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Lymphoma

Concordant bone marrow involvement of diffuse large B-cell lymphoma represents a distinct clinical and biological entity in the era of immunotherapy

Leukemia volume 32, pages 353–363 (2018)Cite this article

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Abstract

In diffuse large B-cell lymphoma (DLBCL), the clinical and biological significance of concordant and discordant bone marrow (BM) involvement have not been well investigated. We evaluated 712 de novo DLBCL patients with front-line rituximab-containing treatment, including 263 patients with positive and 449 with negative BM status. Compared with negative BM disease, concordant BM adversely impacted overall and progression-free survival, independent of the International Prognostic Index (IPI) and cell-of-origin classification. Once BM is concordantly involved, poor prognosis was not associated with the extent of BM involvement. Conversely, patients with discordant BM showed favorable overall survival similar to stage I–II DLBCL. A BM-adjusted IPI, using three parameters: concordant BM involvement, age >60 years, and performance status >1, improves the risk stratification for DLBCL with positive BM. Intensive immunochemotherapy seemingly rendered survival benefit for patients with concordant BM, as did rituximab maintenance for the discordant BM group. Frequently revealing adverse clinical and molecular characteristics, patients with concordant BM demonstrated gene expression signatures relevant to tumor cell proliferation, migration and immune escape. In conclusion, clinical and biological heterogeneity is seen in DLBCL with positive BM but concordant BM involvement represents a distinct subset with unfavorable gene signatures, high-risk clinicopathologic features and poor prognosis.

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References

  1. Pfreundschuh M, Kuhnt E, Trumper L, Osterborg A, Trneny M, Shepherd L et al. CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diffuse large-B-cell lymphoma: 6-year results of an open-label randomised study of the MabThera International Trial (MInT) Group. Lancet Oncol 2011; 12: 1013–1022.

    Article  CAS  PubMed  Google Scholar 

  2. Coiffier B, Thieblemont C, Van Den Neste E, Lepeu G, Plantier I, Castaigne S et al. Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the Groupe d'Etudes des Lymphomes de l'Adulte. Blood 2010; 116: 2040–2045.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Vaidya R, Witzig TE . Prognostic factors for diffuse large B-cell lymphoma in the R(X)CHOP era. Ann oncol 2014; 25: 2124–2133.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Chung R, Lai R, Wei P, Lee J, Hanson J, Belch AR et al. 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: 1278–1282.

    Article  CAS  PubMed  Google Scholar 

  5. Campbell J, Seymour JF, Matthews J, Wolf M, Stone J, Juneja S . The prognostic impact of bone marrow involvement in patients with diffuse large cell lymphoma varies according to the degree of infiltration and presence of discordant marrow involvement. Eur j haematol 2006; 76: 473–480.

    Article  PubMed  Google Scholar 

  6. Hodges GF, Lenhardt TM, Cotelingam JD . Bone marrow involvement in large-cell lymphoma. Prognostic implications of discordant disease. Am j clin pathol 1994; 101: 305–311.

    Article  CAS  PubMed  Google Scholar 

  7. Park MJ, Park SH, Park PW, Seo YH, Kim KH, Seo JY et al. Prognostic impact of concordant and discordant bone marrow involvement and cell-of-origin in Korean patients with diffuse large B-cell lymphoma treated with R-CHOP. J clin pathol 2015; 68: 733–738.

    Article  CAS  PubMed  Google Scholar 

  8. Song MK, Chung JS, Lee JJ, Yang DH, Kim IS, Shin DH et al. High Ki-67 expression in involved bone marrow predicts worse clinical outcome in diffuse large B cell lymphoma patients treated with R-CHOP therapy. Int j hematol 2015; 101: 140–147.

    Article  CAS  PubMed  Google Scholar 

  9. Shim H, Oh JI, Park SH, Jang S, Park CJ, Huh J et al. Prognostic impact of concordant and discordant cytomorphology of bone marrow involvement in patients with diffuse, large, B-cell lymphoma treated with R-CHOP. J clin pathol 2013; 66: 420–425.

    Article  CAS  PubMed  Google Scholar 

  10. Sehn LH, Scott DW, Chhanabhai M, Berry B, Ruskova A, Berkahn L et al. Impact of concordant and discordant bone marrow involvement on outcome in diffuse large B-cell lymphoma treated with R-CHOP. J clin oncol 2011; 29: 1452–1457.

    Article  PubMed  Google Scholar 

  11. International Non-Hodgkin's Lymphoma Prognostic Factors Project. A predictive model for aggressive non-Hodgkin's lymphoma. The International Non-Hodgkin's Lymphoma Prognostic Factors Project. N Engl j med 1993; 329: 987–994.

