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  • 1 Debreceni Egyetem, Általános Orvostudományi Kar, Debrecen, Nagyerdei krt. 98., 4032
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Absztrakt

A diffúz nagy B-sejtes lymphoma a leggyakoribb a non-Hodgkin-lymphomák között. A ciklofoszfamid-vincristin-adriablastin-prednisolon kemoterápiával a betegeknek már közel 50%-a meggyógyítható volt, majd a rituximab hozzáadásával a gyógyulási arány már 60% fölé emelkedett. Ez a javulás jelentős, de további növekedést kellene elérni a betegek gyógyulási arányában. Az utóbbi években elvégzett genetikai vizsgálatok számos új, a patogenezisben is szerepet játszó és terápiás célpontként is szolgáló mutációt azonosítottak a betegségben. A diagnosztika ma már rutinszerűen alkalmazza a 18-fluoro-deoxi-glükóz-pozitronemissziós komputertomográfiás vizsgálatokat a Lugano klasszifikációs rendszer részeként. Ezen adatok alapján egyre pontosabban meghatározható a betegek prognózisa, és kiválaszthatók azok a betegek, akik valamelyik új, szelektíven ható gyógyszerre esetleg reagálhatnak. Mindezeknek a kérdéseknek a megválaszolása, az újabb kezelések bevezetése várhatóan a közeli jövőben tovább fogja javítani a betegek túlélési esélyeit. Az összefoglaló közlemény áttekintést ad a közelmúlt újdonságairól, kiemeli a ma használatos és javasolt kezeléseket, továbbá áttekintést ad a jelenleg kipróbálás alatt álló és bevezetendő kezelésekről is. Orv. Hetil., 2016, 157(31), 1232–1241.

  • 1

    Wright, G., Tan, B., Rosenwald, A., et al.: A gene expression-based method to diagnose clinically distinct subgroups of diffuse large B cell lymphoma. Proc. Natl. Acad. Sci. U.S.A., 2003, 100(17), 9991–9996.

  • 2

    Rosenwald, A., Wright, G., Leroy, K., et al.: Molecular diagnosis of primary mediastinal B cell lymphoma identifies a clinically favorable subgroup of diffuse large B cell lymphoma related to Hodgkin lymphoma. J. Exp. Med., 2003, 198(6), 851–862.

  • 3

    Hans, C. P., Weisenburger, D. D., Greiner, T. C., et al.: Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood, 2004, 103(1), 275–282.

  • 4

    Visco, C., Li, Y., Xu-Monette, Z. Y., et al.: Comprehensive gene expression profiling and immunohistochemical studies support application of immunophenotypic algorithm for molecular subtype classification in diffuse large B-cell lymphoma: a report from the International DLBCL Rituximab-CHOP Consortium Program Study. Leukemia, 2012, 26(9), 2103–2113.

  • 5

    Scott, D. W., Wright, G. W., Williams, P. M., et al.: Determining cell-of-origin subtypes of diffuse large B-cell lymphoma using gene expression in formalin-fixed paraffin-embedded tissue. Blood, 2014, 123(8), 1214–1217.

  • 6

    Scott, D. W., Mottok, A., Ennishi, D., et al.: Prognostic significance of diffuse large B-cell lymphoma cell of origin determined by digital gene expression in formalin-fixed paraffin-embedded tissue biopsies. J. Clin. Oncol., 2015, 33(26), 2848–2856.

  • 7

    Coiffier, B., Lepage, E., Briere, J., et al.: CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N. Engl. J. Med., 2002, 346(4), 235–242.

  • 8

    Fu, K., Weisenburger, D. D., Choi, W. W., et al.: Addition of rituximab to standard chemotherapy improves the survival of both the germinal center B-cell-like and non-germinal center B-cell-like subtypes of diffuse large B-cell lymphoma. J. Clin. Oncol., 2008, 26(28), 4587–4594.

  • 9

    Thieblemont, C., Briere, J., Mounier, N., et al.: The germinal center/activated B-cell subclassification has a prognostic impact for response to salvage therapy in relapsed/refractory diffuse large B-cell lymphoma: a bio-CORAL study. J. Clin. Oncol., 2011, 29(31), 4079–4087.

  • 10

    Vitolo, U., Gaidano, G., Botto, B., et al.: Rearrangements of bcl-6, bcl-2, c-myc and 6q deletion in B-diffuse large-cell lymphoma: clinical relevance in 71 patients. Ann. Oncol., 1998, 9(1), 55–61.

  • 11

    Caponetti, G. C., Dave, B. J., Perry, A. M., et al.: Isolated MYC cytogenetic abnormalities in diffuse large B-cell lymphoma do not predict an adverse clinical outcome. Leuk. Lymphoma, 2015, 56(11), 3082–3089.

  • 12

    Visco, C., Tzankov, A., Xu-Monette, Z. Y., et al.: Patients with diffuse large B-cell lymphoma of germinal center origin with BCL2 translocations have poor outcome, irrespective of MYC status: a report from an International DLBCL rituximab-CHOP Consortium Program Study. Haematologica, 2013, 98(2), 255–263.

