Article

Health Resource Utilization and Cost Associated with Myeloproliferative neoplasms (MPN) in a Large United States Health Plan.

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  • EpidStat Institute
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Abstract

ABSTRACT Myelofibrosis (MF), polycythemia vera (PV) and essential thrombocythemia (ET) may lead to bone marrow fibrosis. Because the disease course of ET and PV are long and the disease course of MF may be fatal, HRU associated costs of these neoplasms is especially important to understand. We used a large US health insurance claim database to describe the costs of these diseases. Compared to age-gender matched comparisons without MPN, all aspects of health care resource utilization (HRU) that we examined, including inpatient, outpatient and emergency room visits and pharmacy, as well as overall healthcare expenditures are significantly higher in MF, PV and ET patients (e.g., MF total costs=$54,168 vs. $10,203; PV=$14,903 vs. $7,913; ET=$29,553 vs. $8,026) than matched comparisons. In order to reduce the burden of illness associated with these diseases, continued efforts in the development of more efficacious treatments for these disorders are needed.

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... 2 The estimated incidence of MF in the US is 1-3 new cases per 100 000 person-years. 3 Myelofibrosis leads to significant health care resource utilization (HCRU) and costs for patients and the US health care system. Patients with MF have higher overall comorbidities, hospitalizations, and outpatient visits, which correspond to a 5-fold increase in health care costs compared with age-and gender-matched control patients without MPNs. ...
... Patients with MF have higher overall comorbidities, hospitalizations, and outpatient visits, which correspond to a 5-fold increase in health care costs compared with age-and gender-matched control patients without MPNs. 3 Overall total utilization costs are higher among patients with MF compared with patients with other MPNs (ie, polycythemia vera and essential thrombocythemia). 3 Treatment options for MF are limited and few patients undergo the only curative therapy, allogenic hematopoietic cell transplantation. ...
... 3 Overall total utilization costs are higher among patients with MF compared with patients with other MPNs (ie, polycythemia vera and essential thrombocythemia). 3 Treatment options for MF are limited and few patients undergo the only curative therapy, allogenic hematopoietic cell transplantation. 4 The clinical manifestations of MF are heterogeneous and treatment choice is often complex, involving management of multiple symptoms including anemia, splenomegaly, constitutional symptoms, bone pain, and bleeding. ...
Article
Full-text available
Background This study analyses treatment patterns, health care resource utilization (HCRU), and costs in patients with myelofibrosis (MF) and a subgroup treated with ruxolitinib (RUX). Materials and Methods Treatment patterns, all-cause and MF-related HCRU, and costs were analyzed in adults with MF with continuous enrollment in a commercial or the Medicare Advantage health plan in the pre-index period, defined as the 12 months immediately prior to the index date (date of primary or secondary MF diagnosis), and the post-index period, defined as ≥6 months following the index date. In a subgroup analysis, outcomes were analyzed in patients treated with optimal RUX (OPT RUX, ≥30 mg) and suboptimal RUX (SUB RUX, <30 mg) in the pre-index RUX period, defined as the 3 months immediately prior to the index RUX date (first date for an RUX claim), and the post-index RUX period, defined as ≥6 months following the index RUX date. Results Of 2830 patients with an MF diagnosis, 1191 met eligibility requirements. The median age of patients was 72 years, 54% were male, and comorbidities were frequent. Sixty percent of patients received ≥1 line of therapy (LOT), of which 46% (n = 331) had ≥2 LOTs during the post-index MF period. Costs increased considerably 6-month pre-index to 6-month post-index (all-cause: cause ($24,216 to $48,966) and MF-related ($16,502 to $39,383), driven by inpatient stays and pharmacy costs. In the subgroup analysis, patients treated with RUX (n = 495) experienced significant disease burden and high costs, regardless of dose. A shorter duration of therapy and a higher rate of discontinuation were observed in patients treated with SUB RUX (n = 191) versus OPT RUX (n = 304). Conclusion These findings suggest a significant disease and economic impacts associated with MF patients that persists with RUX therapy, highlighting the need for additional therapeutic options for MF.
... 9 Elevated hematocrit (≥ 45%), 12 leukocytosis (≥ 11 × 109/L), 13 and higher JAK2V617F allele burden (ratio of mutant to wild-type JAK2 in hematopoietic cells; ≥ 75%) have been associated with a higher risk of TEs. 14 In addition to the disease-related clinical burden of PV, 15 patients carry a greater financial burden compared with age-and sex-matched controls, driven by higher health care resource utilization and associated costs. 16 A large retrospective analysis of insurance claims in the United States reported that patients with PV (n = 5,752) had significantly more hospital admissions and physician office visits and significantly longer hospital stays compared with matched controls. 16 The resulting medical, pharmacy, and total annual costs for patients with PV were almost twice as high as the general population in 2010. ...
... 16 A large retrospective analysis of insurance claims in the United States reported that patients with PV (n = 5,752) had significantly more hospital admissions and physician office visits and significantly longer hospital stays compared with matched controls. 16 The resulting medical, pharmacy, and total annual costs for patients with PV were almost twice as high as the general population in 2010. 16 A key contributor to the elevated costs for patients with PV may be TE-related treatments. ...
... 16 The resulting medical, pharmacy, and total annual costs for patients with PV were almost twice as high as the general population in 2010. 16 A key contributor to the elevated costs for patients with PV may be TE-related treatments. The annual costs associated with prophylaxis or treatment following an arterial TE in the general population (i.e., not limited to patients with PV) are primarily driven by hospitalization and drug costs and have been estimated to range from approximately $13,000 to $66,000 (U.S. dollar values 1998-2008), 17-21 with direct hospital-related admission and treatment costs ranging from $58,000 to $115,000 (U.S. dollar values 2003-2005). ...
Article
Background: Patients with polycythemia vera (PV) are at increased risk of thromboembolic events (TEs), which are key contributors to reduced overall survival compared with the age- and sex-matched general population. In addition to aspirin and phlebotomy to maintain hematocrit level < 45%, many patients receive cytoreduction with hydroxyurea (HU), which is associated with improved survival and may reduce the risk of cardiovascular events and TEs. However, 1 in 4 patients become resistant to or intolerant of HU. In the general population, prophylaxis and treatment following arterial and venous thromboses are associated with increased health care resource utilization and costs. Objective: To describe the health care resource utilization and costs associated with TEs in patients with PV treated with HU in the United States. Methods: This retrospective cross-sectional analysis of the Truven Health Analytics MarketScan Research Databases included adult patients with a PV diagnosis who were newly treated with HU and continuously enrolled in medical and pharmacy benefit plans for ≥ 12 months pre- and post-index. HU treatment administration, persistence, adherence, and related adverse events, as well as TEs, were reported during the 12-month follow-up period. HU treatment patterns were further analyzed in a subgroup analysis comparing patients with and without a ≥ 45-day gap in HU treatment. Health care resource utilization and costs were analyzed in a subgroup analysis comparing patients who had TEs in the 12-month follow-up period with those who did not. Tests for statistically significant differences across the comparison groups were conducted, including chi-square tests for categorical variables and t-tests for continuous variables. Results: The records of 1,322 patients with PV were included in this study. Mean age was 66.0 years; 51.3% were men; and 14.0% had a history of TEs. During the first year of HU treatment, 764 (57.8%) patients had a treatment gap of ≥ 45 days; however, treatment adherence was similar between those with and those without a gap (85.2% vs. 90.7%, respectively). TEs occurred in 216 (16.3%) patients within 12 months of HU initiation. Health care resource utilization was higher for patients with TEs versus those without, including the proportion of patients requiring inpatient services (50.9% vs. 18.4%; P < 0.001) and emergency room visits (48.1% vs. 26.3%; P < 0.001) and the mean number of inpatient admissions (1.7 vs. 1.3; P = 0.004); office visits (18.9 vs. 14.1; P < 0.001); and prescriptions (45.8 vs. 36.2; P<0.001). In addition, total mean health care costs ($45,040 vs. $16,438; P < 0.001); inpatient costs ($18,952 vs. $4,794; P < 0.001); outpatient costs ($20,844 vs. $8,046; P < 0.001); and outpatient pharmacy costs ($5,244 vs. $3,598; P = 0.002) were higher among patients with TEs than those without. Conclusions: Patients with PV receiving treatment with HU remain at risk for TEs. The occurrence of TEs during the 12-month follow-up in this patient population was associated with higher health care resource utilization and costs. Disclosures: This study was funded by Incyte Corporation. Parasuraman and Paranagama are employees and stockholders of Incyte Corporation. Shi and Bonafede are employees of Truven Health Analytics, which was awarded a research contract to conduct this study with and on behalf of Incyte Corporation. Study concept and design were contributed by all of the authors, who also interpreted the data and wrote and revised the manuscript. Bonafede and Shi collected the data. This study was presented as an abstract at the Academy of Managed Care Pharmacy NEXUS Annual Meeting on October 26-29, 2015, in Orlando, Florida.
... The median survival for PV [13,14,26,27] and ET [13,[27][28][29] is longer than 10 years. Thus, the treatment of PV and ET focuses on reducing complications, such as thrombotic events, and actively controlling the patient's blood count with various measures, ranging from phlebotomy to drugs [30]. The reported median survival for PMF, on the other hand, is only 2 to 5 years [12,24,27,31]. ...
... Interestingly, despite the fact that there were fewest patients with PMF and that symptom relief remains the mainstay in PMF treatment, the total medical utilization costs per person were greater for patients with PMF compared to those with ET or PV. This pattern of health resource utilization was observed not only in our study but also in a previous study carried out in the USA [30,32]. Especially now that novel therapies, such as JAK2 inhibitors, are in order, MPNs deserve appropriate attention towards applicable healthcare planning and adequate medical resource allocation. ...
