Updated results from MOMENTUM: Momelotinib vs. Danazol in JAK inhibitor-experienced, symptomatic, and anaemic myelofibrosis patients

The phase 3 MOMENTUM study (NCT04173494) of the ACVR1/JAK1/JAK2 inhibitor momelotinib (MMB) vs. danazol (DAN) in patients with myelofibrosis (MF) previously treated with a JAK inhibitor (JAKi) met the primary endpoint and all key secondary endpoints at week 24 (W24). We provide updated results from week 48 assessments. Eligible patients had primary or post-ET/ PV MF;DIPSS high, Int-2, or Int-1 risk;Total Symptom Score (TSS) >=10;haemoglobin (Hb) <10 g/dL;platelets >=25 x 109/L;prior JAKi for >=90 days (>=28 days if red blood cell [RBC] transfusions >=4 units in 8 weeks or grade 3/4 thrombocytopenia/anaemia/ hematoma);and palpable spleen >=5 cm. Randomisation was 2:1 to MMB 200 mg/day or DAN 600 mg/day for 24 weeks, followed by open-label (OL) MMB. Week 48 endpoints included durations of response (TSS, transfusion independence [TI], splenic) and overall and leukaemia-free survival (OS, LFS). As of 17 May 2022, 93/130 (72%) MMB -> MMB and 41/65 (63%) DAN -> MMB patients received OL MMB;mean MMB durations were 48 weeks and 24 weeks, respectively. Analyses for W24 responders showed the following: of TSS responders, 31/32 (97%) MMB -> MMB and 6/6 DAN -> MMB patients had TSS < baseline;of TI responders, 36/40 (90%) and 10/13 (77%) had no RBC transfusions or Hb <8 g/dL;and of spleen responders, all patients had splenic volume < baseline. In the OL phase, the most common grade >=3 treatment-emergent adverse events (TEAEs) were thrombocytopenia (MMB -> MMB, 9%;DAN -> MMB, 15%) and anaemia (MMB -> MMB, 9%;DAN -> MMB, 2%). Grade >=3 infections occurred in 19% of MMB -> MMB and 10% of DAN -> MMB patients, including grade >=3 (nonfatal) COVID-19. Peripheral neuropathy (PN) occurred in 2% of patients in each arm, and none discontinued MMB due to PN. TEAEs led to MMB discontinuation in 18% (MMB -> MMB) vs. 10% (DAN -> MMB). A trend towards improved OS up to W24 was previously observed with MMB vs. DAN (hazard ratio [HR], 0.506;p = 0.0719);after all patients crossed over to OL MMB, OS and LFS curves for both arms converged (HR, 0.945, 95% CI, 0.528-1.693;HR, 0.830, 95% CI, 0.473-1.4555). Sixty of 81 (74%) MMB -> MMB and 29 of 43 (67%) DAN -> MMB patients with baseline platelets <=150 x 109/L entered the OL phase. Efficacy and safety results in thrombocytopenic subgroups in the OL period were consistent with the intent-to- treat (ITT) population. OL MMB maintained symptom, TI, and spleen responses with continued good survival and safety in the ITT and low platelet populations. MMB may address an unmet need in anaemic patients with MF.

