Effect of adjunctive dipyridamole to DAPT on platelet function profiles in stented patients with high platelet reactivity

2014 ◽  
Vol 112 (12) ◽  
pp. 1198-1208 ◽  
Author(s):  
Yongwhi Park ◽  
Udaya Tantry ◽  
Jong-Hwa Ahn ◽  
Kye Hwan Kim ◽  
Jin-Sin Koh ◽  
...  
Keyword(s):  
Platelet Function ◽  
Platelet Reactivity ◽  
Pde5 Inhibitor ◽  
Light Transmittance ◽  
Reactivity Index ◽  
Double Dose ◽  
High Platelet Reactivity ◽  
Number Of Patients ◽  
The Impact

SummaryAdjunctive use of phosphodiesterase (PDE) inhibitor can enhance antiplatelet and vasoprotective properties in patients with cardiovascular disease. The aim of this study was to evaluate the impact of PDE5 inhibitor dipyridamole on platelet function in stented patients with high platelet reactivity (HPR) during dual antiplatelet therapy (DAPT) with aspirin and clopidogrel. Patients with HPR after 600-mg clopidogrel loading were randomly assigned to adjunctive dipyridamole 75 mg twice daily to standard DAPT (DIP group; n = 45) or double-dose clopidogrel of 150 mg daily (DOUBLE group; n = 46) for 30 days. Platelet function was assessed at baseline and 30-day follow-up with platelet reactivity index (PRI) by vasodilator-stimulated phosphoprotein-phosphorylation (VASP-P) assay and platelet aggregation (PA) by light transmittance aggregometry (LTA). Primary endpoint was PRI at 30-day follow-up. HPR was defined as PRI > 50%. Baseline platelet function did not differ between the groups. Following 30-day therapy, platelet function was significantly reduced in the DIP and DOUBLE groups (all p-values ≤ 0.004 and ≤ 0.068, respectively). PRI values were not significantly different between the two groups (mean difference: 3.1%; 95% confidence interval: –2.8% to 9.0%: p = 0.295). PA values and prevalence of HPR were similar between the groups. However, a significant number of patients still exhibited HPR in the DIP (75.6%) and DOUBLE (67.4%) groups. In conclusion, among stented HPR patients, adding dipyridamole to DAPT does not reduce platelet reactivity and prevalence of HPR compared with double-dose clopidogrel therapy, and therefore both strategies are inadequate to overcome HPR.

The impact of renal function on platelet reactivity and clinical outcome in patients undergoing percutaneous coronary intervention with stenting

2014 ◽  
Vol 112 (12) ◽  
pp. 1174-1181 ◽  
Author(s):  
Nicoline Breet ◽  
Corine de Jong ◽  
Willem Jan Bos ◽  
Jochem van Werkum ◽  
Heleen Bouman ◽  
...  
Keyword(s):  
Renal Function ◽  
Antiplatelet Therapy ◽  
Platelet Function ◽  
Platelet Reactivity ◽  
Light Transmittance ◽  
Clinical Trial Registration ◽  
Platelet Function Test ◽  
Increased Risk ◽  
Function Test ◽  
The Impact

SummaryPatients with chronic kidney disease (CKD) have an increased risk of cardiovascular disease. Previous studies have suggested that patients with CKD have less therapeutic benefit of antiplatelet therapy. However, the relation between renal function and platelet reactivity is still under debate. On-treatment platelet reactivity was determined in parallel by ADP- and AA-induced light transmittance aggregometry (LTA) and the VerifyNow® System (P2Y12 and Aspirin) in 988 patients on dual antiplatelet therapy, undergoing elective coronary stenting. Patients were divided into two groups according to the presence or absence of moderate/severe CKD (GFR<60 ml/min/1.73 m2). Furthermore, the incidence of all-cause death, non-fatal acute myocardial infarction, stent thrombosis and stroke at one-year was evaluated. Patients with CKD (n=180) had significantly higher platelet reactivity, regardless of the platelet function test used. Patients with CKD more frequently had high on-clopidogrel platelet reactivity (HCPR) and high on-aspirin platelet reactivity (HAPR) regardless of the platelet function test used. After adjustment for potential confounders, this was no longer significant. The event-rate was the highest in patients with both high on-treatment platelet reactivity (HPR) and CKD compared to those with neither high on-treatment platelet reactivity nor CKD. In conclusion, the magnitude of platelet reactivity as well as the incidence of HPR was higher in patients with CKD. However, since the incidence of HPR was similar after adjustment, a higher rate of co-morbidities in patients with CKD might be the major cause for this observation rather than CKD itself. CKD-patients with HCPR were at the highest risk of long-term cardiovascular events.Clinical Trial Registration: www.clinicaltrials.gov: NCT00352014.

