Aspirin and Growth of Small Unruptured Intracranial Aneurysm

Background and Purpose: The role of aspirin in unruptured intracranial aneurysm (UIA) growth remains largely unknown. We aim to identify whether aspirin is associated with a lower rate of UIA growth in patients with UIA <7 mm. Methods: This prospective cohort study consecutively enrolled patients with UIAs <7 mm with ischemic cerebrovascular disease between January 2016 and December 2019. Baseline and follow-up patient information, including the use of aspirin and blood pressure level, were recorded. Patients were considered aspirin users if they took aspirin, including standard- and low-dose aspirin, ≥3× per week. The primary end point was aneurysm growth in any direction or an indisputable change in aneurysm shape. Results: Among the 315 enrolled patients, 272 patients (86.3%) underwent imaging examinations during follow-up (mean follow-up time, 19.6±12.7 months). A total of 113 patients were continuously treated with aspirin. UIA growth occurred in 31 (11.4%) patients. In the multivariate Cox analysis, specific aneurysm locations (anterior communicating artery, posterior communicating artery, or middle cerebral artery; hazard ratio, 2.89 [95% CI, 1.22–6.88]; P =0.016) and a UIA size of 5 to <7 mm (hazard ratio, 7.61 [95% CI, 3.02–19.22]; P <0.001) were associated with a high risk of UIA growth, whereas aspirin and well-controlled blood pressure were associated with a low risk of UIA growth (hazard ratio, 0.29 [95% CI, 0.11–0.77]; P =0.013 and hazard ratio, 0.25 [95% CI, 0.10–0.66]; P =0.005, respectively). The cumulative annual growth rates were as high as 40.0 and 53.3 per 100 person-years in the high-risk patients (>1 risk factor) with and without aspirin, respectively. Conclusions: Aspirin therapy and well-controlled blood pressure are associated with a low risk of UIA growth; the incidence of UIA growth in high-risk patients in the first year is high, warranting intensive surveillance in this patient group. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02846259.

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

Gastric Cancer ◽

10.1007/s10120-020-01149-2 ◽

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%.

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Does socioeconomic status make a difference? A register-based study on the extent to which cardiovascular screening in patients with inflammatory arthritis leads to recommended follow-up in general practice

RMD Open ◽

10.1136/rmdopen-2019-000940 ◽

2020 ◽

Vol 6 (2) ◽

pp. e000940

Author(s):

Anette Hvenegaard Kjeldgaard ◽

Kim Hørslev-Petersen ◽

Sonja Wehberg ◽

Jens Soendergaard ◽

Jette Primdahl

Keyword(s):

Blood Pressure ◽

Socioeconomic Status ◽

High Risk ◽

Secondary Care ◽

Inflammatory Arthritis ◽

Low Risk ◽

Risk Screening ◽

High Risk Patients ◽

Eular Recommendations ◽

Risk Patients

ObjectiveTo investigate to what extent patients with inflammatory arthritis (IA) follow recommendations given in a secondary care nurse-led cardiovascular (CV) risk screening consultation to consult their general practitioner (GP) to reduce their CV risk and whether their socioeconomic status (SES) affects adherence.MethodsAdults with IA who had participated in a secondary care screening consultation from July 2012 to July 2015, based on the EULAR recommendations, were identified. Patients were considered to have high CV risk if they had risk Systematic COronary Risk Evaluation (SCORE) ≥5%, according to the European SCORE model or systolic blood pressure ≥145 mmHg, total cholesterol ≥8 mmol/L, LDL cholesterol ≥5 mmol/L, HbA1c ≥42 mmol/mol or fasting glucose ≥6 mmol/L. The primary outcome was a consultation with their GP and at least one action focusing on CV risk factors within 6 weeks after the screening consultation.ResultsThe study comprised 1265 patients, aged 18–85 years. Of these, 336/447 (75%) of the high-risk patients and 580/819 (71%) of the low-risk patients had a GP consultation. 127/336 (38%) of high-risk patients and 160/580 (28%) of low-risk patients received relevant actions related to their CV risk, for example, blood pressure home measurement or prescription for statins, antihypertensives or antidiabetics. Education ≥10 years increased the odds for non-adherence (OR 0.58, 95% CI 0.0.37 to 0.92, p=0.02).Conclusions75% of the high-risk patients consulted their GP after the secondary care CV risk screening, and 38% of these received an action relevant for their CV risk. Higher education decreased adherence.

