Developing Contemporary Survivorship Clinic for Recipients of Hematopoietic Cell Transplantation: A Single Center Experience

Introduction: Survival after hematopoietic cell transplantation (HCT) has improved tremendously over the last few decades. HCT survivors are at increased risk of long-term complications and secondary cancers. This poses unique challenges to the HCT-related healthcare system given the growing need for survivorship care. Developing a HCT survivorship program with a dedicated clinic to survivors ensures equitable access to care and ongoing patient education. Herein, we describe our program survivorship model and our initial experience. Method(s): The Moffitt Cancer Center (MCC) survivorship clinic (SC) planning committee was initiated in September 2019. The SC was launched in January 2021 with the mission to provide high-quality, comprehensive, and personalized survivorship care and to empower patients and community health care providers with education and a roadmap for screening for late effects. The SC initially focused on allogeneic (allo) HCT patients and later opened to autologous (auto) HCT recipients in February 2022. HCT patients are referred by primary HCT team after HCT with an emphasis on preferred timeframe of initial SC visit no earlier than 3 months but less than 12 months from HCT. SC is located at 2 physical locations: main campus and satellite, with virtual visit options to account for the distance from MCC and COVID considerations. SC applies a consultative model. SC is staffed by dedicated advanced practice professional (APP), supervised by SC faculty. The scope of SC care includes but is not limited to prevention of infections (education, vaccinations), surveillance of late effects (endocrine, pulmonary function, cardiac, bone health), and general cancer screenings (breast, colon, skin cancer). Patients' clinical data from SC inception to August 2022 were reviewed. Result(s): From January 2021 to August 2022, a total of 138 patients were seen in SC. The majority were seen in person (62% in clinic, 38% by virtual visit). Median age was 58 years (range, 19-82). Median time to first SC visit was 21 months (range, 3-1464) after HCT. Allo HCT was the most common type of HCT seen in clinic (87%, n=120). Most common diagnoses were acute myeloid leukemia (43%, n=59), myelodysplastic syndrome (17%, n=23), and acute lymphoblastic leukemia (10%, n=14). Only 17 patients (12%) were seen in 2021 but the volume increased significantly in 2022. Currently there are more than 10 patients seen in SC per month. Conclusion(s): We report successful experience in launching a contemporary HCT SC despite the challenges of an ongoing COVID pandemic. As a stand-alone cancer center, we serve a wide geographical location with subspecialty and primary care providers dispersed throughout the community. Our consultative model and experience could provide a useful guide for other programs. In 2023, we plan to expand our SC to a broader population of patients receiving other cellular immunotherapies.Copyright © 2023 American Society for Transplantation and Cellular Therapy

Why Are Patients Not Getting a Graft? An Intent-to-Transplant Analysis in the Times of Universal Coverage and Haploidentical Donors

Introduction: Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a potentially curative option for patients with hematologic diseases. When considered candidates, patients face barriers to receive a transplant. Therefore, we aimed to analyze factors that limit or favor access to an alloHSCT in a population that has been HLA typed and therefore with a potential intent-to-transplant. Method(s): We retrospectively reviewed records from 2015 until the start of the COVID19 pandemic in two Mexican government- funded transplant centers and one private that have in-house HLA typing;in two of them, an outpatient transplant strategy is followed for most patients. HLA-typed patients who were potentially eligible for transplantation were included and their outcomes were assessed in an intent-to-transplant basis. We compared the outcomes of patients who underwent transplantation to those who did not and evaluated contributing barriers to access alloHSCT with multivariate logistic regression. Result(s): A total of n=374 patients were analyzed. The median age at HLA-typing was 35 years (IQR 23-47);59.3% had acute(Table Presented) leukemia, 17.4% bone marrow failure or myelodysplastic neoplasms, 13.1% lymphoma, 8% myeloproliferative neoplasms, 1.1% chronic lymphocytic leukemia and 1.1% multiple myeloma. Most patients (55.9%) had government insurance coverage. Median time from diagnosis to HLA-typing was 8 months (IQR 3-19). The majority had a potential donor (94.4%): 56.4% haploidentical, 37.4% a matched sibling donor and 0.5% an unrelated donor. Almost half of them received a transplant (n=185, 49.5%), the median time from HLA-typing to alloHSCT was 2 months (IQR 1-5.5). Disease activity or progression was the biggest barrier for transplantation;Table 1. Donor availability limited transplant access for 12.1% of patients. Access to transplantation was favored by private/out-of-pocket payment (OR 2.1 95% CI 1.3-3.4), and receiving care in the outpatient center (OR 6.4 95% CI 4-10.0), while HLA matching was not (OR 1.2 95% CI 0.8-1.8). Non-relapse mortality in alloHSCT was 21%. Median overall survival (OS) from the intent-to-transplant cohort was 16 months (CI 95% 12.4-19.6). An OS landmark analysis for patients alive at or beyond 2 months (the median time from HLA-typing to alloHSCT) showed prolonged survival in alloHSCT (30 vs 12 months, p <.001), Figure 1. By the time of the analysis 159 patients (42.5%) were still alive and 115 (30.7%) were event-free.(Figure Presented)Conclusion: The most frequent barrier to transplantation was the disease itself, followed by the transplant waitlist and comorbidities. Access to resources and an outpatient strategy or "center effect" favored alloHSCT. In the era of haploidentical transplantation, donor availability was a smaller issue. Efforts to improve timely referrals and access to effective pre-transplant therapies should be undertaken.Copyright © 2023 American Society for Transplantation and Cellular Therapy

Challenges and Results of Haploidentical Stem Cell Transplantation for Adult Patients in Cuba