Platelet Inhibition and Bleeding in Patients Undergoing Non-Cardiac Surgery—The BIANCA Observational Study

2018 ◽  
Vol 118 (05) ◽  
pp. 864-872 ◽  
Author(s):  
Elisabeth Mahla ◽  
Helfried Metzler ◽  
Helmar Bornemann-Cimenti ◽  
Florian Prueller ◽  
Reinhard Raggam ◽  
...  
Keyword(s):  
Cardiac Surgery ◽  
Observational Study ◽  
Platelet Function ◽  
Platelet Reactivity ◽  
Objective Assessment ◽  
Timing Of Surgery ◽  
Light Transmittance ◽  
Reactivity Index ◽  
Multivariable Logistic Regression Analysis ◽  
Induced Aggregation

AbstractNearly 20% of patients will need non-cardiac surgery within 1 year of coronary stenting and their management is complicated by concomitant antiplatelet therapy. Platelet function testing may optimize the timing of surgery in these patients. In this prospective observational study, we explored the association between platelet reactivity and bleeding in patients undergoing non-cardiac surgery treated with clopidogrel with or without aspirin within 7 days before surgery. The timing of surgery was at the surgeon's discretion. Blood was drawn at induction of anaesthesia and platelet reactivity assessed by light transmittance aggregometry (LTA), vasodilator stimulated phosphoprotein (VASP) assay, Multiplate Analyzer and Innovance PFA-200. The primary endpoint was surgery-related thrombolysis in myocardial infarction (TIMI) bleeding. Among 197 patients enrolled, 72 and 12% underwent surgery within 24 and 48 hours of the last dose of clopidogrel, respectively. The median (interquartile range [IQR]) for pre-operative maximal adenosine diphosphate (ADP)-induced aggregation was 33.0% (21.0–57.5%), for VASP-platelet reactivity index was 61.5% (40.1–75.4%), for Multiplate was 22.0 (14.5–36.0) U*min and for Innovance PFA-200 was 224 (101.0–300.0) seconds. TIMI bleeding, observed in 25% of patients, decreased with increasing tertiles of platelet reactivity to ADP assessed by LTA (p = 0.031). Additionally, in a multivariable logistic regression analysis, platelet reactivity to ADP assessed by LTA was significantly associated with TIMI bleeding, as were age and urgency of surgery. These results demonstrate that in clopidogrel-treated patients, pre-operative platelet reactivity to ADP is associated with surgical bleeding risk. An objective assessment of pre-operative platelet function may optimize the timing of non-cardiac surgery in these patients.

Abstract 5603: Oral Dosing of PRT060128, a Novel Direct-acting, Reversible P2Y 12 Antagonist Overcomes High Platelet Reactivity in Patients Non-responsive to Clopidogrel Therapy

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Paul A Gurbel ◽  
Pamela B Conley ◽  
Patrick Andre ◽  
Gillian Stephens ◽  
Daniel D Gretler ◽  
...  
Keyword(s):  
Oral Dose ◽  
Single Oral Dose ◽  
Platelet Function ◽  
Large Scale ◽  
Platelet Reactivity ◽  
Light Transmittance ◽  
High Platelet Reactivity ◽  
Clopidogrel Therapy ◽  
Direct Acting ◽  
Induced Aggregation

