EBV-related lymphoproliferative disease in Wiskott-Aldrich Syndrome patient

Case: Wiskott-Aldrich Syndrome (WAS) is a rare X-linked inborn error of immunity caused by mutations in the WAS gene. It is classically characterized by immunodeficiency, eczema, and micro-thrombocytopenia. It has been known since the 1960s that patients with WAS have an increased risk of lymphoproliferative disease though the exact incidence remains unknown in the American population. Limited case reports have discussed EBV-related lymphoproliferative disease in patients with WAS. We present a case of a 9-year-old boy with known WAS complicated by eczematous rash, thrombocytopenia, recurrent ear infections, and monoclonal gammopathy who was found to have submandibular EBV-associated lymphoid hyperplasia with associated lung and retroperitoneal lymphadenopathy. Family had been offered treatment with hematopoietic stem cell transplant but declined multiple times in the past. Earlier in the year, he presented with possible MIS-C with negative SARS-CoV-2 PCR. He presented to our hospital with mastoiditis and lymphadenopathy. Physical examination showed severe eczema on hands and tender right mastoid. Laboratory evaluation showed thrombocytopenia, elevated IgG of 6290, IgA of 744, IgE of 827, low IgM of 41, and 14% response to pneumococcal titers. He was empirically treated with intravenous antibiotics. ENT performed right postauricular incision and drainage and the culture grew Hemophilus influenza. Throughout his hospital stay, his submandibular lymphadenopathy became more prominent despite treatment. Core needle biopsy of right submandibular lymph node was suggestive of EBV-associated lymphoid hyperplasia. EBV PCR and antibodies were both positive. CT chest, abdomen, and pelvis revealed multifocal pulmonary lymphadenopathy and a diffuse, bilateral nodularity as well as retroperitoneal and mesenteric lymphadenopathy. He was given four doses of weekly Rituximab, which successfully decreased EBV viremia below linear detectability. Immunoglobulin replacement therapy (IgRT) was initiated. Bronchoalveolar lavage and lung biopsy were performed and are results are currently pending. Discussion(s): We present a case of a 9-year-old boy with known WAS awaiting transplant who was found to have submandibular EBV-associated lymphoid hyperplasia with associated lung and retroperitoneal lymphadenopathy. While lymphoproliferative disease is a known complication of WAS, EBV-related lymphoproliferative disease in WAS patients has only been reported as case reports and remains a rare but known complication of patient with WAS.Copyright © 2023 Elsevier Inc.

Immunotherapy: RAPID ACCESS TO VIRUS-SPECIFIC T CELLS FOR ADOPTIVE IMMUNOTHERAPY FOR COMPASSIONATE USE IN AUSTRALIA

Background & Aim: Adoptive T cell immunotherapy holds great promise for the treatment of viral complications. Our group has been developing and trialling virus-specific T cell therapies for more than 20 years. Recently, we have generated a repository of multi-virus-specific T cells for our clinical trials. Unfortunately, for many patients with viral complications, there is no suitable trial through which to access these therapies. In Australia, the Therapeutic Goods Administration has a Special Access Scheme (SAS) to enable provision of unapproved therapies for compassionate use. Our research group is now a leading Australian provider of "off-the-shelf" and custom-grown allogeneic virus-specific T cells to hospitals for patients with no other treatment options. Methods, Results & Conclusion(s): We have generated a repository of multi-virus-specific T cells from 20 healthy donors, with up to 150 doses of T cells per donor generated from a single blood sample. Each product batch is thoroughly characterised in terms of viral antigen specificity, HLA restriction and alloreactivity. These T cells target a combination of Epstein-Barr virus, cytomegalovirus, BK polyomavirus, John Cunningham virus and adenovirus epitopes. We have also generated a repository of SARS-CoV-2-specific T cells and occasionally grow custom patient-specific batches of T cells from nominated donors, on request. Since 2008, we have provided virus-specific T cells to 15 hospitals across Australia, and the volume of supply requests has significantly increased in recent years, as clinicians have gained interest in adoptive immunotherapy. In 2022, we provided T cells for 26 patients via the SAS. The majority were experiencing post-transplant complications, including cytomegalovirus disease, BK virus-associated haemorrhagic cystitis and post-transplant lymphoproliferative disorder. Through our clinical trials, we have developed rigorous processes for T cell therapy manufacture and characterisation, in addition to a computer-based selection algorithm, which we apply to SAS cases. As these cases are not part of a clinical trial, concomitant therapy varies, and monitoring is not uniform. However, we have received reports of clinical benefit from adoptive T cell therapy. These include cases of reduction in viral load, improvement in symptoms, and complete resolution of infection. We believe that these promising T cell therapies should be available to hospitals through a nationally funded centre for cellular therapies for critically ill patients.Copyright © 2023 International Society for Cell & Gene Therapy

