#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Primární mediastinální velko-buněčný B-lymfom


Primary mediastinal large B-cell lymphoma

Primary mediastinal large B-cell lymphoma is an aggressive tumour characterized by a rapid increase of tumour mass in the anterior mediastinum that occurs in younger patients. Currently, in the age of immunochemotherapy, 5-year overall survival of patients is 80–90%. However, relapse occurs early, usually within one year from the end of therapy and the prognosis of these patients is unsatisfactory. Positron emission tomography combined with computed tomography using 18F-fluorodeoxyglucose is currently widely used not only at the time of diagnosis but also for monitoring response to treatment. The FDG PET/CT has a strong prognostic significance at the time of diagnosis, during treatment and after its termination. Maximum treatment efficacy and reduction of the long-term toxicity risk are key when selecting therapeutic modalities. Standard, anthracycline-based immunochemotherapy (R-CHOP, DA-EPOCH-R), autologous stem cell transplantation or consolidation radiotherapy for residual tumour mass are the current standard of the therapy. New modalities (PD1 inhibitors, brentuximab vedotin or CAR T cell therapy) are available, but require results from ongoing clinical trials to assess their effectivity.

Keywords:

radiotherapy – primary mediastinal large B-cell lymphoma – immunochemotherapy – positronemission tomography


Autoři: V. Hanáčková 1;  F. Folber 2;  L. Henzlová 3;  P. Flodr 4;  V. Procházka 1
Působiště autorů: Hemato-onkologická klinika LF UP a FN Olomouc 1;  Interní hematologická a onkologická klinika LF MU a FN Brno 2;  Klinika nukleární medicíny LF UP a FN Olomouc 3;  Ústav klinické a molekulární patologie, LF UP a FN Olomouc 4
Vyšlo v časopise: Transfuze Hematol. dnes,30, 2024, No. Ahead of Print, p. 1-11.
Kategorie: Souhrnné/edukační práce
doi: https://doi.org/10.48095/cctahd2024prolekare.cz17

Souhrn

Primární mediastinální velkobuněčný B-lymfom je agresivní nádorové onemocnění charakterizované rychlým nárůstem nádorové masy v předním mediastinu, vyskytující se u pacientů mladšího věku. V době imunochemoterapie je 5leté přežívání pacientů 80–90 %, přesto část pacientů časně relabuje do jednoho roku od ukončení terapie a prognóza těchto pacientů je neuspokojivá. Pro diagnostiku, stážování i monitoraci odpovědi na léčbu je v současné době široce využívána pozitronová emisní tomografie kombinovaná s výpočetní tomografií s využitím 18F-fluorodeoxyglukózy. Vyšetření má silný prognostický význam v době diagnózy, v průběhu léčby i po ukončení. Pro volbu terapie je zásadní zvážení snahy o maximální efektivitu a zároveň redukci rizika dlouhodobé toxicity. V terapii je v současné době používána standardní, na antracyklinech založená, imunochemoterapie (R-CHOP, DA-EPOCH-R), konsolidační radioterapie na reziduální nádorovou masu, případně vysocedávkovaná imunochemoterapie doprovázená autologní transplantací periferních kmenových buněk. K dispozici jsou pro terapii také nové léčebné modality (PD1 inhibitory, brentuximab vedotin či CAR-T buněčná terapie), k ověření jejichž efektivity přispívají probíhající klinické studie.

