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1.
Br J Haematol ; 204(5): 1740-1751, 2024 May.
Article in English | MEDLINE | ID: mdl-38351734

ABSTRACT

Thromboembolic events and bleeding are known complications in essential thrombocythaemia (ET) and polycythaemia vera (PV). Using multiple Swedish health care registers, we assessed the rate of arterial and venous events, major bleeding, all-cause stroke and all-cause mortality in ET and PV compared to matched controls. For each patient with ET (n = 3141) and PV (n = 2604), five matched controls were randomly selected. In total, 327 and 405 arterial or venous events were seen in the group of ET and PV patients respectively. Compared to corresponding controls, the rate of venous thromboembolism, major bleeding and all-cause mortality per 100 treatment years was significantly increased among both ET (0.63, 0.79 and 3.70) and PV patients (0.94, 1.20 and 4.80). The PV patients also displayed a significantly higher rate of arterial events and all-cause stroke compared to controls. When dividing the cohort into age groups, we found a significantly higher rate of arterial and venous events in all age groups of PV patients, and the rate of all-cause mortality was significantly higher in both ET and PV patients in all ages above the age of 50. This study confirms that PV and ET are diseases truly marked by thromboembolic complications and bleeding.


Subject(s)
Hemorrhage , Polycythemia Vera , Thrombocythemia, Essential , Thromboembolism , Humans , Thrombocythemia, Essential/mortality , Thrombocythemia, Essential/complications , Thrombocythemia, Essential/epidemiology , Middle Aged , Aged , Male , Female , Hemorrhage/mortality , Hemorrhage/etiology , Hemorrhage/epidemiology , Polycythemia Vera/mortality , Polycythemia Vera/complications , Sweden/epidemiology , Adult , Thromboembolism/mortality , Thromboembolism/epidemiology , Thromboembolism/etiology , Aged, 80 and over , Case-Control Studies , Registries , Young Adult , Adolescent , Stroke/mortality , Stroke/epidemiology , Stroke/etiology
6.
Eur J Haematol ; 106(3): 371-379, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33275803

ABSTRACT

OBJECTIVES: In patients with essential thrombocythemia (ET), after the JAK2V617F driver mutation, mutations in CALR are common (classified as type 1, 52-bp deletion or type 2, 5-bp insertion). CALR mutations have generally been associated with a lower risk of thrombosis. This study aimed to confirm the impact of CALR mutation type on thrombotic risk. METHODS: We retrospectively investigated 983 ET patients diagnosed in Spanish and Polish hospitals. RESULTS: With 7.5 years of median follow-up from diagnosis, 155 patients (15.8%) had one or more thrombotic event. The 5-year thrombosis-free survival (TFS) rate was 83.8%, 91.6% and 93.9% for the JAK2V617F, CALR-type 1 and CALR-type 2 groups, respectively (P = .002). Comparing CALR-type 1 and CALR-type 2 groups, TFS for venous thrombosis was lower in CALR-type 1 (P = .046), with no difference in TFS for arterial thrombosis observed. The cumulative incidence of thrombosis was significantly different comparing JAK2V617F vs CALR-type 2 groups but not JAK2V617F vs CALR-type 1 groups. Moreover, CALR-type 2 mutation was a statistically significant protective factor for thrombosis with respect to JAK2V617F in multivariate logistic regression (OR: 0.45, P = .04) adjusted by age. CONCLUSIONS: Our results suggest that CALR mutation type has prognostic value for the stratification of thrombotic risk in ET patients.


Subject(s)
Calreticulin/genetics , Genetic Predisposition to Disease , Mutation , Thrombocythemia, Essential/complications , Thrombocythemia, Essential/genetics , Thrombosis/etiology , Follow-Up Studies , Genetic Association Studies , Humans , Incidence , Janus Kinase 2/genetics , Odds Ratio , Prognosis , Retrospective Studies , Thrombocythemia, Essential/diagnosis , Thrombocythemia, Essential/mortality , Thrombosis/diagnosis , Thrombosis/mortality
7.
Am J Hematol ; 95(12): 1599-1613, 2020 12.
Article in English | MEDLINE | ID: mdl-32974939

