scholarly journals Caplacizumab, Anti-Vwf Nanobody Potentially Changing the Treatment Paradigm in Thrombotic Thrombocytopenic Purpura: Results of the TITAN Trial

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 229-229 ◽  
Author(s):  
Flora Peyvandi ◽  
Christian Duby
Keyword(s):  
Platelet Count ◽  
Complete Remission ◽  
Primary Endpoint ◽  
Standard Of Care ◽  
Rank Test ◽  
First Episode ◽  
P Value ◽  
Platelet Response ◽  
Platelet Receptor ◽  
Titan Trial

Abstract INTRODUCTION: The TITAN trial achieved its primary endpoint in the ITT analysis of 75 subjects treated either with caplacizumab or placebo added to daily plasma exchange (PE). METHODS: Caplacizumab is a Nanobody which binds the A1 domain of vWF and thereby blocks the interaction of multimeric vWF with the GPIb-IX-V platelet receptor, preventing platelet aggregation typical of TTP. TITAN was a randomized, placebo controlled, single-blind, parallel design study. The primary endpoint was time to confirmed platelet response defined as platelet count normalization confirmed 48 hours later. Analysis was prospectively stratified according to whether or not subjects received a single PE prior to randomization. Treatment consisted of one IV bolus injection of caplacizumab 10mg (CAP) or placebo (PLC) prior to first on-study PE, followed by daily SC administration after PE. Once PE was stopped, CAP or PLC SC administration continued, daily for 30 days. RESULTS: The ITT population consisted of 36 and 39 subjects randomized 1:1 to CAP or PLC, respectively. Treatment arms were well balanced for age, race, body mass index. Presentation of TTP as an initial TTP episode or recurrent TTP was similar for both groups with 2/3 first episode and 1/3 recurrent. Platelet count and LDH were similar as summarized in table 1. Table 1 at baseline CAP N=36 PLC N=39 Platelets (10³/mm³) mean ± SD 21.1 ± 18.2 28.0 ± 20.0 LDH (U/L) mean ± SD 1277 ± 853 1270 ± 939 % subjects with ADAMTS-13 activity < 5% (FRET) 58.3 % 56.4 % Time to reach platelet response was almost 2 days shorter for CAP versus PLC, with a 39% reduction in time to response in the stratum with no prior PE, and 43% reduction in time to response in the stratum with a single prior PE. The overall hazard ratio was 2.197 for obtaining the confirmed platelet response with CAP over PLC, with a significance of p=0.013. The distribution of time to response was narrower for CAP in comparison to the distribution of subjects receiving PLC which was skewed towards longer confirmed platelet response time in table 2. Table 2 CAP PLC Median days to confirmed platelet response – subjects with no prior PE (95% CI) 3.00 (2.74, 3.88)N = 34 4.92 (3.21, 6.59)N = 35 25th & 75th percentile 2.72 & 4.31 3.01 & 11.37 Median days to confirmed platelet response – subjects with one single prior PE (95% CI) 2.44 (1.92, 2.97)N = 2 4.31 (2.91, 5.68)N = 4 25th & 75th percentile 1.92 & 2.97 3.37 & 5.23 N = 36 N = 39 Overall Hazard Rate Ratio for CAP vs. PLC (95% CI) 2.197 (1.278, 3.778) Stratified Log-rank Test p-value 0.013 Exacerbation of TTP occurred in 3 (8%) subjects receiving CAP versus 11 (28%) in the PLC arm. Complete remission defined as confirmed platelet response and absence of exacerbation up to 30 days after end of daily PE was achieved in 29 (81%) subjects of the CAP arm versus 18 (46%) subjects receiving PLC. The greater proportion of complete remission, coupled with the faster and narrower distribution of time to confirmed platelet response supports a greater predictability of patient response to PE in the CAP arm, and is reflected in number of days of PE. The number of consecutive days of PE was (mean ± st dev) 6.6 ± 3.4 days for CAP versus 8.1 ± 6.5 days for PLC with a total plasma volume administered including tapering of 22.5 ± 15.9 liters for CAP versus 28.4 ± 21.3 liters for PLC. The proportion of subjects with exacerbation and/or relapse up to the 1 month follow-up was even for both groups: 13 (36.1%) and 13 (33.3%) for both arms. Higher number of early relapses in the CAP arm substantiates a protective effect and warrants longer CAP treatment in some patients. Treatment emergent adverse events (TEAE) and deaths are summarized in table 3. Table 3 Safety population CAP N=35 PLC N=37 Subjects with any TEAE N (%) 34 (97%) 37 (100%) Subjects with bleeding related TEAEs N (%) 19 (54%) 14 (38%) Subjects with any TE Serious AEs N (%) 20 (57%) 19 (51%) Deaths N (%) 0 2 (5%) CONCLUSIONS: Caplacizumab, as a novel treatment, improved standard of care of patients affected with acquired TTP by a more rapid achievement of platelet normalization and lower number of exacerbations with manageable side effects and bleeding episodes. The TEAEs were consistent with the serious and potentially life-threatening condition of TTP. Further reducing PE and optimizing duration of caplacizumab should be investigated in future clinical trials. Disclosures Peyvandi: Ablynx: Investigator fees Other. Duby:Ablynx: Employment.

