Patterns of survival among patients with myeloproliferative neoplasms diagnosed in Sweden from 1973 to 2008: a population-based study.

To access publisher full text version of this article. Please click on the hyperlink in Additional Links field.Reported survival in patients with myeloproliferative neoplasms (MPNs) shows great variation. Patients with primary myelofibrosis (PMF) have substantially reduced life expectancy, whereas patients with polycythemia vera (PV) and essential thrombocythemia (ET) have moderately reduced survival in most, but not all, studies. We conducted a large population-based study to establish patterns of survival in more than 9,000 patients with MPNs. We identified 9,384 patients with MPNs (from the Swedish Cancer Register) diagnosed from 1973 to 2008 (divided into four calendar periods) with follow-up to 2009. Relative survival ratios (RSRs) and excess mortality rate ratios were computed as measures of survival. Patient survival was considerably lower in all MPN subtypes compared with expected survival in the general population, reflected in 10-year RSRs of 0.64 (95% CI, 0.62 to 0.67) in patients with PV, 0.68 (95% CI, 0.64 to 0.71) in those with ET, and 0.21 (95% CI, 0.18 to 0.25) in those with PMF. Excess mortality was observed in patients with any MPN subtype during all four calendar periods (P < .001). Survival improved significantly over time (P < .001); however, the improvement was less pronounced after the year 2000 and was confined to patients with PV and ET. We found patients with any MPN subtype to have significantly reduced life expectancy compared with the general population. The improvement over time is most likely explained by better overall clinical management of patients with MPN. The decreased life expectancy even in the most recent calendar period emphasizes the need for new treatment options for these patients.Swedish Cancer Society CAN 2009/1203 Stockholm County Council SLL 20090201 Karolinska Institutet SLL 20090201 Karolinska Institutet Foundations 2009Fobi0072 Shire Pharmaceuticals Adolf H. Lundin Charitable Foundatio

Improved patient survival for acute myeloid leukemia: a population-based study of 9729 patients diagnosed in Sweden between 1973 and 2005

We evaluated survival patterns for all registered acute myeloid leukemia (AML) patients diagnosed in Sweden in 1973 to 2005 (N = 9729; median age, 69 years). Patients were categorized into 6 age groups and 4 calendar periods (1973-1980, 1981-1988, 1989-1996, and 1997-2005). Relative survival ratios were computed as measures of patient survival. One-year survival improved over time in all age groups, whereas 5- and 10-year survival improved in all age groups, except for patients 80+ years. The 5-year relative survival ratios in the last calendar period were 0.65, 0.58, 0.36, 0.15, 0.05, and 0.01 for the age groups 0 to 18, 19 to 40, 41 to 60, 61 to 70, 71 to 80, and 80+ years, respectively. Intensified chemotherapy, a continuous improvement in supportive care, and allogeneic stem cell transplantation are probably the most important factors contributing to this finding. In contrast, there was no improvement in survival in AML patients with a prior diagnosis of a myelodysplastic syndrome during 1993 to 2005 (n = 219). In conclusion, AML survival has improved during the last decades. However, the majority of AML patients die of their disease and age remains an important predictor of prognosis. New effective agents with a more favorable toxicity profile are needed to improve survival, particularly in the elderly. (Blood. 2009; 113: 3666-3672

Risk of Arterial and Venous Thrombosis in 11,155 Patients with Myeloproliferative Neoplasms and 44,620 Matched Controls; A Population-Based Study

