Skip to main content

Advertisement

SpringerLink
Log in

Treatment and Prophylaxis of Hematologic Malignancy in the Central Nervous System

  • Neuro-oncology (Neoplasms)
  • Published:
Current Treatment Options in Neurology Aims and scope Submit manuscript

Opinion statement

Central nervous system (CNS) involvement is a serious, and frequently fatal, complication of acute leukemias and very aggressive lymphomas. In patients with no evidence of CNS involvement at the time of diagnosis, the decision to include CNS prophylaxis in the treatment regimen should be based on cytologic diagnosis and other risk factors. Patients with a risk of CNS relapse greater than 10% should receive CNS prophylaxis with high-dose systemic chemotherapy, intrathecal therapy, radiation, or a combination thereof. The most commonly used systemic and intrathecal chemotherapies are methotrexate and cytarabine. Liposomal cytarabine, which increases CNS bioavailability and decreases the number of lumbar punctures needed, is our preference for intrathecal therapy. We usually reserve radiation therapy for patients who may not tolerate other forms of CNS prophylaxis. Patients with evidence of CNS involvement, either at diagnosis or relapse, should be treated until CNS disease clearance or dose-limiting toxicity is reached. Recent studies suggest that autologous stem cell transplantation may offer longer survivals for patients with CNS involvement and should be considered for patients who can tolerate the procedure. The use of rituximab in CNS prophylaxis and treatment has not yet been clearly delineated, but initial reports indicate that this agent and others may soon be available as an effective and tolerable CNS-directed therapy for lymphomas.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Cancer Facts and Figures 2010. American Cancer Society. 2010.

  2. Colocci N, Glantz M, Recht L. Prevention and treatment of central nervous system involvement by non-Hodgkin’s lymphoma: a review of the literature. Semin Neurol. 2004;24:395–404.

    Article  PubMed  Google Scholar 

  3. Lim HY, Thiel E, Glantz MJ. To protect and defend: central nervous system prophylaxis in patients with non-Hodgkin’s lymphoma. Curr Opin Oncol. 2008;20:495–501.

    Article  PubMed  Google Scholar 

  4. Recht L, Straus DJ, Cirrincione C, et al. Central nervous system metastases from non-Hodgkin’s lymphoma: treatment and prophylaxis. Am J Med. 1988;84:425–35.

    Article  PubMed  CAS  Google Scholar 

  5. Zeiser R, Burger JA, Bley TA, et al. Clinical follow-up indicates differential accuracy of magnetic resonance imaging and immunocytology of the cerebral spinal fluid for the diagnosis of neoplastic meningitis - a single centre experience. Br J Haematol. 2004;124:762–8.

    Article  PubMed  Google Scholar 

  6. Strik HM, Proemmel P, Pilgram-Pastor S, Buhk JH. Neoplastic meningitis—Is MRI as sensitive as CSF cytology? [abstract]. J Clin Oncol. 27:15s, 2009 (suppl; abstr 9566).

  7. Hegde U, Filie A, Little RF, et al. High incidence of occult leptomeningeal disease detected by flow cytometry in newly diagnosed aggressive B-cell lymphomas at risk for central nervous system involvement: the role of flow cytometry versus cytology. Blood. 2005;105:496–502.

    Article  PubMed  CAS  Google Scholar 

  8. Bromberg JE, Breems DA, Kraan J, et al. CSF flow cytometry greatly improves diagnostic accuracy in CNS hematologic malignancies. Neurology. 2007;68:1674–9.

    Article  PubMed  CAS  Google Scholar 

  9. Brem SS, Bierman PJ, Black P, et al. Central nervous system cancers. J Natl Compr Canc Netw. 2008;6:456–504.

    PubMed  CAS  Google Scholar 

  10. Schrappe M, Reiter A, Riehm H. Prophylaxis and treatment of neoplastic meningeosis in childhood acute lymphoblastic leukemia. J Neurooncol. 1998;38:159–65.

    Article  PubMed  CAS  Google Scholar 

  11. Burger B, Zimmermann M, Mann G, et al. Diagnostic cerebrospinal fluid examination in children with acute lymphoblastic leukemia: significance of low leukocyte counts with blasts or traumatic lumbar puncture. J Clin Oncol. 2003;21:184–8.

    Article  PubMed  Google Scholar 

  12. Herrlinger U, Klingel K, Meyermann R, et al. Central nervous system Hodgkin’s lymphoma without systemic manifestation: case report and review of the literature. Acta Neuropathol. 2000;99:709–14.

    Article  PubMed  CAS  Google Scholar 

  13. Pohar S, de Metz C, Poppema S, Hugh J. Chronic lymphocytic leukemia with CNS involvement. J Neuro-oncol. 1993;16:35–7.

    Article  CAS  Google Scholar 

  14. Evans AE, Gilbert ES, Zandstra R. The increasing incidence of central nervous system leukemia in children. (Children’s Cancer Study Group A). Cancer. 1970;26:404–9.

