Search

To gain knowledge of underlying risk factors for vascular complications and their impact on life expectancy in myelofibrosis.From a cohort of 392 myelofibrosis patients registered in the Swedish MPN registry 58 patients with vascular complications during follow-up were identified. Patients with vascular complications were compared with both 1:1 matched controls and the entire myelofibrosis cohort to explore potential risk factors for vascular complications and their impact on survival.Incidence of vascular complications was 2.8 events per 100 patient-years and the majority of complications were thrombotic. Patients with complications were significantly older and had lower hemoglobin when compared to the entire cohort. In the case-control analysis, no significant risk factor differences were observed. The major cause of death was vascular complications and median survival was significantly impaired in patients with vascular complications (48 months) compared to controls (92 months). Inferior survival in patients with vascular complications was found to be dependent on IPSS risk category in a Cox regression model.Vascular complications have a considerable impact on survival in MF. At diagnosis, risk assessment by IPSS does not only predict survival but is also associated with the risk of vascular complications.

Pregnancy and childbirth in women with myeloproliferative neoplasms (MPN) are reported to be associated with maternal thrombosis, hemorrhage, and placental dysfunction. To assess the risks of adverse events in pregnancy in women with MPN, we performed a large population-based study using Swedish health care registers, and included all pregnancies that had reached gestational week 22 (prior to 2008, week 28) during the years 1973–2017 in women with MPN. Control pregnancies were matched 1:1 for age, calendar year, and parity. We identified 342 pregnancies in 229 women with MPN. Preterm birth was significantly increased in pregnancies in MPN, 14% compared to 4% of pregnancies in controls (p p = 0.042). Stillbirth was rare, with two events (0.6%) in MPN, none in controls. Maternal thrombotic complications occurred in three (1%) of the pregnancies in MPN patients, compared to none in controls. Pregnancy-related bleeding affected 14% of pregnancies in MPN and 9% in controls (p

Infections are a common complication in patients with many hematologic malignancies, however, whether patients with myeloproliferative neoplasms (MPN) also are at an increased risk of infections is largely unknown. To assess the risk of serious infections, we performed a large population-based matched cohort study in Sweden including 8 363 MPN patients and 32,405 controls using high-quality registers between the years 1992-2013 with follow-up until 2015. The hazard ratio (HR) of any infection was 2.0 (95% confidence interval 1.9-2.0), of bacterial infections 1.9 (1.8-2.0), and of viral infections 2.1 (1.9-2.3). One of the largest risk increases was that of sepsis, HR 2.6 (2.4-2.9). The HR of any infection was highest in primary myelofibrosis 3.7 (3.2-4.1), and significantly elevated in all MPN subtypes; 1.7 (1.6-1.8) in polycythemia vera and 1.7 (1.5-1.8) in essential thrombocythemia. There was no significant difference in risk of infections between untreated patients and patients treated with hydroxyurea or interferon-α during the years 2006-2013. These novel findings of an overall increased risk of infections in MPN patients, irrespective of common cytoreductive treatments, suggest the increased risk of infection is inherent to the MPN.

BACKGROUND: The reported incidence of Philadelphia negative myeloproliferative neoplasms (MPNs) differs substantially between previous reports; likely due to true regional differences in incidence and/or variations in the quality and coverage of the cancer registers. OBJECTIVE: We therefore assessed MPN incidence in Sweden during recent years using prospectively collected information captured in Swedish health registers. METHODS: Patients with MPNs were identified through the Swedish Cancer Register and Swedish Blood Cancer Register between 2000 and 2014. Information on the Swedish population was obtained from the Human Mortality Database. Crude and age-standardized incidence rates of MPNs with 95% confidence intervals (CIs) were calculated. RESULTS: A total of 6,281 MPN cases were reported to the Swedish Cancer Register and Swedish Blood Cancer Register during 2000–2014. The age-standardized, to the Swedish population in 2000, incidence for all MPNs was 4.45 (95% confidence interval [CI] 4.34–4.56) /100,000 person-years. The age-standardized incidence for polycythemia vera was 1.48 (1.42–1.54), for essential thrombocythemia 1.60 (1.53–1.66), and for primary myelofibrosis 0.52 (0.48–0.56) /100,000 person-years, respectively. The incidence rate of MPNs was substantially higher in the older compared to the younger age groups. The incidence increased during the study period, likely to do better reporting and increasing age of the general population. CONCLUSION: The reported MPN incidences in our study, which were in the higher interval of previously published studies, are likely more accurate compared to previous reports due to the population-based setting and high level of coverage in the Swedish Cancer and Blood Cancer Registers.