Article
Full-text available
Myeloproliferative neoplasms (MPNs), with an expected increment in number, impose substantial economic and social burdens. To this end, we conducted a nationwide population-based descriptive epidemiology study. We also investigated medical cost associated with MPNs. Prevalence was the highest for essential thrombocythemia (ET) (range 4.1–9.0 per 100,000), followed by polycythemia vera (PV) (range 2.8–5.4 per 100,000) and primary myelofibrosis (PMF) (range 0.5–0.9 per 100,000). ET incurred the highest cumulative total cost at US$35 million and the most frequent hospital visits, while PMF incurred the highest average cost per person at US$5000. The mean hemoglobin level was 16.9 ± 2.2 g/dL for PV males and 15.5 ± 2.7 g/dL for PV females. Further analyses on hemoglobin levels showed the true positive rate of PV from the significantly elevated hemoglobin group (defined as >18.5 g/dL for men and >16.5 g/dL for women) was 3.01% and that of MPNs was 3.1%. Here, we provide the biggest population-based report on MPN epidemiology that can readily be used as a representative Asian data.
... Although the percentage of misdiagnosis in this study may appear to be modest, these chronic illnesses have a high cost on health expenses. An analysis made by Metha et al. revealed an age-adjusted prevalence of 56.5 per 100 000 of patients who suffer from polycythemia vera and reported that in 2010, the annual cost reached $14 903 dollars of overall health care, outlining a considerable increase in comorbidities in this population 16 . However, these results, as their authors describe, may have limitations and biases for the same reason as this study. ...
Article
Full-text available
Red cell overproduction is seen in polycythemia vera (PV), a bone marrow myeloproliferative neoplasm characterized by trilinear cell proliferation (WBC, platelets), as well as in secondary erythrocytosis (SE), a group of heterogeneous disorders characterized by elevated EPO gene transcription. We aimed to verify the concordance of the International Classification of Diseases (ICD) code-based diagnosis of “polycythemia” or “erythrocytosis” with the true clinical diagnosis of these conditions. We retrospectively reviewed the electronic medical records (January 1, 2005, to December 31, 2016) of adult patients with ICD codes of polycythemia and/or erythrocytosis who had testing done for the presence of the JAK2V617F mutation. We verified the accuracy of the ICD code-based diagnoses by meticulous chart review and established whether these patients fulfilled the criteria by the evaluating physician for PV or SE and according to the World Health Organization 2016 diagnostic guidelines. The reliability of ICD coding was calculated using Cohen's kappa. We identified and chart reviewed a total of 578 patient records. Remarkably, 11% of the patients had concurrent diagnosis codes for PV and SE and were unable to be classified appropriately without individual chart review. The ICD code-based diagnostic system led to misidentification in an important fraction of cases. This represents a problem for the detection of PV or SE cases by ICD-based registries and their derived studies. Research based exclusively on ICD codes could have a potential impact on patient care and public health, and limitations must be weighed when research findings are conveyed.
... A number of economic evaluations have informed treatment availability and affordability in multiple myeloma, acute leukemia, and lymphoma [6][7][8][9][10][11][12][13]. For myeloproliferative neoplasms (MPNs), the cost of treatment is two to six times higher compared to general population using US medicare databases [14]. But the reasons for this high health resource use have not been investigated. ...
Article
Full-text available
Health resource utilization (HRU) and associated factors of high cost are not well understood in myeloproliferative neoplasms (MPNs). In this population-based, retrospective matched-cohort study, we used administrative health databases of Ontario, Canada to measure treatment costs and HRU for patients with MPN from 2004 to 2016 and compared them to matched controls. In 7130 patients with MPN [essential thrombocythemia (ET) = 3481; polycythemia vera (PV) = 2618; myelofibrosis (MF) = 1031], the mean annualized treatment costs were $16,646 for ET (controls, $7070); $16,360 for PV (controls, $7293); and $25,863 for MF (controls, $7386). Out of the total costs, the largest expenditure was on acute hospital care (ET: 57%, PV: 57%, MF: 66%). Older age (≥65), male gender, patients not seen by a specialist, and greater comorbidity burden were independent predictors of higher costs (p < 0.05). In addition, history of venous thrombosis in patients with ET and PV was associated with significantly higher treatment costs (p < 0.05).
... Roughly one-fifth of patients with PV are diagnosed with an arterial or venous thrombotic event as a presenting feature [1,2], and fatal cardiovascular events contribute to the increased mortality rate among patients with PV [1][2][3][4]. Furthermore, healthcare utilization and costs are higher for patients with PV compared with age-and gender-matched persons in a large US health insurance claims database [5] and this is driven in part by arterial and venous thrombotic events. ...
Article
Full-text available
Thrombotic and cardiovascular events are among the leading causes of death for patients with polycythemia vera (PV), and thrombosis history is a key criterion for patient risk stratification and treatment strategy. Little is known, however, about mechanisms of thrombogenesis in patients with PV. This report provides an overview of thrombogenesis pathophysiology in patients with PV and elucidates the roles of conventional and nonconventional thrombotic risk factors. In addition to several conventional risk factors for thrombosis, clinical data have implicated increased hematocrit and red blood cell adhesiveness, activated platelets, leukocytosis, and elevated JAK2(V617F) allele burden in patients with PV. Furthermore, PV-related inflammation may exacerbate thrombogenesis through varied mechanisms, including endothelial damage, inhibition of natural anticoagulant pathways, and secretion of procoagulant factors. These findings suggest a direct link between myeloproliferation and thrombogenesis in PV, which is likely to provide new opportunities for targeted antithrombotic interventions aimed at decreasing PV-related morbidity and mortality. Copyright © 2014. Published by Elsevier Ltd.
... Of the diseases in the MPN category, the classical Philadelphia chromosomenegative MPNs include PV, MF, and ET. Reported worldwide incidence of the classical MPNs combined is approximately 0.5-6/100,000, annually, with peak incidence at the 5th to 7th decades of life (3)(4)(5)(6)(7)(8). However, there have been more recent changes especially regarding accuracy and frequency of the diagnosis of the classical Philadelphia chromosome-negative MPN, owing to the discovery and clinical utilization of mutations in Janus kinase 2 (JAK2) (9) and Calreticulin (CALR) (10,11). ...
Article
Full-text available
The nationwide statistical analysis of each disease of classical myeloproliferative neoplasm (MPN) in Korea has not been reported yet. To this end, we have analyzed incidence rates, survival rates and treatment pattern of polycythemia vera (PV), primary myelofibrosis (MF) and essential thrombocythemia (ET) using Korea National Cancer Incidence Database (KNCIDB) and Health Insurance Review and Assessment Service (HIRA) database. Between 2003 and 2011, a total of 4,342 new cases of MPN were reported to the KNCIDB. ET was the most common, followed by MF and PV. The crude incidence rates for PV, MF, and ET have increased during the period, reaching 0.40, 0.15, and 0.84 per 100,000, respectively. Five-year relative survival rate of all MPN patients was 89.3%, with lowest relative survival rate with MF (53.1%). The prevalence of each disease estimated from HIRA data also increased during the study period. Notably, ET was found to be most prevalent. The prescription rate of hydroxyurea and phlebotomy to PV, MF, and ET patients remained constant over the period, and the prescription rate of hydroxyurea was higher in patients with age over 60 years. This is the first Korean nationwide statistics of MPN, using central registry data. This set of data can be utilized to compare the Korean MPN status to international data and guidelines.
... Many patients even have the same life expectancy as the general population. [5,6] This means that MPN patients live much of their lives with fatigue, other symptoms and the associated detrimental effects on overall functioning and QoL [3,7]. ...
Preprint
BACKGROUND Myeloproliferative neoplasm patients often report a high symptom burden that persists despite best available pharmacologic therapy. Meditation has gained popularity in recent decades as a way to manage symptoms in cancer patients. OBJECTIVE The purpose of this study was to examine the feasibility of the use of two different consumer-based meditation smartphone applications (i.e., apps) in myeloproliferative neoplasm patients. Findings will inform the choice of an app to be used for a larger randomized controlled trial. METHODS Patients (n=128) were recruited nationally through organizational partners and social media. Elibigle and consented patients were enrolled into one of four groups, two of which received varying orders of two consumer-based apps (unnamed consumer-based [CB] app and Calm App) and two that received one of the apps alone for the second four weeks of the eight week intervention after an educational control condition. Participants were asked to perform 10 min/day of smartphone-based meditation irrespective of the app and/or the order in which they received the apps. Feasibility outcomes were measured at week five and nine with an online survey. Feasibility outcomes were acceptability, demand, and limited efficacy for depression, anxiety, pain intensity, sleep disturbance, sexual function, quality of life, global health, and total symptom burden. RESULTS A total of 128 patients were enrolled across all four groups, with 94/128 (27% dropout rate) patients completing the intervention. Of the patients that completed the CB app (n=76), 61% enjoyed it, 66% were satisfied with the content, and 77% would recommend to others. Of those who completed the Calm app (n=68), 83% enjoyed it, 84% were satisfied with the content and 97% would recommend to others. Of those who completed the educational control (n=61), 91% read it, 87% enjoyed it, and 71% learned something. Patients that completed the CB app averaged 31±33 min/wk; patients that completed the Calm app averaged 71±74 min/wk. CB app participants saw small effects on anxiety (d=-0.43), depression (d=-0.38), sleep disturbance (d=-0.40), total symptom burden (d=-0.27), and fatigue (d=-0.30) as well as moderate effects on physical health (d=0.52). Calm app participants saw small effects on anxiety (d=-0.22), depression (d=-0.29), sleep disturbance (d=-0.47), physical health (d=0.44), total symptom burden (d=-0.27), and fatigue (d=-0.27). Educational control participants (n=61) did not have small, moderate, or large effects on any patient-reported outcome except for a moderate effect on physical health (d=0.77). CONCLUSIONS Delivering meditation via the Calm app is feasible and scored higher in terms of feasibility when compared to the CB app. Future randomized controlled trials are needed examining the Calm app and its effects on myeloproliferative neoplasms. CLINICALTRIAL ClinicalTrials.gov, NCT03726944.
... Many patients even have the same life expectancy as the general population [5,6]. This means that MPN patients live much of their lives with fatigue, other symptoms, and the associated detrimental effects on overall functioning and quality of life [3,7]. ...