Klíčová slova:

radioterapie – pozitronová emisní tomografie – primární mediastinální velkobuněčný B-lymfom – imunochemoterapie

Stránka

Zdroje
    1. Campo E, Swerdlow SH, Harris NL, Pileri S, Stein H, Jaffe ES. The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications. Blood. 2011;117:5019–5032. https://doi.org/10.1182/blood-2011-01-293050.
    2. Alaggio R, Amador C, Anagnostopoulos I, et al. The 5th edition of the World Health Organization classification of haematolymphoid tumours:lymphoid neoplasms. Leukemia. 2022;36:1720–1748. https://doi.org/10.1038/s41375-022-01620-2.
    3. Martelli M, Ferreri A, Di Rocco A, Ansuinelli M, Johnson PWM. Primary mediastinal large B-cell lymphoma. Crit Rev Oncol Hematol. 2017;113:318–327. https://doi.org/10.1016/j.crit revonc.2017.01.009.
    4. Addis BJ, Isaacson PG. Large cell lymphoma of the mediastinum: a B-cell tumour of probable thymic origin. Histopathology. 1986;10:379–390. https:/ / doi.org/ 10.1111/ j. 1365-2559.1986. tb02491.x.
    5. Harris NL, Jaffe ES, Stein H, et al. A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. Blood. 1994;84:1361–1392. https://doi.org/10.1182/blood.V84.5.1361.1361.
    6. Rüdiger T, Jaffe ES, Delsol G, et al. Workshop report on Hodgkin’s disease and related diseases (“grey zone” lymphoma). Ann Oncol Off J Eur Soc Med Oncol. 1998;9(Suppl 5):S31–S38. https://doi. org/10.1093/annonc/9.suppl_5.s31.
    7. Higgins JP, Warnke RA. CD30 expression is common in mediastinal large B-cell lymphoma. Am J Clin Pathol. 1999;112:241–247. https://doi. org/10.1093/ajcp/112.2.241.
    8. Dorfman DM, Shahsafaei A, Alonso MA. Utility of CD200 immunostaining in the diagnosis of primary mediastinal large B cell lymphoma: comparison with MAL, CD23, and other markers. Mod Pathol Off J U S Can Acad Pathol Inc. 2012;25:1637–1643. https://doi.org/10.1038/modpathol.2012.129.
    9. Rodig SJ, Savage KJ, LaCasce AS, et al. Expression of TRAF1 and nuclear c-Rel distinguishes primary mediastinal large cell lymphoma from other types of diffuse large B-cell lymphoma. Am J Surg Pathol. 2007;31:106–112. https://doi. org/10.1097/01.pas.0000213334.40358.0e.
    10. Kim H-J, Kim HK, Park G, et al. Comparative pathologic analysis of mediastinal B-cell lymphomas: selective expression of p63 but no GATA3 optimally differentiates primary mediastinal large B-cell lymphoma from classic Hodgkin lymphoma. Diagn Pathol. 2019;14:133. https://doi. org/10.1186/s13000-019-0918-x.
    11. Wang Y, Wenzl K, Manske MK, et al. Amplification of 9p24.1 in diffuse large B-cell lymphoma identifies a unique subset of cases that resemble primary mediastinal large B-cell lymphoma. Blood Cancer J. 2019;9:73. https://doi. org/10.1038/s41408-019-0233-5.
    12. Prochazka V, Papajik T, Flodr P, et al. Programmed death-1 ligand is uniformly expressed on primary mediastinal diffuse large B-cell lymphoma cells with no influence on patient survival. Blood. 2012;120:2671. https:// doi.org/ 10.1182/ blood. V120.21.2671.2671.
    13. Twa DDW, Chan FC, Ben-Neriah S, et al. Genomic rearrangements involving programmed death ligands are recurrent in primary mediastinal large B-cell lymphoma. Blood. 2014;123:2062–2065. https://doi.org/10.1182/ blood-2013-10-535443.
    14. Steidl C, Gascoyne RD. The molecular pathogenesis of primary mediastinal large B-cell lymphoma. Blood. 2011;118:2659–2669. https://doi. org/10.1182/blood-2011-05-326538.
    15. Noerenberg D, Briest F, Hennch C, et al. Genetic characterization of primary mediastinal B-cell lymphoma: pathogenesis and patient outcomes. J Clin Oncol. 2024;42:452–466. https://doi. org/10.1200/JCO.23.01053.
