scholarly journals Validation of a Prognostic Score to Identify Hospitalized Patients with COVID-19 at Increased Risk for Bleeding

Viruses ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2278
Author(s):  
Pablo Demelo-Rodriguez ◽  
Francisco Galeano-Valle ◽  
Lucía Ordieres-Ortega ◽  
Carmine Siniscalchi ◽  
Mar Martín Del Pozo ◽  
...  
Keyword(s):  
Major Bleeding ◽  
Prognostic Score ◽  
Hospitalized Patients ◽  
Low Risk ◽  
Intermediate Risk ◽  
Vte Prophylaxis ◽  
Increased Risk ◽  
Therapeutic Doses ◽  
Risk For Bleeding ◽  
D Dimer

Introduction: Hospitalized patients with COVID-19 are at increased risk for venous thromboembolism (VTE), but also for bleeding. We previously derived a prognostic score including four variables (elevated D-dimer, elevated ferritin, critical illness, and therapeutic-dose anticoagulation) that identified those at increased risk for major bleeding. Methods: We aimed to validate the score in a subsequent cohort of hospitalized patients with COVID-19 receiving standard-, intermediate- or therapeutic doses of VTE prophylaxis. We evaluated its capacity to predict major bleeding, non-major bleeding, and bleeding-related death. Results: The cohort included 972 patients from 29 hospitals, of whom 280 (29%) received standard-; 412 (42%) intermediate-, 157 (16%) therapeutic doses of VTE prophylaxis and 123 (13%) other drugs. Median duration of prophylaxis was 14.7 ± 10.3 days. Major bleeding occurred in 65 patients (6.7%) and non-major bleeding in 67 (6.9%). Thirty patients with major bleeding (46%) died within the first 30 days after bleeding. The prognostic score identified 203 patients (21%) at very low risk, 285 (29%) at low risk, 263 (27%) intermediate-risk and 221 (23%) at high risk for bleeding. Major bleeding occurred in 1.0%, 2.1%, 8.7% and 15.4% of the patients, respectively. Non-major bleeding occurred in 0.5%, 3.5%, 9.5% and 14.2%, respectively. The c-statistics was: 0.74 (95% confidence intervals [CI]: 0.68–0.79) for major bleeding, 0.73 (95% CI: 0.67–0.78) for non-major bleeding and 0.82 (95% CI: 0.76–0.87) for bleeding-related death. Conclusions: In hospitalized patients with COVID-19, we validated that a prognostic score including 4 easily available items may identify those at increased risk for bleeding.

scholarly journals Tinzaparin in Cancer and Renal Impairment: A Systematic Review Focusing on Safety

2020 ◽  
Author(s):  
Ioannis Vathiotis ◽  
Nikolaos Syrigos ◽  
Evangelos Dimakakos
Keyword(s):  
Systematic Review ◽  
Renal Impairment ◽  
Creatinine Clearance ◽  
Cancer Patients ◽  
Major Bleeding ◽  
Severe Renal Impairment ◽  
Vitamin K Antagonists ◽  
Bleeding Events ◽  
Increased Risk ◽  
Therapeutic Doses

Abstract Purpose: Low-molecular-weight heparins are approved for primary and secondary venous thromboembolism prevention. The purpose of this systematic review is to provide an update regarding the safety profile of tinzaparin sodium, prescribed either as a prophylactic or as a therapeutic regimen for VTE in cancer patients and individuals suffering from renal impairment. Method: We identified and studied clinical studies from 2000 until 2020, reporting safety outcomes for cancer patients and individuals with renal impairment receiving either prophylactic or therapeutic doses of tinzaparin. Results: In patients with cancer major bleeding rates fluctuate between 0.8% and 7%; reported major bleeding rates for non-cancer patients with renal impairment on prophylactic tinzaparin regimens were 0%. Non-cancer patients on therapeutic tinzaparin regimens exhibited major bleeding in 0 to 2.3% of cases; major bleeding rates were higher for cancer patients with renal impairment receiving therapeutic doses of tinzaparin (4.3 to 10%). Patients on tinzaparin exhibit significantly lower rates of clinically relevant nonmajor bleeding events in comparison with those on vitamin K antagonists. Bioaccumulation of tinzaparin is not correlated with age, body weight or creatinine clearance. Periodic administration of either prophylactic or therapeutic doses of tinzaparin does not result in bioaccumulation, even in patients with severe renal impairment and creatinine clearance < 20 ml/min. Conclusion: Tinzaparin is safe and can be used without dose adjustment in patients with severe renal impairment and creatinine clearance > 20 ml/min. Tinzaparin represents a thoroughly studied and safe choice for special populations at increased risk for thrombosis and bleeding.