Immunotherapy: FAMILIAL CD45RA DEPLETED T CELLS TO TREAT SEVERE REFRACTORY INFECTIONS IN IMMUNOCOMPROMISED PATIENTS

Background & Aim: Immunocompromised patients are susceptible to high-risk opportunistic infections and malignant diseases. If available, most antiviral and antifungal drugs are quite toxic, relatively ineffective, and induce resistance in the long term. Methods, Results & Conclusion(s): We have previously demonstrated the safety of adoptive cell therapy for COVID-19 patients with CD45RA negative cells containing SARS-CoV-2-specific T cells from a donor, chosen based on HLA compatibility and cellular response to SARS-CoV-2 peptide pools. After finishing a Phase 2 randomized multicenter clinical trial (RELEASE, NCT04578210), we concluded that the infusion is safe, effective, accelerates lymphocyte recovery and shows hallmarks of an immune response. To use adoptive cell therapy to treat COVID-19 it would be necessary to develop a biobank of living drugs. For that, we examined the immune evolution performing a longitudinal analysis from previously SARS-CoV-2 infected and infection- naive individuals covering 21 months from infection. Cellular responses were maintained over time while humoral responses increased after vaccination but were gradually lost. Therefore, the best donors would be recovered individuals and two months after vaccination. We also evaluated the effect of dexamethasone (current standard of care treatment for COVID-19 and other infections involving lymphopenia) and Interleukin-15 (cytokine involved in T-cell maintenance and survival) on CD45RA negative. Dexamethasone did not alter cell functionality, proliferation or phenotype at a clinical-practice concentration, while interleukin-15 increased the memory T-cell and T-regulatory cell activation state, and interferon gamma release. Furthermore, we applied the adoptive passive transfer of CD45RA negative cells containing pathogen-specific memory T-cells to other infectious diseases characterized by sustained lymphopenia. We infused six immunocompromised patients with Cytomegalovirus, BK virus, Aspergillus, and Epstein-Barr virus lymphoproliferative disease. Patients experienced pathogen clearance, resolution of symptoms and lymphocyte increase. Transient microchimerism was detected in three patients. The use of CD45RA negative cells containing specific memory T cells of a third-party donor for treating severe pathogenic diseases in immunocompromised patients is feasible, safe, and effective, and has an advantage over other cell therapies such as lower costs and a less complex regulatory environment.Copyright © 2023 International Society for Cell & Gene Therapy

Remember to Screen the Spleen: A Case Study of Spontaneous Splenic Rupture

Introduction: Splenic rupture is a potentially life-threatening condition often associated with trauma or viral infection. Most cases of splenic rupture are due to trauma, viral infection, lymphoproliferative disease, malaria, tick borne illness, splenic neoplasms, connective tissue disease, or in one case, sneezing. Spontaneous splenic rupture (SSR) is a rare condition with less than five cases reported. In this case, we present a 20-year-old male who was seen with abdominal pain who was found to have an SSR with no clear etiology. Case Description/Methods: A 20-year-old male with no relevant past medical history presented with abdominal pain that radiated to the left shoulder. The patient reported the pain began after an episode of emesis which occurred 12 hours prior to arrival. He reported experiencing shortness of breath and pain on inspiration. He denied any fall or trauma, recent travel or sick contacts, fevers, weight loss, or night sweats. His social history was significant for occasional marijuana use. Upon physical exam, the patient had diffuse abdominal tenderness most pronounced in the left upper quadrant without any palpable masses. Relevant labs included a hemoglobin of 12.2, WBC count within normal limits and unremarkable manual differential, and an INR of 1. Blood parasite, heterophile antibodies, COVID, influenza, CMV, and HIV were negative. Computed tomography angiography (CTA) revealed hematoma at the splenic hilum. Interventional radiology was consulted and did not recommend intervention at time of initial presentation. Patient was admitted;his hemoglobin remained stable and he was monitored with serial abdominal exam then discharged the following day. Imaging was repeated one month later which revealed near complete resolution of hematoma. (Figure) Discussion: SSR should be considered on the differential diagnosis of physicians when encountering patients who present with LUQ pain with unclear etiology. The patient presented with the characteristic Kehr's sign (left diaphragmatic irritation resulting in referred pain to the left shoulder) but not the Ballance sign (palpable tender mass in the left upper quadrant). The incidence of SSR is estimated to be around 1 to 7% with a mortality rate of 12.2% so a broad differential for young patients presenting with abdominal pain must be entertained and should include splenic rupture as it is a potentially life-threatening condition.

