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Background Hepatitis C virus and H.pylori are the world's leading etiologies of bacterial and viral human diseases. Egypt has the world's largest prevalence of HCV, which was estimated to be 14.7 percent nationally. Objective To detect the effect of H. pylori eradication on the platelet counts in hepatitis C virus (HCV)-related CLD patients. Patients and Methods This prospective study was conducted at the Gastroenterology clinic, Internal Medicine department at Ain shams university and El-menofya hospital during the period of September 2017 to June 2018. 30 subjects were included in the study. All of them were chronic HCV infected patients (confirmed by HCV Ab and PCR for HCV) associated with thrombocytopenia (less than 100,000/μ) and were found to be H. pylori-positive (Confirmed active H.pylori infection by positive stool antigen test). Results Our results showed that there was highly statistically significant difference in platelets count with a pre-treatment range of 48-98 with mean±SD 82.40±14.16 and a post-treatment range of 50-123 with mean±SD 96.17±19.27 (10^3/cmm) Conclusion Eradication of Helicobacter Pylori leads to significant improvement of platelet counts in hepatitis C infected patients with thrombocytopenia.

Background Thrombocytopenia is defined as a platelet count below 150,000/μL.It is the most common hematological complication in patients with chronic liver disease (CLD).The prevalence of thrombocytopenia in chronic liver diseases ranges from 6 % among non-cirrhotic patients with chronic liver disease to 70 % among patients with liver cirrhosis. Objective To investigate the association between thrombocytopenia and the risk of higher mortality incidence in hepatic patients in intensive care unit. Patients and Methods The present prospective cohort study was conducted at Ain Shams University hospitals Intensive care units, from October 2019 to August 2020. After obtaining approval of the study protocol from the local ethical committee, as well as fully informed consents signed by the patient closet relative, 130 hepatic patients admitted at ICU with hepatic coma and patients classified according to platelet count on admission into two equal groups. Group A: included 65 Patients with thrombocytopenia on admission ( Results Our study revealed that patients with lower platelet counts had significantly higher risk of death and ICU stay. In our study we showed that there are two independent risk factors affecting the outcome of hepatic patients in the ICU they were thrombocytopenia and high APACHE score. These observations highlight the potential importance of low platelets count in identifying a group of hepatic patients who are at risk for poorer prognosis. Conclusion Thrombocytopenia is a frequent laboratory finding among hepatic patients, which is generally correlated to the severity of illness. Thrombocytopenia is generally associated with higher APACHE II score when compared to normal platelet count indicating that it is associated with higher degree of morbidity and expected higher mortality rate.

This cohort study evaluates bleeding complications in pediatric patients with cancer who have a platelet count of 50 ×10(3)/μL or above vs below 50 ×10(3)/μL during central venous catheter (CVC) placement.

Background and Aims Atypical haemolytic uremic syndrome (aHUS) is a clinical entity characterized by acute kidney injury, thrombocytopenia and microangiopathic hemolytic anemia. There are several cases of AHUS in non-renal solid organ transplants described in the literature, included lung transplant. Kidney and patient survival are compromised by this complication because of the lack of an effective treatment. Eculizumab is C5 complement factor specific blocker already administered in another kind of secondary aHUS with encouraging results Method We analys six lung transplants in a retrospective single-center study between 2018-2020 who developed an aHUS and were treated with eculizumab. Clinical and analytical data were collected along the follow-up. Principal outcome was to explore haematologycal and renal response after treatment with eculizumab. Results We included a total of six patients (83% were female) with a median age of 57 years at the time of transplantation. Aetiologies of lung transplantation were chronic obstructive pulmonary disease in 2 patients, interstitial lung disease in another 2, and cystic fibrosis in the remaining two. Induction and maintenance immunosuppressive therapy were based on tacrolimus, mycophenolate and prednisone in all cases. Baseline serum creatinine after lung transplantation was 1.1 mg/dl (0.9-2.4). Two patients developed an aHUS in the immediate post-transplant, one of them died because of surgical complications. Another four patients developed an aHUS 59 months (33-95) after transplantation. Previously of thrombotic microangiopathy, three patients were on treatment with everolimus instead of mycophenolate and two lung transplants have cytomegalovirus reactivation. At the aHUS onset, median serum creatinine was 4mg/dl (2.4-5-7) and acute dialysis was performed in 50% of patients. Median hemoglobin was 7.2g/dl (6.9-7.7), platelet count was 32x1000/µL (17-58), and DHL was 1343 U/L (581-1597) at the start of eculizumab despite having treated the trigger. After a median of 6 doses of eculizumab, the five surviving patients had haematologycal and renal response. No patients underwent chronic dialysis. Serum creatinine was 2.2 mg/dl (1.7-2.3), hemoglobin 9.8 g/dl and platelet count 159x1000/µL at the end of follow-up. Conclusion AHUS is a critical complication in lung transplantation, shortly related with immunosuppressive therapy. Patients are at risk of end stage renal disease. Eculizumab treatment appears promising.

Background and Aims Both human and animal studies suggest that the gut microbe-derived metabolite Trimethylamine N-oxide (TMAO) is strongly associated with several autoimmune disease including Rheumatoid arthritis and psoriatic arthropathy. TMAO has been previously studied as a discriminator between SLE patients and healthy volunteers with higher reported TMAO levels in the SLE group; this suggests that gut microbiota may enhance TMAO generation in response to disease severity. The aim of this study was to investigate the diagnostic and prognostic validity of TMAO as a potential biomarker in lupus nephritis patients. To the best of our knowledge this is the first study to investigate the gut microbe-derived metabolite Trimethylamine N-oxide (TMAO) in patients with lupus nephritis correlating to the criteria of disease severity. Method A total of 90 subjects were included in this cross-sectional study and divided into 3 equivalent groups; group I (lupus nephritis patients (LN)), group II (SLE patients without nephritis (NN)), and group III (healthy controls). Serum Trimethylamine Levels were assessed, compared between the study groups and correlated to the clinical, laboratory and Histo-pathological criteria obtained from kidney biopsies of the included patients. Results Unpredictably, TMAO levels were found to be significantly higher in healthy controls compared to the total SLE population (p=0.003), and to LN, and NN groups individually (p=0.01). There was no significant statistical difference of TMAO levels between (NN) and (LN) patients (p=0.62). TMAO levels correlated to Anti-dsDNA titres (p=0.02) and Red Blood Cells count (p=0.02) among LN patients while they haven’t shown any correlations to the other studied clinical-laboratory and histopathological factors. Conclusion Contrary to the results of the previous studies, TMAO levels were found to be higher in healthy controls rather than SLE patients and did not discriminate between LN and NN patients as well as did not show significant correlation to most studied criteria of disease severity. The possible confounding effect of the dietary pattern and ingested drugs on the gut microbiome underestimate the diagnostic and prognostic utility of TMAO as a potential marker in different diseases. Further studies considering the dietary pattern of the included patients are still warranted.

Funding Acknowledgements Type of funding sources: None. Purpose Intracranial hemorrhage (ICH) is one of the most serious complications of adult patients treated with venoarterial extracorporeal membrane oxygenation (VA-ECMO) and is associated with increased morbidity and mortality. However, the prevalence and risk factors of ICH in this cohort are still insufficiently understood. Therefore, the purpose of this study was to further investigate prevalence, associated mortality and predictors of ICH in VAECMO patients. Methods We conducted a retrospective multicenter study including adult patients (≥18 years) treated with VA-ECMO in cardiac intensive care units (ICUs) at five clinical sites between January 2016 and March 2020, excluding patients with ICH upon admission. Differences in baseline characteristics and clinical outcome between VA-ECMO patients with and without ICH were analysed. Predictors of ICH were identified by uni- and multivariable regression models. Results Among 598 patients included, 70 (12%) developed ICH during VA-ECMO treatment with mean duration of 82 ± 84h between ECMO initiation and ICH diagnosis. Out of these ICH, 23% were intraparenchymal, 20% subarachnoid, 10% subdural, 3% intraventricular and 44% combined hemorrhage. In-hospital mortality in the ICH cohort was 81% and 1-month mortality 86%, compared to 63% (p = 0.002) and 64% (p Conclusion ICH occurred frequently in VA-ECMO patients and was associated with a significantly higher mortality rate. Diabetes mellitus, low platelet count and low fibrinogen level are independent predictors of ICH. These findings may help to develop effective strategies to prevent and treat ICH and build the basis for further investigations to optimize clinical outcome in patients on VA-ECMO.

Funding Acknowledgements Type of funding sources: None. Background Anorexia nervosa (AN) is one of the most common form of eating disorders and it is a severe and potentially fatal disease with high rates of morbidity and mortality especially in the population aged 15-25 years. Cardiac involvement occurs in approximately 80% of patients with AN. Cardiovascular complications include changes in the autonomic regulation (increased vagal tone, bradycardia, orthostatic hypotension, syncope), arrhythmias, congestive heart failure and sudden death. Few reports have described, in small series, a variety of echocardiographic abnormalities including decreased cardiac mass, mitral valve prolapse, pericardial effusion and reduced left ventricular (LV) dimensions. No previous studies, however, examined if there is a change in these abnormalities with weight fluctuations. Purpose To describe echocardiographic findings among male and female patients with AN and to examine the effect of weight gain on clinical and echocardiographic parameters. Methods We performed a single center, retrospective, study of patients diagnosed with AN using the diagnostic and statistical manual of mental disorders, fifth edition (DSM-5). Clinical, laboratory and ECG-graphic data were obtained by reviewing each patient’s medical records. Echocardiographic parameters were measured off-line. Results The study population consisted of 81 patients, mean age 24.5 ± 11.6 years, 92.6% females. 75% showed an extreme AN degree. Mean body mass index (BMI) was 15.2 ± 2.1 kg/m2. Mean heart rate was 57.2 ± 12.7 beats per minute. Some patients showed right bundle branch block (7.4%) or prolonged QT interval (14.8%). Patients with BMI below the mean value had more often pericardial effusion, smaller LV mass and LV end-diastolic volume and thinner interventricular septum (all p Conclusions Our study showed that patients with AN have a specific echocardiographic pattern which seems to be proportional to the body size, suggesting a pathophysiological adaptation to the lack of substrates, hypothesis confirmed by the regression with weight gain. It is possible that pericardic effusion fills the gap left by mass loss.

Background and Aims Preeclampsia is potentially serious complication of pregnacy and frequently requires admission in ICU. Management of this condition involves treatment with magnesium sulfate to prevent progression to eclampsia or even more adverse outcomes such as maternal or fetal death. However the exact dose of magnesium needed is still to be determined and few studies have analyzed the impact of this therapheutic intervention in women admitted in intensive care units, in terms of outcomes and adverse effects. Herein, we present a series of patients diagnosed with preeclampsia, including its most severe presentations with eclampsia or HELLP syndrome, admitted in an intensive care unit. Method Demographic, clinical and laboratorial data of women admitted between January-2016 and December-2018 to the Polyvalent Intensive Care Unit (ICU) of Hospital Fernando Fonseca, a tertiary Hospital in Portugal, with the diagnosis of preeclampsia, were retrospectively collected. Diagnosis of preeclampsia, HELLP syndrome and eclampsia were performed according to the ISSHP criteria (2004). Acute Kidney Injury (AKI) was defined according to the KDIGO criteria. The study was approved by the Ethical Committee of the institution. Results 42 patients were included, 52.3% (n=22) diagnosed as non-severe preeclampsia; 31% (n=13) as HELLP syndrome and 16.7% (n=7) as eclampsia. Mean age at presentation was 29.6±6.6 years old, with 52,4% (n=22) caucasian and 47.6% (n=20) black. Most patients were admitted in ICU in post-partum period, after cesarian delivery in 95.2% (n=40). Seven patients (16.7%) had a previous diagnosis of hypertension; 11.9% (n=5) were obese; none has previous chronic kidney disease. At presentation, most patients diagnosed with preeclampsia had three diagnostic criteria (28.6%, n=12), including hypertension. Renal dysfunction was found in 80.9% (n=34) of patients, with proteinuria >200mg/dL in 69% (n=29) and AKI in 19% (n=8). Mean Hb of 11.1±2.1g/dL, with median platelet count of 126000/uL (IQR 72000-201500) and median LDH of 388mg/dL (IQR 240-773). Pre-partum magnesium sulfate treatment was initiated in 78.6% (n=33) of patients, but only 2.4% (n=1) had previous magnesemia levels determination. During the stay in ICU, daily levels of seric magnesium levels were obtained, with the highest median values found at day one after admission. Adverse events related to hypermagnesemia (bradipnea) occurred in 50% (n=21) of patients. In six patients (14.3%), treatment was stopped because of high levels of magnesemia or adverse events. 14.3% (n=6) progressed to eclampsia and fetal death occured also in 14.3% (n=6). Maternal deaths did not occur. By logistic binary regression we found out that weight was an independent risk factor for the development of the composite outcome of eclampsia or fetal death, when adjusted to age, race, AKI, hemoglobin, platelet count, ALT, LDH, serum albumin and proteinuria. (p=0.04). However, when Magnesium was included in the analysis, all variables lost significance. An association between SOFA and SAPS scores and the occurrence of the composite outcome has been found (p= 0.03 and p=0.019, respectively). Conclusion Most patients with preeclampsia received treatment with magnesium sulfate without previous measurement of serum levels. Bradipnea occurred in 50% of cases and treatment had to be stooped in almost 15%. Nevertheless, magnesium levels were not independently associated with the composite outcome of fetal death or eclampsia. Future studies should evaluate if a dose adjusted to a specific target of magnesium seric level could be associated with less adverse effects while still reducing the risk associated with preeclampsia.