Improving Patient Safety with Staff Wellbeing

Introduction: The wellbeing of hospital staff can influence the quality of patient care & safety. Following the recent COVID-19 pandemic, the longstanding issues of an overstretched & overstressed workforce within the UK National Health Service has been again highlighted. This has resulted in a renewed organisational drive to provide resources for staff health & wellbeing. Many of these are self-directed & targeted at helping the individual improve their management of external stress independently, but it has been acknowledged in the literature that local primary interventions to modify or eliminate stress to staff wellbeing must also be considered. Method(s): Staff feedback was obtained via informal interviews on the wellbeing interventions established in the local haemophilia service. Interventions evaluated included: The development of practice supporting Standard Operation Procedures (SOPs). DailyMDTwellbeing check during safety huddles. Clinical supervision time. Social interventions such as nutrition focuses, staff feedback methods & physical activity focuses. Result(s): Feedback demonstrates that social interventions implemented such as team building participation in the Haemophilia Society's Race Around the World, the HeamTeam Shoutout Board to recognise a colleague's accomplishment & offer the opportunity to show appreciation for their work, & the formation of weekly Soup & Scoop Clubs to encourage healthier eating in the department were all beneficial for staff's overall wellbeing. There was a greater sense of belonging within the team & improved interpersonal relations. The introduction of interventions such as the SOP & clinical supervision ensured staff were clear of roles & responsibilities, preventing missed opportunities to support patients and develop staff. The daily wellbeing check-in provided recognition and value of an individual's wellbeing. Discussion/Conclusion: The interventions instigated by the Sheffield Haemophilia and Thrombosis team required minimal resources & were not time commitment heavy, focusing on creating a wellness culture with regular, sustainable opportunities to engage in wellbeing conversation. However, a more comprehensive review is required to determine the long-term effects on patient care and safety outcomes.

Frequencies of Adenovirus Types in U.S. Children with Acute Respiratory Illness, 2016-2019

Background. Adenovirus (AdV) is a common cause of acute respiratory illness (ARI). Multiple respiratory AdV types have been identified in humans, but it remains unclear which are the most common in U.S. children with ARI. Methods. We conducted a multicenter, prospective viral surveillance study at seven U.S. children's hospitals, the New Vaccine Surveillance Network, during 12/1/ 16-11/30/19, prior to the COVID-19 pandemic. Children < 18 years of age seen in the emergency department or hospitalized with fever and/or respiratory symptoms were enrolled, and mid-turbinate nasal +/- throat swabs were tested using multiplex respiratory pathogen assays or real time polymerase chain reaction (PCR) test for AdV, respiratory syncytial virus (RSV), human metapneumovirus, rhinovirus/enterovirus (RV), influenza, parainfluenza viruses, and endemic coronaviruses. AdV-positive specimens were subsequently typed using single-plex qPCR assays targeting sequences in the hexon gene specific for types 1-7, 11, 14, 16 and 21. Demographics, clinical characteristics, and outcomes were compared between AdV types. Results. Of 29,381 enrolled children, 2,106 (7.2%) tested positive for AdV. The distribution of types among the 1,330 (63.2%) successfully typed specimens were as follows: 31.7% AdV-2, 28.9% AdV-1, 15.3% AdV-3, 7.9% AdV-5, 5.9% AdV-7, 1.4% AdV-4, 1.2% AdV-6, 0.5% AdV-14, 0.2% AdV-21, 0.1% AdV-11, and 7.0% >=1 AdV type. Most children with AdV-1 or AdV-2 detection were < 5 years of age (Figure 1a). Demographic and clinical characteristics varied by AdV types, including age, race/ethnicity, smoke exposure, daycare/school attendance, and hospitalization (Table 1). Co-detection with other viruses was common among all AdV types, with RV and RSV being the most frequently co-detected (Figure 1b). Fever and cough were the most common symptoms for all AdV types (Figure 2). Children with AdV-7 detected as single pathogen had higher odds of hospitalization (adjusted odds ratio 6.34 [95% CI: 3.10, 12.95], p= 0.027). Conclusion. AdV-2 and AdV-1 were the most frequently detected AdV types among children over the 3-year study period. Notable clinical heterogeneity of the AdV types warrants further surveillance studies to identify AdV types that could be targeted for pediatric vaccine development. (Figure Presented).

Pneumococcal Colonization Among Children 5 years of Age and Younger During SARS-CoV-2 Pandemic

