Upskilling haematological services for WGS and germline assessments through a regional skin biopsy training programme

NHS England Genomics introduced whole genome sequencing (WGS) with standard-of- care (SoC) genetic testing for haemato-oncology patients who meet eligibility criteria, including patients with acute leukaemia across all ages, and exhausted SoC testing. Alongside, the role of germline mutations in haematological cancers is becoming increasingly recognised. DNA samples are required from the malignant cells (somatic sample) via a bone marrow aspirate, and from non-malignant cells (germline sample) for comparator analysis. Skin biopsy is considered the gold-standard tissue to provide a source of fibroblast DNA for germline analysis. Performing skin punch biopsies is not within the traditional skillset for haematology teams and upskilling is necessary to deliver WGS/germline testing safely, independently and sustainably. A teaching programme was designed and piloted by the dermatology and haematology teams in Sheffield and delivered throughout the NHS trusts in North East & Yorkshire Genomic Laboratory Hub. The training programme consisted of a 90-min session, slides, video and practical biopsy on pork belly or synthetic skin, designed to teach up to six students at one time. To disseminate best practice, the standard operating procedure and patient information used routinely in Sheffield were shared, to be adapted for local service delivery. From January 2021 to December 2022, 136 haematology staff from 11 hospitals, including 34 consultants, 41 registrars, 34 nurses and 8 physician associates, across the NEY GLH region completed the skin biopsy training programme. Feedback from the course was outstanding, with consistently high scores in all categories. Practical components of the course were especially valued;98.6% (71/72) trainees scored the practical element of the programme a top score of 5 out of 5, highlighting that despite the challenges of delivering face-to- face teaching due to COVID-19, teaching of practical skills was highly valued;training in this way could not have been replicated virtually. Costs of the programme have been approximately 16 000, including consultant input and teaching/educational materials. Recent support has been provided by a separately funded Genomic Nurse Practitioner (GNP), with succession planning for the GNP to take over leadership from the consultant dermatologist. Plans are in place to use the remaining budget to disseminate the programme nationally. Our training programme has shown that skin biopsy can be formally embedded into training for haematology consultants, trainees, nursing team, and physician associates. Delivery of training can be effective and affordable across regional GLHs with appropriate leadership and inter-speciality coordination, and ultimately sustainable with specialist nursing staff, including GNPs.

Clinical profile and outcomes of COVID-19 infection during the first wave in children with hematological illnesses and cancer: An observational study from a tertiary care center in North India

Background: Patients with cancer are at a higher risk of getting infected with the severe acute respiratory syndrome coronavirus 2 owing to their immunocompromised state. Providing care to these patients amidst the first wave of the coronavirus disease-2019 (COVID-19) pandemic was extremely challenging. Objective(s): This study was aimed at evaluating the clinical profile and disease-related outcomes of pediatric patients with hematological illnesses and cancer. Material(s) and Method(s): This retrospective study was conducted at a tertiary care center in North India during the first wave of the pandemic from March 2020 to December 2020. Children aged up to 18 years, who were treated for a hematological illness or malignancy or underwent hematopoietic stem cell transplantation (HSCT) and tested positive for COVID-19 regardless of symptoms were included in the study. Baseline demographic data related to the age, diagnosis, treatment status, and chemotherapy protocol used were collected. Outcomes including the cure rates, comorbidities, and sequelae were recorded. Result(s): A total of 650 tests for COVID-19 were performed for 181 children;22 patients were found to be COVID-19 positive. The most common diagnosis was acute leukemia (63.6%). None of the patients developed COVID-19 pneumonia. The majority of patients had asymptomatic infection and were managed at home. Among those with a symptomatic infection, the most common symptoms were fever and cough. A total of 3 (13.6%) patients needed oxygen therapy, one developed multisystem inflammatory syndrome of children leading to cardiogenic shock. Three patients required intensive care or respiratory support;all the patients had favorable clinical outcomes. The median time from the onset of COVID-19 to a negative result on the reverse transcription-polymerase chain reaction test was 21.3 days. Cancer treatment was modified in 15 patients (68.2%). Conclusion(s): Our results suggest that children with hemato-oncological illnesses rarely experience severe COVID-19 disease. The impact of the first wave of COVID-19 primarily manifested as disruptions in the logistic planning and administration of essential treatment to these children rather than COVID-19 sequelae.Copyright © 2021 Cancer Research, Statistics, and Treatment Published by Wolters Kluwer - Medknow.