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Changes in patient activation following cardiac rehabilitation using the Active+me digital healthcare platform during the COVID-19 pandemic: a cohort evaluation

BMC Health Services Research ◽

10.1186/s12913-021-07363-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Gabbi Frith ◽

Kathryn Carver ◽

Sarah Curry ◽

Alan Darby ◽

Anna Sydes ◽

...

Keyword(s):

Blood Pressure ◽

High Risk ◽

Cardiac Rehabilitation ◽

Group Analysis ◽

Patient Activation ◽

Low Risk ◽

Smart Device ◽

Face To Face ◽

High Risk Patients ◽

Risk Patients

Abstract Background Restrictions on face-to-face contact, due to COVID-19, led to a rapid adoption of technology to remotely deliver cardiac rehabilitation (CR). Some technologies, including Active+me, were used without knowing their benefits. We assessed changes in patient activation measure (PAM) in patients participating in routine CR, using Active+me. We also investigated changes in PAM among low, moderate, and high risk patients, changes in cardiovascular risk factors, and explored patient and healthcare professional experiences of using Active+me. Methods Patients received standard CR education and an exercise prescription. Active+me was used to monitor patient health, progress towards goals, and provide additional lifestyle support. Patients accessed Active+me through a smart-device application which synchronised to telemetry enabled scales, blood pressure monitors, pulse oximeter, and activity trackers. Changes in PAM score following CR were calculated. Sub-group analysis was conducted on patients at high, moderate, and low risk of exercise induced cardiovascular events. Qualitative interviews explored the acceptability of Active+me. Results Forty-six patients were recruited (Age: 60.4 ± 10.9 years; BMI: 27.9 ± 5.0 kg.m2; 78.3% male). PAM scores increased from 65.5 (range: 51.0 to 100.0) to 70.2 (range: 40.7 to 100.0; P = 0.039). PAM scores of high risk patients increased from 61.9 (range: 53.0 to 91.0) to 75.0 (range: 58.1 to 100.0; P = 0.044). The PAM scores of moderate and low risk patients did not change. Resting systolic blood pressure decreased from 125 mmHg (95% CI: 120 to 130 mmHg) to 119 mmHg (95% CI: 115 to 122 mmHg; P = 0.023) and waist circumference measurements decreased from 92.8 cm (95% CI: 82.6 to 102.9 cm) to 85.3 cm (95% CI 79.1 to 96.2 cm; P = 0.026). Self-reported physical activity levels increased from 1557.5 MET-minutes (range: 245.0 to 5355.0 MET-minutes) to 3363.2 MET-minutes (range: 105.0 to 12,360.0 MET-minutes; P < 0.001). Active+me was acceptable to patients and healthcare professionals. Conclusion Participation in standard CR, with Active+me, is associated with increased patient skill, knowledge, and confidence to manage their condition. Active+me may be an appropriate platform to support CR delivery when patients cannot be seen face-to-face. Trial registration As this was not a clinical trial, the study was not registered in a trial registry.

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Genomic classifiers (ColoPrint/MSI-Print) predict outcome and chemotherapy benefit in stage II and III colon cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.4_suppl.378 ◽

2013 ◽

Vol 31 (4_suppl) ◽

pp. 378-378 ◽

Cited By ~ 2

Author(s):

Scott Kopetz ◽

Zhi-Qin Jiang ◽

Michael J. Overman ◽

Christa Dreezen ◽

Sun Tian ◽

...

Keyword(s):

