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Published in: Journal of Neuro-Oncology 1/2018

01-08-2018 | Clinical Study

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

Authors: A. Dara, B. B. Mook, J. K. Doorduijn, M. J. van den Bent, A. G. Dinmohamed, J. E. C. Bromberg

Published in: Journal of Neuro-Oncology | Issue 1/2018

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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.
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Literature
2.
go back to reference 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 371–384 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 371–384
3.
go back to reference Pui CH, Thiel E (2009) Central nervous system disease in hematologic malignancies: historical perspective and practical applications. Semin Oncol 36(4 Suppl 2):S2–S16 Pui CH, Thiel E (2009) Central nervous system disease in hematologic malignancies: historical perspective and practical applications. Semin Oncol 36(4 Suppl 2):S2–S16
4.
go back to reference 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):193–200CrossRefPubMed 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):193–200CrossRefPubMed
5.
go back to reference 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):2766–2772CrossRefPubMed 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):2766–2772CrossRefPubMed
6.
go back to reference 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):114–119CrossRef 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):114–119CrossRef
7.
go back to reference 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):149–157CrossRefPubMed 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):149–157CrossRefPubMed
8.
go back to reference 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):3150–3156CrossRefPubMed 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):3150–3156CrossRefPubMed
9.
go back to reference 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):395–404CrossRefPubMed 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):395–404CrossRefPubMed
10.
go back to reference 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):3110–3116CrossRefPubMed 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):3110–3116CrossRefPubMed
11.
go back to reference Blaney SM, Balis FM, Poplack DG (1991) Current pharmacological treatment approaches to central nervous system leukaemia. Drugs 41(5):702–716CrossRefPubMed Blaney SM, Balis FM, Poplack DG (1991) Current pharmacological treatment approaches to central nervous system leukaemia. Drugs 41(5):702–716CrossRefPubMed
12.
go back to reference Shapiro WR, Young DF, Mehta BM (1975) Methotrexate: distribution in cerebrospinal fluid after intravenous, ventricular and lumbar injections. N Engl J Med 293(4):161–166CrossRefPubMed Shapiro WR, Young DF, Mehta BM (1975) Methotrexate: distribution in cerebrospinal fluid after intravenous, ventricular and lumbar injections. N Engl J Med 293(4):161–166CrossRefPubMed
13.
go back to reference Chamberlain MC (2000) Neoplastic meningitis: a guide to diagnosis and treatment. Curr Opin Neurol 13(6):641–648CrossRefPubMed Chamberlain MC (2000) Neoplastic meningitis: a guide to diagnosis and treatment. Curr Opin Neurol 13(6):641–648CrossRefPubMed
14.
go back to reference 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):496–502CrossRefPubMed 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):496–502CrossRefPubMed
15.
go back to reference 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):1674–1679CrossRefPubMed 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):1674–1679CrossRefPubMed
16.
go back to reference 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):238–244CrossRefPubMed 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):238–244CrossRefPubMed
17.
go back to reference 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):650–655CrossRefPubMed 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):650–655CrossRefPubMed
18.
go back to reference 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):1947–1952CrossRefPubMed 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):1947–1952CrossRefPubMed
19.
go back to reference 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(CrossRef 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(CrossRef
20.
go back to reference 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):654–662CrossRefPubMed 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):654–662CrossRefPubMed
21.
go back to reference 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):1228–1235CrossRefPubMedPubMedCentral 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):1228–1235CrossRefPubMedPubMedCentral
Metadata
Title
Efficacy of intrathecal chemotherapy in patients with central nervous system involvement of hematological malignancies: a retrospective analysis
Authors
A. Dara
B. B. Mook
J. K. Doorduijn
M. J. van den Bent
A. G. Dinmohamed
J. E. C. Bromberg
Publication date
01-08-2018
Publisher
Springer US
Published in
Journal of Neuro-Oncology / Issue 1/2018
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-018-2849-x

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