Re-humanisation, Recognising the person behind the patient

Submission content Introduction: At the end of a particularly hectic night shift on the intensive care unit (ICU) I found myself sitting in the relatives' room with the mother and aunt of a young patient, listening to their stories of her hopes and aspirations as she grew up. She had been diagnosed with lymphoma aged 14 and received a bone marrow transplant from her younger sister. Fighting through treatment cycles interposed with school studies, she eventually achieved remission and a portfolio of A-levels. Acceptance into university marked the start of a new era, away from her cancer label, where she studied forensic science and took up netball. Halfway through her first year she relapsed. Main body: When I met this bright, ambitious 20-year-old, none of this history was conveyed. She had been admitted to ICU overnight and rapidly intubated for type-1 respiratory failure. The notes contained a clinical list of her various diagnoses and treatments, with dates but no sense of the context. Rules regarding visitation meant her family were not allowed onto the unit, with next-of-kin updates carried out by designated non-ICU consultants to reduce pressures on ICU staff. No photos or personal items surrounded her bedside, nothing to signify a life outside of hospital. She remained in a medically-induced coma from admission onwards, while various organ systems faltered and failed in turn. Sitting in that relatives' room I had the uncomfortable realisation that I barely saw this girl as a person. Having looked after her for some weeks, I could list the positive microbiology samples and antibiotic choices, the trends in noradrenaline requirements and ventilatory settings. I had recognised the appropriate point in her clinical decline to call the family in before it was too late, without recognising anything about the person they knew and loved. She died hours later, with her mother singing 'Somewhere Over the Rainbow' at her bedside. Poignant as this was, the concept of this patient as more than her unfortunate diagnosis and level of organ failure had not entered my consciousness. Perhaps a coping mechanism, but dehumanisation none-the-less. Conclusion(s): Striking a balance between emotional investment and detachment is of course vital when working in a clinical environment like the ICU, where trauma is commonplace and worst-case-scenarios have a habit of playing out. At the start of my medical career, I assumed I would need to consciously take a step back, that I would struggle to switch off from the emotional aspects of Medicine. However, forgetting the person behind the patient became all too easy during the peaks of Covid-19, where relatives were barred and communication out-sourced. While this level of detachment may be understandable and necessary to an extent, the potential for this attitude to contribute to the already dehumanising experience of ICU patients should not be ignored. I always thought I was more interested in people and their stories than I was in medical science;this experience reminded me of that, and of the richness you lose out on when those stories are forgotten.

Fatal COVID-19 in an infant prompted an early diagnosis of ZNFX1 deficiency in a sibling

Background: NFX1-type zinc finger-containing 1 (ZNFX1) is an interferon-stimulated double-stranded RNA sensor that restricts the replication of RNA viruses in mice. ZNFX1 deficiency in humans is very rare;to date, only fifteen cases have been reported by Vavassori S et al. (10.1016/j.jaci.2021.03.045). The disease presented in all cases as severe viral infections complicated by multisystem inflammation evolved to multiorgan failure with a high mortality rate. Pediatric Allergy and Immunology Section at Queen Rania Children's Hospital in Jordan had confirmed the diagnosis of ZNFX1 deficiency in an infant at his first presentation with severe viral illness based on the positive family history of one sibling death caused by complicated COVID-19 infection. Case presentation: A 12-month-old boy was born to consanguineous parents, full-term, with no NICU admission. He was doing well till the age of four months when he was admitted to the hospital with fever, hypoactivity, and maculopapular skin rash. On admission, he was ill, hypoactive, and febrile, and a physical exam showed hepatosplenomegaly and maculopapular skin rash. His lab showed thrombocytopenia, elevated transaminases, hyperferritinemia, and high CRP;he was treated with broad-spectrum antibiotics, but he continued to deteriorate, and his infectious workup was unrevealing, including COVID-19 PCR. His older sibling died at eight months in 2020 when she got a COVID-19 infection, deceased after rapid deterioration evolved to multiorgan failure. Unfortunately, she had no stored DNA, as she was treated at a peripheral hospital. Based on this presentation and the fatal COVID-19 infection, pediatric immunology service got consulted;we did an immunological workup, which showed normal lymphocyte subsets, Immunoglobulins, and bacterial antibodies. Whole exome sequencing showed a homozygous frameshift mutation in the ZNFX1 gene, protein change defect had detected;p.Tyr555MetfsTer6, and nucleotide change variant: c.1663_1665delTACinsAT. Family screening showed heterozygous for the same variant in both parents and a healthy sibling. The patient was diagnosed with the hemophagocytic lymphohistiocytosis-like disease and treated with steroids, intravenous immunoglobulin, and antimicrobials, he showed complete recovery, and we are going to do bone marrow transplantation as his brother is 8/8 HLA matched.Copyright © 2023 Elsevier Inc.