Article
Full-text available
Background: Myeloproliferative neoplasm (MPN) patients often report high symptom burden that persists despite the best available pharmacologic therapy. Meditation has gained popularity in recent decades as a way to manage cancer patient symptoms. Objective: The aim of this study was to examine the feasibility of 2 different consumer-based meditation smartphone apps in MPN patients and to examine the limited efficacy of smartphone-based meditation on symptoms compared with an educational control group. Methods: Patients (n=128) were recruited nationally through organizational partners and social media. Eligible and consented patients were enrolled into 1 of 4 groups, 2 of which received varying orders of 2 consumer-based apps (10% Happier and Calm) and 2 that received one of the apps alone for the second 4 weeks of the 8-week intervention after an educational control condition. Participants were asked to perform 10 min of meditation per day irrespective of the app and the order in which they received the apps. Feasibility outcomes were measured at weeks 5 and 9 with a Web-based survey. Feasibility outcomes were acceptability, demand, and limited efficacy for depression, anxiety, pain intensity, sleep disturbance, sexual function, quality of life, global health, and total symptom burden. Results: A total of 128 patients were enrolled across all 4 groups, with 73.4% (94/128) patients completing the intervention. Of the participants who completed the 10% Happier app, 61% (46/76) enjoyed it, 66% (50/76) were satisfied with the content, and 77% (59/76) would recommend to others. Of those who completed the Calm app, 83% (56/68) enjoyed it, 84% (57/68) were satisfied with the content, and 97% (66/68) would recommend to others. Of those who completed the educational control, 91% (56/61) read it, 87% (53/61) enjoyed it, and 71% (43/61) learned something. Participants who completed the 10% Happier app averaged 31 (SD 33) min/week; patients completing the Calm app averaged 71 (SD 74) min/week. 10% Happier app participants saw small effects on anxiety (P<.001 d=-0.43), depression (P=.02; d=-0.38), sleep disturbance (P=.01; d=-0.40), total symptom burden (P=.13; d=-0.27), and fatigue (P=.06; d=-0.30), and moderate effects on physical health (P<.001; d=0.52). Calm app participants saw small effects on anxiety (P=.29; d=-0.22), depression (P=.09; d=-0.29), sleep disturbance (P=.002; d=-0.47), physical health (P=.005; d=0.44), total symptom burden (P=.13; d=-0.27), and fatigue (P=.13; d=-0.27). Educational control participants (n=61) did not have effects on any patient-reported outcome except for a moderate effect on physical health (P<.001; d=0.77). Conclusions: Delivering meditation via the Calm app is feasible and scored higher in terms of feasibility when compared with the 10% Happier app. The Calm app will be used to implement a randomized controlled trial, testing the effects of meditation on symptom burden in MPNs. Trial registration: ClinicalTrials.gov NCT03726944; https://clinicaltrials.gov/ct2/show/NCT03726944 (Archived by WebCite at http://www.webcitation.org/77MVdFJwM).
... 7 The significant symptom burden associated to MF reflects on high healthcare costs. A recent north-American study showed that medical and pharmacological costs for patients with MF were 5-times higher than for a group of control patients without cancer, 9 reaching values as high as $34 690 (€25 972) per patient and year. Furthermore, a study carried out in Spain to estimate the indirect and non-medical costs associated to MF reported a mean cost of €86 315 per patient, which increased to €104 153 in patients still working, and €168 459 for more symptomatic patients. ...
Article
**Introduction:** Primary myelofibrosis (MF) is a rare hematologic disease belonging to the group of Philadelphia-negative chronic myeloproliferative neoplasms. Identification of the Janus Kinase (JAK) gene mutations inaugurated a new era in the targeted therapy of myeloproliferative diseases. Ruxolitinib is the first JAK1/JAK2 inhibitor specifically approved for the treatment of disease-related splenomegaly or symptoms in adult patients with primary myelofibrosis. The objective of this study was to assess the cost-effectiveness of ruxolitinib vs best available therapy (BAT) in MF patients in Spain. **Methods:** A decision-tree and Markov model were adapted to the Spanish setting to assess the cost-effectiveness of ruxolitinib vs. BAT on a lifetime horizon (≤15 years) from the societal perspective, while healthcare system perspective was included in the one-way sensitivity analysis. The population was assumed to be similar to that of the COMFORT-II clinical trial (CT), which was also the source of treatment efficacy data. BAT composition was derived from the same CT and validated with Spanish experts. Utilities were derived from the COMFORT-I CT. Costs included treatment, management, hospitalizations, emergency and outpatient visits, as well as adverse events and end-of-life costs. Additionally, costs associated to productivity loss were taken into account. Resource use was validated with experts and costs were extracted from Spanish sources. A probabilistic sensitivity analysis was also performed to evaluate the consistency of the results under the uncertainty or variability of the input data. **Results:** Patients on ruxolitinib accumulated 6.1 life years gained (LYGs), resulting in 73% extra life-years compared to patients treated with BAT (3.5LYs gained). Ruxolitinib provided 4.4 quality-adjusted life years (QALYs), with a 99% improvement compared to BAT (2.2 QALYs). This analysis gave an incremental cost of €47 199 per LYG and an incremental cost of €55 616 per QALY gained from the societal perspective. **Conclusions:** Ruxolitinib would be cost-effective in Spain according to the end-of-life criteria defined by the NICE and commonly referred for Spain (cost-effectiveness threshold of €61 500/QALY), in line with results published for other European countries.
... Hospitalization costs are even higher for myocardial infarction [29]. The increased cost of care among the thrombosis group in our study serves as further evidence of the economic burden of Philadelphia-negative MPNs [30]. ...
Article
Full-text available
Background Philadelphia-negative myeloproliferative neoplasms (MPNs) – polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) – often present with thrombosis. We aimed to determine the inpatient mortality, cost of care, and length-of-stay among individuals with Philadelphia-negative MPNs who had arterial or venous thrombosis associated with admission versus those who were admitted for non-thrombosis-related events. Methods Using ICD-10M coding, we identified 7,128,770 patients from the National Inpatient Sample (NIS) database who were hospitalized in 2016. 31,302 patients had a diagnosis of a Philadelphia-negative MPN. Mortality, length-of-stay, and cost of care were compared between patients who had thrombosis included among the top three diagnoses and those who were admitted for other reasons. Chi-squared test for categorical variables and t-test for continuous variables were used to compare baseline characteristics. Final multivariable models were constructed to determine predictors of outcomes. Results Inpatient mortality was significantly higher among individuals with Philadelphia-negative MPN who had thrombosis associated with admission as compared to those who were hospitalized for other reasons (5.7% versus 3.1%, P < 0.001). Unadjusted cost of care was also significantly higher for patients with thrombosis as compared to those without thrombosis ($25,539.06 versus $19,002.72 USD, respectively, P < 0.001). Length-of-stay was longer among the former group as compared to the latter (8.26 versus 7.95 days, P = 0.0963). However, this finding did not reach statistical significance. Conclusions Hospitalization for MPN-related thrombotic events is associated with excess inpatient mortality and higher cost of care. However, thrombosis has no statistically significant effect on length-of-stay among this population. The underlying causes of mortality and cost disparities among patients with MPN-associated thrombosis warrant further investigation.
... The full disease course of a patient may occur over several years or even decades with management, and outside of bone marrow or stem cell transplants, treatment is not curative. Given their chronic nature and limited therapy options, MPNs represent a significant public health cost and are a focus of ongoing research into precision medicine treatments [2]. The success of imatinib in treating chronic myeloid leukemia (CML) is a strong motivation in the search for treatments for other MPNs, particularly given the correlation of the other neoplasms with mutations along the JAK2 and other pathways [3]. ...
Article
Myeloproliferative neoplasms (MPNs) are chronic hematologic malignancies that may progress over long disease courses. The original date of diagnosis is an important piece of information for patient care and research, but is not consistently documented. We describe an attempt to build a pipeline for extracting dates with natural language processing (NLP) tools and techniques and classifying them as relevant diagnoses or not. Inaccurate and incomplete date extraction and interpretation impacted the performance of the overall pipeline. Existing lightweight Python packages tended to have low specificity for identifying and interpreting partial and relative dates in clinical text. A rules-based regular expression (regex) approach achieved recall of 83.0% on dates manually annotated as diagnosis dates, and 77.4% on all annotated dates. With only 3.8% of annotated dates representing initial MPN diagnoses, additional methods of targeting candidate date instances may alleviate noise and class imbalance.
... Classified as rare disorders, MPNs have an estimated global incidence of 0.3-6 per 100,000/year (4,5). The incidence is higher among females compared to males, and among the elderly population; the mean diagnosis of these disorders being 68 years (4)(5)(6)(7)(8)(9). Three main subtypes of MPNs have been identified which are commonly referred to as the 'classical MPN disorders' (1)(2)(3). ...
Thesis
Full-text available
Background: Myeloproliferative neoplasms (MPNs) are rare chronic haematological cancers. Several studies report fatigue as the most common MPN symptom which leads to a reduction in quality of life. There is a distinct lack of research into the lived experience of fatigue and how it affects the lives of people with MPN. Hypothesis and Aim: This study is hypothesis generating and aims to gain insight into the lived experience of fatigue in MPN. Methodology: People diagnosed with MPN were invited to complete an online quality of life survey and if eligible, express interest in further participating in a virtual focus group or interview. Thematic analysis was used to develop themes about the fatigue lived experience. Results: Twenty-three of the 82 survey respondents participated in eight interviews and four focus groups. Fatigue had a significant impact on the physical, cognitive, psychological and social wellbeing of participants. Four qualitative themes describing the experience of fatigue in MPN were developed: (1) Life with an MPN, (2) “It’s not being tired, it’s completely different. It’s fatigue”, (3) “It changes your life completely” and (4) Strategies to “live the best life I can”. These themes encompass the lived experience surrounding the diagnosis of MPN, the description of fatigue, the daily life of people with fatigue and how people manage their fatigue. Conclusions: Fatigue in MPN infiltrates all domains of life. A greater understanding of fatigue as a symptom of an MPN, and its prevention and management is urgently needed to help improve patient quality of life.