Risk Factors for Bleeding in Patients with Nonvalvular Atrial Fibrillation Who Are Receiving Anticoagulant Therapy with Ximelagatran or Warfarin: Findings from the SPORTIF III and V Trials.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 528-528
Author(s):  
James D. Douketis ◽  
Karin Arneklev ◽  
Samuel Goldhaber ◽  
John Spandorfer ◽  
Frank Halperin ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Risk Factors ◽  
Atrial Fibrillation ◽  
Major Bleeding ◽  
Patient Population ◽  
Left Ventricular ◽  
Nonvalvular Atrial Fibrillation ◽  
Increased Risk ◽  
Risk For Bleeding ◽  
Statin Use

Abstract Background: Ximelagatran is a novel oral direct thrombin inhibitor that is as effective as warfarin in preventing stroke and other thromboembolic complications in patients with nonvalvular atrial fibrillation (AF). Risk factors for bleeding with warfarin are known, but risk factors for bleeding with ximelagatran have not been described. Unlike warfarin, ximelagatran has a predictable anticoagulant effect, does not require anticoagulation monitoring, has a low potential for interactions with drugs, food, or alcohol, and is not affected by genetic polymorphisms. We undertook an exploratory analysis of a large patient database to identify conventional and novel risk factors for bleeding in ximelagatran-treated patients, in warfarin-treated patients, and in all patients, irrespective of treatment. Methods: We undertook a pooled analysis of the SPORTIF III and V trials trials, which included 7329 patients with nonvalvular AF who received oral ximelagatran, 36 mg twice daily, or warfarin, administered to achieve a target international normalized ratio of 2.0–3.0. Patients had nonvalvular AF and 1 or more risk factors for stroke: hypertension; age ≥75 years; previous stroke, transient ischemic attack (TIA) or systemic embolism; left ventricular dysfunction; age ≥65 years and coronary artery disease; or age ≥65 years and diabetes mellitus. Major exclusion criteria were: mitral stenosis; previous heart valve surgery; transient AF; increased risk for bleeding. Multivariate logistic regression analysis was used to identify independent risk factors for major bleeding. The hazard ratio (HR) for major bleeding, and corresponding 95% confidence interval (CI), was calculated for each variable in the regression model. Results: The Table presents risk factors in which there was a significant or a non-significant (NS) association with major bleeding in ximelagatran-treated or warfarin-treated patients, and in the combined patient population. Risk factor Ximelagatran-treated patients, HR (95% CI) Warfarin-treated patients, HR (95% CI) Combined patient population, HR (95% CI) Aspirin use 1.65 (1.07, 2.55) 2.40 (1.69, 3.42) 1.96 (1.49, 2.58) Increasing age 1.03 (1.01, 1.05) 1.06 (1.03, 1.08) 1.04 (1.03, 1.06) Prior liver disease NS 4.96 (1.57, 15.62) NS Prior stroke or TIA 1.78 (1.16, 2.73) NS NS Diabetes mellitus 1.80 (1.18, 2.75) NS 1.39 (1.05, 1.86) Asian race NS NS 1.99 (1.16, 3.42) Statin use 0.62 (0.39, 0.97) 0.61 (0.42, 0.88) 0.62 (0.39, 0.97) Conclusions: Overall, the bleeding risk was lower with ximelagatran compared with warfarin. Aspirin use and increasing age were associated with an increased risk of bleeding in both ximelagatran- and warfarin-treated patients. Statin use was associated with a decreased risk for bleeding in both groups.

Do Unexpected and Cryptic FISH Lesions Of Chromosomally Normal MDS Patients Have Any Prognostic Relevance?

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1549-1549
Author(s):  
Paolo Bernasconi ◽  
Irene Dambruoso ◽  
Marina Boni ◽  
Paola Maria Cavigliano ◽  
Ilaria Giardini ◽  
...  
Keyword(s):  
High Risk ◽  
Disease Progression ◽  
Low Risk ◽  
Disease Stage ◽  
Intermediate Risk ◽  
Disease Evolution ◽  
Prognostic Relevance ◽  
Increased Risk ◽  
Very High ◽  
Disease Specific