ABSTRACT

DISEASE OVERVIEW: Polycythemia vera (PV) and essential thrombocythemia (ET) are myeloproliferative neoplasms (MPN) respectively characterized by clonal erythrocytosis and thrombocytosis; other disease features include leukocytosis, splenomegaly, thrombosis, bleeding, microcirculatory symptoms, pruritus and risk of leukemic or fibrotic transformation. DIAGNOSIS: Bone marrow morphology remains the cornerstone of diagnosis. In addition, the presence of JAK2 mutation is expected in PV while approximately 90% of patients with ET express mutually exclusive JAK2, CALR or MPL mutations (so called driver mutations). In ET, it is most important to exclude the possibility of prefibrotic myelofibrosis. SURVIVAL: Median survivals are approximately 15 years for PV and 18 years for ET; the corresponding values for patients age 40 or younger were 37 and 35 years. Certain mutations (mostly spliceosome) and abnormal karyotype might compromise survival in PV and ET. Life-expectancy in ET is inferior to the control population. Driver mutations have not been shown to affect survival in ET but risk of thrombosis is higher in JAK2 mutated cases. Leukemic transformation rates at 10 years are estimated at <1% for ET and 3% for PV. THROMBOSIS RISK: In PV, two risk categories are considered: high (age > 60 years or thrombosis history present) and low (absence of both risk factors). In ET, four risk categories are considered: very low (age ≤ 60 years, no thrombosis history, JAK2 wild-type), low (same as very low but JAK2 mutation present), intermediate (age > 60 years, no thrombosis history, JAK2 wild-type) and high (thrombosis history present or age > 60 years with JAK2 mutation). RISK-ADAPTED THERAPY: The main goal of therapy in both PV and ET is to prevent thrombohemorrhagic complications. All patients with PV require phlebotomy to keep hematocrit below 45% and once-daily or twice-daily aspirin (81 mg), in the absence of contraindications. Very low risk ET might not require therapy while aspirin therapy is advised for low risk disease. Cytoreductive therapy is recommended for high-risk ET and PV, but it is not mandatory for intermediate-risk ET. First-line drug of choice for cytoreductive therapy, in both ET and PV, is hydroxyurea and second-line drugs of choice are interferon-α and busulfan. We do not recommend treatment with ruxolutinib in PV, unless in the presence of severe and protracted pruritus or marked splenomegaly that is not responding to the aforementioned drugs. NEW TREATMENT DIRECTIONS: Controlled studies are needed to confirm the clinical outcome value of twice-daily vs once-daily aspirin dosing and the therapeutic role of pegylated interferons and direct oral anticoagulants.


Subject(s)
Aspirin/therapeutic use , Busulfan/therapeutic use , Interferon-alpha/therapeutic use , Polycythemia Vera , Thrombocythemia, Essential , Age Factors , Aspirin/adverse effects , Busulfan/adverse effects , Calreticulin/genetics , Disease-Free Survival , Humans , Interferon-alpha/adverse effects , Janus Kinase 2/genetics , Mutation , Polycythemia Vera/diagnosis , Polycythemia Vera/drug therapy , Polycythemia Vera/genetics , Polycythemia Vera/mortality , Receptors, Thrombopoietin/genetics , Risk Assessment , Risk Factors , Survival Rate , Thrombocythemia, Essential/diagnosis , Thrombocythemia, Essential/drug therapy , Thrombocythemia, Essential/genetics , Thrombocythemia, Essential/mortality
9.
Eur J Haematol ; 105(4): 408-418, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32557810

ABSTRACT

OBJECTIVE: We report an extension study of patients with essential thrombocythaemia (ET) in the Hungarian Myeloproliferative Neoplasm (HUMYPRON) Registry, which demonstrated that over 6 years anagrelide significantly decreased the number of patients experiencing minor arterial and minor venous thrombotic events (TEs) vs hydroxyurea+aspirin. METHODS: Data on patients with ET were collected through completion of a questionnaire developed according to 2008 WHO diagnostic criteria and with regard to Landolfi, Tefferi and IPSET criteria for thrombotic risk. Data were entered into the registry from 14 haematological centres. TEs, secondary malignancies, disease progression and survival were compared between patients with ET treated with anagrelide (n = 116) and with hydroxyurea+aspirin (n = 121). RESULTS: Patients were followed for (median) 10 years. A between-group difference in the number of patients with TEs was observed (25.9% anagrelide vs 38.0% hydroxyurea+aspirin; P = .052). Minor arterial events were more frequently reported in the hydroxyurea+aspirin group (P < .001); there were marginally more reports of major arterial events in the anagrelide group (P = .049). TE prior to diagnosis was found to significantly influence TE incidence (P > .001). Progression-free survival (P = .004) and survival (P = .001) were significantly increased for the anagrelide group vs hydroxyurea+aspirin. CONCLUSIONS: Anagrelide reduced TEs, and increased progression-free and overall survival vs hydroxyurea+aspirin over (median) 10 years.


