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Leukemia. 2020 Feb;34(2):543-552. doi: 10.1038/s41375-019-0573-y. Epub 2019 Sep 17.

A novel lymphoma-associated macrophage interaction signature (LAMIS) provides robust risk prognostication in diffuse large B-cell lymphoma clinical trial cohorts of the DSHNHL.

Author information

1
Department of Clinical Pathology, Robert-Bosch-Krankenhaus, Stuttgart, Germany.
2
Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, University of Tuebingen, Stuttgart, Germany.
3
Statistical Bioinformatics, Institute of Functional Genomics, University of Regensburg, Regensburg, Germany.
4
Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
5
Institute of Pathology, Hematopathology Section and Lymph Node Registry, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel, Germany.
6
Department of Internal Medicine II, Hematology Laboratory, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel, Germany.
7
Pathodiagnostik Berlin, Berlin, Germany.
8
Haematopathologie Luebeck, Luebeck, Germany.
9
Institute of Pathology, Universitätsklinikum Ulm, Ulm, Germany.
10
Dr. Senckenberg Institute of Pathology, Goethe University Hospital, Frankfurt, Germany.
11
DSHNHL Studiensekretariat, Universitätsklinikum des Saarlandes, Homburg, Germany.
12
Department of Medicine A, University Hospital Muenster, Muenster, Germany.
13
Department of Hematology and Oncology, Georg-August Universität, Göttingen, Germany.
14
Department of Internal Medicine III, Universitätsklinikum Regensburg, Regensburg, Germany.
15
Institute of Pathology, Universität Würzburg and Comprehensive Cancer Center Mainfranken (CCCMF), Würzburg, Germany.
16
Department of Clinical Pathology, Robert-Bosch-Krankenhaus, Stuttgart, Germany. German.Ott@rbk.de.

Abstract

Diffuse large B-cell lymphoma (DLBCL) is a disease with heterogeneous outcome. Stromal signatures have been correlated to survival in DLBCL. Their use, however, is hampered by the lack of assays for formalin-fixed paraffin-embedded material (FFPE). We constructed a lymphoma-associated macrophage interaction signature (LAMIS) interrogating features of the microenvironment using a NanoString assay applicable to FFPE. The clinical impact of the signature could be validated in a cohort of 466 patients enrolled in prospective clinical trials of the German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL). Patients with high expression of the signature (LAMIShigh) had shorter EFS, PFS, and OS. Multivariate analyses revealed independence from IPI factors in EFS (HR 1.7, 95% CI 1.2-2.4, p-value = 0.001), PFS (HR 1.8, 95% CI 1.2-2.5, p-value = 0.001) and OS (HR 1.8, 95% CI 1.3-2.7, p-value = 0.001). Multivariate analyses adjusted for the IPI factors showed the signature to be independent from COO, MYC rearrangements and double expresser status (DE). LAMIShigh and simultaneous DE status characterized a patient subgroup with dismal prognosis and early relapse. Our data underline the importance of the microenvironment in prognosis. Combined analysis of stromal features, the IPI and DE may provide a new rationale for targeted therapy.

PMID:
31530861
DOI:
10.1038/s41375-019-0573-y

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