Introduction: The ADP receptor P2Y 12 plays a central role in platelet function. Clopidogrel therapy is associated with various limitations including irreversible inhibition, a delayed antiplatelet effect, wide response variability, and non-responsiveness that has been linked to adverse ischemic event occurrence. We report the first pharmacodynamic study of a single oral dose of PRT060128 (PRT128), a novel, direct-acting reversible P2Y 12 inhibitor in patients with high platelet reactivity while on maintenance dose clopidogrel therapy(75mg/d) and aspirin. Methods: Previously stented patients (n=27) on maintenance aspirin and clopidogrel therapy were screened for high platelet reactivity (HPR) defined as upper tertile 5μ M ADP-induced aggregation (>43%) based on prior studies conducted at our Center; 7/27 had HPR and were treated with a single oral dose (60 mg) of PRT128. Platelet function was assessed at baseline, 4 hours, 6 hours, and 24 hours post-dosing by light transmittance aggregometry (LTA) stimulated by 5μ M, 20 μ M ADP, and 4μ g/ml collagen; Thrombelastography PlateletMapping (MA ADP ), Accumetrics P2Y12 assay (PRU), platelet reactivity ratio (%) by vasodilator stimulated phosphoprotein phosphorylation (VASP), and Perfusion Chamber Assay (PCA). Results: Results shown in the Table represent means ± standard deviation for the 7 patients at each time point. Conclusion: Based on results using multiple pharmacodynamic assays, PRT060128 is a potent rapid-acting inhibitor of P2Y 12 that overcomes high platelet reactivity in patients non-responsive to clopidogrel therapy. The pharmacodynamic properties of this novel P2Y 12 antagonist warrant future large scale investigations to determine clinical efficacy.

Impact of adjunctive cilostazol therapy on platelet function profiles in patients with and without diabetes mellitus on aspirin and clopidogrel therapy

2011 ◽  
Vol 106 (08) ◽  
pp. 253-262 ◽  
Author(s):  
Dominick J. Angiolillo ◽  
Piera Capranzano ◽  
Jose Luis Ferreiro ◽  
Masafumi Ueno ◽  
Davide Capodanno ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Platelet Function ◽  
Thrombin Generation ◽  
Platelet Reactivity ◽  
Flow Cytometric Analysis ◽  
Light Transmittance ◽  
Reactivity Index ◽  
Pharmacodynamic Effects ◽  
Increased Risk ◽  
Clopidogrel Therapy

SummaryCilostazol is a platelet inhibitor which when added to aspirin and clopidogrel has shown to reduce the risk of recurrent ischaemic events without an increase in bleeding. These clinical benefits have shown to be more pronounced in patients with diabetes mellitus (DM). However, it remains unknown whether cilostazol exerts different pharmacodynamic effects in patients with and without DM. This was a randomised, double-blind, placebo-controlled, cross-over pharmacodynamic study comparing platelet function in patients with and without DM on aspirin and clopidogrel therapy. Patients (n=111) were randomly assigned to either cilostazol 100 mg or placebo twice daily for 14 days and afterwards crossed-over treatment for another 14 days. Platelet function was performed at baseline, 14 days post-randomisation, and 14 days post-cross-over. Functional testing to assess P2Y12 signalling included flow cytometric analysis of phosphorylation status of vasodilatorstimulated phosphoprotein measured by P2Y12 reactivity index (PRI), light transmittance aggregometry and VerifyNow. Thrombin generation processes were also studied using thrombelastography. Significantly lower PRI values were observed following treatment with cilostazol compared with placebo both in DM and non-DM groups (p < 0.0001). The absolute between-treatment differences of PRI between groups was a 35.1% lower in patients with DM (p=0.039). Similar results were obtained using all other functional measures assessing P2Y12 signalling. Thrombin generation was not affected by cilostazol. Cilostazol reduces platelet reactivity both in patients with and without DM, although these pharmacodynamic effects are enhanced in patients with DM. Despite the marked platelet inhibition, cilostazol does not alter thrombin-mediated haemostatic processes, which may explain its ischaemic benefit without the increased risk of bleeding.

