Lymphoproliferative diseases in primary Sjogren's syndrome

During long term follow up (median 10 years) of 412 patients with primary Sjogren's syndrome (pSS) 46; (11,2%) women developed non-Hodgkin's lymphoma (NHL). Median pSS duration before development of NHL was 17 years. 43 (93,3%) patients had B-cell and 3 (6,7%) - T-cell NHL. All types of NHL were present except precursor cell lymphomas. Diffuse large B-cell lymphoma (LBCL) (39%) and MALT lymphomas (21%) prevailed. Nodal NHL with extranodal involvement (52,2%) were the most frequent. Nodal (21,8%) and extranodal (26%) lymphomas were less frequent. The most frequent target organs in lymphoproliferative disease (LPD) were lymph nodes (74%), salivary glands (45,5%), lungs (26%), bone marrow (19,5%), liver (17,5%), spleen (13%), lachrymal glands (6,5%). Waldeyer's throat ring (4%), oral cavity mucous membrane, ovary and brain (2%) were involved rarely. Immunoglobulin-secreting variant of lymphoma was revealed in 53,7% of cases. LPD developed predominantly in patients with systemic features and late stage of pSS. Significant increase of parotis, mixed monoclonal cryoglobulinemia, generalized lymphadenopathy, presence of more than 5 focuses of lymphoid infiltration in small salivary glands biopsies and thrombocytopenia were predictors of NHL development in pSS (p<0,001). Prolonged treatment with small doses of alkylating cytostatic agents (leukeran, cyclophosphan) decreased risk of LPD development in pSS (p><0,001). 5-year survival of patients from the moment LPD was diagnosed was 54% mainly due to high mortality in the group of patients with LCL. Survival of pSS patients with and without LPD s><0,001). Prolonged treatment with small doses of alkylating cytostatic agents (leukeran, cyclophosphan) decreased risk of LPD development in pSS (p<0,001). 5-year survival of patients from the moment LPD was diagnosed was 54% mainly due to high mortality in the group of patients with LCL. Survival of pSS patients with and without LPD significantly differed (p<0,001): after 20-year follow up survival was 32% in group with LPD and 76% in group without LPD. Probability of NHL development after 40-year course of pSS was 40% what allows to consider this disease simultaneously autoimmune and lymphoproliferative.

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