Covid-19 Vaccine-Induced Myositis

Background/Aims Through the COVID pandemic there have emerged reports of autoimmunity or new rheumatic diseases presenting in patients after they had COVID-19. This is thought to be caused by cross-reactivity of the COVID-19 spike protein to human antigens. Given the use of mRNA COVID-19 vaccinations which express the spike protein we might expect to see presentation of new rheumatic diseases following their use. We discuss a case where this appears to have occurred. Methods Our patient is a 24-year-old male with mixed phenotype acute leukaemia who had been treated with allogenic stem cell transplant and was currently in remission. He presented with fevers, palpitations, myalgia and bilateral arm and leg swelling. Symptoms began the day after receiving the first dose of an mRNA COVID-19 vaccination (Pfizer/BioNTech.) There were no other symptoms or recent change in medications. Physical examination revealed tender oedema in his forearms, biceps and thighs bilaterally with sparring of the hands. He had reduced power with shoulder (MRC 3/5), elbow (4), wrist (4+) and hip (4) movements. Observations revealed tachycardia and fevers up to 40C. Results Laboratory studies showed markedly elevated C-reactive protein (202), creatinine kinase (6697) and troponin (593) whilst investigations for infection were negative. An autoimmune panel was positive for anti- PM-SCL-75-Ab. An electrocardiogram showed sinus tachycardia. Echocardiogram was normal. Bilateral upper limb dopplers revealed no deep vein thrombus. An MRI of his thighs showed diffuse symmetrical oedema within the muscles, in keeping with an inflammatory myositis. A quadricep muscle biopsy showed evidence of MHC class 1 up-regulation, suggesting an inflammatory process. In addition, there were numerous macrophages evident in the endomysium. While this can be seen in graft-versus-host disease (GVHD), they would usually be found in the perimysium. After discussion between haematology, rheumatology and neurology, this was felt to be a case of vaccine induced myositis and myocarditis. Autoimmune myositis was thought to be less likely due to the relative sparing of the hands and the absence of Raynaud's phenomenon. 1 gram of intravenous methylprednisolone was then given for 3 days. The patient had a marked response with defervescence, improving laboratory markers, improved myalgia and decreased limb swelling. The patient was stepped down to a reducing regime of prednisolone and discharged. Due to relapse whilst weaning he has started on mycophenalate mofetil and rituximab and now continues to improve. Conclusion There are case reports of myositis following COVID-19 vaccination but our patient's case is complicated by the differential diagnosis of GVHD and concurrent myocarditis. Ongoing work is needed to clarify the exact link between vaccination and the presentation of a new inflammatory myositis, but it is important to recognise and start treatment early in order to preserve muscle bulk and ensure recovery.

Cryopreservation for Allogeneic Hematopoetic Stem Cell Transplants Is Non-Inferior to Fresh Graft Products

