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Leukemia. 2018 Feb;32(2):353-363. doi: 10.1038/leu.2017.222. Epub 2017 Jul 12.

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

Author information

1
Department of Medical Oncology, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China.
2
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
3
Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing, China.
4
Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
5
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
6
University of Basel, Hospital, Basel, Switzerland.
7
San Bortolo Hospital, Vicenza, Italy.
8
Columbia University Medical Center and New York Presbyterian Hospital, New York, NY, USA.
9
Aalborg University Hospital, Aalborg, Denmark.
10
Weill Medical College of Cornell University, New York, NY, USA.
11
Cleveland Clinic, Cleveland, OH, USA.
12
Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
13
San Raffaele H. Scientific Institute, Milan, Italy.
14
Odense University Hospital, Odense, Denmark.
15
Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
16
Hospital Universitario Marqués de Valdecilla, Santander, Spain.
17
Department of Cancer Biology, Cleveland Clinic, Lerner Research Institute, Cleveland, OH, USA.
18
Graduate School of Biomedical Sciences, The University of Texas Health Science Center, Houston, TX, USA.

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.

PMID:
28745330
PMCID:
PMC5985660
DOI:
10.1038/leu.2017.222
[Indexed for MEDLINE]
Free PMC Article

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