Covid-19 Bivalent Booster Effectiveness in People with and without Immune Dysfunction

Background: Data on the effectiveness of the bivalent booster vaccine against COVID-19 breakthrough infection and severe outcomes is limited. Method(s): Using patient-level data from 54 sites in the U.S. National COVID Cohort Collaborative (N3C), we estimated bivalent booster effectiveness against breakthrough infection and outcomes between 09/01/2022 (bivalent vaccine approval date) to 12/15/2022 (most recent data release of N3C) among patients completed 2+ doses of mRNA vaccine. Bivalent booster effectiveness was evaluated among all patients and patients with and without immunosuppressed/compromised conditions (ISC;HIV infection, solid organ/ bone marrow transplant, autoimmune diseases, and cancer). We used logistic regression models to compare the odds of breakthrough infection (COVID-19 diagnosis after the last dose of vaccine) and outcomes (hospitalization, ventilation/ECMO use, or death <=28 days after infection) in the bivalent boosted vs. non-bivalent boosted groups. Models controlled for demographics, comorbidities, geographic region, prior SARS-CoV-2 infection, months since the last dose of non-bivalent vaccine, and prior non-bivalent booster. Result(s): By 12/15/2022, 2,414,904 patients had received 2+ doses of mRNA vaccination, 75,873 of them had received a bivalent booster vaccine, and 24,046 of them had a breakthrough infection. At baseline, the median age was 52 (IQR 36-67) years, 40% male, 63% white, 10% Black, 12% Latinx, 3.5% Asian American/Pacific Islander, and 14% were patients with ISC. Patients received a bivalent booster were more likely to be female and had comorbidities. Bivalent booster was significantly associated with reduced odds of breakthrough infection and hospitalization (Figure). The adjusted odds ratios comparing bivalent vs. non-bivalent group were 0.28 (95% CI 0.25, 0.32) for all patients and 0.33 (95% CI: 0.26, 0.41) for patients with ISC. Compared to the nonbivalent group, the bivalent group had a lower incidence of COVID-19-related hospitalization (151 vs. 41 per 100,000 persons), invasive ventilation/ECMO use (7.5 vs. 1.3 per 100,000 persons), or death (11 vs. 1.3 per 100,000 persons) in all patients during the study period;the incidence of severe outcomes after bivalent boosting was similar among patients with and without ISC. Conclusion(s): A bivalent booster vaccine was highly effective against COVID-19 breakthrough infection and severe outcomes among patients received 2+ doses of mRNA vaccine and offered similar protection in patients with and without ISC. (Figure Presented).

Outcomes of Cryopreserved Vs Fresh Haploidentical Allogeneic Donor Grafts Using Post-Transplant Cyclophosphamide (PTCy) for Gvhd Prophylaxis

