scholarly journals Low-Risk Polycythemia Vera Treated with Phlebotomies: Clinical Characteristics, Hematologic Control and Complications in 358 Patients from the Spanish Registry of Polycythemia Vera

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3621-3621
Author(s):  
Ana Triguero ◽  
Alexandra Pedraza ◽  
Manuel Pérez ◽  
María Isabel Mata ◽  
Beatriz Bellosillo ◽  
...  
Keyword(s):  
Polycythemia Vera ◽  
Research Funding ◽  
Clinical Characteristics ◽  
Treatment Strategies ◽  
Myeloproliferative Disorders ◽  
Primary Prophylaxis ◽  
Low Risk ◽  
Major Hemorrhage ◽  
Risk Patients

Abstract Introduction: Current recommendations for patients with low-risk polycythemia vera (PV) include hematocrit (Htc) control with phlebotomies and primary prophylaxis of thrombosis with low-dose aspirin. There is scarce information regarding the hematological control, the incidence of complications and the need for cytoreduction in PV patients treated with phlebotomies only. Methods: A total of 358 patients with low-risk PV (<60 years old and without history of thrombosis) from the Spanish Registry of Polycythemia Vera were included in the present study. PV-related symptoms and blood counts were collected at 6, 12, 18, 24, 36, 48 and 60 months from diagnosis while the patients were treated with phlebotomies only. The duration of the treatment with phlebotomies, the indication of starting cytoreduction and the incidence of thromboembolic and hemorrhagic events during the cytoreduction-free period was also analyzed. Results: Baseline characteristics at the time of diagnosis are described in Table 1. Table 2 summarizes the main hematological and clinical characteristics under treatment with phlebotomies. Inadequate control of the Htc (> 45%) was reported in 61-70% of the patients, leukocytosis >15x10 9/l in 10% and thrombocytosis >1000x10 9/l in 5%. In addition, about 20% of the patients had pruritus and 10% had microvascular symptoms. Of the 358 patients included, 275 (77%) required cytoreduction, 261 (73%) with hydroxyurea and 14 (4%) with IFN. The main indication of cytoreduction was thrombocytosis (20%), followed by age >60 years old (15%) and microvascular symptoms (13%). Median duration of cytoreduction abstention was 4.7 (0.1-30.4) years being significantly longer in patients younger than 50 years (6 and 2 years for patients younger and older than 50 years, respectively, p<0.0001). With a follow-up of 1659 person-years under phlebotomy only treatment, 14 thrombosis were observed (arterial n=9, venous n= 5), 12 hemorrhages (major n=4, minor n=8) and 4 solid tumors (1 melanoma and 3 non-cutaneous carcinomas). The incidence of complications during the cytoreduction-free period by person-years was: 0.8% for thrombosis, 0.2% for major hemorrhage and 0.2% for second neoplasia. The median follow-up until last visit including the time after starting cytoreductive therapy was 8.4 (0.2-39) years. Of 14 deaths observed, none occurred during the phlebotomy period. Half of the patients died from PV related reasons but the other 50% were not related. The median survival estimation by K-M was 36.5 years. Disease progression was documented in 27 (7.5%) patients, 26 of them to myelofibrosis, 1 to myelodysplastic syndrome and none to acute leukemia. Progression to myelofibrosis occurred during the cytoreduction-free period in 5 patients (1.4%) after a median of 5.8 years (Range: 4.9-8.9). Conclusions The incidence of thrombotic and hemorrhagic complications was very low in this series of low-risk patients treated with phlebotomies, even though only 30-40% of patients maintained the Htc <45%. The data from the present study show that low-risk patients have different therapeutic needs than other PV patients and support the development of new treatment strategies. Representing the Spanish Group of Myeloproliferative Disorders. GEMFIN Figure 1 Figure 1. Disclosures Bellosillo: Qiagen: Consultancy, Speakers Bureau; Roche: Consultancy, Research Funding; Thermofisher Scientific: Consultancy, Speakers Bureau. Ferrer Marin: Cty: Research Funding; Incyte: Consultancy, Research Funding; Novartis: Speakers Bureau. Garcia Gutierrez: Novartis: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Incyte: Consultancy, Honoraria, Research Funding.

Abstract 2640: Clinical Characteristics and Risk Stratification in Symptomatic and Asymptomatic Patients with Brugada Syndrome - Multi-center Study in Japan-

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Masahiko Takagi ◽  
Yasuhiro Yokoyama ◽  
Kazutaka Aonuma ◽  
Naohiko Aihara ◽  
Masayasu Hiraoka
Keyword(s):  
Sudden Death ◽  
Risk Stratification ◽  
Brugada Syndrome ◽  
Clinical Characteristics ◽  
Low Risk ◽  
Cardiac Events ◽  
Asymptomatic Patients ◽  
Risk Patients ◽  
Qrs Duration