... According to a report published in 2014, the health care resource utilization associated costs for patients with MF, PV, and ET in the United States is 5.3, 1.8, and 3.6 times higher, respectively, as compared to age and gender-matched people without Ph-MPN [13]. Increased disease reporting through cancer registries and large population studies can better comprehend the disease process and prevent complications. ...
Article
Hydroxyurea (HU) or hydroxycarbamide is a cytotoxic antimetabolite widely used to treat Philadelphia chromosome-negative Myeloproliferative Neoplasms (Ph-MPN) like Polycythemia Vera (PV), Essential Thrombocythemia (ET), and Primary Myelofibrosis (PMF). Patients with Ph-MPN are at an increased risk of Non-melanoma skin cancers (NMSC). The cause of this finding remains uncertain. In this systematic review, we would like to know if chronic use of HU in this population is responsible for the sudden onset of NMSC. The results obtained will help the patients and clinicians with early diagnosis of cutaneous lesions and in optimizing the current treatment options for MPN. We conducted a multi-database literature search, applied eligibility criteria and quality assessment tools to the studies extracted, with an intention to include only fair to high-quality articles. We analyzed six observational studies and four traditional reviews. Two out of 10 studies concluded that no relationship exists between the incidence of NMSC and HU. The remaining eight studies indicated the association. According to these studies, the possible risk factors include old age, excessive exposure to sunlight, higher doses, and prolonged HU therapy duration. Ultraviolet (UV) radiation and HU play a combined role in carcinogenesis. Periodic dermatologic screening is essential in these patients. Prompt biopsy and accurate diagnosis can prevent the progression of cancer and decrease the associated morbidity and mortality. True incidence and causation cannot be ascertained due to the scarcity of research on this topic. Multi-center prospective studies in large groups of Ph-MPN patients are recommended to determine the temporal relationship between NMSC and HU treatment.
Article
In this retrospective, real-world study, we used medical claims data to evaluate the incidence of thromboembolic events (TEs), time to TE, associated risk factors, and health-care resource utilization (HRU) in Japanese patients with polycythemia vera (PV; N = 606) from April 1, 2008, to August 31, 2015. Baseline characteristics of interest included median age, 67.0 years; previous TEs, 11.6%; cardiovascular conditions (CVCs), 45.7%; and ≥ 3 risk factors, 17.8%. Overall, 100 patients experienced TEs (118 events) at a rate of 8.15/100 person-years [TE-free survival rate, 69.3% (2008–2015)]. The annual total health-care costs [mean (per person)] were significantly impacted by the presence of TEs (yes vs. no: ¥993,000 vs ¥459,000; P < 0.001). These results confirm that the presence of CVCs increases the risk of TEs in Japanese patients with PV; occurrence of TEs was associated with a higher HRU in these patients.
Article
We explored variables associated with patient-reported outcomes (PROs) including symptom burden, impact on daily life and work, obstacles during therapy, satisfaction level with therapy, and health-related quality of life in 1500 respondents with myeloproliferative neoplasms (MPNs) including essential thrombocythemia (ET), polycythemia vera (PV) and myelofibrosis (MF) in a multicenter, cross-sectional study across China, a representative of the developing countries. In multivariate analyses, urban household registration and higher education level were significantly-associated with no symptoms at diagnosis in respondents with ET or MF. CALR mutation was significantly-associated with lower MPN-10 scores in respondents with MF. Higher MPN-10 scores were significantly-associated with negative impact on daily life and work as well as lower satisfaction level in respondents with ET, PV and MF. Receiving ruxolitinib was significantly-associated with high satisfaction and satisfaction in respondents with MF. In addition, other demographics and clinical variables were also impacting PROs.
Article
Background We sought to describe the distribution and impact of comorbidities on outcomes in patients with myelofibrosis, a disease characterized by aberrant bone marrow function with eventual fibrosis. Comorbidities were scored using the Adult Comorbidity Evaluation-27 (ACE-27) and the Hematopoietic Cell Transplant-Comorbidity Index (HCT-CI), where a score of ≥3 indicates severe comorbidities. Patients and Methods We conducted a retrospective study of 306 patients with a confirmed diagnosis of myelofibrosis. Patients were seen from 1999-2014 with a median follow-up 2 years. Multivariable Cox proportional hazards models were constructed to assess the impact of comorbidities on overall survival and leukemic transformation from the date of presentation to our center. A series of descriptive analyses were performed examining the distribution of comorbidities captured by the scales. Results On multivariable survival analysis, an ACE-27 score of 3 was associated with an almost two-fold increase in the risk of all-cause death [HR 1.95 (95% CI 1.06-3.58), p=0.03] compared to a lower score of 0-1. An HCT-CI score of ≥3 was marginally significantly associated with an increased risk of all-cause death [HR 1.60 (95% CI 0.96-2.68), p=0.07]. ACE-27 captured a greater spectrum of cardiovascular and venous thrombotic disease. No impact of comorbidities on leukemic transformation was observed. Conclusions Although the presence of severe comorbidities was lower when assessed by ACE-27 (13%) compared to HCT-CI (23%), and the spectrums of comorbidities captured were different, the overall impact of severe comorbidities as assessed by both scales appears to be similar and associated with a survival disadvantage.
Article
Ruxolitinib is an oral JAK1/JAK2 inhibitor approved for the treatment of patients with myelofibrosis (MF) based on the results of two randomized clinical trials. However, discordant indications were provided by regulatory agencies and scientific societies for selecting the most appropriate candidates to this drug. The European LeukemiaNet and the Italian Society of Hematology shared the aim of building evidence-based recommendations for the use of ruxolitinib according to the GRADE methodology. Eighteen patient-intervention-comparator-outcome profiles were listed, each of them comparing ruxolitinib to other therapies with the aim of improving one of three clinical outcomes: a) splenomegaly, b) disease-related symptoms, and c) survival. Ruxolitinib was strongly recommended for improving symptomatic or severe (>15 cm below the costal margin) splenomegaly in patients with an IPSS/DIPSS risk INT2 or high. Ruxolitinib was also strongly recommended for improving systemic symptoms in patients with a MPN10 score higher than 44, refractory severe itching, unintended weight loss not attributable to other causes or unexplained fever. Because of weak evidence, the panel does not recommend ruxolitinib therapy for improving survival. Also, the recommendations given above do not necessarily apply to patients who are candidates for allogeneic stem cell transplant.Leukemia accepted article preview online, 14 October 2016. doi:10.1038/leu.2016.283.
Article
Background Polycythemia vera (PV) is one of the most common chronic myeloproliferative neoplasms, yet, little data is available on the epidemiology of PV in Spain and the costs of its management. This study aimed to evaluate the hospital incidence and mortality rate of PV in Spain, and to estimate hospital medical costs. Methods Hospital admission records of patients with PV registered between 2005 and 2019 were obtained from a Spanish hospital discharge database and analyzed in a retrospective multicenter study. Results Admission files of 490 patients were reviewed. Median age was 74 years; patients presented numerous conditions associated to age, namely hypertension, diabetes or anemia. Hospital mortality rate was associated to pulmonary heart disease, respiratory conditions and kidney disease. Most of the files analyzed corresponded to inpatient admissions; hospital incidence decreased over the study period in patients over 60 years. Median admission cost was €5580, increasing in patients deceased during the hospitalization. Admission cost increased significantly between 2006 and 2011. Conclusions This study provides an evaluation of hospital management and costs of PV in Spain. Future studies should focus on the revision of disease management in the country and measuring total medical costs, which could be higher than global estimations.
Article
Background: Overall survival (OS) and other important clinical trial end-points seem increasingly more elusive in supporting rapid and efficient incorporation of innovative cancer drugs in clinical practice. This study proposes a clinical trial based pharmacoeconomic framework to assess the therapeutic and economic value of ruxolitinib in patients with intermediate-2 or high-risk myelofibrosis. Methods: Individual patient level 144 week follow-up data from the COMFORT-II trial was used to account for the crossover effect on overall survival. Lifetime treatment benefits and costs were estimated considering detailed patterns of both ruxolitinib dose adjustments and blood transfusion needs. Results: The authors estimate a 3.3 years increment in life expectancy (HR = 0.30; 95% CI = 0.17–0.55; p-value <0.001) and an incremental cost-effectiveness ratio of €40,000 per life year gained with the use of ruxolitinib. Conclusion: This study also demonstrates how valuable information from clinical trials can be used to support informed decisions about the early incorporation of innovative drugs.
Article
Abstract Iron chelation therapies (ICTs) can help eliminate iron surplus in erythrocyte transfusion-dependent (TD) patients with myelofibrosis (MF). The study assessed adjusted incidence rate ratios (aIRRs) of MF-related complications and resource utilization (RU) and adjusted mean monthly inpatient cost differences in TD MF patients treated with vs. without ICT (ICT+ vs. ICT-) using data from two healthcare claims databases. Patients with ≥2 MF ICD-9 diagnosis codes ≥30 days apart were included. Among 571 TD MF patients, 103(18%) were ICT+ and 468(82%) were ICT-. ICT+ patients had lower rates of thrombocytopenia (aIRR: 0.55; p<0.001), pancytopenia (0.53; p<0.001), lower rates of ER visits (0.84[95% CI: 0.74-0.96]) and inpatient stays (0.75[0.64-0.87]), but higher rates of outpatient visits (1.21[1.18-1.23]). Adjusted mean complication-related inpatient cost difference per month was lower in ICT+ patients (-$1,804[$570]; p=0.004). ICT+ patients had significantly lower rates of acute care, but higher rates of outpatient care.
