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Clonal hematopoiesis of indeterminate potential (CHIP) is suspected of being a risk factor for patients with cancer. This study aimed to assess the clinical consequences of CHIP in patients with lymphoma intended for high-dose chemotherapy and autologous stem-cell transplantation (ASCT) in a population-based setting. We identified 892 lymphoma patients who had undergone stem cell harvest at all transplant centers in Denmark. A total of 565 patients had an available harvest sample, which was analysed for CHIP by next-generation sequencing, and the median follow-up was 9.1 years. Of the patients who were intended for immediate ASCT, 25.5% (112/440) carried at least one CHIP mutation. In contrast to previous single-center studies CHIP was not associated with inferior overall survival (OS) in multivariate analyses. However, patients with mutations in genes of the DNA repair pathway (PPM1D, TP53, RAD21, BRCC3) had a significant inferior OS (HR after 1 year of follow-up 2.79, 95% confidence interval 1.71–4.56; p < 0.0001), which also was evident in multivariate analysis (p = 0.00067). These patients had also increased rates of therapy-related leukemia and admission to intensive care. Furthermore, in patients who did not undergo immediate ASCT, a significant inferior OS of individuals with DNA repair mutations was also identified (p = 0.003).

The Danish National Lymphoma Register (LYFO) prospectively includes information on all lymphoma patients newly diagnosed at hematology departments in Denmark. The validity of the clinical information in the LYFO has never been systematically assessed. To test the coverage and data quality of the LYFO. The coverage was tested by merging data of the LYFO with the Danish Cancer Register and the Danish National Patient Register, respectively. The validity of the LYFO was assessed by crosschecking with information from medical records in subgroups of patients. A random sample of 3% (N = 364) was made from all patients in the LYFO. In addition, four subtypes of lymphomas were validated: CNS lymphomas, diffuse large B-cell lymphomas, peripheral T-cell lymphomas, and Hodgkin lymphomas. A total of 1,706 patients from the period 2000-2012 were included. The positive predictive values (PPVs) and completeness of selected variables were calculated for each subgroup and for the entire cohort of patients. The comparison of data from the LYFO with the Danish Cancer Register and the Danish National Patient Register revealed a high coverage. In addition, the data quality was good with high PPVs (87% to 100%), and high completeness (92% to 100%). The LYFO is a unique, nationwide clinical database characterized by high validity, good coverage and prospective data entry. It represents a valuable resource for future lymphoma research.

The Danish National Lymphoma Registry (LYFO) was established in order to monitor and improve the diagnostic evaluation and the quality of treatment of all lymphoma patients in Denmark. The LYFO database was established in 1982 as a seminational database including all lymphoma patients referred to the departments of hematology. The database became nationwide on January 1, 2000. The main variables include both clinical and paraclinical variables as well as details of treatment and treatment evaluation. Up to four forms are completed for each patient: a primary registration form, a treatment form, a relapse form, and a follow-up form. Variables are used to calculate six result quality indicators (mortality 30 and 180 days after diagnosis, response to first-line treatment, and survival estimates 1, 3, and 5 years after the time of diagnosis), and three process quality indicators (time from diagnosis until the start of treatment, the presence of relevant diagnostic markers, and inclusion rate in clinical protocols). Approximately 23,000 patients were registered in the period 1982-2014 with a median age of 65 years (range: 16-100 years) and a male/female ratio of 1.23:1. Patients can be registered with any of 42 different subtypes according to the World Health Organization classifications. LYFO is a nationwide database for all lymphoma patients in Denmark and includes detailed information. This information is used for both epidemiological research and clinical follow-up as well as for administrative purposes.

