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Published in: International Journal of Hematology 5/2009

01-06-2009 | Original Article

Diffuse large B-cell lymphoma with central nervous system relapse: prognosis and risk factors according to retrospective analysis from a single-center experience

Authors: Yutaka Shimazu, Kenji Notohara, Yasunori Ueda

Published in: International Journal of Hematology | Issue 5/2009

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Abstract

The introduction of rituximab for diffuse large B-cell lymphoma (DLBCL) has improved the disease’s overall prognosis. However, relapse in the central nervous system (CNS) is still an issue. We investigated the prognosis and risk factors of CNS recurrence in DLBCL. A total of 403 patients who were diagnosed with DLBCL without CNS involvement between January 1996 and April 2007 at our institution were included in the study. Subsequently, 42 experienced CNS relapse. Clinical information was gathered by chart review. The median disease-free interval to CNS relapse was 625 days. The mean survival periods after relapse in the cases with CNS and extra-CNS involvement were 513 and 1,615 days, respectively (P = 0.0004). Multivariate analysis identified age >60 years (P = 0.031), involvement in two or more extranodal sites (P = 0.040), bone marrow involvement (P = 0.036), an elevated serum lactate dehydrogenase (LDH) level (P = 0.016), and treatment without rituximab before CNS relapse (P = 0.027) as independent predictors of CNS relapse. We have shown that cases of DLBCL occurring in advanced age, involving two or more extranodal sites or the bone marrow, or showing an elevation of LDH have a higher risk of CNS relapse. Rituximab may prevent CNS relapse by reducing the recurrence of DLBCL at all sites. An effective CNS prophylaxis strategy should be determined according to the risk assessment of CNS relapse.
Literature
1.
go back to reference Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. New Eng J Med. 2002;346:235–42.PubMedCrossRef Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. New Eng J Med. 2002;346:235–42.PubMedCrossRef
2.
go back to reference Pfreundschuh M, Trümper L, Osterborg A, Pettengell R, Trneny M, Imrie K, et al. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006;7:379–91.PubMedCrossRef Pfreundschuh M, Trümper L, Osterborg A, Pettengell R, Trneny M, Imrie K, et al. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006;7:379–91.PubMedCrossRef
3.
go back to reference Sehn LH, Donaldson J, Chhanabhai M, Fitzgerald C, Gill K, Klasa R, et al. Introduction of combined CHOP plus rituximab therapy dramatically improved outcome of diffuse large B-cell lymphoma in British Columbia. J Clin Oncol. 2005;23:5027–33.PubMedCrossRef Sehn LH, Donaldson J, Chhanabhai M, Fitzgerald C, Gill K, Klasa R, et al. Introduction of combined CHOP plus rituximab therapy dramatically improved outcome of diffuse large B-cell lymphoma in British Columbia. J Clin Oncol. 2005;23:5027–33.PubMedCrossRef
4.
go back to reference van Besien K, Ha CS, Murphy S, McLaughlin P, Rodriguez A, Amin K, et al. Risk factors, treatment, and outcome of central nervous system recurrence in adults with intermediate-grade and immunoblastic lymphoma. Blood. 1998;91:1178–84.PubMed van Besien K, Ha CS, Murphy S, McLaughlin P, Rodriguez A, Amin K, et al. Risk factors, treatment, and outcome of central nervous system recurrence in adults with intermediate-grade and immunoblastic lymphoma. Blood. 1998;91:1178–84.PubMed
5.
go back to reference Hollender A, Kvaloy S, Lote K, Nome O, Holte H. Prognostic factors in 140 adult patients with non-Hodgkin’s lymphoma with systemic central nervous system (CNS) involvement: a single centre analysis. Eur J Cancer. 2000;36:1762–8.PubMedCrossRef Hollender A, Kvaloy S, Lote K, Nome O, Holte H. Prognostic factors in 140 adult patients with non-Hodgkin’s lymphoma with systemic central nervous system (CNS) involvement: a single centre analysis. Eur J Cancer. 2000;36:1762–8.PubMedCrossRef
