Advertisement

Annals of Hematology

, Volume 96, Issue 1, pp 57–64 | Cite as

Secondary central nervous system relapse in diffuse large B cell lymphoma in a resource limited country: result from the Thailand nationwide multi-institutional registry

  • Kitsada WudhikarnEmail author
  • Udomsak Bunworasate
  • Jakrawadee Julamanee
  • Arnuparp Lekhakula
  • Suporn Chuncharunee
  • Pimjai Niparuck
  • Supachai Ekwattanakit
  • Archrob Khuhapinant
  • Lalita Norasetthada
  • Weerasak Nawarawong
  • Nisa Makruasi
  • Nonglak Kanitsap
  • Chittima Sirijerachai
  • Kanchana Chansung
  • Peerapon Wong
  • Tontanai Numbenjapon
  • Kannadit Prayongratana
  • Tawatchai Suwanban
  • Somchai Wongkhantee
  • Pannee Praditsuktavorn
  • Tanin Intragumtornchai
  • on behalf of Thai Lymphoma Study Group
Original Article

Abstract

Secondary central nervous system (CNS) relapse is a serious and fatal complication of diffuse large B cell lymphoma (DLBCL). Data on secondary CNS (SCNS) relapse were mostly obtained from western countries with limited data from developing countries. We analyzed the data of 2034 newly diagnosed DLBCL patients enrolled into the multi-center registry under Thai Lymphoma Study Group from setting. The incidence, September 2006 to December 2013 to represent outcome from a resource limited pattern, management, and outcome of SCNS relapse were described. The 2-year cumulative incidence (CI) of SCNS relapse was 2.7 %. A total of 729, 1024, and 281 patients were classified as low-, intermediate-, and high-risk CNS international prognostic index (CNS-IPI) with corresponding 2-year CI of SCNS relapse of 1.5, 3.1, and 4.6 %, respectively (p < 0.001). Univariate analysis demonstrated advance stage disease, poor performance status, elevated lactate dehydrogenase, presence of B symptoms, more than one extranodal organ involvement, high IPI, and high CNS-IPI group as predictive factors for SCNS relapse. Rituximab exposure and intrathecal chemoprophylaxis offered no protective effect against SCNS relapse. At the time of analysis, six patients were alive. Median OS in SCNS relapsed patients was significantly shorter than relapsed patients without CNS involvement (13.2 vs 22.6 months) (p < 0.001). Primary causes of death were progressive disease (n = 35, 63.6 %) and infection (n = 9, 16.7 %). In conclusion, although the incidence of SCNS relapse in our cohort was low, the prognosis was dismal. Prophylaxis for SCNS involvement was underused even in high-risk patients. Novel approaches for SCNS relapse prophylaxis and managements are warranted.

Keywords

Secondary CNS relapse Diffuse large B cell lymphoma CNS prophylaxis CNS-IPI 

Notes

Acknowledgment

The authors acknowledge the collective contribution of the medical, nursing, and administrative staff of each member center of Thai Lymphoma Study Group.

Compliance with ethical standards

Ethical statements

The institutional review board committee at each participation site approved the study. All patients provided informed consent granting the investigator to abstract their medical information for research purposes.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

277_2016_2848_MOESM1_ESM.docx (385 kb)
ESM 1 ᅟ(DOCX 384 kb)

