Authors:
Ádám Ónodi Szegedi Tudományegyetem, Szent –Györgyi Albert Klinikai Központ, Belgyógyászati Klinika, Déli Telephely, Haematologia Osztály, Szeged, Magyarország

Search for other papers by Ádám Ónodi in
Current site
Google Scholar
PubMed
Close
https://orcid.org/0009-0002-8280-5779
and
Zita Borbényi Szegedi Tudományegyetem, Szent –Györgyi Albert Klinikai Központ, Belgyógyászati Klinika, Déli Telephely, Haematologia Osztály, Szeged, Magyarország

Search for other papers by Zita Borbényi in
Current site
Google Scholar
PubMed
Close
Restricted access

Diffúz nagy B-sejtes lymphoma (DLBCL) esetén a központi idegrendszeri (CNS) relapsus ritkán előforduló, ám többnyire nehezen kezelhető jelenség, mely az esetek jelentős részében a beteg halálához vezet. A fentiekből következően a CNS-prophylaxis rendkívül hangsúlyos kérdés, melynek kivitelezésére többféle megközelítés létezik. A legelterjedtebb gyakorlat a methotrexát szisztémás vagy intrathecalis alkalmazása, melynek hatékonyságáról jobbára retrospectiv vizsgálatok állnak rendelkezésre. Jelen cikkreferátumban a szerzők a rendelkezésre álló irodalom áttekintésével foglalják össze a CNS-relapsus előrejelzésének és megelőzésének jelenlegi lehetőségeit.

Central nervous system (CNS) relapse in diffuse large B-cell lymphoma (DLBCL) is an uncommon event, however it is hard to treat and in most cases it leads to the patient's death. Because of this, finding the optimal method for CNS-prophylaxis is a pivotal question. In most cases systemic or intrathecal methotrexate is used for this purpose; its efficacy was mostly examined in retrospective studies. The authors in this article summarise the options for prediction and treatment of CNS-relapses based on the available mediacal literature.

  • [1]

    Guirguis HR, Cheung MC, Mahrous M, et al. l. Impact of central nervous system (CNS) prophylaxis on the incidence and risk factors for CNS relapse in patients with difuse large B-cell lymphoma treated in the rituximab era: a single centre experience and review of the literature. Br J Haematol 2012; 159(1): 3949.

    • Search Google Scholar
    • Export Citation
  • [2]

    Roschewski M. Central nervous system prophylaxis in difuse large B-cell lymphoma: a race to the bottom. Haematologica 2021. https://doi.org/10.3324/haematol.2020.266635.

    • Search Google Scholar
    • Export Citation
  • [3]

    Lin Z, Chen X, Liu L, et al. The role of central nervous system (CNS) prophylaxis in preventing DLBCL patients from CNS relapse: a network meta-analysis. Crit Rev Oncol Hematol 2022; 176:103756.

    • Search Google Scholar
    • Export Citation
  • [4]

    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(7): 1099107.

    • Search Google Scholar
    • Export Citation
  • [5]

    Schmitz N, Zeynalova S, Nickelsen M, et al. CNS International prognostic index: a risk model for CNS relapse in patients with difuse large b-cell lymphoma treated with R-CHOP. J Clin Oncol 2016; 34(26): 31506.

    • Search Google Scholar
    • Export Citation
  • [6]

    Hutchings M, Ladetto M, Buske C, et al. ESMO Consensus Conference on malignant lymphoma: management of ‘ultra-high-risk’ patients. Ann Oncol 2018; 29(8): 1687700.

    • Search Google Scholar
    • Export Citation
  • [7]

    McKay P, Wilson MR, Chaganti S, et al. The prevention of central nervous system relapse in difuse large B-cell lymphoma: a British Society for Haematology good practice paper. Br J Haematol 2020; 190(5): 70814.

    • Search Google Scholar
    • Export Citation
  • [8]

    Tomita N, Yokoyama M, Yamamoto W, et al. The standard international prognostic index for predicting the risk of CNS involvement in DLBCL without specifc prophylaxis. Leuk Lymphoma 2018; 59(1): 97104.

    • Search Google Scholar
    • Export Citation
  • [9]

    Alaggio R, Amador C, Anagnostopoulos I, et al. The 5th edition of the World Health Organization classifcation of haematolymphoid tumours lymphoid neoplasms. Leukemia 2022; 36(7): 172048.