Background and Aims Despite the introduction of several new phosphate binders over the last decades, adequate control of hyperphosphatemia in haemodialysis (HD) patients still remains a crucial challenge as more than half of the population still remains hyperphosphataemic in daily practice. A growing amount of clinical data suggests that nicotinamide (NA) represents a complementary and effective treatment option for hyperphosphataemia. Efficacy and safety of once daily intake of modified release (MR) NA were investigated for fixed doses between 250 and 1,000 mg in hyperphosphatemic HD patients. Additionally, the MR formulation was compared to trice daily intake of an immediate release (IR) formulation of NA. Method This multicenter, controlled trial included HD patients with serum phosphate concentrations between 4.7 and 7.5 mg/dL after initial discontinuation of phosphate binder treatment. Patients were randomized to either once daily intake of 250 mg (N=48), 500 mg (N=50), 750 mg (N=50) or 1,000 mg of MR NA (N=53) in a double-blind setting, or intake of 1,000 mg of IR NA (N=51), divided over three daily doses in an open-label setting over a treatment period of 8 weeks. Results Based on the ITT population the study revealed a highly significant (p The most frequently reported adverse events were gastrointestinal symptoms in 31.4% of patients and skin reactions in 19.8% of patients. The study also revealed a nonsignificant decrease in mean platelet count. Overall, the number of adverse events increased in the 750 and both 1,000 mg dosage groups. For individual adverse events, dose dependency was observed for diarrhea, headache, vomiting and nausea. NA treatment resulted in a dose dependent increase of plasma concentrations of NA and its terminal metabolites (N-methyl-2-pyridone-5-carboxamide, N-methyl-4-pyridone-5-carboxamide, Nicotinamide-N-oxide). The tolerability profile as well as the plasma concentrations of NA metabolites were similar for both formulations although the proportion of patients that terminated treatment due to adverse events was higher in the IR arm compared to the MR formulation (33.5% versus 26.4% of patients). However, this study was not powered to reliably assess clinical superiority with regard to AE. Conclusion Our study characterised the NA modified release preparation NoPhos as an effective novel therapeutic option for the treatment of hyperphosphatemia in HD patients. In the monotherapy setting a clear dose-response relationship was revealed for daily doses between 250 and 1,000 mg, while best tolerability was observed at a dose of 500 mg/d.

This cohort study analyzes the association of closure time in response to adenosine diphosphate (CT-ADP) with bleeding score and the associations of platelet transfusions with change in platelet count, CT-ADP, and bleeding scores in preterm neonates with thrombocytopenia.

Background Thalassemias are monogenetic hematologic disorders which are caused by faulty synthesis of one or more of the Hb chains which leads to imbalance in globin chains resulting in hemolysis and impaired erythropoiesis and chronic inflammatory condition. Visfatin is a pro-inflammatory adipocytokine which is mostly expressed in visceral adipose tissue and its testing may help in assessment of severity of the disease. Aim of the work This study aims at measuring serum visfatin level in Beta thalassemia patients and its possible correlation to disease severity (major andintermedia). Patients and methods Forty-one patients diagnosed as β-thalassemia (major, intermedia) and twenty age and sex-matched healthy individuals as the control group were tested for serum visfatin levels by enzyme-linked immunosorbent assay. Results Serum visfatin was higher in theß-thalassemia major(ß-TM) group than in the control group (P Conclusion There is an association between serum visfatin and the degree of severity of β thalassemia disease. Recommendations Testing of the relationship between serum visfatin level and other vascular inflammatory markers in β-thalassemia disease (asadiponectin, resistin, intracellular adhesion molecule (ICAM)) to clarify the exact mechanism of the inflammatory process in the disease and its complications to alter the course of the disease.Also to study serum visfatin in complicated β-thalassemia patients to establish its possible role in cardiac, vascular, endocrine or any other complications and comparing it with non-complicated patients.

Background We sought to evaluate baseline platelet count as a prognostic indicator in patients with acute myocardial infarction (AMI). Methods Data of 13,085 patients with AMI were retrieved from a prospective nationwide AMI registry from November 2011 to December 2015. Using Cox hazards models, cumulative risks for adverse outcomes were compared among patients with baseline platelet count of less than 150 K/µL (lowest quartile), 150 to 249 K/µL, 250 to 349 K/µL (reference) and equal to or greater than 350 K/µL (higher quartile). The primary outcome of interest was all-cause mortality. Secondary outcomes included myocardial infarction, re-hospitalisation for heart failure, and stroke. Results During a median follow-up of 2.1 years, a steep U-shaped association was observed for the occurrence of all-cause mortality (p for non-linearity Conclusions In patients with AMI, baseline platelet count demonstrated a U-shaped association with an increased risk of all-cause mortality at two years. If validated, these findings suggest that baseline platelet count could serve as a preferred prognostic marker in AMI due to its low cost and universal availability.

Growing clinical demands for platelet transfusions combined with supply limitations have created shortages which are trending toward a global crisis. Major efforts have been taken to address key issues of platelet sources, storage, and utilization. Recent progress in ex vivo culture-based production of megakaryocytes (Mk) and platelets, "pharming," has highlighted the potential for novel, donor-independent sources amenable to antigenic editing and cryo-stockpiling. Such cultures can be easily initiated from umbilical cord blood (CB) progenitors, induced pluripotent stem cells (iPSC), or directly re-programmed somatic cells. The major roadblock associated with these Mk sources consists of their fetal ontogenic status, which is beneficial for expansion but severely limits platelet production. The ability to elicit in pre-expanded Mk an adult program of morphogenesis (polyploidization, enlargement, and proplatelet formation) would enable circumvention of this scalability barrier. A master regulator of adult Mk morphogenesis consists of the transcriptional coactivator MKL1 which undergoes nuclear translocation in response to RhoA-mediated actin polymerization, stimulated by thrombopoietin and environmental mechano-sensing. Nuclear MKL1 associates with the transcription factor SRF1 to upregulate cytoskeletal remodeling factors, including filamin A and Hic-5, that act as morphogenesis effectors. Our previous studies identified in infantile CB Mk a failure in MKL1 upregulation resulting from repression by the oncofetal RNA-binding factor IGF2BP3. Pharmacologic suppression of IGF2BP3 with BET inhibitors rescued MKL1 expression and improved platelet production but caused cycle arrest preventing polyploidization. As an alternative approach to abrogate the fetal blockade in Mk morphogenesis, we sought to promote MKL1 activity by targeting a kinase, Dyrk1a, which had been shown to restrain MKL1 from nuclear translocation. Treatment of infantile CB Mk with a variety of Dyrk1-selective inhibitors including harmine and EHT 1610 strongly enhanced polyploidization (p = 0.015 and 0.009 respectively), enlargement (p < 0.005) , and in vitro platelet release (2 fold each, p = 0.001 and 0.007 respectively), attaining levels seen with adult Mk. When xenotransplanted into NSG mice, harmine-treated CB Mk demonstrated enhanced capability for in vivo platelet release (about 5 fold, p = 0.016). CB stem cells expanded with the AHR antagonist SR1 and an iPSC-Mk cell line also responded to Dyrk1 inhibition with robustly increased morphogenesis. Several findings implicated MKL1 in this response: 1) induction of nuclear translocation by the inhibitors, 2) induction of target genes (filamin A and Hic-5) by the inhibitors, and 3) loss of response to inhibitors in Mkl1-ko murine progenitors. Supporting Dyrk1a as a relevant target, mice with Mk-specific loss of one Dyrk1a allele (Dyrk1aflox/wt;Pf4-Cre) displayed increases in platelet counts (p = 0.037) and marrow Mk polyploidization (p = 0.02). In addition, retroviral expression in human progenitors of a dominant negative Dyrk1a mutant K188R promoted Mk enlargement (p = 0.014). shRNA knockdowns could not be obtained due to toxicity of > ~60% loss of Dyrk1a. To determine mechanisms for Dyrk1a control of morphogenesis, we analyzed the actin cytoskeleton, a key regulator of MKL1. Dyrk1 inhibition in all types of Mk progenitors (adult, infantile, and iPSC) induced assembly of cortical filamentous actin (F-actin), as detected by Alexa594-phalloidin staining. Prior studies showed cytoskeletal binding by Dyrk1a and direct phosphorylation of F-actin regulators N-WASP and Ablim1. A survey of human marrow expression patterns for candidate Dyrk1a substrates (The Human Protein Atlas) identified Ablim2, as showing a Mk-specific, cortical staining pattern. Dyrk1 inhibition increased Ablim2 levels ~5-fold in CB Mk (p < 0.005), and immunofluorescence displayed a cortical distribution similar to F-actin. Lentiviral shRNA knockdown of Ablim2 abrogated all effects of Dyrk1 inhibition, blocking: F-actin formation, MKL1 nuclear translocation, activation of the MKL1 targets, and Mk morphogenesis. These findings thus delineate a novel Dyrk1a-Ablim2-MKL1 regulatory module in Mk morphogenesis that can be manipulated to address the problem of scaling ex vivo production and might also serve as a future in vivo therapeutic target for thrombocytopenia. Disclosures Eto: Megakaryon Co. Ltd.: Equity Ownership, Membership on an entity's Board of Directors or advisory committees.

BACKGROUND Tumor hypoxia decreases the response of glioblastoma multiforme (GBM) to radiotherapy (RT) and chemotherapy (temozolomide[TMZ]). The purpose of this study was to evaluate the safety and efficacy of a novel oxygen therapeutic, dodecafluoropentane emulsion (DDFPe), in chemoradiation treatment of GBM and stratify the results based on predicted TMZ response. METHODS With ethics approval and informed consent, 11 adult GBM patients were enrolled. Patients were administered DDFPe via IV infusion (2% w/vol at doses of 0.05, 0.1 or 0.17 mL/kg) within 5–30 minutes prior to each 2 Gy fraction of RT (30 fractions over 6-weeks) while breathing supplemental oxygen. Patients also received standard concurrent and adjuvant TMZ. To evaluate the reversal of tumor hypoxia, patients underwent oxygen-sensitive (TOLD) MRI before and after DDFPe administration. Patients were also studied with serial MRI scans per standard of care and followed for survival. RESULTS The non-serious adverse events considered by the investigator to be possibly, probably, or definitely related to DDFPe administration included fatigue (n=4), headache (n=2) and decrease in platelet count (n=2). Serious adverse events included two patients with symptomatic radiation necrosis: one patient at each of dose levels 0.1 and 0.17 mL/kg. Enrollment continued at the 0.1 mL/kg dose without additional significant DDFPe-related toxicity. Historically, the average overall survival for GBM patients is about 14.6 months. The median overall survival for the study was 591 days, or 19.4 months. According to independent review of the serial MR images, the median time to progression was 555 days, or 18 months, compared to a historical control of 6.9 months. TOLD MRI showed a trend in improved tumor oxygenation. CONCLUSION Although small, this trial shows that DDFPe used as a radiosensitizer appears to be safe and may provide some survival benefit. The FDA has allowed a Phase II clinical trial to assess its effectiveness.

