Diagnostic workup of cancer in patients with new-onset anaemia: a Danish cohort study in general practice.

BACKGROUND: Anaemia is associated with adverse outcomes, including increased morbidity and all-cause mortality. Diagnostic workup of patients with anaemia is essential to detect underlying disease, especially undiagnosed malignancy. OBJECTIVE: To describe the cancer-relevant diagnostic workup in patients with new-onset anaemia detected in general practice. An additional aim was to analyse associations between patient characteristics and the diagnostic workup. DESIGN: Observational population-based cohort study using electronic laboratory and register data. SETTING: Danish general practice. SUBJECTS: Patients aged 40-90 years with new-onset anaemia (no anaemia in the preceding 15 months) detected in general practice. Patients were identified in Danish laboratory information systems and nationwide registries in 2014-2018. MAIN OUTCOME MEASURES: We measured the proportion of patients receiving predefined diagnostic investigations, that is, cancer patient pathway, colonoscopy, gastroscopy, computerised tomography (CT) scan, faecal test for haemoglobin, and bone marrow examination within three months of the anaemia index date. RESULTS: We included 59,993 patients, and around half of the patients with 'iron deficiency anaemia', 'anaemia of inflammation', or 'combined inflammatory iron deficiency anaemia' had no cancer-relevant diagnostic investigations performed. Patients aged 60-79 years and patients with severe anaemia were more likely to have investigations performed, while patients with comorbidity were less likely to have investigations performed. CONCLUSION: Around half of the patients with anaemia subtypes that may indicate underlying cancer had no cancer-relevant diagnostic investigations performed. This may represent missed diagnostic opportunities. Future interventions are needed to improve the diagnostic workup of cancer in patients with anaemia, for example, laboratory alert systems and clinical decision support.KEY POINTSThe general practitioners are often the first to detect anaemia and its underlying disease (e.g. undiagnosed malignancy).Large-scale studies are needed on the diagnostic workup of patients with anaemia in general practice in relation to an underlying malignancy.This study shows that the majority of patients with anaemia had no cancer-relevant diagnostic investigations performed, which may cause diagnostic delay.Interventions seems needed to improve the diagnostic workup of cancer in these patients to ensure timely diagnosis.

Insufficient classification of anaemia in general practice: a Danish register-based observational study.

BACKGROUND: Anaemia can be a pointer of underlying severe disease, including undiagnosed malignancy. Subsequent blood tests are essential to classify the anaemia into subtypes and to facilitate targeted diagnostic investigation to ensure timely diagnosis of underlying disease. OBJECTIVE: We aimed to describe and classify anaemia based on laboratory tests from patients with new-onset anaemia detected in general practice. An additional aim was to analyse associations between patient characteristics and unclassified anaemia (not classifiable according to an algorithm). DESIGN: Population-based cross-sectional study. SETTING: Danish general practice. SUBJECTS: A total of 62,731 patients (age: 40-90 years) with new-onset anaemia were identified in Danish laboratory information systems and nationwide registries, and data were obtained for 2014-2018. MAIN OUTCOME MEASURES: We measured the proportion of patients classified into subtypes of anaemia based on blood tests requested by general practitioners within 31 days of the anaemia index date. RESULTS: Of the 62,731 patients with new-onset anaemia, we identified unclassified anaemia in 78.9% (95% confidence interval (CI): 77.3-80.5) of men and 65.1% (CI: 63.4-66.9) of women. The likelihood of unclassified anaemia increased with age, increasing comorbidity and decreasing severity of anaemia. CONCLUSION: The majority of patients with new-onset anaemia could not be classified through a simple algorithm due to missing blood tests, which highlights a potential missed opportunity for diagnosis. Standardised laboratory testing of patients with anaemia is warranted to ensure adequate follow-up and early detection of underlying severe disease.KEY POINTSAnaemia can be a sign of malignancy, and anaemia classification is an important step in the diagnosis of underlying disorders.The majority of patients with anaemia could not be classified according to a simple algorithm due to missing blood tests.Some patient characteristics were associated with a high risk of unclassified anaemia: high age, high comorbidity, and severe anaemia.Standardised laboratory testing in patients with anaemia is needed to inform targeted diagnostic investigation to ensure timely diagnosis.

Epidemiology and Clinical Significance of Secondary and Therapy-Related Acute Myeloid Leukemia: A National Population-Based Cohort Study.

PURPOSE: 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. PATIENTS AND METHODS: 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. RESULTS: 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). CONCLUSION: 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.