    • Search Google Scholar
    • Export Citation
  • [10]

    Zahid MF, Khan N, Hashmi SK, et al. Central nervous system prophylaxis in difuse large B-cell lymphoma. Eur J Haematol 2016; 97(2): 10820.

    • Search Google Scholar
    • Export Citation
  • [11]

    Savage KJ, Slack GW, Mottok K, et al. Impact of dual expression of MYC and BCL2 by immunohistochemistry on the risk of CNS relapse in DLBCL. Blood 2016; 127(18): 21828.

    • Search Google Scholar
    • Export Citation
  • [12]

    Klanova M, Sehn LH, Bence-Bruckler I, et al. Integration of cell of origin into the clinical CNS International prognostic index improves CNS relapse prediction in DLBCL. Blood 2019; 133(9): 91926.

    • Search Google Scholar
    • Export Citation
  • [13]

    Petrich AM, Gandhi M, Jovanovic B, et al. Impact of induction regimen and stem cell transplantation on outcomes in double-hit lymphoma: a multicenter retrospective analysis. Blood 2014; 124(15): 235461.

    • Search Google Scholar
    • Export Citation
  • [14]

    Reimann M, Masswig S, Schleich K, et al. Modeling the CNS tropism of difuse large B-Cell lymphomas in Vivo. Blood 2015; 126(23): 576.

  • [15]

    Wang X, Gao Y, Shan C, et al. Association of circulating tumor DNA from the cerebrospinal fuid with high-risk CNS involvement in patients with difuse large B-cell lymphoma. Clin Transl Med 2021. https://doi.org/10.1002/ctm2.236.

    • Search Google Scholar
    • Export Citation
  • [16]

    Schmitz R, Wright GW, Huang DW, et al. Genetics and pathogenesis of difuse large B-cell lymphoma. N Engl J Med 2018; 378(15): 1396407.

    • Search Google Scholar
    • Export Citation
  • [17]

    Hegde U, Filie A, Little RF, et al. High incidence of occult leptomeningeal disease detected by fow cytometry in newly diagnosed aggressive B-cell lymphomas at risk for central nervous system involvement: the role of fow cytometry versus cytology. Blood 2005; 105(2): 496502.

    • Search Google Scholar
    • Export Citation
  • [18]

    Bobillo S, Crespo M, Escudero L, et al. Cell free circulating tumor DNA in cerebrospinal fuid detects and monitors central nervous system involvement of B-cell lymphomas. Haematologica 2021; 106(2): 51321.

    • Search Google Scholar
    • Export Citation
  • [19]

    Olszewski AJ, Chorzalska AD, Petersen M, et al. Detection of clonotypic DNA in the cerebrospinal fuid as a marker of central nervous system invasion in lymphoma. Blood Adv 2021; 5(24): 552535.

    • Search Google Scholar
    • Export Citation
  • [20]

    Song YS, Lee WW, Lee JS, et al. Prediction of central nervous system relapse of difuse large B-cell lymphoma using pretherapeutic [18F]2- Fluoro-2- Deoxyglucose (FDG) positron emission tomography/computed tomography. Medicine 2015; 94(44):e1978.

    • Search Google Scholar
    • Export Citation
  • [21]

    Kim TM, Paeng JC, Chun IK, et al. Total lesion glycolysis in positron emission tomography is a better predictor of outcome than the International Prognostic Index for patients with difuse large B cell lymphoma. Cancer 2013; 119(6): 1195202.

    • Search Google Scholar
    • Export Citation
  • [22]

    Eyre TA, Djebbari F, Kirkwood, et al. Efcacy of central nervous system prophylaxis with stand-alone intrathecal chemotherapy in diffuse large B-cell lymphoma patients treated with anthracycline-based chemotherapy in the rituximab era: a systematic review. Haematologica 2020; 105(7): 191424.

    • Search Google Scholar
    • Export Citation
  • [23]

    Gleeson M, Counsell N, Cunningham D, et al. Central nervous system relapse of difuse large B-cell lymphoma in the rituximab era: results of the UK NCRI R-CHOP-14 versus 21 trial. Ann Oncol 2017; 28(10): 25116.