Abstract Conventional cytogenetic (CC) still remains a mandatory step in the routine diagnostic work-up of every MDS patient (pt), is one of the major determinant of disease outcome and guides potential treatment decisions. However, CC is not informative in about 50% of chromosomally normal (CN) pts and provides limited information in those with very rare defects even if the revised IPSS cytogenetic categories have tried to overcome this drawback. More sensitive techniques (aCGH, SNP-a and NGS), still used in the research setting only, suggest that CN pts may instead contain novel unexpected chromosomal lesions which prognosis is still undefined. Thus, the principal goal of our study was to establish whether FISH with disease specific probes (i.e. for chromosomal regions most commonly affected in MDS) along with non-disease specific probes (i.e. for regions which alteration in MDS has been demonstrated by aCGH only) may effectively unmask clonal cryptic defects. Other aims were to establish the nature of these defects, to identify the potentially targeted genes and to estimate their possible prognostic relevance. The one-hundred twenty-seven consecutive CN MDS pts of the present study came to our observation in the period January 2003-December 2012. They were forty-nine females and seventy-eight males, median age 66 years (range 24-88). Twenty-one pts were diagnosed as RARS, 29 as RA, one as CRMDS, one as U-MDS, 25 as RCMD, 26 as RAEB-1 and 24 as RAEB-2. On CC 122 pts presented a normal karyotype and five no mitotic figures. Considering the revised IPSS score, 62 pts were considered very low-risk, 32 low-risk, 23 intermediate risk, 8 high-risk and 2 very high-risk. Median follow-up was 22 months (range 1-90). At the time of the study nine pts have died. FISH probes were chosen based on the frequency of their involvement in MDS and their Mb position determined using UCSC genome browser on Human Mar. 2003 assembly. They were obtained from BACPAC Resources Center at C.H.O.R.I. (Oakland, USA), labelled and applied as previously described. These probes were: RP11-912D8 (19q13.2); RP11-196P12 (17q11.2); RP11-269C4 (14q12); RP11-351O1 (10q21.3); RP11-144G6 (10q11.2); RP11-122A11 (7q34); RP11-951K18 (5q13.1); RP11-101K5 (4p14); RP11-544H14 (2q33). i-FISH cut-off values were fixed at 10%. Thirty-one pts (24.4%) presented at least a single defect, always represented by deletions or gains of chromosomal material. Among them 8 pts (25.8%) presented at least two defects. Bands most commonly targeted by deletions/amplifications were 19q13.2 (61.3%), 14q12 (32.2%), 17q11.2 (16.1%), 5q13.1 (12.9%), 7q34 (12.9%), 4p14 (9.6%). Deletions of bands 10q11.2, 10q21.3 and 2p33 were more rare. As the RMD-1 gene, involved in DNA double strand breaks and homologous recombination, maps at band 19q13.2, the most commonly deleted chromosomal area, additional molecular tests are being developed to analyse this gene. An abnormal FISH pattern was observed in 2/21 (9.5%) RARS, in 7/29 (24.1%) RA, in 5/25 (20.0%) RCMD, in 8/26 (30.6%) RAEB-1 and in 9/24 (37.5%) RAEB-2. Considering IPSS, an abnormal FISH pattern was revealed in 7/62 (11.3%) very low-risk, in 8/32 (25%) low-risk, in 10/23 (43.4%) intermediate risk, in 5/8 (62.5%) high-risk and in 1/2 very high-risk patients. Disease evolution occurred in a total of 34 pts (3 RARS, 7 RA, 5 CRMD, 11 RAEB-1 and 8 RAEB-2), 16 (one RARS, 3 RA, 2 CRMD, 6 RAEB-1 and 4 RAEB-2) with an abnormal FISH pattern. All the 8 patients with at least two chromosomal deletions experienced disease progression. In conclusion, i) FISH reveals novel unexpected karyotype defects, most commonly deletions pinpointing genes involved in DNA repair, in about 24.4% of CN MDS; ii) band 19q13.2 deletion is the most common defect, frequently associated with disease evolution; ii) an abnormal FISH pattern is correlated with an advanced disease stage and an intermediate/high revised IPSS score; iii) >two lesions are associated with an increased risk of disease progression. Disclosures: No relevant conflicts of interest to declare.

