Cardiovascular diseases after high-dose chemotherapy and autologous stem cell transplant for lymphoma: A Danish population-based study.

Cardiovascular diseases, especially congestive heart failure (CHF), are known complications of anthracyclines, but the risk for patients undergoing high-dose chemotherapy and autologous stem cell transplant (HDT-ASCT) is not well established. With T-cell therapies emerging as alternatives, studies of long-term complications after HDT-ASCT are warranted. Danish patients treated with HDT-ASCT for aggressive lymphoma between 2001 and 2017 were matched 1:5 on sex, birth year and Charlson comorbidity score to the general population. Events were captured using nationwide registers. A total of 787 patients treated with HDT-ASCT were identified. Median follow-up was 7.6 years. The risk of CHF was significantly increased in the HDT-ASCT population compared to matched comparators with an adjusted hazard ratio (HR) of 5.5 (3.8-8.1). The 10-year cumulative incidence of CHF was 8.0% versus 2.0% (p < 0.001). Male sex, ≥2 lines of therapy, hypertension and cumulative anthracycline dose (≥300 mg/m2 ) were risk factors for CHF. In a separate cohort of 4089 lymphoma patients, HDT-ASCT was also significantly associated with increased risk of CHF (adjusted HR of 2.6 [1.8-3.8]) when analysed as a time-dependent exposure. HDT-ASCT also increased the risk of other cardiac diseases. These findings are applicable for the benefit/risk assessment of HDT-ASCT versus novel therapies.

Coronary artery calcium in patients with schizophrenia.

BACKGROUND: Coronary heart disease (CHD) is a major cause of increased mortality rates in patients with schizophrenia. Moreover, coronary artery calcium (CAC) score is associated with CHD. We hypothesized that patients with schizophrenia have more CAC than the general population and aimed to investigate the CAC score in patients with schizophrenia compared to norms based on the general population. Additionally, this study investigated if age, sex, diabetes, dyslipidemia and smoking were associated with the CAC score. METHODS: In a cross-sectional study, 163 patients with schizophrenia underwent cardiac computed tomography, and the CAC score was measured and compared to norms by classifying the CAC scores in relation to the age- and gender matched norm 50th, 75th and 90th percentiles. Logistic and linear regression were carried out to investigate explanatory variables for the presence and extent of CAC, respectively. RESULTS: A total of 127 (77.9%) patients had a CAC score below or equal to the matched 50th, 20 (12.3%) above the 75th and nine (5.5%) above the 90th percentile. Male sex (P < 0.05), age (P < 0.001) and smoking (P < 0.05) were associated with the presence of CAC while age (P < 0.001) and diabetes (P < 0.01) were associated with the extent of CAC. CONCLUSIONS: The amount of CAC in patients with schizophrenia follows norm percentiles, and variables associated with the CAC score are similar in patients with schizophrenia and the general population. These findings indicate that the CAC score may not be sufficient to detect the risk of CHD in patients with schizophrenia. Future studies should explore other measures of subclinical CHD, including measures of peripheral atherosclerosis or cardiac autonomic neuropathy to improve early detection and intervention. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02885792 , September 1, 2016.

Second primary malignancies in patients with lymphoma in Denmark after high-dose chemotherapy and autologous haematopoietic stem-cell transplantation: a population-based, retrospective cohort study.

BACKGROUND: Second primary malignancies (SPMs) are known complications after chemotherapy, but the risk is not well characterised for patients with lymphoma treated with high-dose chemotherapy and autologous haematopoietic stem-cell transplantation (HSCT). We aimed to investigate the rate of SPMs in this population relative to matched control individuals from the general population. METHODS: In this retrospective, population-based cohort study, patients aged 18 years or older with an aggressive lymphoma who received high-dose chemotherapy and autologous HSCT in Denmark between Jan 1, 2001, and Dec 31, 2017, were included from the Danish Lymphoma Registry and matched (1:5) to control individuals from the general population on birth year and sex via the Danish Civil Registration System. Patients were eligible if they had a registered date of autologous HSCT and patients with primary CNS lymphoma were excluded. Exclusion criteria for both patients and matched control individuals were HIV infection, organ transplantation, or other malignancies before inclusion. The key endpoint was the incidence of SPMs assessed in all study participants. The effect of treatment on SPMs was also investigated in patients who were followed up from first lymphoma diagnosis, with high-dose chemotherapy and autologous HSCT as a time-dependent exposure. FINDINGS: Of 910 patients with lymphoma assessed, 803 were included (537 [67%] were male and 266 [33%] were female); 4015 matched control individuals were included (2685 [67%] were male and 1330 [33%] were female). Ethnicity data were not available. Median follow-up was 7·76 years (IQR 4·77-11·73). The SPM rate was higher among patients receiving high-dose chemotherapy and autologous HSCT than matched control individuals (adjusted hazard ratio [HR] 2·35, 95% CI 1·93-2·87, p<0·0001). Patients receiving high-dose chemotherapy and autologous HSCT had a higher rate of non-melanoma skin cancer (2·94, 2·10-4·11, p<0·0001) and of myelodysplastic syndrome or acute myeloid leukaemia (AML; 41·13, 15·77-107·30, p<0·0001) than matched control individuals, but there was no significant difference in the rate of solid tumours (1·21, 0·89-1·64, p=0·24). The cumulative risk of SPMs at 10 years was 20% (95% CI 17-23) in patients compared with 14% (13-15) in matched control individuals. High-dose chemotherapy and autologous HSCT was associated with an increased risk of SPMs when analysed as a time-dependent exposure from first lymphoma diagnosis (adjusted HR 1·58, 95% CI 1·14-2·17, p=0·0054). INTERPRETATION: High-dose chemotherapy and autologous HSCT was associated with an increased risk of non-melanoma skin cancer and myelodysplastic syndrome or AML but not with increased risk of solid tumours in patients treated for lymphoma. These findings are relevant for future individualised risk-benefit assessments when choosing between high-dose chemotherapy and autologous HSCT and chimeric antigen receptor T-cell therapy in this setting. FUNDING: Danish Cancer Society.

[Calcium scoring and cardiovascular risk assessment in patients with schizophrenia].

Coronary artery disease is a major contributor to increased mortality rates in patients with schizophrenia in whom less treatment of cardiovascular (CV) risk factors is seen. Risk prediction models used in the general population are not sufficient to predict CV mortality in patients with schizophrenia. Measurement of calcium score (CACS) by cardiac CT-scan improves risk prediction in the general population, but has not been investigated in patients with schizophrenia. CACS might contribute to improved CV risk assessment and treatment in these patients and further studies should address this.