Article
Objectives: To explore health-related quality of life (HRQoL) and identify its associated variables in Chinese patients with Philadelphia-negative myeloproliferative neoplasms (MPNs) . Methods: In this cross-sectional study, anonymous questionnaires were distributed to adult patients with MPNs to assess symptom burden measured by MPN-10 and HRQoL measured by Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) . Results: The data from 1405 respondents with MPNs, including 645 (45.9%) with essential thrombocythemia (ET) , 297 (21.1%) with polycythemia vera (PV) , and 463 (33.0%) with myelofibrosis (MF) , were analyzed. 646 (46.0%) respondents were male. The median age was 56 (range, 18-99) years. The mean MPN-10 scores were 13.0±12.7, 15.0±14.7, and 21.0±16.6 (P<0.001) , and the physical component summary (PCS) and mental component summary (MCS) scores were 48.0±8.5, 47.0±9.0, and 42.0±10.0 (P<0.001) and 51.0±11.0, 50.0±10.8, and 49.0±11.1 (P=0.002) for respondents with ET, PV, and MF, respectively. Respondents with MF reported the lowest score of physical functioning, role functioning, emotional functioning, cognitive functioning, social function, and global health status (all P<0.01) and the highest score of fatigue, pain, dyspnea, appetite loss, diarrhea, and financial problems (all P<0.05) in EORTC QLQ-C30. Multivariate analyses revealed that higher MPN-10 scores were significantly associated with lower PCS (-0.220 to -0.277, P<0.001) and MCS (-0.244 to -0.329, P<0.001) scores; increasing age (-1.923 to -4.869; all P<0.05) , lower PCS score. Additionally, comorbidity (ies) , symptom at diagnosis, splenomegaly, anemia, unknown driver gene, and higher annual out-of-pocket cost were significantly associated with lower PCS and/or MCS scores. However, age ≥ 60 years, urban household registration, concomitant medication, and receiving ruxolitinib therapy in respondents with MF were associated with higher MCS scores. Weak correlations were found between MPN-10 score (except the subscale of appetite loss and constipation) and EORTC QLQ-C30 score in majority of subscales in respondents with ET (|r| = 0.193-0.457, all P<0.001) , PV (|r| = 0.192-0.529, all P<0.01) , and MF (|r| = 0.180-0.488, all P<0.001) , respectively. Conclusions: HRQoL in patients with MPN was significantly reduced, especially in patients with MF. Sociodemographic and clinical variables were significantly associated with the HRQoL in patients with MPNs.
Article
Polycythemia vera (PV) is a chronic myeloproliferative neoplasm characterized by clonal expansion of a hematopoietic progenitor, erythrocytosis, often leukocytosis and/or thrombocytosis, and nearly always an activating mutation in Janus kinase 2 (JAK2). The PV symptom burden can be considerable, in part driven by small or large vessel thrombotic tendency, splenomegaly, fatigue, pruritus, and a chronic risk of disease transformation to myelofibrosis or acute myeloid leukemia. In addition, patients with PV have an increased risk of mortality compared with the general population that often results from cardiovascular complications or disease transformation. Further, healthcare utilization and costs are higher in patients with PV than noncancer controls. First-line therapy options for high-risk patients may effectively manage PV in some instances; however, some patients do not receive adequate benefit from current treatment options and experience a more severe disease burden as a result. This may be especially true for those patients who are resistant to or intolerant of hydroxyurea or interferon-based therapies. New treatments currently being investigated in phase 3 clinical trials may alleviate disease burden in this patient population.
Article
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To observe the effect of the new World Health Organization (WHO) criteria on the incidence of myeloproliferative neoplasms, we performed a retrospective study of a population-based registry in the Côte d'Or area, France, from 1980 to 2007. A total of 524 myeloproliferative neoplasms were registered for the 1980-2007 period, including 135 polycythemia vera, 308 essential thrombocythemia and 81 idiopathic myelofibroses. No change in the incidence of either polycythemia vera or idiopathic myelofibrosis was observed for the 2005-2007 period, compared to 1980-2004. On the contrary, a pronounced increase in the incidence of essential thrombocythemia was noted after 2005, mainly due to the use of JAK2 mutation screening and a lower threshold of platelet count. Our study confirms the relevance of the new WHO diagnostic criteria in allowing earlier diagnosis of essential thrombocythemia.
Article
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In the literature the incidence rates for the chronic Philadelphia chromosome negative (Ph-) myeloproliferative disorders (MPD) are known to vary extensively; only a few studies have, however, been concerned with incidence trends over time. Therefore, the aim of the present work was to investigate possible trends as regards incidence rates over time for Ph-MPD. Herein, we carried out a retrospective population-based survey on the incidence of polycythaemia vera (PV), essential thrombocythaemia (ET) and chronic idiopathic myelofibrosis (IMF), in the city of Göteborg (Sweden), covering the years 1983-99. The study comprised 416 patients with Ph-MPD. There were 205 patients with PV, 153 patients with ET, 34 with IMF and 24 with unclassified MPD. The annual incidence for PV was 1.97 per 10(5) inhabitants; the corresponding figures for ET and IMF were 1.55 per 10(5) and 0.30 per 10(5) inhabitants, respectively. There was a significant increase in the annual incidence rate for ET (P = 0.008); this increase was significant for male subjects (P = 0.015) but did not reach significance for females (P = 0.118). No such increase over time was recorded as regards PV and IMF. The increasing annual incidence rate for ET is most possibly explained by the more frequent use of automated platelet counts whenever a patient consults a doctor. Thereby, an increasing number of patients with overt thrombocytosis of unknown origin are discovered and will be referred to specialists within the field of haematology for a correct diagnosis.
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There is a paucity of epidemiological data on chronic myeloproliferative disorders and myelodysplastic syndromes (MDS), while subtypes of acute myeloid leukemia (AML) are rarely defined. We identified 2,112 adult myeloid malignancies in the South Thames area between 1999 and 2000. The incidence (European standard population) of AML was 3.00/100,000, that of MDS 3.47/100,000, chronic myelomonocytic leukemia (CMML) 0.46/100,000, idiopathic myelofibrosis (IMF) 0.37/100,000, polycythemia vera (PV) 1.08/100,000, primary thrombocythemia (PT) 1.65/100,000 and chronic myeloid leukemia (CML) 1.09/100,000. The 3-year survival for AML was 15%, MDS 45%, CMML 29%, IMF 48%, PV 80%, PT 81% and CML 50% We believe this study reflects the true incidence and outcome of myeloid malignancies in South East England.
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The Janus kinase 2 mutation, JAK2617V>F, is myeloid neoplasm-specific; its presence excludes secondary polycythemia, thrombocytosis, or bone marrow fibrosis from other causes. Furthermore, JAK2617V>F or a JAK2 exon 12 mutation is present in virtually all patients with polycythemia vera (PV), whereas JAK2617V>F also occurs in approximately half of patients with essential thrombocythemia (ET) or primary myelofibrosis (PMF). Therefore, JAK2 mutation screening holds the promise of a decisive diagnostic test in PV while being complementary to histology for the diagnosis of ET and PMF; the combination of molecular testing and histologic review should also facilitate diagnosis of ET associated with borderline thrombocytosis. Accordingly, revision of the current World Health Organization (WHO) diagnostic criteria for PV, ET, and PMF is warranted; JAK2 mutation analysis should be listed as a major criterion for PV diagnosis, and the platelet count threshold for ET diagnosis can be lowered from 600 to 450 x 10(9)/L. The current document was prepared by an international expert panel of pathologists and clinical investigators in myeloproliferative disorders; it was subsequently presented to members of the Clinical Advisory Committee for the revision of the WHO Classification of Myeloid Neoplasms, who endorsed the document and recommended its adoption by the WHO.
Article
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Reporting of myelodysplastic syndromes (MDSs) and chronic myeloproliferative disorders (CMDs) to population-based cancer registries in the United States was initiated in 2001. In this first analysis of data from the North American Association of Central Cancer Registries (NAACCR), encompassing 82% of the US population, we evaluated trends in MDS and CMD incidence, estimated case numbers for the entire United States, and assessed trends in diagnostic recognition and reporting. Based on more than 40 000 observations, average annual age-adjusted incidence rates of MDS and CMD for 2001 through 2003 were 3.3 and 2.1 per 100,000, respectively. Incidence rates increased with age for both MDS and CMD (P < .05) and were highest among whites and non-Hispanics. Based on follow-up data through 2004 from the Surveillance, Epidemiology, and End Results (SEER) Program, overall relative 3-year survival rates for MDS and CMD were 45% and 80%, respectively, with males experiencing poorer survival than females. Applying the observed age-specific incidence rates to US Census population estimates, approximately 9700 patients with MDS and 6300 patients with CMD were estimated for the entire United States in 2004. MDS incidence rates significantly increased with calendar year in 2001 through 2004, and only 4% of patients were reported to registries by physicians' offices. Thus, MDS disease burden in the United States may be underestimated.
Article
To provide basic information about occurrence and outcome of essential thrombocythemia (ET) and agnogenic myeloid metaplasia (AMM), we used the Rochester Epidemiology Project medical record linkage system for residents of Olmsted County, Minnesota. We identified all residents who were diagnosed with ET or AMM from 1976 to 1995. Community inpatient and outpatient medical records were reviewed to verify the diagnosis of ET or AMM, and patients were followed passively through their medical records to determine the outcome after diagnosis. We identified 39 cases of ET and 21 of AMM, with age‐ and sex‐adjusted incidence rates of 2.53 and 1.46 cases/100,000 population annually, respectively. The respective median ages at diagnosis were 72 and 67 years. The female‐to‐male ratios were 1.8 and 1.6 for ET and AMM, respectively, and when adjusted for age, there was no difference in risk. The median follow‐up period was 62.9 months for ET and 33.2 months for AMM. Five‐ and 10‐year survivals were 74.4% and 61.3%, respectively, for ET and were significantly lower than expected for age‐matched controls ( P = 0.012). Prognosis was worse for AMM, with a median progression time of 7 months and a 3‐year survival of 52.4%. This was significantly worse than for age‐matched controls (P < 0.001). This study provides population‐based incidence and comparative survival figures in ET and AMM. Am. J. Hematol. 61:10–15, 1999. © 1999 Wiley‐Liss, Inc.