The World Health Organization (WHO) declared COVID-19 a pandemic in March 2020. Since then, logistical challenges arose regarding the procurement of allogeneic (allo) hematopoietic stem cell (HSC) donor grafts. Little data was available on transplant outcomes using cryo haploidentical (haplo) HSC grafts with post-transplant cyclophosphamide (PTCy) for GVHD prophylaxis. We retrospectively analyzed patients who received a first PTCy-based haplo hematopoietic stem cell transplant (Haplo HCT) at a single outpatient transplant center between January 2015 and December 2021. We identified 294 patients, 179 received a fresh graft and 115 received a cryo graft (Table 1). Both cohorts were similar in terms of median age, diagnoses, HCT-CI score and DRI. Out of 179 fresh haplo grafts, 160 (89.4%) were from peripheral blood stem cells (PBSC) and 19 (10.6%) were bone marrow grafts (BM). There were no cryo BM grafts used. Conditioning intensity were similar amongst both cohorts, with 43% myeloablative, 41.9% non-myeloablative and 15.1% RIC regimens used for fresh Haplo HCT and 39.1% myeloablative, 42.6% non-myeloablative and 18.3% RIC cryo Haplo HCT. Median time to engraftment was 16 days for fresh Haplo HCT and 17 days for cryo HCT (p=0.18). Median time to platelet engraftment was 27 days for fresh Haplo HCT and 27.5 days for cryo HCT (p=0.96). Since March 2020, only 8 transplants performed at our institution were from fresh haplo HSC grafts. Cryo grafts performed after March 2020 accounted for 73 (63.5%) of 115 total cryo Haplo HCT performed in the period reviewed. Using a Cox model to evaluate the effect of graft type and adjusting for significant variables, we found no difference in overall survival (OS), disease free survival (DFS), non-relapse mortality (NRM) and relapse rates between fresh and cryo Haplo HCT performed (Figure 1). While we found no difference in grades III-IV aGVHD (Table Presented) (Figure Presented) between fresh vs cryo Haplo HCT, we found a statistically significant higher incidence of grades II-IV aGVHD (p=0.033). There was no difference in all-grade cGVHD (p=0.53) or moderate- severe cGVHD (p=0.86) (Figure 2).(Figure Presented) The National Marrow Donor Program (NMDP) released a statement requiring cryopreservation of unrelated donor grafts at the start of the COVID-19 pandemic. The cryopreservation of all types of allo HSC grafts has been adopted by many transplant programs including ours. Our results mimic a CIBMTR analysis published at the start of the pandemic, where survival outcomes using fresh vs cryo haplo HSC grafts with PTCy as GVHD prophylaxis were similar. Contrary to other reports, we did not see differences in graft failure or rates of cGVHD between fresh and cryo Haplo HCT. The use of cryopreserved HSC grafts for Haplo HCT with PTCy results in favorable outcomes in an outpatient transplant setting. Further studies are needed to determine the cost-effectiveness of this practice in the post-pandemic era.Copyright © 2023 American Society for Transplantation and Cellular Therapy

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.

Multisystem Imaging Recommendations/Guidelines: In the Pursuit of Precision Oncology

With an increasing rate of cancers in almost all age groups and advanced screening techniques leading to an early diagnosis and longer longevity of patients with cancers, it is of utmost importance that radiologists assigned with cancer imaging should be prepared to deal with specific expected and unexpected circumstances that may arise during the lifetime of these patients. Tailored integration of preventive and curative interventions with current health plans and global escalation of efforts for timely diagnosis of cancers will pave the path for a cancer-free world. The commonly encountered circumstances in the current era, complicating cancer imaging, include coronavirus disease 2019 infection, pregnancy and lactation, immunocompromised states, bone marrow transplant, and screening of cancers in the relevant population. In this article, we discuss the imaging recommendations pertaining to cancer screening and diagnosis in the aforementioned clinical circumstances.Copyright © 2023 Wolters Kluwer Medknow Publications. All rights reserved.

Enrollment Lessons from a Biological Assignment Study of Marrow Transplantation versus Standard Care for Adolescents and Young Adults with Sickle Cell Disease: Considerations for Future Gene and Cellular Therapy Trials.

