effektiver Chemotherapieprotokolle hat sich die Prognose dieser Tumoren insbesondere für jüngere Patienten in den letzten Jahrzehnten deutlich verbessert.
Kernaussagen

  • Primäre ZNS-Lymphome (PZNSL) sind seltene maligne Tumoren des zentralen Nervensystems und überwiegend den diffus großzelligen B-Zell-Non-Hodgkin-Lymphomen zuzuordnen

  • Die operative Entfernung des Tumors spielt keine Rolle.

  • Die Strahlentherapie sollte in der Primärtherapie und im Rezidiv aufgrund neurotoxischer Spätfolgen wann immer möglich vermieden werden.

  • Eine alleinige Chemotherapie basierend auf Hochdosis-Methotrexat (HDMTX) führt insbesondere bei jüngeren Patienten häufig zu Langzeitremissionen.

  • Die Chemotherapie sollte aus einem Induktions- und einem Konsolidierungsteil bestehen.

  • Im Rezidiv besteht keine etablierte Standardtherapie, jedoch stellen hier neue gezielte Therapieansätze, die in klinischen Studien geprüft werden, interessante Möglichkeiten dar.



Publication History

Article published online:
03 September 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • Literatur

  • 1 Ostrom QT, Cioffi G, Gittleman H. et al. CBTRUS Statistical Report: primary brain and other central nervous system tumors diagnosed in the United States in 2012–2016. Neuro Oncol 2019; 21: v1-v100 DOI: 10.1093/neuonc/noz150. (PMID: 31675094)
    CrossrefPubMedGoogle Scholar
  • 2 Camilleri-Broët S, Martin A, Moreau A. et al. Primary central nervous system lymphomas in 72 immunocompetent patients: pathologic findings and clinical correlations. Groupe Ouest Est d’étude des Leucénies et Autres Maladies du Sang (GOELAMS). Am J Clin Pathol 1998; 110: 607-612 DOI: 10.1093/ajcp/110.5.607. (PMID: 9802345)
    CrossrefPubMedGoogle Scholar
  • 3 Mendez JS, Ostrom QT, Gittleman H. et al. The elderly left behind-changes in survival trends of primary central nervous system lymphoma over the past 4 decades. Neuro Oncol 2018; 20: 687-694 DOI: 10.1093/neuonc/nox187. (PMID: 29036697)
    CrossrefPubMedGoogle Scholar
  • 4 Korfel A, Schlegel U. Diagnosis and treatment of primary CNS lymphoma. Nat Rev Neurol 2013; 9: 317-327 DOI: 10.3238/arztebl.2018.0419. (PMID: 29999484)
    CrossrefPubMedGoogle Scholar
  • 5 Küker W, Nägele T, Korfel A. et al. Primary central nervous system lymphomas (PCNSL): MRI features at presentation in 100 patients. J Neurooncol 2005; 72: 169-177 DOI: 10.1007/s11060-004-3390-7. (PMID: 15925998)
    CrossrefPubMedGoogle Scholar
  • 6 Hoang-Xuan K, Bessell E, Bromberg J. et al. Diagnosis and treatment of primary CNS lymphoma in immunocompetent patients: guidelines from the European Association for Neuro-Oncology. Lancet Oncol 2015; 16: e322-e332 DOI: 10.1016/S1470-2045(15)00076-5. (PMID: 26149884)
    CrossrefPubMedGoogle Scholar
  • 7 Ferreri AJ, Reni M, Foppoli M. et al. 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: 1512-1520 DOI: 10.1016/S0140-6736(09)61416-1. (PMID: 19767089)
    CrossrefPubMedGoogle Scholar
  • 8 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, noninferiority trial. Lancet Oncol 2010; 11: 1036-1047 DOI: 10.1016/S1470-2045(10)70229-1. (PMID: 20970380)
    CrossrefPubMedGoogle Scholar
  • 9 Bromberg JEC, Issa S, Bakunina K. et al. Rituximab in patients with primary CNS lymphoma (HOVON 105/ALLG NHL 24): a randomised, open-label, phase 3 intergroup study. Lancet Oncol 2019; 20: 216-228 DOI: 10.1016/S1470-2045(18)30747-2. (PMID: 30630772)
    CrossrefPubMedGoogle Scholar
  • 10 Illerhaus G, Kasenda B, Ihorst G. et al. High-dose chemotherapy with autologous haemopoietic stem cell transplantation for newly diagnosed primary CNS lymphoma: a prospective, single-arm, phase 2 trial. Lancet Haematol 2016; 3: e388-e397 DOI: 10.1016/S2352-3026(16)30050-3. (PMID: 27476790)
    CrossrefPubMedGoogle Scholar