    16. Jacobson JO, Aisenberg AC, Lamarre L, et al. Mediastinal large cell lymphoma: An uncommon subset of adult lymphoma curable with combined modality therapy. Cancer. 1988;62:1893–1898. https:/ / doi.org/ 10.1002/ 1097-0142(198811 01)62:9<1893::AID-CNCR2820620904>3.0.CO;2-X.
    17. Zinzani PL, Bendandi M, Frezza G, et al. Primary mediastinal B-cell lymphoma with sclerosis: clinical and therapeutic evaluation of 22 patients. Leuk Lymphoma. 1996;21:311–316. https://doi.org/10. 3109/10428199209067612.
    18. Johnson PWM, Davies AJ. Primary mediastinal B-cell lymphoma. Hematol Am Soc Hematol Educ Program. 2008:349–358. https:// doi. org/10.1182/asheducation-2008.1.349.
    19. Davnall F, Yip CSP, Ljungqvist G, et al. Assessment of tumor heterogeneity: an emerging imaging tool for clinical practice? Insights Imaging. 2012;3:573– 589. https:/ / doi. org/10.1007/s13244-012-0196-6.
    20. Pugachev A, Ruan S, Carlin S, et al. Dependence of FDG uptake on tumor microenvironment. Int J Radiat Oncol Biol Phys. 2005;62:545–553. https://doi.org/10.1016/j.ijrobp.2005.02.009.
    21. Dunleavy K, Wilson WH. Primary mediastinal B-cell lymphoma and mediastinal gray zone lymphoma: do they require a unique therapeutic approach? Blood. 2015;125:33–39. https://doi. org/10.1182/blood-2014-05-575092.
    22. Nagle SJ, Chong EA, Chekol S, et al. The role of FDG-PET imaging as a prognostic marker of outcome in primary mediastinal B-cell lymphoma. Cancer Med. 2015;4:7–15. https:// doi. org/10.1002/cam4.322.
    23. Procházka V, Henzlová L, Buriánková E, et al. Prognostic impact of interim and final PET in primary mediastinal large B-cell lymphoma treated with intensive etoposide-based therapy. Blood. 2014;124:1729. https:// doi.org/ 10.1182/ blood. V124.21.1729.1729.
    24. Ceriani L, Martelli M, Zinzani PL, et al. Utility of baseline 18FDG-PET/CT functional parameters in defining prognosis of primary mediastinal (thymic) large B-cell lymphoma. Blood. 2015;126:950–956. https://doi.org/10.1182/blood-2014-12-616474.
    25. Ceriani L, Martelli M, Conconi A, et al. Prognostic models for primary mediastinal (thymic) B-cell lymphoma derived from 18-FDG PET/CT quantitative parameters in the International Extranodal Lymphoma Study Group (IELSG) 26 study. Br J Haematol. 2017;178:588–591. https:// doi. org/10.1111/bjh.14728.
    26. Henzlová L, Koranda P, Procházka V, Papajík T, Zapletalová J. Využití interim 18F-FDG PET/CT pro prognostickou stratifikaci pacientů s primárním mediastinálním velkobuněčným B-lymfomem NuklMed. 2017;6:22–27.
    27. Mikhaeel NG, Smith D, Dunn JT, et al. Combination of baseline metabolic tumour volume and early response on PET/CT improves progression-free survival prediction in DLBCL. Eur J Nucl Med Mol Imaging. 2016;43:1209. https:// doi. org/10.1007/s00259-016-3315-7.
    28. van Velden FHP, Cheebsumon P, Yaqub M, et al. Evaluation of a cumulative SUV-volume histogram method for parameterizing heterogeneous intratumoural FDG uptake in non-small cell lung cancer PET studies. Eur J Nucl Med Mol Imaging. 2011;38:1636–1647. https:// doi. org/10.1007/s00259-011-1845-6.
    29. Ceriani L, Milan L, Martelli M, et al. Metabolic heterogeneity on baseline 18FDG-PET/CT scan is a predictor of outcome in primary mediastinal B-cell lymphoma. Blood. 2018;132:179–186. https://doi.org/10.1182/blood-2018-01-826958.
    30. Kurtz DM, Scherer F, Jin MC, et al. Circulating tumor DNA measurements as early outcome predictors in diffuse large B-cell lymphoma. J Clin Oncol. 2018;36:2845–2853. https:// doi. org/10.1200/JCO.2018.78.5246.
    31. Rivas-Delgado A, Nadeu F, Andrade-Campos M, et al. Cell-free DNA for genomic analysis in primary mediastinal large B-cell lymphoma. Diagnostics. 2022;12:1575. https://doi. org/10.3390/diagnostics12071575.