Background. Children <=5 years of age have the highest rates of pneumococcal colonization and play an important role in the spread of pneumococcus. Our objective was to determine whether the public health measures (physical distancing, masking, and shelter-in-place orders) implemented to slow the spread of SARS-CoV-2 pandemic had an impact on pneumococcal colonization rates among children aged <=5 years with and without respiratory symptoms during the first year of SARS-CoV-2 pandemic (4/1/20 to 3/31/21). Methods. This is a single center retrospective cohort study. The study period was divided in 3 four-month periods to represent the initial period of strict adherence to public health measures (period 1: Apr-Jul), relaxation of some of these measures (period 2: Aug-Nov) and Northern hemisphere winter season (period 3: Dec-Mar). We used salvaged mid-turbinate samples obtained as part of routine care from patients without respiratory symptoms but screened for SARS-CoV-2 prior to surgery or aerosol generating procedures (asymptomatic) or from patients with respiratory symptoms tested for SARS-CoV-2 and/or other respiratory viruses (symptomatic). Samples were evaluated for pneumococcal colonization by real-time PCR using CDC lytA primers. Sample size was calculated based on the assumption of lower colonization rates in period 1 and gradual increase (10-15%) in the following study periods. Results. A total of 311 patients were included (185 asymptomatic and 126 symptomatic). Demographics, SARS-CoV-2 PCR and pneumococcal colonization results are shown in Table 1. Pneumococcal colonization rates for asymptomatic and symptomatic children were 14% and 22% (p=0.06), respectively. The odds of colonization of asymptomatic children were similar during period 2 (OR 0.96 [95%CI 0.34-2.67]) and period 3 (OR 0.53 [95%CI 0.17-1.62]), using period 1 as reference and after adjusting for age, sex, and SARS-COV-2 results. The odds of colonization of symptomatic children were also similar across the 3 study periods (period 2 OR 1.28 [95%CI 0.41-4.01] and period 3 OR 0.73 [95% CI 0.24-2.18]). Table 1. Characteristics of asymptomatic and symptomatic groups Conclusion. Pneumococcal colonization rates were not significantly impacted by public health measures implemented during the first year of the SARS-CoV-2 pandemic and did not correlate with SARS-CoV-2 positivity.

Experience with Telemedicine in a Tertiary Academic Otologic Clinic During the COVID-19 Pandemic.

OBJECTIVE: To examine the utility of telemedicine in a tertiary otologic practice. STUDY DESIGN: Retrospective case series. SETTING: Tertiary neurotology clinic. PATIENTS: Consecutive adult patients presenting via video visit between January 2020 and January 2021. INTERVENTIONS: Televideo modality to conduct visits with patients seeking evaluation for new concerns, second opinions, or routine follow-up for established conditions. MAIN OUTCOME MEASURES: Success of the televideo visit defined by the televideo visit being sufficient for determining a definitive plan and not requiring deferment of recommendations for a subsequent in-person visit. RESULTS: A total of 102 televideo visits were performed among 100 unique patients. Of those, 92 (90.2%) visits were for second opinions or evaluation of new concerns, most commonly for vestibular schwannoma (n = 32, 31.4%), followed by sensorineural hearing loss (n = 20, 19.6%). Other visits were conducted for early postoperative follow-up and established general follow-up. In 91.2% of cases (n = 93), patients were successfully evaluated and provided recommendations from the initial video visit. All visits with patients having a diagnosis of meningioma (n = 7), and nearly all with vestibular Schwannoma (97%, n = 31) and sensorineural hearing loss (95%, n = 19) were successful. Of the 79 patients offered surgery as one potential treatment option, 31 patients underwent surgery at our institution by time of review. Patients with unsuccessful visits (n = 9, 8.8%) were advised to schedule additional in-person diagnostic imaging, vestibular testing, or cochlear implant candidacy evaluation to establish a more definitive care plan. CONCLUSION: Virtual televideo visits were successful for a high percentage of selected patients seen at a tertiary neurotology practice, particularly those seeking evaluation of vestibular schwannoma or sensorineural hearing loss.

Resilience in healthcare supply chains: a review of the UK’s response to the COVID19 pandemic

