Immunotherapy: ALLOGENEIC UMBILICAL CORD BLOOD REGULATORY T CELLS DECREASE INFLAMMATION AND PRESERVE ANTI-TUMOR ACTIVITY OF CAR T CELLS

Background & Aim: With larger accessibility and increased number of patients being treated with CART cell therapy, real-world toxicity continues to remain a significant challenge to its widespread adoption. We have previously shown that allogeneic umbilical cord blood derived (UCB) regulatory T cells (Tregs) can resolve uncontrolled inflammation and can treat acute and immune mediated lung injury in a xenogenic model as well as in patients suffering from COVID-19 acute respiratory distress syndrome. The unique properties of UCB Tregs including: i) lack of plasticity when exposed to inflammatory micro-environments;ii) no requirement for HLA matching;iii) long shelf life of cryopreserved Tregs;and iv) immediate product availability for on demand treatment, makes them an attractive source for treating acute inflammatory syndromes. Therefore, we hypothesized that add-on therapy with UCB derived Tregs may resolve uncontrolled inflammation responsible for CART cell therapy associated toxicity. Methods, Results & Conclusion(s): UCB Tregs were added in 1:1 ratio to CART cells, where no interference in their ability to kill CD19+ Raji cells, was detected at different ratios : 8:1 (80.4% vs. 81.5%);4:1 (62.0% vs. 66.2%);2:1 (50.1% vs. 54.7%);1:1 (35.4% vs. 44.1%) (Fig 1A). In a xenogenic B cell lymphoma model, multiple injections of Tregs were administered after CART injection (Fig 1B), which did not impact distribution of CD8+ T effector cells (Fig 1C) or CART cells cells (Fig 1D) in different organs. No decline in the CAR T levels was observed in the Tregs recipients (Fig 1E). Specifically, no difference in tumor burden was detected between the two arms (Fig 2A). No tumor was detected in CART+Tregs in liver (Fig 2B) or bone marrow (Fig 2C). A corresponding decrease in multiple inflammatory cytokines in peripheral blood was observed in CART+Tregs when compared to CART alone (Fig 2D). Here we show "proof of concept" for add-on therapy with Tregs to mitigate hyper-inflammatory state induced by CART cells without interference in their on-target anti-tumor activity. The timing of Tregs administration after CART cells have had sufficient time for forming synapse with tumor cells allows for preservation of their anti-tumor cytotoxicity, such that the infused Tregs home to the areas of tissue damage to bind to the resident antigen presenting cells which in turn collaborate with Tregs to resolve inflammation. Such differential distribution of cells allow for a Treg "cooling blanket" and lays ground for clinical study. [Figure presented]Copyright © 2023 International Society for Cell & Gene Therapy

Non-Hodgkin's lymphoma complicated with human coronavirus HKU1 pneumonia: A case report and literature review.

Objective: To analyze the clinical manifestations, diagnostic methods and treatment process of the patients with non-Hodgkin's lymphoma complicated with human coronavirus(HCoV)-HKU1 pneumonia and improve the clinical medical staff's awareness of the disease, and to reduce the occurrence of clinical adverse events. Method(s): The clinical data of a patient with non-Hodgkin's lymphoma complicated with HCoV-HKU1 pneumonia with hot flashes and night sweats, dry cough and dry throat as the main clinical features who were hospitalized in the hospital in January 2021 were analyzed, and the relevant literatures were reviewed and the clinical manifestations and diagnosis of HCoV-HKU1 were analyzed. Result(s): The female patient was admitted to the hospital due to diagnosed non-Hodgkin's lymphoma for more than 2 months. The physical examination results showed Karnofsky score was 90 points;there was no palpable enlargement of systemic superfical lymph nodes;mild tenderness in the right lower abdomen, no rebound tenderness, and slightly thicker breath sounds in both lungs were found, and a few moist rales were heard in both lower lungs. The chest CT results showed diffuse exudative foci in both lungs, and the number of white blood cells in the urine analysis was 158 muL-1;next generation sequencing technique(NGS) was used the detect the bronchoalveolar lavage fluid, and HCoV-HKU1 pneumonia was diagnosed. At admission, the patient had symptoms such as dull pain in the right lower abdomen, nighttime cough, and night sweats;antiviral treatment with oseltamivir was ineffective. After treatment with Compound Sulfamethoxazole Tablets and Lianhua Qingwen Granules, the respiratory symptoms of the patient disappeared. The re-examination chest CT results showed the exudation was absorbed. Conclusion(s): The clinical symptoms of the patients with non-Hodgkin's lymphoma complicated with HCoV-HKU1 pneumonia are non-specific. When the diffuse shadow changes in the lungs are found in clinic, and the new coronavirus nucleic acid test is negative, attention should still be paid to the possibility of other HCoV infections. The NGS can efficiently screen the infectious pathogens, which is beneficial to guide the diagnosis and treatment of pulmonary infectious diseases more accurately.Copyright © 2023 Jilin University Press. All rights reserved.