6.
go back to reference Bokstein F, Lossos A, Lossos IS, Siegal T. Central nervous system relapse of systemic non-Hodgkin’s lymphoma: results of treatment based on high-dose methotrexate combination chemotherapy. Leuk Lymphoma. 2002;43:587–93.PubMedCrossRef Bokstein F, Lossos A, Lossos IS, Siegal T. Central nervous system relapse of systemic non-Hodgkin’s lymphoma: results of treatment based on high-dose methotrexate combination chemotherapy. Leuk Lymphoma. 2002;43:587–93.PubMedCrossRef
7.
go back to reference Doolittle ND, Abrey LE, Shenkier TN, Tali S, Bromberg JE, Neuwelt EA, et al. Brain parenchyma involvement as isolated central nervous system relapse of systemic non-Hodgkin lymphoma: an International Primary CNS Lymphoma Collaborative Group report. Blood. 2008;111:1085–93.PubMedCrossRef Doolittle ND, Abrey LE, Shenkier TN, Tali S, Bromberg JE, Neuwelt EA, et al. Brain parenchyma involvement as isolated central nervous system relapse of systemic non-Hodgkin lymphoma: an International Primary CNS Lymphoma Collaborative Group report. Blood. 2008;111:1085–93.PubMedCrossRef
8.
go back to reference Hill QA, Owen RG. CNS prophylaxis in lymphoma: who to target and what therapy to use. Blood Rev. 2006;20:319–32.PubMedCrossRef Hill QA, Owen RG. CNS prophylaxis in lymphoma: who to target and what therapy to use. Blood Rev. 2006;20:319–32.PubMedCrossRef
9.
go back to reference Tomita N, Kodama F, Kanamori H, Motomura S, Ishigatsubo Y. Secondary central nervous system lymphoma. Int J Hematol. 2006;84:128–35.PubMedCrossRef Tomita N, Kodama F, Kanamori H, Motomura S, Ishigatsubo Y. Secondary central nervous system lymphoma. Int J Hematol. 2006;84:128–35.PubMedCrossRef
10.
go back to reference Feugier P, Virion JM, Tilly H, Haioun C, Marit G, Macro M, et al. Incidence and risk factors for central nervous system occurrence in elderly patients with diffuse large-B-cell lymphoma: influence of rituximab. Ann Oncol. 2004;15:129–33.PubMedCrossRef Feugier P, Virion JM, Tilly H, Haioun C, Marit G, Macro M, et al. Incidence and risk factors for central nervous system occurrence in elderly patients with diffuse large-B-cell lymphoma: influence of rituximab. Ann Oncol. 2004;15:129–33.PubMedCrossRef
11.
go back to reference Chua SL, Seymour JF, Streater J, Wolf MM, Januszewicz EH, Prince HM. Intrathecal chemotherapy alone is inadequate central nervous system prophylaxis in patients with intermediate-grade non-Hodgkin’s lymphoma. Leuk Lymphoma. 2002;43:1783–8.PubMedCrossRef Chua SL, Seymour JF, Streater J, Wolf MM, Januszewicz EH, Prince HM. Intrathecal chemotherapy alone is inadequate central nervous system prophylaxis in patients with intermediate-grade non-Hodgkin’s lymphoma. Leuk Lymphoma. 2002;43:1783–8.PubMedCrossRef
12.
go back to reference Tomita N, Kodama F, Kanamori H, Motomura S, Ishigatsubo Y. Prophylactic intrathecal methotrexate and hydrocortisone reduces central nervous system recurrence and improves survival in aggressive non-Hodgkin lymphoma. Cancer. 2002;95:576–80.PubMedCrossRef Tomita N, Kodama F, Kanamori H, Motomura S, Ishigatsubo Y. Prophylactic intrathecal methotrexate and hydrocortisone reduces central nervous system recurrence and improves survival in aggressive non-Hodgkin lymphoma. Cancer. 2002;95:576–80.PubMedCrossRef
13.
go back to reference Arkenau HT, Chong G, Cunningham D, Watkins D, Agarwal R, Sirohi B, et al. The role of intrathecal chemotherapy prophylaxis in patients with diffuse large B-cell lymphoma. Ann Oncol. 2007;18:541–5.PubMedCrossRef Arkenau HT, Chong G, Cunningham D, Watkins D, Agarwal R, Sirohi B, et al. The role of intrathecal chemotherapy prophylaxis in patients with diffuse large B-cell lymphoma. Ann Oncol. 2007;18:541–5.PubMedCrossRef