Purpose: The purpose of this explorative research is to analyse the resilience of the United Kingdom's (UK) healthcare supply chains from a customer’s perspective in the light of the coronavirus pandemic. Design/methodology/approach: Using the capabilities of preparedness, robustness, recovery and adaptability as the foundational percept for supply chain resilience, 22 healthcare professionals in 17 of the UK's National Health Scheme (NHS) Trusts were interviewed to explore their personal and organisational approaches adopted relative to the provision of eye protection, gloves, gowns, aprons, masks and respirators. The Dynamic Capabilities View is mapped to the resilience capabilities and used to analyse the data from a transformational supply chain research perspective. Findings: The supply chains were largely unprepared, which was not particularly surprising even though the availability of gloves was significantly better compared to the other personal protective equipment (PPE). Techniques adopted to ensure robustness and recovery revealed the use of unsanctioned methods such as extended use of PPE beyond recommended use, redefinition of guidelines, protocols and procedures by infection control and the use of expired PPE – all of which compromised customer well-being. Research limitations/implications: As the paper views resilience through the lens of customers, it does not provide the perspectives of the supply chain practitioners as to the reasons for the findings and the challenges within these supply chains. Practical implications: The compromise of the well-being of healthcare workers due to the vulnerabilities of healthcare supply chains is highlighted to managers and prescriptions for post-disruption adaptability are made. Originality/value: This paper introduces transformative research to supply chain resilience research by uniquely looking at resilience from the customers' well-being perspective. © 2022, Emerald Publishing Limited.

Clinical and demographic characteristics associated with shorter time to COVID-19 death

Introduction: Cancer patients have been considered a high-risk population in the COVID-19 pandemic. We previously investigated risk of COVID-19 death in COVID-19 positive cancer patients during a median follow-up of 134 days, and identified the following risk factors: male sex, age >60 years, Asian ethnicity, hematological cancer type, cancer diagnosis for >2.5 years, patients presenting with fever or dyspnea, and high levels of ferritin and C-reactive protein (CRP). Here, we further investigate which factors are associated with a COVID-19 related death within 7 days of diagnosis. Methods: Using data from Guy's Cancer Centre and one of its partner trusts (King's College Hospital), we included 306 cancer patients with a confirmed COVID-19 diagnosis (February 29th-July 31st 2020). 72 patients had a COVID-19 related death (24%) of whom 35 died within 7 days (50%). Cox proportional hazards regression was used to identify which factors were associated with a COVID-19 related death <7 days of diagnosis. Results: Of the 72 cancer patients who had a COVID-19 related death, the mean age was 72 years (Standard Deviation (SD) 14). A total of 53 (74%) patients were men. 37 (52%) had a hematological cancer type, 47 (65%) had stage IV cancer, and 42 (58%) had been diagnosed with cancer more than 24 months before COVID-19 related death. In the group of patients who died within 7 days of diagnosis (n= 35), mean age was 73 years (SD 13.96), 24 (68%) were men, 20 (57%) had a hematological cancer type, 26 (74%) had stage IV cancer, and 24 (68%) had been diagnosed with cancer >24 months before COVID-19 diagnosis. Factors associated with COVID-19 related death <7 days of diagnosis were: hematological cancer (Hazard Ratio (HR): 2.74 (95% Confidence Interval (CI): 1.21-6.22)), 2-5 yrs since cancer diagnosis (HR: 4.81 (95%CI: 1.47-15.69)), and >5 yrs since cancer diagnosis (HR: 4.41 (95%CI: 1.38-14.06)). Additionally, patients who presented with dyspnea had increased risk of COVID-19 related death <7 days compared to asymptomatic patients (HR: 5.25 (95%CI 2.14-12.89)). CRP levels in the third tercile (146-528 mg/L) as compared to the first were also associated with increased risk of an early death due to COVID-19. Conclusion: From all the factors identified in our previous COVID-19 related death analysis, only hematological cancer type, a longer-established cancer diagnosis (2-5 years and more than 5 years), dyspnea at time of diagnosis and high levels of CRP were indicative of an early COVID-19 related death (within 7 days of diagnosis) in cancer patients.

Probenecid Inhibits Respiratory Syncytial Virus (RSV) Replication.

RNA viruses like SARS-CoV-2, influenza virus, and respiratory syncytial virus (RSV) are dependent on host genes for replication. We investigated if probenecid, an FDA-approved and safe urate-lowering drug that inhibits organic anion transporters (OATs) has prophylactic or therapeutic efficacy to inhibit RSV replication in three epithelial cell lines used in RSV studies, i.e., Vero E6 cells, HEp-2 cells, and in primary normal human bronchoepithelial (NHBE) cells, and in BALB/c mice. The studies showed that nanomolar concentrations of all probenecid regimens prevent RSV strain A and B replication in vitro and RSV strain A in vivo, representing a potential prophylactic and chemotherapeutic for RSV.

