Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

Primary central nervous system lymphoma: implication of high-dose chemotherapy followed by auto-SCT

Bone Marrow Transplantation volume 47, pages 1265–1268 (2012)Cite this article

Subjects

Abstract

Primary central nervous system lymphoma is a rare and distinct subtype of non-Hodgkin's lymphoma that is sensitive to radiation and chemotherapy. Decisions regarding the initial therapeutic approach are influenced by age and risk of therapy-related neurotoxicity. Despite several albeit small phase II studies, and the acknowledged need for larger prospective trials, there is supporting evidence to consider auto-SCT following induction chemotherapy in patients with good performance status. The international extranodal lymphoma study group is conducting a randomized phase II study comparing consolidative radiation therapy to high-dose therapy. Novel therapeutic options including early aggressive approach with upfront auto-SCT and strategies to prevent relapse following transplantation is an area of focus.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  1. Olson JE, Janney CA, Rao RD, Cerhan JR, Kurtin PJ, Schiff D 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.

    Article  Google Scholar 

  2. Hoffman S, Propp JM, McCarthy BJ . Temporal trends in incidence of primary brain tumors in the United States, 1985–1999. Neuro Oncol 2006; 8: 27–37.

    Article  Google Scholar 

  3. Ferreri AJ, Assanelli A, Crocchiolo R, Ciceri F . Central nervous system dissemination in immunocompetent patients with aggressive lymphomas: incidence, risk factors and therapeutic options. Hematol Oncol 2009; 27: 61–70.

    Article  CAS  Google Scholar 

  4. Lim T, Kim SJ, Kim K, Lee JI, Lim DH, Lee DJ et al. Primary CNS lymphoma other than DLBCL: a descriptive analysis of clinical features and treatment outcomes. Ann Hematol (e-pub ahead of print 9 April 2011; doi:10.1007/S00277-011-1225-0).

  5. Gerstner ER, Batchelor TT . Primary central nervous system lymphoma. Arch Neurol 2010; 67: 291–297.

    Article  Google Scholar 

  6. Herrlinger U, Schabet M, Clemens M, Kortmann RD, Petersen D, Will BE et al. Clinical presentation and therapeutic outcome in 26 patients with primary CNS lymphoma. Acta Neurol Scand 1998; 97: 257–264.

    Article  CAS  Google Scholar 

  7. Grisariu S, Avni B, Batchelor TT, van den Bent MJ, Bokstein F, Schiff D et al. Neurolymphomatosis: an International Primary CNS Lymphoma Collaborative Group report. Blood 2010; 115: 5005–5011.

    Article  CAS  Google Scholar 

  8. Camilleri-Broet S, Martin A, Moreau A, Angonin R, Hénin D, Gontier MF et al. 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: 607–612.

    Article  CAS  Google Scholar 

  9. Shenkier TN, Blay JY, O’Neill BP, Poortmans P, Thiel E, Jahnke K et al. Primary CNS lymphoma of T-cell origin: a descriptive analysis from the international primary CNS lymphoma collaborative group. J Clin Oncol 2005; 23: 2233–2239.

    Article  Google Scholar 

  10. Nelson DF, Martz KL, Bonner H, Nelson JS, Newall J, Kerman HD 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.

    Article  CAS  Google Scholar 

  11. Nelson DF . Radiotherapy in the treatment of primary central nervous system lymphoma (PCNSL). J Neurooncol 1999; 43: 241–247.

    Article  CAS  Google Scholar 

  12. Thiel E, Korfel A, Martus P, Kanz L, Griesinger F, Rauch M 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: 1036–1047.

    Article  CAS  Google Scholar 

  13. Bessell EM, Hoang-Xuan K, Ferreri AJ, Reni M . Primary central nervous system lymphoma: biological aspects and controversies in management. Eur J Cancer 2007; 43: 1141–1152.

    Article  Google Scholar 

  14. Ferreri AJ, Abrey LE, Blay JY, Borisch B, Hochman J, Neuwelt EA et al. Summary statement on primary central nervous system lymphomas from the Eighth International Conference on Malignant Lymphoma, Lugano, Switzerland, June 12 to 15, 2002. J Clin Oncol 2003; 21: 2407–2414.

    Article  Google Scholar 

  15. Gabbai AA, Hochberg FH, Linggood RM, Bashir R, Hotleman K . High-dose methotrexate for non-AIDS primary central nervous system lymphoma. Report of 13 cases. J Neurosurg 1989; 70: 190–194.