Additional file 3: Supplementary Figure 2.

Additional file 2: Supplementary Figure 1.

To determine the risk of a wide range of second malignancies in patients with myeloproliferative neoplasms (MPNs), we conducted a large population-based study and compared the results to matched controls. From national Swedish registers, 9379 patients with MPNs diagnosed between 1973 and 2009, and 35,682 matched controls were identified as well as information on second malignancies, with follow-up until 2010. Hazard ratios (HRs) with 95 % confidence intervals (CIs) were calculated using Cox regression and a flexible parametric model. There was a significantly increased risk of any non-hematologic cancer with HR of 1.6 (95% CI: 1.5-1.7). The HRs for non-melanoma skin cancer was 2.8 (2.4-3.3), kidney cancer 2.8 (2.0-4.0), brain cancer 2.8 (1.9-4.2), endocrine cancers 2.5 (1.6-3.8), malignant melanoma 1.9 (1.4-2.7), pancreas cancer 1.8 (1.2-2.6), lung cancer 1.7 (1.4-2.2), and head and neck cancer 1.7 (1.2-2.6). The HR of second malignancies was similar across all MPN subtypes, sex, and calendar periods of MPN diagnosis. The risk of developing a hematologic malignancy was also significantly increased; the HR for acute myeloid leukemia was 46.0 (32.6-64.9) and for lymphoma 2.6 (2.0-3.3). In conclusion, our study provides robust population-based support of an increased cancer risk in MPN patients.

Background Patients diagnosed with myeloproliferative neoplasms (MPNs) are at an increased risk of vascular events. A paucity of population-based studies investigating risk factors exist. We conducted a nested case-control study to explore the relative importance of risk factors, treatment, and blood counts for vascular complications in Essential Thrombocythemia (ET) and Polycythemia Vera (PV), and their impact on life expectancy. Patients and Methods All newly diagnosed MPN patients (pts) are reported to the Swedish national MPN registry as mandated by Swedish law. 922 ET pts and 763 PV pts diagnosed from January 2010 through September 2015 with a 3 or 6-year follow-up were included. Pts identified as having a vascular complication were assigned a control patient matched by MPN subtype, gender and age. Blood counts, EPO and JAK2V617F mutation status at diagnosis were recorded, as was co-morbidity, smoking habits and vascular complications prior to diagnosis. At the time of vascular complication cytoreduction, anti-thrombotic therapy and blood counts were investigated. In controls these parameters were registered at the corresponding time from diagnosis. MPN therapy is recommended in Nordic guidelines that closely mirror those issued by the ELN. Statistical analyses Differences in the distribution of variables were analyzed using Mann-Whitney test. Chi square test was used for comparison between groups. Overall survival estimations were calculated by Kaplan-Meier analysis and compared using Log Rank test. Multivariate analysis was performed by unconditional logistic regression. Results At diagnosis ET and PV pts with complications were older compared to the whole ET and PV cohorts, mean ages 73 and 65 years respectively in ET (p Seventy-one ET pts (8%) suffered at least one vascular complication during follow-up. 49 thromboembolic and 22 hemorrhagic; 1.4 and 0.6 events/100 patient-years respectively. Median time from diagnosis to vascular complication was 24 months (0-71). Most common thromboembolic events were cardiac, DVT/LE and cerebral. Gastrointestinal (GI) and cerebral were the most frequent hemorrhagic complications. At time of event there were no significant differences in mean hemoglobin (Hgb), hematocrit (Hct) or platelet counts. Mean white blood cell (WBC) count was 9.1 x109/L in the complication group compared to 7.1 x109/L in controls (p=0.063). Frequent use of cytoreductive therapy and/or anti-thrombotics may have contributed to a lack of difference between treated and untreated pts in ET. 81 (11%) of the PV pts had at least one vascular event after a median time of 24 months (0-89). 59 of these thromboembolic and 22 hemorrhagic; 2.5 and 0.9 events/100 patient-years respectively. Cerebral ischemic events were the most frequent, followed by DVT/LE and cardiac, in hemorrhage G-I and cerebral. At time of vascular event the mean WBC was 13.5 x109/L compared to 9.6 x109/L in controls (p The estimated 5-year survival was significantly impaired in ET pts who suffered a vascular event compared the matched controls without vascular complication, 65% and 81%, respectively (p=0.020). The same was seen in PV, 60% compared to 85% in the controls (p Conclusions In this population-based study the main finding was that survival of PV and ET pts with vascular complications is highly reduced compared to controls. At the time of complication blood values, with the exception of WBC in PV, do not show any significance. This finding clearly demonstrates that the cytoreductive treatment per se is protective, and underscores the negative impact of undertreatment in PV. Figure Disclosures Samuelsson: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; CTI Bio: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; AOP Pharma: Honoraria.