Background: The use of cryopreservation for stem cell grafts for both autologous stem cell and allogeneic cord blood transplant has been utilized for years. For other allogeneic stem cell transplant sources, the use of fresh collected grafts has been preferred due to concerns that cryopreservation may result in impaired graft function. With the onset of the COVID-19 pandemic a shift was made at our institution to exclusive use of cryopreservation Methods: In this retrospective single-center analysis a total of 133 patients undergoing allogeneic stem cell transplant at the University of Minnesota between 1/2018-6/2021 for a variety of malignancies were included, with 62 patients receiving fresh stem cell product and 71 patients receiving frozen stem cell product. Univariate statistical analysis was performed. Result(s): There was no significant difference between the two groups with regards to product type, sex, age, diagnosis (acute leukemia vs other), disease risk index, conditioning regimen, Karnofsky score, co-morbidity index, or cell dose (Table 1). Donor type was notably different between the two groups (p<0.01): matched sibling grafts were more commonly used for fresh products than frozen (85% vs. 35%), while matched unrelated donors were used more frequently for frozen than for fresh products (54% vs. 6%). Use of frozen product was associated with delayed neutrophil and platelet engraftment compared to fresh (median days to engraftment 15 vs 12 for neutrophils, 23 vs 17 for platelets, p<0.01 for both). Two-year relapse rates were significantly lower for frozen products (4%) than fresh (24%) (Table 2). This may be partially attributable to differences in follow up between the groups, as fresh products had a total of 910 days of follow up vs 432 for frozen products (P<0.0001). The difference in follow up remained statistically significant if the data was censored at 730 days (P<0.0001). Of note, the use of frozen products was associated with a lower rate of chronic graft-versus-host disease at one year post-transplant (p<0.01). There was no significant difference in the rates of acute GVHD between the groups. There were significant differences in GVHD prophylaxis regimens between the fresh and frozen groups (p<0.01). (Figure Presented)Two-year overall survival did not differ between groups (p=0.96). Conclusion(s): Use of cryopreserved stem cell products is associated with similar efficacy and outcomes as those seen with the use of fresh stem cell products. Although the data presented here suggest novel finding of decreased risk of relapse and chronic GVHD with the use of frozen stem cell products, additional follow up may abrogate these differences. Regardless, the logistical benefits of cryopreservation make this an attractive option for continued use in allogeneic transplants and our data presented here suggests that cryopreserved products remain an appropriate option for allogeneic stem cell transplant.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

COVID-19 infection in hematopoietic stem cell transplant recipients.

Objective. To assess the course and outcomes of COVID-19 in recipients of allogeneic and autologous hematopoietic stem cell transplant (HSCT). Materials and methods. The retrospective study included 44 adult recipients (allogeneic - 33 [75%] and autologous - 11 [25%] of HSCT who diagnosed with COVID-19 after transplantation. Group mostly represented by acute leukemia - 18 (41%) and lymphoma - 10 (22.7%). The median follow-up time since the development of COVID-19 was 231 days (1-818 days), after HSCT - 507.5 days (14-3723 days). Overall and progression-free survival was assessed using the Kaplan-Meier and Log-Rank method. We also evaluated the characteristics of the course of a new coronavirus infection. Results. Median time for the development of COVID-19 from the moment of HSCT was 122.5 days (-1-3490 days). Twelve patients (27.2%) were in grade 3-4 neutropenia at the time of COVID-19 diagnosis, 16 (36.4%) patients were in grade 1-2 neutropenia. Sixteen (48.4%) allo-HSCT recipients had active graft-versus-host disease (GVHD) at the time of COVID-19 development. Disease severity was mild in 19 (43.2%) and moderate in 13 (29.5%) patients. Overall, 200-day survival from the onset of COVID-19 was 78.8% (95% CI [63.1-88.4]). Anemia (p = 0.02) and thrombocytopenia (p = 0.01) significantly decrease OS in patients with COVID-19 after HSCT. Patients with GVHD at the time of COVID-19 onset had a better survival rate (p = 0.02). The timing of COVID-19 development after HSCT did not affect outcomes. Conclusions. The key points of the course of COVID-19 in HSCT recipients are the presence of cytopenia and graft-versus-host disease. Overall survival was 78.8%.Copyright © 2022, Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy. All rights reserved.

Mucormycosis: Modern diagnostics and treatment, existing problems and new trends in antifungal therapy.