We previously conducted a single-arm feasibility study (STRIDE1) of myeloablative bone marrow transplantation (BMT) in adolescents and young adults with sickle cell disease (SCD). The trial identified donors before entry, enrolled well, and found no unexpected regimen-related toxicity. Although many single-arm studies have been published, there are no controlled trials of either BMT or gene therapy in SCD. Therefore, we designed a comparative trial by biological assignment (available donor versus no donor). This multicenter National Institutes of Health-funded study (Blood and Marrow Transplant Clinical Trials Network 1503; STRIDE2) enrolled patients between 2016 and 2021 at 35 sites. Lagging recruitment led to study closure, and here we report the impediments to accrual. The BMT regimen and entry criteria were from STRIDE1, and 2-year survival was the primary endpoint. To minimize selection bias from prior HLA typing, STRIDE2 excluded individuals with previously identified donors. Accrual was stopped at 69% of target (138 enrolled; assigned 28 with donor, 96 with no donor). Barriers to enrollment included lower than expected frequency of HLA-matched related and unrelated donors; loss of enrollees owing to previously identified donors; conventional care arm dissuading some seeking BMT; challenging short-term endpoints in SCD, including incomplete documentation of sickle pain episodes; state Medicaid (primary insurers of SCD) denial of BMT coverage for adult SCD despite the study having secured Coverage with Evidence Development from the Center for Medicare & Medicaid Services; slowed accrual in 2019 to 2021 during the Coronavirus disease 2019 pandemic; and restriction of BMT resourcing for nonmalignant diseases by academic medical (cancer) centers. Social obstacles and access to BMT centers also limited entry, as did practitioner and participant concerns over suitability, cost, and toxicity. Planning for future controlled trials of curative therapy in SCD and other nonmalignant diseases likely will meet these enrollment challenges. Lessons from this trial may aid the development of future comparative studies. © 2022 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

Intestinal Carriage of Carbapenemase-Producing Enterobacteriaceae Members in Immunocompromised Children During COVID-19 Pandemic

Background: Hospital-acquired infection with carbapenem-resistant Enterobacteriaceae (CRE) is a global concern. The administration of antibiotics among the infected and non-infected immunocompromised children with SARS-CoV-2 is associated with an increased risk of intestinal CRE colonization and bacteremia during hospitalization. Objective(s): The present study aimed to detect the correlation between the intestinal colonization of carbapenemase encoding Enterobacteriaceae with SARS-CoV-2 infection and antibiotic prescription among immunocompromised children admitted to the oncology and Bone Marrow Transplantation (BMT) wards. Method(s): Stool samples were collected from the immunocompromised children, and the members of Enterobacteriaceae were isolated using standard microbiological laboratory methods. Carbapenem resistance isolates were initially characterized by the disc diffusion method according to CLSI 2021 and further confirmed by the PCR assay. SARS-CoV-2 infection was also recorded according to documented real-time PCR results. Result(s): In this study, 102 Enterobacteriaceae isolates were collected from the stool samples. The isolates were from Escherichia spp. (59/102, 57.8%), Klebsiella spp. (34/102, 33.3%), Enterobacter spp. (5/102, 4.9%), Citrobacter spp. (2/102, 1.9%), and Serratia spp. (2/102, 1.9%). The carbapenem resistance phenotype was detected among 42.37%, 73.52%, 40%, 50%, and 100% of Escherichia spp., Klebsiella spp., Enterobacter spp., Citrobacter spp., and Serratia spp., respectively. Moreover, blaOXA-48 (49.1%) and blaNDM-1 (29.4%), as well as blaVIM (19.6%) and blaKPC (17.6%) were common in the CRE isolates. SARS-CoV-2 infection was detected in 50% of the participants;however, it was confirmed in 65.45% (36/55) of the intestinal CRE carriers. The administration of antibiotics, mainly broad-spectrum antibiotics, had a significant correlation with the CRE colonization in both the infected and non-infected children with SARS-CoV-2 infection. Conclusion(s): Regardless of the COVID-19 status, prolonged hospitalization and antibiotic prescription are major risk factors associated with the CRE intestinal colonization in immunocompromised children. Copyright © 2023, Author(s).

IVAC Plus in the Time of COVID-19: An Imperfect Metric?