Front-Line FLAG-IDA and Nove-HiDAC Chemotherapy Improves Overall Survival (OS) and Complete Remission Rates (CR) for Patients with Secondary or Therapy-Related AML Compared to 3&7

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4893-4893
Author(s):  
Sita D. Bhella ◽  
Eshetu G Atenafu ◽  
Andre C Schuh ◽  
Mark D. Minden ◽  
Aaron D. Schimmer ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Complete Remission ◽  
Invasive Aspergillosis ◽  
Myeloproliferative Neoplasm ◽  
Rank Test ◽  
P Value ◽  
Front Line ◽  
First Line ◽  
Poor Risk

Abstract Background: Therapy for patients (pts) with high risk AML remains unsatisfactory. Retrospective studies have demonstrated activity of fludarabine, cytarabine, GCSF and idarubicin (FLAG-IDA) and of mitoxantrone, etoposide and cytarabine (NOVE-HiDAC) as salvage therapy in pts with relapsed or refractory AML. A recent randomized trial indicated high complete remission (CR) rates with improved relapsed-free survival when FLAG-IDA is administered as frontline induction therapy (Burnett et al. J Clin Oncol 2013). Since 01/2011, we have used FLAG-IDA as a first line therapeutic option in pts with high risk AML (poor risk cytogenetics, antecedent myeloproliferative neoplasm or myelodysplastic syndrome, and/or therapy-related AML) in an attempt to improve CR rates and permit more patients with AML to advance to allogeneic hematopoietic cell transplantation (alloHCT). Prior to 2011, either 3&7 or NOVE-HiDAC was used as first line therapy in patients with AML. Methods: We conducted a retrospective review of consecutive patients with high risk AML treated with front-line (a) FLAG-IDA between 01/2011 to 03/2015, (b) NOVE-HiDAC from 01/2006 to 12/2014, or (c) 3&7 from January 01/2011 to 12/2014 at the Princess Margaret Cancer Centre, to determine the CR rates and overall survival (OS) associated with the different regimens. Results: Patients characteristics are in Table 1. Fifty-two, 32, and 30 pts received FLAG-IDA, NOVE-HiDAC or 3&7 as first induction, respectively. Patients receiving FLAG-IDA had more high-risk features (i.e. complex cytogenetics, more azacytidine failures) compared to those receiving 3&7. Overall CR rate (i.e. CR + [CRi] + [CRp]) with FLAG-IDA, NOVE-HiDAC, and 3&7 respectively was 86% (n=42/49), 84% (n=21/25) and 50% (n=13/26), respectively. Median CR duration, censored at time of transplant, for pts receiving FLAG-IDA, NOVE-HiDAC and 3&7 was 3 mos (0.5-15), 3.5 mos (1-9) and 5.5 mos (0.5-42), respectively. OS at 1 year with FLAG-IDA, NOVE-HiDAC and 3&7 was 61% (95% CI, 41% -75%), 55% (95% CI, 34%-72%) and 21.6% (95% CI, 7.4%-40.7%), respectively (log-rank test p-value=0.0076). On subgroup analysis, there was no statistical difference in OS for pts ≥70 years. Of those with a donor identified, 35% (n=13/37), 73% (n=11/15) and 29% (n=5/17) of pts who were treated with FLAG-IDA, NOVE-HiDAC and 3&7 underwent an alloSCT, respectively. Pts with sAML may have had a higher transplant rate due to donor searches initiated earlier. Probable and possible invasive aspergillosis infections in pts receiving FLAG-IDA, NOVE-HiDAC and 3&7 were 50%, 34% and 33% respectively. Institution of earlier bronchoscopies led to increased fungal detection in the FLAG-IDA group. Median length of stay and ICU transfers were similar between groups. Induction deaths were secondary to sepsis, respiratory failure, invasive aspergillosis, and hemorrhage; these were similar across groups. Two pts receiving NOVE-HiDAC, with prior MPN, died of progressive splenomegaly and liver failure. Conclusions: Toxicities associated with frontline FLAG-IDA and NOVE-HIDAC induction are acceptable. FLAG-IDA and NOVE-HiDAC induction can result in durable CR, permitting patients with high risk AML to proceed to alloSCT and providing more favourable survival rates than frontline 3&7. Randomized studies are needed to confirm these findings for pts with poor-risk sAML and tAML. Table 1. Patient Characteristics FLAG-IDA(2013-2015) NOVE-HiDAC(2006-2014) 3&7(2011-2014) N=52 N=32 N=30 Median Age,y (range) Age <70 Age ≥ 70 Sex (M:F) 59.5 (21-76) 47 (90%) 5 (10%) 25:27 54.5 (24-74) 31 (97%) 1 (3%) 18:14 61.5 (20-78) 21 (70%) 9 (30%) 23:7 Cytogenetics by MRC Classification Good Intermediate Poor Not available 0 (0%) 25 (48%) 23 (44%) 4 (8%) 0 (0%) 18 (56%) 9 (28%) 5 (16%) 0 (0%) 20 (67%) 6 (20%) 4 (13%) Molecular (Pts ≤70 y with normal karyotype) FLT3-NPM1+ FLT3+ NPM1+ FLT3+ NPM1- FLT3-NPM1- 1/11 (9%) 5/11 (45%) 2/11 (18%) 3/11 (27%) 0/7 (0%) 2/7 (29%) 1/7 (14%) 4/7 (57%) 0/7 (0%) 1/7 (14%) 0/7 (0%) 6/7 (86%) WBC (x 109/L) (range) 5.15 (0.6 -239) 13 (1.3-182.4) 3.2 (0.7-164) sAML IBMFS MPN MDS Prior AZA 27 (52%) 0/27 (0%) 10/27 (37%) 17/27 (63%) 9/17 (53%) 29 (91%) 1/29 (4%) 15/29 (51%) 13/29 (45%) 2/13 (15%) 20 (67%) 2/20 (10%) 0/20 (0%) 18/20 (90%) 5/18 (28%) Therapy-Related (%) 14 (27%) 6 (19%) 15 (50%) De Novo AML with Complex Cytogenetics FLT3+ Other (ie MLL) 15 (29%) 7/15 (47%) 5/15 (33%) 3/15 (20%) 0 (0%) 0 (0%) Donor Identified (%) 37(71%) 16(50%) 17(57%) Disclosures Gupta: Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Honoraria, Research Funding.