The Hermanos Ameijeiras Hospital (HAH) in Havana is the only center performing allogeneic hematopoietic stem cell transplantation (HSCT) in adult patients in Cuba. Because transplants from unrelated donors are not possible due to political restrictions and economic embargo, in 2016 HAH and University of Illinois at Chicago (UIC) started a collaboration to support the training of a physician, annual educational programs and exchange of guidelines and protocols to perform haploidentical transplants. The first haploidentical transplant was performed at HAH in 2016. Because of limited resources, disease risk stratification is based on morphologic assessment, as cytogenetic is tested on an irregular basis. Peripheral blood stem cells (PBSC) were infused based on total nucleated cell count (TNC) due to lack of reagents for flow cytometry. Posttransplant chimerism and CMV monitoring cannot be performed. Transplant activity was stopped in 2020 due to high expenses allocated for COVID19 pandemic in Cuba. From 2016 to 2020, 16 haploidentical HSCT in 15 patients (9 males/ 6 females) were completed at HAH. The median age of patients was 34 years (range:21-54). Diagnoses included: acute leukemia, n=12, myelodysplastic syndrome, n=1, Hodgkin disease, n=1, and severe aplastic anemia, n=1. At the time of transplant, 11 patients were in morphologic remission and 5 had active disease. Conditioning regimens utilized were myeloablative (Flu/Bu) in 10 cases and at reduced intensity (Flu/Cy/ TBI200 +/- ATG) in 6 cases, and GVHD prophylaxis was standard PTCy on D3 and 4, CsA and mycophenolate. The donors were mother (n=10), father (n=1), child (1), or sibling (n=3) and the median age was 48 years (range: 26-68). All patients received fresh stem cells from PBSC(n=13) or bone marrow (n=3). Median cell dose infused was 5.5x108 TNC/kg (range: 2.2-8). All patients but 1 engrafted and median time to neutrophil and platelet engraftment was 17 days (range:12-28) and 16 days (range:11-30), respectively. Acute graft-versus-host disease (GVHD) grade 2-3 occurred in 50% of patients and chronic GVHD in 2 out of 8 that were evaluable. Day 100 and 2-year overall survival rates were 73% and 40%, respectively. With a medium follow-up of 18.8 months (range: 0.3-64), 5 of 15 patients (30%) are alive and complete remission. Causes of death in the remaining 10 patients included relapse of original disease, n= 4;bacterial infection, n=2;brain hemorrhage, n=1;VOD, n=1;graft failure, n=1;and multi-organ failure, n=1. Despite significant difficulties, HAH implemented a haploidentical transplant program for adult patients in Cuba. Among future steps, improving access to molecular testing and using younger donors will be pursued to improve on the results. The partnership between HAH and UIC has been instrumental in building clinical and research capacity and continues to support HAH in its mission to provide care to patients in Cuba.(Figure Presented)Copyright © 2023 American Society for Transplantation and Cellular Therapy

Copper Deficiency Mimicking Myelodysplastic Syndrome: Zinc Supplementation in the Setting of COVID-19

While copper deficiency is rare, it can have serious consequences, including pancytopenia and neuropathy. This treatable micronutrient deficiency can present very similarly to myelodysplastic syndrome (MDS), a group of myeloid neoplasms which can carry devastating prognoses. Copper deficiency is an essential differential diagnosis in suspected MDS, as it can present with similar laboratory findings, bone marrow biopsy, and clinical picture. While copper deficiency has multiple potential causes, it typically occurs in patients with a predisposing gastrointestinal pathology. One possible cause of copper deficiency is zinc overload. Interestingly, zinc over-supplementation has been prevalent during the COVID-19 pandemic, as some believe that zinc can help prevent COVID-19 infection. Multiple case reports have illustrated the similarities between copper deficiency and MDS. They have also highlighted zinc over-supplementation as a potential cause. The following case report is unique in that our patient lacked gastrointestinal pathology. He still presented with the clinical and laboratory findings of MDS in the setting of copper deficiency. These include anemia, leukopenia, fatigue, and neuropathy. Further, this deficiency was caused by zinc over-supplementation in efforts to prevent COVID-19. The deficiency and the accompanying symptoms were treated with copper supplementation and cessation of zinc intake.

Evolution of Clinical Trials in Oncohematology in a Reference Center: Does It Worth a Dedicated Structure?

Introduction: As part of the reorganization of our outpatient activity in onco-hematology (OH), questions were raised about the relevance of dedicating a specific structure to clinical research in this field. These questions arise all the more so as the proportion of OH clinical trials (CT) in our center has increased from 10% to 45% of all CT between 2000 and 2020. The aim of this study is to assess the evolution of this activity and thus to consider the interest of such a structure. Material(s) and Method(s): A retrospective data review of new CT related to OH in our center from 2016 to 2021 was performed. The evolution of 3 key indicators was assessed: distribution of OH CT among all CT, main OH indications and preferred routes of administration. Results and discussion: Over the period 2016-2021, OH CT represented an average of 32% of newly activated CT corresponding to 34% in 2016 and 48% in 2021 (approximately 90 CT start each year for a total of 420 CT in our center). A short decrease was observed in 2019 and 2020, 25% and 24% respectively, probably related to Covid-19. In terms of sterile preparations, OH represented steadily more than 60% of our activity over the period. The main indications were lymphomas (30%), acute myeloid leukemias (AML - 19%), myelodysplastic syndromes (12%) and CT related to transplant center (12%) in steady distribution overtime. Only new CT in myeloma increased from 7% to 18% in relation with increased subcutaneous (SC) use of daratumumab. Regarding preferred routes of administration, an increased trend in oral and SC routes is observed (respectively 53% and 7% in 2016 vs. 69%and 28% in 2021). The increasing use of SC intensified in 2017 as part of the arrival of AML treatments combining azacitidine (SC) with venetoclax (oral). New CT using the intravenous route decreased from 70% in 2016 to 51% in 2021 even if bispecific antibodies araised in 2021. Focusing in 2021, 1359 visits (772 in day hospital for protocol chemotherapy and 597 for oral treatment) were observed, i.e. 6 patients per day. Conclusion(s): This review showed OH's activity growth in our center. The increasingly frequent use of SC and oral routes requires that patients be fully informed and trained about their own management. In this context, a pharmacist has its place and could best inform patients about the adverse effects of new complex therapies (antibodies, targeted therapy). A unique place, organized and dedicated to clinical research in OH, would allow patients benefiting from a structured and exhaustive support as well as meeting all the healthcare professionals involved and finally ensuring the conditions for optimal care.