    Article  CAS  Google Scholar 

  16. Ferreri AJ, Reni M, Villa E . Therapeutic management of primary central nervous system lymphoma: lessons from prospective trials. Ann Oncol 2000; 11: 927–937.

    Article  CAS  Google Scholar 

  17. Doolittle ND, Miner ME, Hall WA, Siegal T, Jerome E, Osztie E 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.

    Article  CAS  Google Scholar 

  18. Neuwelt EA, Goldman DL, Dahlborg SA, Crossen J, Ramsey F, Roman-Goldstein S et al. Primary CNS lymphoma treated with osmotic blood-brain barrier disruption: prolonged survival and preservation of cognitive function. J Clin Oncol 1991; 9: 1580–1590.

    Article  CAS  Google Scholar 

  19. Angelov L, Doolittle ND, Kraemer DF, Siegal T, Barnett GH, Peereboom DM et al. Blood-brain barrier disruption and intra-arterial methotrexate-based therapy for newly diagnosed primary CNS lymphoma: a multi-institutional experience. J Clin Oncol 2009; 27: 3503–3509.

    Article  CAS  Google Scholar 

  20. Rubenstein JL, Johnson JL, Jung SH, Cheson BD, Kaplan LD . Intensive chemotherapy and immunotherapy, without brain irradiation, in newly diagnosed patients with primary CNS lymphoma: results of CALGB 50202. ASH Annu Meet Abstr 2010; 116: 763.

    Google Scholar 

  21. Brevet M, Garidi R, Gruson B, Royer B, Vaida I, Damaj G . First-line autologous stem cell transplantation in primary CNS lymphoma. Eur J Haematol 2005; 75: 288–292.

    Article  CAS  Google Scholar 

  22. Yoon DH, Lee DH, Choi DR, Sohn BS, Kim S, Kim SW et al. Feasibility of BU, CY and etoposide (BUCYE), and auto-SCT in patients with newly diagnosed primary CNS lymphoma: a single-center experience. Bone Marrow Transplant 2011; 46: 105–109.

    Article  CAS  Google Scholar 

  23. Illerhaus G, Muller F, Feuerhake F, Schäfer AO, Ostertag C, Finke J . 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: 147–148.

    Article  CAS  Google Scholar 

  24. Colombat P, Lemevel A, Bertrand P, Delwail V, Rachieru P, Brion A 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: 417–420.

    Article  CAS  Google Scholar 

  25. Abrey LE, Moskowitz CH, Mason WP, Crump M, Stewart D, Forsyth P 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.

    Article  CAS  Google Scholar 

  26. Cheng T, Forsyth P, Chaudhry A, Guttenberger R, Ostertag C, Derigs G et al. High-dose thiotepa, busulfan, cyclophosphamide and ASCT without whole-brain radiotherapy for poor prognosis primary CNS lymphoma. Bone Marrow Transplant 2003; 31: 679–685.

    Article  CAS  Google Scholar 

  27. Illerhaus G, Marks R, Ihorst G, Guttenberger R, Ostertag C, Derigs G et al. High-dose chemotherapy with autologous stem-cell transplantation and hyperfractionated radiotherapy as first-line treatment of primary CNS lymphoma. J Clin Oncol 2006; 24: 3865–3870.

    Article  CAS  Google Scholar 

  28. Montemurro M, Kiefer T, Schuler F, Al-Ali HK, Wolf HH, Herbst R 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 multicenter Ostdeutsche Studiengruppe Hamato-Onkologie OSHO-53 phase II study. Ann Oncol 2007; 18: 665–671.

    Article  CAS  Google Scholar 

  29. Papadopoulos KP, Noguera-Irizarry W, Wiebe L, Hesdorffer CS, Garvin J, Nichols GL et al. Pilot study of tandem high-dose chemotherapy and autologous stem cell transplantation with a novel combination of regimens in patients with poor risk lymphoma. Bone Marrow Transplant 2005; 36: 491–497.

    Article  CAS  Google Scholar 

  30. Glossmann JP, Staak JO, Nogova L, Diehl V, Scheid C, Kisro J et al. Autologous tandem transplantation in patients with primary progressive or relapsed/refractory lymphoma. Ann Hematol 2005; 84: 517–525.

    Article  CAS  Google Scholar 

  31. Abdul-Hai A, Weiss L, Ergas D, Resnick IB, Slavin S, Shapira MY . The effect of high-dose thiotepa, alone or in combination with other chemotherapeutic agents, on a murine B-cell leukemia model simulating autologous stem cell transplantation. Bone Marrow Transplant 2007; 40: 891–896.