Abstract Background Patients with myeloproliferative neoplasms (MPNs) are reported to have a higher risk of thrombosis compared to the general population. However, the magnitude of the increase in risk in MPNs patients is not known since there is a lack of studies including control subjects. Therefore, we conducted a large population-based study to assess the risk of arterial and venous thrombosis in patients with MPNs in relation to matched controls. Patients and Methods All patients with MPNs reported to the Swedish Cancer Register and/or registered in the Inpatient Register from 1980 to 2009 were included. For each patient, four controls matched for age, sex, and county of residence, were randomly identified from the Register of Total Population. End of follow-up was December 31st 2010. Events of arterial and venous thrombosis, including deaths, were identified from the Inpatient and Outpatient Registers and the Cause of Death Register. Arterial thrombosis was defined as myocardial infarction, ischemic stroke, or peripheral arterial thrombus/embolus. Venous thrombosis was defined as pulmonary embolism, deep venous thrombosis (DVT), liver or splanchnic vein thrombosis, cerebral venous sinus thrombosis, or other venous thrombosis/embolus. Odd ratios (ORs) of arterial and venous thrombosis at diagnosis +/-30 days were calculated using logistic regression. Cox regression and flexible parametric models were used to estimate proportional and non-proportional hazard ratios (HRs) with 95% confidence intervals (CIs). Follow-up in all regression models started 30 days after diagnosis to avoid detection bias at time of diagnosis. Results A total of 11,155 patients and 44,620 matched controls were identified. Forty-six percent (n=5,161) were men and median age at MPN diagnosis was 69 years. The OR for arterial and venous thrombosis at time of MPN diagnosis +/- 30 days was 55.0 (95% CI 51.1-59.2 p<0.001) and 64.3 (42.2-98.1 p<0.001) respectively in MPN patients compared to controls. In MPN patients, the risk of arterial thrombosis was significantly 4.9-fold (4.8-5.0 p<0.001) increased compared to matched controls. The HR of myocardial infarction was 3.9 (3.7-4.1 p<0.001) and stroke 4.9 (4.8-5.0 p<0.001) in MPN patients. The HR of arterial thrombosis in MPN patients decreased shortly after diagnosis but thereafter increased with follow-up time in relation to controls (Figure 1a). There was a similar risk of arterial thrombosis in patients of different MPN subtypes compared to controls, the HR in patients with polycythemia vera (PV) was 5.0 (4.8-5.2), essential thrombocythemia (ET) 4.7 (4.6-5.0), primary myelofibrosis (PMF) 5.0 (4.7-5.3), and MPN-unclassifiable (MPN-U) 5.1 (4.8-5.5), respectively. The HR of venous thrombosis in MPN patients was 6.7 (6.2-7.2 p<0.001), where the HRs of pulmonary embolism was 7.5 (6.6-8.5 p<0.001) and DVT was 5.3 (4.8-5.9 p<0.001) compared to matched controls. MPN patients had a substantially increased risk of liver and splanchnic vein thrombosis, HR=41.4 (26.4-64.9 p<0.001). The risk of venous thrombosis in MPN patients decreased shortly after diagnosis and thereafter remained stable in relation to controls during follow-up time (Figure 1b). Compared to controls, patients with PV had a larger increase in risk of venous thrombosis than the other subtypes (HR=9.0; 8.0-10.1), while the HR of venous thrombosis in patients with ET was 5.4 (4.7-6.2), PMF 6.0 (4.9-7.5), and MPN-U 4.6 (3.7-5.7), respectively. Conclusions Patients with MPNs have an overall five- to sevenfold elevated risk of thrombosis compared to the general population. The highest HRs were seen for venous thrombosis, especially abdominal thrombosis. The odds of having a thrombosis at time of MPN diagnosis were high, indicating that thrombosis is an important first symptom of MPN. The elevated risk of arterial thrombosis increased while the elevated risk of venous thrombosis remained stable during follow-up time. This large population-based study is, to our knowledge, the first to quantify the excess risk of thrombosis in MPN patients compared to the general population. Our results indicate that we need to consider time after diagnosis in risk score models and rethink the strategies for thromboprophylaxis in patients with MPN in order to decrease the risk of thrombotic events. Figure 1A Risk of arterial (a) and venous (b) thrombosis in MPN patients compared to matched controls during follow-up time. Figure 1A. Risk of arterial (a) and venous (b) thrombosis in MPN patients compared to matched controls during follow-up time. Figure 1B Figure 1B. Disclosures No relevant conflicts of interest to declare

Temporal trends in the proportion cured among adults diagnosed with acute myeloid leukaemia in Sweden 1973-2001, a population-based study

P>Large age-dependant differences in temporal trends in 1- and 5-year relative survival have been observed in patients with acute myeloid leukaemia (AML) in Sweden. This investigation used an alternative approach to studying patient survival that simultaneously estimated the proportion of patients cured from their cancer and the survival of the 'uncured'. We conducted a population-based study including 6439 AML patients aged 19-80 years in Sweden between 1973 and 2001. Mixture cure models were estimated, with age at diagnosis categorised (19-40, 41-60, 61-70 and 71-80) and year of diagnosis modelled using splines. In 1975 the cure proportion was < 6% in all age groups and the median survival time for 'uncured' patients was < 0 center dot 5 years. In 2000 the cure proportion was 68% (95% confidence interval 56-77%) in the youngest group, and 32% (25-39%), 8% (3-21%), and 4% (2-8%) in the other groups, respectively. The median survival times for 'uncured' were 0 center dot 74 (0 center dot 43-1 center dot 26), 0 center dot 71 (0 center dot 53-0 center dot 97), 0 center dot 69 (0 center dot 51-0 center dot 95) and 0 center dot 37 (0 center dot 31-0 center dot 44) years, respectively. A dramatic improvement in the cure proportion was seen in younger patients, whereas improvement in older ages was mainly within the survival of the 'uncured'. This novel approach of analysing survival data could be a valuable tool for physicians, patients, health care planners and health economists

Characterization and prognostic features of secondary acute myeloid leukemia in a population-based setting: A report from the Swedish Acute Leukemia Registry

Patients with secondary acute myeloid leukemia (AML) often escape inclusion in clinical trials and thus, population-based studies are crucial for its accurate characterization. In this first large population-based study on secondary AML, we studied AML with an antecedent hematological disease (AHD-AML) or therapy-related AML (t-AML) in the population-based Swedish Acute Leukemia Registry. The study included 3,363 adult patients of which 2,474 (73.6%) had de novo AML, 630 (18.7%) AHD-AML, and 259 (7.7%) t-AML. Secondary AML differed significantly compared to de novo AML with respect to age, gender, and cytogenetic risk. Complete remission (CR) rates were significantly lower but early death rates similar in secondary AML. In a multivariable analysis, AHD-AML (HR 1.51; 95% CI 1.26-1.79) and t-AML (1.72; 1.38-2.15) were independent risk factors for poor survival. The negative impact of AHD-AML and t-AML on survival was highly age dependent with a considerable impact in younger patients, but without independent prognostic value in the elderly. Although patients with secondary leukemia did poorly with intensive treatment, early death rates and survival were significantly worse with palliative treatment. We conclude that secondary AML in a population-based setting has a striking impact on survival in younger AML patients, whereas it lacks prognostic value among the elderly patients. Am. J. Hematol. 90:208-214, 2015. (c) 2014 Wiley Periodicals, Inc