PURPOSE Ommaya reservoirs are frequently inserted in patients requiring regular delivery of intrathecal medications. The incidence of intracranial hemorrhage following insertion ranges from 1–3% and is typically associated with thrombocytopenia. However, the exact platelet count at which it is considered safe to insert an Ommaya reservoir has not been previously reported. The purpose of this study is to investigate the nature of the relationship between thrombocytopenia and post-operative hemorrhage following insertion of Ommaya reservoirs for intrathecal chemotherapy. METHODS Consecutive patients requiring insertion of an Ommaya reservoir were enrolled in the study with no minimum platelet count as an exclusion criterion. Patients data were retrospectively reviewed with thrombocytopenia defined as platelet count < 100,000. All thrombocytopenic patients received at least one unit of intraoperative platelet transfusion. Post-operative incidence of hemorrhage, determined through CT scan, was compared between the thrombocytopenic group and normal platelet group. RESULTS 53 patients were enrolled within the study with 23 patients determined to be thrombocytopenic at the time of insertion. Thrombocytopenic patients were found to have 18.6 times the odds of post-operative bleeding when compared to patients with normal platelet counts (p< 0.001). However, no patient in the thrombocytopenic group had a clinically significant bleed, defined as being symptomatic or requiring intervention. CONCLUSIONS Although thrombocytopenia increases the risk of post-operative hemorrhage associated with Ommaya reservoir placement, there is no increase in clinically significant bleeding. With concurrent platelet transfusion and use of neuronavigation, Ommaya reservoir may be safely placed in thrombocytopenic patients.

Background Intra-abdominal abscess is an important clinical complication of Crohn’s disease (CD), which can be diagnosed using computed tomography (CT) or magnetic resonance imaging (MRI). However, a high index of clinical suspicion is needed to diagnose an abscess as abdominal imaging is not routinely used during hospital admission. This study aimed to identify clinical predictors of an intra-abdominal abscess among hospitalized patients with CD. Methods We created an electronic data repository of all patients with CD who visited the emergency department (ED) of our tertiary medical center between 2012 and 2018. Data included tabular demographic and clinical variables, as well as CT and MRI imaging outcomes. We searched the data repository for the presence of an abscess on abdominal imaging within seven days from the ED visit. Machine learning models were trained to predict the presence of an abscess. A logistic regression model was compared to a random forest model. The area under the receiver operator curve (AUC) was used as a metric. To establish statistical significance, bootstrapping of 100 experiments with random 80/20 training/testing splits was performed. We included only patients who were hospitalized due to complaints that can be attributed to CD exacerbation. Patients presenting within 30 days from an abdominal surgery were excluded. Results Overall, 1556 patients with CD visited the ED, of those 555 patients with a CD exacerbation. Of them, 339 patients were hospitalized and underwent abdominal imaging within 7 days from the ED visit. Forty-two patients (12.1%) were diagnosed with an abscess on abdominal imaging. The average length of the abscess was 32 mm (IQR 21.5, 43.5), mainly in the mesentery adjacent to the small bowel (38.1%). On multivariate analysis, high CRP values (64.97 mg/L, aOR 14.42 [95% CI 4.93–42.13]), high platelet count (322.5 K/microL, aOR 4.01 [95% CI 1.97–8.15]), leukocytosis (10.55 K/microL, aOR 3.83 [95% CI 1.71–8.56]) and higher heart rate (over 87.5 beats per minute, aOR 2.58 [95% CI 1.22–5.46]) were independently associated with an intra-abdominal abscess. Overall, random forest and logistic regression showed similar performance. The random forest model showed an AUC of 0.824±0.065 with eight features (CRP, Hemoglobin, WBC, age, current biologic medical treatment, BUN, current immunomodulatory medical treatment, gender). Conclusion In our large tertiary center cohort, the machine-learning model identified features associated with the presentation of an intra-abdominal abscess. Such a decision support tool may assist in triaging CD patients for imaging to exclude this potentially life-threatening complication.

Objective: We characterized acquired von Willebrand syndrome (AVWS) among essential thrombocythemia (ET) and polycythemia vera (PV) patients. Methods: A review of patients with ET or PV evaluated for AVWS. Results: Of 116 patients with ET, 64 (55%) developed AVWS; of 57 with PV, 28 (49%) developed AVWS. Median platelet counts of ET and PV patients who developed AVWS were 920 X 109/L and 679 X 109/L, respectively (P=0.01). Of patients who developed AVWS, 69.5% had platelet counts below 1000 X 109/L. Bleeding was more common in patients with AVWS, among both ET and PV patients (P Conclusion: Among ET and PV patients, AVWS was common and associated with higher bleeding rates and higher platelet count; nonetheless, most AVWS patients had platelet counts under 1000 X 109/L. Thus, AVWS screening should be included in routine assessment of ET and PV patients. Among ET patients, JAK2 V617F was a main driver for the development of AVWS. Disclosures No relevant conflicts of interest to declare.

Background Less than 50% of patients with Crohn’s disease (CD) starting infliximab (IFX) therapy achieve endoscopic remission (ER). Evidence for the benefits of pharmacokinetic (PK) and pharmacodynamic (PD) monitoring remains scarce. We aimed to develop a population (pop)PK/PD model to characterise the IFX dose-exposure-biomarker-response (faecal calprotectin [fCal] and ER) relationship in patients with CD. Methods Analyses were performed using data of a phase 4 dose-escalation study (TAILORIX). Patients started standard 5 mg/kg IFX induction therapy at weeks [w]0, 2 and 6. From w14 through w54, the IFX dose could be irreversibly doubled based on one of the three monitoring algorithms.1 Endoscopies were performed at w0, 12 and 54. Three sequential models were developed: A 2-compartment popPK model linking IFX dose to exposure, an indirect response popPK-PD model describing the inhibitory effect of IFX exposure on fCal, and a first-order Markov popPD model linking fCal to transitions between states of ER (CD endoscopic index of severity Results The study included 116/122 (95%) patients with CD enrolled in TAILORIX who had ≥1 detectable IFX serum concentration. In the developed models, it was shown that IFX clearance increased with increasing fCal, decreasing albumin, increasing CD activity index and presence of antibodies to IFX (transiently). Baseline fCal increased with increasing CRP and decreasing platelet count. Lower fCal increased probability of attaining ER and decreased probability of losing ER. Probability of dropping out given an earlier state of absence of ER increased with elapsing time. Simulations of 150 000 patients receiving 5, 7.5 or 10 mg/kg IFX (1:1:1) resulted in a flat dose–response curve due to large interindividual variability in PK and PD (Figure 2, top panels). The predicted fraction of patients achieving ER at w12 was 45.1% [30.3–60.5] (median [IQR]) when on 5 mg/kg IFX (~46.4% observed in data). However, simulations of 10 mg/kg IFX induction doses predicted only a slight increase in the fraction of patients achieving ER at w12 to 47.5% [32.0–62.6]. This minor benefit at the population level argues against systematic 10 mg/kg induction dosing in all patients. A similar observation was done during maintenance therapy, where 70.8% [62.6–75.5] of all simulated patients maintained ER at w54 (~72.2% observed in data) (Figure 2, right panels). Conclusion Model-informed infliximab dose optimisation towards a predefined fCal concentration—while accounting for PK and PD variability—may improve the effectiveness of infliximab therapy (eg. 64% chance of ER at w12 ~100 μg/g fCal at w6). Reference

This review will discuss how 2 common and morbid conditions, renal disease and liver disease, alter platelet number and function. It will review the impact of thrombocytopenia on bleeding complications in patients with these disorders and whether the low platelet count actually correlates with bleeding risk. Emerging data also suggest that platelets are much more than bystanders in both renal and liver disease, but instead play an active role in the pathobiology of these disorders. This review will briefly cover the emerging information on novel roles of platelets in the biology of renal and liver disease.

Background Studies evaluating the relationship between platelet indices and cardiovascular outcome yielded conflicting results. In particular, the evidence from large, population-based, prospective studies with extended follow-up duration is scarce. Purpose We investigated the incidence of major adverse events in relation to baseline values of platelet count, mean platelet volume (MPV) and platelet distribution width (PDW) in the prospective cohort of the Malmö Diet and Cancer Study. Methods A total of 30,314 middle-aged individuals (mean age 57±8 years; 40% men) were overall included and followed up for a median of 16 years (in total, 468,490 person-years). The following outcome measures were considered: all-cause death, myocardial infarction (MI) and ischemic stroke. Results There was no relationship between increase in MPV or PDW values and adverse events during follow-up. In particular, the incidence of all-cause death, MI and stroke in patients in the 4thquartile of MPV was 19.8% (vs. 20.7% in the 1stquartile; p=0.08), 8.5% (vs. 8.2%; p=0.78) and 7.9% (vs. 7.1%; p=0.09), respectively. The rates of all-cause death, MI and stroke in patients in the 4thquartile of PDW were 20.1% (vs. 20.7% in the 1stquartile; p=0.16), 8.7% (vs. 8.1%; p=0.30) and 8.1% (vs. 7.2%; p=0.09), respectively. There was a significant rise in mortality by platelet count increase (log-rank p264 x 109/L) showed a significantly higher incidence of all-cause death (HR 1.17, 95% CI 1.07–1.28; p=0.001), MI (HR 1.24, 95% CI 1.08–1.43; p=0.003) and stroke (HR 1.20, 95% CI 1.04–1.39; p=0.014) vs the 1stquartile. The higher mortality in the 4thquartile of platelet count was independent of the history of previous stroke, was significant in patients without prior MI (HR 1.18, 95% CI 1.08–1.29; p Conclusions In this population-based, prospective, cohort study there was no difference in the incidence of adverse events across various strata of baseline platelet morphology. However, patients with highest platelet count at baseline showed a significantly higher risk of all-cause death, MI and stroke. Whether or not these individuals should be targeted by more aggressive primary prophylactic measures including antiplatelet treatment, remains to be proven.

Background Thrombocytopenia is sometimes found in routine blood tests and is reported as a risk factor of major bleeding events and incidence of all-cause death after percutaneous coronary intervention. However, the influence of thrombocytopenia on clinical outcomes in patients with atrial fibrillation (AF) remains unknown. Purpose We aimed to investigate relationship between baseline platelet count and clinical outcomes such as all-cause death, hospitalization for heart failure, and the major bleeding event in AF patients. Methods The Fushimi AF Registry was designed to enroll all of the AF patients in Fushimi-ku, Kyoto. Fushimi-ku is densely populated with a total population of 283,000 and is assumed to represent a typical urban community in Japan. Follow-up data with baseline platelet counts were available in 4,179 patients from March 2011 to November 2018. We divided the entire cohort into 3 groups according to baseline platelet level: No thrombocytopenia (≥150,000/μL, n=3,323), Mild thrombocytopenia (100,000–149,999/μL, n=707), and Moderate/severe thrombocytopenia (≤99,999/μL, n=149). Results In the entire cohort, the mean age was 73 years, 40% were women, and the mean body weight and body mass index was 59 kg and 23.1 kg/m2, and the median platelet count were 192,000/μL (interquartile range 156,000 to 232,000/μL), respectively. Compared to No thrombocytopenia, patients with thrombocytopenia were older (No vs. Mild vs. Moderate/severe; 73.3 years vs. 76.5 years vs. 75.8 years, p On Kaplan-Meier analysis, the incidence of all-cause death was higher in Mild group (hazard ratio [HR] 1.51; 95% confidence interval [CI] 1.28–1.77) and Moderate/severe group (HR 2.97; 95% CI 2.28–3.80) than No group (Figure 1). The incidence of hospitalization for heart failure was higher in Mild group (HR 1.62; 95% CI 1.31–1.99) and Moderate/severe group (HR 2.64; 95% CI 1.76–3.81) than No group (Figure 2). The incidence of major bleeding event was higher in Mild group (HR 1.46; 95% CI 1.11–1.91) and Moderate/severe group (HR 2.45; 95% CI 1.41–3.91) than No group (Figure 3). Conclusion Thrombocytopenia in AF patients was associated with higher incidence of all-cause death, hospitalization for heart failure, and major bleeding event in the Fushimi AF Registry. Acknowledgement/Funding Pfizer, Bristol-Myers Squibb, Boehringer Ingelheim, Bayer Healthcare,and Daiichi-Sankyo

OBJECTIVES: We have previously demonstrated that serum lipids can predict clinical immune cell counts at the population level; however, it is unknown whether diet-induced changes in serum lipids correspond to similar shifts in clinical blood cell counts. We hypothesized that whole egg vs. egg white consumption, which is known to differentially affect lipoprotein profiles and inflammatory markers, would induce shifts in clinical immune cells counts that are associated with changes in serum lipids. METHODS: In this ongoing study, healthy men and women (18–35y, BMI

This cohort study examines the use of closure time following stimulation with collagen and adenosine diphosphate vs the platelet count as a marker of bleeding in premature neonates with thrombocytopenia.