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.

Case Report of Succesful Multidisiplinary Treatment for Patient with Metastatic Lung Cancer and Relapsed/Refractory Chronic Lymphatic Leukemia/Small Lymphocytic Lymphoma

Introduction: Croatian National Cancer Registry of Croatian Institute for Public Health reported that in year 2020 lung cancer was the second most common cancer site diagnosed in men with 16% and the third most common in women with 10% incidence among all cancer sites. Unfortunatelly lung cancer has the highest mortality in both men and women. Haematological malignancies had 7% share in all malignancies in both male and female cances cases. In 2020 190 newly diagnosed cases of lymphatic leukemia in men and 128 cases in women were reporeted, meaning 1.5 and 1.2% of all malignancies, respectively. Chronic lymphatic leukemia (CLL) is an advanced age disease and incidence increases with age. Impaired immunity, T and B cell dysfunction in CLL, chromosomal aberations, long-term immunosuppressive therapy and genetic factors can all cause secondary malignancies. Co- occurence of solid tumors and CLL is very rare. Although patiens with CLL have an increased risk of developing second primary malignancies including lung carcinoma, the data about their clinical outcomes are lacking. Parekh et al. retrospectively analyzed patients with simultaneous CLL and lung carcinoma over a 20-year period, and they found that ~2% of patients with CLL actually developed lung carcinoma. The authors claimed that up to 38% of patients will also develop a third neoplasm more likely of the skin (melanoma and basal cell carcinoma), larynx (laryngeal carcinoma) or colon. Currently there are no specific guidelines for concurrent CLL and non-small cell lung carcinoma (NSCLC) treatment. Usually, when the tumors are diagnosed simultaneously, treatment is based to target the most aggressive malignancy, as the clinical outcomes depend on the response of the tumor with the poorest prognosis. For this reason, a multidisciplinary approach is mandatory. Case report: A patient with history of coronary heart disease, myocardial infarction and paroxysmal atrial fibrillation was diagnosed in 2019 (at the age of 71) with B chronic lymphocytic leukemia with bulky tumor (inguinal lymph nodes 8x5 cm), stage B according to Binet, intermediate risk. He was treated with 6 cycles of chemoimmunotherapy (rituximab/cyclofosfamid/fludarabine). In 10/2019 remission was confirmed, but MSCT described tumor in the posterior segment of upper right lung lobe measuring 20x17 mm and bilateral metastases up to 11 mm. Bronchoscopy and biopsy were performed, and EGFR neg, ALK neg, ROS 1 neg, PD-L1>50% adenocarcinoma was confirmed. He was referred to Clinical Hospital Center Osijek where monotherapy with pembrolizumab in a standard dose of 200 mg intravenously was started in 01/2020. Partial remission was confirmed in October 2020. Immunotherapy was discontinued due to development of pneumonitis, dysphagia and severe weight loss (20kg), but without radiologically confirmed disease progression. At that time he was referred to our hospital for further treatment. Gastroscopy has shown erosive gastritis with active duodenal ulcus, Forrest III. Supportive therapy and proton pump inhibitor were introduced. After complete regression of pneumonitis, improvement of general condition and resolution of dysphagia, no signs of lung cancer progression were found and pembrolizumab was reintroduced in 12/2021. Hypothyroidism was diagnosed in 01/2021 and levothyroxine replacement ther apy was started. In 03/2021 he underwent surgical removal of basal cell carcinoma of skin on the right temporal region with lobe reconstruction. From 02/2021, when pembrolizumab was reintroduced, regression in tumor size was continously confirmed with complete recovery of general condition. He was hospitalized for COVID 19 infection in 09/2021, and due to complications pembrolizumab was discontinued till 11/2021. Lung cancer immunotherapy proceeded till 11/2022, when Multidisciplinary team decided to finish pembrolizumab because of CLL relapse. CLL was in remission till August 2022 when due to B symptoms, lymphcytosis, anemia and generalized lymphadenopathy, hematological workup including biopsy of cervical lymph node was performed and CLL/SLL relapse was confirmed. Initially chlorambucil was introduced, but disease was refractory. Based on cytogenetic test results (IGHV unmutated, negative TP53) and due to cardiovascular comorbidity (contraindication for BTK inhibitors) venetoclax and rituximab were started in 01/2023. After just 1 cycle of treatment normal blood count as well as regression of B symptoms and peripheral lymphadenopathy occured, indicating the probability of complete disease remission. In our patient with metastatic lung adenocarcinoma excellent disease control is achieved during 41 month of treatment in first line setting. Furthermore, relapsed/refractory CLL/SLL is currently in confirmed remission. Conclusion(s): Successful treatment of patients with multiple primary malignancies is based on multidisciplinarity, early recognition and management of side effects, treatment of comorbidities with the aim of prolonging life, controlling symptoms of disease and preserving quality of life.