Over the last decade, the introduction of new antifungal drugs and diagnostic procedures has improved the prognosis of hematological patients with invasive fungal disease (IFD), primarily invasive aspergillosis. Despite effective antifungal prophylaxis against the most common IFD caused by Aspergillus spp., rates of IFD due to rare pathogens being resistant to most antifungal drugs, including mucormycosis have been increased. The main group of patients having a high risk of mucormycosis is deeply immunocompromised patients who received chemotherapy for acute leukemia, patients undergoing allogeneic bone marrow transplantation, or treated with corticosteroids for graft-versushost disease. Currently, the urgency of this complication is significantly higher due to COVID-19 pandemic and extensive use of corticosteroids for the treatment of COVID-19. Despite the fact that the criteria for the diagnosis of IFD EORTC/MSG 2008 and 2020 have been developed and implemented into practice in most countries, mucormycosis still remains a difficult-to-diagnose IFD, where the factor of rapid diagnosis is a main factor of treatment success. Medications available for the treatment of IFD include polyenes, triazoles, and echinocandins. For a long time, the drug of choice for the treatment of mucormycosis was liposomal amphotericin B. However, a new effective drug has been approved for the treatment of both mucormycosis and IFD, caused by multiple pathogens - isavuconazole. This review presents new data on the epidemiology of mucormycosis, diagnosis approaches and current international treatment guidelines.Copyright © 2021, Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy. All rights reserved.

Younger Age as a Predictor of Mortality from COVID-19 in Hematological Patients

Background: Determination of predictors of mortality from COVID-19 is important. In general older people have a greater risk of death from COVID-19. The study aimed to investigate whether age is a risk factor of mortality in patients (pts) with hematological diseases. Material(s) and Method(s): Retrospective analysis of medical cards of pts with hematological diseases and confirmed by PCR test COVID-19 in 2020-2021 at the City Hematology Center (Dnipro, Ukraine) was conducted. Result(s): The study included medical cards of 56 pts. 35 (62.5%) women, median age 60 (47-65.5) years. The overall mortality was 35.7%. According to ROC-analysis the age 55 years and less (23 pts) was statistically significant in mortality prediction, with sensitivity 70% and specificity 75%, AUC 0.74, p=0.002. Mortality rate was 60.9% in group of "younger" pts VS 18.2% in another group (p=0.001). Then we compared the profile of hematological diseases in these pts and have identified that they more often had acute leukemia-in 47.8% VS 12.1% in another group (p=0.003) but less common had multiple myeloma - 0% VS 30.3%, p=0.004. Other diseases were equally common. Among key indicators in CBC test, Hb was lower in "younger" pts - 81 (70-98) g/l VS 103.5 (81-122.5) g/l, (p=0.03). However, HB alone has not been shown to be predictor of mortality (p=0.2 by logistic regression). Other indicators were statistically equal. Conclusion(s): Hematologic pts younger than 55 years of age have a higher risk of death from COVID-19, which is most likely due to the higher prevalence of acute leukemia among them. This category of pts requires proactive management tactics even in case of a mild onset of COVID-19.

Atypical presentation of covid-19 as acute leukemia: A case report

In the absence of respiratory system involvement, COVID-19 patients developing ARDS can clinically mimic other diseases including acute leukemia due to presence of atypical lymphocytes in peripheral blood smear and increased serum lactate dehydrogenase and serum uric acid levels. Herein, we report a case who was initially suspected to have acute leukemia based on his atypical symptoms without any respiratory system involvement and deranged laboratory parameters and finally, diagnosed with COVID-19. Our patient presented with fever, myalgia, gum bleed, and petechiae. On clinical and laboratory evaluation, he was suspected to have acute leukemia based on markedly deranged serum lactate dehydrogenase and serum uric acid and the presence of atypical cells in peripheral blood smear and bone marrow. On day 3 of hospitalization, he developed respiratory symptoms, breathing difficulty which progressed to ARDS, and subsequently, he succumbed to his illness. His real-time reverse transcriptase-polymerase chain reaction test for severe acute respiratory syndrome coronavirus-2 yielded positive results. Also, Flow cytometry and fluorescence in situ hybridization studies for leukemia workup did not show any abnormalities. Although we are reporting the findings of only a single case, we aim to enhance and contribute further to the understanding of this novel infection.Copyright © 2021 Necati Ozpinar. All right reserved.