Restoration of Humoral Response to Covid-19 Vaccination in Rituximab-Treated Patients

Background: Previous studies had demonstrated that patients with hematologic malignancies had suboptimal antibody response after receiving COVID-19 vaccines, especially among those having previously treated with anti- CD20 monoclonal antibodies. Method(s): Adult patients with non-Hodgkin's lymphoma or chronic lymphocytic leukemia (CLL) were enrolled before receiving the second dose of SARS-CoV-2 vaccine. Determinations of anti-SARS-CoV-2 spike and nucleocapsid IgG titers were performed every 1-3 months, after they received the second and the third dose of SARS-CoV-2 vaccine, respectively. Patients were excluded from analysis if they were diagnosed with COVID-19. All serum samples were tested for anti-nucleocapsid antibody and those tested positive were excluded from subsequent analyses. Result(s): A total of 85 participants were enrolled, including 42 (49.4%) with diffused large B-cell lymphoma, and 13 (15.3) with follicular lymphoma and 9 with CLL. 72 (84.7%) participants had received anti-CD20 monoclonal antibodies, with a median interval of 24 months between last anti-CD20 treatment and the second dose of vaccine, and 21 (24.7%) had HIV infection. Factors associated with failure to achieve an anti-spike IgG titer >141 BAU/ mL within 12 weeks after the second dose of vaccine included HIV infection (adjusted odds ratio [aOR], 0.14;95% CI, 0.04-0.51), active hematologic disease (aOR, 5.50;95% CI 1.42-21.32), receipt of anti-CD20 monoclonal antibodies (aOR, 6.65;95% CI 1.52-29.07), and receipt of two doses of homologous mRNA vaccination (aOR, 0.17;95% CI 0.05-0.56). In the participants having previously treated with anti-CD20 regimen, only 8.6% achieved an antibody response ( >141 BAU/mL) in the first year, while 78.3% achieved anti-spike IgG titer > 141 BAU/mL after two years post B-cell depleting treatment. After the third dose of SARS-CoV-2 vaccine, 53.6% achieved an antispike IgG titer > 141 BAU/mL in the first year post anti-CD20 treatment. Conclusion(s): Our study demonstrated that previous treatment with anti-CD20 monoclonal antibodies was associated a lower antibody response among patients with lymphoproliferative disorders receiving two doses of SARS-CoV-2 vaccine. While two doses of SARS-CoV-2 vaccines might not be sufficient even one year apart from the last dose of rituximab, a third dose of vaccine may boost anti-spike IgG particularly in the subset of recent exposure to rituximab. Anti-spike IgG determined 1-3 months after the second (A) / third (B) dose of COVID-19 vaccine, stratified by the interval between last anti-CD20 regimen and the second / third dose of COVID-19 vaccine. (Figure Presented).

Progressive multifocal leukoencephalopathy, neuroradiology-neuropathology

Introduction: Progressive multifocal leukoencepha-lopathy (PmL) is an unfavorable demyelinating disease of the CNS caused by reactivation of JC virus (JCV). JCV is a double-stranded DNA human polyomavirus predominatingly acquired in childhood. Blood samples taken from healthy persons indicate that 50-90% of adults have been exposed to this virus. JCV is an opportunistic pathogen, with PmL manifesting primarily in patients with immunodefciency or taking immunomodulatory treatments or with lymphoproliferative diseases. We report a patient who developed PmL shortly after diagnosis of follicular lymphomma. Case presentation: A 70-year-old-woman admitted to the neurological departament with hemiparesis, psy-chomotor slowing down, balance problems, dizziness and in depressed mood. the patient underwent aorto-femoral transplant 12 years ago and for 10 years was under constant observation of a hematologist due to enlarged lymph nodes. Five years ago, the patient had planoepithelial cell carcinoma removed. the patient also sufered from COViD-19 infection and sufered from depression. elevated leukocytosis and D dimers, were the only abnormal results obtained in laboratory tests. However, pulmonary embolism was excluded in Ct angio. Cytometry of blood showed follicular lymphoma. Radiological fndings: mRi and Ct scans showed multiple asymmetrical pathological areas of hyperin-tense signal in t2-dependent images, hypointense in t1-dependent ones and Ct-hypodense regions which extended continuously in control examinations. they were located in the white matter of multiple lobes of both brain hemispheres subcortically and periventric-ullary. the subcortical U-fbers were involed. they did not show contrast enhancement and mass efect. they showed peripheral ring and patchy difusion restriction particularly at their leading edge. in spite of the used steroid therapy the patient's health deteriorated rapidly. the patient died of symptoms of cardio-respiratory failure 1 month after admission to hospital. Neuropathological features: the neuropathological examination revealed numerous foci of demyelination in the white matter of the frontal lobe, the parietal lobe in the pons and in the cerebellum. myelin losses were accompanied by damage to oligodendrocytes and proliferation of macrophages. the nuclei of the damaged oligodendrocytes were enlarged and hyperchromatic, and some had a "ground-glass" appearance typical of viral infection. the astrocytes were bizarre with lobulat-ed, hiperchromatic or hypochromatic nuclei and damage of cytoplasmic procesesses (clasmatodendrosis). Conclusion(s): the triad of neuropathological injuries: destruction of oligodendrocytes with intranuclear viral inclusions ("ground-glass" appearance), multifocal demyelination and bizarre astrocytes allowed for the diagnosis of late form of classical progressive multifo-cal leukoencephalopathy (cPmL), despite the short time since diagnosis of follicular lymphoma, but with many years of enlargement of the lymph nodes.