Calreticulin Mutation Does Not Modify the International Prognostic Score for Predicting the Risk of Thrombosis Among 1,150 Patients with Essential Thrombocythemia

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 404-404
Author(s):  
Guido Finazzi ◽  
Alessandra Carobbio ◽  
Paola Guglielmelli ◽  
Elisa Rumi ◽  
Silvia Salmoiraghi ◽  
...  
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Prognostic Score ◽  
Low Risk ◽  
Intermediate Risk ◽  
Thrombotic Risk ◽  
Exon 9 ◽  
International Prognostic Score ◽  
Risk Categories ◽  
Calr Mutation

Abstract Background An International Prognostic Score for the risk of thrombosis (IPSET-thrombosis) in Essential Thrombocythemia (ET) was developed (Barbui et al. Blood, 2012;120:5128). Risk factors included: age >60 years (1 point), cardiovascular (CV) risk factors (1 point), previous thrombosis (2 points) and the presence of JAK2V617F mutation (2 points). Low, intermediate and high risk categories were identified by scores 0-1; 2; and ≥ 3, respectively. Mutations in the exon 9 of CALreticulin (CALR) gene were recently identified in about 50-60% of patients with JAK2V617F negative ET and associated with a reduced thrombotic risk as compared with JAK2V617F positive patients. Aim To evaluate whether the identification of CALRmutation in patients with ET has any impact on the IPSET-thrombosis score Patients and Methods Under the auspices of AGIMM (AIRC Gruppo Italiano Malattie Mieloproliferative), four Italian centers with recognized experience in myeloproliferative neoplasms participated in the current study. Overall, 1,150 patients who met the 2008 WHO criteria for ET and were molecularly characterized for JAK2V617F, MPLW515L/K and CALR exon 9 mutations were included. The JAK2 and MPL mutations were assessed by real-time quantitative polymerase chain reaction and by high-resolution melting analysis followed by bidirectional Sanger sequencing. Mutations in exon 9 of CALRwere assessed by bidirectional sequencing or next generation sequencing. Results Presenting features of the study population were: median age 58 years (range 5th-95th percentile 27-82 years; 65% females), median hemoglobin 14.1 g/dL (range 5th-95th percentile 11.8-16.3), median leukocyte count 8.7x109/L (range 5th-95th percentile 5.4-14.7), median platelet count 718x109/L (range 5th-95th percentile 486-1313). CV risk factors (at least one among smoke, diabetes and hypertension) were present in 568 (49%) patients. Arterial or venous thrombosis history before or at diagnosis was documented in 167 (15%) patients. JAK2V17F, MPLW515L/K and CALRmutations were detected in 744 (65%), 44 (4%) and 164 (14%) patients respectively. The remaining 198 patients (17%) were wild-type for all three mutations. During a median follow-up of 4.1 years (range 0-29), 104 patients developed an arterial or venous thrombotic event, with a total incidence rate of 1.59% patients/year (pt-ys). The IPSET-thrombosis ability to discriminate the thrombotic risk was confirmed. In fact, in the low risk (reference category), the rate was 0.57% pt-ys; in the intermediate risk was 1.60% pt-ys (Hazard Ratio (HR) 3.10, 95% Confidence Interval (CI) 1.55-6.18, p=0.001) and in the high risk group was 2.34% pts-yr (HR 4.59, 95% CI 2.41-8.77 p<0.0001). As to the impact of CALR mutation in the three categories of the IPSET-thrombosis score, we observed that CALR mutated patients were more frequently distributed in the low risk (48%) and intermediate risk (46%) than in the high risk IPSET groups (6%). In univariate analysis, patients carrying CALR mutation had a lower incidence of thrombosis than those with JAK2V617F (HR 0.61, 95% CI 0.34-1.09, p=0.093). However, CALR mutated patients were significantly younger (median age 53.5 versus 60.8 years, p=0.001) and presented with less previous thrombosis (8% versus 17%, p=0.005) than JAK2V617F mutated patients. This could explain why in multivariable models, CALR mutation did not retain the association with the risk of thrombosis. This was demonstrated in the whole population (HR 0.81, 95% CI 0.30-2.17, p=0.674), as well as in the low risk (HR 1.01, range 0.27-3.81, p=0.987) and intermediate risk categories (HR 1.80, range 0.57-5.72, p=0.317); the high risk category was not evaluable for the low proportion of CALRmutated patients in this group. Conclusions CALR mutation does not have a significant impact on the IPSET-thrombosis prognostic score. The score can be used as it is to predict the risk of thrombosis in molecularly-annotated, WHO-2008 diagnosed ET patients. Disclosures Vannucchi: Novartis Pharmaceuticals Corporation: Consultancy, Honoraria, Research Funding.