14.
go back to reference Haioun C, Besson C, Lepage E, Thieblemont C, Simon D, Rose C, et al. Incidence and risk factors of central nervous system relapse in histologically aggressive non-Hodgkin’s lymphoma uniformly treated and receiving intrathecal central nervous system prophylaxis: a GELA study on 974 patients (Groupe d’Etudes des Lymphomes de l’Adulte). Ann Oncol. 2000;11:685–90.PubMedCrossRef Haioun C, Besson C, Lepage E, Thieblemont C, Simon D, Rose C, et al. Incidence and risk factors of central nervous system relapse in histologically aggressive non-Hodgkin’s lymphoma uniformly treated and receiving intrathecal central nervous system prophylaxis: a GELA study on 974 patients (Groupe d’Etudes des Lymphomes de l’Adulte). Ann Oncol. 2000;11:685–90.PubMedCrossRef
15.
go back to reference Boehme IV, Zeynalova S, Kloess M, Loeffler M, Kaiser U, Pfreundschuh M, et al. Incidence and risk factors of central nervous system recurrence in aggressive lymphoma: a survey of 1, 693 patients treated in protocols of the German High-Grade Non-Hodgkin’s Lymphoma Study Group (DSHNHL). Ann Oncol. 2007;18:149–57.PubMedCrossRef Boehme IV, Zeynalova S, Kloess M, Loeffler M, Kaiser U, Pfreundschuh M, et al. Incidence and risk factors of central nervous system recurrence in aggressive lymphoma: a survey of 1, 693 patients treated in protocols of the German High-Grade Non-Hodgkin’s Lymphoma Study Group (DSHNHL). Ann Oncol. 2007;18:149–57.PubMedCrossRef
16.
go back to reference Hollender A, Kvaloy S, Nome O, Skovlund E, Lote K, Holte H. Central nervous system involvement following diagnosis of non-Hodgkin’s lymphoma: a risk model. Ann Oncol. 2002;13:1099–107.PubMedCrossRef Hollender A, Kvaloy S, Nome O, Skovlund E, Lote K, Holte H. Central nervous system involvement following diagnosis of non-Hodgkin’s lymphoma: a risk model. Ann Oncol. 2002;13:1099–107.PubMedCrossRef
17.
go back to reference Keldsen N, Michalski W, Bentzen SM, Hansen KB, Thorling K. Risk factors for central nervous system involvement in non-Hodgkins-lymphoma: a multivariate analysis. Acta Oncologica. 1996;35:703–8.PubMedCrossRef Keldsen N, Michalski W, Bentzen SM, Hansen KB, Thorling K. Risk factors for central nervous system involvement in non-Hodgkins-lymphoma: a multivariate analysis. Acta Oncologica. 1996;35:703–8.PubMedCrossRef
18.
go back to reference Tsurumi H, Hara T, Goto N, Kanemura N, Kasahara S, Sawada M, et al. A phase II study of a THP-COP regimen for the treatment of elderly patients aged 70 years or older with diffuse large B-cell lymphoma. Hematol Oncol. 2007;25:107–14.PubMedCrossRef Tsurumi H, Hara T, Goto N, Kanemura N, Kasahara S, Sawada M, et al. A phase II study of a THP-COP regimen for the treatment of elderly patients aged 70 years or older with diffuse large B-cell lymphoma. Hematol Oncol. 2007;25:107–14.PubMedCrossRef
19.
go back to reference Cheung CW, Burton C, Smith P, Linch DC, Hoskin PJ, Ardeshna KM. Central nervous system chemoprophylaxis in non-Hodgkin lymphoma: current practice in the UK. Br J Haematol. 2005;131:193–200.PubMedCrossRef Cheung CW, Burton C, Smith P, Linch DC, Hoskin PJ, Ardeshna KM. Central nervous system chemoprophylaxis in non-Hodgkin lymphoma: current practice in the UK. Br J Haematol. 2005;131:193–200.PubMedCrossRef
20.
go back to reference Okamoto M, Maruyama F, Tsuzuki M, Nomura T, Miyazaki H, Wakita M, et al. Salvage chemotherapy for relapsed/refractory aggressive non-Hodgkin’s lymphoma with a combination of dexamethasone, etoposide, ifosfamide and carboplatin. Rinsho Ketsueki. 1994;35:635–41.PubMed Okamoto M, Maruyama F, Tsuzuki M, Nomura T, Miyazaki H, Wakita M, et al. Salvage chemotherapy for relapsed/refractory aggressive non-Hodgkin’s lymphoma with a combination of dexamethasone, etoposide, ifosfamide and carboplatin. Rinsho Ketsueki. 1994;35:635–41.PubMed