    Article  Google Scholar 

  12. Ziepert M, Hasenclever D, Kuhnt E, Glass B, Schmitz N, Pfreundschuh M et al. Standard International prognostic index remains a valid predictor of outcome for patients with aggressive CD20+ B-cell lymphoma in the rituximab era. J clin oncol 2010; 28: 2373–238.

    Article  CAS  PubMed  Google Scholar 

  13. Alizadeh AA, Eisen MB, Davis RE, Ma C, Lossos IS, Rosenwald A et al. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature 2000; 403: 503–511.

    Article  CAS  PubMed  Google Scholar 

  14. Hans CP, Weisenburger DD, Greiner TC, Gascoyne RD, Delabie J, Ott G et al. Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood 2004; 103: 275–282.

    Article  CAS  PubMed  Google Scholar 

  15. Choi WW, Weisenburger DD, Greiner TC, Piris MA, Banham AH, Delabie J 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Meyer PN, Fu K, Greiner TC, Smith LM, Delabie J, Gascoyne RD et al. Immunohistochemical methods for predicting cell of origin and survival in patients with diffuse large B-cell lymphoma treated with rituximab. J clin oncol 2011; 29: 200–207.

    Article  PubMed  Google Scholar 

  17. Visco C, Li Y, Xu-Monette ZY, Miranda RN, Green TM, Li 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: 2103–2113.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Iqbal J, Meyer PN, Smith LM, Johnson NA, Vose JM, Greiner TC et al. BCL2 predicts survival in germinal center B-cell-like diffuse large B-cell lymphoma treated with CHOP-like therapy and rituximab. Clin cancer res 2011; 17: 7785–7795.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Green TM, Young KH, Visco C, Xu-Monette ZY, Orazi A, Go RS et al. Immunohistochemical double-hit score is a strong predictor of outcome in patients with diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. J clin oncol 2012; 30: 3460–3467.

    Article  CAS  PubMed  Google Scholar 

  20. Hu S, Xu-Monette ZY, Tzankov A, Green T, Wu L, Balasubramanyam A et al. MYC/BCL2 protein coexpression contributes to the inferior survival of activated B-cell subtype of diffuse large B-cell lymphoma and demonstrates high-risk gene expression signatures: a report from The International DLBCL Rituximab-CHOP Consortium Program. Blood 2013; 121: 4021–4031.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Valera A, Lopez-Guillermo A, Cardesa-Salzmann T, Climent F, Gonzalez-Barca E, Mercadal S et al. MYC protein expression and genetic alterations have prognostic impact in patients with diffuse large B-cell lymphoma treated with immunochemotherapy. Haematologica 2013; 98: 1554–1562.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Xu-Monette ZY, Tu M, Jabbar KJ, Cao X, Tzankov A, Visco C et al. Clinical and biological significance of de novo CD5+ diffuse large B-cell lymphoma in Western countries. Oncotarget 2015; 6: 5615–5633.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Xu-Monette ZY, Wu L, Visco C, Tai YC, Tzankov A, Liu WM et al. Mutational profile and prognostic significance of TP53 in diffuse large B-cell lymphoma patients treated with R-CHOP: report from an International DLBCL Rituximab-CHOP Consortium Program Study. Blood 2012; 120: 3986–3996.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Bellas C, Garcia D, Vicente Y, Kilany L, Abraira V, Navarro B et al. Immunohistochemical and molecular characteristics with prognostic significance in diffuse large B-cell lymphoma. PloS one 2014; 9: e98169.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 2016; 127: 2375–2390.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ et al. Revised response criteria for malignant lymphoma. J clin oncol 2007; 25: 579–586.

    Article  PubMed  Google Scholar 

  27. Carbone PP, Kaplan HS, Musshoff K, Smithers DW, Tubiana M . Report of the Committee on Hodgkin's Disease Staging Classification. Cancer res 1971; 31: 1860–1861.

    CAS  PubMed  Google Scholar 

  28. Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J clin oncol 2014; 32: 3059–3068.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Robertson LE, Redman JR, Butler JJ, Osborne BM, Velasquez WS, McLaughlin P et al. Discordant bone marrow involvement in diffuse large-cell lymphoma: a distinct clinical-pathologic entity associated with a continuous risk of relapse. J clin oncol 1991; 9: 236–242.

    Article  CAS  PubMed  Google Scholar 

  30. Thiele J, Zirbes TK, Kvasnicka HM, Fischer R . Focal lymphoid aggregates (nodules) in bone marrow biopsies: differentiation between benign hyperplasia and malignant lymphoma—a practical guideline. J clin pathol 1999; 52: 294–300.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Campbell JK, Matthews JP, Seymour JF, Wolf MM, Juneja SK, Australasian Leukaemia Lymphoma G. Optimum trephine length in the assessment of bone marrow involvement in patients with diffuse large cell lymphoma. Ann oncol 2003; 14: 273–276.