Adult and Paediatric Case-based Conference 2021

The proceedings contain 68 papers. The topics discussed include: post-transplant lymphoproliferative disorder (PTLD) in a patient with rheumatoid arthritis;cancer, covid and control of RA - a toxic combination?;continuation of golimumab (anti-TNF) in a patient with SpA and low-risk prostate cancer, what is the right decision?;orbital lymphoma in a 72-year-old lady with rheumatoid arthritis: an argument for rituximab;a case of cancer mimicking inflammatory arthritis;managing relapsing and refractory lupus nephritis in juvenile systemic lupus erythematosus: a case report;a case of juvenile systemic lupus erythematosus with pyrexia of unknown origin;recurring brachial plexopathy- the zebra among the horses;and Neisseria meningitidis as a cause of isolated bilateral polyarticular native knee joint septic arthritis.

Spotting the Needle Amongst the Haystack - When Asthma Isn't Asthma

Introduction/Background: Eosinophilic granulomatosis with polyangiitis (EGPA), previously known as Churg-Strauss Syndrome, is a rare, small to medium vessel ANCA associated vasculitis. Hallmarks of EGPA include asthma, chronic rhinosinusitis, and peripheral neuropathy. EGPA is characterized by a prodrome of asthma and allergic rhinitis, followed by peripheral blood hyper-eosinophilia and accumulation of extravascular eosinophils, and finally systemic vasculitis. Extrapulmonary involvement is common, sometimes with fatal outcomes. The onset of EPGA is typically between 25-50 years;however, EGPA also occurs during childhood and has a significant morbidity and mortality. Description/Method: Our patient presented to the emergency department with a 2-week history of lethargy, wheeze and left sided neck swelling. After testing COVID-19 positive eight months prior to this, she developed wheezy episodes and was subsequently diagnosed with asthma which was managed with bronchodilators as required. She was reviewed by an allergist who confirmed a dust mite allergy and prescribed Montelukast. She remained well during the summer months however during winter she had 3 distinctive episodes of wheeze and cough which were managed by antibiotics and prednisolone. In the emergency department, an echocardiogram was performed which showed a cardiac tamponade. She was transferred to CICU where she had a pericardial drain inserted. The fluid was abundant with inflammatory cells. Multiple investigations were performed as follows: Hb: 135g/L, wbc: 20.30 x 10 9/L, Eosinophils: 12.77 x 10 9/L, CRP: 51 mg/L, ESR: 75 mm/hr, LDH: 1188 IU/L, IgE: 8000 UI/ml, ANA, ANCA: negative. CT chest showed mediastinal lymphadenopathy and patchy bilateral infiltrate and cardiac MRI showed myopericarditis and LV fibrosis. BMA showed no malignant cells and sinusitis was confirmed by CT. On examination, she was underweight. Her nasal mucosa looked inflamed. Otherwise systemic examination was unremarkable. In the context of poor ejection fraction (20%) with LV fibrosis, urgent MDT was arranged and concluded that our working diagnosis was EGPA. The decision was made to start IV methylprednisolone 10mg/kg/day for 3 days and Ivermectin. That night our patient had a VF arrest which required a single shock conversion 4J/kg. There was 7-minute downtime. Treatment was escalated to include cyclophosphamide, rituximab and plasmapheresis. The patient made a remarkable recovery, extubated and transferred to a normal ward. Her eosinophils count and inflammatory markers improved dramatically following treatment. However, she developed severe neuropathic left leg pain and NCS confirmed peripheral neuropathy Discussion/Results: EGPA is a very rare disease and diagnosis can be challenging especially with the absence of histopathology diagnosis. Early empirical treatment especially in a very ill child in intensive care unit can save lives and divert the progress of the disease. This patient has fulfilled the American College of Rheumatology criteria to diagnose EGPA including asthma, eosinophil count > 10% of upper normal, peripheral neuropathy, pulmonary infiltrates on CT thorax and paranasal sinuses abnormalities. Cardiac biopsy of the fibrotic mass may be a useful tool for diagnosis;however, this invasive procedure may expose this patient with high risk of fatal arrhythmias. Since other causes of eosinophilia were ruled out including parasitic infections, lymphoproliferative disorders, and rare primary immunodeficiency syndromes (hyper-IgE syndrome due to STAT3 or DOCK8 deficiency and Omenn syndrome) and the patient responded well to treatment, the diagnosis of EGPA was supported. Key learning points/Conclusion: Asthma not responding to bronchodilator could be another diagnosis Eosinophilia should be interpreted with caution. Defer the need for histopathology diagnosis in critically ill children Cardiac involvement is a life-threatening marker Early diagnosis prevents life threatening complications.

Cancer, Covid and Control of Ra - a Toxic Combination?