Bleeding manifestations in patients with immune thrombocytopenia (ITP) range from mild skin bruises to life-threatening intracranial hemorrhage (ICH). Severe bleeding is distinctly uncommon when the platelet count is >30 × 109/L and usually only occurs when the platelet count falls

Introduction/Objective Thrombocytopenia is one of the major extra-hepatic manifestations of Hepatitis C virus (HCV) infection. There are numerous studies suggesting several pathophysiology mechanisms explaining the association of thrombocytopenia with HCV infection; however occasional presence of thrombocytopenia with normal liver function, or presence of significance hepatic damage with normal platelet count has not been well explained. Biological factors, such as ethnicity, age, smoking status and gender have been suggested as the probable causes, but not enough studies exist showing such predispositions. The goal of this study is to evaluate the association of degree of thrombocytopenia with liver function abnormalities in different ethnicity in HCV infected patients. Methods Forty -five patients with thrombocytopenia and HCV infection were included. Data was collected on ALT level, ethnicity, platelet count, and liner regression study was performed. Clinical predictors included in the analysis were age, gender, liver fibrosis stage, smoking status and ALT level. Results: Severe thrombocytopenia (110,000/ µL) is not significantly different among people of different ethnicity infected with HCV. Results Our study suggests that chronic HCV infection is associated with variable degree on thrombocytopenia., and only severe thrombocytopenia (platelet count < 80,000/ µL) can be explained by liver function abnormalities. Conclusion As liver disease advances, platelet count decreases only in patients with platelet count is below 80,000 / µL and, it is more prominent in Hispanic/Latina population.

Background Despite its increasing incidence, large-scale data regarding the demographics and characteristics of paediatric inflammatory bowel disease (IBD) at diagnosis in Korea is scarce. We aimed to compare the differences of paediatric Crohn’s disease (CD) and ulcerative colitis (UC) at diagnosis in Korea. Methods This analysis was conducted using data from a multicentre, registry-based, retrospective cohort study conducted at five centres in Korea between 2013 and 2018. Baseline demographics, clinical characteristics, results from laboratory, endoscopic, radiologic examinations were compared between paediatric CD and UC patients who were Results A total 307 patients were included in this analysis. Among them 227 patients were diagnosed with CD (73.9%), and 80 patients (26.1%) with UC. The male to female ratio was 2.49:1 for CD, and 1.29:1 for UC (p = 0.019). Median age at diagnosis was 14.4 years (IQR 12.4–16.2) for CD, and 14.4 (11.7–16.5) for UC (p = 0.962). Symptoms at presentation that were dominant in CD patients compared with UC patients were abdominal pain (76.2% vs. 51.2%, p < 0.001), weight loss (51.5% vs. 22.5%, p < 0.001), perianal fistulas (18.9% vs. 0%, p < 0.001), perianal skin tags (15.9% vs. 1.2%, p < 0.001), fever (20.3% vs. 6.2%, p = 0.007), and oral ulcers (13.7% vs. 3.8%, p = 0.026), while hematochezia was the only dominant symptom in UC patients compared with CD patients (86.2% vs. 30.8%, p < 0.001). White blood cell counts, platelet counts, ESR, CRP were significantly higher, and serum albumin level was significantly lower in CD patients. ASCA was positive in 44.5% and 16.2% of CD and UC patients, respectively (p < 0.001), and ANCA was positive in 15.0% and 58.8% of CD and UC patients, respectively (p < 0.001). Terminal ileal involvement on endoscopy was prominent in CD (62.1% vs. 16.2%, p < 0.001), while rectal involvement was more prominent in UC (52.4% vs. 83.8%, p < 0.001). Small bowel involvement and perianal perforating diseases on radiologic exams were also more prominent in CD. Conclusion Clinical symptoms, laboratory test results, radiologic findings, endoscopic findings were significantly different between paediatric Crohn’s disease and ulcerative colitis at diagnosis in Korea. A large-scale study on a nationwide basis is expected to better clarify this difference in the future.

Introduction Myelofibrosis (MF) is a chronic myeloproliferative neoplasm frequently associated with debilitating disease-related symptoms and shortened overall survival (OS). Ruxolitinib, a Janus kinase (JAK)1/JAK2 inhibitor, was approved on November 16, 2011 for patients with intermediate- and high-risk MF. The phase 3 COMFORT trials demonstrated that ruxolitinib reduced spleen volume, improved MF-related symptoms, and prolonged OS. In the COMFORT trials, the median duration of ruxolitinib treatment was 2.8 years (5-year pooled analysis). The objective of this real-world chart review study is to describe persistence of ruxolitinib treatment early on in the treatment course in patients with MF at community hematology/oncology practices in the United States. Methods Medical charts from community hematology/oncology practices in Cardinal Health Oncology Provider Extended Network (OPEN) were reviewed and abstracted into electronic case report forms by physicians. Physicans were instructed to abstract data from the earliest eligible patients and then chronologically, thereafter. This analysis included adult patients diagnosed with primary MF, post-polycythemia vera MF, or post-essential thrombocythemia MF between 01/2012 and 12/2016. Patients were required to have intermediate- or high-risk MF (based on a data-derived International Prognostic Scoring System [IPSS] risk categorization), have platelet count >50 × 109/L at the time of diagnosis, have received ruxolitinib as first-line treatment, and have ≥6 months of follow up after the initiation of ruxolitinib; patients who died within 6 months of initiation of ruxolitinib were considered as discontinued patients and were included in the analysis. Three- and 6-month persistence rates are reported. Results A total of 141 patients from 22 community hematology/oncology practices were included in the analysis; 3 patients who were still on ruxolitinib at the end of the study period, but with less than 6 months of follow up, were excluded from the analysis. Mean (SD) age at diagnosis was 69.8 (10.2) years, 61.7% were male, 71.6% had primary MF, and 56.7% were high-risk at diagnosis. Median time from diagnosis to ruxolitinib initiation was 36 (interquartile range [IQR], 20-91) days. The majority of patients initiated ruxolitinib in 2016 or later (Figure). The starting dose of ruxolitinib was 5 mg twice daily [BID] in 7.8%, 10 mg BID in 9.9%, 15 mg BID in 39.7%, 20 mg BID in 34.8%, and 25 mg BID in 7.8%. Three- and 6-month persistence rates were 97.2% and 91.5%, respectively (Table). Discussion A previous retrospective chart review of prescription claims and patient level data evaluated a cohort of patients with MF prescribed ruxolitinib just prior to and shortly after its approval (November 1, 2011 to August 31, 2012); in that study, 3- and 6-month persistence rates of 39.1% and 27.0%, respectively, were reported (Blood. 2013[122]:2833). In the current study, the 3- and 6-month persistence rates were notably higher at 97.2% and 91.5%, respectively. These higher rates are likely attributable to a number of factors. The current analysis was limited to patients treated first-line with ruxolitinib. Furthermore, the index period in the current analysis extended almost 5 years beyond ruxolitinib approval; in this 5-year period, there were a number of publications in support of ruxolitinib dose optimization with particular focus on the first 8-12 weeks of treatment (J Hematol Oncol. 2013[6]:79; Int J Hematol. 2016[104]4:420-9). The 3- and 6-month persistence rates reported here demonstrate that only a small proportion of patients with myelofibrosis treated with first-line ruxolitinib discontinued the drug early on in their treatment course. Conclusion This contemporary analysis demonstrates high rates of 3- and 6-month persistence of first-line ruxolitinib in patients with MF treated in community practices. Proper monitoring and management of the expected mechanism-based toxicity of a JAK inhibitor and proper dose titration for insufficient response, early in the treatment course, may help patients derive maximum, long-term benefits from ruxolitinib. Disclosures Yu: Incyte: Employment, Equity Ownership. Kish:Cardinal Health: Employment. Paranagama:Incyte: Employment, Equity Ownership. Colucci:Incyte: Employment, Equity Ownership.

Background DNA hypomethylating agents (HMAs), including azacytidine (AZA) and decitabine, have been established as key drugs for higher-risk myelodysplastic syndromes (MDS). Recently, a marked efficacy of decitabine has been reported in TP53-mutated myeloid malignancies, although it is not approved for MDS in many countries. Thus it is of an urgent interest whether the excellent response to TP53-mutated myeloid neoplasms is recapitulated with AZA and if so, what is the biomarkers reliably predicting response to AZA. Methods In this study we enrolled a total of 384 AZA-treated MDS patients, including 179 from a Japanese prospective study (JALSG MDS-212 trial), 163 from Karolinska Institute, and 42 from a Japanese multi-institutional registry, and analyzed mutations in 66 genes commonly mutated in myeloid neoplasms together with copy number abnormalities, using targeted-capture sequencing. For all patients, sequencing was performed on pre-AZA samples. Post-AZA samples were also analyzed for the majority (279/394, 73%) of patients. Results Analysis of pre-AZA specimens identified 1,085 driver mutations in 53 genes in 361 (94%) patients with a mean of 3.0 mutations/sample. CNAs were detected in 258 (67%) cases. Most frequently observed were mutations in TP53, RUNX1, TET2, SRSF2, and ASXL1, and other high-risk CNAs, such as -7/7q LOH, 5q LOH, and 17p LOH. TP53 lesions were found in 102 (27%) cases, of which 87 cases (85%) had biallelic lesions caused by either multiple mutations (N=28) or 17p LOH involving the TP53 locus (N=59). Sixty-seven cases (17%) achieved complete remission (CR) with a median observation period of 7.5 months. TP53 mutation, found in 48% of the cases, was the only lesion that was significantly associated with CR (OR=3.4, p72 years old, hazard ratio: HR 1.36, p=0.03) and high karyotype risks (Very High/High according to IPSS-R-based classification system, HR 1.31, p=0.04) were associated with a shorter OS, while mutations in DDX41 predicted a significantly better OS (HR 0.62, p Conclusions Our study revealed distinct response profile to AZA treatment according to TP53 mutation status, underscoring the need of different tools to estimate treatment outcomes for them. High remission rate in TP53-mutated cases does not lead to long-term outcomes due to short remission duration, if ever obtained. Successive transplantation to AZA treatment during remission phase might rescue patients from this intractable disease. Disclosures Takaori: Novartis: Honoraria. Miyazaki:Chugai: Research Funding; Otsuka: Honoraria; Novartis: Honoraria; Nippon-Shinyaku: Honoraria; Dainippon-Sumitomo: Honoraria; Kyowa-Kirin: Honoraria. Papaemmanuil:Celgene: Research Funding. Ogawa:Asahi Genomics: Equity Ownership; Dainippon-Sumitomo Pharmaceutical, Inc.: Research Funding; ChordiaTherapeutics, Inc.: Consultancy, Equity Ownership; Qiagen Corporation: Patents & Royalties; RegCell Corporation: Equity Ownership; Kan Research Laboratory, Inc.: Consultancy.