    • Search Google Scholar
    • Export Citation
  • [24]

    Pardridge WM. Drug transport in brain via the cerebrospinal fuid. Fluids Barriers CNS 2011. https://doi.org/10.1186/2045-8118-8-7.

  • [25]

    Eyre TA, Kirkwood AA, Wolf J, et al. Stand-alone intrathecal central nervous system (CNS) prophylaxis provide unclear beneft in reducing CNS relapse risk in elderly DLBCL patients treated with R-CHOP and is associated increased infectionrelated toxicity. Br J Haematol 2019; 187(2): 18594.

    • Search Google Scholar
    • Export Citation
  • [26]

    Bobillo S, Jofe E, Sermer D, et al. Prophylaxis with intrathecal or high-dose methotrexate in difuse large B-cell lymphoma and high risk of CNS relapse. Blood Cancer J 2021; 11(6): 113.

    • Search Google Scholar
    • Export Citation
  • [27]

    Ghose A, Elias HK, Guha G, et al. Infuence of rituximab on central nervous system relapse in difuse large b-cell lymphoma and role of prophylaxis—a systematic review of prospective studies. Clin Lymphoma Myeloma Leuk 2015; 15(8): 4517.

    • Search Google Scholar
    • Export Citation
  • [28]

    Boehme V, Schmitz N, Zeynalova S, et al. CNS events in elderly patients with aggressive lymphoma treated with Chua et al. Experimental Hematology & Oncology (2024) 13:1 Page 17 of 19 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(17): 3896902.

    • Search Google Scholar
    • Export Citation
  • [29]

    Ferreri AJM, Bruno-Ventre M, Donadoni G, et al. Risk-tailored CNS prophylaxis in a mono-institutional series of 200 patients with difuse large B-cell lymphoma treated in the rituximab era. Br J Haematol 2015; 168(5): 65462.

    • Search Google Scholar
    • Export Citation
  • [30]

    Ong SY, de Mel S, Grigoropoulos NF, et al. Highdose methotrexate is efective for prevention of isolated CNS relapse in difuse large B cell lymphoma. Blood Cancer J 2021; 11(8): 143.

    • Search Google Scholar
    • Export Citation
  • [31]

    Lewis KL, Jakobsen LH, Villa D, et al. High-dose methotrexate as CNS prophylaxis in high-risk aggressive B-cell lymphoma. J Clin Oncol 2023. Available from: https://doi.org/10.1200/JCO.23.00365.

    • Search Google Scholar
    • Export Citation
  • [32]

    Siegal T, Zylber-Katz E. Strategies for increasing drug delivery to the brain: focus on brain lymphoma. Clin Pharmacokinet 2002; 41(3): 17186.

    • Search Google Scholar
    • Export Citation
  • [33]

    Wilson MR, Eyre TA, Kirkwood AA, et al. Timing of high-dose methotrexate CNS prophylaxis in DLBCL: a multicenter international analysis of 1384 patients. Blood 2022; 139(16): 2499511.

    • Search Google Scholar
    • Export Citation
  • [34]

    Hande KR, Stein RS, McDonough DA, et al. Efects of high-dose cytarabine. Clin Pharmacol Ther 1982; 31(5): 66974.

  • [35]

    Holte H, Leppä S, Björkhlom M, et al. Dosedensifed chemoimmunotherapy followed by systemic central nervous system prophylaxis for younger high-risk difuse large B-cell/follicular grade 3 lymphoma patients: results of a phase II Nordic Lymphoma Group study. Ann Oncol 2013; 24(5): 138592.

    • Search Google Scholar
    • Export Citation
  • [36]

    Leppä S, Jørgensen J, Tierens A, et al. Patients with high-risk DLBCL beneft from dose-dense immunochemotherapy combined with early systemic CNS prophylaxis. Blood Adv 2020; 4(9): 190615.

    • Search Google Scholar
    • Export Citation
  • [37]

    González-Barca E, Canales M, Salar A, et al. Central nervous system prophylaxis with intrathecal liposomal cytarabine in a subset of high-risk patients with difuse large B-cell lymphoma receiving frst line systemic therapy in a prospective trial. Ann Hematol 2016; 95(6): 8939.

