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.
BackgroundTreatment 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.Methods and patientsThe 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.ResultsOf 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.ConclusionIn 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.
Acute promyelocytic leukemia (APL) is highly curable. To achieve high cure rates, targeted therapy with retinoic acid (ATRA) must be started promptly at time of suspected diagnosis. Early death rates (EDRs, ≤30 days from diagnosis) differ markedly in patients treated on clinical trials compared to the general population. Objectives and methods: We used the comprehensive Danish National AcuteLeukemia Registry (DNLR) to investigate the incidence, treatment, EDR, and longterm clinical outcome in APL between 2000 and 2014.Results: Twenty-two of 41 deaths occurring in 122 APL patients were EDs which were primarily caused by intracranial hemorrhage, disseminated intravascular coagulation (DIC), sepsis, and multiorgan failure. The overall EDR was 18.0%, whereas clinical trial participants had an EDR of 6.7%. Fifteen patients recruited to the NCRI AML17 APL trial from 2010 to 2013 were younger and had decreased mortality (HR 0.18, CI 0.04-0.86, P = 0.02) compared to contemporarily treated patients (n = 15) not recruited to a clinical trial. Performance status, leukemia origin, and Sanz-score were independent prognostic variables. Conclusions:The very low EDR for on-trial patients is not observed in the general cohort of APL patients. Diagnostic awareness emerges as the greatest clinical challenge in management of APL. K E Y W O R D Sacute promyelocytic leukemia, diagnostic awareness, early death, prognosis
23. Frederiksen BL, Dalton SO, Osler M, Steding-Jessen M, de Nully Brown P. Socioeconomic position, treatment, and survival of non-Hodgkin lymphoma in Denmark-a nationwide study. Br J Cancer. 2012;106(5):988-995.
Background: Studies have shown that patients with chronic lymphocytic leukemia (CLL) are at increased risk of developing second lung cancer. The underlying mechanisms for this increased risk have yet not been identified. Risk factors may differ between histological lung cancer subtypes. However, though relevant to the clarification of the association between the two malignancies, little is known about the lung cancer subtype distribution in CLL patients. Methods: We investigated the occurrence of second lung cancer overall and its major histological subtypes in all patients diagnosed with CLL in Denmark between 1943 and 1999 in a retrospective registry-based cohort study. The relative risk was expressed as the standardized incidence ratio (SIR), i.e. the ratio of the observed to the expected number of lung cancer cases, based on age-, sex-, and calendar year specific incidence rates for the Danish population, available from the Danish Cancer Registry. Results: Overall, 9,541 patients diagnosed with CLL between 1943 and 1999 were followed for lung cancer occurrence. The median age at onset was 70 years and the male-to-female ratio was 1.6. Second lung cancer occurred in 147 patients (122 men and 25 women) during 36,604 person-years of follow-up (median 2.5 years) corresponding to a statistically significantly increased relative risk (SIR=1.83, 95% CI 1.55–2.15). There was no difference in risk between women and men (phom=0.27). The relative risk for lung cancer varied slightly by age at CLL being particularly high in younger age groups (≤59 years SIR=2.18 (1.53–3.10), 60–69 years SIR=2.26 (1.78–2.86), 70–79 years SIR=1.28 (0.93–1.76), ≥80 years SIR=1.51 (0.79–2.90); phom=0.02). In contrast, SIR for lung cancer did not vary by time since CLL diagnosis (phom=0.64). In 95 cases (72 men, 23 women) of second lung cancer information about major histological subtypes were available. We found a statistically significantly elevated risk for all major subtypes, except small-cell carcinoma (adenocarcinoma SIR=2.85 (2.04–3.99), large-cell carcinoma SIR=2.31 (1.04–5.15), squamous cell carcinoma SIR=2.30 (1.68–3.14), small cell carcinoma SIR=1.47 (0.90–2.39)). Discussion: In one of the largest and most detailed register-based cohort studies so far, we found an increased occurrence of lung cancer among CLL patients, which was apparent for major lung cancer subtypes. While increased medical surveillance of the CLL patients cannot be ruled out as explanation for the increased risk, the uniform distribution over time since CLL diagnosis suggests that it is unrelated to initial therapy. Tobacco smoking is the major risk factor in lung cancer. Data on smoking history were not available in our study, however, previous studies suggest that smoking is not associated with CLL. Family aggregation found for both lung cancer and CLL may indicate hereditary predisposition to the two conditions. Furthermore, individual susceptibility to malignant diseases may be influenced by polymorphisms in enzymes metabolizing carcinogenes, suggested independently for CLL and lung cancer. Given the prolonged survival of patients with CLL, further studies are needed to address the causal relationship between CLL and second malignancies, including lung cancer.
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