Colon Cancer ◽

High Risk ◽

Adjuvant Chemotherapy ◽

Cancer Patients ◽

Additional Treatment ◽

Low Risk ◽

Stage Ii ◽

High Risk Patients ◽

Risk Patients

378 Background: Although the benefit of chemotherapy in stage II and III colon cancer patients is significant, many patients might not need adjuvant chemotherapy because they have a good prognosis even without additional treatment. ColoPrint is a gene expression classifier that distinguish patients with low or high risk of disease relapse. It was developed using whole genome expression data and has been validated in public datasets, independent European patient cohorts and technical studies (Salazar 2011 JCO, Maak 2012 Ann Surg). Methods: In this study, the commercial ColoPrint test was validated in stage II (n=96) and III patients (n=95) treated at the MD Anderson Cancer Center from 2003 to 2009. Frozen tissue specimen, clinical parameters, MSI-status and follow-up data (median follow-up 64 months) were available. The 64-gene MSI-signature developed to identify patients with deficient mismatch repair system (Tian 2012 J Path) was evaluated for its accuracy to identify MSI patients and also for prognosis. Results: In this cohort, ColoPrint classified 56% of stage II and III patients as being at low risk. The 3-year Relapse-Free-Survival (RFS) was 90.6% for Low Risk and 78.4% for High Risk patients with a HR of 2.33 (p=0.025). In uni-and multivariate analysis ColoPrint and stage were the only significant factors to predict outcome. The MSI-signature classified 47 patients (24.6%) as MSI-H and most MSI-H patients were ColoPrint low risk (81%). Patients who were ColoPrint low risk and MSI-H by signature had the best outcome with a 3-year RFS of 95% while patients with ColoPrint high risk had a worse outcome independently of the MSI-status. Low risk ColoPrint patients had a good outcome independent of stage or chemotherapy treatment (90.1% 3-year RFS for treated patients, 91.4% for untreated patients) while ColoPrint high risk patients treated with adjuvant chemotherapy had 3-year RFS of 84%, compared to 70.1% 3-year RFS in untreated patients (p=0.026). Conclusions: The combination of ColoPrint and MSI-Print improves the prognostic accuracy in stage II and stage III patients and may help the identification of patients at higher risk who are more likely to benefit from additional treatment

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Should adult medulloblastoma patients at low risk receive adjuvant chemotherapy? Long-term results of a prospective study

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.2018 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 2018-2018

Author(s):

E. Franceschi ◽

A. Tosoni ◽

M. Ermani ◽

V. Blatt ◽

P. Amistà ◽

...

Keyword(s):

High Risk ◽

Adjuvant Chemotherapy ◽

Survival Rates ◽

Low Risk ◽

Long Term Results ◽

High Risk Patients ◽

Significant Difference ◽

Risk Patients

2018 Background: Due to the rarity of medulloblastoma (MB) in adults, the few studies available on this condition are retrospective, and the follow-up tends to be short. Furthermore, the different therapeutic strategies used in these patients makes it difficult to assess survival rates and prognostic factors. Methods: Between January 1989 and February 2001, a prospective phase II trial was performed to evaluate the efficacy of treatment for adults with medulloblastoma. Patients were completely staged with a neuroradiological examination of the brain and neuraxis and by CSF cytology, according to Chang’s staging system. Low risk patients received radiotherapy alone, while high risk patients were given 2 cycles of upfront chemotherapy followed by radiotherapy and adjuvant chemotherapy. The results of the preliminary analysis of this study at a median follow-up of 3.7 years are reported elsewhere. The present papers reports on the long- term results of the same trial. Results: After a median follow up of 7.6 years, among a total of 36 enrolled adults with medulloblastoma, overall progression free survival (PFS) and overall survival (OS) at 5 years were 72% (range 59% to 84%) and 75% (62% to 91%), respectively. No difference was found between low and high risk patients in terms of PFS and OS at 5 years: in low-risk patients the 5-year PFS was 80% (range, 59–100%) and the 5-year OS, 80% (range, 58 - 100%); in high-risk patients the 5-year PFS was 69% (range, 54 -89%) and the 5-year OS, 73% (range, 58 - 92%). Conclusions: A long-term follow-up is essential to evaluate the real impact of treatments in adult patients with MB. Since there is no significant difference between low-risk and high-risk patients for PFS and OS, the use of chemotherapy is also questionable in low-risk patients. No significant financial relationships to disclose.

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

Blood ◽

10.1182/blood-2020-142549 ◽

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 > 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< 60 with no TE history) and 3,017 (71%) patients as High Risk. Within the High-Risk group, 2,224 (52%) were age>60 without prior TE, 204 (5%) were age<60 with prior TE and 589 (14%) were age>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> 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.

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Cardiovascular outcomes, bleeding risk, and achieved blood pressure in patients on long-term anticoagulation with the thrombin antagonist dabigatran or warfarin: data from the RE-LY trial

European Heart Journal ◽

10.1093/eurheartj/ehaa247 ◽

2020 ◽

Vol 41 (30) ◽

pp. 2848-2859 ◽

Cited By ~ 1

Author(s):

Michael Böhm ◽

Martina Brueckmann ◽

John W Eikelboom ◽

Michael Ezekowitz ◽

Mandy Fräßdorf ◽

...