Case report - Introduction: This case highlights the dilemma of keeping rheumatoid arthritis disease under control in active cancer cases and establishing a consistent multidisciplinary dialogue during a pandemic and staffing crises. During chemotherapy and active cancer treatment, disease-modifying therapies (conventional and biologic) are often stopped. In some cases, the potential benefits versus risks of restarting usual therapies have to be balanced against risks of suppressing disease activity with highdose steroids. Risks of infection (common and atypical) need to be considered. Case report - Case description: A is a 67-year-old female nonsmoker diagnosed with seropositive rheumatoid arthritis (RF, anti - CCP positive) in 2008. Other conditions include type 2 diabetes, atrial fibrillation (on warfarin), hypothyroidism and obstructive sleep apnoea. Due to active disease, despite triple therapy (methotrexate, sulphasalazine and hydroxychloroquine), anti-TNF therapy (etanercept) commenced in 2009 with primary non-response. However, she responded well to B-cell therapy (rituximab) in conjunction with oral methotrexate (25mg weekly) receiving annual infusions from 2010 to 2016. In 2017, an elective sleeve gastrectomy procedure for high BMI was abandoned after peritoneal deposits of concern were noted. Histology and CT imaging were consistent with a primary peritoneal malignancy (Stage 3c low-grade serous adenocarcinoma). Treatment involved debulking surgery (total abdominal hysterectomy, bilateral salpinoophorectomy, omentectomy) and tamoxifen. Treatment for rheumatoid arthritis stalled during this period but as frequent steroids were required for active joint inflammation, in agreement with the oncologists, she had a rituximab cycle in 2018. Unfortunately, in 2019 she had signs of cancer progression (elevated tumour markers, CT imaging) and has subsequently started carboplatin chemotherapy. She has been unable to continue methotrexate or rituximab pending completion of the chemotherapy cycles (ongoing). However, her arthritis is now uncontrolled without increased steroids. Due to recurrent flares, her maintenance dose has been increased from 5mg to 7.5-10mg prednisolone daily until we can establish if it is safe and appropriate to recommence her usual arthritis regime. Even without disease-modifying therapy like methotrexate and rituximab, risk of infection (including atypical ones) is still significant with the combination of chemotherapy and steroids. Risk of progressive joint damage and adverse quality of life with active arthritis also needs to be considered. Staffing crises, exacerbated by COVID pandemic issues, have added to complexity of decision making and coordination of regular multidisciplinary discussions regarding treatment. Case report - Discussion: Cancer is a known association in rheumatoid arthritis patients with a twofold higher risk of lymphoma compared to the general population. Whether condition or treatment affects risk remains unclear as immune dysregulation is relevant in both autoimmunity and cancer. Paraneoplastic, recent onset arthritis, chemotherapy- or immunotherapy-induced arthralgia/arthritis are also well documented. This case had a seropositive rheumatoid arthritis phenotype quite a few years prior to cancer diagnosis. Primary peritoneal cancer is uncommon, often presenting as in this case as an incidental finding. It is usually treated like ovarian cancer Whilst methotrexate has been implicated in lung cancer, melanoma and non-Hodgkin lymphoma, overall safety data suggest any risk is quite low (e.g., EBV-associated lymphoproliferative disorders usually resolve with drug discontinuation). It is also a known chemotherapeutic agent. Anti-TNF treatment algorithms generally exclude patients with recent cancer. Rituximab, originally developed as a cancer drug, is not thought to affect risk of cancer development or progression. Treatment with disease-modifying therapy (conventional and biologics) is often withheld in patients with active malignancy undergoing chemotherapy due to a theo etical risk of potentiated immunosuppression and toxicity, particularly cytopaenias. However, maintaining arthritis control with glucocorticoids also has short- and long-term risks. Combining chemotherapy agents like carboplatin with methotrexate has been used for urothelial carcinoma and can be well tolerated with close monitoring of haematological parameters. Thus, it could be argued this patient is at risk of infections whichever treatment approach is taken and regaining control of arthritis with recommencement of methotrexate and rituximab is much better for her quality of life. Regular multidisciplinary discussions are important to outline risks versus benefits of combined treatment. This may be difficult in practice during staffing crises. Covid risk in patients receiving rituximab and/or chemotherapy, timing and response to COVID vaccination are also important considerations. Case report - Key learning points: . Primary peritoneal cancer is uncommon and can present as an incidental finding . Whilst treatment for progressive cancer is important, withholding rheumatoid arthritis treatment can have a significant adverse impact on quality of life . Morbidity and mortality risks of stopping treatment versus combined treatment (cancer therapy and disease-modifying therapy) ideally needs to be fully discussed and agreed with the patient and all care providers - lack of "named" providers, restructuring, redeployment, multi-specialty care and a global pandemic can make coordination of this difficult.