References

  1. 1.
    Friedberg JW (2011) Relapsed/refractory diffuse large B-cell lymphoma. Hematology Am Soc Hematol Educ Program 2011:498–505PubMedGoogle Scholar
  2. 2.
    Boehme V, Zeynalova S, Kloess 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 18:149–157CrossRefPubMedGoogle Scholar
  3. 3.
    Deng L, Song Y, Zhu J et al (2013) Secondary central nervous system involvement in 599 patients with diffuse large B-cell lymphoma: are there any changes in the rituximab era? Int J Hematol 98:664–671CrossRefPubMedGoogle Scholar
  4. 4.
    Tomita N, Yokoyama M, Yamamoto W et al (2012) Central nervous system event in patients with diffuse large B-cell lymphoma in the rituximab era. Cancer Sci 103:245–251CrossRefPubMedGoogle Scholar
  5. 5.
    Villa D, Connors JM, Shenkier TN et al (2010) Incidence and risk factors for central nervous system relapse in patients with diffuse large B-cell lymphoma: the impact of the addition of rituximab to CHOP chemotherapy. Ann Oncol 21:1046–1052CrossRefPubMedGoogle Scholar
  6. 6.
    Aviles A, Jesus Nambo M, Neri N (2013) Central nervous system prophylaxis in patients with aggressive diffuse large B cell lymphoma: an analysis of 3,258 patients in a single center. Med Oncol 30:520CrossRefPubMedGoogle Scholar
  7. 7.
    Schmitz N, Zeynalova S, Glass B et al (2012) CNS disease in younger patients with aggressive B-cell lymphoma: an analysis of patients treated on the Mabthera International Trial and trials of the German High-Grade Non-Hodgkin Lymphoma Study Group. Ann Oncol 23:1267–1273CrossRefPubMedGoogle Scholar
  8. 8.
    Boehme V, Schmitz N, Zeynalova S et al (2009) 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 113:3896–3902CrossRefPubMedGoogle Scholar
  9. 9.
    Zhang J, Chen B, Xu X (2014) Impact of rituximab on incidence of and risk factors for central nervous system relapse in patients with diffuse large B-cell lymphoma: a systematic review and meta-analysis. Leuk Lymphoma 55:509–514CrossRefPubMedGoogle Scholar
  10. 10.
    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):3150–6Google Scholar
  11. 11.
    Guirguis HR, Cheung MC, Mahrous M et al (2012) Impact of central nervous system (CNS) prophylaxis on the incidence and risk factors for CNS relapse in patients with diffuse large B-cell lymphoma treated in the rituximab era: a single centre experience and review of the literature. Br J Haematol 159:39–49CrossRefPubMedGoogle Scholar
  12. 12.
    Kridel R, Dietrich PY (2011) Prevention of CNS relapse in diffuse large B-cell lymphoma. Lancet Oncol 12:1258–1266CrossRefPubMedGoogle Scholar
  13. 13.
    Kumar A, Vanderplas A, LaCasce AS et al (2012) Lack of benefit of central nervous system prophylaxis for diffuse large B-cell lymphoma in the rituximab era: findings from a large national database. Cancer 118:2944–2951CrossRefPubMedGoogle Scholar
  14. 14.
    Shimazu Y, Notohara K, Ueda Y (2009) Diffuse large B-cell lymphoma with central nervous system relapse: prognosis and risk factors according to retrospective analysis from a single-center experience. Int J Hematol 89:577–583CrossRefPubMedGoogle Scholar
  15. 15.
    Tai WM, Chung J, Tang PL et al (2011) Central nervous system (CNS) relapse in diffuse large B cell lymphoma (DLBCL): pre- and post-rituximab. Ann Hematol 90:809–818CrossRefPubMedGoogle Scholar
  16. 16.
    Yamamoto W, Tomita N, Watanabe R et al (2010) Central nervous system involvement in diffuse large B-cell lymphoma. Eur J Haematol 85:6–10PubMedGoogle Scholar
  17. 17.
    Intragumtornchai T, Bunworasate U, Siritanaratkul N et al (2013) Inferior progression-free survival for Thai patients with diffuse large B-cell lymphoma treated under Universal Coverage Scheme: the impact of rituximab inaccessibility. Leuk Lymphoma 54:83–89CrossRefPubMedGoogle Scholar
  18. 18.
    Cheng SC, Fine JP, Wei LJ (1998) Prediction of cumulative incidence function under the proportional hazards model. Biometrics 54:219–228CrossRefPubMedGoogle Scholar
  19. 19.