Subject(s)
Thrombocythemia, Essential/complications , Thrombocythemia, Essential/mortality , Thrombosis/etiology , Thrombosis/mortality , Aspirin/administration & dosage , Aspirin/therapeutic use , Drug Therapy, Combination , Health Care Surveys , Humans , Hungary , Hydroxyurea/administration & dosage , Hydroxyurea/therapeutic use , Quinazolines/administration & dosage , Quinazolines/therapeutic use , Registries , Thrombocythemia, Essential/epidemiology , Thrombosis/epidemiology , Thrombosis/prevention & control , Treatment Outcome
10.
Cancer Med ; 9(6): 2096-2105, 2020 03.
Article in English | MEDLINE | ID: mdl-31994332

ABSTRACT

To explore the risk factors of thrombosis in patients with JAK2V617F -mutated myeloproliferative neoplasms (MPNs), a cohort of 1537 Chinese patients with JAK2V617F -mutated MPN was retrospectively analyzed. The Kaplan-Meier method and multivariate Cox analysis were used to study the risk factors of thrombosis in patients with JAK2V617F -mutated MPN. Among the 1537 MPN patients, 931, 468, and 138 had polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), respectively. The median follow-up time was 7 years (range 1-47), and 12.8% of patients (197/1537) died during this period. A total of 16.8% (259/1399) of PV and ET patients had secondary myelofibrosis, and 2.5% (38/1537) of patients developed acute myeloid leukemia (AML). Thrombotic events occurred in 43.9% (675/1537) of patients, among which 91.4% (617/675) were arterial thrombosis and 16.6% (112/675) were venous thrombosis. The number of thrombotic events in PV, ET, and PMF patients was 439 (47.2%), 197 (42.1%) and 39 (28.2%), respectively. The multivariate analysis indicated that age ≥60 years old, HCT ≥48%, at least one cardiovascular risk factor, a history of thrombosis, and JAK2V617F allele burden (V617F%) ≥50% are risk factors for thrombosis in JAK2V617F -mutated MPN. According to the results of the multivariate analysis, a risk model of thrombosis was established and comprised low-risk (0 points), intermediate-risk (1 points) and high-risk (≥2 points) groups, among which the incidence of thrombosis was 9.1%, 33.7% and 72.9%. For elderly patients with JAK2V617F -mutated MPN and a history of thrombosis, reducing the V617F%, controlling HCT and preventing cardiovascular risk factors are necessary measures to prevent thrombosis.


Subject(s)
Janus Kinase 2/genetics , Polycythemia Vera/complications , Primary Myelofibrosis/complications , Thrombocythemia, Essential/complications , Thrombosis/epidemiology , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Alleles , China/epidemiology , Disease-Free Survival , Female , Follow-Up Studies , Humans , Incidence , Male , Middle Aged , Mutation , Polycythemia Vera/genetics , Polycythemia Vera/mortality , Primary Myelofibrosis/genetics , Primary Myelofibrosis/mortality , Proportional Hazards Models , Retrospective Studies , Risk Assessment/methods , Risk Factors , Thrombocythemia, Essential/genetics , Thrombocythemia, Essential/mortality , Thrombosis/genetics , Young Adult
11.
Eur J Haematol ; 104(3): 271-278, 2020 Mar.
Article in English | MEDLINE | ID: mdl-31863513

ABSTRACT

OBJECTIVE: To explore the relative importance of risk factors, treatments, and blood counts for the occurrence of vascular complications and their impact on life expectancy in essential thrombocythemia (ET) and polycythemia vera (PV). METHODS: Nested case-control study within the Swedish MPN registry. From a cohort of 922 ET patients and 763 PV patients, 71 ET and 81 PV cases with vascular complications were compared with matched controls. RESULTS: Incidence of vascular complications was 2.0 and 3.4 events per 100 patient-years in ET and PV, respectively. At diagnosis, no significant risk factor differences were observed between cases and controls in neither of the diseases. At the time of vascular event, ET complication cases did not differ significantly from controls but in PV, cases had significantly higher WBCs and were to a lesser extent treated with anti-thrombotic and cytoreductive therapy. Life expectancy was significantly decreased in both ET and PV cases compared with controls. CONCLUSIONS: The risk of vascular complications is high in both ET and PV, and these complications have a considerable impact on life expectancy. The protective effect of anti-thrombotic and cytoreductive therapy for vascular complications in PV underscores the importance of avoiding undertreatment.


