Background: Risk of primary central nervous system lymphoma (PCNSL) is greatly increased in immunosuppressed HIV-infected people. Case series describe PCNSL in 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 (aIRRs) of PCNSL across subgroups of SOTRs. Logistic regression was used for case-case comparisons of PCNSL with other non-Hodgkin lymphomas (NHLs).

Results: We included 288,637 SOTs. There were 173 PCNSL cases (SIR 57.7; 95%CI 49.4-66.9) and 2583 other NHL (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 (0.9; 0.6-1.5) and higher in other/multiple SOTRs (2.4; 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 (1.9; 1.3-2.8) had higher PCNSL risk. SOTRs 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 increased sharply 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 subsequently decreased over time (ptrend<0.0001). Risk did not differ according to 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 polyclonal antibody induction (p=0.002), and less likely to be liver or heart and/or lung SOTRs (p=0.02).

Conclusions: PCNSL risk is very elevated in 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 SOT, in people who receive multiple non-thoracic organs, and associated with induction therapy with alemtuzumab or polyclonal antibodies. Case-case differences with other NHL suggest unique etiologic factors leading to PCNSL.

CITATION INFORMATION: Engels E, Mahale P, Shiels M. Risk of Primary Central Nervous System Lymphoma in Solid Organ Transplant Recipients. Am J Transplant. 2017;17 (suppl 3).

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