Introduction: Chronic liver disease (CLD) results in thrombocytopenia [1]. Depression of thrombopoietin (TPO) levels in CLD leads to thrombocytopenia. Thrombocytopenia increases the risk of bleeding in patients undergoing invasive diagnostic or therapeutic procedures [2]. TPO agonists have been depicted to be safe and efficacious in the treatment of thrombocytopenia due to idiopathic immune thrombocytopenia and aplastic anemia. Several studies have evaluated the use of TPO agonist versus placebo for pre-procedural treatment of thrombocytopenic patients with chronic liver disease. These studies were of limited sample sizes. We conducted a meta-analysis to determine if TPO agonists reduce the need of platelet transfusions before procedures in chronic liver disease patients. Methods: We performed a computerized search of Medline, Cochrane and Google Scholar databases through March 2019 for studies evaluating the efficacy of thrombopoietin (TPO) agonists versus placebo in the treatment of thrombocytopenia of chronic liver disease patients undergoing procedures. We screened 295 studies and only 5 of them met our inclusion and exclusion criteria. Inclusion criteria were studies with adults >18 years old, English literature, randomized controlled trials utilizing a TPO agonists in chronic liver disease patients. Exclusion criteria were studies with patients The primary study outcomes were proportion of patients responding to TPO agonists in comparison to placebo (an increase of 20000 of platelet count /ul and a value of more than 50000 count/ul). Our secondary outcomes were evaluating the proportion of patients not requiring platelet transfusion and evaluating the percentage of patients who developed a portal venous thrombosis (PVT) on study. Statistical analyses were calculated using Cumulative Meta-Analysis software (version 3.0) Results: The final analysis included 5 studies with a total of 1098 patients. Please see Image 1 for Individual Trial data. The proportion of responders for TPO agonists odds ratio was 0.060 (0.038-0.095) with P value All 5 trials demonstrated that TPO agonists compared to placebo significantly increased the platelet count and reduced the need of platelet transfusion pre-procedural with a P-value of Conclusion: Our analysis shows that TPO-agonists provide significant benefit compared to placebo in regard to increasing platelet count and reducing the need for platelet transfusions. The risk of developing PVT in patients receiving TPO agonists was not significantly increased when compared to those receiving placebo. More trials are needed to validate the comparison for PVT outcome. Figure Disclosures Jaglal: NOVARTIS: Consultancy.

Background: Immune Thrombocytopenia Purpura (ITP) can result in severely low platelet counts and while most of the 4,000 new cases of pediatric ITP diagnosed each year self-resolve, 10% of these patients have major bleeding episodes. The platelet count remains the mainstay method for predicting hemorrhage and unfortunately has only proven to be loosely correlated to bleeding severity. Consequently, there currently exists no biomarker that accurately and reliably predicts which patients need immediate medical treatment, all of which have side effects, and which patients only require monitoring. To that end, we leveraged our Platelet Contraction Cytometer (PCC), a versatile system that measures platelet contraction forces at the single-cell level and at high-throughput, to study platelets of patients with ITP prospectively. Buchanan bleeding scores were used to distinguish patients with severe symptoms from asymptomatic patients. With 49 patients, we observed two significant findings: 1) Tracking both single platelet force measurements and platelet count enables stratifying patients into having major, minor, or no risk for bleeding. Accordingly, patients in the major risk category have a combined low platelet force and low platelet count. 2) Longitudinal studies showed that when major risk patients had increased platelet force or higher platelet counts, this was associated with the alleviation of major symptoms. Thus, when utilized together, platelet force and platelet count can more accurately predict bleeding severity in pediatric ITP patients. Platelet Contraction Cytometry: Our PCC utilizes a large array of fibrinogen "microdot" pairs patterned on a flat hydrogel of known stiffness. Thrombin-activated platelets adhere to these microdots, spread to the neighboring microdot, and contract, pulling the microdots closer together. As platelet force is directly proportional to the microdot displacement, only a single microscopy measurement is necessary to determine the force applied by each single platelet (Fig 1). As such, hundreds of platelets are measured in a controlled mechanical and biochemical environment (Myers et al, 2017) Results: With our cohort of 49 ITP patients, we observed that low average single cell platelet contraction forces highly correlate with severe bleeding symptoms (Buchannan scores 2-4). Using a regression tree, we found that an average force of 26nN best separates symptomatic from asymptomatic patients with a diagnostic sensitivity of 100% and specificity of 86.8% (AUC 0.97, 95% CI: 0.9361-1). However, platelets from some asymptomatic patients exerted forces of less than 26nN as well. In a more thorough examination, we found that majority of those asymptomatic patients with low platelet forces had platelet counts > 40,000/uL. Although our data shows that platelet count alone is a poor predictor of severe bleeding symptoms (AUC 0.8, 95% CI: 0.6757-0.9189), when a platelet count Moreover, when tracking individual patients (n=4) over time, we demonstrate that whenever a patient's blood sample is associated with increased single platelet average contraction force >26 nN or platelet count >40k/uL, bleeding symptoms are alleviated. Conversely, whenever a patient exhibited high platelet contractile force and low platelet count, the onset of bleeding symptoms correlated with a decrease in platelet forces. Unlike bulk or micro-clot assays, our assay functions as a "stress test" of single platelets by placing them in conditions that maximize contractility, and in both cases, the reduction in the subpopulation of highly contractile platelets is correlated with bleeding severity. As such, our work suggests that single platelet forces could be used as a diagnostic biomarker to assess bleeding risk in patients with ITP regardless of count (Fig 2C-D). Disclosures Bennett: Novartis: Research Funding. Lam:Sanguina, LLC: Equity Ownership.

BACKGROUND: T-cell prolymphocytic leukemia (T-PLL) is a rare, aggressive, post thymic lymphoid malignancy, with an incidence of approximately 0.1/100,000 people. T-PLL accounts for ~2% of all mature lymphocytic leukaemias in adults >30 years. Median overall survival (OS) ~20 months and long term remissions are infrequent. Intravenous alemtuzumab, a monoclonal antibody directed against CD52 remains the most effective treatment in T-PLL. At the Royal Marsden Hospital (RMH) we have been using alemtuzumab for T-PLL since the early 1990s. We describe our experience over the last 3 decades. METHODS: We included 174 T-PLL patients that were diagnosed or treated at RMH between 1989-2019. Immunophenotyping data was available through our hematological malignancy diagnostic service (HMDS) from 1998 onwards. Kaplan-Meier analysis was used for OS and disease free interval (DFI) RESULTS: There were 174 patients in total. Mean age at diagnosis was 61 years old (range 32-88) and M: F ratio was ~2:1 (113:61). 90 patients had reliable information on complete blood count (CBC) at diagnosis with median white blood cell count of 74 x 109/L (range 10-918), median hemoglobin 126 g/L (range 59-175) and median platelet count 116 x 109/L (range 7-513). Sufficient immunophenotyping data was available for analysis in 135/174 patients. The results showed predictably high expression of CD2, CD3, CD5, CD7, CD52 and TCRαβ. CD25 was positive in 67/135 (50%) of cases which is higher than the 18-35% seen in the current literature. CD4+/CD8- cases comprised 83/135 (61%) with CD4-/CD8+ 19/135 (14%), CD4+/CD8+ 32/135 (23%) and CD4-/CD8- 2/135 (2%). These results are summarized in table 1. Karyotyping/FISH (fluorescent in-situ hybridization) records showed a clonal result in 84 patients and of these 65/84 (77%) had an aberration of chromosome 14. These comprised 48/65 with inv(14), 6/65 t(14;14), 2/65 t(X;14), 1/65 TCL1 gene rearrangement by FISH and 8/65 with TRA/TRD involvement by FISH. Other frequent abnormalities seen were i(8)(q10) in 31/84 (39%) and complex karyotypic abnormality in 40/84 (48%). Lower frequency abnormalities seen were monosomy 11 in 8/84 (9%), monosomy 12 in 8/84 (9%), trisomy 8 in 6/84 (7%), 17p loss in 5/84 (6%) and mononsomy 13 in 4/84 (5%). Alemtuzumab was used in 116 patients, 69/116 (59%) receiving it as frontline treatment and 47/116 (41%) as salvage therapy. In 50/116 (43%) alemtuzumab was used as single agent, the remaining 66/116 (57%) receiving combination therapy, mostly pentostatin. Mean time from diagnosis to receiving alemtuzumab was 6.8 months (range 0-53 months). Overall response rate (ORR) to alemtuzumab was 94/116 (81%) with complete remission (CR) 69/116 (59%), partial remission (PR) 25/116 (22%) and no response (NR) 20/116 (17%). Alemtuzumab produced better response rates when used as frontline therapy. Table 2 summarizes these results and OS and DFI are shown in figures B and C. Allogeneic stem cell transplant (allo-SCT) was performed in 34 patients. Median OS post allo-SCT was 22 months and median DFI 31 months. Relapse rate post allo-SCT was 47%, non-relapse mortality 38% and transplant related mortality 29%. Figures D and E show OS and DFI post allo-SCT. Although relapse rates are high post allo-SCT there is a small cohort of patients who are achieving long term remission. We analysed OS by decade of diagnosis covering 3 decades 1990-1999, 2000-2009 and 2010-2019. The median OS for the whole cohort was 20.6 months with median OS of 21 months, 23 months and 19 months for each decade respectively. Results are shown in figure A. There was no statistically significant difference between the curves by log-rank analysis. DISCUSSION: Immunophenotyping results were similar to previous published data on T-PLL except for an increase in CD25 expression at 50%. Our data shows that outcomes in T-PLL have remained unchanged since the first decade of alemtuzumab usage, with no improvement in OS in the last 20 years. Despite improvements in diagnostic techniques and supportive care median OS is static at approximately 20 months. These results highlight the need for novel therapies in T-PLL. Given the rarity of T-PLL, international, multi-center, randomised trials are needed to improve outcomes. Disclosures Cross: Royal Marsden Cancer Charity: Other: MD Residency, Research Funding. Iyengar:Abbvie: Honoraria; Janssen: Honoraria. Dearden:Janssen: Honoraria; Genentech: Honoraria; Abbvie: Honoraria; Sanofi: Honoraria.

