Inflammatory and Autoimmune Manifestations Associated with Lymphoid Neoplasms: A French Multicenter Retrospective Study
Authors: Jachiet Vincent , Grignano Eric , Mekinian Arsène , Coppo Paul , Fain Olivier 
Published: October 2019

Abstract
INTRODUCTION
Lymphomas are hematopoietic stem cell malignancies derived variously from mature T lymphocytes (cytotoxic T cells, helper T cells, or T regulatory cells) or mature B lymphocytes (B cells or plasma cells). Few reports have described lymphoma associated SIADs (Dührsen et al, Br J Haematol 1987) and the impact of SIADs on lymphoma outcome remains unknown. We conducted a French retrospective study to describe the different types of systemic inflammatory and autoimmune diseases (SIADs) associated with lymphoma, the characteristics of the associated lymphomas and the outcomes of both disorders.
METHODS
We retrospectively collected data of patients with lymphoma hospitalized between 1st January 2005 and 31st August 2016 in 3 French centers (Saint Antoine Hospital, Tenon Hospital and Trousseau Hospital, Paris 6 University). The ICD-10 (International Statistical Classification of Diseases and Related Health Problems) was used to extract patients with both codes for lymphoid neoplasms (Hodgkin lymphoma, mature B-cell, T-cell or NK-cell neoplasms ; excepted precursor lymphoid neoplasms). Among lymphoma patients, autoimmune and/or inflammatory diseases were extracted from database of the DIM (Département d'Information Médicale). The follow-up was determined from the time of lymphoma diagnosis to last news and/or death.
RESULTS
During the period of study, 3284 patients with lymphoma have been included, and among them 112 (3.4%) have associated SIADs. SIADs were classified as autoimmune cytopenias in 79 cases (71%) (autoimmune hemolytic anemia, n=57 ; immune thrombocytopenia, n=20), neurological diseases in 11 cases (10%) (Guillain-Barré syndrome, n=6 ; peripheral neuropathy, n=5, including 2 patients with anti-MAG neuropathy), inflammatory arthritis in 6 cases (5%) (rheumatoid arthritis and polymyalgia rheumatica), systemic vasculitis in 5 cases (4%) (giant cell arteritis, n=3 ; cryoglobulinemic vasculitis, n=2), kidney diseases in 5 cases (4%) (membranoproliferative glomerulonephritis in 2 cases), autoimmune liver diseases in 5 cases (4%). Others SIADs were cutaneous diseases (n=3) (bullous pemphigoid, Sweet's syndrome and eosinophilic fasciitis), myositis (n=3) (dermatomyositis, antisynthetase syndrome and polymyositis), one mixed connective tissue disease and one acquired von Willebrand disease. In 7 patients (6%), several types of SIADS were associated, mostly with autoimmune cytopenias. Among patients with SIADs, the underlying lymphoma was B-cell chronic lymphocytic leukemia (CLL) in 41%, B-cell non-Hodgkin lymphomas (B-NHL) in 29%, diffuse large B-cell lymphoma (DLBCL) in 11%, T-cell non-Hodgkin lymphomas (T-NHL) in 10%, Hodgkin lymphoma (7%) and unspecified non-Hodgkin lymphomas (unspecified NHL) in 3%. In comparison to patients without SIADs, patients with SIADs were older (median age 74 [21-97] years versus 66 [18-102] years, p<0.0001), with similar sex ratio. Median time between the diagnosis of SIADs and lymphoma was 20 months, [range 0-304]. The diagnosis of SIADs and lymphoma was concomitant in 32 cases (30%), diagnosis of lymphoma preceded SIADs in 49 cases (46%) and followed diagnosis of SIADs in 25 cases (24%). In comparison to patients without SIADs, the CLL (41% versus 17%, p<0,0001), B-NHL (29% versus 19%, p=0,02) and T-NHL (10% versus 5%, p=0,02) types were more frequent, whereas Hodgkin (7% versus 15%, p=0,02) and DLBCL lymphoma were less frequent. In comparison to patients without SIADs, mortality was increased in patients with SIADs (28% versus 11,3%, p<0,0001), even median follow-up was more important in patients with SIADs (21 [0-119] months versus 6 [0-137] months, p<0,0001).
CONCLUSION
In this retrospective study, various systemic inflammatory and autoimmune diseases (mostly autoimmune cytopenias) have been associated with lymphoma (mostly CLL, B-NHL and T-NHL) and seem to be associated with an increased mortality, that need to be confirmed in a prospective study.

Disclosures
No relevant conflicts of interest to declare.