  • 11 Houillier C, Taillandier L, Dureau S. et al. Radiotherapy or autologous stem-cell transplantation for primary CNS lymphoma in patients 60 years of age and younger: Results of the intergroup ANOCEF-GOELAMS randomized phase II PRECIS study. J Clin Oncol 2019; 37: 823-833 DOI: 10.1200/JCO.18.00306. (PMID: 30785830)
    CrossrefPubMedGoogle Scholar
  • 12 Ferreri AJM, Cwynarski K, Pulczynski E. et al. Whole-brain radiotherapy or autologous stem-cell transplantation as consolidation strategies after high-dose methotrexate-based chemoimmunotherapy in patients with primary CNS lymphoma: results of the second randomisation of the International Extranodal L. Lancet Haematol 2017; 4: e510-e523 DOI: 10.1016/S2352-3026(17)30174-6. (PMID: 29054815)
    CrossrefPubMedGoogle Scholar
  • 13 Ferreri AJM, Cwynarski K, Pulczynski E. et al. Chemoimmunotherapy with methotrexate, cytarabine, thiotepa, and rituximab (MATRix regimen) in patients with primary CNS lymphoma: Results of the first randomisation of the International Extranodal Lymphoma Study Group-32 (IELSG32) phase 2 trial. Lancet Haematol 2016; 3: e217-e227
    CrossrefPubMedGoogle Scholar
  • 14 Juergens A, Pels H, Rogowski S. et al. Long-term survival with favorable cognitive outcome after chemotherapy in primary central nervous system lymphoma. Ann Neurol 2010; 67: 182-189 DOI: 10.1002/ana.21824. (PMID: 20225195)
    CrossrefPubMedGoogle Scholar
  • 15 Seidel S, Pels H, Schlömer S. et al. Twenty years follow-up of a pilot/phase II-trial on the Bonn protocol for primary CNS lymphoma. Neurology 2020; 95: e3138-e3144 DOI: 10.1212/WNL.0000000000010949. (PMID: 32989105)
    CrossrefPubMedGoogle Scholar
  • 16 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: 3061-3068 DOI: 10.1200/JCO.2012.46.9957. (PMID: 23569323)
    CrossrefPubMedGoogle Scholar
  • 17 Nelson DF. Radiotherapy in the treatment of primary central nervous system lymphoma (PCNSL). Journal of Neuro-Oncology 1999; 43: 241-247 DOI: 10.1023/a:1006206602918. (PMID: 10563430)
    CrossrefPubMedGoogle Scholar
  • 18 Abrey LE, Yahalom J, De Angelis LM. Treatment for primary CNS lymphoma: the next step. J Clin Oncol 2000; 18: 3144-3150
    CrossrefPubMedGoogle Scholar
  • 19 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: 3971-3979 DOI: 10.1200/JCO.2013.50.4910. (PMID: 24101038)
    CrossrefPubMedGoogle Scholar
  • 20 Kasenda B, Ferreri AJM, Marturano E. et al. First-line treatment and outcome of elderly patients with primary central nervous system lymphoma (PCNSL)-a systematic review and individual patient data meta-analysis. Ann Oncol Off J Eur Soc Med Oncol 2015; 26: 1305-1313
    CrossrefPubMedGoogle Scholar
  • 21 Omuro A, Chinot O, Taillandier L. et al. Methotrexate and temozolomide versus methotrexate, procarbazine, vincristine, and cytarabine for primary CNS lymphoma in an elderly population: an intergroup ANOCEF-GOELAMS randomised phase 2 trial. Lancet Haematol 2015; 2: e251-259 DOI: 10.1016/S2352-3026(15)00074-5. (PMID: 26688235)
    CrossrefPubMedGoogle Scholar
  • 22 Fritsch K, Kasenda B, Schorb E. et al. High-dose methotrexate-based immuno-chemotherapy for elderly primary CNS lymphoma patients (PRIMAIN study). Leukemia 2017; 31: 846-852 DOI: 10.1038/leu.2016.334. (PMID: 27843136)
    CrossrefPubMedGoogle Scholar
  • 23 Houillier C, Ghesquières H, Chabrot C. et al. Rituximab, methotrexate, procarbazine, vincristine and intensified cytarabine consolidation for primary central nervous system lymphoma (PCNSL) in the elderly: a LOC network study. J Neurooncol 2017; 133: 315-320 DOI: 10.1007/s11060-017-2435-7. (PMID: 28432587)
    CrossrefPubMedGoogle Scholar
  • 24 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
    CrossrefPubMedGoogle Scholar
  • 25 Pulczynski EJ, Kuittinen O, Erlanson M. et al. Successful change of treatment strategy in elderly patients with primary central nervous system lymphoma by de-escalating induction and introducing temozolomide maintenance: results from a phase II study by the Nordic Lymphoma Group. Haematologica 2015; 100: 534-540