Treatment strategies for immune thrombocytopenia (ITP) aim to achieve a platelet count associated with adequate hemostasis while maximizing patient (pt) quality of life (QoL) and minimizing treatment-emergent toxicities. However, physicians' (MDs) and pts' treatment goals have not been studied and compared. I-WISh is a cross-sectional survey of 1507 ITP pts and 472 MDs across 13 countries studying burden of ITP and pt QoL using a global pt and MD sampling frame; pts were recruited via MDs and pt advocacy groups (PAGs). ITP expert MDs and PAG representatives designed and endorsed the survey. We report treatment goals that MDs and pts perceive as being most important and how these vary among countries and different healthcare systems. Pt-reported use of ITP treatments at time of survey and any prior time are also described. Top-ranked treatment goals for MDs were reduction in spontaneous bleeds (72%), better QoL (64%), and healthy blood counts (51%). The top treatment goals for pts were healthy blood counts (64%), preventing episodes of ITP worsening (44%), and increasing energy levels (41%). More MDs than pts selected reduction in spontaneous bleeds (72% vs 38%) and QoL (64% vs 38%) as top priorities; fewer MDs vs pts selected healthy blood counts (51% vs 64%) and reduction of fatigue (15% vs 41%). MD and pt rankings of their top 3 treatment goals by country are shown in Fig.1 A&B and differences in MD vs pt perceptions in Fig. 1C. The largest differences in the percentage of MDs and pts who ranked reduction in spontaneous bleeds as a top goal were observed in France, India, Canada, UK, and USA; in each country, MDs ranked this treatment goal more often in their top 3 than pts. In contrast, lighter menstrual periods had a < 10% difference between pts and MDs in all but 2/13 countries. In certain countries, responses appeared to be balanced across similar goals, i.e. ~40% difference in ranking of reduction in spontaneous bleeds by MDs vs pts and healthy blood counts by pts vs MDs in the UK. Similarly, an 11% difference in MD vs pt ranking of improved QoL and pt vs MD ranking of increasing energy levels were observed. The largest differences in the percentages of MDs and pts who ranked healthy blood counts in their top 3 goals were observed in UK and Colombia. The largest differences between MDs and pts in their perception of reduction of fatigue as a top 3 goal were in Canada, Egypt, USA, and UK; MDs generally ranked it less important than pts, except in India. Corticosteroids (CSs) were prescribed in 79% of pts for treatment of ITP, with 26% of pts on CSs at time of survey. Countries with the highest CS use at any time were Colombia, France, and USA; Colombia, India, and Egypt had the highest CS use at time of survey. Lowest CS use at any time prior to the survey was reported by pts in Japan, Turkey, and Germany. Thrombopoietin receptor-agonists (TPO-RAs) were prescribed in 27% of pts, with 17% of pts on TPO-RA at time of survey. Countries with highest TPO-RA use at any time were Turkey, UK, Egypt, and USA. At the time of survey, TPO-RAs were most frequently used by pts in Egypt, with the lowest use in Japan. Anti-CD20 was prescribed in 29% of pts, with 5% on anti-CD20 at the time of survey. Countries with highest anti-CD20 use at any time were USA, France, and Canada. At the time of survey, anti-CD20s were most frequently used by pts in India, with no use in Turkey or Egypt. CSs were the most prevalent ITP treatments prior to and at time of survey. While this was to be expected, the high use of steroids in the USA and France compared with other countries was unanticipated. TPO-RAs and anti-CD20 have changed the landscape of second-line ITP therapies, but their utilization varies greatly among countries. Access to advanced/costly therapies is one factor that differs between countries and may influence treatment trends, but others are also important. The I-WISh survey showed that certain specific treatment goals are perceived differently by MDs and pts. Interpretation of the data is limited by the similarity of answer choice (eg, healthy blood counts and absence of spontaneous bleeds; fatigue, a key component of QoL; and QoL), which may have led to differences in responses despite similar understanding. Nonetheless, an overall agreement was generally observed, which may have been facilitated by increased MD and pt access to information through the internet and other sources, eg, medical education activities. Figure 1 Disclosures Bussel: Tranquil: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; argenx: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Kezar Life Sciences: Consultancy, Membership on an entity's Board of Directors or advisory committees; UCB: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; RallyBio: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Physician Education Resource: Speakers Bureau; 3S Bio: Speakers Bureau; Rigel: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees; Dova Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Momenta Pharmaceuticals: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Regeneron: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Ghanima:Amgen: Consultancy, Honoraria; Bayer: Honoraria, Research Funding; Pfizer/BMS: Research Funding; Novartis: Consultancy, Honoraria, Research Funding. Tomiyama:Chugai: Honoraria; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Kyowa-Kirin: Honoraria. Arnold:Rigel: Consultancy, Research Funding; Novartis: Honoraria, Research Funding; Bristol-Myers Squibb: Research Funding; Principia: Consultancy. Provan:Rigel ONO: Consultancy, Research Funding; ONO Pharmaceutical: Consultancy; Amgen: Consultancy, Honoraria, Research Funding; MedImunne: Consultancy; UCB: Consultancy; Novartis: Consultancy, Honoraria, Research Funding. Santoro:Grifols: Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Shire: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CSL: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sobi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Speakers Bureau; GSK: Speakers Bureau; Bayer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Membership on an entity's Board of Directors or advisory committees. Kruse:UCB: Honoraria; Amgen: Research Funding; Argenx: Research Funding; Dova: Research Funding; Novartis: Research Funding; Momenta: Research Funding; Principia: Research Funding; Octapharma: Research Funding; CSL Behring: Research Funding; UCB: Research Funding; Novartis: Consultancy. Waller:Adelphi Real World: Employment; Novartis: Consultancy. Haenig:Novartis: Employment. Cooper:Principia: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Rigel: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Background: Kindlin-3 which is expressed mainly in hematopoietic cells, is essential for platelet fibrinogen receptor integrin αIIbβ3 (GPIIb-IIIa) activation and kindlin-3 deficiency causes severe bleeding problems. αIIbβ3 activation is tightly regulated by inside-out signaling, and the direct interaction of talin and kindlin-3 with β3-cytoplasmic tail following CalDAG-GEFI-induced Rap1 activation is critical for αIIbβ3 activation. We have reported that immediate and sustained αIIbβ3 activation by inside-out signaling is important for thrombus formation under physiological conditions (Blood 2016). However, the details of inside-out signaling are not still fully understood. Recently we identified patient with kindlin-3 deficiency as the first Japanese patient with kindlin-3 deficiency caused by novel p.W277X nonsense mutation. To clarify the role of kindlin-3 and the molecular mechanism of inside-out signaling, we analyzed single platelet behavior adhered on collagen under physiological flow conditions, and established kindlin-3 deficient human erythroleukemia HEL cell line. Case: The patient was 8-month old female, born to Japanese consanguineous parents. She has been suffering from bleeding tendency shortly after birth. Her peripheral blood showed slightly decreased platelet count (95x103/L), anemia (Hb 6.9 g/L), and elevated leukocyte count of 37.2x106/L with 1.0% blast. Although the surface expressions of glycoproteins were comparable to healthy control, her platelet aggregations and αIIbβ3 activation were strongly impaired in all agonist stimulations due to defective kindlin-3 expression. The sequencing analysis revealed the homozygous novel nonsense mutation, p.W277X (c.918G>A) in kindlin-3. Methods: Human platelets were obtained from healthy control subjects (CT) and patients with kindlin-3 deficiency and Glanzmann thrombasthenia (GT). Whole blood was perfused at a shear rate 1,250s-1 on collagen surface and shear-induced in vitro thrombus formation during 10 minutes was observed. To evaluate the single platelet behavior after the initial attachment on collagen, each single platelet was analyzed by CellTracker software (Pccinini F. et al. Bioinformatics 2015). To further determine the role of kindlin-3 in inside-out signaling, Kindlin-3 was knocked out by CRISPR-Cas9 system and established kindlin-3 deficient HEL cell line. Results: First, we compared shear-induced thrombus formation between CT, GT, and kindlin-3 deficiency. In contrast to the stable and large platelet aggregate formation in CT after 10 minutes blood perfusion, almost no aggregate was observed in both GT and Kindlin-3 deficiency. In kindlin-3 deficiency, the initial platelet attachment on collagen seemed comparable to that of CT and GT. However, the single adherent platelets looked unstable. Next, we determined the behavior of initially attached platelets. Between CT, GT, and kindlin-3 deficiency, the numbers of platelets attached on collagen during 10 seconds were comparable. Between the initially attached platelets, 31.25% of CT platelets formed stable adhesion followed by platelet aggregation. Similar to CT, 33% of GT platelets adhered stably. However, these GT platelets did not proceed to aggregate formation due to αIIbβ3 deficiency. In contrast to GT, kindlin-3 deficient platelets showed increased detachment, only 9% of initially attached platelets stably adhered. These results suggest that kindlin-3 is indispensable for platelet initial adhesion to collagen by integrin α2β1 activation and explains severe bleeding symptoms in kindlin-3 deficiency than GT. To further investigate how kindlin-3 contributes in initial platelet adhesion to collagen, we established kindlin-3 deficient HEL cell line. In contrast to parental HEL cells, PMA stimulation did not induce αIIbβ3 activation in kindlin-3 deficient HEL cells suggesting impaired inside-out signaling. The introduction of wild type kindlin-3 cDNA, but not W227X mutant, rescued αIIbβ3 activation. Conclusion: The detailed analyses by tracking single adherent platelet on collagen confirmed the role of kindlin-3 in initial step of physiological thrombus formation. Newly established kindlin-3 deficient HEL cell line is useful for further exploration of the role of kindlin-3 and inside-out signaling in platelets and expected contribution for development of new antiplatelet therapy. Disclosures Tomiyama: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Chugai: Honoraria; Kyowa-Kirin: Honoraria.

The diverse functions played by platelets such as immune evasion, subendothelium adhesion, and pathogen interactions hinge on unique surface moieties presented on the platelet membrane. This has inspired our recent development of platelet-mimicking nanoparticles by collecting and translocating human platelet membrane onto the surface of synthetic nanoparticles. The resulting platelet-like nanoparticles (denoted 'PNPs') possess a right-side-out unilamellar membrane coating functionalized with immunomodulatory and adhesion antigens associated with platelets. The PNPs faithfully present the entire surface antigens and their functions that are otherwise difficult to replicate using bottom-up approaches. First, we demonstrate the use of PNPs to leverage the natural interaction of platelet membrane markers with multiple components present during atherogenesis for multifactored biological targeting and detection of atherosclerosis. In an experimental rat model of coronary restenosis, we demonstrate that the PNPs can selectively deliver loaded drugs to the damaged vasculatures, resulting in enhanced therapeutic efficacy as compared to nanocarriers without platelet membrane coating. We also show that the PNPs can effectively target imaging payloads to sites of atherosclerosis. We find that the PNPs bind not only to regions with significant plaque formation but also to areas that are preatherosclerotic and prone to plaque formation. Beyond simply providing contrast, this strategy also provides information about the underlying biology of the targeted regions, which may eventually be used to give a more complete picture of disease development over time. By using MRI imaging as a proof-of-concept modality, the PNP platform may be adapted toward a variety of imaging modalities for improving the prevention and management of cardiovascular diseases. To further demonstrate PNP platform technology, we use PNPs as platelet decoys to remove pathological autoantibodies in immune thrombocytopenia purpura (ITP) that otherwise cause a reduction in platelet counts. We show that PNPs can specifically bind with anti-platelet autoantibodies, which are directly responsible for reducing platelet counts. Upon binding, the interaction between the PNPs and the antibodies is strong, effectively neutralizing biological activity in vivo. In an antibody-induced thrombocytopenia animal model, mice treated with PNPs after challenging with antibodies can retain their platelet counts. Further, in a bleeding time assay, mice treated with PNPs exhibit normal hemostasis via effective clot formation, and average values are nearly identical to unchallenged controls. However, untreated mice or those administered with control nanoparticles bleed excessively due to lowered platelets counts and impaired hemostasis capacity. The ability to specifically neutralize anti-platelet antibodies in ITP presents a new option in the current landscape of treatment for the disease. Overall, these results demonstrate that coating with the platelet membrane is an effective approach for functionalizing nanomaterials. This development is expected to generate a variety of attractive nanomedicines for wide biomedical applications. Disclosures Zhang: Cellics Therapeutics, Inc: Consultancy, Equity Ownership; Cello Therapeutics, Inc: Consultancy, Equity Ownership.

Introduction Fostamatinib is a first in its class oral inhibitor of spleen tyrosine kinase (Syk) pathway for treatment of adults with immune thrombocytopenia (ITP) with insufficient response to previous treatment. Choice of treatment for relapsed ITP varies greatly according to clinician and patient preference. It is common for patients to switch between available thrombopoietin (TPO) agonists and now fostamatinib. Titration of these agents is often cumbersome and labor intensive; romiplostim in particular requires weekly visits with lab draws and consumes nurse, pharmacy and provider effort. Here we present real world experience with fostamatinib use in an academic medical center. Methods. We retrospectively identified four patients who were prescribed fostamatinib within the past nine months at Boston Medical Center Health System. All patients had a diagnosis of chronic ITP and were previously treated with corticosteroids, intravenous immunoglobulin (IVIG), and rituximab. With respect to previous TPO receptor use, two of four patients had received both eltrombopag and romiplostim. Patients were started on fostamatinib at a dose of 100 mg by mouth twice daily and titrated up to 150 mg by mouth twice daily if platelet counts were Results. Three of four patients initiated on fostamatinib had a baseline platelet count 100K or greater and the fourth patient had ITP refractory to multiple lines of therapy with a baseline platelet count of 7K at therapy initiation. Three patients sought alternative therapy given side effects from TPO agonists or inconvenience of romiplostim. Three patients had platelets counts >50K at 4 weeks and one patient had a platelet count Conclusion. The ideal place in therapy for fostamatinib in ITP therapy is not yet clear. However, the availability as an oral option for patients with refractory disease is appealing. One of our patients required rescue therapy which should be considered when transitioning patients to fostamatinib from TPO agonists. Additionally, side effect management with anti-hypertensives and anti-diarrheal agents may be required to continue therapy. Effectiveness of romiplostim may predict responsiveness to fostamatinib, although additional data are needed. Table Disclosures Shah: Rigel Pharmaceutical: Consultancy, Speakers Bureau. Sarosiek:Acrotech: Research Funding. Sloan:Merck: Other: endpoint review commitee; Abbvie: Other: Endpoint Review Committee; Stemline: Consultancy.