Background. Prior to the COVID-19 pandemic, the incidence of infection related ventilator associated complications plus possible ventilator associated pneumonias (IVAC+) was decreasing;however, as the number of COVID-19 hospitalizations increased, so did the number of IVAC+. Our goal was to investigate if there was a relationship between these two occurrences. Methods. This was a retrospective study at the Audie Murphy VA Hospital (ALMVA) from October 2017 to December 2021. ALMVA is a level 1A facility with 232 beds and an active bone marrow transplant program in San Antonio, Texas. This study included acute care COVID-19 hospitalizations per 10,000 bed days of care and IVAC+ per 1000 ventilator days. Monthly acute and intensive care COVID-19 hospitalization rates were correlated with IVAC+ rates using Pearson correlation for the overall study period and in the subgroup of COVID pandemic months (Mar 2020-December 2021). Results. During the overall study period, COVID-19 hospitalization rates were significantly associated with IVAC+ rates: acute care correlation 0.86 (p< 0.01) and intensive care correlation 0.33 (p=0.04). During the COVID-19 pandemic months, acute care COVID-19 hospitalizations but not intensive care COVID-19 hospitalizations, were correlated with IVAC+ (correlation 0.90, p< 0.01 and correlation 0.21, p=0.53, respectively). There were 0 IVAC+ before the pandemic months and this rose to 14 during (0 per 1000 ventilator days and 3.05 per 1000 ventilator days, respectively). All but 2 cases of IVAC+ had COVID-19. COVID-19 Hospitalizations and IVAC Plus, October 2017 to December 2021 A sharp increase in COVID-19 hospitalizations correlated with a rise in patients meeting criteria for IVAC Plus. Conclusion. The natural history of COVID-19 disease has presented challenges for IVAC+ monitoring. COVID-19 can cause persistent fevers and worsening oxygenation, and antibiotic use is common during periods of clinical deterioration. These factors can fulfill criteria for IVAC+. In this study, each IVAC+ case was traced for safety bundle compliance. These bundles were followed, along with conservative fluid management, low tidal volume ventilation, and sedation breaks. Patients met NHSN criteria for IVAC+ despite these measures and most had COVID-19. Given the common occurrence of IVAC+ in COVID-19 patients, futures studies are needed to define if IVAC+ are preventable in this population and whether IVAC+ surveillance has any value among COVID-19 patients. (Figure Presented).

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.

Cryptococcal disease in Covid-19 infection: Case series from South Texas

Background. Covid-19 infection is associated with a lack of immune resilience that may be magnified using immunomodulators to suppress the cytokine storm, facilitating the emergence of opportunistic infections. We describe five cases of cryptococcal infection complications among Covid-19 hospitalized patients. Methods. This was a retrospective cohort study based on chart review performed at the Audie Murphy Veteran Affairs Hospital from 8/2020 to 8/2021;a level 1A facility with 232 beds and an active bone marrow transplantation program. We included patients aged >= 18 with a diagnosis of Covid-19 and subsequent Cryptococcal infection based on cultures or antigen testing. Results. Our patients were all male with ages ranging between 64 to 80 years. Three had underlying type II diabetes, hypertension, and two had end-stage renal disease. Only one had underlying immunosuppression with hydroxychloroquine for rheumatoid arthritis and one had underlying cirrhosis. Four patients had disseminated disease/fungemia while one had localized pulmonary disease. All the cases had low CD4 counts (158-300) and low CD8 counts (92-290). Two of the fungemia cases were diagnosed by blood culture and the other two by serum cryptococcus antigen test. All the patients had received corticosteroids with or without remdesivir, while one received additional tocilizumab, one baricitinib and one convalescent plasma infusion. Four cases of fungemia received liposomal amphotericin B and three of them received additional flucytosine. The patient with cryptococcal pulmonary disease received only fluconazole. Four patients expired at 28 days after diagnosis, only one recovered and is still alive at 1-year follow up. Table 1. Case details. ESRD: end stage renal disease;DM-2: diabetes mellitus type ;HTN: hypertension;A-fib: Atrial Fibrillation;HFpEF: heart failure with preserved ejection fraction;PVD: peripheral vascular disease;RA: rheumatoid arthritis;PTSD: post traumatic stress disorder;BPH: benign prostatic hyperplasia;CAD: coronary artery disease;HLD: hyperlipidemia;CVA: cerebrovascular accident. Conclusion. Cryptococcus infection has been described among patients with Covid-19 during the pandemic. This may be due to immunosuppression caused by the Covid-19 infection and its related-treatments. Most of our patients presented with disseminated cryptococcus infection complicating covid-19 with resulting high mortality rates. Low CD4/CD8 counts and corticosteroid use were documented in all cases. Further studies are needed to better characterize at-risk patients for cryptococcal infection that may benefit from cryptococcal prophylaxis.