Platelet function profiles in the elderly: Results of a pharmacodynamic study in patients on clopidogrel therapy and effects of switching to prasugrel 5 mg in patients with high platelet reactivity

2011 ◽  
Vol 106 (12) ◽  
pp. 1149-1157 ◽  
Author(s):  
Claudia Tamburino ◽  
Davide Capodanno ◽  
Eligio Miccichè ◽  
Lucia D’Urso ◽  
Valeria Calvi ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Platelet Function ◽  
Platelet Reactivity ◽  
The Elderly ◽  
Platelet Inhibition ◽  
Light Transmittance ◽  
Considerable Proportion ◽  
Old Patients ◽  
High Platelet Reactivity ◽  
Clopidogrel Therapy

SummaryStudies specifically designed to assess clopidogrel response in the elderly as well as treatment alternatives to improve platelet inhibition in this highrisk population are lacking. This study aimed to define phar-macodynamic (PD) profiles, including high platelet reactivity (HPR) rates, among elderly patients on maintenance clopidogrel therapy and to assess the PD effects of prasugrel 5 mg/day in elderly with HPR. This was a prospective observational PD study enrolling consecutive ≥75-year-old patients on maintenance clopidogrel therapy (75 mg/day) who were tested for clopidogrel response by the VerifyNow P2Y12 assay and light transmittance aggregometry (LTA). HPR rates were estimated using multiple definitions. HPR patients identified by the VerifyNow P2Y12 assay [P2Y12 reaction unit (PRU) ≥230] were switched to prasugrel 5 mg/day, and platelet function testing was performed after 15 days of treatment. PD testing was completed in 100 patients. The HPR prevalence varied between 25% and 32%, depending on the definition used. A PRU ≥230 was observed in 25 patients; of these, 20 switched to prasugrel 5 mg/day. This resulted in significant reduction in PRU mean values (279.8 ± 45.1 vs. 171.7 ± 65.2, p=0.0002) with an absolute between-treatment difference of 108.1 (95% confidence intervals 75.2–140.9). Accordingly, switching to prasugrel 5 mg/day overcame HPR in most (80%) patients. Consistently, all LTA measures were significantly lower after prasugrel compared with clopidogrel. In conclusion, a considerable proportion of elderly patients exhibit HPR while on standard clopidogrel therapy. Switching to 5 mg/day prasugrel in elderly patients with HPR is associated with enhanced platelet inhibition and overcomes HPR in the majority of these patients.

scholarly journals Biomarkers-based personalized follow-up in chronic heart failure improves patient’s outcomes and reduces care associate cost

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Antonio Leon-Justel ◽  
Jose I. Morgado Garcia-Polavieja ◽  
Ana Isabel Alvarez-Rios ◽  
Francisco Jose Caro Fernandez ◽  
Pedro Agustin Pajaro Merino ◽  
...  
Keyword(s):  
Heart Failure ◽  
Hospital Admissions ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Secondary Outcome ◽  
Ventricular Ejection Fraction ◽  
Number Of Patients ◽  
Ed Visits ◽  
The Impact