Second versus first wave of covid-19 in patients with mpn

Introduction. MPN-COVID is a European LeukemiaNet cohort study, launched in March 2020 in patients with myeloproliferative neoplasms (MPN) with COVID-19. The first cohort of 175 cases was analyzed at the end of first wave (July 2020) and results provided estimates and risk factors of overall mortality (Barbui T. Leukemia, 2021), thrombosis incidence (Barbui T. Blood Cancer J, 2021), and post-COVID outcomes (Barbui T. Blood Cancer J, 2021). In the second wave of pandemic (June 2020 to June 2021), case-fatality risk in the general population has been found variable across different countries, and no information is available in MPN patients with COVID-19 diagnosed during the second wave in comparison with those of the first wave. Methods. In an electronic case report form, we registered a total of 479 cases of ET (n=161, 34%), PV (n=135, 28%), pre-PMF (n=49, 10%) and overt MF (n=134, 28%), from 39 European hematology units (Italy, Spain, Germany, France, UK, Poland, Croatia). Of these, 304 were diagnosed COVID-19 during the second wave. Results. Patients in the second wave were significantly different from those in the first wave, including parameters such as age (median: 63 vs. 71 years, p<.001), sex (females: 52% vs. 42%, p=0.037), MPN category (MF 24% vs. 34%, p=0.020), comorbidity (at least one comorbidity 63% vs. 74%, p=0.012), disposition (home: 68% vs. 23%, regular ward: 29% vs. 66%, ICU: 3% vs. 11%, p<.001), need of respiratory support (28% vs. 59%, p<.001) and degree of systemic inflammation (C-Reactive Protein: 51% vs. 74%, p=0.008;Neutrophil to Lymphocyte Ratio: 4.1 vs. 5.4, p=0.038). In regard to COVID-19-directed therapy, in the second wave steroids were more frequently prescribed (28% vs. 40%, p=0.007), while the use of antibiotics, antivirals, hydroxychloroquine and experimental therapies was significantly less frequent (p<.001 for all the differences). Interestingly, only 4 out of 46 patients (8.7%) discontinued Ruxolitinib during second-wave acute COVID (all MF admitted to regular ward). In the two waves, distribution probability of COVID-19 incidence by Kernel method showed a substantially similar shape, whereas the two incidence peaks were associated with very different mortality, as reported in Fig. 1A. The difference between the probability of death was highly significant during the first (n=175) vs. second (n=304): 31% vs. 9% at 60 days from COVID-19 diagnosis, respectively (p<.001) (Fig. 1B). Of note, among 26 deaths, 4 (15%) occurred at home, 19 (73%) on regular wards and 3 (12%) in the ICU, and death more frequently afflicted patients with (n=17, 65%) than ET (n=5, 19%) and PV (n=4. 15%) (p<.001). Independent risk factors for death in a multivariate Cox regression model fitted on the whole cohort and adjusted for the wave to which patients belonged, were age over 70 years (HR=5.2, 95% CI 1.8-15.1, p=0.002), male sex (HR=1.9, 95% CI 1.1-3.1, p=0.016), COVID-19 severity revealed by the need for respiratory support (HR=4.5, 95% CI 1.9-10.7, p=0.001), and Ruxolitinib discontinuation (HR=3.0, 95% CI 1.3-6.9, p=0.011). Conversely, in patients who continued this drug, no risk was documented (HR=1.21, p=0.566). Taking into account death as competing event, the second outcome of interest was the incidence of thrombosis, wich occurred in a significantly lower proportion of patients in the second wave compared to the first one (n=5 [1.6%] vs. n=14 [8.0%] at +60 days, respectively, SHR=0.20, p=0.002) (Fig. 1C). All the events, but one (n=4/5) were venous and were reported in patients with ET (SHR=4.4, 95% CI 1.8-10.7, p=0.001). Conclusions. This is the largest series of MPN patients who incurred COVID-19 from June 2020 onward, namely during the 'second COVID-19 wave'. Compared to the first wave, the second one recorded a lower overall COVID-19 severity, but Ruxolitinib discontinuation still remained a risk factor for a dismal outcome. Greater vulnerability of ET than PV in developing venous thrombosis was confirmed also during the second wave. This finding suggests that ET warrants a specific antithrombo ic prophylaxis in addition to heparin.