Keyword(s):

Atrial Fibrillation ◽

Blood Pressure ◽

High Risk ◽

Major Bleeding ◽

Oral Anticoagulation ◽

Bleeding Events ◽

High Risk Patients ◽

Increased Risk ◽

Risk Patients

Abstract Aims A J-shaped association of cardiovascular events to achieved systolic (SBP) and diastolic (DBP) blood pressure was shown in high-risk patients. This association on oral anticoagulation is unknown. This analysis from RELY assessed the risks of death, stroke or systemic emboli, and bleeding according to mean achieved SBP and DBP in atrial fibrillation on oral anticoagulation. Methods and results RE-LY patients were followed for 2 years and recruited between 22 December 2005 until 15 December 2007. 18.113 patients were randomized in 951 centres in 54 countries and 18,107 patients with complete blood pressure (BP) data were analysed with a median follow-up of 2.0 years and a complete follow-up in 99.9%. The association between achieved mean SBP and DBP on all-cause death, stroke and systemic embolic events (SSE), major, and any bleeding were explored. On treatment, SBP >140 mmHg and <120 mmHg was associated with all-cause death compared with SBP 120–130 mmHg (reference). For SSE, risk was unchanged at SBP <110 mmHg but increased at 140–160 mmHg (adjusted hazard ratio (HR) 1.81; 1.40–2.33) and SBP ≥160 mmHg (HR 3.35; 2.09–5.36). Major bleeding events were also increased at <110 mmHg and at 110 to <120 mmHg. Interestingly, there was no increased risk of major bleeding at SBP >130 mmHg. Similar patterns were observed for DBP with an increased risk at <70 mmHg (HR 1.55; 1.35–1.78) and >90 mmHg (HR 1.88; 1.43–2.46) for all-cause death compared to 70 to <80 mmHg (reference). Risk for any bleeding was increased at low DBP <70 mmHg (HR 1.46; 1.37–1.56) at DBP 80 to <90 mmHg (HR 1.13; 1.06–1.31) without increased risk at higher achieved DBP. Dabigatran 150 mg twice daily showed an advantage in all patients for all-cause death and SSE and there was an advantage for 110 mg dabigatran twice daily for major bleeding and any bleeding irrespective of SBP or DBP achieved. Similar results were obtained for baseline BP, time-updated BP, and BP as time-varying covariate. Conclusion Low achieved SBP associates with increased risk of death, SSE, and bleeding in patients with atrial fibrillation on oral anticoagulation. Major bleeding events did not occur at higher BP. Low BP might identify high-risk patients not only for death but also for high bleeding risks. Clinical trial registration ClinicalTrials.gov—Identifier: NCT00262600.

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Use of all-trans retinoic acid plus arsenic trioxide as an alternative to chemotherapy in untreated acute promyelocytic leukemia

Blood ◽

10.1182/blood-2005-10-4006 ◽

2006 ◽

Vol 107 (9) ◽

pp. 3469-3473 ◽

Cited By ~ 259

Author(s):

Elihu Estey ◽

Guillermo Garcia-Manero ◽

Alessandra Ferrajoli ◽

Stefan Faderl ◽

Srdan Verstovsek ◽

...

Keyword(s):

Retinoic Acid ◽

High Risk ◽

Arsenic Trioxide ◽

Promyelocytic Leukemia ◽

Low Risk ◽

High Risk Patients ◽

Trans Retinoic Acid ◽

All Trans Retinoic Acid ◽

Risk Patients

We examined whether combining all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) might be an alternative to ATRA plus chemotherapy in untreated acute promyelocytic leukemia (APL). Twenty-five low-risk patients (white blood cell [WBC] count less than 10 × 109/L [10 000/μL]) received ATRA (45 mg/m2 daily) and ATO (0.15 mg/kg daily, beginning day 10 of ATRA), and in complete remission (CR) received ATO plus ATRA, without chemotherapy, unless they were reverse transcriptase–polymerase chain reaction (RT-PCR)–positive 3 months from CR date or had molecular relapse. Nineteen high-risk patients were treated identically, but received chemotherapy, generally 9 mg/m2 gemtuzumab ozogamycin (GO) on day 1 of induction. The CR rate was 39 of 44 (24 of 25 in low-risk, 15 of 19 in high-risk). Disease recurred at 9, 9, and 15 months, respectively, in 3 high-risk patients. The median follow-up time from CR date in the 36 patients alive in first CR is 16 months (15 months in low-risk, 20 months in high-risk), with 9 patients followed for at least 24 months. Each of the 36 patients was PCR-negative at last follow-up. Thus, none of the low-risk patients has received chemotherapy, and only 3 high-risk patients (the 3 with relapsed disease) have received chemotherapy past induction. ATRA plus ATO may serve as an alternative to chemotherapy in low-risk untreated APL (eg, in older patients) and, when combined with GO, may improve outcome in high-risk patients.