INTRODUCTION TP53 mutated myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) have a poor outcome. TP53 mutations occur throughout the coding region leading to functionally distinct downstream deleterious effects. The impact of the type and functional effects of TP53 mutations on the disease presentation (diagnosis, AML vs. MDS), prognosis and outcome has not been explored. Evolutionary action (EA) score is a novel computational approach to quantify the deleterious impact of missense TP53 mutations. In this study, we evaluated the effect of EAp53 score on these parameters in AML and MDS patients (pts). METHODS We selected all newly diagnosed MDS and AML pts (2013-2018) with at least 1 TP53 missense mutation detected by next generation sequencing (NGS) with 1% detection sensitivity. EAp53 score was obtained from the web server. The median overall survival (OS) was calculated by Kaplan-Meier method. Optimal EAp53 cutoffs were determined based on survival independently for AML and MDS using the lowest AIC. Univariate and multivariable Cox proportional hazards were used to identify association between risk factors and survival. Responses were evaluated using the 2006 IWG criteria. TP53 immunohistochemistry (clone DO-7) scoring was based on both intensity and percentage of positive cells. RESULTS The study group had 362 newly diagnosed pts with 471 TP53 mutations (221 MDS, 141 AML). This included 216 (59.6%) men and 146 (40.4%) women with a median age of 69 years (range, 18-90.4). 261 pts (72%) had a single TP53 mutation while 101 (28%) had >1 TP53 mutations. The median VAF was 36.4 (range, 1-94.4); median EAp53 score was 78.5 [range, 0.6 - 97.9]. No differences in the TP53 mutation characteristics including type, VAF and EAp53 scores were identified by diagnosis: EAp53 score [MDS: 79.0 (range, 0.6-97.9), AML: 78.5 (1.4-97.7)]; median VAF [MDS: 33.7 (1.0-93.6), AML: 43.9 (1.2-94.4)]. Over a median follow-up of 21.0 months, the median OS for AML was shorter than MDS (4.7 vs. 11.5 months); p < 0.001]. Within both AML and MDS subsets, EAp53 score cut-off of ≥60 predicted worse OS; this was determined as the best cut-off by AIC. Evaluation of outcomes based on both diagnosis and EAp53 scores demonstrated that EAp53 score ≥60 predicted for worse OS when corrected for diagnosis: [p=0.014; HR 1.63 (95% CI: 1.10-2.41)] (Figure 1A). Within MDS, low vs. high EAp53 score had a trend to correlate with OS (median OS 16.8 vs. 11.5 mo, p=0.07) but not in AML (7.1 vs. 4.7 mo; p = 0.17). Since low EA-AML pts and high EA-MDS pts showed similar outcome, EA score identified 3 distinct prognostic subsets within the entire cohort [TIER 1, Low EA-MDS; median OS: 16.8 mo; TIER 2, High EA-MDS plus low EA-AML; median OS: 11.1 mo; and TIER 3, High EA-AML, median OS: 4.7 mo; p < 0.001] (Figure 1B). By multivariate analysis, diagnosis (AML vs. MDS), EAp53 score (cut-off of 60), TP53 VAF, age, gender, platelet count and hemoglobin were independent predictors of OS within the study cohort. EA did not independently predict OS within AML or MDS subsets. Comparison of TIERS 3 vs. 2 vs. 1 groups showed increasing frequencies of complex karyotype (CK), del(5q), del(17p), lower frequencies of diploid karyotype (p=0.01) and a trend for higher number of TP53 mutations (p=0.08) more likely involving DNA-binding domain (p=0.014). These differences were retained between low and high EA pts in AML and MDS subsets. In addition, low-EA MDS pts belonged to very good/good/intermediate IPSS-R. By immunohistochemistry, median TP53 protein expression level (H-score, intensity and percentage) was significantly lower in low-EA versus high EA pts (p=0.038) and correlated with both TP53 VAF and EA score. In contrast, comparison within TIER 2 (between high-EA MDS and low-EA AML) showed no significant differences including age distribution, prior history of chemoradiation and TP53 VAF [high-EA MDS, 34.1 (1.1-93.6) vs. low-EA AML, 47 (1.2-82.2)]. High-EA MDS pts had a tendency for CK and a higher number of TP53 mutations. High-EA MDS pts were preferentially treated with HMA-based regimens (p=0.0001) while low-EA AML pts received chemotherapy (p=0.0002). CONCLUSION EAp53 score identifies prognostic subsets with distinct clinicopathologic characteristics within both AML and MDS pts with missense TP53 mutations, and can independently predict OS along with VAF. EA score should be used as a biomarker for baseline risk assessment in prognostic models and treatment decisions. Figure 1 Disclosures Sasaki: Otsuka: Honoraria; Pfizer: Consultancy. Jabbour:Takeda: Consultancy, Research Funding; Adaptive: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Cyclacel LTD: Research Funding; AbbVie: Consultancy, Research Funding. Kadia:Genentech: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Research Funding; Bioline RX: Research Funding; BMS: Research Funding; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Jazz: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding. Bueso-Ramos:Incyte: Consultancy. Borthakur:Eli Lilly and Co.: Research Funding; Bayer Healthcare AG: Research Funding; AbbVie: Research Funding; BMS: Research Funding; FTC Therapeutics: Membership on an entity's Board of Directors or advisory committees; BioTheryX: Membership on an entity's Board of Directors or advisory committees; Merck: Research Funding; Oncoceutics: Research Funding; Novartis: Research Funding; Oncoceutics, Inc.: Research Funding; Eisai: Research Funding; Tetralogic Pharmaceuticals: Research Funding; Arvinas: Research Funding; Strategia Therapeutics: Research Funding; Polaris: Research Funding; Cantargia AB: Research Funding; Xbiotech USA: Research Funding; NKarta: Consultancy; Argenx: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Research Funding; PTC Therapeutics: Consultancy; GSK: Research Funding; Cyclacel: Research Funding; Agensys: Research Funding; BioLine Rx: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Research Funding; Incyte: Research Funding. Ravandi:Macrogenix: Consultancy, Research Funding; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Xencor: Consultancy, Research Funding; Menarini Ricerche: Research Funding; Selvita: Research Funding; Cyclacel LTD: Research Funding. Kantarjian:Ariad: Research Funding; Takeda: Honoraria; Agios: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Actinium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Research Funding; Immunogen: Research Funding; Cyclacel: Research Funding; AbbVie: Honoraria, Research Funding; Astex: Research Funding; BMS: Research Funding; Jazz Pharma: Research Funding; Daiichi-Sankyo: Research Funding. Garcia-Manero:Helsinn: Research Funding; Novartis: Research Funding; AbbVie: Research Funding; Celgene: Consultancy, Research Funding; Astex: Consultancy, Research Funding; Onconova: Research Funding; H3 Biomedicine: Research Funding; Merck: Research Funding; Amphivena: Consultancy, Research Funding.

Introduction: Carcinocythemia means circulating tumor cells in peripheral blood. It is a very rare finding I routine practice. The first ever case was reported in 1869 by Ashworth, but it was not till 1976 that the terminology carcinocythemia was coined by Cary et al [1,2]. Only a handful of cases have been reported in literature [3]. We present one such rare case which had an additional finding of micro-filaria in it. Case Report: A 60-year-old male patient, hailing from Eastern Ghats of India, presented to the emergency with sudden onset paresis of bilateral lower limbs, hemoptysis, abdominal distention, and urine retention, constipation and persistent chest pain. On evaluation the power of bilateral lower limb was ¼. He was a known case of Stage IV adenocarcinoma of lungs with bilateral adrenal metastasis. He had received four cycles of PEM + Carboplatin followed by 3 cycles of Carboplatin and Paclitaxel. Last dose of chemotherapy was administered fifteen days prior to presentation. The patient was not responding to chemotherapy. He was receiving blood transfusion. The peripheral smear of the patient revealed circulating tumor cells along with micro-filaria. Cell block was prepared from the sample but unfortunately did not reveal much for special staining. The species of filaria was that of Wuchereria bankrofti. Interestingly, the patient lacked eosinophilia. The total count was 11,000/cumm; Hemoglobin: 8.2gm/dl and Platelet count was 2,10,000/cumm. The counter had flagged for atypical lymphocytes. The patient deteriorated fast and expired within few hours of presentation. Thus, further evaluation was not possible. Conclusion: Carcinocythemia is a rare phenomenon but as a hemato-pathologist vigilance is mandated while evaluating peripheral blood smears to detect such extra-ordinary findings. References: 1. Ashworth T. A case of cancer in which cells similar to those in the tumors were seen in the blood after death. Aust Med J. 1869;14:146-149. 2. Carey RW, Taft PD, Bennett JM, et al. Carcinocythemia (carcinoma cell leukemia). An acute leukemia-like picture due to metastatic car- cinoma cells. Am J Med. 1976;60(2):273-278. 3. Ronen S., Kroft S.H.,Olteanu H., Hosking P.R.,Harrington A.M.Carcinocythemia: A rare entity becoming more common? A 3-year, single institution series of seven cases and literature review. Int J Lab Hematol. 2019;41:69-79. Figure Disclosures No relevant conflicts of interest to declare.

Introduction Primary immune thrombocytopenia (ITP) is an autoimmune disease characterized by isolated thrombocytopenia. The pathogenesis of ITP mainly included immune-mediated platelet destruction and megakaryocyte maturation disorder. The first line therapy is steroid, but about one-third of patients do not respond to steroid. Recent studies have shown abnormalities in megakaryocyte growth and development and poorly compensated thrombopoiesis. It may be presumed that patients with these abnormalities may respond poorly to steroid and may be a candidate for therapy with thrombopoietin (TPO). The morphological classification of megakaryocytes in bone marrow may reflect the development of megakaryocytes, and may be associated with the response to steroid. Here, we intended to find out whether megakaryocytic morphology could be used to differentiate steroid-sensitive patients from primary ITP. Methods We retrospectively analyzed 170 patients with primary ITP who presented to the First Affiliated Hospital, Zhejiang University between May 2015 and Dec 2018. The diagnosis was made according to the International Working Group classification. Cases with secondary diseases that may cause thrombocytopenia were excluded. All patients were initially started on prednisolone 2 mg/kg. Response to steroid was defined as rise in platelet count to 50*109/L in 14 days. The patients who did not respond to steroid were given TPO along with the continuing dose of steroid. According to efficacy, patients were classified into 2 groups: steroid-sensitive and non-steroid-sensitive. Bone marrow aspiration was performed at the time of diagnosis. The total number of megakaryocytes on whole slide was calculated by low-power microscope, and the morphology of as many as 50 megakaryocytes was analyzed by oil lens and classified to naïve, granular, thromocytogenic and naked nucleus megakaryocytes. The correlation between the patients' clinical parameters and steroid-sensitive ITP was assessed using univariate logistic regression analyses. ROC curve analysis was performed to determine optimal cut-off values. We categorized these variables according to the cutoff values, and included these categorized variables for further multivariate logistic regression analyses. Then we constructed the predictive index on the basis of the independent factors included in the final multivariable logistic model. Results The clinical parameters of the included patients are shown in Table 1. A total of 109 and 61 patients were diagnosed as steroid-sensitive ITP and non-steroid-sensitive ITP. In univariate logistic model, the variables significantly associated with steroid-sensitive ITP were gender, thromocytogenic megakaryocyte count (TMC), the ratio of granular megakaryocyte count to total megakaryocyte count (GMC/TM ratio), and the ratio of naked nucleus megakaryocyte count to total megakaryocyte count (NNMC/TM ratio). Among the variables, female, reduced TMC with a cut-off value of 7, increased GMC/TM ratio with a cutoff value of 70% and elevated NNMC/TM ratio with a cutoff value of 1% showed diagnostic values with AUC values more than 0.5 in predicting steroid-sensitive ITP. Multivariate logistic regression was used for the four significant variables identified by univariate analysis. According to the cut-off values, patients were classified into two categories. Gender (female; OR=2.569, 95%CI 1.29-5.08; P=0.007), reduced TMC (≤6; OR=2.7, 95%CI 1.29-5.63; P=0.008) and increased GMC/TM ratio (≥70%; OR=3.27, 95%CI 1.23-8.65; P=0.017) were found to be significantly independent predictors of steroid sensitivity (Table 2). On the basis of the regression coefficient and odds ratios, weighted risk scores of 1 were assigned to gender, TMC and GMC/TM ratio, respectively. The index resulted in total risk scores between 0 and 3. ROC analysis showed that an index greater than or equal to 2 points had the best AUC value (0.63) with 47.7% of sensitivity and 78.7% of specificity for predicting steroid sensitivity. The non-steroid-sensitive ITP were subsequently treated with TPO, and 73% (30/41) responded to treatment. Conclusions The results showed that megakaryocytic morphology could be a good predictive marker for steroid-sensitivity. Steroid-sensitive ITP could be identified when primary ITP patients have a predictive index ≥ 2 points. These findings may help guide early treatment strategy in ITP. Disclosures No relevant conflicts of interest to declare.