21.
go back to reference Takasu S, Wakabayashi T, Kajita Y, Hatano N, Hatano H, Usui T, et al. Effectiveness of DeVIC chemotherapy for recurrent primary central nervous system lymphoma. No Shinkei Geka. 2000;28:789–94.PubMed Takasu S, Wakabayashi T, Kajita Y, Hatano N, Hatano H, Usui T, et al. Effectiveness of DeVIC chemotherapy for recurrent primary central nervous system lymphoma. No Shinkei Geka. 2000;28:789–94.PubMed
22.
go back to reference Simpson L, Ansell SM, Colgan JP, Habermann TM, Inwards DJ, Ristow KM, et al. Effectiveness of second-line salvage chemotherapy with ifosfamide, carboplatin, and etoposide in patients with relapsed diffuse large B-cell lymphoma not responding to cis-platinum, cytosine arabinoside, and dexamethasone. Leuk Lymphoma. 2007;48:1332–7.PubMedCrossRef Simpson L, Ansell SM, Colgan JP, Habermann TM, Inwards DJ, Ristow KM, et al. Effectiveness of second-line salvage chemotherapy with ifosfamide, carboplatin, and etoposide in patients with relapsed diffuse large B-cell lymphoma not responding to cis-platinum, cytosine arabinoside, and dexamethasone. Leuk Lymphoma. 2007;48:1332–7.PubMedCrossRef
23.
go back to reference Gutierrez M, Chabner BA, Pearson D, Steinberg SM, Jaffe ES, Cheson BD, et al. Role of a doxorubicin-containing regimen in relapsed and resistant lymphomas: an 8-year follow-up study of EPOCH. J Clin Oncol. 2000;18:3633–42.PubMed Gutierrez M, Chabner BA, Pearson D, Steinberg SM, Jaffe ES, Cheson BD, et al. Role of a doxorubicin-containing regimen in relapsed and resistant lymphomas: an 8-year follow-up study of EPOCH. J Clin Oncol. 2000;18:3633–42.PubMed
24.
go back to reference Philip T, Guglielmi C, Hagenbeek A, Somers R, Van der Lelie H, Bron D, et al. High-dose therapy and autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin’s lymphoma. New Engl J Med. 1995;333:1540–5.PubMedCrossRef Philip T, Guglielmi C, Hagenbeek A, Somers R, Van der Lelie H, Bron D, et al. High-dose therapy and autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin’s lymphoma. New Engl J Med. 1995;333:1540–5.PubMedCrossRef
25.
go back to reference Lin DY. Non-parametric inference for cumulative incidence functions in competing risks studies. Stat Med. 1997;16:901–10.PubMedCrossRef Lin DY. Non-parametric inference for cumulative incidence functions in competing risks studies. Stat Med. 1997;16:901–10.PubMedCrossRef
26.
go back to reference Kaplan EI, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958;55:457.CrossRef Kaplan EI, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958;55:457.CrossRef
27.
go back to reference Collet D. Modelling survival data in medical research. Boca Raton: Chapman & Hall/CRC; 1999. p. 80–1. Collet D. Modelling survival data in medical research. Boca Raton: Chapman & Hall/CRC; 1999. p. 80–1.
29.
go back to reference Kikuchi A, Kawada H, Iwaki Y, Machida S, Tsuchiya T, Fukuda R, et al. Measurement of rituximab concentration in the cerebrospinal fluid in CNS lymphoma. Rinsho Ketsueki. 2004;45:1255–7.PubMed Kikuchi A, Kawada H, Iwaki Y, Machida S, Tsuchiya T, Fukuda R, et al. Measurement of rituximab concentration in the cerebrospinal fluid in CNS lymphoma. Rinsho Ketsueki. 2004;45:1255–7.PubMed
Metadata
Title
Diffuse large B-cell lymphoma with central nervous system relapse: prognosis and risk factors according to retrospective analysis from a single-center experience
Authors
Yutaka Shimazu
Kenji Notohara
Yasunori Ueda
Publication date
01-06-2009
Publisher
Springer Japan
Published in
International Journal of Hematology / Issue 5/2009
Print ISSN: 0925-5710
Electronic ISSN: 1865-3774
DOI
https://doi.org/10.1007/s12185-009-0289-2

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