Mechanism-based approaches of 1,3,4 thiadiazole scaffolds as potent enzyme inhibitors for cytotoxicity and antiviral activity

Significant progress in understanding cancer pathogenesis, it remains one of the leading causes of death after cardiovascular diseases. Similarly viral infections have emerged from wildlife or re-emerged, generating serious threats to the global health. As a result, there is an urgent need for the development of novel, more effective anticancer and antiviral therapeutics. Scientists, medicinal chemists and researchers are continuously finding novel targets, mechanisms and molecules against theses severe and dangerous infections. Therefore, ongoing extensively study and research emphasizes 1,3,4 thiadiazole pharmacophore have versatile pharmacological actions. Due to mesoionic behaviour of 1,3,4 thiadiazole pharmacophore allows to enter and easily cross biological membrane which allow to interact various biological proteins. In this review study an attempt has been made of various mechanisms involved in cancer and viral prevalence with updated studies done so far. This review study also findings the role of 1,3,4 thiadiazole motif in the management of various cancers and viral infection. This study also highlighting research statics on clinical trials and various patents containing 1,3,4 thiadiazole derivatives. © 2022 The Author(s)

GATA2 deficiency presenting as fever and rash

Case Report: Our patient is an 8-year-old Caucasian female with a history of choanal atresia, first degree heart block, recurrent urinary tract infections, and recent COVID-19 infection, who initially presented with an episode of syncope and vomiting. By history, she had two weeks of daily fever and an intermittent nonspecific rash. She was diagnosed with a UTI 5 days prior to presentation but had not defervesced despite treatment. Shewas initially found to be in shock with tachycardia and poor perfusion and was treated with fluid resuscitation, antipyretics, and empiric antibiotics. Labs were significant for leukopenia, elevated inflammatory markers, lactic acidosis, coagulopathy, and mildly elevated troponin. Chest x-ray showed abnormal but non-specific widespread infiltrates. She was initially treated with IVIG and pulse steroids for a working diagnosis of MIS-C, however she did not improve and a more extensive infectious, oncologic, and rheumatologic work-up was performed. Her workup revealed a disseminated Mycobacterium abscessus infection. Bone marrow biopsy revealed myelodysplasia with monosomy 7. Her buccal swab testing revealed a heterozygous germline mutation in the GATA2 gene, a variant that is predicted to cause loss of normal protein function. She is presently on multidrug regimen for her mycobacterial infection. Her myelodysplasia evolved into an acute leukemia, and she is undergoing chemotherapy for that at this time. Discussion(s): GATA2 deficiency, first identified in 2011, is a rare immune disorder resulting in a wide variety of clinical presentations. It is caused by a germline mutation of the GATA2 gene that disrupts blood cell differentiation, resulting in decreased or absent monocytes, B cells, NK cells, and dendritic cells1. This case presented multiple challenges due to the broad range of differential diagnoses. This patient was ultimately diagnosed with myelodysplastic syndrome associated with monosomy 7 and GATA2 deficiency, confirmed by FISH testing. Due to the presentation and lab derangements this patient had, there was a delay in targeted treatment while managing her cytopenias and presumed pulmonary infection. GATA2 deficiency carries a high risk of progression from myelodysplastic syndrome to acute myelogenous leukemia. The best long-term treatment for GATA2 deficiency is hematopoietic stem cell transplant, which is the ultimate goal for our patient. Copyright © 2023 Southern Society for Clinical Investigation.

Patient Reported Outcome Measure-Select App

IntroductionA patient/person-reported outcome measure (PROM) is a questionnaire that measures patient's health self-assessment (PROs), such as pain/wellbeing. HTx is a Horizon 2020 project supported by the European Union lasting for 5 years from January 2019. The main aim of HTx is to create a framework for the Next Generation Health Technology Assessment (HTA) to support patient-centred, societally oriented, real-time decision-making on access to and reimbursement for health technologies (HTs) throughout Europe. Individual values, needs, and preferences should be taken into account when appraising HTs and in clinical decision-making. Better guidance is needed about how to develop and select generic and/or more specific outcome measures that are relevant to patients and fit-for-purpose. Our goal is to provide that guidance via the PROM toolbox and enable users to select PROMs by using this. The HTx project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement N° 825162.MethodsA framework for the assessment of PROMs was discussed with experts, tested for a subset of PROMs (Linnean menu) and resulted in the PROM-cycle. Multiple literature studies were performed on PROMs, their properties, and characteristics. The general population was studied as well as cancer, diabetes, multiple sclerosis, myelodysplastic syndrome, and (long-lasting) COVID-19. This resulted in an Excel database (PROM-overview) made available via a user-friendly web-application helping users to select PROMs: the PROM select app via https://www.prom-select.eu/proms.ResultsMultiple tools were developed and are available in the PROM toolbox starting with the PROM-guide, Literature review on the use of PROMs, PROM-cycle accompanied by the Linnean menu. In addition, PROM-links, The making of the PROM-overview & PROM-select app, PROM-overview, PROM-select app, its usability test report and PROM toolbox presentation can be found on https://www.zorginzicht.nl/ondersteuning/prom-toolbox-summary-in-english#what-is-the-prom-cycle.ConclusionsThe PROM toolbox guides users and helps them to select PROMs and trustworthy information and finding relevant scientific articles.