Background Neither the clinical characteristics nor risk stratification of symptomatic and asymptomatic patients with Brugada syndrome have been clearly determined. We compared clinical and ECG characteristics of symptomatic and asymptomatic patients with Brugada syndrome to identify new markers for distinguishing high- from low-risk patients. Methods A total of 216 consecutive individuals with Brugada syndrome (mean age 52±14 years, 197 males) were enrolled in the Japan Idiopathic Ventricular Fibrillation Study (J-IVFS). Clinical and ECG characteristics were compared among 3 groups of patients: VF group; patients with aborted sudden death and documented VF (N=34), Syncope (Sy) group; patients with syncope without documented VF (N=70), and Asymptomatic (As) group; subjects without symptoms (N=112). Comparisons were made among the 3 groups as well as between the symptomatic (VF/Sy) and asymptomatic (As) groups. Short-term prognosis was also compared among the 3 groups, and between the VF/Sy and As groups. Results 1) Clinical characteristics: incidence of past history of AF was significantly higher in the VF and Sy groups than in the AS group (26, 26, and 12 %, respectively; [p=0.04]), though no other clinical parameters differed among the groups. 2) On resting 12-lead ECG, r-J interval (interval from QRS onset to J point) in lead V2 and QRS duration in lead V6 were highest in the VF group (104, 98, and 92 msec in V2 [p<0.001]; 106, 103, and 94 msec in V6 [p<0.0001], respectively, VF vs. Sy vs. As). 3) Positive late potential and inducibility of VF by EPS did not differ in incidence among the 3 groups. 4) Clinical follow-up: during a mean follow-up of 36±16 months, incidence of cardiac events (sudden death and/or VF) was higher in the VF/Sy groups than in the As group (29, 8, and 0 %, respectively [p<0.001]). Multivariate analysis showed that the frequencies of r-J interval ≥ 90 msec in lead V2 and QRS duration ≥ 90 msec in lead V6 were significantly higher in patients with cardiac events (p=0.02, 0.02, respectively). Conclusions In symptomatic patients, prolonged ventricular depolarization in precordial leads of the ECG was prominent in the VF group, and this sign can be used to distinguish high- from low-risk patients with Brugada syndrome.

Real-World Treatments and Thrombotic Events in Polycythemia Vera Patients: A Retrospective Analysis between 2018-2019 in US Population

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 1-2
Author(s):  
Srdan Verstovsek ◽  
Ariel Han ◽  
Karin Chun Hayes ◽  
Tracy Woody ◽  
Frank Valone ◽  
...  
Keyword(s):  
High Risk ◽  
Real World ◽  
Blood Cells ◽  
Initial Treatment ◽  
Research Funding ◽  
Treatment Initiation ◽  
Low Risk ◽  
High Risk Patients ◽  
Risk Patients

BACKGROUND Polycythemia Vera (PV) is a rare myeloproliferative neoplasm associated with an increased production of red blood cells, white blood cells, and platelets. Most frequent treatment includes phlebotomy, hydroxyurea, interferon, and ruxolitinib. Current NCCN guideline recommends managing HCT levels to below 45%. The objective of this study was to determine real-world standards of care and patient characteristics, and to observe how treatment decisions vary by HCT level and thrombosis risk. METHODOLOGY We conducted a retrospective study using Symphony Health's longitudinal transactional healthcare claims database that includes prescription, medical and hospital claims across &gt; 4,900 US payers representing 86% of US lives. Eligible patients had at least one ICD-10 diagnosis code for PV and at least one of the treatments including phlebotomy, hydroxyurea, busulfan, interferon, and ruxolitinib between Jan 1, 2018 and Dec 31, 2019 (index period). For eligible patients, all prior treatment history initiated as far back as January 2010 was used to report therapy changes. Patients were also required to have at least one PV diagnosis within a year of treatment initiation and at least 2 HCT lab results during the index period. PV treatment changes and characteristics were studied. RESULTS Out of 28,306 patients with PV, 4,264 patients had HCT lab data for 2 years (index period). Median duration of follow-up was 854 days (range 98-3,373days). Patient therapy duration was from 1 to 9 years. Median patient age was 65 (range 11-94), with 1,451 (34%) patients aged less than 60, 2,813 (66%) 60 years or older, and a substantial male predominance (62% vs 38%). 1,247 (29%) patients were classified as Low Risk (age&lt; 60 with no TE history) and 3,017 (71%) patients as High Risk. Within the High-Risk group, 2,224 (52%) were age&gt;60 without prior TE, 204 (5%) were age&lt;60 with prior TE and 589 (14%) were age&gt;60 with prior TE. For Low Risk patients' initial treatment was phlebotomy alone (85%) and a total of 73% of all Low Risk patients remained on phlebotomy alone. For High Risk patients' initial treatment was phlebotomy alone (60%) and 43% all of High-Risk patients remained on phlebotomy alone (Figure 1). The median HCT prior to treatment initiation was 52.9% and 48% during treatment. 936 (22%) patients achieved NCCN treatment guidelines with HCT levels always remaining under 45%, and 1,226 (29%) patients had HCT levels controlled between 45% and 50%. However, 2,102 (49%) patients had some or all HCT levels&gt; 50% (Figure 2). With the most recent lab test, 2,180 (51%) of patients still had HCTs above 45% and 804 (19%) were still above 50%. In a sub-cohort of 653 High Risk patients with a prior TE and up to 5 years of follow up, 236 (36%) had at least one other TE; for the 1,774 High Risk patients who did not have the history of thrombosis, 161(9%) had at least one TE (Table 2). The most common TE since treatment began in patients with prior TE were deep vein thrombosis (n= 92 patients, 14%) and stroke (n= 95 patients, 15%). Among High Risk patients (n=397) who had another thrombotic event, 180 (45%) were treated by phlebotomy only and never switched to any other therapies. CONCLUSIONS Despite currently available treatments in US, patients' HCT level after treatment were higher than recommended as per guidelines. Failure to maintain HCT less than 45% increases the risk of future thrombotic events as shown by 36% of patients with prior TE experiencing another TE within the next 5 years. Disclosures Verstovsek: Sierra Oncology: Consultancy, Research Funding; ItalPharma: Research Funding; Blueprint Medicines Corp: Research Funding; NS Pharma: Research Funding; Promedior: Research Funding; Incyte Corporation: Consultancy, Research Funding; Protagonist Therapeutics: Research Funding; Novartis: Consultancy, Research Funding; Roche: Research Funding; AstraZeneca: Research Funding; PharmaEssentia: Research Funding; Genentech: Research Funding; Celgene: Consultancy, Research Funding; Gilead: Research Funding; CTI Biopharma Corp: Research Funding. Han:Protagonist Therapeutics: Consultancy. Chun Hayes:Protagonist: Consultancy. Woody:Protagonist: Current Employment. Valone:Protagonist: Current Employment. Gupta:Protagonist: Current Employment.