scholarly journals A HOSPITAL BASED COMPARATIVE STUDY OF SERUM MEAN PLATELET VOLUME IN ISCHEMIC STROKE PATIENTS.

2019 ◽  
Vol 3 (9) ◽  
Author(s):  
Dr. Atul Baid ◽  
Dr. Chhavi Raman Baid
Keyword(s):  
Platelet Count ◽  
Ischemic Stroke ◽  
Mean Platelet Volume ◽  
Normal Subjects ◽  
Rank Test ◽  
P Value ◽  
Modified Rankin Scale ◽  
Platelet Volume ◽  
Laboratory Findings ◽  
Significant Difference

Objectives: This study was evaluated the association of serum means platelet volume, functional outcome and various parameters in patients of ischemic stroke. Methods: Detail history clinical examinations and relevant investigations were performed to all subjects. Lab parameters included as platelets counts, mean platelet volume and others were performed. The diagnosis of ischaemic stroke was made clinically with the evidence of acute lesions (infarct) confirmed by brain CT or MRI within the first 24 h of presentation of symptoms. Each patient condition was assessed by modified Rankin Scale. Results: Data was analyzed using SPSS version 26 software. Related-Samples Wilcoxon Signed Rank Test was applied. Mean and standard deviation were calculated. P value was taken less than or equal to 0.05 for significant differences (p ≤ 0.05). Conclusions: There was no significant difference seen in platelet count of ischemic stroke cases with control. Mean platelet volume was significantly higher in ischemic stroke cases than normal subjects. Majorities of ischemic stroke cases had moderate disability, required some help but able to walk without assistance. MPV was higher in ischemic stroke cases that had higher Modified Rankin scale.  Hence, serum MPV can be used as meaningful laboratory findings for early detection of ischemic stroke. Key words: Ischemic stroke, mean platelet volume, platelet count, modified Rankin score

A multicenter, randomized, double-blind, placebo-controlled trial of thalidomide plus dexamethasone versus dexamethasone alone as initial therapy for newly diagnosed multiple myeloma

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7517-7517 ◽  
Author(s):  
S. V. Rajkumar ◽  
M. Hussein ◽  
J. Catalano ◽  
W. Jedrzejcak ◽  
S. Sirkovich ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Primary Endpoint ◽  
Interim Analysis ◽  
Controlled Trial ◽  
Data Monitoring Committee ◽  
Rank Test ◽  
P Value ◽  
Primary Therapy ◽  
Double Blind ◽  
Significance Level