Subject(s)
Polycythemia Vera/complications , Polycythemia Vera/mortality , Thrombocythemia, Essential/complications , Thrombocythemia, Essential/mortality , Vascular Diseases/etiology , Adolescent , Adult , Aged , Aged, 80 and over , Biomarkers , Case-Control Studies , Female , Follow-Up Studies , Humans , Male , Middle Aged , Polycythemia Vera/diagnosis , Polycythemia Vera/epidemiology , Public Health Surveillance , Registries , Sweden/epidemiology , Thrombocythemia, Essential/diagnosis , Thrombocythemia, Essential/epidemiology , Vascular Diseases/diagnosis , Vascular Diseases/epidemiology , Young Adult
13.
Hematol Oncol ; 37(4): 434-437, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31465530

ABSTRACT

The conventional thrombotic risk stratification in essential thrombocythemia (ET) distinguishes patients in two risk groups based on previous thrombosis and age (< or >60). The IPSET-thrombosis takes into account four risk factors: age greater than 60 years and the presence of CV risk factors, thrombosis history and JAK2 V617F presence. The revised IPSET-thrombosis uses three adverse variables to delineate four risk categories: age greater than 60, thrombosis history, and JAK2 V617F presence. We compared different risk models in the estimation of thrombotic risk in 191 patients with ET and the role of specific driver mutations affecting overall survival, according to thrombotic risk. We also evaluated the mutational status of patients showing history of thrombosis or cardiovascular events versus patients who did not. Finally, we verified whether the thrombotic risk had a significant impact on survival in our ET patients. The data analysis has been performed through the conventional statistics and overall survival estimated by using the Kaplan-Meyer method. Interestingly, either using the traditional system for thrombotic risk or the IPSET-t prognostic score or the current stratification for the thrombotic risk, high-risk patients are always highly represented. This evidence is of note, being the high-risk category indicated for cytoreduction, affecting quality of life, despite the good overall prognosis of patients with ET diagnosis in general. The analysis of overall survival in our patients, according to different models for thrombotic risk, highlighted the poor prognosis of high-risk patients compared with those with a lower thrombotic risk, in particular when using traditional stratification and current stratification. In conclusion, the occurrence of thrombotic or cardiovascular events represents one of the most severe complications at diagnosis or during follow-up of ET despite current recommendations, having a significant impact on morbidity and survival.


Subject(s)
Severity of Illness Index , Thrombocythemia, Essential/complications , Thrombophilia/etiology , Thrombosis/etiology , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Calreticulin/genetics , Female , Follow-Up Studies , Humans , Incidence , Janus Kinase 2/genetics , Kaplan-Meier Estimate , Male , Middle Aged , Models, Biological , Mutation, Missense , Prognosis , Receptors, Thrombopoietin/genetics , Recurrence , Retrospective Studies , Risk Assessment/methods , Risk Factors , Thrombocythemia, Essential/genetics , Thrombocythemia, Essential/mortality , Thrombophilia/genetics , Thrombosis/epidemiology , Young Adult
15.
Biol Blood Marrow Transplant ; 25(6): e204-e208, 2019 06.
Article in English | MEDLINE | ID: mdl-30930192