scholarly journals Low Von Willebrand Factor: Cut-Off Value for Diagnosis and Risk Score to Predict Bleeding Incidence

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 18-19
Author(s):  
Ferdows Atiq ◽  
Esmee Wuijster ◽  
Moniek P.M. de Maat ◽  
Marieke J.H.A. Kruip ◽  
Marjon H. Cnossen ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Score ◽  
Research Funding ◽  
Low Risk ◽  
Intermediate Risk ◽  
Spontaneous Bleeding ◽  
High Risk Patients ◽  
Risk Patients ◽  
Surgical Bleeding

Introduction Although large studies have recently provided valuable insights on the diagnosis, bleeding phenotype, and treatment outcomes of VWD patients, these aspects remain poorly understood in individuals with low VWF. Firstly, there is no clear evidence which cut-off value should be used to diagnose low VWF. Although 0.50 IU/mL is the most recommended cut-off value, some centers use the lower limit of normal (0.60 IU/mL). Secondly, the incidence of post-surgical bleeding, postpartum hemorrhage (PPH) and traumatic- or spontaneous bleeding after diagnosis of low VWF are still unknown. Lastly, it is hard to predict which individuals with low VWF have an increased bleeding risk. Therefore, we investigated the bleeding phenotype of individuals with historically lowest VWF levels of 0.31-0.50 IU/mL and 0.51-0.60 IU/mL, and the incidence of post-surgical bleeding, PPH and traumatic- and spontaneous bleeding after their initial diagnosis of "low VWF". Methods We performed a retrospective cohort study from January 2007 to November 2019 at the Erasmus MC, University Medical Center Rotterdam. All patients evaluated for the presence of a bleeding disorder with VWF antigen (VWF:Ag) and/or VWF activity (VWF:Act) and/or VWF collagen binding (VWF:CB) levels between 0.31-0.60 IU/mL, were included. Patients with VWF:Ag and/or VWF:Act and/or VWF:CB ≤0.30 IU/mL, acquired VWD and those with a concomitant bleeding disorder were excluded. For each individual we collected data from electronic patient files on baseline characteristics, reason for referral, family history of bleeding disorders, ISTH-BAT and laboratory measurements at diagnosis. Retrospective follow-up started from initial date of low VWF diagnosis through November 2019, during which we collected data on surgical procedures, pregnancies, and incidence of spontaneous- and traumatic bleeding. Results We included 439 patients; 269 patients with historically lowest VWF levels 0.31-0.50 IU/mL and 170 patients 0.51-0.60 IU/mL. Mean age at diagnosis was 28.8 ±17.7 years. Most patients were female (74.3%) and had blood group O (76.4%, Table 1). The bleeding score (BS) was similar in patients with historically lowest VWF levels of 0.31-0.50 IU/mL (3.7 ±3.0) and 0.51-0.60 IU/mL (4.0 ±2.9, p=0.209, Table 1). During the mean follow-up period of 6.3 ±3.7 years, 259 surgical procedures were performed in 146 patients, 81 deliveries in 56 women, and 109 spontaneous- or traumatic bleedings in 71 patients. The incidence of post-surgical bleeding was 7 (2.7%) during follow-up, whereas 8 deliveries (10%) were complicated by PPH. Overall, 65 out of 439 patients (14.8%) had a bleeding episode requiring treatment during follow-up, resulting in an incidence of bleeding requiring treatment of 0.5 ±1.9 per patient per decade. No difference was found in the incidence of bleeding requiring treatment between patients with historically lowest VWF levels of 0.31-0.50 IU/mL and 0.51-0.60 IU/mL (Figure 2A, p=0.154). We found that referral for a personal bleeding diathesis, a younger age at diagnosis and an abnormal BS at diagnosis were strong and independent risk factors for bleeding requiring treatment during follow-up, respectively HR=2.32 (95%CI: 1.16-4.63), HR=1.18 (95%CI: 1.01-1.38) and HR=1.77 (95%CI: 1.04-3.01). These risk factors were combined to develop a risk score to identify low VWF patients with an increased risk for bleeding requiring treatment (Figure 2B). The risk score performed excellent to differentiate in bleeding requiring treatment between low risk, intermediate risk and high risk patients (p&lt;0.001, Figure 2C). The number of patients with bleeding requiring treatment was 8/126 (6.3%) in patients with low risk, 18/143 (12.6%) in intermediate risk and 39/170 (22.9%) in high risk patients (p&lt;0.001). Likewise, the incidence of bleeding requiring treatment per patient per decade was 0.22 ±1.08 in low risk, 0.28 ±1.25 in intermediate risk and 0.87 ±2.61 in high risk patients (p=0.004, Figure 2D). Conclusion To conclude, there is no difference in the bleeding phenotype of individuals with historically lowest VWF levels of 0.31-0.50 IU/mL and 0.51-0.60 IU/mL. Therefore, the cut-off value to diagnose low VWF should be set at 0.60 IU/mL. Furthermore, the risk score developed in the current study may assist to identify low VWF patients with low, intermediate and high risk for future bleeding. Disclosures Atiq: SOBI: Other: travel grant; CSL Behring: Research Funding. Kruip:Boehringer Ingelheim: Research Funding; Pfizer: Research Funding; Bayer: Research Funding; Daiichi Sankyo: Research Funding; SOBI: Research Funding; Bayer: Speakers Bureau. Cnossen:Takeda: Research Funding; Shire: Research Funding; Baxter: Research Funding; Bayer: Research Funding; Sobi: Research Funding; CSL behring: Research Funding; Nordic Pharma: Research Funding; Novo Nordisk: Research Funding; Pfizer: Research Funding. Leebeek:CSL Behring: Research Funding; Shire/Takeda: Research Funding; Uniqure: Consultancy; Shire/Takeda: Consultancy; Novo Nordisk: Consultancy; SOBI: Other: Travel grant; Roche: Other: DSMB member for a study.