A retrospective observational study of CAR T-cell therapy outcomes-Experience from MSE Foundation Trust

The most common non-Hodgkin's lymphoma (NHL) is diffuse large B-cell lymphoma (DLBCL), an aggressive lymphoma that can be cured with standard frontline chemo-immunotherapy in 60%-70% of patients but with historically poor outcomes for relapsed/refractory disease. Patients with relapsed DLBCL after autologous stem cell transplant (ASCT) or with chemotherapy-refractory disease have a particularly dismal prognosis, with a median overall survival (OS) of only 6 months. Chimeric antigen receptor (CAR) T-cell therapy has significantly improved outcomes for patients with relapsed/refractory large B-cell lymphoma, mantle cell lymphoma and follicular lymphoma, with multiple FDA approved CAR T products now commercially available in many developed world including European countries. Ongoing studies seek to move CAR T cells to earlier lines of therapy and to characterise the efficacy and safety of CAR T-cell approaches in additional lymphoma histologies including relapsed/refractory follicular lymphoma and chronic lymphocytic leukaemias. Other areas of active research address CAR T in combination with other lymphoma-directed therapies, and mechanisms of CAR T resistance. We conducted a retrospective observational study assessing the outcomes of patients referred to our tertiary centre, University College London hospital NHS foundation Trust (UCLH) from January 2018 to December 2022, over a 48-month period. We collected data including patients' demographics, types of lymphomas, prior lines of therapies including stem cell transplantation, bridging therapies as appropriate, complications and overall response rate. We also analysed the communication between teams during the challenging period of the COVID-19 pandemic.