COVID-19 Severity and Survival over Time in Patients with Hematologic Malignancies: A Population-Based Registry Study.

Mortality rates for COVID-19 have declined over time in the general population, but data in patients with hematologic malignancies are contradictory. We identified independent prognostic factors for COVID-19 severity and survival in unvaccinated patients with hematologic malignancies, compared mortality rates over time and versus non-cancer inpatients, and investigated post COVID-19 condition. Data were analyzed from 1166 consecutive, eligible patients with hematologic malignancies from the population-based HEMATO-MADRID registry, Spain, with COVID-19 prior to vaccination roll-out, stratified into early (February-June 2020; n = 769 (66%)) and later (July 2020-February 2021; n = 397 (34%)) cohorts. Propensity-score matched non-cancer patients were identified from the SEMI-COVID registry. A lower proportion of patients were hospitalized in the later waves (54.2%) compared to the earlier (88.6%), OR 0.15, 95%CI 0.11-0.20. The proportion of hospitalized patients admitted to the ICU was higher in the later cohort (103/215, 47.9%) compared with the early cohort (170/681, 25.0%, 2.77; 2.01-3.82). The reduced 30-day mortality between early and later cohorts of non-cancer inpatients (29.6% vs. 12.6%, OR 0.34; 0.22-0.53) was not paralleled in inpatients with hematologic malignancies (32.3% vs. 34.8%, OR 1.12; 0.81-1.5). Among evaluable patients, 27.3% had post COVID-19 condition. These findings will help inform evidence-based preventive and therapeutic strategies for patients with hematologic malignancies and COVID-19 diagnosis.

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.

Clinical course and impact on oncological care of COVID-19 in patients with underlying malignant diseases: First results of the prospective, observational COVIDHELP trial of the University Cancer Center Hamburg (UCCH)

Introduction: The COVID-19 pandemic afects everyday life, hospital infrastructures and cancer care worldwide and in Germany. While current infection rates nationwide are decreasing, a continuous long-term infection rate is expected until vaccine development. First data from China suggested that cancer patients are particularly susceptible and at higher risk of a severe course of the disease. Despite more data being available now, many open questions remain regarding the course of COVID-19 in cancer patients and the impact of cancer treatment. To prospectively address these questions, we initiated a multicentric, observational trial including cancer patients with COVID-19 in the Hamburg metropolitan region and parts of Schleswig-Holstein. Method(s): Patients with diagnosis of cancer and COVID-19, who were treated in the University Cancer Center Hamburg (UCCH), its contracted partner network or at the University Cancer Centers Kiel and Lubeck are included into the trial, which was initiated in April 2020. Data are collected as available from routine clinical care and include demographic and biometric data, medical history, baseline infection data at inclusion as well as inpatient and intensive care unit admissions. Upon consent, patients provide peripheral blood samples for a prospective biobanking with the aim of investigating immune response, immunity and predictive outcome markers. Recruitment is planned for a one-year period. Result(s): As of June 30th 2020, 17 patients of which 13 were male were included afer signing informed consent. Median age was 64 years. 12 of the 17 patients had hematologic disease, mostly acute leukemia. Two patients had solid tumors and three patients had both hematologic and solid malignancy. In 71 % of included patients COVID-infection was diagnosed while being hospitalized due to their oncologic disease. Five patients required mechanical ventilation in the course of disease, one patient died due to the infection. Updated data will be presented at the meeting. Conclusion(s): The prospective registrational COVIDHELP trial will continuously include patients with malignant diseases and COVID-19 during the current pandemic. Our analysis will help to better understand the clinical course, potential impact of intrinsic and extrinsic factors as well as immune response to COVID-19 infection in cancer patients and thus facilitate clinical decision making concerning therapy discontinuation and identifcation of subgroups at specific risk.