Article
Recombinant granulocyte colony-stimulating factor (G-CSF) was administered to healthy young (n = 32) and elderly (n = 19) volunteers (0 microgram/d, 30 microgram/d, or 300 microgram/d) to determine its effect on neutrophil production, blood kinetics, and tissue migration. Measurements included blood counts (daily), marrow neutrophil pool sizes and neutrophil tissue migration (baseline and day 5), blood kinetics (day 6), and marrow transit time while on drug (days 6 to 14). G-CSF markedly expanded the marrow neutrophil mitotic pool and shortened the transit time of the postmitotic pool (control, mean = 6.4 days; 300 microgram/d, mean = 2.9 d). G-CSF increased neutrophil production without significantly altering blood neutrophil half-life or margination. Compared to control, neutrophil accumulation in skin chambers decreased by about 50% in the 300 microgram/d group in both young and elderly subjects. G-CSF induced neutrophilia by stimulating proliferation of marrow neutrophil precursors and accelerating neutrophil entry into the blood. Decreased neutrophil inflammatory responses measured with the skin chamber technique may be because of the relative immaturity of the circulating cells or to alterations in neutrophil phenotype induced by G-CSF.
Article
2060 Background Three subtypes of MPN (myelofibrosis (MF), polycythemia vera (PV) and essential thrombocythemia (ET)) are characterized by activation of JAK2 signaling, with the majority having the JAK2 V617F mutation. Median survival in these subtypes ranges from months to years for MF (Gangat JCO 2011) and up to a decade or more for some patients with PV and ET. Some symptomatic treatment options exist, but with the exception of hematopoietic stem cell transplant, none are curative. Little is known about healthcare costs associated with these diseases. Objective To compare annual medical and pharmacy costs in three subtypes of MPN patients (MF, PV, ET) to matched non-cancer controls using a large US commercial claims database. Methods Data were drawn from the Thomson Reuters MarketScan database, which contains claims for insured employees, retirees and dependents from approximately 100 US payers. Index date was the first claim with an MPN diagnosis code in the time period 2005 to 2008. Eligible patients had one year continuous enrollment post-index with no evidence of non-AML secondary malignancy. Controls had one year of continuous enrollment after their match date and were matched to patients in a ratio of 5:1 based on gender, year of birth, geographic region and insurance type (Comprehensive, Health Maintenance Organization, Preferred Provider Organization, etc.). Controls were excluded if they had a service claim with a diagnosis for cancer or a pharmacy claim for chemotherapy. Costs were based on total gross payments to the provider, which equals the amount eligible for payment under the medical plan terms after applying rules for discounts, but before applying coordination of benefits, copayments and deductibles. Total cost was the sum of MPN and non-MPN related medical costs which included inpatient, outpatient and emergency room service and pharmacy. Pharmacy included injectable and non-injectable chemotherapy, supportive care and other prescription drug costs. Results A total of 25,145 MPN patients (MF: 509, PV: 16,165, ET: 8,471) were included and assigned matching controls. The mean cost (standard deviation) for cases and controls are shown in the table. Medical and Pharmacy Costs: Conclusions Annual medical and pharmaceutical costs for patients with MPNs are 2 to 6 times those of matched non-cancer patients and represent medical management challenges and payer burden. Outpatient visits accounted for about half of the total healthcare costs, followed by inpatient visits, pharmaceutical costs and ER visits. Disclosures Price: Elil Lilly and Company: Employment; Eli Lilly and Company: Equity Ownership. Pohl:Eli Lilly and Company: Employment; Eli Lilly and Company: Equity Ownership. Xie:Eli Lilly and Company: Employment; Eli Lilly and Company: Equity Ownership. Walgren:Eli Lilly and Company: Employment; Eli Lilly and Company: Equity Ownership.
Article
4273 Background Non-CML myeloproliferative neoplasms (MPNs), which include essential thrombocythemia (ET), polycythemia vera (PV), myelofibrosis (MF) and MPN not otherwise specified (MPN-NOS), are characterized by activation of JAK2 signaling and abnormal blood cell production. Median survival ranges from months to years for MF and up to a decade or more for PV and ET. Some symptomatic treatment options exist, but with the exception of hematopoietic stem cell transplant, none are curative. Although MPN incidence is highest in persons aged ≥65 years, little is known about overall health care utilization and costs in elderly persons with these diseases. MPNs are more prevalent in the elderly and therefore Medicare enrollees are a highly relevant source for US-based resource utilization and cost data for these diseases. Objective To compare all-cause health care utilization and costs from four subtypes of elderly MPN patients (ET, PV, MF and MPN-NOS) with matched non-MPN/non-cancer controls. Methods Retrospective data were taken from the Survey, Epidemiology, and End Results (SEER)-Medicare linked database in the US, which combines clinical information from the SEER cancer registry (MPN reporting has been required since 2001) with medical and pharmacy claims for Medicare enrollees. Patients with a new MPN diagnosis between Jan 1, 2001 and Dec 31, 2007 were selected and evaluated for all-cause health care utilization and costs from Jan 1, 2008 (index date) through Dec 31, 2008 (follow-up end date). Patients were classified by MPN subtype based on the most recent diagnosis information (ICD-O-3 from the SEER registry or ICD-9-CM from Medicare claims) before the index date. Patients who died before follow-up end, had HMO or discontinuous Medicare enrollment during the follow-up year, had enrollment based on end stage renal disease, or a diagnosis of a non-MPN malignancy before follow-up end were excluded from the study. Separate non-MPN/non-cancer control groups were selected for each MPN subtype and matched (5:1) on birth year, gender, ethnicity, geography, and reason for Medicare eligibility. Per patient health care utilization and costs during the follow-up year were aggregated and stratified by care setting. Costs were adjusted to 2010 US$ and represent amounts reimbursed by Medicare to providers. Costs were compared between MPN cases and controls using univariate t-tests. Results A total of 1,355 MPN patients (n = 445 ET, 684 PV, 81 MF, 145 MPN-NOS) were identified for study inclusion and assigned matching controls. For ET, PV, MF and MPN-NOS cases, respectively, mean [SD] age at index was 75.5 [9.7], 70.8 [11.3], 70.8 [10.4] and 74.1 [8.9] years and % female was 69.0, 43.9, 54.3, and 55.2. Mean [SD] years between first MPN diagnosis and study index date was 3.1 [2.0], 3.4[1.9], 2.7 [2.0], and 3.1 [2.1] for ET, PV, MF and MPN-NOS cases, respectively. A significantly (p<0.05) higher proportion of MPN cases, regardless of subtype, had ≥1 hospitalization during follow-up vs. controls (ET vs. control: 22% vs. 16%, PV vs. control: 27% vs. 15%, MF vs. control: 31% vs. 12%, MPN-NOS vs. control: 36% vs. 17%). Mean [SD] total days of hospital care were similarly higher in MPN cases (ET vs. control: 2.7 [12.8] vs. 1.6 [6.6], PV vs. control: 2.6 [7.0] vs. 1.7 [9.5], MF vs. control: 2.5 [6.2] vs. 1.2 [5.9], MPN-NOS vs. control: 4.0 [10.0] vs. 2.1 [13.7]), although the PV vs. control difference was not statistically significant. The ER visit rate during follow-up was also significantly (p<0.05) higher in MPN cases (ET vs. control: 34% vs. 24%, PV vs. control: 38% vs. 25%, MF vs. control: 46% vs. 21%, MPN-NOS vs. control: 44% vs. 29%). All-cause costs for MPN cases vs. matched controls are presented in the figure. Mean total costs per patient, driven equally by inpatient and outpatient services, were significantly (p<0.001) higher in MPN cases (ET vs. control: $11,259 vs. $8,897, PV vs. control: $13,337 vs. $8,530, MF vs. control: $20,917 vs. $7,367, MPN-NOS vs. control: $20,174 vs. $9,800). Conclusions Total health care costs during a given year for elderly patients with MPNs are 1.3 to 3 times higher (depending on subtype) than those of matched controls. These findings may help inform future cost effectiveness evaluations of novel MPN treatments, as well as decision making in the provision of optimal MPN care within a Medicare system in which resources are finite and must be allocated ethically and efficiently. Disclosures Karve: RTI Health Solutions: Consultancy, Research Funding. Price:Eli Lilly and Company: Employment, Equity Ownership. Davis:Eli Lilly, Merck, GlaxoSmithKline, Bristol-Myers Squibb, Pfizer, Eisai, Sanof-Aventis, Gilead Sciences, MedImmune: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Pohl:Eli Lilly and Company: Employment, Equity Ownership. Walgren:Eli Lilly and Company: Employment, Equity Ownership.
Article
The objective of this study was to develop a prospectively applicable method for classifying comorbid conditions which might alter the risk of mortality for use in longitudinal studies. A weighted index that takes into account the number and the seriousness of comorbid disease was developed in a cohort of 559 medical patients. The 1-yr mortality rates for the different scores were: "0", 12% (181); "1-2", 26% (225); "3-4", 52% (71); and "greater than or equal to 5", 85% (82). The index was tested for its ability to predict risk of death from comorbid disease in the second cohort of 685 patients during a 10-yr follow-up. The percent of patients who died of comorbid disease for the different scores were: "0", 8% (588); "1", 25% (54); "2", 48% (25); "greater than or equal to 3", 59% (18). With each increased level of the comorbidity index, there were stepwise increases in the cumulative mortality attributable to comorbid disease (log rank chi 2 = 165; p less than 0.0001). In this longer follow-up, age was also a predictor of mortality (p less than 0.001). The new index performed similarly to a previous system devised by Kaplan and Feinstein. The method of classifying comorbidity provides a simple, readily applicable and valid method of estimating risk of death from comorbid disease for use in longitudinal studies. Further work in larger populations is still required to refine the approach because the number of patients with any given condition in this study was relatively small.