Circulation of Rhinovirus/Enterovirus Respiratory Infections in Children during 2020-21 in the United States

Background. Sharp declines in influenza and respiratory syncytial virus (RSV) circulation across the U.S. have been described during the pandemic in temporal association with community mitigation for control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to determine relative frequencies of rhinovirus/ enterovirus (RV/EV) and other respiratory viruses in children presenting to emergency departments or hospitalized with acute respiratory illness (ARI) prior to and during the COVID-19 pandemic. Methods. We conducted a multi-center active prospective ARI surveillance study in children as part of the New Vaccine Surveillance Network (NVSN) from December 2016 through January 2021. Molecular testing for RV/EV, RSV, influenza, and other respiratory viruses [i.e., human metapneumovirus, parainfluenza virus (Types 1-4), and adenovirus] were performed on specimens collected from children enrolled children. Cumulative percent positivity of each virus type during March 2020-January 2021 was compared from March-January in the prior seasons (2017-2018, 2018-2019, 2019-2020) using Pearson's chi-squared. Data are provisional. Results. Among 69,403 eligible children, 37,676 (54%) were enrolled and tested for respiratory viruses. The number of both eligible and enrolled children declined in early 2020 (Figure 1), but 4,691 children (52% of eligible) were enrolled and tested during March 2020-January 2021. From March 2020-January 2021, the overall percentage of enrolled children with respiratory testing who had detectable RV/EV was similar compared to the same time period in 2017-2018 and 2019-2020 (Figure 1, Table 1). In contrast, the percent positivity of RSV, influenza, and other respiratory viruses combined declined compared to prior years, (p< 0.001, Figure 1, Table 1). Figure 1. Percentage of Viral Detection Among Enrolled Children Who Received Respiratory Testing, New Vaccine Surveillance Network (NVSN), United States, December 2016 - January 2021 Table 1. Percent of Respiratory Viruses Circulating in March 2020- January 2021, compared to March-January in Prior Years, New Vaccine Surveillance Network (NVSN), United States, March 2017 - January 2021 Conclusion. During 2020, RV/EV continued to circulate among children receiving care for ARI despite abrupt declines in other respiratory viruses within this population. These findings warrant further studies to understand virologic, behavioral, biological, and/or environmental factors associated with this continued RV/EV circulation.

Hypofractionated radiotherapy to the pancreas: U.K. experience

Background: During the COVID19 pandemic, many centres in the UK, shifted towards utilising hypofractionated radiotherapy (RT) to pancreas. We aim to report the UK experience hypofractionated (3-5 fractions) RT to the pancreas from 7 centres in the UK. Rates of toxicity, progression, death and potential prognostic factors were assessed. Univariate and multivariate Cox proportional hazards analyses were performed. Results: 92 patients from 7 centres were included in the analysis (median age 71 (range 49-88). 90% had performance status of 0-1. 66% had locally advanced disease. 53% had RT delivered over 3- 5 fractions (n = 49, median: 30Gy/5f, range:30- 40Gy in 3-5f). The rest had 15-fraction RT with or without concurrent chemotherapy (n = 43, median: 45Gy/15f, range: 36-45Gy/15f). Induction chemotherapy (CT) was used in 64% (FOLFIRINIOX -42/59). Median follow-up was 13 months from first treatment (induction CT or RT). Median overall survival (OS) among all patient was 17 months, (95% CI-14.5-19.5 months). On multivariable analysis, induction CT was the only predictor of improved PFS (median survival (MS) 12 vs 5 months;hazard ratio [HR] 0.23;95% confidence interval [CI]: 0.12-0.44, p < 0.001) and OS (MS 24 vs 11 months;HR 0.15;95% CI: 0.07 - 0.34, p < 0.001). There were no deaths. 4 patients had grade 3+ toxicities (transaminitis, cholecystitis and gall bladder perforation, small bowel obstruction and diarrhoea) -all had concurrent CT. Conclusions: Our survival outcome appears to be comparable with published data from CT + concurrent chemoradiotherapy. Induction CT appears to improve outcome. Careful selection of patients can help maximise advantage in this patient population.