scholarly journals Disease and Clinical Characteristics of Patients with Myelofibrosis Enrolled in the MOST Study

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4190-4190
Author(s):  
Aaron T. Gerds ◽  
Roger M. Lyons ◽  
Philomena Colucci ◽  
Patricia Kalafut ◽  
Dilan Paranagama ◽  
...  
Keyword(s):  
Research Funding ◽  
Clinical Characteristics ◽  
The United States ◽  
Treatment Patterns ◽  
Low Risk ◽  
Normal Range ◽  
Employment Equity ◽  
Oncology Research ◽  
Risk Patients ◽  
Equity Ownership

Introduction: Myelofibrosis (MF) is a chronic Philadelphia chromosome-negative myeloproliferative neoplasm characterized by progressive bone marrow (BM) fibrosis, extramedullary hematopoiesis, splenomegaly, constitutional symptoms, and shortened survival. Data pertaining to the clinical characteristics and treatment patterns of patients with low-risk MF are limited; most studies have focused on patients with intermediate- and high-risk MF. The ongoing Myelofibrosis and Essential Thrombocythemia Observational STudy (MOST) was designed to characterize the demographics, disease burden, patient-reported outcomes, and management of patients with MF or essential thrombocythemia (ET) in clinical practices throughout the United States (NCT02953704). This analysis describes demographic and clinical characteristics of patients with low-risk MF enrolled in MOST. Methods: MOST is an ongoing multicenter, non-interventional, longitudinal, prospective, observational study in patients with MF or ET. Eligible patients with MF were at least 18 years old and had low- or intermediate-1 (INT-1) risk by age alone according to the Dynamic International Prognostic Scoring System (DIPSS). Patients participating in blinded investigational drug trials, having life expectancy ≤6 months, or having other concurrent myeloid malignancies were excluded. Data from patient records were entered into an electronic case report form during usual-care visits over a planned 36-month observation period. Data were analyzed with descriptive statistics. Results: A total of 232 patients with MF were enrolled between November 29, 2016 and March 29, 2019 at 124 sites. Two-hundred patients with low-risk (n=77) or INT-1 risk by age alone (n=123) MF were included in this analysis (data cut-off date, June 17, 2019); 32 patients were excluded due to incorrect risk categorization (n=27) or unanswered prognostic factors at enrollment (n=5). At enrollment, the median age was 68 (range, 35-88) years, 58% were aged >65 years, 49% were women, and 89% were white. Thirteen patients (7%) had a documented family history of MF, ET, or polycythemia vera. Of 157 patients with manual spleen assessment at enrollment, 55 (35%) had palpable splenomegaly; median spleen length was 7 (range, 1‒22) cm in 35 patients with available measurements. The median time from MF diagnosis to enrollment was 1.7 (range, 0.0-37.7) years; most patients (75%) were diagnosed within 5 years of enrollment. Of patients with available data, 93% (185/200) were reported to have undergone BM biopsy/aspiration and 82% (162/198) had mutation testing (MT) at the time of diagnosis; most patients had received both BM biopsy and MT (151/196 [77%]). Data from MT conducted prior to or within 30 days of diagnosis were available for 142 patients (71%); 134/142 patients (94%) were tested for a JAK2 mutation, of whom 95/134 (71%) were positive (Table 1). At enrollment, approximately half of patients with available data (97/190 [51%]) had hemoglobin below normal range, and approximately one-third had platelets (68/188 [36%]) or leukocytes (58/186 [31%]) above normal range (Table 2). The most common signs reported at the time of enrollment included lactate dehydrogenase greater than the upper limit of normal (41%), palpable spleen (31%), and leukocytosis (>11 × 109/L; 24%). Across both risk groups, 111 patients (56%) were receiving MF-directed monotherapy at enrollment (low-risk, 43/77 [56%]; INT-1 by age alone, 68/123 [55%]). Low-risk patients received hydroxyurea (HU; 23/43 [54%]), ruxolitinib (15/43 [35%]), interferon (4/43 [9%]), or anagrelide (1/43 [2%]); INT-1 patients received ruxolitinib (30/68 [44%]), HU (28/68 [41%]), interferon (8/68 [12%]), or anagrelide (2/68 [3%]). Five patients (3%) were receiving >1 MF-directed therapy. Less than half of low- (34/77 [44%]) and INT-1- (50/123 [41%]) risk patients were receiving no MF-directed therapy at enrollment. Conclusion: These real-world data provide insight into the clinical characteristics, diagnosis, and treatment patterns of patients with low- or INT-1 risk (by age alone) MF in the United States. Data from this trial will help characterize the rate at which patients transition from low- or INT-1-risk disease to higher risk categories of disease and how management is affected by disease progression. Disclosures Gerds: Sierra Oncology: Research Funding; Imago Biosciences: Research Funding; Incyte: Consultancy, Research Funding; Celgene Corporation: Consultancy, Research Funding; CTI Biopharma: Consultancy, Research Funding; Pfizer: Consultancy; Roche: Research Funding. Lyons:Texas Oncology: Equity Ownership; Amgen: Consultancy; McKesson: Other: Leadership. Colucci:Incyte: Employment, Equity Ownership. Kalafut:Incyte: Employment, Equity Ownership. Paranagama:Incyte: Employment, Equity Ownership. Verstovsek:Promedior: Research Funding; Blueprint Medicines Corp: Research Funding; CTI BioPharma Corp: Research Funding; Genetech: Research Funding; Pragmatist: Consultancy; Pharma Essentia: Research Funding; Astrazeneca: Research Funding; Ital Pharma: Research Funding; Protaganist Therapeutics: Research Funding; Constellation: Consultancy; Incyte: Research Funding; Roche: Research Funding; NS Pharma: Research Funding; Celgene: Consultancy, Research Funding; Gilead: Research Funding; Novartis: Consultancy, Research Funding; Sierra Oncology: Research Funding.