    32. Camus V, Viennot M, Lévêque E, et al. Circulating tumor DNA in primary mediastinal large B-cell lymphoma versus classical Hodgkin lymphoma: a retrospective study. Leuk Lymphoma. 2022;63:834–844. https://doi.org/10.1080/10428194.2021.2010060.
    33. Todeschini G, Secchi S, Morra E, et al. Primary mediastinal large B-cell lymphoma (PMLBCL): long-term results from a retrospective multicentre Italian experience in 138 patients treated with CHOP or MACOP-B/VACOP-B. Br J Cancer. 2004;90:372–376. https:// doi. org/10.1038/sj.bjc.6601460.
    34. Zinzani PL, Martelli M, Bertini M, et al. Induction chemotherapy strategies for primary mediastinal large B-cell lymphoma with sclerosis: a retrospective multinational study on 426 previously untreated patients. Haematologica. 2002;87:1258–1264.
  1. Dunleavy K, Pittaluga S, Maeda LS, et al. Dose-adjusted  EPOCH-Rituximab  therapy in primary mediastinal B-cell lymphoma. N Engl J Med. 2013;368:1408–1416. https:// doi. org/10.1056/NEJMoa1214561.
  2. Giulino-Roth L, O’Donohue T, Chen Z, et al. Outcomes of adults and children with primary mediastinal B-cell lymphoma treated with dose-adjusted EPOCH-R. Br J Haematol. 2017;179:739–747. https://doi.org/10.1111/bjh.14951.
  3. Malenda A, Kołkowska-Leśniak A, Puła B, et al. Outcomes of treatment with dose-adjusted EPOCH-R or R-CHOP in primary mediastinal large B-cell lymphoma. Eur J Haematol. 2020;104:59–66. https://doi.org/10.11 11/ejh.13337.
  4. Shah NN, Szabo A, Huntington SF, et al. R-CHOP versus dose-adjusted R-EPOCH in frontline management of primary mediastinal B-cell lymphoma: a multi-centre analysis. Br J Haematol. 2018;180:534–544. https://doi.org/10.1111/ bjh.15051.
  5. Martelli M, Ceriani L, Zucca E, et al. 18F.fluorodeoxyglucose positron emission tomography predicts survival after chemoimmunotherapy for primary mediastinal large B-cell lymphoma: results of the International Extranodal Lymphoma Study Group IELSG-26 Study. J Clin Oncol. 2014;32:1769–1775. https:// doi. org/10.1200/JCO.2013.51.7524.
  6. Zucca E, Davies A, Kryachok I, et al. Observation vs. radiotherapy in primary mediastinal B-cell lymphoma patients with complete response to standard immunochemotherapy: The IELSG37 randomized trial. J Clin Oncol. 2023;41:LBA7505– LBA7505.  https:/ / doi.org/10.1200/JCO.2023.41.17_suppl.LBA7505.
  7. Hayden AR, Tonseth P, Lee DG, et al. Outcome of primary mediastinal large B-cell lymphoma using R-CHOP: impact of a PET-adapted approach. Blood. 2020;136:2803–2811. https://doi. org/10.1182/blood.2019004296.
  8. Polgarova K, Janíková A, Belada D, et al. Survival of patients with primary mediastinal B-cell lymphoma treated by immunochemotherapy with or without radiotherapy. Blood. 2022;140:3831–3832. https://doi.org/10.1182/blood-2022-163113.
  9. Schmitz N, Zeynalova S, Nickelsen M, et al. 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. 2016;34:3150–3156. https:// doi. org/10.1200/JCO.2015.65.6520.
  10. Papageorgiou SG, Diamantopoulos P, Levidou G, et al. Isolated central nervous system relapses in primary mediastinal large B-cell lymphoma after CHOP-like chemotherapy with or without Rituximab. Hematol Oncol. 2013;31:10–17. https://doi. org/10.1002/hon.2012.
  11. Vassilakopoulos TP, Panitsas F, Mellios Z, et al. Incidence and risk factors for central nervous system relapse in patients with primary mediastinal large B-cell lymphoma in the rituximab era. Hematol Oncol. 2023;41:97–107. https:// doi. org/10.1002/hon.3096.
  12. 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;41:5376–5387. https://doi.org/10.1200/JCO.23.00365.