7517 Background: Thalidomide plus dexamethasone (Thal/Dex) yields superior response rates versus dexamethasone (Dex) but its impact as primary therapy for multiple myeloma (MM) is unknown. Methods: Patients (pts) with previously untreated, symptomatic MM were eligible and were randomized in this double-blind trial to Thal/Dex (Arm A) or placebo plus Dex (Arm B). Pts in Arm A received Thal 50 mg PO daily, escalated to 100 mg on day 15, and to 200 mg from day 1 of cycle 2; Dex 40 mg PO was given on days 1–4, 9–12, and 17–20. Pts in Arm B received placebo instead of Thal, and Dex as in Arm A. Cycles were 28 days long, repeated until progression or undue toxicity. The primary endpoint was time to progression (TTP) defined using EBMT criteria. All analyses were intent to treat. Planned sample size was 218 eligible pts in each arm. Full information for one-sided log rank test with significance level of 0.025 (allowing for 1interim analysis) to have 80% power to detect a 40% improvement in TTP (16.8 mo in Arm A vs. 12 mo in Arm B) would be achieved when 282 pts have progressed. A pre-planned interim analysis of the primary endpoint and safety was performed by an independent Data Monitoring Committee (DMC). P value < 0.0015 at this interim analysis would indicate that Arm A is superior to Arm B based on an alpha-spending function of the O’Brien-Fleming type. The DMC recommended release of results. Results: 470 pts were enrolled: 235 randomized to Thal/Dex and 235 to placebo/Dex. Median follow-up was 25 months. Median age was 65 yrs. TTP was significantly superior with Thal/Dex vs placebo/Dex, median TTP 17.4 months (95% CI: 8.1 months-NE) vs 6.4 months (95% CI: 5.6–7.4 months), respectively, P < 0.000065, crossing the upper boundary for superiority. DVT was higher with Thal/Dex vs placebo/Dex, 15.4% vs 4.3%, respectively. Median survival was not reached in either arm. Conclusions: Thal/Dex is significantly superior to Dex alone as first-line therapy for multiple myeloma. [Table: see text] [Table: see text]

Race as a predictor of outcome in young patients with myeloma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e20019-e20019
Author(s):  
Francesca Cottini ◽  
Alicia Bao ◽  
Nidhi Sharma ◽  
Abdullah Mohammad Khan ◽  
Naresh Bumma ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplant ◽  
Young Patients ◽  
Standard Of Care ◽  
Disease Stage ◽  
Comprehensive Cancer Center ◽  
Rank Test ◽  
Cancer Center ◽  
P Value ◽  
Cell Transplant

e20019 Background: Multiple myeloma (MM) is a malignancy that affects Black Americans (BA) more often and at earlier age than White Americans (WA). BAs still frequently receive suboptimal care and are underrepresented in clinical trials or retrospective analyses. However, recent studies have shown that BA MM patients treated with standard-of-care regimens have similar if not superior outcomes than WA patients. The median age of MM diagnosis is 69 years; but ten percent of individuals develop MM before age of 50 years. Limited data are available regarding the outcomes and characteristics of this younger patient population. Herein, we specifically investigate the outcome of young MM patients. Methods: We retrospectively analyzed young MM patients (age < 50) diagnosed between 1992 and 2016 at The Ohio State University Comprehensive Cancer Center. After informed consent, data pertaining to patient demographics and MM characteristics were collected in a coded database. Descriptive statistics was used to summarize disease characteristics; chi-square or Wilcoxon rank-sum tests were used to compare outcomes between BA and WA patients. Overall Survival (OS) was estimated by Kaplan-Meier method, with log-rank test applied to test the statistical differences between survival curves. Two-sided p-values <0.05 were considered statistically significant. Results: In our institutional database, we identified 264 individuals who developed MM before age of 50 years (median age=46; range: 17-50 years). 211 of them had matched cytogenetic studies and were included in the final analysis. The majority of these patients were male (66%), had IgG disease (47%), and stage II-III at presentation (52%). 196 of patients (93%) underwent at least one autologous stem cell transplant-ASCT, with 23 of them receiving more than one ASCT (15%) and 9 of them undergoing allogeneic stem cell transplant (4%). In all, median OS was 9.84 years (95% CI, 6.75-12.92 years), which is higher than in unselected older MM patients. 24% of the patients (n=51) were BA while the remaining (n=160) were WA. We observed no statistical differences in terms of patient characteristics, disease stage, or cytogenetics between BA or WA, except for a statistically significant prevalence of del(13q) in WA patients (39% vs. 30%; p= 0.012). In our cohort, BA and WA patients received transplant at similar rates (94% vs. 88%, p-value=0.137). Finally, we observed an inferior median OS of 8.59 years (95% CI, 6.40-10.78 years) in WA compared with BA patients (median OS: not reached; p-value= 0.038), with 5-year OS of 86% in BA compared with 65% in WA patients. Conclusions: We report a retrospective cohort of young MM patients. In our cohort, we observed less prevalence of del(13q) and superior OS of BA compared with age-matched WA patients. This suggests that young BA MM patients benefit from standard-of-care approaches and strategies should continue to be pursued to improve access to care and optimize treatments.

