Combined Therapy with Rituximab Plus Cyclophosphamide/Vincristine/Prednisone for Sjogren’s Syndrome-Associated B-Cell Non-Hodgkin’s Lymphoma

Abstract

Sjogren's syndrome (SS) is characterized by an increased risk of developing non-Hodgkin's lymphoma (NHL). Optimal treatment for NHL-complicating SS is not clearly established. NHL, which expresses the CD20 antigen on tumor cell surfaces, is a disease entity candidate to treatment with anti-CD20 monoclonal antibodies. We report clinical and immunological data of a patient with SS and NHL who was treated with a regimen consisting of cyclophosphamide/vincristine/prednisone (CVP) plus rituximab. A 68-year-old women had a 26-year history of SS and autoimmune thyroiditis. The clinical course of SS was complicated with severe splenomegaly. An increased percentage of CD19+ B cells (up to 30%) was detected in peripheral blood during follow-up. Clonal rearrangement of immunoglobulin heavy chain was detected. Low-grade B marginal zone lymphoma was diagnosed (peripheral blood immunophenotype: CD19+CD20+CD23+sIg+Kappa; bone marrow immunophenotype: 25% lymphocytes; CD19+CD20+CD79A/BCL2+). She received a total of six cycles of CVP plus rituximab (375 mg/m2). Therapy was well tolerated, and B lymphocytes were depleted from the peripheral blood. Splenomegaly normalized. No evidence of neoplastic infiltration was detected in bone marrow after completion of therapy, while certain symptoms of SS (sicca and arthralgia) improved with treatment. CVP plus rituximab proved effective in a patient with SS with NHL.

Anti‐CD20 treatment in Primary Sjögren’s Syndrome

“…Four case studies demonstrate improvements in subjective assessments of dryness [41, 42, 44, 48], and two cases also report [43, 46] modest improvement in objective measures like stimulated whole saliva/salivary flow rate and Schirmers test. Noteworthy objective improvements are otherwise lacking in the cases reported here.…”

“…One case study listed in Table 1.describes complete remission of MALT‐associated lymphoma following Rtx monotherapy [43]. Another case describes complete remission of pSS associated NHL, after giving combined therapy with Rtx plus cyclophosphamid, vincristine and prednisolone [48].…”

“…As listed in Table 1, there are 10 relevant case reports on Rtx and pSS [39][40][41][42][43][44][45][46][47][48]. Common for the majority of cases is a notable effect of Rtx on systemic manifestations of pSS.…”

Controversies on Rituximab Therapy in Sjögren Syndrome-Associated Lymphoproliferation

“…Since 2002 up to the time of searching (February 2009), 26 patients with SS and lymphoma treated with RTX have been reported in 11 PubMed indexed articles by combining the key words “Sjögren's syndrome”, “rituximab”, and “lymphoma” [3, 11, 14–22]. Sixteen (17/26) were in Ann Arbor Stage I-II, while the remaining were in stage III (1/26) or IV (8/26).…”

“…Then, a careful use of RTX in selected cases seemed more rationale, in the lack of additional clear-cut evidence of some benefits. By contrast, RTX monotherapy or RTX combined with cytotoxic agents in chemotherapeutic regimens may have a stronger rationale in SS patients with CD20-positive B-cell NHL [3, 11, 14–22]. …”