CLABSIs in the Time of COVID

Background. With the COVID-19 pandemic, acute care facilities experienced an initial increase in hospital-acquired infections, most notably Central Line-Associated Bloodstream Infections (CLABSIs). Interestingly, the positive correlation between COVID-19 and CLABSIs appeared to wane post surge. We sought to define the pre and post-pandemic CLABSI rates. Methods. Single-center, retrospective review of the CLABSIs reported to the National Healthcare Safety Network (NHSN) for the five years previous to COVID and through to the First Quarter of 2022. Our center is a quaternary care, level 1 trauma center in New York, which serves a highly ill critical care population, including solid organ and bone marrow transplants, acute leukemias, and patients requiring extracorporeal membrane oxygenation (ECMO). Results. Between January 2015 and December 2019, our Medical Intensive Care Unit (MICU) reported 15 CLABSIs with an overall Standardized Infection Ratio (SIR) of 1.007. During the second winter surge of COVID, we saw a sharp rise in CLABSIs. Between October 2020 and March 2021, our MICU reported eight CLABSIs, with an overall SIR of 4.601 and a p-value of 0.0005 (CI 2.137 - 8.737), representing a statistically significant increase (p-value 0.0019) in comparison to prior years. Of these patients, seven had COVID. All patients received high-dose steroids. The average number of days between hospital admission to CLABSI was 16.38 days, and mortality was 87.5%. Since that spike in CLABSI, we have reported seven CLABSIs in NHSN for a SIR of 2.026. After 2019 patients with CLABSI tended to be younger and had a higher Body Mass Index. Conclusion. We reported a spike in CLABSIs in our adult medical Intensive Care during the second wave of COVID-19 that affected the Northeast United States in the winter of 2020/2021. Despite experiencing a sharp rise, our CLABSI rates are returning to pre-pandemic low levels even during subsequent surges in COVID-19, including the recent Omicron surge. It remains to be determined if the improvements in infection control measures, differences in the patient illness severity, and/or variations of COVID management have contributed to the stabilization of the CLABSI rate.

Chemotherapy of hematological malignancies in patients with COVID-19

In the era of COVID-19, the chemotherapy of patients with hematological malignancies has become the cornerstone in hematology. Secondary immunodeficiency as a result of hemoblastosis, predisposes to a more severe course of coronavirus infection, and specific antitumor treatment only exacerbates patients immunodeficiency. Thus, there is a problem of conducting chemotherapy during the COVID-19 pandemic. At the moment, there are no unified recommendations for risk assessment and choice of treatment for patients with oncohematological diseases and concomitant coronavirus infection. In this article, we present a series of clinical cases of patients with hematological malignancies diagnosed with coronavirus infection at the onset of a hematological disease or after chemotherapy. Patients with long-term persistent coronavirus infection requiring specific anticancer treatment were allocated to a separate group. We hope that this article will help to set a vector for further research, as well as serve as a clear example of the clinical situations that a hematologist may face during the COVID-19 pandemic. Copyright © 2022 ABV-Press Publishing House. All rights reserved.

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;

DOES COVID-19 INCREASE YOUR RISK OF DEVELOPING HAIRY CELL LEUKEMIA?