    Article  PubMed  CAS  Google Scholar 

  15. Pui CH, Evans WE. Treatment of acute lymphoblastic leukemia. N Engl J Med. 2006;354:166–78.

    Article  PubMed  CAS  Google Scholar 

  16. Hollender A, Kvaloy S, Nome O, et al. Central nervous system involvement following diagnosis of non-Hodgkin’s lymphoma: a risk model. Ann Oncol. 2002;13:1099–107.

    Article  PubMed  CAS  Google Scholar 

  17. Dohner H, Estey EH, Amadori S, et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. 2010;115:453–74.

    Article  PubMed  Google Scholar 

  18. Veerman AJ, Kamps WA, van den Berg H, et al. Dexamethasone-based therapy for childhood acute lymphoblastic leukaemia: results of the prospective Dutch Childhood Oncology Group (DCOG) protocol ALL-9 (1997–2004). Lancet Oncol. 2009;10:957–66.

    Article  PubMed  CAS  Google Scholar 

  19. 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, non-inferiority trial. Lancet Oncol. 2010;11:1036–47.

    Article  PubMed  CAS  Google Scholar 

  20. Balis FM, Savitch JL, Bleyer WA, et al. Remission induction of meningeal leukemia with high-dose intravenous methotrexate. J Clin Oncol. 1985;3:485–9.

    PubMed  CAS  Google Scholar 

  21. Lopez JA, Nassif E, Vannicola P, et al. Central nervous system pharmacokinetics of high-dose cytosine arabinoside. J Neurooncol. 1985;3:119–24.

    Article  PubMed  CAS  Google Scholar 

  22. Glantz MJ, Hall WA, Cole BF, et al. Diagnosis, management, and survival of patients with leptomeningeal cancer based on cerebrospinal fluid-flow status. Cancer. 1995;75:2919–31.

    Article  PubMed  CAS  Google Scholar 

  23. Bleyer W, Poplack D. Clinical studies on the central-nervous-system pharmacology of methotrexate. In: Pinedo H, editor. Clinical pharmacology of anti-neoplastic drugs. Amsterdam: Elsevier/North-Holland Biomedica; 1978. p. 115.

    Google Scholar 

  24. 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;16:1561–7.

    PubMed  CAS  Google Scholar 

  25. Seki R, Ohshima K, Nagafuji K, et al. Rituximab in combination with CHOP chemotherapy for the treatment of diffuse large B cell lymphoma in Japan: a retrospective analysis of 1,057 cases from Kyushu Lymphoma Study Group. Int J Hematol. 2010;91:258–66.

    Article  PubMed  CAS  Google Scholar 

  26. Boehme V, Schmitz N, Zeynalova S, et al. CNS events in elderly patients with aggressive lymphoma treated with modern chemotherapy (CHOP-14) with or without rituximab: an analysis of patients treated in the RICOVER-60 trial of the German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL). Blood. 2009;113:3896–902.

    Article  PubMed  CAS  Google Scholar 

  27. Silverman LB, Gelber RD, Dalton VK, et al. Improved outcome for children with acute lymphoblastic leukemia: results of Dana-Farber Consortium Protocol 91–01. Blood. 2001;97:1211–8.

    Article  PubMed  CAS  Google Scholar 

  28. Pui CH, Sandlund JT, Pei D, et al. Improved outcome for children with acute lymphoblastic leukemia: results of Total Therapy Study XIIIB at St Jude Children’s Research Hospital. Blood. 2004;104:2690–6.

    Article  PubMed  CAS  Google Scholar 

  29. Johnston DL, Alonzo TA, Gerbing RB, et al. The presence of central nervous system disease at diagnosis in pediatric acute myeloid leukemia does not affect survival: a Children’s Oncology Group study. Pediatr Blood Cancer. 2010;55:414–20.

    Article  PubMed  Google Scholar 

  30. Shapiro WR, Young DF, Mehta BM. Methotrexate: distribution in cerebrospinal fluid after intravenous, ventricular and lumbar injections. N Engl J Med. 1975;293:161–6.

    Article  PubMed  CAS  Google Scholar 

  31. Bleyer WA, Poplack DG, Simon RM. "Concentration × time" methotrexate via a subcutaneous reservoir: a less toxic regimen for intraventricular chemotherapy of central nervous system neoplasms. Blood. 1978;51:835–42.

    PubMed  CAS  Google Scholar 

  32. Ettinger LJ, Chervinsky DS, Freeman AI, Creaven PJ. Pharmacokinetics of methotrexate following intravenous and intraventricular administration in acute lymphocytic leukemia and non-Hodgkin’s lymphoma. Cancer. 1982;50:1676–82.

    Article  PubMed  CAS  Google Scholar 

  33. Moser AM, Adamson PC, Gillespie AJ, et al. Intraventricular concentration times time (C × T) methotrexate and cytarabine for patients with recurrent meningeal leukemia and lymphoma. Cancer. 1999;85:511–6.