P5591Efficacy and safety of lower dose slow infusion of t-PA for intermediate-risk pulmonary embolism patients with risk for bleeding

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
S Obradovic ◽  
B Dzudovic ◽  
I Sekulic ◽  
B Subotic ◽  
J Matijasevic ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
Major Bleeding ◽  
Dose Range ◽  
Bleeding Risk ◽  
Intermediate Risk ◽  
Efficacy And Safety ◽  
Bleeding Events ◽  
Slow Infusion ◽  
Basic Characteristics ◽  
Risk For Bleeding

Abstract Background Current guidelines do not recommend thrombolytic therapy for the treatment of intermediate-risk pulmonary embolism (PE) because of the tight balance between the benefit and safety with classic protocols. Aim The aim of this study was to compare the new thrombolytic protocol with lower-dose slow-infusion (LDSI) of tissue plasminogen activator (tPA) to classic 2-hours tPA infusion protocol or no-reperfusion in patients with intermediate-high risk PE with higher bleeding risk regarding 30-day efficacy and safety. Methods Among 849 patients with PE from the Serbian multicenter registry, 469 patients who fulfilled criteria for intermediate-risk PE were involved in the study. After propensity score matching 425 patients [263 (61.9%), 99 (23.3%) and 63 (14.8%) were treated with no-reperfusion, classic tPA protocol (100 mg for 2 hours) and LDSI of tPA (2–5 mg/hour either vie local catheter or systemic venous infusion with dose range of 25–50 mg)]. The basic characteristics of patients were well balanced between groups except that patients treated with LDSI of tPA had significantly higher usage of drugs which can be associated to bleeding and more previous bleeding events. Thirty day all-cause and PE-caused mortality and 7-day major bleeding were the main efficacy and safety end-points, respectively. Results All-cause and PE-cause 30-day mortality were 8.7% vs 16.2% vs 1.6% (Log rank p=0.007) and 4.5% vs 11.0% vs 0.0% (Log rank p=0.008) in patients with no-reperfusion, classic tPA protocol and LDSI of tPA protocol, respectively. Major bleeding at 7 days were 2.7% vs 8.1% vs 14.3% (Log rank p=0.001) in patients with no-reperfusion, classic tPA protocol and LDSI of tPA protocol, respectively. There was one fatal intracranial bleeding during catheter infusion of tPA. Conclusion Lower-dose slow-infusion of tPA protocol decreased significantly all-cause and PE-cause mortality at 30-day at the cost of excess of non-fatal major bleeding at 7-day in patients with intermediate-risk PE and higher risk for bleeding. Acknowledgement/Funding None

External validation of the Glasgow prognostic score (mGPS) for renal cancer.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 378-378
Author(s):  
Viraj A. Master ◽  
Timothy V. Johnson ◽  
Omer Kucuk ◽  
Daniel Canter ◽  
John Pattaras ◽  
...  
Keyword(s):  
High Risk ◽  
Cox Regression ◽  
Inflammatory Responses ◽  
Prognostic Score ◽  
External Validation ◽  
Glasgow Prognostic Score ◽  
Low Risk ◽  
High Risk Patients ◽  
Increased Risk ◽  
Risk Patients

378 Background: Inflammation has been termed the 7th hallmark of cancer (Hanahan and Weinberg Cell 2011). Measurement of systemic inflammatory responses in malignancy is possible using a selective combination of two commonly available, cost-effective serum assays. The combination of these two serum markers, C-reactive protein (CRP) and albumin, is termed the modified Glasgow prognostic score (mGPS), and is strongly correlated with outcome in a variety of cancers, including mRCC. Recently, mGPS has been shown to be predictive of outcome in localized RCC (ASCO GU 2010 #390). We sought to externally validate these results. Methods: Nephrectomized patients with clinically localized (T1-T4N0M0) clear cell RCC with negative surgical margins were followed for a mean of 25 months (range: 1-81 months). Relapse and survival was identified through routine follow-up. Patients were categorized by mGPS score as Low Risk (mGPS = 0 points), Intermediate Risk (mGPS = 1 point), and High Risk (mGPS = 2 points). One point was assigned to patients for an elevated CRP (>10 mg/L) and hypoalbuminemia (<3.5 mg/dL). Patients with normal CRP and hypoalbuminemia were assigned 0 points. Kaplan-Meier and multivariate Cox regression analyses examined relapse-free survival (RFS) and overall survival (OS) across patient and disease characteristics. Results: Of 248 patients, 17.9% relapsed and 18.6% died. Of Low, Intermediate, and High Risk patients, 7.2%, 7.7%, and 45.5%, respectively relapsed and 5.2%, 15.4%, and 39.4%, respectively died during the study. In multivariate analysis including stage and grade, mGPS was significantly associated with RFS and OS. Compared to Low-Risk patients, High-Risk patients experienced a 3-fold (OR: 2.906, 95% CI: 1.055-8.001) increased risk of relapse and 4-fold (HR: 3.722, 95% CI: 1.046-13.245) increased risk of mortality. AUC is 0.813, which compares very favorably to existing prognostic algorithms. Conclusions: In this external validation cohort of US patients, mGPS continues to be a predictor of relapse and overall mortality following nephrectomy for localized RCC. Clinicians may consider using mGPS as an adjunct to identify high-risk patients for possible enrollment into clinical trials, or for patient counseling.