    • Search Google Scholar
    • Export Citation
  • [38]

    Conconi A, Chiappella A, Orsucci L, et al. Intensifed (Intravenous and Intrathecal) Cns prophylaxis in primary testicular difuse large B-cell lymphoma: 5-year results of the Ielsg30 trial. Hematol Oncol 2021. https://doi.org/10.1002/hon.48_2879.

    • Search Google Scholar
    • Export Citation
  • [39]

    Antonini G, Cox MC, Montefusco E, et al. Intrathecal anti-CD20 antibody: an efective and safe treatment for leptomeningeal lymphoma. J Neurooncol 2007; 81(2): 1979.

    • Search Google Scholar
    • Export Citation
  • [40]

    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(11): 13506.

    • Search Google Scholar
    • Export Citation
  • [41]

    Schulz H, Pels H, Schmidt-Wolf I, et al. Intraventricular treatment of relapsed central nervous system lymphoma with the anti-CD20 antibody rituximab. Haematologica 2004; 89(6): 7534.

    • Search Google Scholar
    • Export Citation
  • [42]

    Liu C-Y, Teng H-W, Lirng J-F, 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(10): 201821.

    • Search Google Scholar
    • Export Citation
  • [43]

    Boehme V, Zeynalova S, Kloess M, et al. 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 2007; 18(1): 14957.

    • Search Google Scholar
    • Export Citation
  • [44]

    Pfreundschuh M, Schubert J, Ziepert M, et al. Six versus eight cycles of bi-weekly CHOP-14 with or without rituximab in elderly patients with aggressive CD20+ B-cell lymphomas: a randomised controlled trial (RICOVER-60). Lancet Oncol 2008; 9(2): 10516.

    • Search Google Scholar
    • Export Citation
  • [45]

    Bartlett NL, Wilson WH, Jung S-H, et al. Dose-Adjusted EPOCH-R compared with r-chop as frontline therapy for difuse large b-cell lymphoma: clinical outcomes of the phase III intergroup trial alliance/CALGB 50303. J Clin Oncol 2019; 37(21): 17909.

    • Search Google Scholar
    • Export Citation
  • [46]

    Puckrin R, El Darsa H, Ghosh S, et al. Inefectiveness of high-dose methotrexate for prevention of CNS relapse in diffuse large B-cell lymphoma. Am J Hematol 2021; 96(7): 76471.

    • Search Google Scholar
    • Export Citation
  • [47]

    Terasaki Y, Shimizu H, Miyazav Y, et al. Risk factors for central nervous system (CNS) relapse after autologous stem cell transplant (ASCT) in difuse large B-cell lymphoma (DLBCL). Blood 2019; 134: 5344.

    • Search Google Scholar
    • Export Citation
  • [48]

    Kamdar M, Solomon SR, Arnason J, et al. Lisocabtagene maraleucel versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as second-line treatment in patients with relapsed or refractory large B-cell lymphoma (TRANSFORM): results from an interim analysi. The Lancet 2022; 399(10343): 2294308.

    • Search Google Scholar
    • Export Citation
  • [49]

    Locke FL, Miklos DB, Jacobson CA, et al. Axicabtagene ciloleucel as second-line therapy for large B-cell lymphoma. N Engl J Med 2021; 386(7): 64054.

    • Search Google Scholar
    • Export Citation
  • [50]

    Frigault MJ, Dietrich J, Martinez-Lage M, et al. Tisagenlecleucel CAR T-cell therapy in secondary CNS lymphoma. Blood 2019; 134(11): 8606.

    • Search Google Scholar
    • Export Citation
  • [51]

    Ahmed G, Hamadani M, Shah NN, et al. CAR T-cell therapy for secondary CNS DLBCL. Blood Adv 2021; 5(24): 562630.

  • [52]

    Neelapu SS, Dickinson M, Munoz J, et al. Axicabtagene ciloleucel as frst-line therapy in high-risk large B-cell lymphoma: the phase 2 ZUMA-12 trial. Nat Med 2022; 28(4): 73542.

    • Search Google Scholar
    • Export Citation
  • Collapse
  • Expand
The author instructions are available in PDF.
Please, download the file from HERE.