Extended Follow-up of the Multi-Center Multi-National Prospective Cohort Study That Derived the “Men Continue and HERDOO2” Clinical Decision Rule Which Identifies Low Risk Patients Who May Be Able to Discontinue Oral Anticoagulants (Oac) 5-7 Months After Treatment for Unprovoked Venous Thromboembolism (VTE).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 451-451 ◽  
Author(s):  
Marc Rodger ◽  
Michael J. Kovacs ◽  
Susan Kahn ◽  
Phil Wells ◽  
David Anderson ◽  
...  
Keyword(s):  
High Risk ◽  
Board Of Directors ◽  
Research Funding ◽  
Low Risk ◽  
Advisory Committees ◽  
High Risk Women ◽  
Risk Patients ◽  
Recurrent Vte ◽  
Annual Risk

Abstract Abstract 451 Introduction: To continue or discontinue OAC after 6 months of therapy for VTE is one of the most important unanswered questions in VTE management. In 2007, we developed a clinical decision rule to identify low risk patients with unprovoked VTE who could safely discontinue OAC after 5-7 months of therapy. This clinical decision rule was developed from a large prospective cohort study of patients with unprovoked VTE who discontinued anticoagulants after 5-7 months of OAC and were subsequently followed for a mean of 18 months for recurrent VTE. The “MEN continue and HERDOO2” rule states that men and high risk women should continue anticoagulants indefinitely after unprovoked VTE. High risk women are women with ≥2 of the following 1)Hyperpigmentation, Edema or Redness (HER) on exam in either leg, 2)Vidas D-Dimer >250, 3)Obesity- BMI >30 or 4)Older age over 65. Given that the OAC treatment decision is a long-term treatment decision that needs to be counter-balanced with long-term bleeding risk from OAC (1-3% annual risk of major hemorrhage) it is important to determine long-term risks of recurrent VTE in unprovoked VTE patients, high risk patients and low risk patients. Objective: We sought to confirm that the risk of recurrent VTE in high risk patients remains elevated and conversely that the risk remains low in low risk women over longer term follow-up. Methods: Multi-centre prospective cohort study of first unprovoked VTE patients who had potential predictors collected while on OAC (including D-Dimer) enrolled from 2001 to March 2006. Patients were excluded if they had: 1) recurrent unprovoked VTE, 2) known high risk thrombophilia or 3) no consent. Symptomatic suspected VTE during subsequent follow-up (up to july 2009) off of OAC was investigated with reference to baseline imaging and then independently adjudicated. Results: 646 participants were enrolled in 11 centers. At enrolment, mean age of 53 (range 17-95) and 49% were female. During a mean 3.1 years (range 0.01-6.5) of follow-up, 131/512 suspected VTE were adjudicated as recurrent VTE resulting in an annual risk of recurrent VTE of 6.7% (95% CI 5.5-7.6%) in patients with unprovoked VTE. Men had a 9.9% (95% CI 8.3-11.8%) annual risk of recurrent VTE. High risk women with 2 or more HERDOO points had an annual risk of recurrent VTE of 8.3% (95%CI 5.7-11.3%). Low risk women (1 or 0 HERDOO points) had 1.3% (95% CI 0.5-2.8%) annual risk of recurrent VTE compared to 9.5% (8.1-11.0%) annual risk of recurrent VTE in high risk patients (men and high risk women). Conclusions: Men and high risk women with unprovoked VTE should be considered for long-term OAC therapy given a high risk of recurrent VTE over 3 year follow-up . Women with a low HER DOO 2 score may be able to safely discontinue anticoagulants. Disclosures: Rodger: Bayer: Research Funding; Leo Pharma: Research Funding; Pfizer: Research Funding; Boehringer Ingelheim: Membership on an entity's Board of Directors or advisory committees; Biomerieux: Research Funding; GTC Therapeutics: Research Funding. Crowther:BI: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Bayer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria, Research Funding; Leo Pharma: Consultancy, Honoraria, Research Funding; Sanofi-Aventis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Artisan Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees.

scholarly journals A Clinical Review of the Co-Occurrence of Myeloproliferative and Lymphoproliferative Neoplasms

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4285-4285
Author(s):  
Spencer Krichevsky ◽  
Erica B Bhavsar ◽  
Richard R. Furman ◽  
Ruben Niesvizky ◽  
Ellen K. Ritchie ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Polycythemia Vera ◽  
Bone Marrow Biopsy ◽  
Research Funding ◽  
B Cell Lymphoma ◽  
Low Risk ◽  
Diagnostic Code ◽  
Intermediate Risk ◽  
Early Stage Disease