Are men with favorable intermediate-risk prostate cancer candidates for active surveillance?

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 82-82
Author(s):  
Ann Caroline Raldow ◽  
Danjie Zhang ◽  
Ming-Hui Chen ◽  
Michelle H. Braccioforte ◽  
Brian Joseph Moran ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Active Surveillance ◽  
Locally Advanced ◽  
Low Risk ◽  
P Value ◽  
High Dose ◽  
Intermediate Risk ◽  
Increased Risk ◽  
Risk Prostate Cancer

82 Background: Active surveillance (AS) is considered appropriate for patients with low-risk prostate cancer (PC) and a life expectancy of at least 10 years. However, with grade migration following the 2005 International Society of Urologic Pathology consensus conference, AS may also be an initial option for men with favorable intermediate-risk PC. We estimated and compared the risk of PC-specific mortality (PCSM) following high dose radiation therapy and androgen deprivation therapy as appropriate amongst men with low, favorable intermediate, unfavorable intermediate, and high-risk PC. Methods: The study consisted of 6,595 consecutively treated men (median age: 68 years) with localized or locally advanced PC at the Chicago PC Center between 1997 and 2013. Fine and Gray competing risks regression analyses (table) were used to assess the risk of PCSM in men with favorable intermediate, unfavorable intermediate or high-risk compared to low-risk PC, adjusting for age at and year of treatment. Results: After median follow-up of 7.76 years, 820 men died: 72 of PC. While men with favorable intermediate-risk did not have significantly increased risk of PCSM as compared to low-risk PC (adjusted hazard ratio (HR) 1.28, 0.63-2.62 95% confidence interval (CI), p-value 0.49), men with high (adjusted HR 9.91, 5.48-17.94 95% CI, p-value <0.0001) or unfavorable intermediate-risk PC (adjusted HR 3.17, 1.60-6.30, p-value 0.001) did. Eight-year point estimates of PCSM were low: 0.68% [0.32-1.31% 95% CI] and 0.44% [0.25-0.75% 95% CI] for men with favorable intermediate and low-risk PC, respectively. Conclusions: Men with low and favorable intermediate-risk PC have similar and low estimates of PCSM during the first decade following standard management. These results provide evidence to support AS as an initial approach for men with favorable intermediate-risk PC. [Table: see text]

Incidence of venous thromboembolic disease (VTE) in a cohort of patients with colorectal cancer (CRC) according to KRAS, NRAS and BRAF status.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15136-e15136
Author(s):  
Pilar Garcia-Alfonso ◽  
Laura Ortega Morán ◽  
Iria Gallego Gallego ◽  
Gonzalo García González ◽  
Gabriela Torres Pérez-Solero ◽  
...  
Keyword(s):  
High Risk ◽  
Predictive Model ◽  
Metastatic Disease ◽  
Statistical Significance ◽  
Univariate Analysis ◽  
Low Risk ◽  
Intermediate Risk ◽  
Vein Thrombosis ◽  
Increased Risk ◽  
Cancer Associated Thrombosis

