Summary Incidence of post-transplant lymphoproliferative disorder (PTLD) is bimodal, suggesting distinct early-onset and late-onset subtypes. We evaluated differences in risk factors for early-onset and late-onset PTLD in a retrospective cohort study of U.S. kidney transplant recipients using data from the Scientific Registry of Transplant Recipients (N=156,740, 1999–2007). Multivariate hazard ratios (HRs) for risk factors were estimated using proportional hazards models. 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), and seronegativity for Epstein Barr virus (EBV) and cytomegalovirus at transplantation (HRs 3.13 and 1.49, respectively). By comparison, younger and older age (HRs 2.68 and 1.28 for <20 and >50, respectively, vs. 20–50 years) and non-Hispanic white race/ethnicity (HR 1.77) increased late-onset PTLD risk. The association with young age was weaker for late-onset than early-onset PTLD (p=0.06), and EBV and cytomegalovirus serostatus were not associated with late-onset PTLD risk. These results support somewhat different etiologies for early-onset and late-onset PTLD. For early-onset PTLD, associations with young age and EBV seronegativity highlight the etiologic role of primary EBV infection. For late-onset PTLD, higher risk with older age is consistent with lymphoma patterns in the general population.

OBJECTIVEThis trial tested whether mycophenolate mofetil (MMF) alone or with daclizumab (DZB) could arrest the loss of insulin-producing β-cells in subjects with new-onset type 1 diabetes.RESEARCH DESIGN AND METHODSA multi-center, randomized, placebo-controlled, double-masked trial was initiated by Type 1 Diabetes TrialNet at 13 sites in North America and Europe. Subjects diagnosed with type 1 diabetes and with sufficient C-peptide within 3 months of diagnosis were randomized to either MMF alone, MMF plus DZB, or placebo, and then followed for 2 years. The primary outcome was the geometric mean area under the curve (AUC) C-peptide from the 2-h mixed meal tolerance test.RESULTSOne hundred and twenty-six subjects were randomized and treated during the trial. The geometric mean C-peptide AUC at 2 years was unaffected by MMF alone or MMF plus DZB versus placebo. Adverse events were more frequent in the active therapy groups relative to the control group, but not significantly.CONCLUSIONSNeither MMF alone nor MMF in combination with DZB had an effect on the loss of C-peptide in subjects with new-onset type 1 diabetes. Higher doses or more targeted immunotherapies may be needed to affect the autoimmune process.

Background: By assessing the spectrum of hematologic malignancies associated with solid-organ transplantation in the elderly, we provide information on the pathogenesis of lymphoid and myeloid neoplasms and the clinical manifestations of immunosuppression.Methods: Using data from the U.S. Surveillance, Epidemiology, and End Results Medicare database, we identified 83,016 cases with a hematologic malignancy (age 66-99 years) and 166,057 population-based controls matched to cases by age, sex, and calendar year. Medicare claims were used to identify a history of solid-organ transplantation. We used polytomous logistic regression to calculate odds ratios (OR) comparing transplantation history among cases with various hematologic malignancy subtypes and controls, adjusting for the matching factors and race.Results: A prior solid-organ transplant was identified in 216 (0.26%) cases and 204 (0.12%) controls. Transplantation was associated with increased risk for non-Hodgkin lymphomas [OR, 2.13; 95% confidence interval (95% CI), 1.67-2.72], especially diffuse large B-cell lymphoma (OR, 3.29; 95% CI, 2.28-4.76), marginal zone lymphoma (OR, 2.48; 95% CI, 1.17-5.22), lymphoplasmacytic lymphoma (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 elevated risk of Hodgkin lymphoma (OR, 2.53; 95% CI, 1.01-6.35) and plasma cell neoplasms (OR, 1.91; 95% CI, 1.24-2.93). Risks for myeloid neoplasms were also elevated (OR, 1.99; 95% CI, 1.41-2.81).Conclusion: Solid-organ transplantation is associated with a wide spectrum of hematologic malignancies in the elderly. Risk was increased for four specific non-Hodgkin lymphoma subtypes for which a viral agent has been implicated, supporting an added role for immunosuppression.Impact: Our results support monitoring for a wide spectrum of hematologic malignancies following solidorgan transplant. Cancer Epidemiol Biomarkers Prev; 19(5); 1229-37. ©2010 AACR.