  • 13

    Perry, A. M., Alvarado-Bernal, Y., Laurini, J. A., et al.: MYC and BCL2 protein expression predicts survival in patients with diffuse large B-cell lymphoma treated with rituximab. Br. J. Haematol., 2014, 165(3), 382–391.

  • 14

    Green, T. M., Nielsen, O., de Stricker, K., et al.: High levels of nuclear MYC protein predict the presence of MYC rearrangement in diffuse large B-cell lymphoma. Am. J. Surg. Pathol., 2012, 36(4), 612–619.

  • 15

    Dunleavy, K.: Aggressive B cell lymphoma: optimal therapy for MYC-positive, double-hit, and triple-hit DLBCL. Curr. Treat. Options Oncol., 2015, 16(12), 58.

  • 16

    Cuccuini, W., Briere, J., Mounier, N., et al.: MYC+ diffuse large B-cell lymphoma is not salvaged by classical R-ICE or R-DHAP followed by BEAM plus autologous stem cell transplantation. Blood, 2012, 119(20), 4619–4624.

  • 17

    Schiefer, A. I., Kornauth, C., Simonitsch-Klupp, I., et al.: Impact of single or combined genomic alterations of TP53, MYC, and BCL2 on survival of patients with diffuse large B-cell lymphomas: A retrospective cohort study. Medicine (Baltimore), 2015, 94(52), e2388.

  • 18

    Lenz, G., Davis, R. E., Ngo, V. N., et al.: Oncogenic CARD11 mutations in human diffuse large B cell lymphoma. Science, 2008, 319(5870), 1676–1679.

  • 19

    Wang, J. Q., Jeelall, Y. S., Beutler, B., et al.: Consequences of the recurrent MYD88(L265P) somatic mutation for B cell tolerance. J. Exp. Med., 2014, 211(3), 413–426.

  • 20

    Kraan, W., Horlings, H. M., van Keimpema, M., et al.: High prevalence of oncogenic MYD88 and CD79B mutations in diffuse large B-cell lymphomas presenting at immune-privileged sites. Blood Cancer J., 2013, 3(9), e139.

  • 21

    Zhang, J., Grubor, V., Love, C. L., et al.: Genetic heterogeneity of diffuse large B-cell lymphoma. Proc. Natl. Acad. Sci. U.S.A., 2013, 110(4), 1398–1403.

  • 22

    Maurer, M. J., Ghesquières, H., Jais, J. P., et al.: Event-free survival at 24 months is a robust end point for disease-related outcome in diffuse large B-cell lymphoma treated with immunochemotherapy. J. Clin. Oncol., 2014, 32(10), 1066–1073.

  • 23

    Pattullo, V.: Hepatitis B reactivation in the setting of chemotherapy and immunosuppression – prevention is better than cure. World J. Hepatol., 2015, 7(7), 954–967.

  • 24

    Cheson, B. D., Fisher, R. I., Barrington, S. F., et al.: Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J. Clin. Oncol., 2014, 32(27), 3059–3068.

  • 25

    Vaidya, R., Witzig, T. E.: Prognostic factors for diffuse large B-cell lymphoma in the R(X)CHOP era. Ann. Oncol., 2014, 25(11), 2124–2133.

  • 26

    Bari, A., Marcheselli, L., Sacchi, S., et al.: Prognostic models for diffuse large B-cell lymphoma in the rituximab era: a never-ending story. Ann. Oncol., 2010, 21(7), 1486–1491.

  • 27

    Maurer, M. J., Jais, J. P., Ghesquières, H., et al.: Personalized risk prediction for event-free survival at 24 months in patients with diffuse large B-cell lymphoma. Am. J. Hematol., 2016, 91(2), 179–184.

  • 28

    Ghielmini, M., Vitolo, U., Kimby, E., et al.: ESMO Guidelines consensus conference on malignant lymphoma 2011 part 1: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL). Ann. Oncol., 2013, 24(3), 561–576.

  • 29

    Barrington, S. F., Mikhaeel, N. G., Kostakoglu, L., et al.: Role of imaging in the staging and response assessment of lymphoma: consensus of the International Conference on Malignant Lymphomas Imaging Working Group. J. Clin. Oncol., 2014, 32(27), 3048–3058.

  • 30

    Stiff, P. J., Unger, J. M., Cook, J. R., et al.: Autologous transplantation as consolidation for aggressive non-Hodgkin’s lymphoma. N. Engl. J. Med., 2013, 369(18), 1681–1690.

  • 31

    Dunleavy, K., Pittaluga, S., Maeda, L. S., et al.: Dose-adjusted EPOCH-rituximab therapy in primary mediastinal B-cell lymphoma. N. Engl. J. Med., 2013, 368(15), 1408–1416.

  • 32

    Dunleavy, K., Steidl, C.: Emerging biological insights and novel treatment strategies in primary mediastinal large B-cell lymphoma. Semin. Hematol., 2015, 52(2), 119–125.