A mechanistic radiographic and biologic phase 2 study of sunitinib in relapsed/refractory esophageal (E) and gastroesophageal (GE) cancers.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 149-149
Author(s):  
Christina Sing-Ying Wu ◽  
Sameh Mikhail ◽  
Lai Wei ◽  
Ludmila Katherine Martin ◽  
Xiaobai Li ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Stable Disease ◽  
Tumor Size ◽  
Kinase Inhibitor ◽  
Mutational Analysis ◽  
Progression Free Survival ◽  
Clinical Results ◽  
Rank Test ◽  
P Value ◽  
Initial Reduction

149 Background: Patients (pts) with relapsed or treatment-refractory E and GE cancers carry a poor prognosis. Inhibition of the vascular endothelial growth factor (VEGF) pathway may be a potential treatment approach. We conducted a phase II trial to assess the efficacy of sunitinib, a tyrosine kinase inhibitor that inhibits VEGFR 1 and 2. Methods: Pts received sunitinib 37.5 mg orally, daily. Primary endpoint was progression free survival (PFS) at 24 weeks. Secondary endpoints included overall response rate (ORR), overall survival (OS), PFS, and toxicity. Pts underwent serial functional imaging with DCE-MRI and measurements of serum VEGF, PIGF, VEGFR 2 and 3. Gene expression profiling and somatic mutational analysis using next-generation sequencing were also performed on tumor specimens (results to be presented at the symposium). Results: Clinical results are in the table. The PFS in the group that had clinical benefit [partial response (PR) + stable disease (SD)] with sunitinib was 99 days (95% CI: 74-161) vs. 39 days (95% CI: 26-42; Log-rank test p-value is <0.0001) in pts who had progressive disease (PD). By RECIST criteria, sunitinib non-responders demonstrated an initial reduction in tumor size but then subsequent rapid tumor size increase by week 6 as compared to baseline values. In contrast, sunitinib responders demonstrated at least stable disease through weeks 2-6. Changes in serum VEGF-A and VEGF-C levels from baseline to 2 weeks were associated with PFS (p=0.04 and p=0.03, respectively). Furthermore, baseline VEGF-C was also associated with PFS (p=0.03) and RECIST response (p=0.04). Conclusions: Although the primary endpoint was not met, these results suggest that there is a subgroup of patients with clinical response to sunitinib. Our correlative analysis indicated that circulating biomarkers, such as VEGF-C, are worthy of further research to help us identify this subgroup. Clinical trial information: NCT00702884. [Table: see text]

Efficacy and Safety of a New Intravenous Immunoglobulin Product in Patients with Chronic Immune Thrombocytopenic Purpura.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1307-1307
Author(s):  
Tadeusz Robak ◽  
Abdulgabar Salama ◽  
Lidia Kovaleva ◽  
Yaroslava I. Vyhovska ◽  
Simon Davies ◽  
...  
Keyword(s):  
Platelet Count ◽  
Adverse Events ◽  
Intravenous Immunoglobulin ◽  
Primary Endpoint ◽  
Immune Thrombocytopenic Purpura ◽  
Efficacy And Safety ◽  
Platelet Response ◽  
Thrombocytopenic Purpura ◽  
Platelet Counts ◽  
Chronic Itp

Abstract Background Intravenous immunoglobulin (IVIG) is an accepted treatment for immune thrombocytopenic purpura (ITP). A new liquid 10% human IgG preparation stabilized with proline at a pH of 4.8 (trade name: Privigen) was recently developed. It can be stored at room temperature and is therefore always ready to use. Here we report its efficacy and safety in patients with chronic ITP. Patients and Methods Fifty-seven patients with chronic ITP and a platelet count below 20 x 109/L were included in this open-label, single arm, multi-center Phase III trial. IVIG was given at a dose of 1 g/kg on 2 consecutive days at a maximum infusion rate of 4 mg/kg/min. A subset (56.1%) of the patients received premedication (acetaminophen or diphenhydramine) to avoid adverse events. The primary endpoint was the platelet response rate, defined as the percentage of patients showing an increase in platelet count to ≥50 x 109/L within 7 days of the first infusion. Secondary endpoints included platelet counts at specified time points, time to platelet response, duration of platelet response, and regression of hemorrhages at different bleeding sites. Safety was evaluated by the frequency and severity of adverse events. Results The primary endpoint, an increase in platelet counts to ≥50 x 109/L, was achieved by 81% of the subjects (95% CI: 69–89%). The highest median platelet count (149 x 109/L) was observed on day 8. Median time to response was 2.5 days, with 43% of subjects responding within 1 day. Median duration of platelet response (days with platelet count ≥ 50 x 109/L) was 15.4 days. Regression rates for various bleeding sites ranged from 78% to 100%. Regression of bleeding correlated with increases in platelet counts. Adverse events were reported in 52 (91%) subjects. The most common adverse event was headache (67%), the incidence and severity of which was attenuated by premedication with acetaminophen/diphenhydramine. There were 3 serious adverse events, one of which (aseptic meningitis) was considered related to the study medication. Conclusions The present study has shown the safety and significant efficacy of a novel, 10% liquid, ready for use IVIG preparation, in patients with chronic ITP. A rapid increase in platelet counts to a level where severe bleeding episodes become more unlikely was seen in the majority of patients, as expected with IVIG given at 1 g/kg on 2 consecutive days. The increase in platelet counts was associated with a regression of bleeding. Adverse events were generally mild to moderate in severity, corresponded to those expected with IVIG, and could be prevented with premedication.

