Diffuse large B-cell lymphoma with monoclonal immunoglobulin secretion


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Abstract

Aim. To provide the clinical characteristics of patients with diffuse large B-cell lymphoma (DLBCL) with monoclonal immunoglobulin secretion and to evaluate the efficiency of intensified mNHL-BFM-90 or R-DA-EPOCH/R-HMA therapy programs in patients with Ig-secreting DLBCL. Subjects and methods. A clinical trial was conducted in 93 patients with newly diagnosed DLBCL, among whom 21 (22.6%) were found to have monoclonal immunoglobulin secretion. Results. Ig-secreting DLBCL is shown to be characterized by bone marrow involvement (p<0.001), as well as generalized injury (Ann Arbor Stage 4) and a high risk in accordance with the international prognostic index (p=0.001 and p=0.026, respectively). Analysis of overall and event-free survival rates has indicated that the patients have a poor prognosis versus those with non-Ig-secreting DLBCL and poor prognostic factors even when implementing intensified therapy programs, such as mNHL-BFM-90 or R-DA-EPOCH/R-HMA ones. Conclusion. The investigation has demonstrated that there is a high association of the secretion of monoclonal paraproteins with bone marrow involvement in DLBCL (p<0.001). The intensified therapy using the mNHL-BFM-90 and R-DA-EPOCH/R-HMA programs involving autologous hematopoietic stem cell transplantation also permits the patients with Ig-secreting DLBCL to achieve long-term sustained remissions in not all cases.