  • 33

    Omuro, A., Correa, D. D., DeAngelis, L. M., et al.: R-MPV followed by high-dose chemotherapy with TBC and autologous stem-cell transplant for newly diagnosed primary CNS lymphoma. Blood, 2015, 125(9), 1403–1410.

  • 34

    Madle, M., Krämer, I., Lehners, N., et al.: The influence of rituximab, high-dose therapy followed by autologous stem cell transplantation, and age in patients with primary CNS lymphoma. Ann. Hematol., 2015, 94(11), 1853–1857.

  • 35

    Takasaki, H., Yamamoto, W., Ishii, Y., et al.: Post-treatment PET-CT findings may predict the prognosis of DLBCL with a bulky mass. Indian J. Hematol. Blood Transfus., 2015, 31(3), 346–351.

  • 36

    Mounier, N., Canals, C., Gisselbrecht, C., et al.: High-dose therapy and autologous stem cell transplantation in first relapse for diffuse large B cell lymphoma in the rituximab era: an analysis based on data from the European Blood and Marrow Transplantation Registry. Biol. Blood Marrow Transplant., 2012, 18(5), 788–793.

  • 37

    Alcantara, M., Dupuis, J., Mareschal, S., et al.: PET/CT before autologous stem cell transplantation predicts outcome in refractory/relapsed follicular lymphoma. Eur. J. Nucl. Med. Mol. Imaging, 2015, 42(2), 215–221.

  • 38

    Evens, A. M., Rosen, S. T., Helenowski, I., et al.: A phase I/II trial of bortezomib combined concurrently with gemcitabine for relapsed or refractory DLBCL and peripheral T-cell lymphomas. Br. J. Haematol., 2013, 163(1), 55–61.

  • 39

    Offner, F., Samoilova, O., Osmanov, E., et al.: Frontline rituximab, cyclophosphamide, doxorubicin, and prednisone with bortezomib (VR-CAP) or vincristine (R-CHOP) for non-GCB DLBCL. Blood, 2015, 126(16), 1893–1901.

  • 40

    Dunleavy, K., Pittaluga, S., Czuczman, M. S., et al.: Differential efficacy of bortezomib plus chemotherapy within molecular subtypes of diffuse large B-cell lymphoma. Blood, 2009, 113(24), 6069–6076.

  • 41

    Velichutina, I., Shaknovich, R., Geng, H., et al.: EZH2-mediated epigenetic silencing in germinal center B cells contributes to proliferation and lymphomagenesis. Blood, 2010, 116(24), 5247–5255.

  • 42

    Nowakowski, G. S., LaPlant, B., Macon, W. R., et al.: Lenalidomide combined with R-CHOP overcomes negative prognostic impact of non-germinal center B-cell phenotype in newly diagnosed diffuse large B-cell lymphoma: a phase II study. J. Clin. Oncol., 2015, 33(3), 251–257.

  • 43

    Martín, A., Redondo, A. M., Dlouhy, I., et al.: Lenalidomide in combination with R-ESHAP in patients with relapsed or refractory diffuse large B-cell lymphoma: a phase 1b study from GELTAMO group. Br. J. Haematol., 2016, 173(2), 245–252.

  • 44

    Witzig, T. E., Reeder, C. B., LaPlant, B. R., et al.: A phase II trial of the oral mTOR inhibitor everolimus in relapsed aggressive lymphoma. Leukemia, 2011, 25(2), 341–347.

  • 45

    Micallef, I. N., Maurer, M. J., Wiseman, G. A., et al.: Epratuzumab with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy in patients with previously untreated diffuse large B-cell lymphoma. Blood, 2011, 118(15), 4053–4061.

  • 46

    Jacobsen, E. D., Sharman, J. P., 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(9), 1394–1402.

  • 47

    Viardot, A., Goebeler, M. E., Hess, G., et al.: Phase 2 study of the bispecific T-cell engager (BiTE) antibody blinatumomab in relapsed/refractory diffuse large B-cell lymphoma. Blood, 2016, 127(11), 1410–1416.

  • 48

    De Vos, S., Forero-Torres, A., Ansell, S. M., et al.: A phase II study of dacetuzumab (SGN-40) in patients with relapsed diffuse large B-cell lymphoma (DLBCL) and correlative analyses of patient-specific factors. J. Hematol. Oncol., 2014, 7, 44.

  • 49

    Palanca-Wessels, M. C., Czuczman, M., Salles, G., et al.: Safety and activity of the anti-CD79B antibody-drug conjugate polatuzumab vedotin in relapsed or refractory B-cell non-Hodgkin lymphoma and chronic lymphocytic leukaemia: a phase 1 study. Lancet Oncol., 2015, 16(6), 704–715.

  • 50

    Preliminary results of a phase II randomized study (ROMULUS) of polatuzumab vedotin or pinatuzumab vedotin plus rituximab in patients with relapsed/refractory non-Hodgkin lymphoma (NHL). Clin. Adv. Hematol. Oncol., 2014, 12(8 Suppl. 16), 15–18.

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