CHRONIC EMPYEMA MANAGED WITH TUBE THORACOSTOMY

SESSION TITLE: Problems in the Pleura Case Posters 2 SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Hematologic malignancies can often be complicated by pleural effusion due to leukemic infiltration of the pleura (1). Long term management of resulting chronic plural effusion can be complicated when there is evidence of trapped lung. Subsequent infection may lead to development of chronic empyema which can be difficult to manage in chronically ill patients (2). CASE PRESENTATION: A 65-year-old male with history of chronic myeloid leukemia status post stem cell transplant was admitted with dyspnea and cough. Computed tomography (CT) chest imaging revealed increased volume loss on the left with new air fluid level in a chronic left pleural effusion. (Image 1) Patient's history was significant for chronic left pleural effusion, which was first identified in 2015 and found to be a malignant effusion with evidence of leukemia involvement. Repeat imaging in 2018 (Image 2) revealed continued chronic pleural effusion. Patient was admitted in August 2021 with COVID-19 pneumonia and CT Chest showed chronic loculated left sided pleural effusion. Patient elected to continue to monitor the chronic effusion, which was completed as outpatient every 4 to 6 weeks (Image 3). He remained clinically stable until the presentation to a hospital in January 2022. The chronic empyema was initially managed with tube thoracostomy, intrapleural fibrinolytics and antibiotics. Cultures were significant for Moraxella catarrhalis and Streptococcus pneumoniae. He was determined to be a poor surgical candidate for decortication and treatment with empyema tube was initiated. The empyema tube was incrementally withdrawn as an outpatient and subsequently removed with good clinical recovery. DISCUSSION: Chronic empyema is characterized by thickened parietal and visceral pleura which limits the ability of the lung to re-expand. Surgical management with decortication is the definitive management, however, in poor surgical candidates, management becomes more complicated. Open pleural drainage with an open pleural window can be considered. An alternative option converts tube thoracostomy to open pleural drainage, as was utilized in this patient (2). While comparison of surgical vs non-surgical management of empyema suggests similar mortality (3), non-surgical management of chronic empyema needs more investigation to determine the optimal treatment modality. CONCLUSIONS: Empyema remains a difficult condition to manage. Treatment modalities of chronic empyema are limited in those patients who remain poor surgical candidates. Reference #1: Faiz SA, Sahay S, Jimenez CA. Pleural effusions in acute and chronic leukemia and myelodysplastic syndrome. Curr Opin Pulm Med. 2014 Jul;20(4):340-6. Reference #2: Biswas A, Jantz MA, Penley AM, Mehta HJ. Management of chronic empyema with unexpandable lung in poor surgical risk patients using an empyema tube. Lung India. 2016;33(3):267-271. Reference #3: Redden MD, Chin TY, van Driel ML. Surgical versus non-surgical management for pleural empyema. Cochrane Database Syst Rev. 2017;3(3):CD010651. Published 2017 Mar 17. DISCLOSURES: No relevant relationships by Shannon Burke No relevant relationships by Abigail Go No relevant relationships by Jen Minoff no disclosure on file for Ravi Nayak;

IMPORTANCE OF STEROIDS: A CASE OF SPONTANEOUS BILATERAL ADRENAL HEMORRHAGE DUE TO THROMBOCYTOPENIA IN A PATIENT WITH MYELODYSPLASTIC SYNDROME

SESSION TITLE: Emergency Endocrine Disorders SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 10:15 am - 11:10 am INTRODUCTION: Spontaneous bilateral adrenal hemorrhage (BAH) resulting in adrenal crisis is a rare, but serious condition that can easily be missed as patients may present with non-specific symptoms (weakness, fatigue, nausea, vomiting, dizziness). It can escalate to hemodynamic instability in the setting of adrenal crisis. The most common cause is meningococcal disease, other causes include trauma, septicemia, and coagulopathies. Without treatment it is fatal and carries a high mortality rate of 15%;Waterhouse-Friderichsen syndrome has been reported with 55-60% mortality. Here, we describe a case of a patient with a history of myelodysplastic syndrome (MDS) who presented with multiple readmissions with a septic shock picture with unknown source of infection and was finally diagnosed with bilateral adrenal hemorrhage causing adrenal crisis. CASE PRESENTATION: An 85-year old independently living man with past medical history of MDS and hypertension presented after a syncopal episode at home with altered mental status. Treatment was initiated for a urinary tract infection which progressed to shock. His labs were notable for leukocytosis in the 40,000s and a platelet count in the 30s. He was found to have BAH on imaging. He was started on broad-spectrum antibiotics, vasopressors and stress-dose steroids with improvement in his condition and eventually discharged home. He was readmitted to the ICU twice within a month for shock, each time with a negative infection workup, as he had been discharged home without steroids to follow up with an endocrinologist. After his third readmission, he was discharged on steroids and he did not have any further readmissions to the hospital. Exhaustive investigations were made into possible infectious causes of his BAH as well as possible vasculitis and hematologic causes. It was determined to likely be in the setting of thrombocytopenia brought on by his MDS. DISCUSSION: Thrombocytopenia is a rare cause of BAH and adrenal crisis. Review of literature mostly describes cases of heparin-induced thrombocytopenia, a few cases of COVID19 and vaccine-induced immune thrombocytopenia after the COVID vaccine. In our patient, it was thought that MDS predisposed him to spontaneous BAH and subsequently adrenal crisis, which has only been described once before in the literature. Stress dose steroids are commonly used in the ICU for relative adrenal insufficiency. Due to the acuity of his condition and concern for relative adrenal insufficiency, our patient was tapered off steroids and discharged home with endocrinology follow up which led to his frequent readmissions as his underlying problem was not addressed. CONCLUSIONS: Adrenal insufficiency is rare and may be difficult to diagnose especially in the acute setting. It is important to recognize and treat adrenal crisis as it has a high mortality rate. MDS is a rare cause. Reference #1: Manganaro L, Al Ansari N, Barchetti F, et al. Bilateral Adrenal Hemorrhage in a Patient with Myelodysplastic Syndrome: Value of MRI in the Differential Diagnosis. Case Reports in Radiology. 2013;2013:e479836. doi:10.1155/2013/479836 Reference #2: Rosenberger LH, Smith PW, Sawyer RG, Hanks JB, Adams RB, Hedrick TL. Bilateral adrenal hemorrhage: the unrecognized cause of hemodynamic collapse associated with heparin-induced thrombocytopenia. Crit Care Med. 2011;39(4):833-838. doi:10.1097/CCM.0b013e318206d0eb Reference #3: Fatima Z, Tariq U, Khan A, et al. A Rare Case of Bilateral Adrenal Hemorrhage. Cureus. 2018;10(6):e2830. Published 2018 Jun 18. doi:10.7759/cureus.2830 DISCLOSURES: No relevant relationships by Robbert Crusio No relevant relationships by Justyna Michalik No relevant relationships by Aditya Saholi

