Hematologic manifestations and predictors of lymphoma development in primary sjögren syndrome: Clinical and pathophysiologic aspects

The diverse hematologic manifestations of primary Sjögren syndrome (pSS) have not been systematically investigated, and their prognostic relevance remains unclear. We conducted a retrospective study of 536 consecutive patients followed in our institution to assess the prevalence of hematologic abnormalities and their associations with various disease manifestations in pSS. We also aimed to identify risk factors for the development of non-Hodgkin lymphoma (NHL) overall and by subtype.Anemia of chronic disease and hypergammaglobulinemia were the most prevalent hematologic manifestations encountered at diagnosis and during the course of pSS. Univariate analysis between cytopenias and glandular manifestations revealed a statistically significant correlation between lymphocytopenia and parotid gland enlargement (p = 0.002), as well as between neutropenia and xerostomia (p = 0.019). Anemia, lymphocytopenia, thrombocytopenia, hypergammaglobulinemia, the presence of monoclonal serum proteins, and cryoglobulinemia correlated significantly with the presence of extraglandular symptoms such as palpable purpura, lymphadenopathy, and splenomegaly.Lymphoma was diagnosed in 7.5% (95% confidence interval [CI], 5.4%-10%) of patients. Marginal zone B-cell lymphomas (MZBCLs) were the predominant histologic type (65%; 95% CI, 48.3%-79.4%), while diffuse large B-cell lymphomas (DLBCLs) accounted for 17.5% (95% CI, 7.3%-32.8%) of all cases. The development of NHL in patients with pSS could be predicted by the presence of simple clinical and laboratory factors at diagnosis: neutropenia (p = 0.041), cryoglobulinemia (p = 0.008), splenomegaly (p = 0.006), lymphadenopathy (p = 0.021), and low C4 levels (p = 0.009). Patients carrying any of these factors had a more than 5-fold increased risk of NHL compared to patients with no risk factors at all. The above set of disease characteristics could predict subsequent development of MZBCL; the presence of lymphocytopenia (p = 0.044) at diagnosis served as a risk factor for the development of a non-MZBCL, most commonly DLBCL.Anemia of chronic disease and hypergammaglobulinemia are common hematologic manifestations at diagnosis and during the course of pSS. Neutropenia and cryoglobulinemia at diagnosis are significantly associated with an increased risk of lymphoma development. Copyright © 2009 by Lippincott Williams & Wilkins

Prognosis and outcome of non-hodgkin lymphoma in primary sjögren syndrome

Sjögren syndrome (SS) has been associated with the development of non-Hodgkin lymphoma (NHL). From a cohort of 584 SS patients followed in our department from 1980 to 2010, we retrospectively analyzed 53 consecutive NHL cases. Considerations included histologic type, clinical manifestation and NHL staging, treatment, response rate and overall survival (OS), event-free survival (EFS), and standardized mortality ratio (SMR).Mucosa-associated lymphoid tissue (MALT) lymphomas constituted the majority (59%) of NHL subtypes, followed by nodal marginal zone lymphomas (NMZLs) (15%) and diffuse large B-cell lymphomas (DLBCLs) (15%). Six lymphoma patients died during the median follow-up of 40.8 months. The corresponding age/sex-adjusted SMR of SS with and without NHLs versus the general population was 3.25 (95% confidence interval [CI] 1.32-6.76) and 1.08 (95% CI, 0.79-1.45), respectively. A "watch and wait" policy was adopted for 9 patients with asymptomatic localized salivary MALT lymphomas. Eight patients with limited-stage MALT lymphomas and extraglandular manifestations were treated with rituximab. Ten MALT lymphoma patients with disseminated disease received chemotherapy with or without rituximab. The 3-year OS and EFS in patients with MALT lymphomas was 97% and 78%, respectively. Rituximab plus CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) was the chosen therapeutic intervention for patients with DLBCLs. A successful outcome was recorded for this group, with 100% OS and EFS at 3 years. Patients with NMZLs had a less favorable outcome, with a 3-year OS of 80% and EFS of 53%. Our results describe the course and prognosis of SS-associated NHL and highlight the need for a risk-stratified treatment approach. Copyright © 2012 by Lippincott Williams & Wilkins