Managing hematological cancer patients during the COVID-19 pandemic: an ESMO-EHA Interdisciplinary Expert Consensus.

BACKGROUND: The COVID-19 pandemic has created enormous challenges for the clinical management of patients with hematological malignancies (HMs), raising questions about the optimal care of this patient group. METHODS: This consensus manuscript aims at discussing clinical evidence and providing expert advice on statements related to the management of HMs in the COVID-19 pandemic. For this purpose, an international consortium was established including a steering committee, which prepared six working packages addressing significant clinical questions from the COVID-19 diagnosis, treatment, and mitigation strategies to specific HMs management in the pandemic. During a virtual consensus meeting, including global experts and lead by the European Society for Medical Oncology and the European Hematology Association, statements were discussed and voted upon. When a consensus could not be reached, the panel revised statements to develop consensual clinical guidance. RESULTS AND CONCLUSION: The expert panel agreed on 33 statements, reflecting a consensus, which will guide clinical decision making for patients with hematological neoplasms during the COVID-19 pandemic.

Probenecid Inhibits Respiratory Syncytial Virus (RSV) Replication (preprint)

RNA viruses like SARS-CoV-2, influenza virus, and respiratory syncytial virus (RSV) are dependent on host genes for replication. We investigated if probenecid prophylaxis or treatment inhibited RSV replication in three epithelial cell lines used in RSV studies, i.e., Vero E6 cells, HEp-2 cells, and in primary normal human bronchoepithelial (NHBE) cells, and in BALB/c mice. The studies showed that nanomolar concentrations of all probenecid regimens prevent RSV strain A and RSV B replication in vitro and RSV strain A in vivo, representing a potential prophylactic and chemotherapeutic for RSV.

Immunopathology of RSV: An Updated Review.

RSV is a leading cause of respiratory tract disease in infants and the elderly. RSV has limited therapeutic interventions and no FDA-approved vaccine. Gaps in our understanding of virus-host interactions and immunity contribute to the lack of biological countermeasures. This review updates the current understanding of RSV immunity and immunopathology with a focus on interferon responses, animal modeling, and correlates of protection.

Low Frequency of T Cell and Antibody Responses to Vaccination Against Sars-Cov-2 in Patients Post Allogeneic Stem Cell Transplantation in Comparison with Chronic Myeloid Malignancy Patients