Background Patients diagnosed with Philadelphia-negative myeloproliferative neoplasms (MPNs) have been reported to have an elevated risk of thromboembolism. Although some data also indicate a higher risk of bleeding in this population, no study has yet compared the risk of bleeding in MPN patients to a control population. Therefore, using population-based data from Swedish registers, we evaluated the risk of bleeding in patients with MPN compared to matched controls. Patients and Methods All patients diagnosed with MPN between 1987 and 2009, and reported to the Swedish Cancer Register and the Swedish National Inpatient Register were included in the study. Four controls for each patient were randomly selected from the Register of Total Population and matched based on age, and sex. The outcome-data were collected from the Inpatient Register, the Outpatient Register and the Cause of Death Register. Major bleedings were defined as bleedings requiring hospital admission and/or with a fatal outcome. All other bleedings were considered minor bleedings.Cox regression models were used to obtain proportional hazard ratios with 95% confidence intervals (CIs), whereas flexible parametric survival models were used to assess time-varying HRs when there was no evidence of proportional hazards.Patients were followed until the time of event or to censoring due to death, immigration, or the end of follow-up 31st December 2009, whichever occurred first. Results A total of 9,429 patients and 35,820 matched controls were included in this study. The median age at diagnosis was 72 years and 54% of patients were women. Essential thrombocythemia and polycythemiaverawere the most frequent subtypes, representing 3,462 and 3,001 patients, respectively, whereas 1,488 patients had primary myelofibrosis and 1,478 patients were diagnosed as MPN unclassifiable. The overall HR of bleeding for MPN patients was 1.6 (95% CI 1.5-1.7, p-value Conclusions In this large population-based study we found that patients withMPN, especially primary myelofibrosis, hada higher risk of bleeding compared to the control population. MPN patients were particularly prone to contract bleedings in the ear-nose-throat tract, kidney and urinary tract, gastrointestinal tract, and the central nervous system. Interestingly, the overall risk of bleeding in our cohort was highest shortly after diagnosis. This could partially be dueto the secondary coagulopathies sometimes associated with initially untreated MPNs, aspirin used for primary thrombosis prophylaxis as well as anticoagulation treatment following thrombotic events. From a clinical point of view, these findings underline the importance of keeping a vigilant watch on bleedings early after diagnosis and point to the need to evaluate the global bleeding risk for each patient. Disclosures No relevant conflicts of interest to declare.