CLINICAL IMPACT OF COMMUNITY ACQUIRED RESPIRATORY VIRUSES IN PATIENTS WITH SOLID ORGAN TRANSPLANTS

SESSION TITLE: Not the Normal Host: Infections Still Matter SESSION TYPE: Rapid Fire Original Inv PRESENTED ON: 10/17/2022 12:15 pm - 1:15 pm PURPOSE: Community Acquired Respiratory Viruses (CARVs) are associated with poor outcome in Solid Organ Transplant (SOT) recipients. We reviewed some of these outcomes such as respiratory support, length of stay (LOS), ICU admission, steroid use & 30-day all-cause mortality. METHODS: Multihospital, single center, retrospective review of electronic health records from 01/01/2014-12/31/2019. RESULTS: 23 SOT recipients (M=20, F=3) who tested positive for CARVs were identified. SOT distribution was heart=2, kidney=4, liver=3, lung=11, heart-lung=1, lung-kidney=1 & heart-kidney=1. Mean age at admission was 60 years, average LOS was 8 days with 2 pts needing >2 weeks. 6 pts required intensive care unit;8 pts required supplemental oxygen support. 16 pts had infiltrates on chest imaging. 15 pts had a 90-day readmission with respiratory complaints. 8 pts had bronchoscopy & 20 had positive nasal swab. 3 pts had a negative nasal swab but positive Bronchoalveolar lavage (BAL) for CARV while 2 pts had negative BAL but positive nasal swab. CARV distribution was Rhinovirus 48%, Parainfluenza 29%, Metapneumovirus 12%, Respiratory syncytial virus 0.03%, Adenovirus 0.03% & Non-novel Coronavirus 0.06%. 5 pts had bacterial coinfection (Pseudomonas aeruginosa, Corynebacterium striatum & Stenotrophomonas maltophilia). All pts were immunosuppressed, intravenous immunoglobulins (IVIG) were used in 3 pts, antivirals in 7 pts (ribavirin in 6 & oseltamivir in 1) & steroids in 10 pts. 12 pts had transplant organ biopsy with 5 showing acute cellular rejection. 11 pts had underlying Coronary artery disease and 17 pts had hematologic disorders (Post-transplant lymphoproliferative disorder, leukemia, Myelodysplastic syndrome, & multiple myeloma). 35% pts died within 1 year (2 during same admit). Cause of death was refractory septic shock (1), respiratory failure (3), cardiac arrest (3) & chronic lung allograft dysfunction (CLAD) (1). CONCLUSIONS: In this cohort, we assessed the SOT recipients positive for CARVs who required admission & evaluated the impact on their clinical course. This analysis noted a significant rate of acute & chronic rejections, bronchiolitis obliterans and CLAD in these patients. Newer tests like multiplex NAT & (semi) quantitative NAT (QNAT) can diagnose CARVs in addition to Human Influenza Virus. Patients can present with wheezing, croup, bronchiolitis, pneumonitis & pneumonia. Impact of CARVs seems to vary by the type of organ transplant, level of neutropenia/lymphopenia, upper versus lower respiratory infection and intrinsic pathogenicity of virus. Various preventive & therapeutic measures were employed in an attempt to improve outcomes in these patients. CLINICAL IMPLICATIONS: Transplant receipients are at a high risk of infections especially CARVs which may increase morbidity and mortality. This analysis emphasizes the value of timely diagnosis and treatment in this specific patient population who are immunocompromised. DISCLOSURES: No relevant relationships by Supriya Singh

Abstract of 17th Congress of Pediatric Emergencies and Common Diseases

The proceedings contain 81 papers. The topics discussed include: anaphylaxis to COVID-19 vaccines;multisystem inflammatory syndrome in children (MIS-C): clinical manifestation, evaluation & diagnosis;clinical characteristics of children with COVID-19 complicated by acute kidney injury;a referral center experience;antenatal hydronephrosis;a myelodysplastic syndrome evolution;neonatal thrombosis and related risk factors;the biologics in multisystem inflammatory system in children;side effects and contraindications of COVID-19 vaccines;hematopoietic stem cell transplantation (HSCT) in children;epidemiology and pathophysiology of foreign bodies of the esophagus and gastrointestinal tract in children;and co-administration of COVID-19 vaccine and routine vaccines and influenza vaccine.