ABSTRACT

We aimed to validate the MYelofibrosis SECondary to PV and ET prognostic model (MYSEC-PM) in 159 patients with myelofibrosis secondary to polycythemia vera (PV) and essential thrombocythemia (ET) from the European Society for Blood and Marrow Transplantation registry undergoing transplantation from matched siblings or unrelated donors. Furthermore, we aimed to test its prognostic performance in comparison with the Dynamic International Prognostic Scoring System (DIPSS). Score performance was analyzed using the concordance index (C): the probability that a patient who experienced an event had a higher risk score than a patient who did not (C > .5 suggesting predictive ability). Median follow-up of the total cohort was 41 months (range, 34 to 54), 45 months in post-PV and 38 months in post-ET myelofibrosis. Survival at 1, 2, and 4 years was 70% (95% CI, 63% to 77%), 61% (95% CI, 53% to 69%), and 52% (95% CI, 43% to 61%) for the total cohort; 70% (95% CI, 59% to 80%), 61% (95% CI, 49% to 73%), and 51% (95% CI, 38% to 64%) for post-PV; and 71% (95% CI, 61% to 81%), 61% (95% CI, 50% to 72%), and 54% (95% CI, 42% to 66%) for post-ET myelofibrosis (P = .78). Overall, the DIPSS was not significantly predictive of outcome (P = .28). With respect to the MYSEC-PM, overall survival at 4 years was 69% for the low-risk, 55% for the intermediate 1-risk, 47% for the intermediate 2-risk, and 22% (0% to 45%) for the high-risk groups. The prognostic model was predictive of survival overall (P = .05), whereas groups with intermediate 2 and high risk showed no significant difference (P = .44). Assessment of prognostic utility yielded a C-index of .575 (95% CI, .502 to .648) for the DIPSS, whereas assessment of the MYSEC-PM resulted in a C-statistics of .636 (95% CI, .563 to .708), indicating improvement in prediction of post-transplant survival using the new MYSEC-PM. In addition, transplantations from an unrelated donor in comparison with an HLA-identical sibling showed worse outcome (P = .04), and transplant recipients seropositive for cytomegalovirus in comparison with seronegative recipients (P = .01) showed worse survival. In conclusion, incorporating transplant-specific and clinical and mutational information together with the MYSEC-PM may enhance risk stratification.


Subject(s)
Hematopoietic Stem Cell Transplantation/methods , Polycythemia Vera/therapy , Primary Myelofibrosis/therapy , Thrombocythemia, Essential/therapy , Transplantation, Homologous/methods , Adult , Aged , Humans , Middle Aged , Polycythemia Vera/mortality , Primary Myelofibrosis/mortality , Prognosis , Survival Analysis , Thrombocythemia, Essential/mortality , Treatment Outcome
16.
J Natl Compr Canc Netw ; 17(3): 211-219, 2019 03 01.
Article in English | MEDLINE | ID: mdl-30865915

ABSTRACT

ABSTRACTBackground: Current guidelines recommend hydroxyurea (HU) as frontline therapy for patients with high-risk essential thrombocythemia (ET) to prevent thrombosis. However, little is known about the impact of HU on thrombosis or survival among these patients in the real-world setting. PATIENTS AND METHODS: A retrospective cohort study was conducted of older adults (aged ≥66 years) diagnosed with ET from 2007 through 2013 using the linked SEER-Medicare database. Multivariable Cox proportional hazards regression models were used to assess the effect of HU on overall survival, and multivariable competing risk models were used to assess the effect of HU on the occurrence of thrombotic events. RESULTS: Of 1,010 patients, 745 (73.8%) received HU. Treatment with HU was associated with a significantly lower risk of death (hazard ratio [HR], 0.52; 95% CI, 0.43-0.64; P<.01). Every 10% increase in HU proportion of days covered was associated with a 12% decreased risk of death (HR, 0.88; 95% CI, 0.86-0.91; P<.01). Compared with nonusers, HU users also had a significantly lower risk of thrombotic events (HR, 0.51; 95% CI, 0.41-0.64; P<.01). CONCLUSIONS: Although underused in our study population, HU was associated with a reduced incidence of thrombotic events and improved overall survival in older patients with ET.


Subject(s)
Hydroxyurea/adverse effects , Hydroxyurea/therapeutic use , Thrombocythemia, Essential/complications , Thrombocythemia, Essential/drug therapy , Thrombosis/etiology , Thrombosis/mortality , Aged , Aged, 80 and over , Female , Health Care Surveys , Humans , Hydroxyurea/administration & dosage , Kaplan-Meier Estimate , Male , Prognosis , Risk Assessment , Risk Factors , SEER Program , Thrombocythemia, Essential/epidemiology , Thrombocythemia, Essential/mortality , Thrombosis/diagnosis , Thrombosis/epidemiology , Treatment Outcome
17.
Mayo Clin Proc ; 94(4): 599-610, 2019 04.
Article in English | MEDLINE | ID: mdl-30824279