    Article  CAS  PubMed  Google Scholar 

  32. Deng L, Xu-Monette ZY, Loghavi S, Manyam GC, Xia Y, Visco C et al. Primary testicular diffuse large B-cell lymphoma displays distinct clinical and biological features for treatment failure in rituximab era: a report from the International PTL Consortium. Leukemia 2016; 30: 361–372.

    Article  CAS  PubMed  Google Scholar 

  33. Hwang HS, Yoon DH, Suh C, Huh J . A new extranodal scoring system based on the prognostically relevant extranodal sites in diffuse large B-cell lymphoma, not otherwise specified treated with chemoimmunotherapy. Ann hematol 2016; 95: 1249–1258.

    Article  CAS  PubMed  Google Scholar 

  34. Zhou Z, Sehn LH, Rademaker AW, Gordon LI, Lacasce AS, Crosby-Thompson A et al. An enhanced International Prognostic Index (NCCN-IPI) for patients with diffuse large B-cell lymphoma treated in the rituximab era. Blood 2014; 123: 837–842.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Chigrinova E, Mian M, Scandurra M, Greiner TC, Chan WC, Vose JM et al. Diffuse large B-cell lymphoma with concordant bone marrow involvement has peculiar genomic profile and poor clinical outcome. Hematol Oncol 2011; 29: 38–41.

    Article  PubMed  Google Scholar 

  36. Juneja SK, Wolf MM, Cooper IA . Value of bilateral bone marrow biopsy specimens in non-Hodgkin's lymphoma. J clin pathol 1990; 43: 630–632.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Friedl P, Alexander S . Cancer invasion and the microenvironment: plasticity and reciprocity. Cell 2011; 147: 992–1009.

    Article  CAS  PubMed  Google Scholar 

  38. Cheng L, Ruan Z . Tim-3 and Tim-4 as the potential targets for antitumor therapy. Hum Vaccin Immunother 2015; 11: 2458–2462.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Kremer M, Spitzer M, Mandl-Weber S, Stecker K, Schmidt B, Hofler H et al. Discordant bone marrow involvement in diffuse large B-cell lymphoma: comparative molecular analysis reveals a heterogeneous group of disorders. Lab invest 2003; 83: 107–114.

    Article  CAS  PubMed  Google Scholar 

  40. Kridel R, Mottok A, Farinha P, Ben-Neriah S, Ennishi D, Zheng Y et al. Cell of origin of transformed follicular lymphoma. Blood 2015; 126: 2118–2127.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Purroy N, Bergua J, Gallur L, Prieto J, Lopez LA, Sancho JM et al. Long-term follow-up of dose-adjusted EPOCH plus rituximab (DA-EPOCH-R) in untreated patients with poor prognosis large B-cell lymphoma. A phase II study conducted by the Spanish PETHEMA Group. Br j haematol 2015; 169: 188–198.

    Article  CAS  PubMed  Google Scholar 

  42. Oki Y, Westin JR, Vega F, Chuang H, Fowler N, Neelapu S et al. Prospective phase II study of rituximab with alternating cycles of hyper-CVAD and high-dose methotrexate with cytarabine for young patients with high-risk diffuse large B-cell lymphoma. Br j haematol 2013; 163: 611–620.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Mato A, Feldman T, Zielonka T, Singavi A, Gadaletta G, Waksmundzki K et al. Rituximab, cyclophosphamide-fractionated, vincristine, doxorubicin and dexamethasone alternating with rituximab, methotrexate and cytarabine overcomes risk features associated with inferior outcomes in treatment of newly diagnosed, high-risk diffuse large B-cell lymphoma. Leukemia lymphoma 2013; 54: 2606–2612.

    Article  CAS  PubMed  Google Scholar 

  44. Howlett C, Snedecor SJ, Landsburg DJ, Svoboda J, Chong EA, Schuster SJ et al. Front-line, dose-escalated immunochemotherapy is associated with a significant progression-free survival advantage in patients with double-hit lymphomas: a systematic review and meta-analysis. Br j haematol 2015; 170: 504–514.

    Article  PubMed  Google Scholar 

  45. Barta SK, Li H, Hochster HS, Hong F, Weller E, Gascoyne RD et al. Randomized phase 3 study in low-grade lymphoma comparing maintenance anti-CD20 antibody with observation after induction therapy: A trial of the ECOG-ACRIN Cancer Research Group (E1496). Cancer 2016; 122: 2996–3004.

    Article  CAS  PubMed  Google Scholar 

  46. Greil R, Obrtlikova P, Smolej L, Kozak T, Steurer M, Andel J et al. Rituximab maintenance versus observation alone in patients with chronic lymphocytic leukaemia who respond to first-line or second-line rituximab-containing chemoimmunotherapy: final results of the AGMT CLL-8a Mabtenance randomised trial. Lancet Haematol 2016; 3: e317–e329.