HUMORAL RESPONSE TO MRNA-BASED COVID-19 VACCINE IN PATIENTS WITH MYELOID MALIGNANCIES

Background: The end of the pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease-19 (COVID-19), is not foreseen. Vaccination using two subtypes of mRNA-based vaccines, BNT162b2 or mRNA-1273, is an effective public health measure to reduce the risk of infection and severe complications from COVID-19. However, COVID-19 vaccine response data for patients with myeloid malignancy, who are at severe risk in case of infection, has not emerged. Aims: We investigated the antibody titers of COVID-19 in patients with myeloid malignancies who received two doses of mRNA-based COVID-19 vaccine. Methods: Previously treated, currently treated, and newly diagnosed 46 patients with acute myeloid leukemia (AML) and 23 patients with myelodysplastic syndrome (MDS) were included in this study. Anti-spike SARS-CoV-2 antibody titers were measured at 3 months after the second vaccination and compared them to those in healthy controls. Results: Seroconversion rates for AML and MDS were 94.7% and 100%, without significant difference from healthy controls (100%). In AML patients, the median antibody titers of patients in complete remission (CR) (816.5 [interquartile range (IQR): 250.0-2063.5] U/ml vs 1023.0 [640.0-1535.0] U/ml, P=0.668), especially those who were under treatment-free observation in CR (1630.0 [806.0-2454.0] U/ml vs 1023.0 [640.0-1535.0] U/ml, P=0.1220), were comparable to those in healthy controls. On the other hand, even in CR, the antibody titer in AML patients under maintenance therapy was significantly lower than that in patients under treatment-free observation (154.0 [126.0-289.0] U/ml vs 1630.0 [806.0-2454.0] U/ml, P=0.0003). Among the AML patients in CR, patients receiving maintenance treatment had a significantly lower median absolute lymphocyte count (0.81 [0.71-1.46] x 109/l vs 1.58 [1.29-1.93] x 109/l, P=0.0094) and a significantly lower median absolute neutrophil count (1.45 [1.15-1.64] x 109/l vs 3.45 [2.68-4.28] x 109/l, P<0.0001) than that in patients under treatment-free observation. Significantly lower antibody titers were associated with current active treatment (92.2 [37.5-216.3] U/ml vs 1630.0 [806.0-2454.0] U/ml, P<0.0001), AML with myelodysplasia-related changes (50.8 U/ml [39.9-109.1] vs 816.5 [283.0-1935.3] U/ml, P=0.0022), advanced age more than the median age of 68 years (195.0 [43.3-743.0] U/ml vs 1630.0 [806.0-3391.0] U/ml, P=0.0002), and vaccine subtypes of BNT162b2 (285.0 [127.8-1045.3] U/ml vs 3037.0 [2198.50-4537.0] U/ml, P=0.0002) in AML patients and with current active treatment (41.0 [10.7-227.5] U/ml vs 623.5 [173.8-1613.3] U/ml, P=0.0233), subtypes of excess blasts (11.1 [4.8-34.1] U/ml vs 212.0 [81.7-600.0] U/ml, P=0.0293), and high and very high risk of the revised international prognostic scoring system in MDS patients (9.0 [3.4-41.0] U/ml vs 169.0 [48.5-327.0] U/ml, P=0.0380). Summary/Conclusion: This is one of the first studies on the effect of COVID-19 vaccines focusing on patients with AML and MDS, and there are many new findings. The response to COVID-19 vaccine appears to be related to disease and treatment status. Myeloid malignancies may have less impact than lymphoid malignancies on the vaccine response. AML patients under treatment-free observation in CR could be expected to have a vaccine effect that is comparable to that in healthy individuals. In contrast, since the response to vaccination might be insufficient in AML patients undergoing maintenance therapy, maintenance therapy should be continued with strict measures for prevention of infection even after vaccination.

CHARACTERISTICS AND OUTCOMES OF PATIENTS WITH ACUTE MYELOID LEUKAEMIA TREATED WITH VENETOCLAX COMBINATION THERAPY: REAL-WORLD EXPERIENCE IN BOTH FRONTLINE AND RELAPSED/REFRACTORY SETTINGS

Background: Venetoclax (Ven) in combination with hypomethylating agents, such as azacitidine (Aza) and low dose cytarabine (LDAC) has been shown to be effective therapy in acute myeloid leukaemia (AML) and has become standard of care for newly-diagnosed patients unfit for intensive chemotherapy (DiNardo et al., 2020;Wei et al., 2019;Pollyea et al., 2020). Efficacy has also been shown in the relapsed/refractory (R/R) setting in more limited data sets (Báez-Gutiérrez et al., 2021;Pollyea et al., 2020, Stahl et al., 2020;DiNardo et al., 2019). Ven combination therapy has become widely used in newly-diagnosed patients in the UK since its approval during the COVID-19 pandemic as an alternative to intensive chemotherapy and subsequently for patients unfit for intensive therapy. Aims: We describe the characteristics and outcomes of patients with AML or high risk myelodysplastic syndrome (HRMDS) receiving Ven combinations in frontline and R/R settings to provide real-world insight into their use in UK clinical practice. Methods: A retrospective analysis was performed of all patients with AML or HR-MDS who received Ven combination therapy at University College London Hospital between April 2020 and September 2021. Patient demographics, treatment history and bone marrow results were obtained from electronic health care and laboratory records. Disease stratification and response assessments were made as per European LeukemiaNet (ELN) criteria (Döhner et al., 2017). Results: At the time of analysis, 95 patients received Ven combinations (61 as frontline treatment and 34 for R/R AML), with a median follow up of 14 months. The majority of patients in both groups had adverse risk ELN classification (70.5% of frontline patients, 64.7% of R/R) and received Ven-Aza (100% frontline and 91.1% R/R) (Table 1). The median ages were 72 and 59 years respectively. The incidence of composite CR/CRi was 70.5% in the frontline setting, with median duration of response (DoR) of 8.3 months and overall survival (OS) of 7.1 months. In R/R AML, the CR/CRi rate was 64.7%, median DoR 10.5 months and median OS 9.8 months. Four out of the 43 patients who achieved CR/CRi (9.3%) following frontline treatment and 9 of the 22 R/R (40.9%) patients proceeded to allogeneic stem cell transplant (alloSCT) post induction. The median survival for all patients who underwent alloSCT is not reached in this analysis. The highest CR/CRi rates were observed in intermediate risk patients (90.9% in frontline treatment, 71.4% in R/R), with lower rates in both favourable (80% and 66.7%) and adverse risk patients (65.1% and 59.1% respectively). The presence of NPM1 and IDH1/2 mutations were associated with high CR/CRi rates in both the frontline (85.7% and 84.6% respectively) and R/R groups (100% and 81.8%), with below average response rates seen in TP53 mutated AML (62% in frontline, 40% in R/R). Notable responses were seen in patients with RUNX1 mutations in both settings (77.8% frontline, 66.6% R/R). Summary/Conclusion: Our data describes real world effectiveness for venetoclax combinations as both frontline and salvage therapy in UK clinical practice, similar to that seen in clinical trials. This further contributes to our understanding of these therapies, in particular their use as a viable treatment option in R/R patients and as a bridge to alloSCT, and highlights the importance of further characterisation of genetic predictors of response to inform treatment decisions in real-world practice.