scholarly journals Platelet Receptor Activity for Predicting Survival in Patients with Intracranial Bleeding

2021 ◽  
Vol 10 (10) ◽  
pp. 2205
Author(s):  
Barbara Dragan ◽  
Barbara Adamik ◽  
Malgorzata Burzynska ◽  
Szymon Lukasz Dragan ◽  
Waldemar Gozdzik
Keyword(s):  
Platelet Aggregation ◽  
Function Analysis ◽  
Strong Predictor ◽  
Adenosine Diphosphate ◽  
Intracranial Bleeding ◽  
Rank Test ◽  
Blood Coagulation Disorders ◽  
Platelet Response ◽  
Normal Platelet ◽  
Platelet Receptor

Blood coagulation disorders in patients with intracranial bleeding as a result of head injuries or ruptured aneurysms are a diagnostic and therapeutic problem and appropriate assessments are needed to limit CNS damage and to implement preventive measures. The aim of the study was to monitor changes in platelet aggregation and to assess the importance of platelet dysfunction for predicting survival. Platelet receptor function analysis was performed using the agonists arachidonic acid (ASPI), adenosine diphosphate (ADP), collagen (COL), thrombin receptor activating protein (TRAP), ristocetin (RISTO) upon admission to the ICU and on days 2, 3, and 5. On admission, the ASPI, ADP, COL, TRAP, and RISTO tests indicated there was reduced platelet aggregation, despite there being a normal platelet count. In ‘Non-survivors’, the platelet response to all agonists was suppressed throughout the study period, while in ‘Survivors’ it improved. Measuring platelet function in ICU patients with intracranial bleeding is a strong predictor related to outcome: patients with impaired platelet aggregation had a lower 28-day survival rate compared to patients with normal platelet aggregation (log-rank test p = 0.014). The results indicated that measuring platelet aggregation can be helpful in the early detection, diagnosis, and treatment of bleeding disorders.

scholarly journals AN ASSESSMENT OF CLINICAL EFFICACY OF HYPOTHERMIC THERAPY FOLLOWING MILD TRAUMATIC BRAIN INJURY IN THE ADOLESCENT ATHLETE AS COMPARED TO AN UNTREATED ACTIVE CONTROL POPULATION

2020 ◽  
Vol 8 (4_suppl3) ◽  
pp. 2325967120S0017
Author(s):  
Joseph Congeni ◽  
Tamara Murray ◽  
John Zak ◽  
Neil L. McNinch ◽  
Peyton Kline ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Cardiac Arrest ◽  
Brain Injury ◽  
Mild Traumatic Brain Injury ◽  
Clinical Efficacy ◽  
Primary Endpoint ◽  
Standard Of Care ◽  
Post Treatment ◽  
P Value ◽  
Pivotal Phase