Abstract Background Heart failure (HF) is a major and growing medical and economic problem, with high prevalence and incidence rates worldwide. Cardiac Biomarker is emerging as a novel tool for improving management of patients with HF with a reduced left ventricular ejection fraction (HFrEF). Methods This is a before and after interventional study, that assesses the impact of a personalized follow-up procedure for HF on patient’s outcomes and care associated cost, based on a clinical model of risk stratification and personalized management according to that risk. A total of 192 patients were enrolled and studied before the intervention and again after the intervention. The primary objective was the rate of readmissions, due to a HF. Secondary outcome compared the rate of ED visits and quality of life improvement assessed by the number of patients who had reduced NYHA score. A cost-analysis was also performed on these data. Results Admission rates significantly decreased by 19.8% after the intervention (from 30.2 to 10.4), the total hospital admissions were reduced by 32 (from 78 to 46) and the total length of stay was reduced by 7 days (from 15 to 9 days). The rate of ED visits was reduced by 44% (from 64 to 20). Thirty-one percent of patients had an improved functional class score after the intervention, whereas only 7.8% got worse. The overall cost saving associated with the intervention was € 72,769 per patient (from € 201,189 to € 128,420) and €139,717.65 for the whole group over 1 year. Conclusions A personalized follow-up of HF patients led to important outcome benefits and resulted in cost savings, mainly due to the reduction of patient hospitalization readmissions and a significant reduction of care-associated costs, suggesting that greater attention should be given to this high-risk cohort to minimize the risk of hospitalization readmissions.

scholarly journals 288. Follow-Up Blood Cultures in Gram-Negative Bacteremia: How Do They Impact Outcomes

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S144-S144
Author(s):  
Azza Elamin ◽  
Faisal Khan ◽  
Ali Abunayla ◽  
Rajasekhar Jagarlamudi ◽  
aditee Dash
Keyword(s):  
Clinical Outcomes ◽  
Antibiotic Treatment ◽  
Readmission Rate ◽  
Blood Cultures ◽  
Categorical Variables ◽  
Gram Negative ◽  
Number Of Patients ◽  
Significant Difference ◽  
The Impact

Abstract Background As opposed to Staphylococcus. aureus bacteremia, there are no guidelines to recommend repeating blood cultures in Gram-negative bacilli bacteremia (GNB). Several studies have questioned the utility of follow-up blood cultures (FUBCs) in GNB, but the impact of this practice on clinical outcomes is not fully understood. Our aim was to study the practice of obtaining FUBCs in GNB at our institution and to assess it’s impact on clinical outcomes. Methods We conducted a retrospective, single-center study of adult patients, ≥ 18 years of age admitted with GNB between January 2017 and December 2018. We aimed to compare clinical outcomes in those with and without FUBCs. Data collected included demographics, comorbidities, presumed source of bacteremia and need for intensive care unit (ICU) admission. Presence of fever, hypotension /shock and white blood cell (WBC) count on the day of FUBC was recorded. The primary objective was to compare 30-day mortality between the two groups. Secondary objectives were to compare differences in 30-day readmission rate, hospital length of stay (LOS) and duration of antibiotic treatment. Mean and standard deviation were used for continuous variables, frequency and proportion were used for categorical variables. P-value &lt; 0.05 was defined as statistically significant. Results 482 patients were included, and of these, 321 (67%) had FUBCs. 96% of FUBCs were negative and 2.8% had persistent bacteremia. There was no significant difference in 30-day mortality between those with and without FUBCs (2.9% and 2.7% respectively), or in 30-day readmission rate (21.4% and 23.4% respectively). In patients with FUBCs compared to those without FUBCs, hospital LOS was longer (7 days vs 5 days, P &lt; 0.001), and mean duration of antibiotic treatment was longer (14 days vs 11 days, P &lt; 0.001). A higher number of patients with FUBCs needed ICU care compared to those without FUBCs (41.4% and 25.5% respectively, P &lt; 0.001) Microbiology of index blood culture in those with and without FUBCs Outcomes in those with and without FUBCs FUBCs characteristics Conclusion Obtaining FUBCs in GNB had no impact on 30-day mortality or 30-day readmission rate. It was associated with longer LOS and antibiotic duration. Our findings suggest that FUBCs in GNB are low yield and may not be recommended in all patients. Prospective studies are needed to further examine the utility of this practice in GNB. Disclosures All Authors: No reported disclosures

scholarly journals SP9.1.1 The Impact of Anaesthetic Use on Healing in Sub-cutaneous Abscess Management: A Retrospective Before and After Cohort Study