A nationwide intervention to improve pneumococcal vaccination rate among immunocompromised individuals

Background. Immunocompromised individuals (ICI) are at high risk for infections, some of which are preventable by vaccines. The Israeli MOH recommends PCV13 and PPSV23 vaccines for ICI, but vaccine coverage is suboptimal. The aim of this study was to assess the effectiveness of a project to improve pneumococcal vaccination (PV) rate among ICI in outpatient settings. Methods. An automated validated, population-based registry of patients with ICI was developed in an Israeli health organization, Maccabi Healthcare Services, serving over 2.5 million members. Included in the registry were patients aged 18 and above, receiving immunosuppressive therapy (IT);patients living with HIV (PLWH);solid organ and bone marrow transplant recipients (TR);patients with advanced kidney disease (AKD);and patients with asplenia. Based on the registry and the Israeli MOH vaccination guidelines, a nationwide quality improvement project aimed at improving PV was implemented which began in October 2019. As part of the project, ICI were waived the need for preapproval for PCV13. During an eligible patient visit, physicians and nurses were prompted with an EHR alert reminding them to consider providing pneumococcal vaccine. In addition, eligible patients were invited via their patient health record (both desktop and mobile) to vaccinate. Vaccination rates during pre- and post-intervention periods were compared using the Chi square test. Results. A total of 32,297 ICI were identified. Of them, 22,721 were on IT, 1651 PLWH, 1829 were TR ,5267 had AKD, and 1920 were asplenic. During the period October 2019 to October 2021, PCV13 vaccination rates went up from 12% to 54.1% (p< 0.0001), and PPSV23 vaccination rate improved from 44.7% to 62.6% (P < 0.0001). Conclusion. Using one of the first real-world automated registries for ICI and implementation of targeted automated patient and provider alerts, markedly improved pneumococcal vaccine uptake was observed in this vulnerable population. Similar interventions may be used to increase the adherence for other vaccines, including COVID-19 vaccines.

AN UNUSUAL PRESENTATION OF CHRONIC LYMPHOCYTIC LEUKEMIA AS ORGANIZING PNEUMONIA

SESSION TITLE: Pulmonary Manifestations of Systemic Disease Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Organizing pneumonia (OP) is a form of interstitial lung disease with a distinct histopathological pattern where bronchioles and alveoli become inflamed. It is associated with many clinical conditions including infections and connective tissue disease. OP has also been seen in patients with hematologic malignancies, however, primary pulmonary presentation of chronic lymphocytic leukemia (CLL) is uncommon. We present a rare case of OP as an initial presentation of CLL. CASE PRESENTATION: A 62 year-old male with a sixty pack year smoking history and COVID-19 infection one month ago presents with complaints of worsening dyspnea, headaches, productive cough, and congestion of 10 days duration. Patient is unvaccinated and did not require hospitalization for his COVID-19 infection. His vital signs on admission were significant for tachypnea with respiratory rate of 35 and hypoxia with oxygen saturation of 84% on room air. He initially required oxygen supplementation via non-rebreather mask to maintain oxygen saturation >88%. A chest tomography (CT) scan was completed and revealed bilateral dense consolidations with ground-glass opacities and air bronchograms consistent with OP. The scan was also significant for bulky mediastinal lymphadenopathy. The patient denied any personal or family history of autoimmune disease, occupational exposures, and recent travel. Evaluation for infection and for underlying connective tissue disease was unremarkable. He was started on broad spectrum antibiotics and high dose steroids. Due to fluctuating lymphocytosis, bulky lymphadenopathy, and negative infectious workup despite clinical improvement, he underwent a bronchoscopy with endobronchial ultrasound guided transbronchial needle aspiration of lymph nodes. Immunohistochemical (IHC) stains of these samples were compatible with CLL. Additionally, peripheral blood flow cytometry was also diagnostic of CLL. Oncology was consulted for further evaluation and treatment of CLL. The patient's respiratory symptoms improved and oxygen requirements decreased with steroid treatment and he was discharged home. DISCUSSION: OP occurring in patients with hematologic malignancies has multiple etiologies. Most case reports describe patients with previous exposure to chemotherapy, radiotherapy, or bone marrow transplant. However, our patient had no such exposure history and no prior diagnosis of a hematologic malignancy. Infectious and autoimmune etiology were considered, but serologic evaluation was unremarkable. Flow cytometric analysis of lymph node tissue along with lymphocytic bronchoalveolar lavage was consistent with initial diagnosis of CLL. CONCLUSIONS: Despite the low incidence, hematologic malignancy should be considered as a differential diagnosis in all patients who present with organizing pneumonia. Prednisone therapy for 6-12 month duration has been shown to reduce respiratory symptoms and may improve survival. Reference #1: Craig E. Daniels, Jeffrey L. Myers, James P. Utz, Svetomir N. Markovic, Jay H. Ryu. Organizing pneumonia in patients with hematologic malignancies: A steroid-responsive lesion. Respiratory Medicine, 101 (1) (2007), pp. 162-168. Reference #2: M. Mokhtari, P.B. Bach, P.A. Tietjen, D.E. Stover. Bronchiolitis obliterans organizing pneumonia in cancer: a case series. Respiratory Medicine, 96 (4) (2002), pp. 280-286. DISCLOSURES: no disclosure on file for Guillermo Garrido;No relevant relationships by Anita Gopalakrishnan No relevant relationships by Rameez Rao No relevant relationships by Mohammad Salimian

