Caspar da Cunha-Bang

Factors associated with the development of cytomegalovirus infection following solid organ transplantation

Abstract Background: Infection with cytomegalovirus (CMV) remains a potentially serious complication in transplant patients. In this study we explored the risk factors for CMV infection in the 12 months following a solid organ transplantation (n = 242) in patients monitored for CMV infection from 2004 to 2007. Methods: CMV infection was defined as 2 consecutive quantifiable CMV-polymerase chain reaction (PCR) values or 1 measurement of >3000 copies/ml. Data describing pre- and post-transplantation variables were extracted from electronic health records. Time to CMV infection was investigated using Cox proportional hazards analysis. Results: Overall, 31% (75/242) of solid organ transplant patients developed CMV infection: 4/8 (50.0%) heart, 15/43 (34.9%) liver, 30/89 (33.7%) lung and 26/102 (25.5%) kidney transplant patients. The risk of CMV infection according to donor (D)/recipient (R) CMV serostatus (positive + or negative−) was highest for D+/R−(adjusted hazard ratio 2.6, 95% confidence interval 1.6–4.2) vs D+/R+, and was reduced for D−/R+(adjusted hazard ratio 0.2, 95% confidence interval 0.2–0.8) vs D+/R+. Conclusion: Positive donor CMV-serostatus is a major risk factor for CMV-infection in CMV-na ve recipients, but also in recipients with positive CMV-serostatus. Conversely, if donor is CMV serostatus is negative, the risk of CMV infection is low, irrespective of recipients CMV-serostatus. These findings suggest poorer immune function towards donor-induced strains of CMV versus recipient own latent strains.

The Danish National Chronic Lymphocytic Leukemia Registry

Aim In 2008, the Danish National Chronic Lymphocytic Leukemia Registry was founded within the Danish National Hematology Database. The primary aim of the registry is to assure quality of diagnosis and care of patients with chronic lymphocytic leukemia (CLL) in Denmark. Secondarily, to evaluate adherence to national guidelines and to provide source data for research purposes. Study population All patients diagnosed with CLL in Denmark from 2008 onward are included in the registry. Patients are followed in one of nine hematology centers. All centers participate in the registry and are all obliged to collect data. Main variables Predefined data are collected at the time of diagnosis, and follow-up at the time of significant events: treatment, progression, transplantation, and death. Parameters included in the International Workshop on Chronic Lymphocytic Leukaemia criteria for diagnosis, and for decision on treatment initiation as well as characteristics included in the CLL International Prognostic Index are collected. Descriptive data To ensure full coverage of Danish CLL patients in the registry, both continuous queries in case of missing data, and cross-referencing with the Danish National Patient Registry are performed. Data from the registry are published in an annual report summarizing the collected data, the overall survival for yearly cohorts, and the degree of data coverage. Per year approximately 450 new patients with CLL are registered in the registry, cumulative as of July 1, 2015, 3,082 patients have been registered. Conclusion The Danish National CLL Registry is based within the Danish National Hematology Database. The registry covers a cohort of all patients diagnosed with CLL in Denmark since 2008. It forms the basis for quality assessment of CLL treatment in Denmark and offers a unique opportunity for population-based research.

Incidence and predictors of infection among patients prior to treatment of chronic lymphocytic leukemia: a Danish nationwide cohort study

With the international prognostic index for patients with chronic lymphocytic leukemia (CLL-IPI), we have a tool to identify patients with a high risk of progression. Despite improved supportive care, infections are a significant cause of morbidity and mortality prior to treatment; one third of patients with CLL will die following an infection. Though infections in CLL patients have been a subject of interest in many studies, reporting incidences between 0.13-0.19 per patient-year, there is still no consensus on how to identify patients who are at an increased risk of infection. Studies on infectious risk prior to treatment in CLL are scarce and very heterogeneous in terms of study populations. Consequently, the identification of prognostic markers for risk of infections are warranted. Infections in patients with CLL are believed to correlate with the progressive immune dysfunction. The progressive immune dysfunction in CLL is characterized by a cell-mediated and an antibody-mediated dysfunction. The CLL-microenvironmental interaction may play a major role in this progressive immune dysfunction. The neoplastic B cells co-evolve together with the microenvironmental changes, which promotes the leukemia cell survival and growth while inhibiting normal B-cell and T-cell function as well as causing hypogammaglobulinemia and cytokine changes. The rate, severity and prognostic factors for infections in CLL prior to treatment constitute a gap in our knowledge of the infection-prone nature of CLL. By means of the unique Danish National CLL registry, a nationwide cohort of all patients diagnosed with CLL in Denmark between 2008 and 2016, and a national Danish Microbiology database, we conducted a retrospective study to address this issue. All patients diagnosed with CLL in Denmark between January 1 2010 and July 1 2016, which was also the end of follow-up, were included. The CLL-IPI variables and data on treatment and survival were retrieved from the Danish National CLL registry. Information on immunoglobulin levels was included if data were available within six months of diagnosis. Information on blood cultures was retrieved from the Danish Microbiology Database. The event of the first blood culture prior to CLL therapy was used as a proxy for severe infection, regardless of whether an infectious agent was identified. The time to event was calculated from the date of diagnosis or the first date of the measurement of immunoglobulin at or after diagnosis, whichever came last. Patients were followed until the date of infection, initiation of CLL-specific treatment, death or end of follow-up, whichever came first. Estimates of cumulative incidence for each of the competing risks were calculated using the AalenJohansen estimator. We examined the difference in the cumulative incidence of infection using Gray’s test. We fitted a cause-specific hazard model and a Fine-Gray model. All models were compared to the non-parametric