  13. Gisselbrecht C, Glass B, Mounier N, et al. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol. 2010;28:4184–4190. https://doi.org/10.1200/JCO.2010.28.1618.
  14. Herrera AF, Chen L, Khajavian S, et al. Allogeneic stem cell transplantation provides durable remission in patients with primary mediastinal large B cell lymphoma. Biol Blood Marrow Transplant. 2019;25:2383–2387. https://doi.org/10.1016/j.bb mt.2019.07.041.
  15. Le Calvez B, Tessoullin B, Renaud L, et al. Outcomes after allogeneic hematopoietic stem cell transplantation for adults with primary mediastinal B cell lymphoma: a SFGM-TC and LYSA study. Acta Oncol. 2022;61:1332–1338. https://doi.org/1 0.1080/0284186X.2022.2130709.
  16. Armand P, Rodig S, Melnichenko V, et al. Pembrolizumab in relapsed or refractory primary mediastinal large B-cell lymphoma. J Clin Oncol. 2019;37:3291–3299. https:// doi. org/10.1200/JCO.19.01389.
  17. Zinzani PL, Thieblemont C, Melnichenko V, et al. Pembrolizumab in relapsed or refractory primary mediastinal large B-cell lymphoma: final analysis of KEYNOTE-170. Blood. 2023;142:141– 145. https:/ / doi.org/ 10.1182/ blood.2022019340.
  18. Jacobsen ED, Sharman JP, Oki Y, et al. Brentuximab vedotin demonstrates objective responses in a phase 2 study of relapsed/refractory DLBCL with variable CD30 expression. Blood. 2015;125:1394– 1402. https:/ / doi. org/10.1182/blood-2014-09-598763.
  19. Zinzani PL, Pellegrini C, Chiappella A, et al. Brentuximab vedotin in relapsed primary mediastinal large B-cell lymphoma: results from a phase 2 clinical trial. Blood. 2017;129:2328–2330. https://doi. org/10.1182/blood-2017-01-764258.
  20. Svoboda J, Bair SM, Landsburg DJ, et al. Brentuximab vedotin in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone as frontline treatment for patients with CD30-positive B-cell lymphomas. Haematologica. 2020;106:1705–1713. https:// doi. org/10.3324/haematol.2019.238675.
  21. Zinzani PL, Santoro A, Gritti G, et al. Nivolumab combined with brentuximab vedotin for relapsed/ refractory primary mediastinal large B-cell lymphoma: efficacy and safety from the phase II CheckMate 436 study. J Clin Oncol. 2019;37:3081–3089. https:// doi. org/10.1200/JCO.19.01492.
  22. Abramson JS, Palomba ML, Gordon LI, et al. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. Lancet. 2020;396:839–852. https:// doi. org/10.1016/S0140-6736(20)31366-0.
  23. Abramson JS, Solomon SR, Arnason J, et al. Lisocabtagene maraleucel as second-line therapy for large B-cell lymphoma: primary analysis of the phase 3 TRANSFORM study. Blood. 2023;141:1675–1684. https://doi. org/10.1182/blood.2022018730.
  24. Neelapu SS, Jacobson CA, Ghobadi A, et al. Five-year follow-up of ZUMA-1 supports the curative potential of axicabtagene ciloleucel in refractory large B-cell lymphoma. Blood. 2023;141:2307– 2315. https:/ / doi. org/10.1182/blood.2022018893.
  25. Bock AM, Nowakowski GS, Wang Y. Bispecific antibodies for non-Hodgkin lymphoma treatment. Curr Treat Options Oncol. 2022;23:155– 170. https://doi.org/10.1007/s11 864-021-00925-1.
  26. Hutchings M, Morschhauser F, Iacoboni G, et al. Glofitamab, a novel, bivalent CD20-targeting T-cell–engaging bispecific antibody, induces durable complete remissions in relapsed or refractory B-cell lymphoma: a phase I trial. J Clin Oncol. 2021;39:1959–1970. https:// doi. org/10.1200/JCO.20.03175.
  27. Thieblemont C, Phillips T, Ghesquieres H, et al. Epcoritamab, a novel, subcutaneous CD3xCD20 bispecific T-cell– engaging antibody, in relapsed or refractory large B-cell lymphoma: dose expansion in a phase I/II trial. J Clin Oncol. 2023;41:2238–2247. https:// doi. org/10.1200/JCO.22.01725.
  28. PODÍL AUTORŮ NA PŘÍPRAVĚ RUKOPISU

