Secondary and therapy-related acute myeloid leukemia (sAML and tAML, respectively) remain therapeutic challenges. Still, it is unclear whether their inferior outcome compared with de novo acute ...myeloid leukemia (AML) varies as a result of previous hematologic disease or can be explained by differences in karyotype and/or age.
In a Danish national population-based study of 3,055 unselected patients with AML diagnosed from 2000 to 2013, we compared the frequencies and characteristics of tAML, myelodysplastic syndrome (MDS) -sAML, and non-MDS-sAML (chronic myelomonocytic leukemia and myeloproliferative neoplasia) versus de novo AML. Limited to intensive therapy patients, we compared chance of complete remission by logistic regression analysis and used a pseudo-value approach to compare relative risk (RR) of death at 90 days, 1 year, and 3 years, overall and stratified by age and karyotype. Results were given crude and adjusted with 95% CIs.
Overall, frequencies of sAML and tAML were 19.8% and 6.6%, respectively. sAML, but not tAML, was associated with low likelihood of receiving intensive treatment. Among intensive therapy patients (n = 1,567), antecedent myeloid disorder or prior cytotoxic exposure was associated with decreased complete remission rates and inferior survival (3-year adjusted RR for MDS-sAML, non-MDS-sAML, and tAML: RR, 1.14; 95% CI, 1.02 to 1.32; RR, 1.27; 95% CI, 1.16 to 1.34; and RR, 1.16; 95% CI, 1.03 to 1.32, respectively) compared with de novo AML. Among patients ≥ 60 years old and patients with adverse karyotype, previous MDS or tAML did not impact overall outcomes, whereas non-MDS-sAML was associated with inferior survival across age and cytogenetic risk groups (adverse risk cytogenetics: 1-year adjusted RR, 1.47; 95% CI, 1.23 to 1.76; patients ≥ 60 years old: 1-year adjusted RR, 1.31; 95% CI, 1.06 to 1.61).
Our results support that de novo AML, sAML, and tAML are biologically and prognostically distinct subtypes of AML. Patients with non-MDS-sAML have dismal outcomes, independent of age and cytogenetics. Previous myeloid disorder, age, and cytogenetics are crucial determinants of outcomes and should be integrated in treatment recommendations for these patients.
Changes in acute myeloid leukaemia (AML) treatment may affect requirement for admission to and treatments in intensive care units (ICUs). We evaluated trends in ICU admission, use of organ support, ...and 1-year mortality in Danish AML patients. Of 1417 AML patients diagnosed 2005-2016, 28.0% (n=397) were ICU-admitted within 3 years, with no major change in admission rate during the 12-year period. Use of mechanical ventilation and dialysis decreased (66.7% to 40.6%), while use of non-invasive ventilation increased (20.0% to 50.0%). Concurrently, 1-year mortality declined among all patients (36.0% in 2005 to 28.8% in 2016) and ICU-admitted patients (80.0% to 65.6%).
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Monocytosis (≥0.5 × 109/L in peripheral blood) is the hallmark of chronic myelomonocytic leukaemia (CMML) but may be present in a spectrum of diseases including other haematological malignancies. In ...the primary care sector, monocytosis is a relatively common finding, but its predictive value for haematological malignancy is unknown. We included 663 184 adult primary care patients from the greater Copenhagen area with one or more differential cell counts registered between 2000 and 2016 and followed them in the extensive nationwide Danish health data registers for 3 years after blood sampling. We used logistic regression to model the risk of haematological malignancy and death following monocytosis. Monocytosis was associated with an increased risk of all types of haematological malignancy with the greatest relative risk increase observed in CMML with an OR of 105.22 (95% confidence interval: 38.27–289.30). Sustained monocytosis (at least two requisitions in 3 months) further increased CMML risk, although the diagnosis was still very rare, that is, observed in only 0.1% of these individuals. Outside the haematological setting, the absolute risk of haematological malignancy associated with monocytosis is low and haematological malignancy should mainly be suspected when monocytosis is sustained or the clinical presentation raises suspicion of malignancy.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Background
The Danish National Patient Registry holds data on hematological procedure codes including date and type of treatment from all hematological departments in Denmark. The validity of the ...hematological procedure codes remains to be clarified before they are used in epidemiological research.
Patients and Methods
Using the Danish Myelodysplastic Syndromes Database, we identified 897 patients diagnosed with myelodysplastic syndromes or chronic myelomonocytic leukemia treated at five Danish Hospitals between 1 January 2012 and 30 April 2019. From the Danish National Patient Registry, we ascertained information about hematological procedure codes and date of procedure registered on each patient and generated random samples. Using medical record review as the reference standard, we validated procedure codes in the Danish National Patient Registry and calculated positive predictive values (PPVs) with 95% confidence intervals (CIs) for each procedure code.