    Article  PubMed  CAS  Google Scholar 

  34. Van Glantz MJ, Horn A, Fisher R, Chamberlain MC. Route of intracerebrospinal fluid chemotherapy administration and efficacy of therapy in neoplastic meningitis. Cancer. 2010;116:1947–52.

    Article  PubMed  Google Scholar 

  35. Matsumoto Y, Horiike S, Fujimoto Y, et al. Effectiveness and limitation of gamma knife radiosurgery for relapsed central nervous system lymphoma: a retrospective analysis in one institution. Int J Hematol. 2007;85:333–7.

    Article  PubMed  Google Scholar 

  36. Alvarnas JC, Negrin RS, Horning SJ, 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;6:352–8.

    Article  PubMed  CAS  Google Scholar 

  37. Kasamon YL, Jones RJ, Piantadosi S, et al. High-dose therapy and blood or marrow transplantation for non-Hodgkin lymphoma with central nervous system involvement. Biol Blood Marrow Transplant. 2005;11:93–100.

    Article  PubMed  CAS  Google Scholar 

  38. Chamberlain MC, Johnston SK. High-dose methotrexate and rituximab with deferred radiotherapy for newly diagnosed primary B-cell CNS lymphoma. Neuro Oncol. 2010 Feb 8 (Epub ahead of print).

  39. 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;25:1350–6.

    Article  PubMed  CAS  Google Scholar 

  40. Antonini G, Cox MC, Montefusco E, et al. Intrathecal anti-CD20 antibody: an effective and safe treatment for leptomeningeal lymphoma. J Neurooncol. 2007;81:197–9.

    Article  PubMed  Google Scholar 

  41. Liu CY, Teng HW, Lirng JF, et al. Sustained remission and long-term survival of secondary central nervous system involvement by aggressive B-cell lymphoma after combination treatment of systemic high-dose chemotherapy and intrathecal rituximab. Leuk Lymphoma. 2008;49:2018–21.

    Article  PubMed  CAS  Google Scholar 

  42. Villela L, Garcia M, Caballero R, et al. Rapid complete response using intrathecal rituximab in a patient with leptomeningeal lymphomatosis due to mantle cell lymphoma. Anticancer Drugs. 2008;19:917–20.

    Article  PubMed  CAS  Google Scholar 

  43. Kurzwelly D, Glas M, Roth P, et al. Primary CNS lymphoma in the elderly: temozolomide therapy and MGMT status. J Neurooncol. 2010;97:389–92.

    Article  PubMed  CAS  Google Scholar 

  44. Enting RH, Demopoulos A, DeAngelis LM, Abrey LE. Salvage therapy for primary CNS lymphoma with a combination of rituximab and temozolomide. Neurology. 2004;63:901–3.

    PubMed  CAS  Google Scholar 

  45. Omuro AM, Taillandier L, Chinot O, et al. Temozolomide and methotrexate for primary central nervous system lymphoma in the elderly. J Neurooncol. 2007;85:207–11.

    Article  PubMed  CAS  Google Scholar 

  46. Omuro AM. Is single-agent temozolomide the treatment of choice for recurrent primary central nervous system lymphoma? Nat Clin Pract Oncol. 2007;4:514–5.

    Article  PubMed  Google Scholar 

  47. Abdel-Karim I, Plunkett Jr WK, O’Brien S, et al. A phase I study of pemetrexed in patients with relapsed or refractory acute leukemia. Invest New Drugs. 2011;29:323–31.

    Article  PubMed  CAS  Google Scholar 

  48. Grossman SA, Finkelstein DM, Ruckdeschel JC, et al. Randomized prospective comparison of intraventricular methotrexate and thiotepa in patients with previously untreated neoplastic meningitis. Eastern Cooperative Oncology Group. J Clin Oncol. 1993;11:561–9.

    PubMed  CAS  Google Scholar 

  49. Groves MD, Glantz MJ, Chamberlain MC, et al. A multicenter phase II trial of intrathecal topotecan in patients with meningeal malignancies. Neuro-Oncology. 2008;10:208–15.

    Article  PubMed  CAS  Google Scholar 

Download references

Disclosure

No potential conflicts of interest relevant to this article were reported.

Author information

Authors and Affiliations

  1. Stanford Cancer Center, 875 Blake Wilbur Drive CC2221, Stanford, CA, 94305, USA

    Seema Nagpal MD & Lawrence Recht MD

Authors
  1. Seema Nagpal MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lawrence Recht MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lawrence Recht MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nagpal, S., Recht, L. Treatment and Prophylaxis of Hematologic Malignancy in the Central Nervous System. Curr Treat Options Neurol 13, 400–412 (2011). https://doi.org/10.1007/s11940-011-0128-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11940-011-0128-7

Keywords

Search

Navigation