FDG-avid lymph nodes (LN) in response to vaccines for SARS-CoV-2

Aim/Introduction: Vaccines against SARS-CoV-2 virus were developed due to the impetuous coronavirus pandemic. Vaccines hold a possibility to provoke side effects. The aim of our study was to examine the impact of COVID-19 vaccination on the incidence and duration of false-positive FDG-avid lymphadenopathy after vaccination with different types of vaccines and to determine its relationship with age, gender, and vaccine type. Material(s) and Method(s): The retrospective study included 103 patients who met the following criteria:18F-FDG PET/CT scan performed (in the period from August 2021 to December 2021) for staging or restaging of diagnosed oncological diseases at different time periods after vaccination Pfizer-BioNTech, Moderna-BioNTech and Oxford-AstraZeneca. Exclusion criteria were incomplete information about vaccination, patients with a diagnosed malignant lymphoproliferative disease, concomitant benign pathology of the lymphatic system, history of acute viral infection up to 3 months from the date of PET/CT. Result(s): False-positive reactive lymphadenopathy was identified in 35 (34%) of 103 patients included in our study cohort, which occurred during the first 2 weeks to 12 weeks after vaccination and manifested as increased metabolic activity in regional non-enlarged lymph nodes: ipsilateral axillary lymph nodes of levels I-III, as well as cervical LN of levels IV and VB). A significant moderate decline in metabolic activity in the LN over time was reported, as well as a decrease in the detection rate of PET-positive reactive findings with time. The results showed a trend of a positive relationship - the occurrence of reactive lymphadenopathy more often in women than in men. The detection rate, as well as the intensity of the activity of glucose metabolism, were higher in patients under the age of 50 compared to those >= 50 years. However, we did not find significant differences between the studied types of vaccines (p >0.05). Conclusion(s): Multidisciplinary physician awareness is essential regarding the possibility of false-positive FDG lymphadenopathy in relation to local inflammation and as a manifestation of the immune response due to COVID-19 RNA vaccination and adenoviral vector-based vaccine up to 12 weeks after injection, in order to optimize the clinical interpretation of hybrid scan results that determine the subsequent therapeutic approach of cancer patients. The results of the present study demonstrate the importance of vaccination on the contralateral side of the tumor drainage, as well as taking a thorough anamnesis. Keywords: FDG PET/CT, false positive lymphadenopathy, vaccination.

Monoclonal anti-CD20 antibodies in lymphomas therapy during the COVID-19 pandemic: pro and contra

The review presents the results of a combined analysis of literature data and own clinical observations regarding the safety and feasibility of using monoclonal anti-CD20 antibodies in the treatment of B-cell lymphoproliferative diseases during the COVID-19 pandemic. The main points of the pathogenesis of the influence of monoclonal anti-CD20 antibodies on the course of COVID-19 are described. The current trends in the modification of the accepted algorithms of lymphoproliferative diseases therapy with the inclusion of monoclonal anti-CD20 antibodies are summarized, and the possibilities of specific prevention by vaccination against COVID-19 are also considered. Copyright © 2022 ABV-Press Publishing House. All rights reserved.