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to unprecedented healthcare challenges on a global scale. Impressive efforts have led to rapid development of multiple efficacious vaccines against SARS-CoV-2, however concerns remain over the degree of protection vaccination offers to immunocompromised recipients. To answer this question, we have designed a prospective study to evaluate response to vaccination in patients with haematological malignancies (Harrington, Leukaemia 2021;Harrington, BJHaem, 2021). 103 patients were included with samples collected in 60 patients after first dose and 71 patients following second dose. We have analysed humoral and T cell response to a first dose of vaccine against SARS-CoV-2 in patients post allogeneic stem cell transplantation (HSCT) and compared those to patients with CML or MPN. Methods: ELISA plates were coated with antigen Nuclear (N) protein or the S protein. Serial dilutions of plasma were added to wells and incubated for 2 h at room temperature. Control reagents included N-specific monoclonal antibody, S-specific monoclonal antibody, negative control plasma, positive control plasma and blank wells. Secondary antibody was added and incubated for 1h at room temperature. IgG was detected using goat-anti-human-Fc-AP and plates read at 405 nm. Where an EC50 was not reached at 1:25, a plasma was considered seropositive if the OD at 405nm was 4-fold above background and a value of 25 was assigned. T cell functionality was assessed using intracellular cytokine staining after incubation with SARS-CoV-2 specific peptides covering immunogenic domains of the Spike (S) protein. A response was considered positive if there was a 3-fold increase in pro-inflammatory cytokine expression from baseline, and above a threshold of 0.01. Specific peptides (0.25 µg/ml), anti-CD28 and BFA were added to cells. Unstimulated cells were utilised as negative controls. Cells were stained with viability dye, then with antibodies directed against surface markers, and fixed and permeabilised prior to staining for intracellular cytokines TNFa and IFNg. Gating on lymphocytes, single cells, live cells, CD3+ cells, CD4+ cells and CD4- (CD8+) was performed. Results: Of the 103 patients included in this study, post vaccination evaluation on 56 patients have been analysed so far, including 37 patients with chronic myeloid malignancies (MPN n=21 and CML n=16) and 19 patients post HSCT. From the latter group, median time since transplant was 53.9 months (18.7 to 76.8) with 12 participants on extracorporeal photopheresis (ECP) therapy for graft versus host disease (GvHD) with median frequency of 24.5 days (14-42). BNT162b2 vaccine was administered to 48 patients (85.7%). An anti-S IgG response was observed after a first dose in 16/21 (76.1%) of the MPN group and 14/16 (87.5%) of CML patients, but in only 7/19 (36.8%) of post HSCT patients (Fishers Exact Test - p=0.02/0.002, Fig 1a). Of the latter group a low positive value where an EC50 was not reached was observed in 4/19 (21.1%) and a moderate response in 3/19 patients (15.8%). Of the 12 patients with active GvHD on ECP, a positive response was observed in 4 patients (33.3%), however only one patient recorded a response where an EC50 was measurable. A T cell response was observed in 16/20 (80%) of the MPN group and 14/15 (93.3%) of those with CML after a single dose, with a polyfunctional T cell response (>1 cytokine) observed in 65% and 80% respectively. In comparison only 5/19 patients (38.5%) post HSCT mounted a T cell response (p=0.027/p=0.002, Fig 1b), with a CD4+ response in 4 (30.8%) and a CD8+ response in 3 (23.1%). In this group, a polyfunctional T cell response was found in 4/19 patients (30.8%). 33.3% of patients with GVHD requiring ECP had a T cell response, compared with 42.9% in post HSCT without GVHD. Summary: Despite encouraging results of antibody and T cell response to a first vaccination dose in patients with chronic myeloid malignancies, these results raise concerns regarding the humoral and T cell respo ses to vaccination in patients post HSCT, recognised as a particularly immunosuppressed group. Further longitudinal data is required to determine if these results translate into a reduction in cases and severity of infection in these groups. We are currently analysing the response to a second vaccine injection and responses to sequential doses of vaccination across the whole cohort will be presented. [Formula presented] Disclosures: Harrington: Bristol Myers Squibb: Research Funding;Incyte: Honoraria. Radia: Blueprint Medicines Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Study steering group member, Research Funding;Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Education events;Cogent Biosciences Incorporated: Other: Study Steering Committee;EXPLORER and PATHFINDER studies: Other: Member of the Response Adjudication Committee. Kordasti: Beckman Coulter: Honoraria;Celgene: Research Funding;Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding;Alexion: Honoraria. Dillon: Menarini: Membership on an entity's Board of Directors or advisory committees;Novartis: Membership on an entity's Board of Directors or advisory committees, Other: Session chair (paid to institution), Speakers Bureau;Astellas: Consultancy, Other: Educational Events, Speakers Bureau;Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Research Support, Educational Events;Amgen: Other: Research support (paid to institution);Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: educational events;Jazz: Other: Education events;Shattuck Labs: Membership on an entity's Board of Directors or advisory committees. Harrison: Promedior: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;AOP Orphan Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Incyte Corporation: Speakers Bureau;Gilead Sciences: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Constellation Pharmaceuticals: Research Funding;Galacteo: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Geron: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau;Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau;Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Sierra Oncology: Honoraria;Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Janssen: 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;CTI BioPharma: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Keros: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. de Lavallade: Bristol Myers Squibb: Research Funding;Incyte: Honoraria, Research Funding;Novartis: Speakers Bureau.