2021 ◽  
Vol 108 (Supplement_7) ◽  
Author(s):  
Hannah Elkadi ◽  
Eleanor Dodd ◽  
Theodore Poulton ◽  
William Bolton ◽  
Joshua Burke ◽  
...  
Keyword(s):  
Wound Healing ◽  
Local Anaesthetic ◽  
Surrogate Endpoints ◽  
Incision And Drainage ◽  
Number Of Patients ◽  
Significant Difference ◽  
Patient Reported ◽  
Before And After ◽  
The Impact

Abstract Aims Despite being the most common surgical procedure, there is wide variation that exists in the management of simple subcutaneous abscesses with no national guideline describing best practice. During the COVID-19 Pandemic national guidelines promoted the use of regional or local anaesthetic (LA) instead of general anaesthesia (GA) to avoid aerosol generating intubation associated with GA. This study aimed to assess the impact of anaesthetic choice in outcomes following incision and drainage of subcutaneous abscesses. Methods Two cohorts of patients undergoing abscess incision and drainage at St. James’ University Hospital Leeds were retrospectively identified over a 14-week period before and after the introduction of the new COVID-19 anaesthetic guidelines. Wound healing surrogate endpoints were used: i) total number of follow up appointments and ii) attendance to healthcare services after 30 days from I&D. Result 133 patients were included. Significantly more procedures were performed under LA after the intervention (84.1% vs 5.7%; p &lt; 0.0001) with a significant reduction in wound packing (68.3% vs 87.1%. p=0.00473). Follow up data found no significant difference in the average number of follow-up appointments (7.46 vs 5.11; p = 0.0731) and the number of patients who required ongoing treatment after 30 days (n = 14 vs n = 14, p = 0.921). Conclusion Drainage of simple subcutaneous abscess under 5 cm is safe under local anaesthetic with no significant difference in surrogate endpoints of wound healing observed in this patient cohort. Recurrent packing may not be required. Future work should explore patient reported measures such as pain management and the health economics of this intervention.

scholarly journals Impact of Vein of Marshall Ethanol Infusion on Mitral Isthmus Block

2020 ◽  
Vol 13 (12) ◽  
Author(s):  
Takashi Nakashima ◽  
Thomas Pambrun ◽  
Konstantinos Vlachos ◽  
Cyril Goujeau ◽  
Clémentine André ◽  
...  
Keyword(s):  
Index Procedure ◽  
Ethanol Infusion ◽  
Number Of Patients ◽  
Mitral Isthmus ◽  
Acute Mi ◽  
Isthmus Block ◽  
The Impact ◽  
Repeat Procedures

Background: Achieving bidirectional mitral isthmus (MI) block using radiofrequency catheter ablation (RFCA) alone is challenging, and MI reconnection is common. Adjunctive vein of Marshall (VOM) ethanol infusion (VOM-Et) can facilitate acute MI block. However, little is known about its long-term success. This study sought to evaluate the impact of adjunctive VOM-Et on MI block achievement and durability compared with RFCA alone. Methods: Patients undergoing the first attempt of posterior MI ablation were grouped according to their MI block index strategy: adjunctive VOM-Et and RFCA alone. Rates of acute MI block and MI reconnection observed during repeat procedures were compared between the 2 groups. Results: The VOM-Et group consisted of 152 patients (63.8±9.4 years) undergoing adjunctive VOM-Et for MI block. The RFCA group consisted of 110 patients (60.9±9.2 years) undergoing MI ablation using RFCA alone. Acute MI block was more frequently achieved in the VOM-Et group (98.7% [150/152] versus 63.6% [70/110]; P <0.001) with shorter RFCA duration (5.00 [3.00–7.00] versus 19.0 [13.6–22.0] minutes; P <0.001). Of the 220 patients with MI block achieved during the index procedure, 81 underwent a repeat procedure during follow-up (VOM-Et group: 23.3% [35/150] versus RFCA group: 65.7% [46/70], respectively; P <0.001). A significantly greater number of patients exhibited durable MI block in the VOM-Et group (62.9% [22/35] versus 32.6% [15/46], respectively; P =0.008). Conclusions: Beyond facilitating acute MI block, VOM-Et is associated with greater lesion durability as evidenced by higher rates of MI block during repeat procedures.

