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.
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
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.
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
Treatment of acute myeloid leukemia (AML) is widely centralized. Longer distances to a specialized treatment center may affect patients' access to curative-intended treatment. Especially during ...outpatient treatment, distance may also affect survival.
The authors conducted a national population-based cohort study including all AML patients diagnosed in Denmark between 2000 and 2014. We investigated effects of distance (<10 kilometers km; reference, 10-25, 25-50, 50-100, >100) to the nearest specialized treatment facility on the probability of receiving intensive chemotherapy, HSCT, and achieving a complete remission (CR) using logistic regression analysis (odds ratios; ORs). For overall survival, we used Cox proportional hazards regression (hazard ratios HRs) and adjusted (a) for relevant baseline characteristics.
Of 2,992 patients (median age=68.5 years), 53% received intensive chemotherapy and 12% received low-dose chemotherapy outpatient regimens. The median distance to a specialized treatment center was 40 km (interquartile range=10-77 km). No impact of distance to specialized treatment centers was seen on the probability of receiving intensive chemotherapy (10-25 km, aOR=1.1 (CI=0.7-1.7), 25-50 km, aOR=1.1 (CI=0.7-1.7), 50-100 km, aOR=1.3 (CI=0.9-1.9), and >100 km, aOR=1.4 CI=0.9-2.2). Overall survival in patients regardless of therapy (<10 km, aOR=1.0 vs >100 km, aOR=1.0 CI=0.9-1.2), in intensive therapy patients, or in patients' choice of post-remission was not affected by distance to specialized treatment center. Distance to a transplant center also did not affect the probability of HSCT or survival post-HSCT.
In Denmark, distance to a specialized treatment facility offering remission-induction chemotherapy and HSCT does not negatively affect access to curative-indented therapy, treatment-response, or survival in AML patients.
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
The Danish Myelodysplastic Syndromes Database (DMDSD) comprises nearly all patients diagnosed with myelodysplastic syndromes (MDS) in Denmark since 2010. The DMDSD has not yet been used for ...epidemiological research and the quality of registered variables remains to be investigated.
To describe characteristics of the patients registered in the DMDSD and to calculate predictive values and the proportion of missing values of registered data records.
We performed a nationwide cross-sectional validation study of recorded disease and treatment data on MDS patients during 2010-2019. Patient characteristics and the proportion of missing values were tabulated. A random sample of 12% was drawn to calculate predictive values with 95% confidence intervals (CIs) of 48 variables using information from medical records as a reference standard.
Overall, 2284 patients were identified (median age: 76 years, men 62%). Of these, 10% had therapy-related MDS, and 6% had an antecedent hematological disease. Hemoglobin level was less than 6.2 mmol/L for 59% of patients. Within the first two years of treatment, 59% received transfusions, 35% received erythropoiesis-stimulating agents, and 15% were treated with a hypomethylating agent. For the majority of variables (around 80%), there were no missing data. A total of 260 medical records were available for validation. The positive predictive value of the MDS diagnosis was 92% (95% CI: 88-95). Predictive values ranged from 64% to 100% and exceeded 90% for 36 out of 48 variables. Stratification by year of diagnosis suggested that the positive predictive value of the MDS diagnosis improved from 88% before 2015 to 95% after.
In this study, there was a high accuracy of recorded data and a low proportion of missing data. Thus, the DMDSD serves as a valuable data source for future epidemiological studies on MDS.
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