e15136 Background: A recent study has suggested that KRAS mutation could increase the risk of VTE in patients with CRC. The role of others biomarkers, such as BRAF, in this setting is unknown. The aim of this study is to analyze the incidence of cancer-associated thrombosis in a cohort of patients with CRC based on KRAS, NRAS and BRAF status. Methods: We performed a retrospective review of patients with metastatic CRC and KRAS/NRAS/BRAF status known, attended in the Medical Oncology Department of the Hospital General Universitario Gregorio Marañón (Madrid, Spain) between January 2010 and January 2018. Results: 194 patients were identified and included in the analysis. The median age was 64 years (18-86). Most were metastatic at diagnosis (58.1%). Khorana’s predictive model: low-risk 67.7%, intermediate-risk 31.0%, high-risk 2.3%. The median follow-up was 35 months (2-240). 41 patients (21.1%) experienced VTE (11 pulmonary embolism, 15 lower extremity deep-vein thrombosis, 12 visceral vein thrombosis, 2 catheter-related thrombosis, 1 unknown). Most had metastatic disease at the moment of VTE (90.2%). 40% of the events occurred at the time of diagnosis or within the first 6 months. 65% were incidental events. Khorana’s predictive model in VTE patients: low-risk 63.4%, intermediate-risk 24.5%, high-risk 7.3%. According to biomarkers, the incidence was 19.1% (13/68) in KRAS/NRAS mutated patients, 28.6% (6/21) in BRAF mutated patients and 21% (22/105) in triple-wild-type patients. 6/38 patients (15.8%) developed recurrent thrombosis. In the univariate analysis, the presence of chronic kidney disease (p = 0.022), ECOG ≥ 2 (p = 0.038) and high-risk Khorana score (p = 0.011) were significantly associated with increased risk of VTE. Metastatic disease showed a trend towards the statistical significance (p = 0.053). In the multivariate model, including this variables, age, sex and biomarkers, only ECOG ≥ 2 remained independent predictor of VTE (OR 8.73; CI 95% 1.32-57.82; p = 0.025). Conclusions: The biomarkers have not been associated with the risk of VTE. We have observed a high incidence of VTE in BRAF mutated patients that should be investigated in further studies.

Validation of Mantle Cell International Prognostic Index (MIPI) in Mantle Cell Lymphoma (MCL) in a Retrospective Single Institution Series

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2828-2828
Author(s):  
Annalisa Chiappella ◽  
Barbara Botto ◽  
Filippo Marmont ◽  
Ernesta Audisio ◽  
Ileana Baldi ◽  
...  
Keyword(s):  
High Risk ◽  
Clinical Course ◽  
Prognostic Score ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Low Risk ◽  
Intermediate Risk ◽  
Single Institution ◽  
Mantle Cell

Abstract Introduction: The clinical course of MCL is characterized by a continuous pattern of relapse and a poor long term outcome with a median Overall Survival (OS) of four years and a 15% of long term survivors. Recently a new clinical prognostic score (MIPI), including performance status, age, LDH level and leukocyte count has been reported. This score allows a more reliable estimation of individual clinical course. We retrospectively applied the MIPI score to patients with MCL. Patients and methods: Between 1999 and 2007, 40 patients with MCL diagnosed and treated in a single institution entered into the study. Clinical characteristics were as follows: median age 56 years (range 37–81), 80% male; 82% stage IV; 78% bone marrow involvement and 15% MCL with blastoid variant. First line treatments were: high dose chemoimmunotherapy including Rituximab (R) with autologous stem cell transplantation (R-HDC) in 26 patients and Rituximab-CHOP like chemotherapy (R-CHOP) in 14. Crude Kaplan-Meier OS and progression-free survival (PFS) curves were estimated both overall and stratified by MIPI and International Prognostic Index (IPI) score. Differences between curves were tested using the 2-tailed log-rank test. In order to quantify the predictive discrimination of MIPI and IPI scores, univariate logistic models (with death and progression event as binary outcomes) were fitted and the area under the receiver operating characteristic (ROC) curves (c index) was estimated. Results: According to MIPI score 17 patients (43%) were at low risk (LR, score 0–3), 13 patients (32%) at intermediate risk (IR, score 4–5) and 10 patients (25%) at high risk (HR, score &gt;5). According to IPI score 14 patients (35%) were at low risk (LR), 16 patients (40%) at low-intermediate risk (LIR) and 10 patients (25%) at intermediate-high and high risk (IH-HR). At the end of the treatment, 30 patients achieved a CR, five a PR and five did not respond. Relapses occurred in 17 patients and seven of them died of lymphoma. With a median follow-up (FU) of 29 months, OS was 85% (95% CI: 66%–93%); with a median FU of 21 months, PFS was 70% (95% CI: 51%–83%). Twenty-nine months OS rates for MIPI score were: LR 100%, IR 81%, HR 66% respectively (p=.07) and for IPI score were: LR 92%, LIR 94%, IH-HR 65% respectively (p=.09). Twenty-one months PFS rates for MIPI score were: LR 92%, IR 59%, HR 45% respectively (p=.006) and for IPI score were: LR 73%, LIR 87%, IH-HR 44% respectively (p=.09). MIPI score was more predictive than IPI score for the death event and for the progression event: the c index was 74% and 73% for MIPI compared to 72% and 69% for IPI respectively. In a subgroup analysis performed on 26 R-HDC patients, OS and PFS rates stratified for MIPI were: for OS, LR 100% vs IR 80% vs HR 69% (p=.4) and for PFS, LR 91% vs IR 80% vs HR 57% (p=.04) respectively. Discussion: in our retrospective series of patients, MIPI prognostic score discriminates among patients with different PFS. Relapses remain the most important issue for all patients affected by MCL, namely in HR group according to MIPI. New therapeutic strategies are warranted to improve the prognosis of MCL.