US drug approvals rise in 2020 over previous year

Several medicines were approved as first treatments, including Gilead Sciences' Veklury (remdesivir) for patients with COVID-19 who require hospitalization (4);Amivas' artesunate for injection for severe malaria (5);Horizon Therapeutics Ireland DAC's Tepezza (teprotumumab-trbw), an antibody drug conjugate (ADC) for treating thyroid eye disease (6);and Ultragenyx Pharmaceutical's Dojolvi (triheptanoin) and Alnylam Pharmaceuticals' Oxlumo (lumasiran), both first treatments for metabolic disorders-Dojolvi for treating paediatric and adult patients with molecularly confirmed long-chain fatty acid oxidation disorders (7) and Oxlumo (lumasiran) for treating the rare genetic disorder, primary hyperoxaluria type 1 (8). Blueprint Medicines Corporation) for treating unresectable or metastatic gastrointestinal stromal tumours harboring a platelet-derived growth factor receptor alpha exon 18 mutation (9);Koselugo (selumetinib, AstraZeneca Pharmaceuticals), for neurofibromatosis type 1 (10);Pemazyre (pemigatinib, Incyte Corporation), for certain types of previously treated, advanced bile duct cancer (cholangiocarcinoma) (11);Tabrecta (capmatinib, Novartis) for non-small cell lung cancer that has spread to other parts of the body and whose tumours have mutations that lead to MET exon 14 skipping (12);and Retevmo (selpercatinib, Loxo Oncology, a subsidiary of Eli Lilly and Company) for treating three types of tumours with alterations of the "rearranged during transfection" gene (13). Gilead, "U.S. FDA Approves Kite's Tecartus, the First and Only CAR T Treatment for Relapsed or Refractory Mantle Cell Lymphoma," Press Release, 24 July 2020.

COVID-19 pre-exposure prophylaxis with tixagevimab/cilgavimab in patients with haematological malignancy: A single-centre experience

Background: COVID-19 pandemic still pose a substantial threat worldwide despite increasing vaccine availability. Patients with haematological malignancies have been shown to have increased risk of contracting COVID-19 and are more susceptible to develop severe illness from SARS-CoV- 2 infection. The immune response to vaccines is impaired in patients with haematological malignancy due to underlying disease or antineoplastic therapies. The monoclonal-antibody combination, Evusheld is composed of tixagevimab and cilgavimab, two neutralising antibodies against SARS-CoV- 2. It has been shown to be safe and have efficacy for the prevention of COVID-19. Our aim of study is to describe the incidence and outcome of breakthrough COVID-19 infection among patients who received Evusheld in our centre and analyse the factors that possibly increase the risk of breakthrough infection. Material(s) and Method(s): A retrospective review of all adult patients with haematological malignancy who received tixagevimab/ cilgavimab 150/150 mg injection in Hospital Pulau Pinang from 1 July 2022 to 31 August 2022 with a follow-up period to 30 November 2022 was conducted. Demographic data, clinical characteristics and outcome will be retrieved from patient's medical records. Data were analysed using Statistical Package for Social Sciences software (version 21.0). Result(s): A total of 96 patients (50 males and 46 females) received tixagevimab/cilgavimab injection during the study period with a median age of 61 years (range 19-82). Majority of them were diagnosed with multiple myeloma (42.7%), followed by lymphoma (33.3%) and leukaemia (24%). One third of them had history of therapy with monoclonal antibody and 20% had haematopoietic stem cell transplantation. No major adverse effects of tixagevimab/cilgavimab injection were noted among the study population. Of the 12 patients (12.5%) who had COVID-19 infection, all of them had mild infection;three were asymptomatic and six patients received Paxlovid antiviral therapy. The median time from tixagevimab/cilgavimab to the onset of COVID-19 infection was 35 days (range 5-97 days). The mean age of patients with breakthrough COVID-19 infection were older compared to those without breakthrough infection but was not statistically significant. The incidence of breakthrough COVID-19 infection was not affected by type of haematological malignancy, history of monoclonal antibody therapy or COVID-19 vaccination. Discussion and Conclusion(s): Our findings showed that tixagevimab/cilgavimab was safe and effective in preventing COVID-19- related morbidity and mortality among patients with haematological malignancy during the study period. However, the limitation is the lack of access to whole genome sequencing for detection of resistant variants for breakthrough infections.