LESSONS LEARNED FROM THE MYPAL DIGITAL HEALTH INTERVENTION: CAPITALIZING ON THE PATIENT REPORTED OUTCOMES (PRO) PARADIGM TOWARDS A PARTICIPATORY HEALTHCARE FOR PATIENTS WITH HEMATOLOGICAL MALIGNANCIES

Background: Chronic lymphocytic leukemia (CLL) and myelodysplastic syndromes (MDS) are two of the most frequent hematological malignancies. CLL and MDS are also considerably heterogeneous in terms of clinical course and response to treatment, ranging from relatively indolent to extremely aggressive. Thus, open issues abound regarding the impact of CLL and MDS and their treatment on patients' quality of life (QoL). Patient-reported outcomes (PROs) have been identified as an emerging paradigm, aiming to capture the patient's perspective onselfassessed health status. Obviously, these data are critical with regards to the evaluation of the treatment effects and the patients' QoL, while also enabling the positioning of the patient as a key stakeholder within the healthcare decision making process. Novel methodologies and eHealth approaches can be valuable for the adoption of the PRO paradigm in real-world settings as they can promote richer, less obtrusive and preemptive communication which could facilitate early recognition of potential symptoms of disease or treatment adverse effects (e.g., adverse drug reactions, lack of physical activity, worsening of QoL etc.). Aims: In this , we present the lessons learned thus far from the implementation of the MyPal project, a Horizon 2020 Research & Innovation Action aiming to foster palliative care for patients with CLL and MDS by leveraging the ePRO paradigm. Methods: MyPal aspires to empower patients and their caregivers to more accurately capture their symptoms/conditions, communicate them in a seamless and effective way to their healthcare providers (HCPs);and, ultimately, to foster action through advanced methods of identification of important deviations relevant to the patient's state and QoL. To this end, MyPal developed a technical platform including a mobile app for patients with CLL and MDS, collecting information via standardized questionnaires and other information sources (e.g., wearable sensors), also enabling spontaneous symptoms reporting, educational material provision, motivational messages, discussion guides, notifications etc. A data intensive web-based dashboard platform is also provided for healthcare professionals, providing real-time analytics, enabling a better view of collected PROs and other relevant information on patients' health status. Currently, a randomised clinical study is being conducted in 4 European countries to evaluate the proposed intervention and its potential impact on patients' QoL. Results: Based on this experience, a number of key issues have emerged: (a) while patients are generally positive about the use of eHealth, they are still reluctant about engaging in eHealth clinical studies;(b) digital literacy levels differ across different age groups as well as among different cultural contexts;(c) the COVID-19 pandemic seriously hindered patient recruitment due to the widely adopted recommendations for patients to avoid visits to hospitals unless absolutely necessary but (d) the COVID-19 pandemic also highlighted the potential benefits for HCPs of using eHealth tools in order to deliver patient care in a more decentralized and patient-centric fashion. Summary/Conclusion: In conclusion, MyPal is likely to provide important new evidence about how digital health systems can be used to improve QoL and facilitate better communication between patients with hematological malignancies and HCPs.

CONSOLIDATION OF ERN-EUROBLOODNET: THE EUROPEAN REFERENCE NETWORK ON RARE HEMATOLOGICAL DISEASES FIRST 5 YEARS OF IMPLEMENTATION

