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. Liu; Y. Song; R. Z. Orlowski; H. Kantarjian; L. J. Medeiros; Y. Li; J. Cortes; K. H. Young

doi:10.1038/leu.2017.222

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

^*Corresponding author for this work

Medicine, Hematology Oncology Division

Research output: Contribution to journal › Article › peer-review

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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.

Original language	English (US)
Pages (from-to)	353-363
Number of pages	11
Journal	Leukemia
Volume	32
Issue number	2
DOIs	https://doi.org/10.1038/leu.2017.222
State	Published - Feb 1 2018

Funding

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.

ASJC Scopus subject areas

Hematology
Oncology
Cancer Research

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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., ... Young, K. H. (2018). Concordant bone marrow involvement of diffuse large B-cell lymphoma represents a distinct clinical and biological entity in the era of immunotherapy. Leukemia, 32(2), 353-363. https://doi.org/10.1038/leu.2017.222

@article{3bcf9cbc7fd349cf8ac4e33ed8abbdee,

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

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.",

author = "Z. Yao and L. Deng and Xu-Monette, {Z. Y.} and Manyam, {G. C.} and P. Jain and A. Tzankov and C. Visco and G. Bhagat and J. Wang and K. Dybkaer and W. Tam and Hsi, {E. D.} and {Van Krieken}, {J. H.} and M. Ponzoni and Ferreri, {A. J.M.} and M{\o}ller, {M. B.} and Winter, {J. N.} and Piris, {M. A.} and L. Fayad and Y. Liu and Y. Song and Orlowski, {R. Z.} and H. Kantarjian and Medeiros, {L. J.} and Y. Li and J. Cortes and Young, {K. H.}",

year = "2018",

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doi = "10.1038/leu.2017.222",

language = "English (US)",

volume = "32",

pages = "353--363",

journal = "Leukemia",

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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

TY - JOUR

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

Abstract

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