    CrossrefPubMedGoogle Scholar
  • 26 Seidel S, Kowalski T, Margold M. et al. HDMTX-based polychemotherapy including intraventricular therapy in elderly patients with primary CNS lymphoma: a single center series. Ther Adv Neurol Disord 2020; 13 DOI: 10.1177/1756286420951087. (PMID: 33101460)
    CrossrefPubMedGoogle Scholar
  • 27 Omuro AMP, Taillandier L, Chinot O. et al. Temozolomide and methotrexate for primary central nervous system lymphoma in the elderly. J Neurooncol 2007; 85: 207-211 DOI: 10.1007/s11060-007-9397-0. (PMID: 17896079)
    CrossrefPubMedGoogle Scholar
  • 28 Taylor AL, Marcus R, Bradley JA. et al. Post-transplant lymphoproliferative disorders (PTLD) after solid organ transplantation. Crit Rev Oncol Hematol 2005; 56: 155-167 DOI: 10.1016/j.critrevonc.2005.03.015. (PMID: 15979320)
    CrossrefPubMedGoogle Scholar
  • 29 Kaulen LD, Karschnia P, Dietrich J. et al. Autoimmune disease-related primary CNS lymphoma: systematic review and meta-analysis. J Neurooncol 2020; 149: 153-159 DOI: 10.1007/s11060-020-03583-9. (PMID: 32683530)
    CrossrefPubMedGoogle Scholar
  • 30 Fischer L, Thiel E, Klasen HA. et al. Prospective trial on topotecan salvage therapy in primary CNS lymphoma. Ann Oncol 2006; 17: 1141-1145 DOI: 10.1093/annonc/mdl070. (PMID: 16603598)
    CrossrefPubMedGoogle Scholar
  • 31 Voloschin AD, Betensky R, Wen PY. et al. Topotecan as salvage therapy for relapsed or refractory primary central nervous system lymphoma. J Neurooncol 2008; 86: 211-215 DOI: 10.1007/s11060-007-9464-6. (PMID: 17896078)
    CrossrefPubMedGoogle Scholar
  • 32 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. (PMID: 17325700)
    CrossrefPubMedGoogle Scholar
  • 33 Enting RH, Demopoulos A, De Angelis LM. et al. Salvage therapy for primary CNS lymphoma with a combination of rituximab and temozolomide. Neurology 2004; 63: 901-903
    CrossrefPubMedGoogle Scholar
  • 34 Mappa S, Marturano E, Licata G. et al. Salvage chemoimmunotherapy with rituximab, ifosfamide and etoposide (R-IE regimen) in patients with primary CNS lymphoma relapsed or refractory to high-dose methotrexate-based chemotherapy. Hematol Oncol 2013; 31: 143-150 DOI: 10.1002/hon.2037. (PMID: 23161567)
    CrossrefPubMedGoogle Scholar
  • 35 Soussain C, Hoang-Xuan K, Taillandier L. et al. 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: 2512-2518 DOI: 10.1200/JCO.2007.13.5533. (PMID: 18413641)
    CrossrefPubMedGoogle Scholar
  • 36 Kasenda B, Ihorst G, Schroers R. et al. High-dose chemotherapy with autologous haematopoietic stem cell support for relapsed or refractory primary CNS lymphoma: a prospective multicentre trial by the German Cooperative PCNSL study group. Leukemia 2017; 31: 2623-2629 DOI: 10.1038/leu.2017.170. (PMID: 28559537)
    CrossrefPubMedGoogle Scholar
  • 37 Ghesquieres H, Chevrier M, Laadhari M. et al. Lenalidomide in combination with intravenous rituximab (REVRI) in relapsed/refractory primary CNS lymphoma or primary intraocular lymphoma: a multicenter prospective 'proof of concept' phase II study of the French Oculo-Cerebral lymphoma (LOC) Network and the Lymphoma Study Association (LYSA). Ann Oncol 2019; 30: 621-628 DOI: 10.1093/annonc/mdz032. (PMID: 30698644)
    CrossrefPubMedGoogle Scholar
  • 38 Korfel A, Schlegel U, Herrlinger U. et al. Phase II Trial of Temsirolimus for Relapsed/Refractory Primary CNS Lymphoma. J Clin Oncol 2016; 34: 1757-1763 DOI: 10.1200/JCO.2015.64.9897. (PMID: 26976424)
    CrossrefPubMedGoogle Scholar
  • 39 Grommes C, Nayak L, Tun HW. et al. Introduction of novel agents in the treatment of primary CNS lymphoma. Neuro Oncol 2019; 21: 306-313 DOI: 10.1093/neuonc/noy193. (PMID: 30423172)
    CrossrefPubMedGoogle Scholar