Background: ERN-EuroBloodNet was established in 2017 as the European Reference Network on Rare Hematological Disorders (RHDs) bringing together nationally recognized centres of excellence with the goal of promoting EU best health care in RHDs. ERN-EuroBloodNet has been recently enlarged integrating 103 HCP from 24 EU-MS. Aims: ERN-EuroBloodNet was conceived to contribute to innovative, efficient and sustainable health systems and facilitate access to better and safer healthcare for EU citizens while decreasing the cross-border health barriers. Methods: Since 2017, ERN-EuroBloodNet established the state-of-the art of RHD allowing the implementation of transversal and disease-specific strategies, where actions on very rare RHD were prioritized. Results: Profile. 182 expert profiles were created freely accessible. Expert centers follow 65,000 RHD patients and treat 5,000 new patients per year, while 24 patients requested support for cross-border health assistance. Expertise. The need to improve access to next-generation sequencing for non-oncological RHD and bone marrow transplantation for sickle cell disease (SCD) was identified. Also, significant disparities in the clinical practice of primary vitreoretinal lymphoma were found and we demonstrated that less than 30% of children with SCD benefit from adequate annual stroke risk monitoring. Guidelines. A repository of 68 Clinical Practice Guidelines (CPG) classified on quality of evidence and consensus approach was created. Recommendations for diagnosis and treatment of methemoglobinemia was published in collaboration with EHA. A CPG on Adult Burkitt Lymphoma is under development. Next topics focus long-term complications in hemoglobinopathies and patients' pathways&summary. Education. ERN-EuroBloodNet Webinars were launched for professionals with 26 Thursdays Webinars and 3 EBAH accredited Topic on Focus on Cutaneous Lymphoma, Thrombotic Microangiopathies, and Bone Marrow Failures. A collaboration was established for EHA & ERN-EuroBloodNet Spotlight on Castleman Disease. For patients, 3 Topic on Focus were launched for Myelodysplastic syndromes, SCD, and Cutaneous lymphoma. Past webinars are available at EuroBloodNet EDU Youtube channel. Preceptorships on SCD will be launched soon. Telemedicine. 43 complex cases have been inter-professionally discussed in the Clinical Patient Management System with 21 outcome reports delivered. Registries. 184 Registries were identified through the European Rare Blood Diseases Platform (ENROL), endorsed by the EHA. The ENROL project, which includes rare anemias, dendritic cell leukemia and von Villebrand's disease pilots, aims to collect exhaustive and therefore epidemiological data for RHDs. The final objective is a possibility of EU health planningl and the promotion of research by identifying cohorts of patients. ERNEuroBloodNet launched the collaborative platform on patients with red blood cells and COVID-19 containing so far 373 patients. Collaborations. collaborative research projects were encouraged like EC-funded projects i.e., genomics and personalized medicine in hematological diseases (GenoMed4All) and the properties and viability of erythrocytes (EVIDENCE), or the International Hemoglobinopathy Research Network (INHERENT) for genomic and phenotypic correlations. Summary/Conclusion: The implementation of well-defined strategies but above all adapted to the specific and not yet covered needs of RHD has led to the realization of concrete projects. This has laid the foundations to strengthen health systems in the field of RHD and allow them to flourish under the new EU4Health programme.

CLI120-001 PHASE1B DOSE ESCALATION STUDY OF RVU120 IN PATIENTS WITH AML OR HIGH RISK MDS SAFETY AND EFFICACY DATA UPDATE

Background: CDK8 and its paralog CDK19 have central roles in maintenance of cancer cell viability and undifferentiated state for a variety of tumor types. (Dannappel et al. 2019;Rzymski et al. 2015;Philip et al. 2018). RVU120 (SEL120), a novel CDK8/CDK19 kinase inhibitor with significant efficacy in preclinical AML models, has shown clinical efficacy in a currently ongoing phase Ib trial in patients with relapsed/refractory (R/R) AML or HR-MDS (NCT04021368). This paper provides update with new available data on disease evaluation from ongoing patients and further enrolment into next cohort level 85 mg. Aims: The primary objective of the study is to determine preliminary safety profile, dose limiting toxicities (DLTs), maximum tolerated dose (MTD) and the recommended phase 2 dose of RVU120 as a single agent. Secondary objectives include PK, antileukemic activity and exploratory PD characterization. Methods: The study comprises at least 7 dose escalating cohorts. The first 3 cohorts followed an accelerated scheme, 1 patient enrolled/cohort from 10 to 50 mg dose levels, from cohort 4 (75 mg) to 7 (100 mg) doses onwards a 3+3 design is followed. Data from each cohort is evaluated by a data review committee (DRC). RVU120 is administered orally every other day, for a total of 7 doses, in a 3-week treatment cycle until disease progression/unacceptable toxicity. Adverse events are graded according to NCI-CTCAE v.5.0. DLTs are assessed at completion of C1. Disease evaluation is performed according to Dohner 2017 and Cheson 2006 response criteria for AML and MDS respectively. PK parameters are calculated by non-compartmental analysis. Pharmacodynamic (PD) activity is assessed by flow cytometry measure of pSTAT5 Ser725 levels, that are highly dependent on the activity of CDK8 and CDK19 in AML/MDS cells. Results: At data cut off of 23rd Feb22, 13 pts have been enrolled, median age 73 years and median 2 previous lines of therapy, ECOG PS 2 in 4 pts, 1 in 7, 0 in 2. No DLTs were observed, all 14 Serious Adverse Events, including 1 COVID19 death and 1 pancreatitis, were not related to study drug (G1 fever, G2 Upper Respiratory Infection, G3: pseudomonas sepsis;urinary tract infection;febrile neutropenia;lung infection, pain, hemoptysis, pleural effusion, G5 pneumonitis, death NOS, pancreatitis). Cohort 1 pt, 10 mg dose level, and cohort 2 pt, 25 mg, showed stable (SD) and progressive disease (PD) respectively at the end of C1. Cohort 3 pt, an 81 YO male HR-MDS, escalated from 50 to 75 mg dose from C7, is SD at C24D13 with Erythroid Hematological Improvement on C5, C7, C10, C18. Cohort 4, 75 mg dose pt, a 62 YO male with AML DNMT3A pos, relapsing after Ven/Dec, achieved CRi at the end of C1 and CR in C7, and progressed at the end of C8. Two out of the remaining 4 pts treated at 75 mg reached SD (1 still ongoing at C3D15 and another died on C3D20 while on SD), 1 pt died of COVID-19 pneumonitis on C1D18, 1 pt with AML secondary to MPN was SD at C2 and progressed on C4. Two pt were treated at 110 mg (cohort 5), 1 not evaluable died for pancreatitis and 1 was SD at the end of C1. 2 pt entered cohort 6, 85 mg, and will be evaluable at the end of March 2022. Summary/Conclusion: Preliminary results from the first 6 cohorts have shown a favorable safety and a predictable PK profile of RVU120. Meaningful PD activity and clinical efficacy were observed at 50 and 75 mg doses. Enrollment is currently ongoing at 85 mg cohort.