    Article  PubMed  Google Scholar 

  47. Zahid MF, Khan N, Hashmi SK, Kizilbash SH, Barta SK . Central nervous system prophylaxis in diffuse large B-cell lymphoma. Eur j haematol 2016; 97: 108–120.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by National Cancer Institute/National Institutes of Health grants R01CA138688, R01CA187415 and 1RC1CA146299 to YL and KHY. This work was also partially supported by National Cancer Institute and National Institutes of Health grants P50CA136411 and P50CA142509, and by MD Anderson’s Cancer Center Support Grant CA016672. ZY and LD are the recipients of the Hematology/Oncology Scholarship Award. KHY is also supported by The University of Texas MD Anderson Cancer Center Institutional Research and Development Fund, an Institutional Research Grant Award, an MD Anderson Cancer Center Lymphoma Specialized Programs on Research Excellence (SPORE) Research Development Program Award, an MD Anderson Cancer Center Myeloma SPORE Research Development Program Award, a Gundersen Lutheran Medical Foundation Award, the University Cancer Foundation via the Sister institution network Fund at The University of Texas MD Anderson Cancer Center and is partially supported by grants from the National Cancer Institute/National Institutes of Health (P50CA136411 and P50CA142509). KHY receives research support from Roche Molecular System, Gilead Sciences Pharmaceutical, Seattle Genetics, Dai Sanyo Pharmaceutical, Adaptive Biotechnology, Incyte Pharmaceutical, and HTG Molecular Diagnostics.

Author contributions

Conception, design and writing: ZY, KHY. Research performance: ZY, LD, ZYX-M, GCM, AT, YL, KHY. Provision of study thought, materials, key reagents and technology: ZY, LD, ZYX-M, GCM, PJ, AT, CV, GB, JW, KD, AO, EDH, JH, MP, AJMF, MBM, JNW, MAP, JF, YL, YS, RZO, HK, LJM, YL, JC, KHY. Collection and assembly of data under approved IRB and Material Transfer Agreement: ZY, LD, ZYX-M, PJ, AT, CV, GB, JW, KD, AO, EDH, JH, MP, AJMF, MBM, JNW, MAP, JF, YL, YS, YL, KHY. Data analysis and interpretation: ZY, LD, ZYX-M, GCM, LJM, YL, JC, KHY. Manuscript editing: ZY, LD, ZYX-M, AT, LJM, YL, JC, KHY. Final approval of manuscript: All authors.

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Author notes

  1. Z Yao and L Deng: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Medical Oncology, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China

    Z Yao, Y Liu & Y Song

  2. Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Z Yao, Z Y Xu-Monette, L J Medeiros & K H Young

  3. Department of Lymphoma, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China,

    L Deng

  4. Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    G C Manyam & J Wang

  5. Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    P Jain, L Fayad, R Z Orlowski, H Kantarjian & J Cortes

  6. University of Basel, Hospital, Basel, Switzerland

    A Tzankov

  7. San Bortolo Hospital, Vicenza, Italy

    C Visco

  8. Columbia University Medical Center and New York Presbyterian Hospital, New York, NY, USA

    G Bhagat

  9. Aalborg University Hospital, Aalborg, Denmark

    K Dybkaer

  10. Weill Medical College of Cornell University, New York, NY, USA

    W Tam

  11. Cleveland Clinic, Cleveland, OH, USA

    E D Hsi

  12. Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

    J H van Krieken

  13. San Raffaele H. Scientific Institute, Milan, Italy

    M Ponzoni & A J M Ferreri

  14. Odense University Hospital, Odense, Denmark

    M B Møller

  15. Feinberg School of Medicine, Northwestern University, Chicago, IL, USA

    J N Winter

  16. Hospital Universitario Marqués de Valdecilla, Santander, Spain

    M A Piris

  17. Department of Cancer Biology, Cleveland Clinic, Lerner Research Institute, Cleveland, OH, USA

    Y Li

  18. Graduate School of Biomedical Sciences, The University of Texas Health Science Center, Houston, TX, USA

    K H Young

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  1. Z Yao
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  2. L Deng
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  3. Z Y Xu-Monette
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  20. Y Liu
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  21. Y Song
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  22. R Z Orlowski
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  25. Y Li
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  26. J Cortes
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  27. K H Young
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Correspondence to Y Song or K H Young.

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Yao, Z., Deng, L., Xu-Monette, Z. et al. Concordant bone marrow involvement of diffuse large B-cell lymphoma represents a distinct clinical and biological entity in the era of immunotherapy. Leukemia 32, 353–363 (2018). https://doi.org/10.1038/leu.2017.222

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