Abstract The co-occurrence of myeloproliferative (MPN) and lymphoproliferative neoplasms (LPN) is rare and many publications have been limited to small case reports. Others have involved a considerable number of patients, but the coexistence remains underreported and inadequately studied. A recent retrospective review reported that a MPN patients have a 2.8-fold higher relative risk of developing LPN. A database developed at Weill Cornell Medicine (WCM) was queried for patients with ≥3 visits between 1998-2018 with a diagnostic code for a MPN and lymphoma or myeloma subtype. Patients identified were verified to ensure that study inclusion criteria were satisfied. Observed co-occurrence was compared to nation-wide reported prevalence. Demographic and clinical details of 24 patients with a MPN and LPN were recorded (Table 1). The ratio of males to females was 1.7. Essential thrombocythemia and polycythemia vera, and chronic lymphocytic leukemia (CLL) were the leading MPN and LPN subtypes, respectively. Patients were assigned to risk or staging categories at diagnosis based on subtype-specific criteria (Table 2). Median values for diagnostic bone marrow biopsy findings in 14 patients were 2% [0-5] for myeloblasts and 80% [15-100] for cellularity. Additionally, 10 patients had evaluated reticulin fibrosis: 5 (50.0%) presented as MF-0, 4 (40.0%) as MF-1, and 1 (10.0%) as MF-2. Progression to myelofibrosis was confirmed by morphology in 1 (4.2%) patient 10.1 years after a polycythemia vera diagnosis and 5.4 years after a diffuse large B-cell lymphoma (DLBCL) diagnosis. Progression to acute myeloid leukemia was confirmed by morphology in 1 (4.2%) patient 2.4 years after a chronic myelomonocytic leukemia diagnosis and 1.2 years after a smoldering myeloma (SM) diagnosis. Interphase fluorescence in situ hybridization (iFISH) detected cytogenetic abnormalities in 5/8 (62.5%) CLL patients: 2/5 (40.0%) and 5/5 (100.0%) patients harbored deletions in trisomy 12 and 13q14, respectively. Immunoglobulin heavy chain variable region gene (IGVH) status was unmutated in 2 (25.0%) patients. One (12.5%) patient was CD38+ and 2/6 (33.0%) patients were ZAP-70+. At diagnosis, all 8 patients presented with early stage disease (Rai stage 0-II). Based on the CLL-specific international prognostic index (IPI), 3/8 (37.5%) and 5/8 (62.5%) presented as low-risk and intermediate-risk, respectively. Of the 6 lymphoma patients: 5 (83.0%) patients presented with Ann Arbor stage-IV disease at diagnosis. Four (66.7%) patients presented as low/intermediate-risk, and 2 (33.3%) presented as high-risk based on disease-specific IPIs. One patient presented with -17p by iFISH. All 4 patients that were evaluated for Ki-67 had moderate/high expression. Of the 7 multiple myeloma (MM) patients, 6 (85.7%) presented as stage 1 and 1 (14.3%) as stage 3. Of the 3 SM patients, all 3 presented as low risk [12]. In addition, these patients were categorized as IgG-K (4; 40.0%), IgG-L (2; 20.0%), IgA-K (1; 10.0%), IgA-L (1; 10.0%), IgM (1; 10.0%), and biclonal IgG-L/IgA-L (1; 10.0%) [13]. Mutation statuses were identified by commercially tested myeloid or lymphoid molecular panels. As expected in this MPN subtype distribution, 11 (45.8%) are JAK2+, 2 (8.3%) are MPL+, 1 (4.2%) is BCR-ABL+, and 1 (4.2%) is CALR+ (Table 3). The risk of a co-occurrent MPN and LPN is higher than expected if they are mutually exclusive (Table 4A-4B, 5). Of interest, 13 (54.2%) patients were diagnosed with a MPN 11.8±18.8 years prior to a LPN; conversely, 11 (45.9%) were diagnosed with a LPN 6.5±6.2 years prior to a MPN. In addition, MPN therapy was started 2.0±2.3 years after a MPN diagnosis, and LPN therapy was started 2.6±4.0 years after a LPN diagnosis. A review of survival analysis requires larger subtype populations since the degree of survival can vary greatly, but it has been reported that patients with a MPN or LPN have significantly reduced life expectancy when compared to the general population. Median follow-up for our patient is 8.2 years (1.5-28.0) with 17/24 (70.8%) patients still being actively followed at our institution, 6 (25.0%) are been lost to follow-up, and 1 (4.2%) is deceased. The significant prevalence of these hematologic malignancies in combination emphasizes the importance of performing a bone marrow biopsy, which we espouse at our institution, cytogenetic analysis, and myeloid and lymphoid molecular testing to identify mutations. Disclosures Furman: Loxo Oncology: Consultancy; Gilead: Consultancy; Verastem: Consultancy; Acerta: Consultancy, Research Funding; TG Therapeutics: Consultancy; Incyte: Consultancy, Other: DSMB; Pharmacyclics LLC, an AbbVie Company: Consultancy; Genentech: Consultancy; Sunesis: Consultancy; Janssen: Consultancy; AbbVie: Consultancy. Niesvizky:Amgen Inc.: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Takeda: Consultancy, Research Funding. Ritchie:Bristol-Myers Squibb: Research Funding; Novartis: Consultancy, Other: Travel, Accommodations, Expenses, Research Funding, Speakers Bureau; Astellas Pharma: Research Funding; NS Pharma: Research Funding; Celgene: Consultancy, Other: Travel, Accommodations, Expenses, Speakers Bureau; Pfizer: Consultancy, Research Funding; Incyte: Consultancy, Speakers Bureau; ARIAD Pharmaceuticals: Speakers Bureau.

scholarly journals REVEAL: Characteristics of Patients with Polycythemia Vera Who Were Diagnosed within 6 Months of Enrollment

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5370-5370
Author(s):  
Aaron T. Gerds ◽  
Ivy Altomare ◽  
Philomena Colucci ◽  
Dilan Paranagama ◽  
John M Burke
Keyword(s):  
High Risk ◽  
Polycythemia Vera ◽  
Research Funding ◽  
Clinical Characteristics ◽  
Prospective Observational Study ◽  
Low Risk ◽  
Early Satiety ◽  
High Risk Disease ◽  
History Of ◽  
Equity Ownership