    Article  CAS  Google Scholar 

  32. Lee SC, Kim SJ, Lee DH, Kim WS, Suh C, Won JH . Excessive toxicity of once daily i.v. BU, melphalan and thiotepa followed by auto SCT on patients with non-Hodgkin′s lymphoma. Bone Marrow Transplant 2010; 45: 801–802.

    Article  Google Scholar 

  33. Cacchione A, LeMaitre A, Couanet DV, Benhamou E, Amoroso L, Simonnard N et al. Risk factors for hepatic veno-occlusive disease: a retrospective unicentric study in 116 children autografted after a high-dose BU-thiotepa regimen. Bone Marrow Transplant 2008; 42: 449–454.

    Article  CAS  Google Scholar 

  34. Nguyen PL, Chakravarti A, Finkelstein DM, Hochberg FH, Batchelor TT, Loeffler JS . Results of whole-brain radiation as salvage of methotrexate failure for immunocompetent patients with primary CNS lymphoma. J Clin Oncol 2005; 23: 1507–1513.

    Article  Google Scholar 

  35. Hoang-Xuan K, Taillandier L, Chinot O, Soubeyran P, Bogdhan U, Hildebrand J 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.

    Article  CAS  Google Scholar 

  36. Taoka K, Okoshi Y, Sakamoto N, Takano S, Matsumura A, Hasegawa Y et al. A nonradiation-containing, intermediate-dose methotrexate regimen for elderly patients with primary central nervous system lymphoma. Int J Hematol 2010; 92: 617–623.

    Article  CAS  Google Scholar 

  37. Hong SJ, Kim JS, Chang JH, Kim KM, Kim SJ, Lee HW et al. A successful treatment of relapsed primary CNS lymphoma patient with intraventricular rituximab followed by high-dose chemotherapy with autologous stem cell rescue. Yonsei Med J 2009; 50: 280–283.

    Article  Google Scholar 

  38. Soussain C, Hoang-Xuan K, Taillandier L, Fourme E, Choquet S, Witz F et al. Intensive chemotherapy followed by hematopoietic stem-cell rescue for refractory and recurrent primary CNS and intraocular lymphoma: Societe Francaise de Greffe de Moelle Osseuse-Therapie Cellulaire. J Clin Oncol 2008; 26: 2512–2518.

    Article  Google Scholar 

  39. Reddy N, Savani BN . Treatment options for transformed lymphoma: incorporating allogeneic stem cell transplantation in a multimodality approach. Biol Blood Marrow Transplant 2011; 17: 1265–1272.

    Article  Google Scholar 

  40. Alvarnas JC, Negrin RS, Horning SJ, Hu WW, Long GD, Schriber JR 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: 352–358.

    Article  CAS  Google Scholar 

  41. 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. J Clin Oncol 2002; 20: 4643–4648.

    Article  Google Scholar 

  42. Ferreri AJ, Crocchiolo R, Assanelli A, Govi S, Reni M . High-dose chemotherapy supported by autologous stem cell transplantation in patients with primary central nervous system lymphoma: facts and opinions. Leuk Lymphoma 2008; 49: 2042–2047.

    Article  CAS  Google Scholar 

  43. Clark WB, Strickland SA, Barrett AJ, Savani BN . Extramedullary relapses after allogeneic stem cell transplantation for acute myeloid leukemia and myelodysplastic syndrome. Haematologica 2010; 95: 860–863.

    Article  Google Scholar 

  44. Varadi G, Or R, Kapelushnik J, Naparstek E, Nagler A, Brautbar C et al. Graft-versus-lymphoma effect after allogeneic peripheral blood stem cell transplantation for primary central nervous system lymphoma. Leuk Lymphoma 1999; 34: 185–190.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study was funded by NR support through Grant No. NIH/5K-12 CA090625-09.

Author information

Authors and Affiliations

  1. Division of Hematology/Oncology, Department of Medicine, Hematology and Stem Cell Transplantation Section, Vanderbilt University Medical Center, Nashville, TN, USA

    N Reddy & B N Savani

Authors
  1. N Reddy
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. B N Savani
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to N Reddy.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Reddy, N., Savani, B. Primary central nervous system lymphoma: implication of high-dose chemotherapy followed by auto-SCT. Bone Marrow Transplant 47, 1265–1268 (2012). https://doi.org/10.1038/bmt.2011.204

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2011.204

Keywords

This article is cited by

Search

Advanced search

Quick links