Sharing the knowledge and expertise of BSH members throughout the global Haematology community

'BSH Global Speakers' was established in 2015 as a core project of the BSH Global Haematology Special Interest Group (SIG). As the project enters its eighth year, we present an update and reflection on the successes and challenges encountered. Initially known as the 'Plenary Speaker Scheme', the project was developed following a stakeholder meeting in 2015 at the inception of the SIG. Haematology colleagues from the UK and low-and middle-income countries (LMIC) came together to discuss how the BSH may be best placed to support haematologists practicing in LMICs. Sharing of expertise and building collaborative networks were identified as key priorities. The 'Plenary Speaker Project' was conceived;BSH haematologists would be supported in delivering plenaries at the meetings of colleagues in LMICs, with the aim that each visit could act as a catalyst for creating networks and developing collaborative projects in education, research, and capacity building. We established a yearly cycle of inviting applications from LMIC societies for a funded speaker at their scientific meetings, selecting the most impactful meetings, then recruiting appropriate UK-based speakers. We place emphasis on the likelihood of ongoing collaborative working or other impacts, for example engagement with local haematology trainees. To date, ten speakers have represented BSH at the meetings of LMIC societies, presenting on diverse topics, from molecularly guided interventions to prevent relapse in AML, to adapting lymphoma treatment strategies for low resource settings. Recently we have opened applications to nurse specialists and scientists, with our first scientific speaker presenting in Thailand May 2023. The COVID-19 pandemic created significant challenges for the project due to the disruption in international travel and the cancellation of many haematology meetings around the globe. We were, however, able to adapt the project to support virtual speakers at meetings in South Africa, Vietnam, and Ghana. Although virtual meetings do not naturally lend themselves to collaborative working, we were pleased that a longer term joint educational program in haemoglobinopathy care has been established with the Vietnamese Society of Haematology as a result of BSH support. The impact of BSH Global Speakers is significant. Even at smaller meetings, speakers will have the ear of the majority of practicing haematologists in a country. From the relationships built between societies and speakers we have seen the development of fellowship programmes, online education programmes, laboratory support, and numerous networks for informal advice in clinical care, research, and more.

Lymphoproliferation- a clue towards an underlying monogenic disorder of immune dysregulation- a retrospective analysis from a single center in India

Background: Lymphoproliferation is the persistent proliferation of lymphoid cells and it's incidence in inborn errors of immunity varies from 0.7 to 18%. Material(s) and Method(s): This is a retrospective analysis of patients referred to the department of Immunology, B. J. Wadia Hospital for Children, Mumbai between March 2017 to December 2022. Inclusion criteria consisted of 3 months duration of significant lymphadenopathy and/or splenomegaly or history of lymphoma. The clinical characteristics, laboratory and molecular findings of the included patients were analyzed. Result(s): A total of 66 patients were included. There was a male preponderance with male:female ratio of 25:8. Median age of onset of lymphoproliferation was 4.75 years(Range 1 year to 60 years). Splenomegaly was seen in 75%. Infections included recurrent pneumonia (14/66), recurrent ear infections(5/66), COVID(4/66), one episode of pneumonia(6/66), herpes zoster(3/66), recurrent subcutaneous abscess (3/66), abdominal koch(3/66), chronic sinusitis(2/66), dermatophytosis(2/66), esophageal candidiasis(2/66), recurrent malaria(1/66), recurrent varicella(1/66), cryptococcal meningitis(1/66), gram negative sepsis(1/66), BCG adenitis(1/66), pseudomonas osteomyelitis(1/66), impetigo (1/66), pseudomonas urinary tract infection (1/66), chicken pox(1/66), herpes keratitis(1/66), dengue(1/66), Other manifestations included Evans plus phenotype(10/66), Evans phenotype(8/66), Autoimmune hemolytic anemia(5/66), bronchiectasis(5/66), Type 1 diabetes(3/66), hyper reactive airway disease(2/66), inflammatory bowel disease(4/66), autoimmune thrombocytopenia(2/66), stroke(3/66), hemophagocytic lymphohistiocytosis(2/66), hypertriglyceridemia(2/66), hypothyroidism(2/66), celiac disease(1/66), Type 2 diabetes(1/66), autoimmune encephalitis(1/66), autoimmune hepatitis(2/66), anti-parietal cell antibody(1/66), arthritis(1/66), autoimmune enteropathy(1/66), systemic lupus erythromatosus(1/66), primary biliary cirrhosis requiring liver transplant(1/66), nephrotic syndrome(1/66), lymphoedema(1/66), hypersplenism(1/66), recurrent oral ulcers(1/66), gout(1/66), dermatitis(1/66), ovarian teratoma(1/66), alopecia areata(1/66). Hodgkin's lymphoma(HL) was the most common malignancy(9/66), followed by non Hodgkin lymphoma(NHL)(6/66), transformation from NHL to HL(1/66), Burkitt to T-cell lymphoma(1/66), HL to DLBCL(1/66), HL to anaplastic T-cell lymphoma(1/66). EBV driven lymphoproliferation was seen in biopsy of21/66. Genetic testing showed mutations in LRBA(11/66), PIK3CD(5/66), CTLA4(3/66), TET2(2/66), IL2RA (1/66), IL12RB1(1/66), BACH2(1/66), PRKCD(1/66), TNFSFR13B(1/66), TNFAIP3(1/66), FAS(2/66), FASL(1/66), Caspase8(1/66), CARD11(1/66), RTEL1(1/66), AICD(1/66), PIK3R1(1/66), IKBKB(1/66). Treatment included IVIG, chemotherapy, rituximab, sirolimus, abatacept, HSCT. Conclusion(s): All children with persistent lymphoproliferation, with or without autoimmunity and/or infections should be worked up for an underlying monogenic disorder of immune dysregulation. Lymphomas presenting at abnormal site and/or age, relapse and EBV driven lymphomas require further evaluation. Presence of monogenic cause helps in providing targeted therapy.Copyright © 2023 Elsevier Inc.

