Efficacy of intrathecal chemotherapy in patients with central nervous system involvement of hematological malignancies: a retrospective analysis

  • A. Dara
  • B. B. Mook
  • J. K. Doorduijn
  • M. J. van den Bent
  • A. G. Dinmohamed
  • J. E. C. Bromberg
Clinical Study

Abstract

Introduction

Central nervous system (CNS) involvement, especially involvement of the cerebrospinal fluid (CSF), is common in several haematological malignancies. Intrathecal (IT) chemotherapy can be used to manage CSF involvement.

Methods

Here we evaluated the effectiveness of IT chemotherapy among 80 patients with haematological malignancies and CSF localization who were treated with IT chemotherapy from 2001 to 2012.

Results

The majority of patients was diagnosed with diffuse large B-cell lymphoma (26%) or acute lymphoblastic leukaemia/lymphoblastic lymphoma (19%). After first-line IT chemotherapy, which mainly consisted of methotrexate (MTX) and corticosteroids, CSF complete response (CSF CR) was achieved in 76% of patients. 91% reached CSF CR when including second-line IT-chemotherapy. Clinical response was documented in 75%. Although most patients were additionally treated with systemic chemotherapy, response rate did not differ between patients treated with CNS-penetrating and CNS-non-penetrating drugs. CNS progression/relapse occurred in 40% of patients with median progression-free survival of 12.2 months. The median overall survival was 18.3 months; 55% of the patients died during follow-up.

Conclusions

Our analysis shows a high response rate after first-line IT chemotherapy, but also a relatively high progression/relapse percentage.

Keywords

Intrathecal chemotherapy Hematological malignancies Methotrexate Cerebrospinal fluid 

Notes

Compliance with ethical standards

Conflict of interest

All authors report no conflict of interest.

Supplementary material

11060_2018_2849_MOESM1_ESM.docx (13 kb)
Supplementary material 1 (DOCX 13 KB)