    VH – příprava rukopisu

    FF – příprava kazuistiky a revize textu

    LH, PF – příprava obrazových podkladů a revize textu

    VP – léčba pacientů, revize textu, závěrečná kontrola rukopisu

    PODĚKOVÁNÍ

    Podpořeno granty: MZ ČR – RVO (FNOl, 00098892), IGA_LF_2024_001 a AZV NU21-03-00411.

    ČESTNÉ PROHLÁŠENÍ

    Autoři práce prohlašují, že v souvislosti s tématem, vznikem a publikací tohoto článku nejsou ve střetu zájmů a vznik ani publikace článku nebyly podpořeny žádnou farmaceutickou firmou.

    Do redakce doručeno dne: 3. 5. 2024.
    Přijato po recenzi dne: 4. 7. 2024.

    MUDr. Veronika Hanáčková
    Hemato-onkologická klinika LF UP a FN Olomouc
    Zdravotníků 248/7
    779 00 Olomouc
    e-mail:
    veronika.hanackova@fnol.cz

Štítky
Hematologie a transfuzní lékařství Interní lékařství Onkologie

Článek vyšel v časopise

Transfuze a hematologie dnes

Číslo Ahead of Print

2024 Číslo Ahead of Print
Nejčtenější tento týden
Nejčtenější v tomto čísle
Kurzy

Zvyšte si kvalifikaci online z pohodlí domova

plice
INSIGHTS from European Respiratory Congress
nový kurz

Současné pohledy na riziko v parodontologii
Autoři: MUDr. Ladislav Korábek, CSc., MBA

Svět praktické medicíny 3/2024 (znalostní test z časopisu)

Kardiologické projevy hypereozinofilií
Autoři: prof. MUDr. Petr Němec, Ph.D.

Střevní příprava před kolonoskopií
Autoři: MUDr. Klára Kmochová, Ph.D.

Všechny kurzy
Kurzy Podcasty Doporučená témata Časopisy
Přihlášení
Zapomenuté heslo

Zadejte e-mailovou adresu, se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.

Přihlášení

Nemáte účet?  Registrujte se

#ADS_BOTTOM_SCRIPTS#