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The Risk and Timing of Hematologic Malignancy Following Solid Organ Transplant Open Access

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Purpose: To develop a better understanding of the risk and timing of hematologic malignancy (HM) following solid organ transplantation. Methods: To examine the association between specific HM subtypes and solid organ transplantation we conducted a population-based case-control study using the Surveillance, Epidemiology, and End Results-Medicare linked database. The prevalence of solid organ transplant history was compared between HM subtypes and frequency-matched controls using polytomous logistic regression. To compare the characteristics and risk factors between early-onset and late-onset post-transplant lymphoproliferative disorder (PTLD) we conducted a retrospective cohort study of U.S. kidney recipients using data from the Scientific Registry of Transplant Recipients. Hazard ratios (HRs) for risk factors for early-onset and late-onset PTLD were estimated using proportional hazards models. Results: In the U.S. elderly population, transplantation was associated with increased risk for non-Hodgkin lymphoma (NHL, OR=2.13, 95%CI 1.67-2.72), especially diffuse large B-cell lymphoma (OR=3.29, 95%CI 2.28-4.76), the most common NHL subtype; marginal zone (OR=2.48, 95%CI 1.17-5.22), lymphoplasmacytic (OR=3.32, 95%CI 1.41-7.81), and T-cell lymphoma (OR=3.07, 95%CI 1.56-6.06). Transplantation was also associated with Hodgkin lymphoma (OR=2.53, 95%CI 1.01-6.35), plasma-cell (OR=1.91, 95%CI 1.24-2.93) and myeloid neoplasms (OR=1.99, 95%CI 1.41-2.81). For early-onset PTLD, significantly increased risk was associated with young age at transplantation (HR 3.97 for <20 vs. 20-50 years), non-Hispanic white race/ethnicity (HR 1.82, vs. other races/ethnicities), and glomerular disease, tubular/interstitial disease, or malignancy leading to kidney transplant (HRs 1.57, 1.71, and 4.38, respectively, vs. hypertensive nephrosclerosis), while EBV and CMV seropositivity at transplantation decreased risk (HR 0.32 and 0.67, respectively). Late-onset PTLD risk was associated with younger and older age (HR 2.68 and 1.28 for <20 and >50 respectively, vs. 20-50 years) and non-Hispanic white race/ethnicity (HR 1.77, vs. other races/ethnicities).Conclusion: Solid organ transplantation is associated with the increased risk of a wide spectrum of HMs in the elderly. The increased risk is not confined to the period immediately following transplantation, but extends for many years thereafter. The characteristics and risk factors for malignancies that occur shortly after transplantation are different from those that occur later. Our results support monitoring for a wide spectrum of HM for many years following solid organ transplantation.

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