Article
Objective: To reassess the natural history of polycythemia vera and to obtain reliable estimates of both incidence of thrombosis and survival for use in defining the sample size for therapeutic clinical trials. Study design: Retrospective cohort study of patients with polycythemia who had been followed for 20 years. Setting: 11 Italian hematology institutions. Patients: 1213 patients with polycythemia vera, which was diagnosed according to criteria established by the Polycythemia Vera Study Group and commonly used in clinical practice. Main outcome measures: All-cause mortality, venous and arterial thrombosis, and hematologic and nonhematologic neoplastic disease. Myocardial infarction and stroke were classified as major thrombotic events, and venous and peripheral arterial thrombosis were considered minor thrombotic events. The number of patients who died and the number of those who had major thrombotic events (combined end point) were used as a comprehensive measure of the benefit-risk ratio associated with the use of myelosuppressive agents. Results: 634 fatal and nonfatal arterial and venous thromboses were recorded in 485 patients (41%); 36% of these episodes occurred during follow-up in 230 patients (19%), and 64% occurred either at presentation or before diagnosis. Thrombotic events occurred more frequently in the 2 years preceding diagnosis, suggesting a causal relation between the latent myeloproliferative disorder and the vascular event. The incidence of thrombosis during follow-up was 3.4%/y; older patients or those with a history of thrombosis had a higher risk for thrombosis. Overall mortality was 2.9/100 patients per year; thrombotic events and hematologic or nonhematologic cancers had similar effects on mortality. Patients receiving chemotherapy died three to four times more frequently than those not receiving chemotherapy. The increased risk for cancer in patients receiving myelosuppressive agents was seen approximately 6 years after diagnosis. In addition, the combined end point, computed as the sum of the hardest available events (death, nonfatal myocardial infarction, or stroke), suggests that myelosuppressive agents have an overall unfavorable effect. Conclusions: Cytoreduction favorably affects the incidence of thrombotic events, but aggressive treatment seems to be associated with increased risk for neoplasm. These results provide a basis for reevaluating the therapeutic strategy in patients with polycythemia vera and for estimating the size of clinical trials aimed at testing new therapeutic approaches.
Article
An estimation of the incidence of polycythaemia vera (PV), essential thrombocythaemia (ET) and chronic idiopathic myelofibrosis (CIM) in the city of Göteborg, Sweden during the period 1983–1992 was made from a retrospective case analysis of patients registered as chronic myeloproliferative disorders (CMPD) at the Departments of Medicine and the Department of Pathology of the two major hospitals in the city. A total of 125 cases of PV, 56 males and 69 females were identified. The number of cases as well as the age‐specific incidence increased with age. The over all annual gender‐specific incidence was 2.69 cases per 105 male inhabitants and 3.12 cases per 105 female inhabitants. The incidence of PV in relation to the European Standard Population was 2.02 cases per 105 inhabitants and year. There were 72 cases, 20 males and 52 females, with ET. The age‐specific incidence was in all ages higher for females than for males and increased with age. The annual gender‐specific incidence was 0.96 per 105 male inhabitants and 2.35 per 105 female inhabitants. The incidence of ET in relation to the European Standard Population was 1.28 per 105 persons and year. There were 20 cases of CIM, 11 males and 9 females. The annual gender‐specific incidence of CIM was 0.53/105 male inhabitants and 0.41/105 female inhabitants. The incidence of CIM in relation to the European Standard Population was 0.31 per 105 persons and year. Seven persons, 2 males and 5 females, had a CMPD that could not be included in any of the above‐mentioned groups, but were registered as CMPD, unclassified.
Article
In an attempt to characterise the clinical features, incidence and outcome of essential thrombocythaemia (ET) we report our experience in a large unselected series of patients from a well defined region. All new cases of ET in the County of Copenhagen were registered during the period 1977–98. We identified 96 cases of ET, yielding an age- and sex-adjusted annual incidence rate of 0.59/100.000 and a point-prevalence at last follow up of 11/100.000. The overall incidence rate was 0.31 and 1.00 per 100.000 population during the consecutive periods 1977–89 and 1990–98, respectively, corresponding to a 3.2-fold increase. Median age at diagnosis was 67 yr (females 68 yr, males 66 yr, range 18–87 yr), and the female to male (F/M) ratio was 2.6:1. At diagnosis, 52% of the patients displayed no ET-related symptoms and were discovered fortuitously by a routine platelet count. Forty-eight percent presented with thrombohaemorrhagic phenomena, of which microvascular disturbances of the central nervous system (CNS), extremities and skin were most frequently observed (23%). Compared to patients diagnosed after 1989, patients diagnosed before 1990 had a significantly higher mean platelet count, white blood cell (WBC) count, lactate dehydrogenase (LDH) value and alkaline phosphatase value. With a median follow up of 70 months, 5-yr survival was 76%, significantly lower than the expected survival of an age- and sex-matched control group (p=0.0052). Thirty-seven patients experienced a total of 55 thrombohaemorrhagic events during follow-up, corresponding to an incidence of thrombosis and microvascular disturbances or haemorrhage of 8.1% per pt-yr and 2.5% per pt-yr, respectively. The number of patients experiencing thrombosis or microvascular disturbances was significantly higher among the 29 patients who never received acetylsalicylic acid (ASA) compared to the 67 patients who received ASA during follow up (45% vs. 21%; p=0.017). This study provides population-based data suggesting the benefit of treatment with low-dose ASA in a non-selected population of patients with ET.
Article
In this retrospective investigation from Malmö, a city well-suited for epidemiologic studies, 177 patients (88 males and 89 females) with polycythemia vera (PV) were identified between 1950 and 1984. The incidence rate (number of cases/100 000/yr) in both sexes increased significantly, being 1.0 in 1950–1959 and 2.6 in 1980–1984 (adjusted to the European age-standardized population). This is the highest rate reported to date. In 1970–1984 the highest age-specific incidence rates (number of cases/100 000/yr) were found in males ≥ 80 yr and females 70–79 yr of age, being 18.3 and 14.6, respectively. A subgroup of 12 (7%) was identified where the PV diagnosis was not obvious on entry into the study but where it became clear during follow-up. 16 PV patients (9%) had verified or suspected arterial hypoxemia caused by a concomitant condition. We conclude that the increasing PV incidence rates, mainly confined to older age groups, are probably due to better case ascertainment.
Article
THE National Institute on Aging (NIA) Geriatrics and Clinical Gerontology (GCG) Program convened an interdisciplinary Task Force on Comorbidity to foster the development of a research agenda on the multiple concurrent health problems that often occur in older persons. This report summarizes Task Force discussions held in Bethesda, Maryland (October 21-22, 2003; July 20-21, 2004) and serves as an introduction to the following three articles that address specific issues such as the nosological classification of impairment for the construction of comorbidity measures, staging and classification of disease severity, and methodological and analytical issues. The risk of developing concomitant chronic illnesses and physiological limitations escalates with aging. Diabetes, respiratory diseases, cancer, cardiovascular problems, arthritis, hypertension, and certain other chronic conditions are more common in older than in younger persons. As a consequence, a new diagnosis of any common chronic health condition is likely to be made in the context of preexisting health problems.
Article
To assess life expectancy and prognostic factors for survival in patients with polycythemia vera and essential thrombocythemia. The study sample consisted of 831 consecutive patients with polycythemia vera (n = 396; 4184 person-years of follow-up) or essential thrombocythemia (n = 435; 4304 person-years of follow-up). Mortality in each group was compared with the Italian population using the standardized mortality ratio (SMR) based on life expectancy data obtained from the Italian Institute of Statistics. The 15-year survival was 65% in patients with polycythemia and 73% in those with thrombocythemia. By Cox regression analysis, the independent predictors of death were a history of thrombosis for polycythemia (hazard ratio [HR] = 2.2; P = 0.0002) and thrombocythemia (HR = 2; P = 0.01), and male sex (HR = 1.8; P = 0.03) for thrombocythemia. Mortality compared with the general population was 1.6-fold higher (P <0.001) in patients with polycythemia but was not increased in those with thrombocythemia (SMR = 1; P = 0.8). Life expectancy of patients with polycythemia vera (especially if younger than 50 years) was reduced compared with the general population, whereas life expectancy of patients with essential thrombocythemia was not affected significantly by the disease, reflecting the more indolent nature of the proliferation. History of thrombosis was the main predictor of death in both diseases.
Article
Symptomatic burden in myeloproliferative neoplasms is present in most patients and compromises quality of life. We sought to validate a broadly applicable 18-item instrument (Myeloproliferative Neoplasm Symptom Assessment Form [MPN-SAF], coadministered with the Brief Fatigue Inventory) to assess symptoms of myelofibrosis, essential thrombocythemia, and polycythemia vera among prospective cohorts in the United States, Sweden, and Italy. A total of 402 MPN-SAF surveys were administered (English [25%], Italian [46%], and Swedish [28%]) in 161 patients with essential thrombocythemia, 145 patients with polycythemia vera, and 96 patients with myelofibrosis. Responses among the 3 administered languages showed great consistency after controlling for MPN subtype. Strong correlations existed between individual items and key symptomatic elements represented on both the MPN-SAF and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30. Enrolling physicians' blinded opinion of patient symptoms (6 symptoms assessed) were highly correlated with corresponding patients' responses. Serial administration of the English MPN-SAF among 53 patients showed that most MPN-SAF items are well correlated (r > 0.5, P < .001) and highly reproducible (intraclass correlation coefficient > 0.7). The MPN-SAF is a comprehensive and reliable instrument that is available in multiple languages to evaluate symptoms associated with all types of MPNs in clinical trials globally.
Article
Quality of life (QoL) in patients with myelofibrosis (MF) is severely compromised by severe constitutional symptoms (i.e. fatigue, night sweats, fever, weight loss), pruritus, and symptoms from frequently massive hepatosplenomegaly. Given that no current instrument of patient reported outcomes (PRO) exists that covers the unique spectrum of symptomatology seen in MF patients, we sought to develop a new PRO instrument for MF patients for use in therapeutic clinical trials. Utilizing data from an international Internet-based survey of 458 patients with MF we created a 20-item instrument (MFSAF: Myelofibrosis Symptom Assessment Form) which measures the symptoms reported by >10% of MF patients and includes a measure of QoL. We subsequently validated the MFSAF in a prospective trial of MF patients involving patient and provider feedback, as well as comparison to other validated instruments used in cancer patients. The MFSAF results were highly correlated with other instruments, judged comprehensive and understandable by patients, and should be considered for evaluation of MF symptoms in therapeutic trials.
