Lymphoma risk in systemic lupus: effects of disease activity versus treatment

Abstract

Objective To examine disease activity versus treatment as lymphoma risk factors in systemic lupus erythematosus (SLE). Methods We performed case–cohort analyses within a multisite SLE cohort. Cancers were ascertained by regional registry linkages. Adjusted HRs for lymphoma were generated in regression models, for time-dependent exposures to immunomodulators (cyclophosphamide, azathioprine, methotrexate, mycophenolate, antimalarial drugs, glucocorticoids) demographics, calendar year, Sjogren’s syndrome, SLE duration and disease activity. We used adjusted mean SLE Disease Activity Index scores (SLEDAI-2K) over time, and drugs were treated both categorically (ever/never) and as estimated cumulative doses. Results We studied 75 patients with lymphoma (72 non-Hodgkin, three Hodgkin) and 4961 cancer-free controls. Most lymphomas were of B-cell origin. As is seen in the general population, lymphoma risk in SLE was higher in male than female patients and increased with age. Lymphomas occurred a mean of 12.4 years (median 10.9) after SLE diagnosis. Unadjusted and adjusted analyses failed to show a clear association of disease activity with lymphoma risk. There was a suggestion of greater exposure to cyclophosphamide and to higher cumulative steroids in lymphoma cases than the cancer-free controls. Conclusions In this large SLE sample, there was a suggestion of higher lymphoma risk with exposure to cyclophosphamide and high cumulative steroids. Disease activity itself was not clearly associated with lymphoma risk. Further work will focus on genetic profiles that might interact with medication exposure to influence lymphoma risk in SLE.

Burkitt’s Lymphoma in a patient with systemic lupus erythematosus

“…This has been demonstrated in a study done by Bernatsky et.al. 18 However, the present patient did not have clinical features like dryness of mouth or eyes and her anti-Ro and anti-La antibodies were negative.…”

Survival of human lymphoma cells requires B-cell receptor engagement by self-antigens

“…To a lesser extent, V H 4-34 use is enriched in CLL (8.9% of cases) and MCL (14.6% of cases) (5,6), suggesting that the intrinsic autoreactivity of V H 4-34 could play + antibodies to n-acetyl-lactosamine moieties on glycoproteins is presumed to anergize these B cells, potentially accounting for their relative inability to enter productive immune responses. Of the V H 4-34 + B cells that do make it into the memory B-cell pool in healthy individuals, 43% acquire mutations that disrupt the FR1 AVY motif that is essential for autoreactivity, presumably as one mechanism to escape anergy (31 (44,45), which is notable because the autoreactive potential of V H 4-34 antibodies contributes substantially to disease flares in SLE (46). SLE epidemiological studies to date have not distinguished between the ABC and GCB DLBCL subtypes, but our studies would predict that patients with SLE would have a particular predisposition to ABC DLBCL, given the importance of V H 4-34 to both diseases.…”

Malignancies in systemic lupus erythematosus

“…To date, preliminary results, controlling for disease activity, support a possible increased risk of lymphoma in cyclophosphamide users, without definitively demonstrating an increased risk for any other medications (adjusted for demographics and disease activity, the odds ratio for cyclophosphamide was 1.99, 95% CI: 1.00-3.96) [42]. More detailed analyses specifically looking at dose, routes and scheduling are underway.…”