POST-TRANSPLANT LYMPHOPROLIFERATIVE DISORDER (PTLD) IN RENAL TRANSPLANT PATIENTS WITH COVID-19

SESSION TITLE: Pulmonary Issues in Transplantation Case Report Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Post-transplant lymphoproliferative disorder (PTLD) is a life-threatening complication after transplantation. While there is evidence that hematologic malignancy is associated with increased severity in COVID-19 infection, there is little description of PTLD and COVID-19. CASE PRESENTATION: A 68-year-old man and a 68-year-old female, both of whom had prior renal transplantation, were admitted to the hospital with COVID-19 pneumonia. Both patients were vaccinated against COVID-19, though were negative for spike protein antibodies. The man was treated with remdesivir and the woman was treated with remdesivir and dexamethasone. Both patients improved and were discharged. Within a month, both had recurrent symptoms of dyspnea and fever requiring re-admission. They were hypoxic, the man requiring high flow nasal cannula and the woman requiring nasal cannula to maintain SpO2>90%. They had positive COVID-19 PCR tests, with cycle threshold lower than in their initial admissions, as well as chest imaging with bilateral infiltrates. The man had a pleural effusion with cytology consistent with PTLD and perinephric mass and retroperitoneal lymphadenopathy with biopsy confirming PTLD. The woman had a renal sinus mass with biopsy confirming PTLD. Both patients were treated with another 5 days of remdesivir and started on dexamethasone. The medical team discussed monoclonal antibody treatment, but the patients did not meet EUA criteria and compassionate use request was denied. To treat PTLD, both were initiated on Rituximab, Cyclophosphamide, Hydroxydaunomycin, Oncovin, and Prednisone (R-CHOP). Since then, both patients have had complicated and prolonged hospital courses. The woman developed renal failure and severe C.diff colitis complicated by toxic megacolon requiring total colectomy. The man developed renal failure, CMV viremia, and pseudomonas UTI. The patients were able to be weaned to room air, though ultimately the woman had to be intubated due to poor mental status and remains on low oxygen settings. Both patients continue to be persistently positive for COVID-19 by PCR. DISCUSSION: This case illustrates diagnosis and treatment of PTLD in two patients with COVID-19 infection. Of particular interest was the use of Rituximab, an anti-CD-20 antibody which impairs humoral immunity, in the treatment of PTLD, as the drug has been associated with increased risk of severe COVID-19 infection. Rituximab was particularly concerning as both patients had persistent COVID-19 without development of immunity despite prior vaccination, and both continue to be positive despite two months of active infection. The patients had improvement of their respiratory status, though have had poor and complicated clinical courses with renal and infectious complications. CONCLUSIONS: Treatment of PTLD in patient's with active COVID-19 may impair ability to clear virus, though impact on outcomes is unclear. Reference #1: Simpson-Yap, S., de Brouwer, E., Kalincik, T., Rijke, N., Hillert, J. A., Walton, C., Edan, G., Moreau, Y., Spelman, T., Geys, L., Parciak, T., Gautrais, C., Lazovski, N., Pirmani, A., Ardeshirdavanai, A., Forsberg, L., Glaser, A., McBurney, R., Schmidt, H., … Peeters, L. (2021). Associations of Disease-Modifying Therapies With COVID-19 Severity in Multiple Sclerosis. Neurology, 97(19). https://doi.org/10.1212/WNL.0000000000012753 Reference #2: Andersen, K. M., Bates, B. A., Rashidi, E. S., Olex, A. L., Mannon, R. B., Patel, R. C., Singh, J., Sun, J., Auwaerter, P. G., Ng, D. K., Segal, J. B., Garibaldi, B. T., Mehta, H. B., Alexander, G. C., Haendel, M. A… Chute, C. G. (2022). Long-term use of immunosuppressive medicines and in-hospital COVID-19 outcomes: a retrospective cohort study using data from the National COVID Cohort Collaborative. The Lancet Rheumatology, 4(1). https://doi.org/10.1016/S2665-9913(21)00325-8 Reference #3: Passamonti, F., Cattaneo, C., Arcaini, L. Bruna, R., Cavo, M., Merli, F., Angelucci, E., Krampera, M., Cairoli, R., della Porta, M. G., Fracchiolla, N., Ladetto, M., Gambacorti Passerini, C., Salvini, M., Marchetti, M., Lemoli, R., Molteni, A., Busca, A., Cuneo, A., … Corradini, P. (2020). Clinical characteristics and risk factors associated with COVID-19 severity in patients with haematological malignancies in Italy: a retrospective, multicentre, cohort study. The Lancet Haematology, 7(10). https://doi.org/10.1016/S2352-3026(20)30251-9 DISCLOSURES: No relevant relationships by Ian Mahoney No relevant relationships by Caroline Motschwiller

CHEST-WALL CASTLEMAN DISEASE MIMICKING THYMOMA DROP METASTASIS

SESSION TITLE: Amazing Chest Imaging Findings SESSION TYPE: Case Reports PRESENTED ON: 10/19/2022 11:15 am - 12:15 pm INTRODUCTION: Thoracic Castleman disease is challenging to diagnose and can mimic various lymphoproliferative disorders. Herein we present a case of unicentric thoracic castleman disease co-existing with thymoma, mimicking a thymoma drop metastasis. CASE PRESENTATION: A 50-year-old previously healthy Caucasian female presented to the emergency room with COVID-19 related respiratory symptoms. CTA was consistent with COVID-19 pneumonia and incidentally showed a 4.2 x 3.1 cm mass in the right anterosuperior mediastinum abutting the ascending aorta and superior right atrium, and a 3.3 x 2.1 cm mass in right posterior costophrenic sulcus abutting the right 11th rib raising suspicion for thymoma with a "drop metastases.” CT abdomen/pelvis was unrevealing. For proper staging, US guided biopsy of chest wall mass was performed which showed reactive lymphoid tissue. CT guided biopsy of the mediastinal mass revealed a thymoma. Due to ongoing concern for pleural metastases and possible sampling error with prior biopsy of the costophrenic lesion, she underwent surgical resection of the anterior mediastinal mass and chest wall lesion including part of 11th rib. The chest wall lesion was noted to be extrapleural. Surgical biopsy confirmed WHO grade B1 Thymoma and the chest wall lesion showed hyaline vascular Castleman disease. DISCUSSION: Pleural "Drop” metastasis from a thymoma or thymic carcinoma should be considered in patients with an anterior mediastinal mass and pleural based lesions. Imaging shows one or more pleural nodules or masses, which can be smooth, nodular, or diffuse. [1]. In our case, a basilar, discrete, nodular mass was suspicious for a drop metastasis. At the time of surgery, the lesion was noted to be extrapleural. Unicentric Castleman disease is a benign lymphoproliferative disorder which presents as a homogeneous, well-marginated, highly vascularized enhancing mass commonly involving the mediastinum. These lesions can mimic thymoma, lymphoma, sarcoma, hemangiopericytoma, and neural crest derived neoplasms. Pleural Castleman disease can arise from visceral and parietal pleura with extension into the chest wall or lung fissures and can cause pleural effusion. Intercostal disease can resemble other chest wall masses and cause rib erosions [2]. Chest-wall localization is a rare manifestation of Castleman disease often diagnosed due to non-specific thoracic symptoms such as dyspnea, cough, chest-wall pain or generalized malaise.[3] Complete excision of the lesion is generally curative with cure rate of 95-100%, with recurrence reported with partially resected lesions. CONCLUSIONS: Castleman disease located in the chest wall can present diagnostic and management challenges particularly when present in the context of other lesion with metastatic potential. Reference #1: 1.Benveniste, M.F.K., Rosado-de-Christenson, M.L., Sabloff, B.S., Moran, C.A., Swisher, S.G. and Marom, E.M. (2011). Role of Imaging in the Diagnosis, Staging, and Treatment of Thymoma. RadioGraphics, 31(7), pp.1847–1861. Reference #2: 2.Ko, S.-F., Hsieh, M.-J., Ng, S.-H., Lin, J.-W., Wan, Y.-L., Lee, T.-Y., Chen, W.-J. and Chen, M.-C. (2004). Imaging Spectrum of Castleman's Disease. American Journal of Roentgenology, 182(3), pp.769–775 Reference #3: 3. Rena, O., Casadio, C. and Maggi, G. (2001). Castleman's disease: unusual intrathoracic localization. European Journal of Cardio-Thoracic Surgery, 19(4), pp.519–521. DISCLOSURES: No relevant relationships by Peter LaCamera, value=Consulting fee Removed 04/06/2022 by Peter LaCamera No relevant relationships by Peter LaCamera, value=Consulting fee Removed 04/06/2022 by Peter LaCamera No relevant relationships by Alina Wasim