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.

Identifying factors that affect barriers to lymphoma treatment during the COVID - 19 pandemic

Introduction: Barriers to therapy for patients with lymphoma are an essential topic. The Lymphoma Coalition biennial global patient survey collects data on patient experiences, including challenges or limitations patients face in seeking medical attention or access to treatment. Due to Covid-19, patients with lymphoma have experienced high barriers. This study aims to rank the influence of core demographic variables in their ability to predict barriers to lymphoma treatment in 2020 and 2022. Method(s): The survey was deployed globally to lymphoma patients and caregivers in 2020 & 2022. The outcome variable was the identification of any barrier to receiving lymphoma treatment. Logit regression was used to model the outcome against core demographics. Variable importance was quantified with independent Monte Carlo resampling. Result(s): Barriers were significantly elevated in all regions in 2022 (p<0.0001). Those who are of older age were found to have fewer barriers to treatment: Unit OR = 0.965;95%CI [0.962 - 0.968]. Age was consistently a variable of high importance across most regions in both survey years (Table 1). In 2022, treatment delay due to concerns over COVID-19 was the second-ranked variable of importance in three regions. Conclusion(s): Barriers to treatment for patients with lymphoma increased dramatically across all regions from 2020-2022. Increased barriers to treatment in those of younger age were an unexpected finding. Heterogeneity in the impact of variables that influence access to treatment appears to be enhanced by participants' psychosocial impacts due to the pandemic. Policymakers and providers should actively rectify access disparities in their respective regions.

Thoracic Myelopathy in a Teenager Caused by Stage IV Hodgkin's Lymphoma.

We report the case of a 19-year-old Native American woman who presented with bilateral lower extremity weakness due to spinal cord compression from late-stage Hodgkin's lymphoma. Hodgkin's lymphoma rarely has an initial presentation of spinal cord compression, except in cases of late-stage disease. The patient partially attributed her delayed pursuit of care to the difficulty of scheduling an appointment during the coronavirus (COVID-19) pandemic. The COVID-19 pandemic has impacted access to care and the potential for early detection of disease, as seen in this patient. Additionally, Native Americans on South Dakota Reservations face unique challenges that affect access to healthcare and health outcomes.

A Hepatitis B Virus Reactivation Case Potentially Triggered by the Onset of Diffuse Large B Cell Lymphoma.