Over-The-Counter Aspirin Use In Patients Diagnosed With Multiple Myeloma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1961-1961
Author(s):  
Susan A Oliveria ◽  
Nancy Brandenburg ◽  
Syd Phillips ◽  
Kimberley J Woodcroft ◽  
Karen Wells ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Care Delivery ◽  
The United States ◽  
Low Risk ◽  
High Dose ◽  
Related Factors ◽  
Over The Counter ◽  
Vte Prophylaxis ◽  
Increased Risk ◽  
Daily Aspirin

Abstract Patients with multiple myeloma (MM) are at increased risk for venous thromboembolism (VTE) due to patient, disease, and treatment-related factors. Current National Comprehensive Cancer Network (NCCN) guidelines for VTE suggest that patients with MM receiving thalidomide or lenalidomide in combination with high-dose dexamethasone (480 mg per month) receive VTE prophylaxis. For MM patients at high risk for VTE (≥2 risk factors), low molecular weight heparin or full-dose warfarin is recommended. For MM patients at low risk for VTE (0-1 risk factor), aspirin 81-325 mg once daily is recommended for VTE prophylaxis. Eighty-five percent of patients diagnosed with MM are aged ≥55 and many of them are prescribed aspirin for primary or secondary prevention of cardiovascular or cerebrovascular disease, independent of their MM diagnosis. According to the 2010 National Health Interview survey, the prevalence of regular aspirin use among persons in the United States ≥50 years of age is 35.9%. Because aspirin use may provide effective prophylaxis of venous events in MM patients at low risk for VTE, it is important to understand the prevalence of aspirin use among MM patients. As part of a larger study examining the risk of VTE among patients diagnosed with MM and treated with thalidomide or lenalidomide, the objective of this study was to estimate the prevalence of over-the-counter (OTC) aspirin use among MM patients. Patients ≥18 years of age diagnosed with MM between January 1, 2005 and September 30, 2012 were identified from the tumor registry at the Henry Ford Health System (HFHS), a large integrated health care delivery system located in southeastern Michigan; whose data are included in the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute. We developed a telephone survey, and then contacted all eligible patients (i.e. they were alive and/or not documented as deceased) to quantify OTC aspirin use. Data analyses included descriptive statistics to assess the demographic, clinical, and aspirin use characteristics. We identified 381 patients diagnosed with MM; of those, 177 were eligible for the survey. We contacted these patients and achieved a 67% (n=119) response rate. The median age of survey respondents was 64 years (range 41-93) and 93 (78%) were aged ≥55. Sixty-two (52%) of the survey responders were female, 82 (69%) were African American, and 36 (30%) were white. Of the respondents, 46 (39%) reported weekly aspirin use and 43 of the 46 (94%) reported daily aspirin use. The average daily dose was 114 mg/day (standard deviation 93) and most patients (n=39 of 46; 85%) reported taking an 81 mg dose. The reason for daily aspirin use was cited as “Other reason for prophylaxis” by 36 (of 43; 84%) of the patients. In this case, patients indicated that they were taking aspirin for prophylaxis, but did not provide enough information to determine the reason for daily aspirin use. Only 5 patients (12%) reported taking aspirin for heart disease prophylaxis. Roughly one-quarter of the MM patients (n=31 of 119; 26%) indicated that they had a health problem that made aspirin use unsafe. Twenty-seven (23%) reported that they had a parent or sibling who had a heart attack before the age of 60; fourteen patients (12%) reported that they had a parent or sibling who has or ever had a VTE. Seventeen patients (14%) reported a history of ever having a VTE event themselves. Our data indicate that over one-third of patients diagnosed with MM use OTC aspirin daily. When treating patients diagnosed with MM, assessing risk for VTE and determining an appropriate VTE prophylaxis therapy is of the utmost importance. Disclosures: Brandenburg: Celgene Corporation: Employment, Equity Ownership.

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