Background: The risk of primary central nervous system lymphoma (PCNSL) is greatly increased in HIV-infected people. Case series have described PCNSL in immunosuppressed solid organ transplant (SOT) recipients (SOTRs). Herein, we examine the incidence and risk factors for PCNSL in SOTRs.
Methods: We used data from the Transplant Cancer Match Study, which links the US transplant registry with 17 cancer registries (1987 - 2014). PCNSL risk relative to the general population was estimated as a standardized incidence ratio (SIR = observed/expected cases). Poisson regression was used to estimate adjusted incidence rate ratios (aIRR) of PCNSL across subgroups of SOTRs. Logistic regression was used for case-case comparisons of PCNSL with other non-Hodgkin lymphomas (NHL).
Results: We included 288,637 SOTs. There were 173 PCNSL cases (SIR 57.7; 95%CI 49.4-66.9) and 2,583 other NHLs (SIR 7.3; 95%CI 7.0-7.6). Most PCNSL were diffuse large B-cell lymphomas (n=118; 68.2%). Compared to kidney SOTRs, PCNSL risk was lower in liver SOTRs (aIRR 0.5; 95%CI 0.3-0.9), not different in heart and/or lung SOTRs (aIRR 0.9; 95%CI 0.6-1.5) and higher in other/multiple SOTRs (aIRR 2.4; 95%CI 1.5-3.8). Asians/Pacific Islanders had higher PCNSL risk than non-Hispanic whites (aIRR 2.0; 95%CI 1.2-3.3). People who received induction therapy with alemtuzumab (aIRR 2.8; 95%CI 1.5-5.5) or polyclonal antibodies (aIRR 1.9; 95%CI 1.3-2.8) had higher PCNSL risk. SOTRs who were seronegative for Epstein-Barr virus (EBV) at transplant had higher risk (aIRR 2.0; 95%CI 1.1-3.5) than seropositive SOTRs. PCNSL risk was high in the first 1.5 years after SOT (0.5-1 year, aIRR 2.6; 1-1.5 years, aIRR 2.3; vs. 0-0.5 year) and progressively decreased over time (ptrend<0.0001). Risk did not differ according to the age at SOT, sex, or maintenance immunosuppressive regimen. Compared to other NHL, PCNSL cases were more likely to be middle aged (18-64 years) at transplant (p=0.009), Asians/Pacific Islanders (p=0.02), or have received induction therapy with polyclonal antibodies (p=0.002), and less likely to be liver or heart and/or lung SOTRs (p=0.02). EBV serostatus did not differ between PCNSL and other NHL (p=0.11). Conclusions: PCNSL risk is very elevated among SOTRs. Because EBV-seronegative SOTRs are at risk of primary infection after SOT, these results highlight the important contribution of EBV to PCNSL. Risk is highest within 1.5 years after transplant, in people who receive multiple non-thoracic organs, and is associated with induction therapy with alemtuzumab or polyclonal antibodies. Case-case differences with other NHLs suggest unique etiologic factors leading to PCNSL.
Citation Format: Parag Mahale, Meredith S. Shiels, Eric A. Engels. Risk of primary central nervous system lymphomas in solid organ transplant recipients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 273. doi:10.1158/1538-7445.AM2017-273