Haploidentical CD3+ TCR αß/CD19+ depleted HSCT for MHC Class II deficiency and persistent SARS-CoV-2 pneumonitis.

Background & Objectives: SARS-CoV-2 infection leads to coronavirus disease 2019 (COVID-19), which can range from a mild illness to a severe phenotype characterised by acute respiratory distress, needing mechanical ventilation. Children with combined immunodeficiencies might be unable to mount a sufficient cellular and humoral immune response against Covid-19 and have persistent disease. The authors describe a child with combined immunodeficiency, with favorable post-HSCT course following a haploidentical haematopoietic stem cell transplant in the presence of persistent SARS-CoV-2 infection. Methods & results: A 13-month-old girl with MHC class II deficiency developed persistent pre-HSCT SARS-CoV-2 infection. Faced with a significant challenge of balancing the risk of progressive infection due to incompetent immune system with the danger of inflammatory pneumonitis peri-immune reconstitution post-HSCT, she underwent a maternal (with a recent history of Covid-19 infection) haploidentical haematopoietic stem cell transplant. The patient received Regdanvimab® (post stem cell infusion) and Remdesivir (pre and post stem cell infusion). We noted a gradual increase in the Ct (cycle threshold) values, implying reduction in viral RNA with concomitant expansion in the CD3 lymphocyte subset and clinical/radiological improvement. Conclusions: Combination of adoptive transfer of maternal CD45RO+ memory add-back T-lymphocytes after haploidentical HSCT, use of Regdanvimab® (SARS-CoV-2 neutralising monoclonal antibody) and Remdesivir may have led to the successful outcome in our patient with severe immunodeficiency, undergoing HSCT. Our case highlights the role of novel antiviral strategies (monoclonal antibodies and CD45RO+ memory T-lymphocytes) in contributing to viral clearance in a challenging clinical scenario.

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.

Impact of COVID-19 pandemic on collection of allogeneic hematopoietic stem cells

Introduction: COVID-19 pandemic brought challenges in the organization of hematopoietic stem cell (HSC) transplantation. Availability of HSCs was decreased due to donor infection and transport limitations. Accordingly, a series of measures was introduced to ensure the protection of patients and donors and availability of transplants during the pandemic. The goal of this study was to show the impact of COVID-19 pandemic on the collection of allogeneic HSCs in University Hospital Centre (UHC) Zagreb. Methods: We conducted a retrospective analysis for the period from March 1, 2020, to June 30, 2021. The data were collected from hospital computer database and meeting reports of the HSC Transplantation Committee of UHC Zagreb. Results: In the reported period peripheral blood stem cells (PBSC) were preferred, except when bone marrow (BM) transplantation was strongly indicated. Allogeneic HSC grafts were cryopreserved before conditioning to ensure availability on the day of transplantation. Thirteen patients were excluded from the program due to COVID-19 infection. HSCs were collected from related and unrelated donors from the Croatian HSC Donor Registry and World Marrow Donor Assocciation for the total of 135 patients. All 17 (12.5%) harvested BM grafts were transplanted. Sixteen patients were transplanted with PBSC instead of BM. Out of the collected PBSC 94.1% were transplanted but in 17 patients transplantations were delayed due to COVID-19 infection of the donor and/or the patient. Of the total 118 PBSC transplants 100 (84.7%) were cryopreserved in 540 cryo bags. Seven (5.9%) cryopreserved grafts have not been infused because of the progression of the main disease (5), COVID-19 infection of the patient (1) and poor product viability (1). Conclusion: COVID-19 pandemic adversely impacted HSC collection and transplantation with many organizational and logistical challenges. Cryopreservation of allogeneic grafts enabled efficient management of the transplantation programs but was accompanied with the risk of not infusing some grafts, which exposed donors to unnecessary risks and increased the cost of treatment. © 2022 Hrvatski Lijecnicki Zbor. All rights reserved.