Background Polycythemia vera (PV), characterized by erythrocytosis and JAK2 mutations, is associated with increased morbidity and mortality. Patients (pts) are at risk for thrombotic events and experience symptoms (sxs) that may impact quality of life. Data describing the clinical characteristics of pts with PV at the time of diagnosis (dx) are limited. The Prospective Observational Study of Patients with Polycythemia Vera in US Clinical Practices (REVEAL) is a multicenter, prospective, observational study designed to collect data on disease burden, clinical management, and pt-reported outcomes (PROs) of adult pts (aged ≥18) with PV. This analysis describes pt demographic and clinical characteristics, treatment patterns, and sxs of newly dxed pts with PV. Methods Pts enrolled in REVEAL who were dxed ≤6 months prior to enrollment were included in this analysis. Descriptive statistics were used to summarize pt demographic and clinical characteristics, tests at dx, and management patterns at dx. Sxs were assessed with a validated PRO instrument: the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS). Mean and standard deviation for individual sx scores and total sx score (TSS) at enrollment are reported. Results Of the 2510 pts enrolled in REVEAL, 321 dxed within 6 months of enrollment were included in this analysis. Median age at enrollment was 67.0 (range, 23.0-94.0) years, 54.8% were male, and most (74.5%) had high-risk disease (aged ≥60 years and/or history of thrombosis). The most common physician-reported symptoms at the time of presentation included fatigue (24.6%), pruritus (17.1%), insomnia (10.3%), and muscle aches/bone pain (9.7%). Of those pts reported to have undergone mutation testing at dx (n=201), 99.5% were JAK2V617F positive. A history of thrombosis was reported for 15.9% of pts (arterial, 8.1%; venous, 8.7%), and the most common relevant comorbidities were hypertension (58.6%), obesity (19.6%), and diabetes mellitus (15.9%). Of 188 pts with lab values within 1 month before dx, 95.2% had elevated (≥45%) hematocrit and 59.6% had elevated (>10 × 109/L) white blood cell counts. Most high-risk and low-risk pts were reported to have received phlebotomies within 6 months after dx (71.7% and 78.4%, respectively). A higher proportion of pts with high-risk disease initiated a pharmacologic therapy for PV compared with those who had low-risk disease (60.5% vs 23.9%); hydroxyurea (HU) was the most common cytoreductive therapy (n=151 [93.2%]). Most of these pts (n=137 [90.7%]) were still receiving HU 2 years after dx. Of those who initiated HU within 6 months of dx, 5.3% (n=8) received an alternative cytoreductive therapy following HU. A total of 287 pts provided PRO data at enrollment (Table 1). The most common pt-reported sxs were fatigue (77.2%), early satiety (61.1%), and inactivity (58.0%); the mean (SD) MPN-SAF TSS was 18.5 (15.6). The sxs with the highest reported mean (SD) scores were fatigue (3.4 [2.7]), inactivity (2.6 [2.9]), and early satiety (2.5 [2.6]) and were largely similar between low-risk and high-risk pts. Conclusions Compared with all 2510 pts enrolled in REVEAL (Clin Lymphoma Myeloma Leuk 2018[18]12:788-95), this subgroup of 321 pts dxed within 6 months of enrollment was similar with respect to age and sex. However, in the newly dxed subgroup, a slightly lower proportion of pts (74.5%) had high-risk disease (77.3% of the full cohort). In the newly dxed subgroup, a higher proportion of pts (62.6%) underwent mutation testing (49.2% of all enrolled pts). The HU discontinuation rate early in the treatment course was approximately 9.3%, which is similar to the rate (6.3%) of HU discontinuation due to toxicity in patients with PV in a large, multicenter, MPN cohort (Am JHematol 2012[87]5:552-4). Sx burden in pts who completed the MPN-SAF TSS at enrollment was similar in the newly dxed pts (mean TSS, 18.5) and all pts enrolled in REVEAL (18.8; Clin Lymphoma Myeloma Leuk 2018[18]9:590-6); the most frequent pt-reported sxs (fatigue, early satiety, and inactivity) in this smaller pt subgroup were the same as those observed in the larger pt cohort. Overall, near the time of dx, a greater proportion of pts had low-risk disease. Despite this difference, the sx constellation and severity tends to be very similar to the larger cohort. It also appears that only a very small proportion of pts are unable to tolerate HU early on in the course of the disease. Disclosures Gerds: Sierra Oncology: Research Funding; Imago Biosciences: Research Funding; Incyte: Consultancy, Research Funding; CTI Biopharma: Consultancy, Research Funding; Pfizer: Consultancy; Celgene Corporation: Consultancy, Research Funding; Roche: Research Funding. Altomare:Novartis: Consultancy; Amgen: Consultancy; Incyte: Consultancy, Speakers Bureau; Rigel: Consultancy. Colucci:Incyte: Employment, Equity Ownership. Paranagama:Incyte: Employment, Equity Ownership. Burke:Roche/Genentech: Consultancy; Celgene: Consultancy; Gilead: Consultancy.

Prospective 12-Year Follow-up Study of Clinical and Hemodynamic Sequelae After Deep Vein Thrombosis in Low-Risk Patients (Zürich Study)

Circulation ◽  
1996 ◽  
Vol 93 (1) ◽  
pp. 74-79 ◽  
Author(s):  
Ulrich K. Franzeck ◽  
Ilse Schalch ◽  
Kurt A. Jäger ◽  
Ernst Schneider ◽  
Jörg Grimm ◽  
...  
Keyword(s):  
Deep Vein Thrombosis ◽  
Low Risk ◽  
Vein Thrombosis ◽  
Follow Up Study ◽  
Risk Patients ◽  
Deep Vein

scholarly journals Accuracy of upper endoscopies with random biopsies to identify patients with gastric premalignant lesions who can safely be exempt from surveillance

2021 ◽  
Vol 24 (3) ◽  
pp. 680-690
Author(s):  
Michiel C. Mommersteeg ◽  
Stella A. V. Nieuwenburg ◽  
Wouter J. den Hollander ◽  
Lisanne Holster ◽  
Caroline M. den Hoed ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
High Risk ◽  
Low Risk ◽  
Premalignant Lesions ◽  
High Risk Patients ◽  
European Guidelines ◽  
Progression Of Disease ◽  
Risk Patients ◽  
Progression Risk