Study ObjectiveTo estimate the incidence and relative risk of a hospitalization or emergency visit for noninfectious liver injury in users of eight oral antimicrobials—amoxicillin, amoxicillin-clavulanic acid, clarithromycin, cefuroxime, doxycycline, levofloxacin, moxifloxacin, telithromycin—compared with nonusers of these antimicrobials.DesignRetrospective, observational cohort study with a nested case-control analysis.Data SourceHealthCore Integrated Research Database.PatientsAdults with continuous health plan enrollment for at least 6 months before study entry who had a new dispensing of a study antimicrobial between July 1, 2001, and March 31, 2009. Cases had diagnoses indicating noninfectious liver injury during follow-up. To control for potentially confounding risk factors, 10 controls at risk for liver injury during follow-up were matched to each case by age, sex, and event date (liver injury date of the case), and analyses were adjusted for medical history, concomitant drugs, and health care service use.Measurements and Main ResultsTwo physician reviewers (blind to exposure) validated the cases. Among 1.3 million antimicrobial users, we identified 607 cases of liver injury, including 82 cases of severe hepatocellular injury and 11 cases of liver failure. Liver injury incidence in nonusers of study antimicrobials was 35/100,000 person-years (95% confidence interval [CI] 29–42/100,000 person-years). For valid cases, the adjusted relative risk among current users of multiple antimicrobials was 3.2 (95% CI 1.6–6.7). Levofloxacin had the highest relative risk for current single use (3.2, 95% CI 1.8–5.8). Relative risks were also elevated for amoxicillin-clavulanic acid (2.5, 95% CI 1.3–5.0), doxycycline (2.5, 95% CI 1.2–5.2), moxifloxacin (2.3, 95% CI 1.1–4.7), and amoxicillin (2.3, 95% CI 1.1–4.7).ConclusionThe results support a comparatively high adjusted relative risk of liver injury among patients exposed concurrently to multiple antimicrobials and modest elevations in the risk for several antimicrobials used alone; however, we found little evidence of any strong effect of commonly used antimicrobials on the risk of liver injury.

Background To assess the risk and identify risk factors of Hodgkin lymphoma (HL) in solid organ transplant recipients. Prior research has been limited by the rarity of HL and the requirement for extended follow-up after transplantation. Methods Using data from the Scientific Registry of Transplant Recipients (SRTR), we conducted a retrospective cohort study of U.S. solid organ transplant recipients (1997–2007). We estimated hazard ratios (HRs) for HL risk factors using proportional hazards regression. Standardized incidence ratios (SIRs) compared HL risk in the transplant cohort with the general population. Results The cohort included 283,190 transplant recipients (average follow-up 3.7 years after transplantation). Based on 73 cases, HL risk factors included male gender (HR 2.1, 95%CI 1.2–3.7), young age (4.0, 2.3–6.8), and EBV seronegativity at the time of transplantation (3.1, 1.2–8.1). Among tumors with EBV status information, 79% were EBV positive, including all tumors in recipients who were initially seronegative. Overall, HL risk was higher than in the general population (SIR 2.2) and increased monotonically over time following transplantation (SIR 4.1 at 8–10 years post-transplant). Excess HL risk was especially high following heart and/or lung transplantation (SIR 3.2). Conclusion HL is a late complication of solid organ transplantation. The high HL risk in recipients who were young or EBV seronegative at the time of transplant, and the fact that most HL tumors were EBV positive, highlight the role of primary EBV infection and poor immune control of this virus. The occurrence of HL may rise with improved long-term survival in transplant recipients.