Background: Hypothermic therapy has been shown to have clinical efficacy in a variety of cardiovascular injuries including cardiac arrest and myocardial infarction.1 It is standard of care for the treatment of neonates with hypoxic-ischemic encephalopathy (HIE) and has shown improved outcomes with traumatic brain injury (TBI)2, and sports-related injuries. Additionally, in several anecdotal studies, cold therapy has been hypothesized to be equally as effective in limiting the damaging effects of the body’s response to mild traumatic brain injury, commonly known as concussion; but the primary limitation of these studies has been sample size.3, 4 Hypothesis/Purpose: This study is being conducted to quantify the clinical safety and efficacy of head and neck cooling when applied after mild traumatic brain injury (mTBI) among adolescents participating in sporting activities. Methods: A multi-center, prospective, randomized, non-blinded, dual-arm comparator study employing an adaptive design with two-phases: the 60-patient pilot study presented here, and the pivotal phase currently underway. After randomization, subjects in the standard of care arm receive brain rest. Subjects in the treatment group receive brain rest plus 30 minutes of cooling therapy at the initial and 72 hour visits. Primary endpoint: SCAT5 symptom severity score, evaluated from initial clinic visit through 4 weeks post injury. SCAT5 measured at initial visit (pre/post treatment, both arms), 72 hour visit (pre/post treatment for intervention arm, once for standard of care arm) and once at 10 day and 4 week follow up visits for both arms. Results: To evaluate primary endpoint, a Repeated Measures Analysis of Variance was conducted as intended for pivotal phase, with unstructured covariance and utilizing last observation carried forward technique. Dependent variable modelled as absolute change from initial SCAT5. Significant main effects and interaction effects noted (p-value < 0.01, < 0.01 and 0.02 respectively). To evaluate secondary endpoint, a Wilcoxon Rank Sum Test was conducted to examine potential differences in ImPACT Cognitive Efficiency Index, there was no evidence in the sample of significant differences (p-value = 0.600). All testing evaluated at alpha level of significance = 0.05. Conclusion: Preliminary results from pilot phase indicate significant treatment effects that change differently over time, depending on group. Pivotal phase to determine efficacy is currently underway. Tables/Figures: [Table: see text][Figure: see text] References: The effect of mild induced hypothermia on outcomes of patients after cardiac arrest: a systematic review and meta-analysis of randomized controlled trials. Zhang et al. Critical Care (2015) 19:417. Therapeutic hypothermia for acute brain injuries. Andresen et al. Scandinavian Journal of trauma, Resuscitation and Emergency Medicine (2015) 23:42. The effect of selective head-neck cooling on physiological and cognitive functions in healthy volunteers. Jackson et al. Translational Neuroscience (2015) 6:131. Neurobiological effect of selective brain cooling after concussive injury. Walter et al. Brain imaging and behavior (2018) 2:891.

scholarly journals Treatment Outcome and Prognostic Factors of Korean Patients with Chronic Lymphocytic Leukemia: Multicenter Retrospective Study

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5669-5669
Author(s):  
Yunsuk Choi ◽  
Jung-Hee Lee ◽  
Chul Won Jung ◽  
Jin Seok Kim ◽  
Inho Kim ◽  
...  
Keyword(s):  
Platelet Count ◽  
Prognostic Factor ◽  
Chronic Lymphocytic Leukemia ◽  
Complete Remission ◽  
Prognostic Significance ◽  
Lymphocytic Leukemia ◽  
P Value ◽  
First Line ◽  
Hematopoietic Stem ◽  
Line Chemotherapy