ABSTRACT

OBJECTIVE: To document the Mayo Clinic decades-long experience with myeloproliferative neoplasms (MPNs) and provide mature risk-stratified survival data and disease complication estimates. PATIENTS AND METHODS: All Mayo Clinic patients with World Health Organization-defined MPNs constituted the core study group and included those with polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). RESULTS: A total of 3023 consecutive patients (median age, 62 years; range, 18-96 years) were considered: 665 PV, 1076 ET, and 1282 PMF. From October 27, 1967, through December 29, 2017, 1631 deaths (54%), 183 leukemic transformations (6%), 244 fibrotic progressions (14%), and 516 thrombotic events (17%) were recorded. Median overall survival (OS) was 18 years for ET, 15 years for PV, and 4.4 years for PMF (P<.05 for all intergroup comparisons). Inferior survival was documented in patients with ET diagnosed more recently (post-1990) (P<.001), whereas survival data were time independent in PV and PMF. After conventional risk stratification, OS in low-risk ET and low-risk PV were superimposed (P=.89) but each differed significantly from that of age- and sex-matched controls (P<.001). Leukemia-free survival was similar for ET and PV (P=.22) and significantly worse with PMF (P<.001). Compared with ET, PV was associated with higher risk of fibrotic progression (P<.001). Thrombosis risk after diagnosis was highest in PV and lowest in PMF (P=.002 for PV vs ET; P=.56 for ET vs PMF; and P=.001 for PV vs PMF). CONCLUSION: This study provides the most mature survival and outcomes data in MPNs and highlights MPN subgroup risk categorization as key in appraising disease natural history. The OS was only marginally better in ET compared with PV, and PV displayed a higher risk of thrombosis and fibrotic progression.


Subject(s)
Polycythemia Vera/mortality , Primary Myelofibrosis/mortality , Thrombocythemia, Essential/mortality , Adult , Aged , Disease Progression , Female , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , Survival Analysis
20.
Am J Hematol ; 94(1): 5-9, 2019 01.
Article in English | MEDLINE | ID: mdl-30252953

ABSTRACT

First-line cytoreductive drug of choice in high risk essential thrombocythemia (ET) is currently hydroxyurea, a practice based on the results of a randomized study; second-line drugs of choice include pegylated interferon-α, busulfan and anagrelide. Anagrelide clinical trials were pioneered by the late Murray N. Silverstein (1928-1998) of the Mayo Clinic whose studies led to FDA approval in March 1997. The current study represents a retrospective examination of the potential impact of anagrelide therapy on survival and disease complications in ET. 1076 patients with ET were considered (median age 58 years; females 63%); risk distribution, according to the international prognostic score for ET (IPSET), was 28% high, 42% intermediate, and 30% low. Overall (OS), myelofibrosis-free (MFFS) and thrombosis-free survival data were compared for ET patients diagnosed before and after the 1997 FDA approval date for anagrelide; a significant difference was apparent in OS (P = .006; HR 1.4, 95% CI 1.1-1.7) and MFFS (P < .001; HR 4.2, 95% CI 2.7-6.5), in favor of patients diagnosed prior to 1997; the difference was sustained during multivariable analysis that included IPSET. Similarly stratified survival data in polycythemia vera (n = 665) and primary myelofibrosis (n = 1282) showed no similar impact on survival (P = .3 and .17, respectively). The current study represents a retrospective analysis and suggests significantly decreased OS and MFFS in ET patients diagnosed after the FDA approval date of anagrelide. Whether or not anagrelide therapy was to blame for the worsening of OS and MFFS over time cannot be assumed and requires validation in a prospective study.


Subject(s)
Platelet Aggregation Inhibitors/therapeutic use , Quinazolines/therapeutic use , Thrombocythemia, Essential/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Bone Marrow/pathology , Disease Progression , Disease-Free Survival , Drug Approval , Female , Fibrosis , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Mortality/trends , Platelet Aggregation Inhibitors/adverse effects , Polycythemia Vera/drug therapy , Polycythemia Vera/mortality , Primary Myelofibrosis/drug therapy , Primary Myelofibrosis/mortality , Prognosis , Proportional Hazards Models , Quinazolines/adverse effects , Retrospective Studies , Severity of Illness Index , Thrombocythemia, Essential/mortality , Thrombocythemia, Essential/pathology , Thrombosis/etiology , Thrombosis/prevention & control , Treatment Outcome , Young Adult
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