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Introduction: The diagnosis of a life-threatening disease can lead to depression and anxiety resulting in pharmacological treatment. However, use of psychotropic drugs (antidepressants, anxiolytics, and antipsychotics) in acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) is undetermined.Methods: Prescription of psychotropic drugs in Danish AML and MDS patients was compared to a cohort matched on age, sex, and country of origin from the Danish background population using national population-based registries.Results: In total, 2404 AML patients (median age 69 years) and 1307 MDS patients (median age 75 years) were included and each matched to five comparators from the background population. Two-year cumulative incidences showed that AML (20.6%) and MDS (21.2%) patients had a high risk of redemption of a psychotropic drug prescription compared to the background population (7.0% and 7.9%). High age, low educational level, and Charlson Comorbidity Index score ≥1 was associated with a higher risk in AML and MDS patients. Furthermore, non-curative treatment intent and performance status in AML patients, and high risk MDS were associated with elevated risk of psychotropic drug prescription.Conclusion: In conclusion, diagnoses of AML and MDS were associated with a higher rate of psychotropic drugs prescription compared to the background population.

Introduction: We performed a single-center study of real-world health data to investigate the direct clinical consequence of targeted next-generation sequencing (NGS) results integrated in the clinicopathological evaluation of patients with cytopenia suspected of myelodysplastic syndrome (MDS). Methods: The study included 87 newly referred patients, who had a bone marrow examination, which included targeted NGS analysis. NGS was requested at the discretion of either examining pathologist or hematologist. Data were collected retrospectively from patient files including pathology reports with integrated NGS results. Results: The NGS results had a diagnostic impact in 67 cases (77%) when combining both histopathological and final clinical evaluation and provided prognostic value in 19 cases (22%). NGS supported a confident or tentative histopathological diagnosis in 52 cases (60%). Twenty cases (23%) had a final diagnosis of either Clonal Cytopenia of Undetermined Significance (CCUS) or Idiopathic Cytopenia of Undetermined Significance (ICUS). In 4 cases, NGS results affected the choice of principal treatment strategy, including considerations of allotransplantation. Twenty-one patients (24%) could be discharged to primary care physician. Conclusion: In a multidisciplinary clinicopathological real-world setting, NGS analysis of bone marrow samples from selected patients contributed substantially to the diagnostic evaluation and management of patients with cytopenia suspected of MDS. Consequently, we have now included NGS analysis in most routine bone marrow examinations from patients with MDS or unexplained cytopenia.

Background: The calreticulin (CALR) exon 9 mutations that are identified in 20% of patients with Philadelphia chromosome negative chronic myeloproliferative neoplasms (MPN) generate immunogenic antigens. Thus, therapeutic cancer vaccination against mutant CALR could be a new treatment modality in CALR-mutant MPN. Methods: The safety and efficacy of vaccination with the peptide CALRLong36 derived from the CALR exon 9 mutations was tested in a phase I clinical vaccination trial with montanide as adjuvant. Ten patients with CALRmut MPN were included in the trial and received 15 vaccines over the course of one year. The primary end point was evaluation of safety and toxicity of the vaccine. Secondary endpoint was assessment of the immune response to the vaccination epitope (www.clinicaltrials.gov identifier NCT03566446). Results: Patients had a median age of 59.5 years and a median disease duration of 6.5 years. All patients received the intended 15 vaccines, and the vaccines were deemed safe and tolerable as only two grade three AE were detected, and none of these were considered to be related to the vaccine. A decline in platelet counts relative to the platelets counts at baseline was detected during the first 100 days, however this did not translate into neither a clinical nor a molecular response in any of the patients. Immunomonitoring revealed that four of 10 patients had an in vitro interferon (IFN)-γ ELISPOT response to the CALRLong36 peptide at baseline, and four additional patients displayed a response in ELISPOT upon receiving three or more vaccines. The amplitude of the immune response increased during the entire vaccination schedule for patients with essential thrombocythemia. In contrast, the immune response in patients with primary myelofibrosis did not increase after three vaccines. Conclusion: Therapeutic cancer vaccination with peptide vaccines derived from mutant CALR with montanide as an adjuvant, is safe and tolerable. The vaccines did not induce

In the present study, we quantify the progress in overall survival (OS) during the period 2000-2016 among Danish patients with acute myeloid leukaemia (AML). This population-based study, including 3820 adult patients with AML, demonstrates a significantly improved OS over time with the 2-year age-standardised OS increasing from 22% in 2002 to 31% in 2016. The improvement in OS was exclusively seen in patients with AML aged ≥50 years, with absolute improvements in 2-year OS from 2002 to 2016 of ≥10% among patients aged 50-75 years and a small absolute increase in those aged >75 years.

The prognosis of ipsilateral supraclavicular lymph node recurrence after early breast cancer appears to be worse than for other loco-regional recurrences, but better than for distant metastases. The purpose of the present study was to investigate the relationship between different types of salvage treatment and primary patient characteristics, treatment response, and survival after supraclavicular recurrence (SR) in a large patient population. From the Danish Breast Cancer Cooperative Group treatment database 1977-2003, 305 patients were identified with SR without distant disease as site of first recurrence. Salvage treatment types as well as other factors were related to response and survival. The median follow-up time for progression after SR was 25 months. Complete remission was 76% among patients receiving excision surgery, 67% with combined loco-regional and systemic therapy, and 48% with systemic therapy alone. Median progression-free survival (PFS) and overall survival was 18 and 29 months, respectively. The 5-year PFS probability was 15%. In univariate analysis, combination salvage therapy, negative nodal status and low malignancy grade were related to longer PFS. In multivariate analysis, salvage therapy and malignancy grade remained independent factors for survival. In conclusion, the prognosis of SR is generally poor. However, it appears to be a curable condition. An independent marker of improved outcome is local and systemic combination salvage treatment, which can be considered.