Abstract Backgrounds: The incidence of chronic lymphocytic leukemia (CLL) in Asian population is very low, while CLL is the most common type of leukemia in Western countries. Asian CLL has been reported to have different immunophenotypes and clinical outcomes compared to those of western CLL. But, data on CLL in Asian countries is very limited because of the disease rarity. Thus, we evaluated the clinical characteristics and treatment outcome of Korean CLL patients and also analyzed prognostic significance of clinical parameters. Methods: We retrospectively analyzed 73 newly diagnosed CLL patients who had received chemotherapy at the 5 centers in Korea between 2000 and 2012. The CLL diagnosis and response evaluation were based on the International Workshop on CLL criteria updated in 2008. Small lymphocytic lymphoma was excluded in this study. Results: The median age of all patients was 60 years (range, 25-93 years). Compared to Western data, the positivity of atypical immunophenotypic markers such as CD 22 and FMC7 were frequently observed (45.5% and 69.2% of evaluable patients, respectively). As the first line chemotherapy, the various regimens were used as followings: chlorambucil (n=45), fludarabine (n=13), fludarabine, cyclophosphamide, and rituximab (FCR) (n=4), cyclophosphamide, vincristine, and prednisolone (CVP) (n=4), fludarabine and cyclophosphamide (FC) (n=3), and the other regimens (n=4). Patients were at Binet A (49.3%), B (11.6%) with active disease or stage C (39.1%) at the time of chemotherapy. The overall response rate after the first line chemotherapy was 69.9% with the complete remission (CR) rate of 15.1%. The FCR regimen achieved the highest CR rate (50%). Fifty patients were treated with the second line chemotherapy. Two patients received allogeneic hematopoietic stem cell transplantation at the refractory state and they are still alive without relapse. Of all included patients, the probability of overall survival (OS) and progression free survival (PFS) at 5-years was 84.9% and 28.7%, respectively. The 5-year relapse free survival (RFS) rate of the 17 patients attaining CR was 42.4%. Univariate and multivariate analyses showed that the higher WBC count (>100x103/¥ìL), the lower platelet count (<80x103/¥ìL), and the constitutional symptoms had a significantly adverse impact on OS (hazard ratio [HR], 6.584, p=0.002; HR, 15.692, p<0.001; HR, 4.769, p=0.010, respectively) (Table 1). The platelet count between 80x103/¥ìL and 110x103/¥ìL, however, had no prognostic significance. Compared to the kappa type of immunoglobulin light chain, the presence of lambda type on leukemic cells was a significant negative prognostic factor for PFS (HR, 2.775, p=0.037), although there was no significant difference on OS. The CR achievement after the second line chemotherapy or more was significantly related to shorter RFS (HR, 7.343, p=0.021) compared to that of the CR achievement after the first line chemotherapy. Conclusion: Thrombocytopenia (<80x103/¥ìL) is the most significant prognostic factor predicting worse survival in Korean CLL patients. In addition, hyperleukocytosis (>100x103/¥ìL), constitutional symptoms, and the lambda type of light chain restriction need to be reflected into the risk stratification system for CLL. Keywords: chronic lymphocytic leukemia, outcome, prognostic factor Abstract 5669. Table 1. multivariate analysis OS PFS RFS HR (95% CI) p-value HR (95% CI) p-value HR (95% CI) p-value WBC count (n=68), >100 x103/¥ìL, <100 x103/¥ìL 6.584 (1.950-22.231) 1 0.002 - - - - Platelet count (n=68), <80 x103/¥ìL 80 - <110 x103/¥ìL > 110 x103/¥ìL 15.692 (3.974-61.963) 1.561 (0.383-6.364) 1 <0.001 0.535 - - - - Constitutional symptoms (+) (n=71) 4.769 (1.452-15.660) 0.010 - - - - Surface immunoglobulin (n=41) kappa (+) - - 1 - lambda (+) 2.775 (1.063-7.246) 0.037 both negative 2.781 (0.882-8.767) 0.081 Chemotherapy response (n=72) - - CR1 1 CR2 / CR3 7.343 (1.357-39.736) 0.021 CR after Allo-HCT 0 0.993 WBC, white blood cell; CR1, complete remission after 1st line chemotherapy; CR2, complete remission after 2nd line chemotherapy; CR3, complete remission after 3rd line chemotherapy; Allo-HCT, allogeneic hematopoietic stem cell transplantation Disclosures No relevant conflicts of interest to declare.

scholarly journals LTBK-08. TOCA 511 & TOCA FC VERSUS STANDARD OF CARE IN PATIENTS WITH RECURRENT HIGH GRADE GLIOMA

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi284-vi284 ◽  
Author(s):  
Timothy Cloughesy ◽  
Kevin Petrecca ◽  
Tobias Walbert ◽  
Nicholas Butowski ◽  
Michael Salacz ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Single Agent ◽  
Standard Of Care ◽  
High Grade Glioma ◽  
Geographic Region ◽  
Rank Test ◽  
High Grade ◽  
Open Label ◽  
Durable Response ◽  
Secondary Endpoints

Abstract BACKGROUND Toca 511 (vocimagene amiretrorepvec) is a cancer-selective, retroviral replicating vector encoding a codon optimized, heat stabilized cytosine deaminase that converts Toca FC (extended-release 5-fluorocytosine, 5-FC) into the anticancer agent 5-fluorouracil. Three Ph1 studies in patients with recurrent high grade glioma have demonstrated a tolerable safety profile and encouraging efficacy. METHODS Toca 5 is a multi-national, randomized, open-label Ph3 trial (NCT02414165) of Toca 511 & Toca FC versus standard of care (SOC) options that comprises Investigator’s choice of single agent chemotherapy (lomustine, temozolomide) or bevacizumab in patients who have undergone resection for first or second recurrence of glioblastoma or anaplastic astrocytoma. 403 patients were randomized 1:1 to the Toca arm or the SOC arm and stratified by IDH1 status, KPS, and geographic region. Primary endpoint was overall survival (OS), and secondary endpoints were durable response rate, durable clinical benefit rate, duration of durable response, and 12-month survival rate. The study used group sequential design including 2 interim analyses and 1 final analysis, and the stratified log-rank test are used for the analysis. RESULTS 271 events were observed for this analysis. Median follow-up was 22.8 months, and the Toca arm missed the primary endpoint (OS) compared to the SOC arm (11.1 months median compared to 12.2 months, HR=1.06, p=0.6154). All secondary endpoints showed no meaningful difference between the arms of the trial. The safety, tolerability and adverse event profile of Toca 511 and Toca FC was as expected for this patient population, with low incidences of Grade 3–4 adverse events. Pre-planned subgroup analyses showed compelling OS improvement in patients with secondary recurrence, and favorable trends in IDH1 mutant and AA population. Detailed data will be presented at the time of the conference.

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