EXPERIENCE WITH HIGH-THROUGHPUT SEQUENCING, BONE MARROW TRANSPLANTATION AND TARGETED THERAPY FOR ACUTE MYELOID LEUKEMIA WITH A POOR PROGNOSIS

The study presents a clinical case of treating acute myeloid leukemia with an unfavorable genetic prognosis due to genotyping by high-throughput sequencing. The patient underwent related allogeneic bone marrow transplantation with targeted chemotherapy. The disease manifested itself after a new coronavirus infection. Mutations R140Q in the IDH2 gene and P799S in the DNMT3A gene were detected by high throughput sequencing. Given the unfavorable genetic prognosis, bone marrow transplantation from an HLA-compatible sibling was performed. On day 22, COVID-19 was detected, and ruxolitinib was added to the treatment. On the 25th day, hematopoiesis was restored with the preservation of clinical and hematological remission. Ten months after transplantation, a relapse was diagnosed, for which the patient started targeted therapy with 5-azacytidine with venetoclax in combination with transfusions of donor leukocytes. The second remission was achieved after the first course. The total duration of follow-up was 24 months. © Group of authors, 2022.

The efficacy and safety of second allogeneic hematopoietic stem cell transplantation

Background: Second allogeneic hematopoietic cell transplant (sAHCT) might be indicated following a graft failure or disease relapse after the first one;although it might emerge with high rates of morbidities and mortality. Currently, there is a limited number of publications on this matter in the literature, here we aimed to share our sAHCT experience from a single center. Methods: Data from 51 patients who were eligible for sAHCT between 2001 and 2021 was evaluated retrospectively. All data was obtained from the Ankara University Faculty of Medicine, Department of Hematology and Bone Marrow Transplant Unit. Results: 51 patients were included in the present study. Median age at sAHCT was 34 (18- 65) and female/ male ratio 19/ 32 (37.3% / 62.7%). The same donor from the first transplant was eligible for sAHCT for most patients (n= 46, 90.2 %). sAHCT indication was graft failure for 11 patients (21.6 %) whereas 40 (78.4 %) patient went on sAHCT for disease relapse. Patients' diagnoses were as follows: acute myeloid leukemia (n= 26, 50.9 %), acute lymphoblastic leukemia (n=9, 17.6 %), myelodysplastic syndrome (n= 6, 11.8 %), aplastic anemia (n= 6, 11.8 %) and others (CMML, CML, biphenotypic leukemia). Median number of transplanted CD34+ hematopoietic cells was 5.77 x x106/ kg (1.11- 8.29). Stem cell source was either bone marrow (n= 5, 9.8%) or peripheral blood (n= 46, 90.2 %). Myeloablative conditioning regimens were used for most sAHCTs (n= 30, 58.8%). Median overall survival (OS) rates for graft failure and disease relapse groups were 12.8 and 18.7 months, respectively (p= 0.63). During early transplant phase, 20 patients (39.2 %) died due to bone marrow aplasia, transplant failure or other complications. 1 year OS of the entire cohort was 33.3 % whereas 2-y- OS was 21.6% (95% CI= 25-45). 2 patients (3.9 %) died due to COVID19 during transplant process. On univariate analysis, sex, time from the first transplant (<12 months/ ≥12 months), conditioning intensity, sAHCT indication did not statistically significantly influence OS. Multivariate analysis confirmed a lower ECOG score (<2) at sAHCT significantly increased OS (p= 0.001). Conclusions: Based on this single center study, sAHCT is an efficacious treatment modality especially for patients with lower ECOG scores. sAHCT may offer long term survival for both graft failure and disease relapse states.