    Schmitz N, Zeynalova S, Nickelsen M et al (2013) A new prognostic model to assess the risk of CNS disease in patients with aggressive B-cell lymphoma. Hematol Oncol 31:96–150Google Scholar
  20. 20.
    Savage KJ, Zeynalova S, Kansara RR et al (2014) Validation of a prognostic model to assess the risk of CNS disease in patients with aggressive B-cell lymphoma. Blood 124:394–394Google Scholar
  21. 21.
    Savage KJ, Slack GW, Mottok A et al (2016) Impact of dual expression of MYC and BCL2 by immunohistochemistry on the risk of CNS relapse in DLBCL. Blood 127:2182–2188CrossRefPubMedGoogle Scholar
  22. 22.
    Nitta H, Terui Y, Yokoyama M et al (2015) Absolute peripheral monocyte count at diagnosis predicts central nervous system relapse in diffuse large B-cell lymphoma. Haematologica 100:87–90CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Song YS, Lee WW, Lee JS, Kim SE (2015) Prediction of central nervous system relapse of diffuse large B-cell lymphoma using pretherapeutic [18F]2-fluoro-2-deoxyglucose (FDG) positron emission tomography/computed tomography. Medicine (Baltimore) 94, e1978CrossRefGoogle Scholar
  24. 24.
    Gonzalez-Barca E, Canales M, Salar A et al (2016) Central nervous system prophylaxis with intrathecal liposomal cytarabine in a subset of high-risk patients with diffuse large B-cell lymphoma receiving first line systemic therapy in a prospective trial. Ann Hematol 95:893–899CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Cheah CY, Herbert KE, O’Rourke K et al (2014) A multicentre retrospective comparison of central nervous system prophylaxis strategies among patients with high-risk diffuse large B-cell lymphoma. Br J Cancer 111:1072–1079CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Ferreri AJ, Bruno-Ventre M, Donadoni G et al (2014) 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 HaematolGoogle Scholar
  27. 27.
    Fletcher CD, Kahl BS (2014) Central nervous system involvement in diffuse large B-cell lymphoma: an analysis of risks and prevention strategies in the post-rituximab era. Leuk Lymphoma 55:2228–2240CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Kitsada Wudhikarn
    • 1
    Email author
  • Udomsak Bunworasate
    • 1
  • Jakrawadee Julamanee
    • 2
  • Arnuparp Lekhakula
    • 2
  • Suporn Chuncharunee
    • 3
  • Pimjai Niparuck
    • 3
  • Supachai Ekwattanakit
    • 4
  • Archrob Khuhapinant
    • 4
  • Lalita Norasetthada
    • 5
  • Weerasak Nawarawong
    • 5
  • Nisa Makruasi
    • 6
  • Nonglak Kanitsap
    • 7
  • Chittima Sirijerachai
    • 8
  • Kanchana Chansung
    • 8
  • Peerapon Wong
    • 9
  • Tontanai Numbenjapon
    • 10
  • Kannadit Prayongratana
    • 10
  • Tawatchai Suwanban
    • 11
  • Somchai Wongkhantee
    • 12
  • Pannee Praditsuktavorn
    • 13
  • Tanin Intragumtornchai
    • 1
  • on behalf of Thai Lymphoma Study Group
  1. 1.Division of Hematology, Department of Internal MedicineFaculty of Medicine, Chulalongkorn UniversityBangkokThailand
  2. 2.Department of Internal MedicinePrince of Songkla UniversitySongkhlaThailand
  3. 3.Department of Internal MedicineRamathibodi Hospital, Mahidol UniversityBangkokThailand
  4. 4.Department of Internal MedicineSiriraj Hospital, Mahidol UniversityBangkokThailand
  5. 5.Department of Internal MedicineChiang Mai UniversityChiang MaiThailand
  6. 6.Department of Internal MedicineSrinakharinwirot UniversityNakhon NayokThailand
  7. 7.Department of Internal MedicineThammasart UniversityBangkokThailand
  8. 8.Department of Internal MedicineKhon Kaen UniversityKhon KaenThailand
  9. 9.Department of Internal MedicineNaresuan UniversityPhitsanulokThailand
  10. 10.Department of Internal MedicinePhramongkutklao Hospital and College of MedicineBangkokThailand
  11. 11.Department of Internal MedicineRajavithi HospitalBangkokThailand
  12. 12.Department of Internal MedicineKhonkaen Regional HospitalKhon KaenThailand
  13. 13.Department of Internal MedicineChulabhorn HospitalBangkokThailand

Personalised recommendations