Results
A total of 523 medical records (99% of the total sample) were available for review. PPVs for specific procedure codes ranged from 71% to 100%. The overall PPV was 91% (95% CI: 88%–92%), reflecting PPVs of 95% (95% CI: 92%–97%) for low‐dose‐chemotherapy, 90% (95% CI: 81%–96%) for high‐dose chemotherapy, 99% (95% CI: 93%–100%) for allogeneic stem cell transplantation, 75% (95% CI: 62%–85%) for immuno‐modulating agents, 80% (95% CI: 74%–85%) for growth factors, and 99% (95% CI: 99%–100%) for bone marrow examination. The accuracy of coding was consistent across geographic regions and year of registration/coding.
Conclusions
Hematological procedure codes reported to the Danish National Patient Registry had high PPVs and are suitable for epidemiological research.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Background The time interval from first symptom and sign until a cancer diagnosis significantly affects the prognosis. Therefore, recognising and acting on signs of cancer, such as anaemia, is ...essential. Evidence is sparse on the overall risk of cancer and the risk of specific cancer types in persons with new-onset anaemia detected in an unselected general practice population. We aimed to assess the risk of cancer in persons with new-onset anaemia detected in general practice, both overall and for selected cancer types. Methods This observational population-based cohort study used individually linked electronic data from laboratory information systems and nationwide healthcare registries in Denmark. We included persons aged 40-90 years without a prior history of cancer and with new-onset anaemia (no anaemia during the previous 15 months) detected in general practice in 2014-2018. We measured the incidence proportion and standardised incidence ratios of a new cancer diagnosis (all cancers except for non-melanoma skin cancers) during 12 months follow-up. Results A total of 48,925 persons (median interquartile interval age, 69 55-78 years; 55.5% men) were included in the study. In total, 7.9% (95% confidence interval (CI): 7.6 to 8.2) of men and 5.2% (CI: 4.9 to 5.5) of women were diagnosed with cancer during 12 months. Across selected anaemia types, the highest cancer incidence proportion was seen in women with 'anaemia of inflammation' (15.3%, CI: 13.1 to 17.5) (ferritin > 100 ng/mL and increased C-reactive protein (CRP)) and in men with 'combined inflammatory iron deficiency anaemia' (19.3%, CI: 14.5 to 24.1) (ferritin < 100 ng/mL and increased CRP). For these two anaemia types, the cancer incidence across cancer types was 10- to 30-fold higher compared to the general population. Conclusions Persons with new-onset anaemia detected in general practice have a high cancer risk; and markedly high for 'combined inflammatory iron deficiency anaemia' and 'anaemia of inflammation'. Anaemia is a sign of cancer that calls for increased awareness and action. There is a need for research on how to improve the initial pathway for new-onset anaemia in general practice. Keywords: Anemia, Cancer risk, Cohort studies, Denmark, General practice
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Low socioeconomic position (SEP) may be associated with adverse outcomes in patients with myelodysplastic syndromes (MDS) inherent to for example, delayed diagnosis or reduced treatment intensity, ...but firm evidence is limited. In this study, we examined the association between SEP and clinical outcomes. We conducted a population‐based cohort study (2010–2018) of 2233 Danish patients with MDS. SEP measures included individual‐level information on education, cohabitation status and income retrieved from Statistics Denmark. Associations between SEP measures and disease severity at diagnosis were examined using binomial regression analysis. Using time‐to‐event analysis, we examined the association between SEP measures and treatment with allogeneic stem cell transplantation (allo‐HSCT), risk of progression to acute myeloid leukemia (AML), and death. Estimates were adjusted for covariates selected based on direct acyclic graphs and reported with 95% confidence intervals. Patients with a short education were more likely to be transfusion‐dependent at diagnosis (RR = 1.25, 95% CI: 1.04–1.45) and more likely to be diagnosed with higher risk MDS according to the International Prognostic Scoring System (RR = 1.29, 95% CI: 1.03–1.62), than patients with a long education. We found no clear association between SEP and risk of progression to AML. In adjusted models, the 1‐year risk of dying was higher in patients with short versus long education (RR = 1.34, 95% CI: 1.08–1.65), in patients with low versus high income (RR = 1.42, 95% CI: 1.14–1.77), and among patients who lived alone compared to those who lived with a partner (RR = 1.15, 0.98–1.35). These associations persisted after 3 years and 5 years of follow‐up. Notably, patients with a short education had a markedly lower rate of undergoing treatment with allo‐HSCT compared to patients with a long education (HR = 0.51, 95% CI: 0.31–0.84). In conclusion, low SEP and especially short education, were poor prognostic factors for adverse clinical outcomes among patients with MDS.