Article
The objective of this study was to develop a prospectively applicable method for classifying comorbid conditions which might alter the risk of mortality for use in longitudinal studies. A weighted index that takes into account the number and the seriousness of comorbid disease was developed in a cohort of 559 medical patients. The 1-yr mortality rates for the different scores were: "0", 12% (181); "1-2", 26% (225); "3-4", 52% (71); and "greater than or equal to 5", 85% (82). The index was tested for its ability to predict risk of death from comorbid disease in the second cohort of 685 patients during a 10-yr follow-up. The percent of patients who died of comorbid disease for the different scores were: "0", 8% (588); "1", 25% (54); "2", 48% (25); "greater than or equal to 3", 59% (18). With each increased level of the comorbidity index, there were stepwise increases in the cumulative mortality attributable to comorbid disease (log rank chi 2 = 165; p less than 0.0001). In this longer follow-up, age was also a predictor of mortality (p less than 0.001). The new index performed similarly to a previous system devised by Kaplan and Feinstein. The method of classifying comorbidity provides a simple, readily applicable and valid method of estimating risk of death from comorbid disease for use in longitudinal studies. Further work in larger populations is still required to refine the approach because the number of patients with any given condition in this study was relatively small.
Article
The epidemiology of polycythaemia rubra vera (PV) has not been studied extensively in the past. In 1968 PV became subject to cancer registration in England and Wales. The mortality rates and registration rates for PV were abstracted for 1968-1982. The average annual mortality rates were 3.0/million/y (men, 1068 cases) and 2.3/million/y (women, 886 cases), there being no significant increase over the time period. The average annual registration rates were 10.7/million/y (men, 3321 cases) and 6.7/million/y (women, 2207 cases) and showed a large increase from 1968 to 1974 with a stable rate subsequently. This increase was concentrated in the 65+ age groups. The median age of registration was 60--64 y with a peak of mortality and incidence between ages 75 and 84 y. The data suggest some degree of overdiagnosis for PV registrations, however the rates are comparable with those seen in other studies in developed countries. The routine data sources require further validation, but they appear to provide useful information for the study of the epidemiology of PV.
Article
In the present study we analyzed the prognostic significance of several clinical, hematological, and histological parameters recorded at diagnosis in a consecutive series of 72 patients with primary myelofibrosis (PMF). Univariate analysis showed that the most significant indicators of poor survival were the following: age greater than 60, splenomegaly, anemia (hemoglobin > 10 g/dl), leukopenia (WBC < 4 x 10(9)/l or leukocytosis > 14 x 10(9)/l), and any of these histological features: adipose tissue and megakaryocyte reduction, prominent osteoblastic rims along the trabecular bone, presence of peritrabecular megakaryocytes (Mk), absence of normal or giant Mk. The multivariate analysis showed that only the level of hemoglobin and the presence of both normal Mk and fever independently influenced the prognosis. These parameters were used to set up a prognostic scoring system, allowing a feasible prognosis to be made for each patient at the time of diagnosis and identifying those patients in urgent need of new therapeutic approaches.
Article
To investigate the suggestion that the incidence of polycythemia vera has increased in recent decades, we ascertained secular trends in the incidence of polycythemia vera in Olmsted County, Minnesota, over the 55-year period, 1935-1989. The inpatient and outpatient medical records of all potential cases of polycythemia vera in Olmsted County residents were reviewed and the diagnostic criteria of the Polycythemia Vera Study Group were applied. We found no indication of an increase in the age- and sex-adjusted incidence of polycythemia vera, which averaged 1.9 per 100,000 person-years (95% C.I., 1.4-2.5) over the study period. Incidence rates increased with age, and age-adjusted incidence rates were greater for men (2.8 per 100,000 person-years; 95% C.I., 1.8-3.9) than for women (1.3 per 100,000 person-years; 95% C.I., 0.7-1.9), with the highest incidence rate (23.5 per 100,000 person-years) among men aged 70-79 years. Survival was reduced in this inception cohort of 50 cases, compared to that expected for individuals of like age and sex (P < 0.0001); median survival following diagnosis was 7.2 years.
Article
The distribution and the development of fibrosis were evaluated from bone marrow biopsies of patients with chronic myeloproliferative disorders (CMPD), regarding two groups of patients: (1) 564 with follow-up biopsies over a period of up to twelve years observation time, and (2) 1.787 diagnostic bone marrow biopsies from CMPD patients. Fibrosis was divided into three grades of fiber increase: early myelosclerosis, myelofibrosis, and advanced myelofibrosis. The first group of sequential BMB showed a significant progress to myelofibrosis in so-called "Chronic Megakaryocytic-Granulocytic Myelosis"--CMGM-, which corresponds to Agnogenic Myeloid Metaplasia-AMM-in 72.4% (21/29 patients), as well as in CML with megakaryocytic increase-CML.MI-in 39.2% (20/51). In the second group of diagnostic biopsies, only 30% of CMGM cases showed no fibrosis. In P. vera, 16.2% (18/111) developed myelofibrosis up to twelve years later. This figure was 4.3% (2/46) in Primary Thrombocythemia. Increase of megakaryocytes in CML indicates a high risk for developing fibrosis, combined with reduced life expectancy.
Article
To provide basic information about occurrence and outcome of essential thrombocythemia (ET) and agnogenic myeloid metaplasia (AMM), we used the Rochester Epidemiology Project medical record linkage system for residents of Olmsted County, Minnesota. We identified all residents who were diagnosed with ET or AMM from 1976 to 1995. Community inpatient and outpatient medical records were reviewed to verify the diagnosis of ET or AMM, and patients were followed passively through their medical records to determine the outcome after diagnosis. We identified 39 cases of ET and 21 of AMM, with age- and sex-adjusted incidence rates of 2.53 and 1.46 cases/100,000 population annually, respectively. The respective median ages at diagnosis were 72 and 67 years. The female-to-male ratios were 1.8 and 1.6 for ET and AMM, respectively, and when adjusted for age, there was no difference in risk. The median follow-up period was 62.9 months for ET and 33.2 months for AMM. Five- and 10-year survivals were 74.4% and 61.3%, respectively, for ET and were significantly lower than expected for age-matched controls (P = 0.012). Prognosis was worse for AMM, with a median progression time of 7 months and a 3-year survival of 52.4%. This was significantly worse than for age-matched controls (P < 0.001). This study provides population-based incidence and comparative survival figures in ET and AMM.
Article
In an attempt to characterise the clinical features, incidence and outcome of essential thrombocythaemia (ET) we report our experience in a large unselected series of patients from a well defined region. All new cases of ET in the County of Copenhagen were registered during the period 1977-98. We identified 96 cases of ET, yielding an age- and sex-adjusted annual incidence rate of 0.59/100.000 and a point-prevalence at last follow up of 11/100.000. The overall incidence rate was 0.31 and 1.00 per 100.000 population during the consecutive periods 1977-89 and 1990-98, respectively, corresponding to a 3.2-fold increase. Median age at diagnosis was 67 yr (females 68 yr, males 66 yr, range 18-87 yr), and the female to male (F/M) ratio was 2.6:1. At diagnosis, 52% of the patients displayed no ET-related symptoms and were discovered fortuitously by a routine platelet count. Forty-eight percent presented with thrombohaemorrhagic phenomena, of which microvascular disturbances of the central nervous system (CNS), extremities and skin were most frequently observed (23%). Compared to patients diagnosed after 1989, patients diagnosed before 1990 had a significantly higher mean platelet count, white blood cell (WBC) count, lactate dehydrogenase (LDH) value and alkaline phosphatase value. With a median follow up of 70 months, 5-yr survival was 76%, significantly lower than the expected survival of an age- and sex-matched control group (p = 0.0052). Thirty-seven patients experienced a total of 55 thrombohaemorrhagic events during follow-up, corresponding to an incidence of thrombosis and microvascular disturbances or haemorrhage of 8.1% per pt-yr and 2.5% per pt-yr, respectively. The number of patients experiencing thrombosis or microvascular disturbances was significantly higher among the 29 patients who never received acetylsalicylic acid (ASA) compared to the 67 patients who received ASA during follow up (45% vs. 21%; p = 0.017). This study provides population-based data suggesting the benefit of treatment with low-dose ASA in a non-selected population of patients with ET.
Article
As to the epidemiology of myeloproliferative disorders (MPD) very little solid information is available in the literature. The present work attempted to study the incidence of MPD in the city of Göteborg, Sweden during a period of ten years. Therefore, retrospectively we assessed the number of subjects afflicted with polycythaemia vera (PV), essential thrombocythaemia (ET) and idiopathic myelofibrosis (IM) over the study period of 1983-1992. The yearly calculated incidence for PV was 2.8 per 100,000 population. For ET and IM the corresponding figures were 1.5 and 0.4, respectively. The results for PV demonstrated the highest incidence rate reported in literature so far. As to ET and IM our results largely agree with what has been reported previously in the literature.
Article
You are creating a data abstraction form to assess the case mix, treatments, and treatment outcome for patients with cancer of the larynx at your center. You plan to perform univariate analysis including Kaplan-Meier curves with log-rank tests and multiple variable analysis to account for effect of disease and age on outcome. At your center some patients have radiotherapy, some have chemotherapy in association with radiotherapy, and some have primary surgery. A specific patient's treatment is based on the extent of disease and overall health. Patients with cancer of the larynx frequently have a variety of comorbid illnesses, often related to smoking and alcohol. For example, Mr. J.B. presented to the coronary care unit with his third myocardial infarction and was found to have a new cancer of the larynx. Due to his chronic obstructive pulmonary disease (COPD), diabetes, and past pulmonary embolus, he is not a candidate for either coronary revascularization or laryngectomy. How do you measure the impact of the comorbid illnesses on the decisions and the outcomes?
Article
The myeloproliferative disorders polycythaemia vera (PV), essential thombocythaemia (ET), and primary myelofibrosis (PMF) are clonal disorders of multipotent haematopoietic progenitors. The genetic cause of these diseases was not known until 2005, when several independent groups demonstrated that most patients with PV, ET and PMF acquire a single point mutation in the cytoplasmic tyrosine kinase JAK2 (JAK2V617F). These discoveries have changed the landscape for diagnosis and classification of PV, ET and PMF, and show the ability of genomic technologies to identify new molecular targets in human malignancies with pathogenetic, diagnostic and therapeutic significance.
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