Comprehensive analysis of non-transplant central nervous system lymphoproliferative disease associated with immunosuppressant use.

Abstract

e14043 Background: Primary central nervous system lymphomas (PCNSLs) have historically had dismal survival rates until the advent of high-dose methotrexate (HD-MTX) based chemotherapy regimens, with additional survival benefit gained by CD-20 targeting with rituximab. With increasing prevalence of autoimmune disease and a corresponding rapid rate of development and approval of new immunosuppressant medications, a new type of lymphoproliferative disorder (LPD) has been described, known as iatrogenic immunodeficiency associated LPD. These disorders are typically EBV positive and have distinct histologic and genetic features. Furthermore, many of them arise in the setting of prior methotrexate use, raising the question of whether standard HD-MTX based regimens would still be effective. Our objective was to further characterize this disorder, with a focus on cases with central nervous system involvement, and to determine the optimal management strategy. Methods: We describe a case of a 76-year-old female with iatrogenic immunodeficiency associated PCNSL following 10 years of mercaptopurine, which was successfully treated with surgical resection followed by an antiviral and rituximab based regimen. We then performed a systematic literature review and identified 58 cases of non-transplant iatrogenic immunodeficiency associated LPD involving the central nervous system (CNS). We used a linear probability statistical model to determine correlations with outcome. Results: While the majority of immunosuppressants were associated with EBV positive tumors, natalizumab was associated with EBV negative tumors (95% CI -0.951, -0.076), and EBV positive tumors were associated with improved outcomes (95% CI 0.074, 0.687). Surgical resection (95% CI 0.028, 0.574) was associated with improved outcomes, although limited by potential confounding effect. Although they did not reach statistical significance, antiviral treatment (95% CI -0.039, 0.459) and rituximab (95% CI -0.073, 0.524) showed a trend toward improved outcomes. The remaining treatments including methotrexate showed no improvement. Conclusions: Based on this data, we propose that surgical resection, rituximab, and antiviral treatment may be considered as an alternative to standard HD-MTX based regimens when managing iatrogenic immunodeficiency associated LPD of the CNS. However, further study through randomized clinical trials is warranted.