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Further temporal data on incidence, treatment patterns, and prognosis for patients with myelodysplastic syndromes (MDS) are needed. This study examined 10-year trends in incidence, treatment ...patterns, and all-cause mortality in a population-based cohort of 2309 MDS patients using Danish nationwide registries (2010–2019). We computed annual incidence rates overall and according to sex and age-groups. We examined temporal changes in the cumulative incidence of MDS specific treatments initiated within one year from diagnosis and temporal changes in the absolute risk of death and five-year adjusted hazard ratios (aHRs) for death, adjusting for age, sex and comorbidity. The age-standardized incidence rate of MDS per 100,000 person-years increased slightly from 5.3 in 2010 to 6.4 in 2019. Between 2010-2012 to 2016–2017, the use of azacitidine increased overall (8% to 22%), in patients with intermediate risk MDS (12% to 34%), and in patients with high-risk MDS (22% to 50%), while it remained stable (around 5%) for patients with low-risk MDS. The five-year aHR for death in the most recent calendar period compared to the earliest calendar period remained unchanged in patients with low-risk MDS, aHR = 0.90 (95% CI, 0.72–1.12) and in patients with high-risk MDS, aHR = 1.19 (95% CI, 0.89–1.61), while survival improved over time among patients with intermediate risk MDS, aHR = 0.67 (95% CI, 0.48–0.92). In conclusion the incidence of MDS slightly increased during a 10-year period in Denmark. The use of azacitidine increased markedly but five-year overall survival remained unchanged.
•The incidence of MDS increased in individuals aged 80 years or older (2010–2019).•The use of erythropoiesis-stimulating agents decreased (2010–2018).•The use of azacitidine increased (2010–2018).•Survival was unchanged in patients with low-risk and high-risk MDS (2010–2021).•Survival improved in patients with intermediate-risk MDS (2010–2021).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Identifying risk factors for intensive care unit (ICU) admission in acute leukemia (AL) patients may guide decision-making and improve prognosis. We included all adult AL patients receiving ...high-intensive chemotherapy in Denmark from 2005 to 2016. We examined risk factors crude and adjusted (a) relative risks (RRs) with 95% confidence intervals (CI) and calculated RRs of death after 1-, 3-, and 5-years in ICU-admitted patients compared with matched cohorts. In 1417 AML and 306 ALL patients, the 1-year risk of ICU admission was 28.1% for AML and 26.4% for ALL patients, with the majority related to the first course of chemotherapy. Performance status >1 was associated with increased risk. The 1-year mortality was higher in ICU-admitted patients (AML: 69.7 vs. 35.0% aRR 2.74;CI = 2.17-3.47; ALL 65.0 vs. 20.0% aRR 3.04;CI = 1.54-6.02). The excess mortality decreased with time. In this study, performance status was associated with increased risk of ICU admission and identifies high-risk patients. ICU admission was associated with high mortality, especially within the first year.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Purpose Previous US studies have shown that socioeconomic status (SES) affects survival in acute myeloid leukemia (AML). However, no large study has investigated the association between education or ...income and clinical characteristics, treatment, and outcome in AML. Methods To investigate the effects of education and income in a tax-supported health care system, we conducted a population-based study using individual-level SES and clinical data on all Danish patients with AML (2000 to 2014). We compared treatment intensity, allogeneic transplantation, and response rates by education and income level using logistic regression (odds ratios). We used Cox regression (hazard ratios HRs) to compare survival, adjusting for age, sex, SES, and clinical prognostic markers. Results Of 2,992 patients, 1,588 (53.1%) received intensive chemotherapy. Compared with low-education patients, highly educated patients more often received allogeneic transplantation (16.3% v 8.7%). In intensively treated patients younger than 60 years of age, increased mortality was observed in those with lower and medium education (1-year survival, 66.7%; adjusted HR, 1.47; 95% CI, 1.11 to 1.93; and 1-year survival, 67.6%; adjusted HR, 1.55; CI, 1.21 to 1.98, respectively) compared with higher education (1-year survival, 76.9%). Over the study period, 5-year survival improvements were limited to high-education patients (from 39% to 58%), increasing the survival gap between groups. In older patients, low-education patients received less intensive therapy (30% v 48%; adjusted odds ratio, 0.65; CI, 0.44 to 0.98) compared with high-education patients; however, remission rates and survival were not affected in those intensively treated. Income was not associated with therapy intensity, likelihood of complete remission, or survival (high income: adjusted HR, 1.0; medium income: adjusted HR, 0.96; 95% CI, 0.82 to 1.12; low income: adjusted HR, 1.06; CI, .88 to 1.27). Conclusion In a universal health care system, education level, but not income, affects transplantation rates and survival in younger patients with AML. Importantly, recent survival improvement has exclusively benefitted highly educated patients.
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