Chromosomal abnormalities can be founder lesions (e.g., t (8; 21), inv (16), inv (3)), initiate or advance disease progression (both founder and secondary hits e.g., ASXL1, TP53, RUNX1) or can be obligatory secondary hits (FLT3, NPM1). Hence, the rank of these mutations may determine the biological properties and clinical outcomes. However, while many mechanistic studies have been undertaken without identifying the key pathogenetic factors resulting from SF3B1 mutations, important biological clues can be derived from the consequences of SF3B1 alterations in the context of the clonal architecture of myeloid neoplasia (MN). SF3B1 mutant patients often have a homogeneous phenotype with isolated erythroid dysplasia, ring sideroblasts (RS) and favorable prognoses. Studies in primary MDS cells have suggested that SF3B1 mutations are initiating lesions and provide a marked clonal advantage to MDS-RS cells by propagating from rare lympho-myeloid hematopoietic stem cells. However, there is significant diversity of clinical phenotypes and outcomes including the observation that the disappearance of RS can be observed during the disease course of clonal MN and might suggest cellular shifts due to acquisition of additional hits. In such scenarios, the cell's fate in the context of SF3B1 mutations is pre-defined by the predominance of expanded hits. We took advantage of our detailed database of molecularly and clinical annotated cases with MN to study the SF3B1 mutatome and describe whether the clonal nature (ancestral vs. secondary) might change the clinical and phenotypic trajectories of MDS cells and whether the concatenation of mutations decreases the competitiveness of SF3B1 clones, leading to the dominance of other driver genes and subsequently to clonal evolution. The clonal hierarchy was resolved using our in-house designed VAF-based bioanalytic method and confirmed by the PyClone pipeline, which showed a high level of concordance. We first assigned clonal hierarchy to SF3B1 mutations by using VAFs (adjusted for copy number and zygosity) and classifying the mutations into dominant (if a cutoff of at least 5% difference between VAFs existed), secondary (any subsequent sub-clonal hit) and co-dominant hits (if the difference of VAFs between two mutations was In conclusion, our study of the clonal architecture of SF3B1 mutations highlights that clonal progression of cases with MN harboring SF3B1 mutations might be inferred by the rank of additional genetic lesions cooperating with SF3B1. Disclosures Meggendorfer: MLL Munich Leukemia Laboratory: Employment. Advani:Abbvie: Research Funding; Macrogenics: Research Funding; Pfizer: Honoraria, Research Funding; Amgen: Research Funding; Glycomimetics: Consultancy, Research Funding; Kite Pharmaceuticals: Consultancy. Nazha:Tolero, Karyopharma: Honoraria; Novartis: Speakers Bureau; MEI: Other: Data monitoring Committee; Daiichi Sankyo: Consultancy; Jazz Pharmacutical: Research Funding; Incyte: Speakers Bureau; Abbvie: Consultancy. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Sekeres:Syros: Membership on an entity's Board of Directors or advisory committees; Millenium: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Maciejewski:Alexion: Consultancy; Novartis: Consultancy.

Introduction: The classical BCR-ABL1 negative myeloproliferative neoplasms (MPNs) are clonal disorders of marrow overproliferation. Clinical phenotypes include polycythemia vera (PV), essential thrombocytosis (ET), and primary myelofibrosis (PMF). In adults, both risk stratifications and treatment guidelines are available to physicians. Various agents, including clinical trial agents, are utilized for treatment in adults. Conversely, there are no management guidelines for children with MPNs, and therapeutic options are limited. Hydroxyurea (HU) is the most commonly used agent in children, likely because of physician experience using this medication for sickle cell anemia. Children with MPN have been treated with HU with effective cytoreduction, although its use is controversial because of the concern for leukemogenicity. While it is still considered as first-line therapy in adults with MPNs, some guidelines recommend avoiding hydroxyurea in younger adult patients. Interferon (IFN) has been utilized in adults with MPNs for many years, and pegylated forms (PEG) have made the medication more tolerable. Enthusiasm in IFN is increasing, due to reports in adult patients of hematologic remissions and significant molecular responses, including molecular remissions in rare cases. Given its improved tolerability and potential benefits, IFN may be an appropriate choice for treatment in many children with MPNs. Given the limited experience in this population and available literature, we sought to review a small cohort of pediatric MPNs treated with PEG. Methods: We reviewed the charts of pediatric patients with MPNs who have been treated with PEG and pooled de-identified data. Demographic, mutational, laboratory, and treatment-specific information was documented. This study was approved by institutional IRBs. Results: Six children were identified at four institutions who had been treated with IFN (Table 1). Age at diagnosis of MPN ranged from 2-14 years, and age at onset of PEG therapy ranged from 3-16 years. Two children are female, and four are male. Three children were diagnosed with PV and three with ET. One child with PV is positive for a JAK2 Exon 12 mutation, three children have JAK2V617F mutations (two with PV and one with ET), one child with ET has a CALR mutation, and one child has triple-negative ET. Cytoreductive therapy was started in this cohort for a variety of reasons, including worsening counts, concerning marrow findings, and symptoms (headache being the most common.) Three of the children in this cohort had been treated with HU prior to starting PEG. Reasons for switching cytoreduction to PEG included family concern for increased risk of malignancy and concern for negative effects on future fertility, interest in a disease-modifying agent, and poor side-effect profile of HU. PEG doses ranged from 45 to 90 mcg per dose (Table 2), with dosing frequency ranging from one dose every 1-4 weeks. Blood counts remained generally stable or improved in this cohort; no children required stopping and switching to another cytoreductive agent. One subject developed a pulmonary embolism while on PEG, but was able to remain on therapy; no other MPN-related complications occurred while on PEG. Some children experienced improvement in clinical disease-related symptoms. Mild side-effects reported by subjects included headache, flu-like symptoms, injection site reaction, and abdominal pain. One child had PEG dosed less frequently because of issues with depression and anxiety, and ultimately had therapy discontinued due to normalization of platelet counts. No other dose-limiting drug-related toxicity was reported. All other subjects remain on therapy with PEG, and the duration of therapy ranges from 3-168 months. Conclusion: This cohort of young MPN patients has been treated with PEG with no major dose-limiting toxicity, and with sustained tolerability. While further study is needed, it is clear that PEG can have a role to play in the management of children with MPNs. Having multiple options for cytoreduction available for families to discuss with their pediatric practitioners allows for greater family autonomy. Our results to date highlight the need for prospective study of a larger group of young patients with MPNs treated with PEG. Disclosures Bergmann: Novartis: Research Funding, Speakers Bureau; Genentech: Membership on an entity's Board of Directors or advisory committees; Octapharma: Membership on an entity's Board of Directors or advisory committees; Pfizer: Research Funding; Shire/Takeda: Research Funding; NovoNordisk: Research Funding. Mascarenhas:Pharmaessentia: Consultancy, Membership on an entity's Board of Directors or advisory committees; Merus: Research Funding; Promedior: Research Funding; Janssen: Research Funding; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Roche: Consultancy, Research Funding; Merck: Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; CTI Biopharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Verstovsek:Gilead: Research Funding; Promedior: Research Funding; CTI BioPharma Corp: Research Funding; Genetech: Research Funding; Blueprint Medicines Corp: Research Funding; Novartis: Consultancy, Research Funding; Sierra Oncology: Research Funding; Pharma Essentia: Research Funding; Astrazeneca: Research Funding; Ital Pharma: Research Funding; Protaganist Therapeutics: Research Funding; Constellation: Consultancy; Pragmatist: Consultancy; Incyte: Research Funding; Roche: Research Funding; NS Pharma: Research Funding; Celgene: Consultancy, Research Funding. Hoffman:Merus: Research Funding. OffLabel Disclosure: Use of interferon and hydroxyurea in children with MPNs is off-label

Background Ruxolitinib, an oral JAK 1/JAK 2 inhibitor, has been approved for the treatment of intermediate-2 or high-risk myelofibrosis, including primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (PPV-MF), and post-essential thrombocythemia myelofibrosis (PET-MF) in Taiwan since 2014. This registry aimed to examine the real-world safety profile and treatment pattern of ruxolitinib in Taiwan. Methods This is an observational, multi-center, post-marketing registry study. A total of 98 patients with intermediate-2 or high-risk PMF, PPV-MF, or PET-MF and receiving ruxolitinib (73.5%) or newly initiating ruxolitinib (26.5%) per clinical judgment were enrolled and analyzed in a 2-year follow-up. The primary objective was to collect the safety profile of ruxolitinib under routine practice in Taiwan. Results This interim analysis included results of 98 patients who had received ruxolitinib treatment. The median age was 68.1 years (range, 38 -87 years), 50.0% of patients were male. Of the 98 patients, 51.0% were diagnosed with PMF, 27.1% were PET-MF, and 21.9% were PPV-MF; 70.4% were categorized as Dynamic International Prognostic Scoring System (DIPSS) intermediate-2-risk group and 28.6% were high-risk group when ruxolitinib was initiated. JAK2 mutation was identified in 77.8% of 63 patients examined, while CALR mutation was identified in 6 of the 14 (42.9%) JAK2-unmutated cases. At the time of data cut-off, 23 patients (23.2%) discontinued the study mainly due to death (9.1%), adverse events (2.0%), withdrawal of consent (2.0%), and interruption of ruxolitinib ≥ 3 months (2.0%). The median exposure to ruxolitinib was 14.2 months (range, 0.8 - 37.9 months) from the time of study enrollment. At baseline, 75.4% of patients receiving a starting dose of > 5 - 10 mg bid, 11.2 % receiving > 10 - 15 mg bid, 10.2% receiving 20 mg bid. The prescription appeared to be more conservative than the suggested dose. The dose of 5 - 10 mg bid was prescribed for most patients at study enrollment regardless of different platelet counts (56.5% with platelet counts > 200 × 109/L, 54.5% with platelet counts 100 - 200 × 109/L, 50.0% with platelet counts < 100 × 109/L). The median dose after 6 months was maintained at 10 mg bid. At the time of data cut-off, adverse events (AE) were reported in 77.6% of patients and serious AEs (SAE) observed in 35.7% of patients. The most common non-hematologic AEs (≥ 5% of patients) were infections (pneumonia [9.2%], upper respiratory tract infection [8.2%], urinary tract infection [7.1%]), pyrexia (9.2%), diarrhea (8.2%), hyperkalemia (6.1%), and cough (5.1%). The infections were mainly grade 1/2, without tuberculosis or hepatitis B reactivation reported. Consistent with findings from other ruxolitinib studies, the most common hematologic AEs were anemia (10.2%) and thrombocytopenia (10.2%). However, we observed a lower incidence of anemia and thrombocytopenia compared to other studies (42.2 - 56.3%) and no one discontinued the treatment, indicating that these AEs were tolerable and manageable. Ten patients died but none of them was related to ruxolitinib. Over 48 weeks, ruxolitinib provided a sustained clinical benefit (n = 59), with a significant reduction in MPN-10 total score from 21.4 to 12.0 (P < 0.001). The improvement of symptoms was particularly prominent in naïve patients (change in total score: -12.8, P < 0.001) compared to non-naïve patients (change in total score: -6.1, P = 0.023), especially in itching (-2.7 vs. -0.5, respectively), problems with concentration (-1.8 vs. -0.9, respectively), and filling up quickly when eating (-2.2 vs. -1.1, respectively). In addition, the spleen size was reduced from baseline by 10.9 % in 27 evaluable patients at Week 12 and 16.4% in 13 evaluable patients at Week 24. Conclusions The interim analysis demonstrated that ruxolitinib for patients with intermediate-2 or high-risk myelofibrosis, was well-tolerated in the real-world setting in Taiwan. With a lower starting dose, the incidence of hematological AEs and infection rate appeared to be lower than previous reports. The safety profile was consistent with published data, with neither new safety signal, tuberculosis, nor hepatitis B reactivation detected. Ruxolitinib also provided continuous symptom improvement; however, spleen size reduction, an important goal of ruxolitinib therapy of myelofibrosis, was relatively modest, highlighting the need for dose optimization. Disclosures Hou: Celgene: Research Funding; Abbvie, Astellas, BMS, Celgene, Chugai, Daiichi Sankyo, IQVIA, Johnson & Johnson, Kirin, Merck Sharp & Dohme, Novartis, Pfizer, PharmaEssential, Roche, Takeda: Honoraria. Chen:Novartis: Employment. Lee:Novartis: Employment. Ku:Novartis: Employment.