An 81-year-old man underwent rituximab-containing chemotherapy for chronic lymphocytic leukemia (CLL). Thirteen years after his last chemotherapy, he was diagnosed with hepatitis B virus (HBV) reactivation. He was then treated with entecavir, and improvement was seen in his liver injury. He developed diffuse large B cell lymphoma (DLBCL) after improvement in his hepatitis. Despite chemotherapy, he contracted the coronavirus disease 2019 (COVID-19) and died of COVID-19. We suspect that HBV reactivation was triggered by DLBCL. When HBV reactivation occurs a long time after chemotherapy has concluded, the onset of DLBCL should be considered.

Anaplastic Large-Cell Lymphoma (ALCL) First Manifested as a Rapidly Progressive Acute Respiratory Failure (RF): Lymph Node Biopsy Negative Presentation Posing a Diagnostic Challenge.

Anaplastic large-cell lymphoma (ALCL) is an aggressive subtype of non-Hodgkin lymphoma. There are two forms of ALCL: primary and secondary. Primary can be systemic, affecting multiple organs, or cutaneous, affecting mainly the skin. A secondary form occurs when another lymphoma undergoes an anaplastic transformation. ALCL rarely presents as initial symptoms of respiratory failure. In most of these situations, the trachea or bronchial involved with an obstruction was present. We present an unusual case of ALCL where the patient rapidly progressed to acute hypoxic respiratory failure with a patent bronchus and trachea. Unfortunately, the patient rapidly deteriorated and died before diagnosis. Only upon at autopsy, it was found that his lung parenchyma was diffusely involved with ALCL. The autopsy report showed that the patient had CD-30 anaplastic lymphoma kinase (ALK)-negative ALCL diffusely involving all lung fields.

COVID-19 in hospitalized solid organ transplant recipients in a nationwide registry study.

OBJECTIVES: Underlying immunodeficiency has been associated with worse clinical presentation and increased mortality in patients with COVID-19. We evaluated the mortality of solid organ transplant (SOT) recipients (SOTR) hospitalized in Spain due to COVID-19. METHODS: Nationwide, retrospective, observational analysis of all adults hospitalized because of COVID-19 in Spain during 2020. Stratification was made according to SOT status. The National Registry of Hospital Discharges was used, using the International Classification of Diseases, 10th revision coding list. RESULTS: Of the 117,694 adults hospitalized during this period, 491 were SOTR: kidney 390 (79.4%), liver 59 (12%), lung 27 (5.5%), and heart 19 (3.9%). Overall, the mortality of SOTR was 13.8%. After adjustment for baseline characteristics, SOTR was not associated with higher mortality risk (odds ratio [OR] = 0.79, 95% confidence interval [CI] 0.60-1.03). However, lung transplantation was an independent factor related to mortality (OR = 3.26, 95% CI 1.33-7.43), while kidney, liver, and heart transplantation were not. Being a lung transplant recipient was the strongest prognostic factor in SOT patients (OR = 5.12, 95% CI 1.88-13.98). CONCLUSION: This nationwide study supports that the COVID-19 mortality rate in SOTR in Spain during 2020 did not differ from the general population, except for lung transplant recipients, who presented worse outcomes. Efforts should be focused on the optimal management of lung transplant recipients with COVID-19.

An extremely rare tracheal tumor in coronavirus disease-2019 screening: Marginal zone lymphoma.

Mucosal-associated lymphoid tissue lymphoma is extremely rare due to the scarcity of lymphoid tissue in the trachea. To date, approximately 20 cases of tracheal mucosa-associated lymphoid tissue lymphoma have been reported. This case report presents a primary tracheal extranodal marginal zone lymphoma case detected incidentally during the coronavirus disease-2019 screening.

Diseases associated with feline leukemia virus and feline immunodeficiency virus infection: A retrospective study of 1470 necropsied cats (2010-2020).

Feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) are retroviruses affecting cats worldwide, and the prevalence of infection varies considerably according to the geographic area. We retrospectively described FIV- and FeLV-associated diseases in a population of 1470 necropsied cats, of which 396 (26.9%) were infected with FeLV, 199 (13.5%) with FIV, and 134 (9.1%) with FeLV and FIV concomitantly. Cats infected with FeLV (OR 3.4) and co-infected with FeLV and FIV (OR 1.9) were more likely to have neoplasms. The diagnosis of lymphoma and leukemia was higher in cats infected with FeLV (OR 3.9 and 19.4, respectively) and coinfected with FeLV and FIV (OR 1.9 and 19.3, respectively). The odds of diagnosing bacterial diseases were higher in cats coinfected with FeLV and FIV (OR: 2.8), whereas the odds of viral diseases were higher in those infected with FeLV (OR: 2.8), with 2.2 times more diagnoses of feline infectious peritonitis. Neoplastic and infectious diseases in FIV-infected cats did not differ significantly from those in uninfected cats. According to our results, a high prevalence of retroviral infections was observed in southern Brazil, mainly in relation to FeLV. Infected cats were significantly younger than uninfected cats. The main causes of death associated with FeLV infection and FeLV and FIV coinfection were neoplastic and infectious diseases. In contrast, FIV infection was not associated with any specific condition.

INTERIM RESULTS OF THE PML-16, PML-19 PROTOCOLS FOR PRIMARY MEDIASTINAL LARGE B-CELL LYMPHOMA THERAPY

Introduction. Primary mediastinal lymphoma (PML) is an aggressive lymphoid tumor treatment success of which is determined by induction therapy. To date, none of the standard chemotherapy regimens (CT) have demonstrated an advantage in efficacy. Intensive therapy programs are associated with high toxicity. Aim - to evaluate the efficacy and toxicity of two pilot prospective treatment protocols PML-16 and PML-19 as well as the possibility of using the analysis of freely circulating tumor DNA (ctDNA) to assess MRD in patients with PML. Materials and methods. From January 2016 to January 2022, 34 previously untreated PML patients were included in the study;average age - 32;stage > I - in 60 %;extramediastinal lesions - in 14.7 %;bulky disease - in 73.5 % of patients. Positron emission tomography combined with computed tomography (PET-CT) was performed;ctDNA was determined to assess the completeness of remission. Results. Eighteen patients received treatment according to the PML-16 protocol (6 courses of chemotherapy;2 blocks of RmNHL-BFM-90 + 4 courses of R-EPOCH). After the end of therapy, all 18 patients achieved PET-negative remission. The next 16 patients received treatment according to the PML-19 protocol (4 courses of chemotherapy;2 blocks of R-mNHL-BFM-90 + 2 courses of R-EPOCH) in combination with lenalidomide. After the end of therapy, 9 (56 %) patients achieved PET-negative remission;7 (44 %) retained pathological activity (D4-5 points). After 3 and 6 months 15 (94 %) patients achieved normalization of metabolic activity. Considering the high frequency of false-positive results in patients with PML, a ctDNA study was performed to determine the depth of remission in 15 patients. After the end of therapy, all 15 patients had complete elimination of ctDNA. Of these, 5 (33 %) remained PET-positive at the end of treatment. During further observation, after 3-6 months, in 4 patients the level of metabolic activity decreased to physiological without the use of consolidating therapy. After the end of therapy, one patient suffered the new coronavirus infection, COVID-19. A month later, residual formation of SUVmax 14.2 remained in the mediastinum. The patient is currently under observation. With a median follow-up of 36 months (9 to 76 months) all 34 patients are in remission. Conclusion. The effectiveness of PML-16 made it possible to abandon the consolidation therapy and refuted the idea of the need for 6 courses of CT. The combination of programs based on the application of the principle of high-dose short-pulse induction of remission (R-mNHL-BFM-90) in combination with the prolonged administration of medium doses (R-EPOCH) was crucial in achieving a successful result. The inclusion of lenalidomide in the "PML-19" program made it possible to achieve complete remission in 100 % of cases after 4 courses. The possibility of using DNA analysis to assess MRD in patients with PML was shown.Copyright © 2022 Izdatel'stvo Meditsina. All rights reserved.