High-dose chemotherapy with autologous stem cell transplantation (ASCT) is considered to be the only curative treatment option for patients with refractory or relapsed diffuse large B-cell lymphoma (DLBCL). Due to toxicity, not all patients are eligible for this treatment leading to different treatment intensities. Here, we aim to analyze the impact of treatment intensity on survival in patients previously treated with rituximab and chemotherapy, and, furthermore, to analyze the association between socioeconomic position and treatment intensity, defined as palliation, non-salvage, and salvage regimens. We identified patients with refractory or relapsed DLBCL diagnosed in 2000-2015 in the Danish National Lymphoma Registry (n=1,228). We analyzed the impact of treatment intensity on survival in patients previously treated with rituximab (n=277) using a Cox proportional hazards model. Multinomial regression analyses were performed to identify associations between socioeconomic factors and treatment intensity for the entire cohort. In the rituximab era, the 5-year overall survival (OS) was 31% for patients receiving salvage regimens (n=194), and 17% for patients receiving non-salvage regimens (n=83). In the adjusted analysis, HR was 1.88, 95% CI: 0.9-3.9 for patients receiving salvage regimens. Patients living alone were significantly less likely to receive salvage regimens, as were patients with two or more comorbidities. We observed a better OS in patients treated with salvage regimens compared with non-salvage regimens; however, the adjusted analysis contradicts this. Furthermore, our results indicate that there is a chance of remission for patients not eligible for ASCT.

Autologous stem cell transplantation (ASCT) is the standard treatment for patients with relapsed diffuse large B-cell lymphoma (DLBCL) or transformed indolent lymphoma (TIL). The treatment is mainly considered for younger patients still available for the work market. In this study, social outcomes after ASCT in terms of return to work (RTW) are described. Information from national administrative registers was combined with clinical information on patients, who received ASCT for relapse of DLBCL or TIL between 2000 and 2012. A total of 164 patients were followed until RTW, disability or old-age pension, death, or December 31, 2015, whichever came first. A total of 205 patients were followed with disability pension as the event of interest. Cox models were used to determine cause-specific hazards. During follow-up, 82 (50%) patients returned to work. The rate of returning to work in the first year following ASCT was decreased for patients being on sick leave at the time of relapse (hazard ratio [HR] 0.3 [0.2;0.5]) and increased for patients aged ≥55 years (HR 1.9 [1.1;3.3]). In all, 56 (27%) patients were granted disability pension. Being on sick leave at the time of relapse was positively associated with receiving a disability pension in the first 2 years after ASCT (HR 3.7 [1.8;7.7]). Patients on sick leave at the time of relapse have a poorer prognosis regarding RTW and have a higher rate of disability pension. Furthermore, patients >55 are more likely to RTW compared to younger patients. These results indicate an unmet need for focused social rehabilitation.

Recently, β-blockers have been suggested as a potential maintenance treatment option for asthma. The aim of this review is to provide an overview of the current knowledge of the potential benefits and risks of β-blocker therapy for asthma. Systematic literature review. No significant increase in the number of patients requiring rescue oral corticosteroid for an exacerbation of asthma has been observed after initiation of β-blocker treatment. Patients with mild to moderate reactive airway disease, probably both asthma and chronic obstructive pulmonary disease, may have a limited fall in forced expiratory volume in 1 second (FEV1) following single-dose administration of β-blocker, whereas no change in FEV1 has been reported following long-term administration. In a murine model of asthma, long-term administration of β-blockers resulted in a decrease in airway hyperresponsiveness, suggesting an anti-inflammatory effect. In keeping with this, long-term administration of a nonselective β-blocker to steroid-naïve asthma patients has shown a dose-dependent improvement in airway hyperresponsiveness, and either an asymptomatic fall in FEV1 or no significant change in FEV1. Furthermore, available studies show that bronchoconstriction induced by inhaled methacholine is reversed by salbutamol in patients on regular therapy with a β-blocker. On the other hand, a recent placebo-controlled trial of propranolol and tiotropium bromide added to inhaled corticosteroids revealed no effect on airway hyperresponsiveness and a small, not statistically significant, fall in FEV1 in patients classified as having mild to moderate asthma. The available, although limited, evidence suggests that a dose-escalating model of β-blocker therapy to patients with asthma is well tolerated, does not induce acute bronchoconstriction, and, not least, may have beneficial effects on airway inflammation and airway hyperresponsiveness in some patients with asthma. Further studies addressing the potential role of β-blocker therapy for asthma are clearly needed, but careful selection of the target population is warranted.