SESSION TITLE: Pathology Identifying Chest Infections Case Report Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Coronavirus disease 2019 (COVID-19) patients presented in a wide variety and had multiple complications. The well-known associations found are myocardial infraction, pulmonary embolism, meningitis, encephalitis. We are presenting a new diagnosis of Hairy cell leukemia in COVID 19 patients. CASE PRESENTATION: We present a 55-year-old pleasant female with no significant past medical history;non immunocompromised who presented with 7 days history of shortness of breath on exertion, fever, fatigue, and cough. Her physical exam was unremarkable, but she was desaturating on presentation hence was placed on oxygen via nasal canula. On work up she tested positive for COVID-19. Initial chest Xray revealed bilateral diffuse pulmonary infiltrates. Complete blood count (CBC) showed pancytopenia with white blood cell count (WBC) 0.8 × 103/μL (4–10 × 103/μL), absolute neutrophil count (ANC) 0.5 × 103/μL (2–7 × 103/μL), hemoglobin (Hgb) 10.4 g/dL (13.0–17.0 g/dL), and platelet count 156× 103/μL (150–400 × 103/μL). She received treatment for COVID 19 pneumonia as per the protocol. On repeat CBC check there was minimal improvement in her counts. The rest of her WBC differential showed a lymphopenia with ALC ranging from 350–500 with no other obvious immature cells or blasts to suggest a myeloid neoplasm such as acute leukemia. Work-up including vitamin B12, folate, TSH, EBV, ANA, and hepatitis were unremarkable. She also received treatment with supportive granulocyte colony-stimulating factor (G-CSF) but there was minimal improvement. As her pancytopenia persisted for 1 week the peripheral blood smear was done which showed pancytopenia (with prominent red cell agglutination, with rare, atypical lymphoid cells with multiple hairy projections. A bone marrow (BM) aspirate was hypocellular showing markedly decreased trilineage hematopoiesis with atypical lymphoid cells with oval or indented nuclear borders, unclumped chromatin, absent or inconspicuous nucleoli, and moderate to abundant pale blue cytoplasm with multiple circumferential cytoplasmic projections (hairy cells) [Figure:1]. The hairy cells showed strong positivity for CD20[Figure:2]. She was followed up by hematology and was started on treatment. DISCUSSION: Hairy cell leukemia (HCL) is a rare B cell lymphoproliferative disease with marked cytopenia and circulating leukemia cells. Multiple viruses (EBV, HTLV1) were found to be associated with multiple different malignancies. It is found that COVID19 is not associated with any malignancy so far, but our patient got diagnosed with HCL during COVID19 illness. CONCLUSIONS: The association of HCL could be an incidental finding but we need to do further studies to clarify the associations Reference #1: Kohla, Samah et al. "A Rare Case of Hairy Cell Leukemia with Unusual Loss of CD123 Associated with COVID-19 at the Time of Presentation.” Case reports in oncology vol. 13,3 1430-1440. 4 Dec. 2020, doi:10.1159/000512830 DISCLOSURES: No relevant relationships by Apurwa Karki No relevant relationships by Shobha Mandal No relevant relationships by Rajamurugan Meenakshisundaram

COVID-19 and Adult Acute Leukemia: Our Knowledge in Progress.

The majority of publications regarding SARS-CoV-2 infections in adult patients with acute leukemia (AL) refer to hematological patients in general and are not focused on acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL). We herein report a review of the current literature on adult AL patients infected with SARS-CoV-2. Overall, SARS-CoV-2-associated mortality ranges from 20-52% in patients with adult AL. AML patients have a particularly high COVID-19-related mortality. Of note, most of the available data relate to the pre-vaccination era and to variants before Omicron. The impact of COVID-19 infections on AL treatment is rarely reported. Based on the few studies available, treatment delay does not appear to be associated with an increased risk of relapse, whereas therapy discontinuation was associated with worse outcomes in AML patients. Therefore, the current recommendations suggest delaying systemic AL treatment in SARS-CoV-2-positive patients until SARS-CoV-2 negativity, if immediate AL treatment is not required. It is recommended to offer vaccination to all AL patients; the reported antibody responses are around 80-96%. Seronegative patients should additionally receive prophylactic administration of anti-SARS-CoV-2 monoclonal antibodies. Patients with AL infected with SARS-CoV-2 should be treated early with antiviral therapy to prevent disease progression and enable the rapid elimination of the virus.

Seroconversion to mRNA SARS-CoV-2 Vaccines in Hematologic Patients.

