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

Z. Yao, L. Deng, Z. Y. Xu-Monette, G. C. Manyam, P. Jain, A. Tzankov, C. Visco, G. Bhagat, J. Wang, K. Dybkaer, W. Tam, E. D. Hsi, J. H. Van Krieken, M. Ponzoni, A. J.M. Ferreri, M. B. Møller, J. N. Winter, M. A. Piris, L. Fayad, Y. LiuY. Song, R. Z. Orlowski, H. Kantarjian, L. J. Medeiros, Y. Li, J. Cortes, K. H. Young

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)353-363
Number of pages11
JournalLeukemia
Volume32
Issue number2
DOIs
StatePublished - Feb 1 2018
Externally publishedYes

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Lymphoma, Large B-Cell, Diffuse
Immunotherapy
Bone Marrow
Bone Marrow Diseases
Survival
Transcriptome
Disease-Free Survival
Cell Movement

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Concordant bone marrow involvement of diffuse large B-cell lymphoma represents a distinct clinical and biological entity in the era of immunotherapy. / Yao, Z.; Deng, L.; Xu-Monette, Z. Y.; Manyam, G. C.; Jain, P.; Tzankov, A.; Visco, C.; Bhagat, G.; Wang, J.; Dybkaer, K.; Tam, W.; Hsi, E. D.; Van Krieken, J. H.; Ponzoni, M.; Ferreri, A. J.M.; Møller, M. B.; Winter, J. N.; Piris, M. A.; Fayad, L.; Liu, Y.; Song, Y.; Orlowski, R. Z.; Kantarjian, H.; Medeiros, L. J.; Li, Y.; Cortes, J.; Young, K. H.

In: Leukemia, Vol. 32, No. 2, 01.02.2018, p. 353-363.

Research output: Contribution to journalArticle

Yao, Z, Deng, L, Xu-Monette, ZY, Manyam, GC, Jain, P, Tzankov, A, Visco, C, Bhagat, G, Wang, J, Dybkaer, K, Tam, W, Hsi, ED, Van Krieken, JH, Ponzoni, M, Ferreri, AJM, Møller, MB, Winter, JN, Piris, MA, Fayad, L, Liu, Y, Song, Y, Orlowski, RZ, Kantarjian, H, Medeiros, LJ, Li, Y, Cortes, J & Young, KH 2018, 'Concordant bone marrow involvement of diffuse large B-cell lymphoma represents a distinct clinical and biological entity in the era of immunotherapy', Leukemia, vol. 32, no. 2, pp. 353-363. https://doi.org/10.1038/leu.2017.222
Yao, Z. ; Deng, L. ; Xu-Monette, Z. Y. ; Manyam, G. C. ; Jain, P. ; Tzankov, A. ; Visco, C. ; Bhagat, G. ; Wang, J. ; Dybkaer, K. ; Tam, W. ; Hsi, E. D. ; Van Krieken, J. H. ; Ponzoni, M. ; Ferreri, A. J.M. ; Møller, M. B. ; Winter, J. N. ; Piris, M. A. ; Fayad, L. ; Liu, Y. ; Song, Y. ; Orlowski, R. Z. ; Kantarjian, H. ; Medeiros, L. J. ; Li, Y. ; Cortes, J. ; Young, K. H. / Concordant bone marrow involvement of diffuse large B-cell lymphoma represents a distinct clinical and biological entity in the era of immunotherapy. In: Leukemia. 2018 ; Vol. 32, No. 2. pp. 353-363.
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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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T1 - Concordant bone marrow involvement of diffuse large B-cell lymphoma represents a distinct clinical and biological entity in the era of immunotherapy

AU - Yao, Z.

AU - Deng, L.

AU - Xu-Monette, Z. Y.

AU - Manyam, G. C.

AU - Jain, P.

AU - Tzankov, A.

AU - Visco, C.

AU - Bhagat, G.

AU - Wang, J.

AU - Dybkaer, K.

AU - Tam, W.

AU - Hsi, E. D.

AU - Van Krieken, J. H.

AU - Ponzoni, M.

AU - Ferreri, A. J.M.

AU - Møller, M. B.

AU - Winter, J. N.

AU - Piris, M. A.

AU - Fayad, L.

AU - Liu, Y.

AU - Song, Y.

AU - Orlowski, R. Z.

AU - Kantarjian, H.

AU - Medeiros, L. J.

AU - Li, Y.

AU - Cortes, J.

AU - Young, K. H.

PY - 2018/2/1

Y1 - 2018/2/1

N2 - 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.

AB - 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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