References

  1. Swerdlow S, Campo E, Harris NL et al. International Agency for Research on Cancer. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissue. Geneva, Switzerland: World Health Organization; 2008. doi: 10.1002/9781118853771.ch51
  2. Shipp MA, Harrington DP, Anderson JR et al. The International Non-Hodgkin’s Lymphoma Prognostic Factors Project: a predictive model for aggressive non-Hodgkin’s lymphoma. New Engl J Med. 1993;329(14):987-994. doi: 10.1056/NEJM199309303291402
  3. Muller C, Murawski N, Wiesen MH et al. The role of sex and weight on rituximab clearance and serum elimination half-life in elderly patients with DLBCL. Blood. 2012;119:3276-3284. doi:http://dx.doi.org/10.1182/blood-2011-09-380949
  4. Pfreundschuh M, Ho AD, Cavallin-Stahl E et al. Prognostic significance of maximum tumor (bulk) diameter in young patients with good-prognosis diffuse large-B-cell lymphoma treated with CHOP-like chemotherapy with or without rituximab: an exploratory analysis of the MabThera International Trial Group (MInT) study. Lancet Oncol. 2008;9:435-444. doi: 10.1016/S1470-2045(08)70078-0
  5. Chung R, Lai R, Wei P, Lee J, Hanson J, Belch AR, Turner AR, Reiman T. Concordant but not discordant bone marrow involvement in diffuse large B-cell lymphoma predicts a poor clinical outcome independent of the International Prognostic Index. Blood. 2007;110(4):1278-1282. doi:http://dx.doi.org/10.1182/blood-2007-01-070300
  6. Choi WW, Weisenburger DD, Greiner TC et al. A new immunostain algorithm classifies diffuse large B-cell lymphoma into molecular subtypes with high accuracy. Clin Cancer Res. 2009;15:5494-5502. doi: 10.1158/1078-0432.CCR-09-0113
  7. Hans CP, Weisenburger DD, Greiner TC et al. Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood. 2004;103:275-282. doi:http://dx.doi.org/10.1182/blood-2003-05-1545
  8. Aukema SM, Siebert R, Schuuring E et al. Double-hit B-cell lymphomas. Blood. 2011;117(8):2319-2331. doi:http://dx.doi.org/10.1182/blood-2010-09-297879
  9. Barrans S, Crouch S, Smith A et al. Rearrangement of MYC is associated with poor prognosis in patients with diffuse large B-cell lymphoma treated in the era of rituximab. J Clin Oncol. 2010;28:3360-3365. doi: 10.1200/JCO.2009.26.3947
  10. Johnson N, Slack G, Savage K et al. Concurrent expression of MYC and BCL2 in R-CHOP treated diffuse large B cell lymphoma. J Clin Oncol. 2012. doi: 10.1200/JCO.2011.41.0985
  11. Savage KJ, Johnson NA, Ben-Neriah S et al. MYC gene rearrangements are associated with a poor prognosis in diffuse large B-cell lymphoma patients treated with R-CHOP chemotherapy. Blood. 2009;114:3533-3537. doi:http://dx.doi.org/10.1182/blood-2009-05-220095
  12. Alizadeh AA, Elsen MB, Davis RE et al. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature. 2000;403:503-511. doi: 10.1038/35000501
  13. Fernández-Rodríguez C, Bellosillo B, García-García M et al. MYD88 (L265P) mutation is an independent prognostic factor for outcome in patients with diffuse large B-cell lymphoma. Leukemia. 2014;10:2104-2106. doi: 10.1038/leu.2014.184
  14. Maurer MJ, Micallef INM, Cerhan JR et al. Elevated serum free light chains are associated with event-free and overall survival in two independent cohorts of patients with diffuse large B-cell lymphoma. J Clin Oncol. 2011;2912:1620-1626. doi: 10.1200/JCO.2010.29.4413
  15. Jardin F, Molina TJ, Copie Bergman C et al. Immunoglobulin heavy chain/light chain pair measurement is associated with survival in diffuse large B-cell lymphoma. Leuk Lymphoma. 2013;54:1898-1907. doi: 10.3109/10428194.2013.767456
  16. Cox MC, Di Napoli A, Scarpino S, Cavalieri E et al. Diffuse-Large-B-Cell Lymphoma Patients With Secreting IgM Monoclonal Component is A Very Poor Prognostic Subset. Blood. 2012;120:2659.
  17. Yi S, Liu W, Lyu R, Li Z, Xu Y, Sui W, Huang W, Wang T, Deng S, Liu H, Fu M, Zou D, Qiu L. Dose-intensive immunochemotherapy with or without autologous hematopoietic stem cell transplantation in the treatment of 29 newly diagnosed young patients with medium/high risk diffuse large B-cell lymphoma. Zhonghua Xue Ye Xue Za Zhi. 2014;35(6):546-650. doi: 10.3760/cma.j.issn.0253-2727.2014.06.016
  18. Магомедова А.У. Диффузная В-крупноклеточная лимфосаркома лимфоидных органов: клинические формы, лечение: Дис. ... д-ра мед. наук. M.; 2008.
  19. Гаврилина О.А. Исследование В-клеточной клональности и мутационного статуса гена SOCS1 у больных диффузной В-крупноклеточной лимфомой: Дис. ... канд. мед. наук. М.; 2015. Доступно по: http://blood.ru/dc/gavrilina.pdf
  20. Gomyo H, Shimoyama M, Minagawa K, Yakushijin K, Urahama N, Okamura A., Yamamoto K, Ito M, Chihara K, Hayashi Y, Matsui T. Morphologic, flow cytometric and cytogenetic evaluation of bone marrow involvement inB-cell lymphoma. Haematologica. 2003;88(12):1358-1365.
  21. Kim S, Kim H, Kang H, Kim J, Eom H., Kim T, Yoon SS, Suh C, Lee D. Clinical significance of cytogenetic aberrations in bone marrow of patients with diffuse large Bcell lymphoma: prognostic significance and relevance to histologic involvement. J Hematol Oncol. 2013;6:76. doi: 10.1186/1756-8722-6-76
  22. Merli M, Arcaini L, Boveri E, Rattotti S, Picone C, Passamonti F, Tenore A, Sozzani L, Lucioni M, Varettoni M, Rizzi S, Morello L, Ferretti V, Pascutto C, Paulli M, Lazzarino M. Assessment of bone marrow involvement in nonHodgkin’s lymphomas: comparison betweenhistology and flow cytometry. Eur J Haematol. 2010;85(5):405-415. doi: 10.1111/j.1600-0609.2010.01503.x
  23. Talaulikar D, Shadbolt B, Dahlstrom JE, McDonald A. Routine use of ancillary investigations in staging diffuse large B-cell lymphoma improves the International Prognostic Index (IPI). J Hematol Oncol. 2009;22(2):49. doi: 10.1186/1756-8722-2-49

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