Impact Of Age On Toxicity Associated With Chemotherapy For Acute Lymphoblastic Leukaemia (ALL): Results From The UK Prospective Study UKALL2003

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 840-840
Author(s):  
Rachael E. Hough ◽  
Clare Rowntree ◽  
Rachel Wade ◽  
Nicholas Goulden ◽  
Chris Mitchell ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Residual Disease ◽  
Age Groups ◽  
Serious Adverse Events ◽  
Number Of Patients ◽  
Teenagers And Young Adults ◽  
The Uk ◽  
Cure Rates ◽  
The Impact

Abstract Despite the substantial improvements made in the outcomes of paediatric ALL, with ‘cure' rates now in excess of 90%, survival in teenage and young adult (TYA) patients has remained inferior. The reasons for this are likely multifactorial, including tumour biology, toxicity, compliance, access to clinical trials and protocol (adult or paediatric) used. We report the toxicity profiles observed in children, teenagers and young adults treated on the UK intensive, minimal residual disease (MRD) directed ALL protocol, UKALL2003. Of a total of 3126 patients treated, 1520 patients were under 5 years old, 767 were aged 5-9 years, 610 aged 10-15 years and 229 aged 16-24 years, with a median overall follow-up of 4 year and 10 months. The risk of serious adverse events (SAEs) was higher in patients older than 10 years (56% in 10-15 year olds, 53% in 16-24 year olds) compared to those aged 9 or younger (30% in under 5 years and 31% in 5-9 years)(p<0.0001), with no difference in the those aged 16-24 compared to younger teenagers (p=0.5). The incidence (per number of patients in each group) and distribution of toxicities according to age group is summarised in the table.Table 1Age in years<55-910-1516-24AllTotal number of patients1520767610229 NB: 56 pts≥20 years3126Infection n (%)328 (21.6%)130 (17.0%)145 (23.8%)72 (31.4%)675 (21.6%)Asaparaginase n (%)57 (3.8%)57 (7.4%)64 (10.5%)31 (13.5%)209 (6.7%)Methotrexate n (%)100 (6.6%)74 (9.6%)123 (20.2%)33 (14.4%)330 (10.6%)Steroid n (%)54 (3.6%)37 (4.8%)141 (23.1%)52 (22.7%)284 (9.0%)Vincristine n (%)34 (2.2%)11 (1.4%)22 (3.6%)7 (3.0%)74 (2.4%)Other SAEs94 (6.2%)42 (5.5%)90 (14.8%)25 (10.9%)251 (8.0%) The incidence of certain toxicities including viral infection (5.3%), asparaginase hypersensitivity (1.9%) and vincristine neurotoxicity (2.1%) appeared equivalent across all age groups. Avacular necrosis was seen predominantly in adolescents (83% of 147 events in 10-19 year olds) and was rare in those younger than 10 years (n=18) or older than 20 years (n=7). Asparaginase thrombotic events increased in frequency with increasing age (1.5% in under 5 years, 3.3% in 5-9 years, 4.4% in 10-15 years and 8.3% in 16-24 year olds)(p<0.0001). All other toxicities were more frequently observed in over 10 year olds compared to patients aged 9 or younger, with no difference between 16-24 year olds and 10-15 year olds. The impact of age on SAEs associated with intensive ALL chemotherapy varies according to specific toxicities. In general, toxicity is higher in those over 10 years compared to younger patients, with no excess toxicity in those aged 16-24 compared to 10-15 years. However, specific toxicities may increase with increasing age (thrombosis), be restricted to adolescence (AVN) or be unrelated to age (vincristine neurotoxicity, asparaginase hypersensitivity). Disclosures: No relevant conflicts of interest to declare.

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