 

 

  • Árpád ILLÉS (Debreceni Egyetem, főszerkesztő)
  • Csaba BÖDÖR (Semmelweis Egyetem, főszerkesztő-helyettes)
  • Judit DEMETER (Semmelweis Egyetem, főszerkesztő-helyettes)
  • Lajos GERGELY (Debreceni Egyetem, főszerkesztő-helyettes)
  • Imelda MARTON (Szegedi Tudományegyetem, főszerkesztő-helyettes)
  • Gábor MIKALA (Dél-Pesti Centrumkórház, Országos Hematológiai és Infektológiai Intézet, főszerkesztő-helyettes)
  • Sándor FEKETE (Dél-Pesti Centrumkórház, Országos Hematológiai és Infektológiai Intézet, emeritus főszerkesztő)
  • Hussain ALIZADEH (Pécsi Tudományegyetem, szerkesztő)
  • Hajnalka ANDRIKOVICS (Dél-Pesti Centrumkórház, Országos Hematológiai és Infektológiai Intézet, szerkesztő)
  • Zita BORBÉNYI (Szegedi Tudományegyetem, szerkesztő)
  • Miklós EGYED (Somogy Megyei Kaposi Mór Oktató Kórház, szerkesztő)
  • Zsuzsanna FAUST (Pécsi Tudományegyetem, szerkesztő)
  • Béla KAJTÁR (Pécsi Tudományegyetem, szerkesztő)
  • Gergely KRIVÁN (Dél-Pesti Centrumkórház, Országos Hematológiai és Infektológiai Intézet, szerkesztő)
  • András MASSZI (Országos Onkológiai Intézet, szerkesztő)
  • Tamás MASSZI (Semmelweis Egyetem, szerkesztő)
  • Zsolt György NAGY (Semmelweis Egyetem, szerkesztő)
  • Márk PLANDER (Vas Vármegyei Markusovszky Egyetemi Oktatókórház, szerkesztő)
  • György PFLIEGLER (Debreceni Egyetem, szerkesztő)
  • Péter REMÉNYI (Dél-Pesti Centrumkórház, Országos Hematológiai és Infektológiai Intézet, szerkesztő)
  • Marienn RÉTI (Dél-Pesti Centrumkórház, Országos Hematológiai és Infektológiai Intézet, szerkesztő)
  • János SINKÓ (Semmelweis Egyetem, szerkesztő)
  • László SZERAFIN (Szabolcs-Szatmár-Bereg Megyei Jósa András Oktatókórház, Nyíregyháza, szerkesztő)

Hematológia-Transzfuziológia Szerkesztőség
Dr. Illés Árpád
Debreceni Egyetem Klinikai Központ
Belgyógyászati Intézet B épület
4012 Debrecen, Nagyerdei krt. 98. Pf.: 20.
E-mail: illesarpaddr@gmail.com

  • CABELLS Journalytics

Hematológia-Transzfuziológia
Publication Model Hybrid
Submission Fee none
Article Processing Charge 900 EUR/article
Regional discounts on country of the funding agency World Bank Lower-middle-income economies: 50%
World Bank Low-income economies: 100%
Further Discounts Editorial Board / Advisory Board members: 50%
Corresponding authors, affiliated to an EISZ member institution subscribing to the journal package of Akadémiai Kiadó: 100%
Subscription fee 2025 Online subsscription: 100 EUR / 110 USD
Print + online subscription: 112 EUR / 124 USD
Subscription Information Online subscribers are entitled access to all back issues published by Akadémiai Kiadó for each title for the duration of the subscription, as well as Online First content for the subscribed content.
Purchase per Title Individual articles are sold on the displayed price.

Hematológia-Transzfuziológia
Language Hungarian
Size A4
Year of
Foundation
2004
Volumes
per Year
1
Issues
per Year
4
Founder Magyar Hematológiai és Transzfuziológiai Társaság
Founder's
Address
Szent László Kórház, Hematológiai Osztály H-1097 Budapest, Hungary Gyáli út 5-7.
Publisher Akadémiai Kiadó
Publisher's
Address
H-1117 Budapest, Hungary 1516 Budapest, PO Box 245.
Responsible
Publisher
Chief Executive Officer, Akadémiai Kiadó
ISSN 1786-5913 (Print)

Monthly Content Usage

Abstract Views Full Text Views PDF Downloads
Feb 2024 0 0 0
Mar 2024 0 0 0
Apr 2024 0 0 0
May 2024 0 0 0
Jun 2024 114 20 28
Jul 2024 37 1 1
Aug 2024 0 0 0