BACKGROUND: Studies have inconsistently reported an association between tobacco smoking and Hodgkin lymphoma (HL) risk. The conflicting finding may reflect etiologic heterogeneity between HL subtypes, warranting further characterization of the relationship. METHODS: We collected information on tobacco-smoking habits in 586 classic HL cases and 3,187 population controls in a Danish-Swedish case-control study. HL EBV status was established for 499 cases by standard techniques. Odds ratios (OR) for an association with cigarette smoking were calculated by logistic regression for HL overall and stratified by age, sex, major histology subtypes, and tumor EBV status, adjusting for known confounders. RESULTS: Compared with never smokers, current cigarette smokers were at an increased overall HL risk [adjusted OR, 1.57; 95% confidence interval (95% CI), 1.22-2.03]. The association was strongest for EBV-positive HL (adjusted OR, 2.36; 95% CI, 1.51-3.71), but also applied to EBV-negative HL (adjusted OR, 1.43; 95% CI, 1.05-1.97; P(homogeneity EBV-pos) versus P(homogeneity EBV-neg) = 0.04). The association did not vary appreciably by age, sex, or histologic subtype, the apparent EBV-related difference present in all strata. There was no evidence of a dose-response pattern, whether by age at smoking initiation, daily cigarette consumption, number of years smoking, or cumulative number of cigarettes smoked. Similar results were obtained in analyses using non-HL patients (n = 3,055) participating in the founding study as comparison group. CONCLUSION: The observed association between cigarette smoking and HL risk is consistent with previous findings and biologically credible. Although not easily dismissed as an artifact, the limited evidence of a dose-response pattern renders the overall evidence of causality weak.

Background: Studies have inconsistently reported an association between tobacco smoking and Hodgkin lymphoma (HL) risk. The conflicting finding may reflect etiologic heterogeneity between HL subtypes, warranting further characterization of the relationship. Methods: We collected information on tobacco-smoking habits in 586 classic HL cases and 3,187 population controls in a Danish-Swedish case-control study. HL EBV status was established for 499 cases by standard techniques. Odds ratios (OR) for an association with cigarette smoking were calculated by logistic regression for HL overall and stratified by age, sex, major histology subtypes, and tumor EBV status, adjusting for known confounders. Results: Compared with never smokers, current cigarette smokers were at an increased overall HL risk [adjusted OR, 1.57; 95% confidence interval (95% CI), 1.22-2.03]. The association was strongest for EBV-positive HL (adjusted OR, 2.36; 95% CI, 1.51-3.71), but also applied to EBV-negative HL (adjusted OR, 1.43; 95% CI, 1.05-1.97; Phomogeneity EBV-pos versus Phomogeneity EBV-neg = 0.04). The association did not vary appreciably by age, sex, or histologic subtype, the apparent EBV-related difference present in all strata. There was no evidence of a dose-response pattern, whether by age at smoking initiation, daily cigarette consumption, number of years smoking, or cumulative number of cigarettes smoked. Similar results were obtained in analyses using non-HL patients (n = 3,055) participating in the founding study as comparison group. Conclusion: The observed association between cigarette smoking and HL risk is consistent with previous findings and biologically credible. Although not easily dismissed as an artifact, the limited evidence of a dose-response pattern renders the overall evidence of causality weak.

Udgivelsesdato: 2007

The reasons for the positive association between skin cancer and non-Hodgkin's lymphoma are not known but may be due to common susceptibility involving suboptimal DNA repair. Therefore, we investigated selected polymorphisms and haplotypes in three DNA repair genes, previously associated with skin cancer and DNA repair capacity, in risk of follicular lymphoma, including possible gene interaction with cigarette smoking and sun exposure. We genotyped 19 single nucleotide polymorphisms (SNP) in the ERCC2, XRCC1, and XRCC3 genes in 430 follicular lymphoma patients and 605 controls within a population-based case-control study in Denmark and Sweden. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using unconditional logistic regression and haplotype associations were assessed with a global score test. We observed no associations between variation in the ERCC2 and XRCC1 genes and follicular lymphoma risk. In XRCC3, increased risk of follicular lymphoma was suggested for rare homozygotes of three SNPs [Rs3212024: OR, 1.8 (95% CI, 1.1-2.8); Rs3212038: OR, 1.5 (95% CI, 1.0-2.4); Rs3212090: OR, 1.5 (95% CI, 1.0-2.5)]. These results were strengthened in current cigarette smokers. However, evidence of differences in XRCC3 haplotype distributions between follicular lymphoma cases and controls was weak, both overall and in current smokers. We conclude that polymorphic variation in the XRCC3 gene, but not in ERCC2 or XRCC1, may be of importance for susceptibility to follicular lymphoma, perhaps primarily in current smokers. The link between skin cancer and follicular lymphoma is unlikely to be mediated through common variation in the studied DNA repair gene polymorphisms.