Abstract Introduction Guidelines recommend endoscopy with biopsies to stratify patients with gastric premalignant lesions (GPL) to high and low progression risk. High-risk patients are recommended to undergo surveillance. We aimed to assess the accuracy of guideline recommendations to identify low-risk patients, who can safely be discharged from surveillance. Methods This study includes patients with GPL. Patients underwent at least two endoscopies with an interval of 1–6 years. Patients were defined ‘low risk’ if they fulfilled requirements for discharge, and ‘high risk’ if they fulfilled requirements for surveillance, according to European guidelines (MAPS-2012, updated MAPS-2019, BSG). Patients defined ‘low risk’ with progression of disease during follow-up (FU) were considered ‘misclassified’ as low risk. Results 334 patients (median age 60 years IQR11; 48.7% male) were included and followed for a median of 48 months. At baseline, 181/334 (54%) patients were defined low risk. Of these, 32.6% were ‘misclassified’, showing progression of disease during FU. If MAPS-2019 were followed, 169/334 (51%) patients were defined low risk, of which 32.5% were ‘misclassified’. If BSG were followed, 174/334 (51%) patients were defined low risk, of which 32.2% were ‘misclassified’. Seven patients developed gastric cancer (GC) or dysplasia, four patients were ‘misclassified’ based on MAPS-2012 and three on MAPS-2019 and BSG. By performing one additional endoscopy 72.9% (95% CI 62.4–83.3) of high-risk patients and all patients who developed GC or dysplasia were identified. Conclusion One-third of patients that would have been discharged from GC surveillance, appeared to be ‘misclassified’ as low risk. One additional endoscopy will reduce this risk by 70%.

Outcome of Severe Vaso-Occlusive Crisis in Sickle Cell Disease Adults Admitted to Referral Centers in Africa and Europe. Introduction of Machine Learning Methods to Improve the Presev Score

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 14-15
Author(s):  
Yamna Ouchtar ◽  
Christian Kassasseya ◽  
Kene Sekou ◽  
Anne-Laure Pham Hung D'Alexandry D'Orengiani ◽  
Mehdi Kellaf ◽  
...  
Keyword(s):  
Machine Learning ◽  
Sickle Cell Disease ◽  
Decision Tree ◽  
Predictive Value ◽  
Research Funding ◽  
Low Risk ◽  
Cell Disease ◽  
Risk Patients ◽  
Decision Tree Method ◽  
Tree Method

Introduction: Sickle Cell Disease (SCD) is one of the most common genetic disease worldwide. The Acute Chest Syndrome (ACS) is a leading cause of death for SCD patients. The PRESEV1 study was set to produce a predictive score to assess the risk of an ACS development (Bartolucci et al., 2016). PRESEV2 was an international, multicenter prospective confirmatory study to validate the PRESEV score. This study aims at improving these predictions with the addition of a machine learning (ML) method. Patients and methods: Included patients follow PRESEV1 and PRESEV2 studies 'rules. The dataset thus contains 97 patients who developed an ACS episode (18.3%) against 434 patients who did not (81.7%). To compute the PRESEV score, we firstly used the method developed previously with the following variables as input: leukocytes, reticulocytes, hemoglobin levels and cervical spine pain. This method is based on a decision tree with fixed rules and is referred to as the decision tree method throughout this abstract. Secondly we used a ML method using a combined sampling method named SMOTEENN to balance the data and a C-Support Vector Classification (SVC) with fixed parameters to predict the score. This method produces a probability, with a threshold of 0.2, under which the patient is predicted to declare an ACS. We considered the dataset composed of PRESEV1 dataset and 80 percent of PRESEV2 with a randomly choice. The test dataset is thus composed of the remaining 20 percent of PRESEV2. This technique of random choice allowed us to use a 50-cross-validation and compute with Python an average score and a standard deviation (std). In order to allow comparison of the developed score with or without the addition of the ML method, rates were calculated by adding the weight of ACS representation in the dataset. Results: Among all parameters analyzed, the SVC method considered the following variables for calculation of the score: leukocytes, LDH, urea, reticulocytes and hemoglobin levels. A hundred and two adult patients with a severe VOC requiring hospitalization were included. Out of this pool of patients, 26 (25.5%) were predicted with a low risk of developing an ACS episode (SVC method). Sensibility and specificity were of 94.7% and 26.8%, respectfully. The negative predictive value (NPV) was of 95.8% and the positive predictive value (PPV) of 22.4%. Results are resumed in table 1. When compared to the PRESEV score (decision tree method), 44 patients out of 372 were identified with a low risk score (11.8%), Discussion and Conclusion: While the addition of a ML method did not allow the improvement of the sensibility or the NPV of the PRESEV score, it improved both the specificity and the PPV. The addition of artificial intelligence thus provides a better prediction with a higher percentage of "low-risk" patients. As highlighted in the international PRESEV study, this score could represent a useful tool for physicians in hospital settings, with limited beds. While the PRESEV score could allow a better management of "low risk" patients on one side, the identification of "high-risk" patients could also represent a serious advantage to physicians, as it could improve the feasibility of clinical trials for the prevention of this lethal complication in SCD patients. Disclosures Bartolucci: Innovhem: Other; Novartis: Research Funding; Roche: Consultancy; Bluebird: Consultancy; Emmaus: Consultancy; Bluebird: Research Funding; Addmedica: Research Funding; AGIOS: Consultancy; Fabre Foundation: Research Funding; Novartis: Consultancy; ADDMEDICA: Consultancy; HEMANEXT: Consultancy; GBT: Consultancy.

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