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

Blood ◽

10.1182/blood-2020-142375 ◽

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<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<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.

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Evaluation of Integrated CLL Scoring System (ICSS) in 420 Patients with Chronic Lymphocytic Leukemia

Blood ◽

10.1182/blood.v128.22.5563.5563 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5563-5563 ◽

Cited By ~ 1

Author(s):

Andrea Visentin ◽

Federica Frezzato ◽

Silvia Imbergamo ◽

Valentina Trimarco ◽

Veronica Martini ◽

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Keyword(s):

High Risk ◽

Predictive Accuracy ◽

Lymphocytic Leukemia ◽

Low Risk ◽

Rank Test ◽

High Risk Patients ◽

Log Rank Test ◽

Risk Patients ◽

Normal Fish

Abstract BACKGROUND Chronic Lymphocytic Leukemia (CLL) is one of the most common hematological malignancies in Western countries. The disease is characterized by heterogeneous clinical course and outcome. During the last 15 years several clinical, biological and molecular prognostic factors have been identified, validated and some of them are currently used in patients' and treatment management. To improve the predictive accuracy of these markers, they have been combined into prognostic indexes (W. Wierda, JCO 2011, D. Rossi, Blood 2012, J. Bahlo, Haematologica 2015). Werecently proposed the Integrated CLL Scoring System (ICSS) based on cytogenetic abnormalities by FISH, IGHV mutational status and CD38 expression from 212 patients (A. Visentin et al, Clin Lymph Myeloma & Leuk 2015). The aim of this study was to validate the prognostic power of our index into a larger series of 420 CLL patients. METHODS 420 CLL patients referred to the Hematology Unit of Padua University Hospital from 1989 to 2015 were recruited in this study. According to ICSS, patients were classified as: low-risk, those patients with 13q deletion or normal FISH, IGVH mutated and CD38<30%; high-risk, subjects with 17p or 11q deletion and/or IGVH unmutated and CD38>30%; intermediate-risk, all remaining patients. Treatment free survival (TFS) was calculated as time from diagnosis to treatment (event), death or last known follow-up (censored). Overall survival (OS) was calculated from the date of diagnosis to death for any cause (event) or last known follow-up (censored). TFS and OS were compared with log-rank test and plotted using Kaplan-Meier method. The predictive accuracy of ICSS was evaluated by the Harrel's concordance index (c-index); a value >0.5 implies a good predictive ability. RESULTS The median age of our cohort was 62 years; 64% were male and 85% were Binet stage A at diagnosis. Cytogenetic analysis by FISH showed that 41 patients harbored 17p deletion, 50 11q deletion, 236 13q deletion, 44 trisomy 12 and 49 had normal FISH. 236 (56%) patients had IGHV gene homology >98% (i.e. mutated IGHV) and 103 (25%) expressed more then 30% of CD38. According to ICSS 202 (48%) subjects were classified as low-risk, 83 (20%) intermediate-risk and 135 (32%) high-risk. After a median follow-up of 81 months, the median TFS for ICSS classes of risk were 211, 70 and 27 months (log-rank test, p<0.0001, Figure 1A). The estimated 10-year TFS were 61%, 37% and 10% for low, intermediate and high-risk patients. The median OS were 213 and 136 months for intermediate and high-risk, while it was not reached for low-risk patients (Log-rank test, p<0.0001, Figure 1B). After 10 years from diagnosis the estimated OS were 88%, 79% and 57%, respectively. These data were confirmed by a multivariate analyses. In fact, high-risk patients had 5.3 and 4.0 times risk of start treatment and death than low-risk subjects, respectively (p<0.0001). This model was statistically internally validated, showing c-indexed of 0.712 and 0.693 for TFS and OS, respectively. In multivariate analyses, variables confirmed to predict adverse prognosis were male gender (p=0.0183), age>65years (p<0.0001), Rai III-IV (p=0.0025), Binet C (p=0.0002), 17p deletion (p=0.0002), TP53 abnormalities (p=0.0051), unmutated IGVH (p<0.0001), CD38>30% (p=0.0044) and high-risk ICSS (p<0.0001). CONCLUSIONS We herein provide evidence of the prognostic power and feasibility of ICSS into a large population of CLL patients. The use of this prognostic index could help physician into follow-up schedule, since high-risk patients should be monitored more often given the estimated increased risk of progression. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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