Hematologic patients show lower responses to SARS-CoV-2 vaccines, but predictors of seroconversion are lacking. In this prospective cohort study, hematologic patients undergoing SARS-CoV-2 mRNA vaccination at a single center in Milan, Italy, were sampled for anti-Spike and anti-Nucleocapsid IgG titer at 5 ± 1 weeks and at 3 months from the second vaccine dose. Patients (N = 393) received either BNT162b2 (Pfizer-BioNTech, 48%) or MRNA-1273 (Moderna, 52%), and 284 (72%) seroconverted and 100% persisted at 3 months. Non-response was higher in chronic lymphocytic leukemia (CLL) and lymphoma patients, and in those treated with small molecules and monoclonal antibodies. In myeloid neoplasms, lower responses were detected in patients with acute myeloid leukemia treated with venetoclax plus hypomethylating agents and in patients with myelofibrosis receiving ruxolitinib. Multivariable analysis showed that seroconversion was favorably associated with a diagnosis other than indolent lymphoma/CLL [OR 8.5 (95% CI 4.1-17.6)], lack of B-cell-depleting therapy [OR 3.15 (1.7-5.9)], and IgG levels within the normal range [OR 2.2 (1.2-4.2)]. We developed a simple algorithm according to these 3 risk factors [(A) diagnosis of indolent lymphoma/CLL, (B) B-cell-depleting treatment, and (C) low IgG] to predict non-response. IgG levels and treatment may be modifiable risk factors and should be considered for timing of vaccine administration.

A Case Series of SARS-CoV-2 Omicron Variant in Patients With Acute Leukemia.

Coronavirus disease 2019 (COVID-19) is a respiratory viral illness caused by coronavirus 2 (SARS-CoV-2). The disease often presents with non-specific symptoms, including fever, and fatigue, usually associated with respiratory symptoms (eg., cough) and other systemic involvement. The primary strategy to prevent transmission and reduce the disease severity of the SARS-CoV-2 infection is through vaccination. However, the virus had shown significant changes and mutations that resulted in the emergence of different strains. Each strain varies in its virulence, disease severity, and the body's immune system response. Previous reports showed that the Omicron variant causes mild disease. Little is known about the effect of Omicron in patients with acute leukemia. We present three patients with acute leukemia who had an infection with the Omicron variant of the SARS-CoV-2 virus.

IONA - Interdisciplinary Oncological Follow-Up Clinic in Vienna

Introduction: Cancer in childhood and adolescence can be cured in many cases nowadays. In Vienna, patients are treated either in the St. Anna Children's Hospital or at the University Clinic for Pediatrics and Adolescent Medicine (Neuro-Oncology). Short-term follow-up is usually performed in the children's hospitals. Afterwards patients had to organize the necessary examinations themselves for many years. This so-called transition was not successful in many cases, as the detection and treatment of therapy and disease-associated secondary diseases requires appropriate expertise. Methods: “IONA - Interdisciplinary Oncological Follow-Up Clinic” is now offering age-appropriate, medical and psychosocial long-term follow-up since the beginning of 2020. A team of one experienced hemato/oncologist, two clinical psychologists and a social worker are offering the so-called “survivors” a specialized care, including medical check-ups tailored to the treatment and advices on risk fac-tors in order to identify and treat possible late effects early on. In addition, there is psychosocial care and, if necessary, neuropsycho-logical diagnostics. The health center where IONA is located also offers an optimal multi-professional network for this group of pa-tients. Results: More than 300 survivors have been transitioned since IONA started in early 2020. The majority of them suffered from CNS tumor, acute leukemia or lymphoma and were assigned directly by the hospitals, which guarantees continuous care. There is also reg-ular exchange between the attending physicians as well as the psy-chologists, social workers and administrative employees. During the COVID pandemic, video and audio telephony were also used to hold joint conversations. Conclusions: IONA offers interdisciplinary, standardized long-term follow-up care for patients from the age of 18 who had a hemato/oncologic disease in their childhood, adolescence or young adulthood and who have completed their medical therapy and short-term follow- up care at the responsible clinic. IONA accompanies patients in their transition process through close cooperation with the referring hospitals.