References

  1. 1.
    Chamberlain MC (2006) Neoplastic meningitis. Neurologist 12(4):179–187CrossRefPubMedGoogle Scholar
  2. 2.
    O’Neill BP (2003) Neurologic complications of Hodgkins’s disease and the non-Hodgkin’s lymphomas. In: Schiff D, Wen PY (eds) Cancer neurology in clinical practice, 1st edn. Humana Press, Totowa, pp 371–384Google Scholar
  3. 3.
    Pui CH, Thiel E (2009) Central nervous system disease in hematologic malignancies: historical perspective and practical applications. Semin Oncol 36(4 Suppl 2):S2–S16Google Scholar
  4. 4.
    Cheung CW, Burton C, Smith P, Linch DC, Hoskin PJ, Ardeshna KM (2005) Central nervous system chemoprophylaxis in non-Hodgkin lymphoma: current practice in the UK. Br J Haematol 131(2):193–200CrossRefPubMedGoogle Scholar
  5. 5.
    Vitolo U, Chiappella A, Ferreri AJ, Martelli M, Baldi I, Balzarotti M et al (2011) First-line treatment for primary testicular diffuse large B-cell lymphoma with rituximab-CHOP, CNS prophylaxis, and contralateral testis irradiation: final results of an international phase II trial. J Clin Oncol 29(20):2766–2772CrossRefPubMedGoogle Scholar
  6. 6.
    Bernstein SH, Unger JM, Leblanc M, Friedberg J, Miller TP, Fisher RI (2016) Natural history of CNS relapse in patients with aggressive non-Hodgkin’s lymphoma: a 20-year follow-up analysis of SWOG 8516—the Southwest Oncology Group. J Clin Oncol 27(1):114–119CrossRefGoogle Scholar
  7. 7.
    Boehme V, Zeynalova S, Kloess M, Loeffler M, Kaiser U, Pfreundschuh M et al (2007) Incidence and risk factors of central nervous system recurrence in aggressive lymphoma—a survey of 1693 patients treated in protocols of the German High-Grade Non-Hodgkin’s Lymphoma Study Group (DSHNHL). Ann Oncol 18(1):149–157CrossRefPubMedGoogle Scholar
  8. 8.
    Schmitz N, Zeynalova S, Nickelsen M, Kansara R, Villa D, Sehn LH, Glass B, Scott DW, Gascoyne RD, Connors JM, Ziepert M, Pfreundschuh M, Loeffler M, Savage KJ (2016) CNS International Prognostic Index: a risk model for CNS relapse in patients with diffuse large B-cell lymphoma treated with R-CHOP. J Clin Oncol 34(26):3150–3156CrossRefPubMedGoogle Scholar
  9. 9.
    Colocci N, Glantz M, Recht L (2004) Prevention and treatment of central nervous system involvement by non-Hodgkin’s lymphoma: a review of the literature. Semin Neurol 24(4):395–404CrossRefPubMedGoogle Scholar
  10. 10.
    Glantz MJ, LaFollette S, Jaeckle KA, Shapiro W, Swinnen L, Rozental JR et al (1999) Randomized trial of a slow-release versus a standard formulation of cytarabine for the intrathecal treatment of lymphomatous meningitis. J Clin Oncol 17(10):3110–3116CrossRefPubMedGoogle Scholar
  11. 11.
    Blaney SM, Balis FM, Poplack DG (1991) Current pharmacological treatment approaches to central nervous system leukaemia. Drugs 41(5):702–716CrossRefPubMedGoogle Scholar
  12. 12.
    Shapiro WR, Young DF, Mehta BM (1975) Methotrexate: distribution in cerebrospinal fluid after intravenous, ventricular and lumbar injections. N Engl J Med 293(4):161–166CrossRefPubMedGoogle Scholar
  13. 13.
    Chamberlain MC (2000) Neoplastic meningitis: a guide to diagnosis and treatment. Curr Opin Neurol 13(6):641–648CrossRefPubMedGoogle Scholar
  14. 14.
    Hegde U, Filie A, Little RF, Janik JE, Grant N, Steinberg SM et al (2005) 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 105(2):496–502CrossRefPubMedGoogle Scholar
  15. 15.
    Bromberg JE, Breems DA, Kraan J, Bikker G, van der HB, Smitt PS, et al (2007) CSF flow cytometry greatly improves diagnostic accuracy in CNS hematologic malignancies. Neurology 68(20):1674–1679CrossRefPubMedGoogle Scholar
  16. 16.
    Gokbuget N, Hartog CM, Bassan R, Derigs HG, Dombret H, Greil R et al (2011) Liposomal cytarabine is effective and tolerable in the treatment of central nervous system relapse of acute lymphoblastic leukemia and very aggressive lymphoma. Haematologica 96(2):238–244CrossRefPubMedGoogle Scholar
  17. 17.
    Parasole R, Petruzziello F, Messina C, Barisone E, Pession A, Locatelli F et al (2015) Toxicity and efficacy of intrathecal liposomal cytarabine in children with leukemia/lymphoma relapsing in the central nervous system: a retrospective multicenter study. Leuk Lymphoma 56(3):650–655CrossRefPubMedGoogle Scholar
  18. 18.
    Glantz MJ, Van HA, Fisher R, Chamberlain MC (2010) Route of intracerebrospinal fluid chemotherapy administration and efficacy of therapy in neoplastic meningitis. Cancer 116(8):1947–1952CrossRefPubMedGoogle Scholar
  19. 19.
    Abramson JS, Hellmann M, Barnes JA, Hammerman P, Toomey C, Takvorian T et al (2010) Intravenous methotrexate as central nervous system (CNS) prophylaxis is associated with a low risk of CNS recurrence in high-risk patients with diffuse large B-cell lymphoma. Cancer 15(18):4283–4290 116(CrossRefGoogle Scholar
  20. 20.
    Ferreri AJ, Bruno-Ventre M, Donadoni G, Ponzoni M, Citterio G, Foppoli M et al (2015) Risk-tailored CNS prophylaxis in a mono-institutional series of 200 patients with diffuse large B-cell lymphoma treated in the rituximab era. Br J Haematol 168(5):654–662CrossRefPubMedGoogle Scholar
  21. 21.
    Wilson WH, Bromberg JE, Stetler-Stevenson M, Steinberg SM, Martin-Martin L, Muniz C et al (2014) Detection and outcome of occult leptomeningeal disease in diffuse large B-cell lymphoma and Burkitt lymphoma. Haematologica 99(7):1228–1235CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of NeurologyHaga Teaching HospitalDen HaagThe Netherlands
  2. 2.Department of Hematology, Erasmus MC Cancer InstituteUniversity Medical Center RotterdamRotterdamThe Netherlands
  3. 3.Department of Neuro-oncology, Erasmus MC Cancer InstituteUniversity Medical CenterRotterdamThe Netherlands
  4. 4.Department of NeurologyReinier de Graaf HospitalDelftThe Netherlands
  5. 5.Department of ResearchNetherlands Comprehensive Cancer Organisation (IKNL)UtrechtThe Netherlands
  6. 6.Department of Public HealthErasmus University Medical CenterRotterdamThe Netherlands

Personalised recommendations