HEMORRHAGIC PLEURAL EFFUSION IN A PATIENT WITH CHRONIC LYMPHOCYTIC LEUKEMIA ON IBRUTINIB THERAPY

SESSION TITLE: Problems in the Pleura Case Posters 1 SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Ibrutinib is an irreversible inhibitor of Bruton's tyrosine kinase (Btk), approved for treatment of a variety of B-cell malignancies, including chronic lymphocytic leukemia (CLL). There is an association of increased risk of bleeding with ibrutinib due to platelet dysfunction caused by the medication. Bleeding is usually non-life threating such as subcutaneous or mucosal bleeding, epistaxis, and ecchymosis. But major bleeding has been reported such as intracranial hemorrhage and gastrointestinal hemorrhage. Thoracic complications from ibrutinib are rare. Below is a case report discussing a hemorrhagic pleural effusion thought to be caused by Ibrutinib. CASE PRESENTATION: Patient is a 78-year-old male initially diagnosed with CLL on flow cytometry showing a low-grade B cell lymphoproliferative process. Patient was monitored by Hematology and when kappa light chain numbers began to rise, a bone marrow biopsy was performed showing 90% infiltration of the marrow with lymphoid cells. Patient was started on Ibrutinib therapy and responded well to treatment. A year after starting therapy, patient presented to the emergency room with increased shortness of breath and fatigue. Patient was found to be COVID-19 positive and chest x-ray showed a large right sided pleural effusion. Thoracentesis was performed draining 1650cc of bloody fluid. Fluid studies revealed a lymphocytic effusion with RBC count 1,185375, WBC of 1751. Cultures and cytology were negative. On further history, patient was without recent trauma or surgery, CTA chest was negative for pulmonary embolism. QuantiFERON Gold test was negative, indicating low likelihood of tuberculosis. Patient was not on any antiplatelet or systemic anticoagulation medications. Ibrutinib therapy was held during hospitalization and pleural effusion did not reaccumulate. Patient passed away during hospital stay secondary to respiratory failure due to COVID-19. DISCUSSION: Ibrutinib is an orally bioavailable bruton tyrosine kinase inhibitor (BTKi) and forms an irreversible covalent bound to BTK at the Cysteine-481 residue. Ibrutinib predisposes to bleeding by inhibiting BTK and Tec, which play a role in the inhibitory signaling pathway of platelet collagen receptors such as glycoprotein VI (GP VI) and C-type lectin-like receptor 2 (CLEC-2). Our patient had no other risk factors for developing a hemorrhagic effusion. CLL itself can cause malignant effusions, one study found the incidence of malignant effusions among patients with CLL to be 9%, but the effusion was noted to be serous or serosanguinous and there was pleural involvement in all patients which was not the case in our patient. CONCLUSIONS: There is currently a minimal amount of data to guide clinicians regarding the use of ibrutinib in patients at high risk of bleeding or on anticoagulant or antiplatelet therapy. It is important to realize bleeding complications related to ibrutinib therapy can occur. Reference #1: Shatzel JJ, Olson SR, Tao DL, McCarty OJT, Danilov AV, DeLoughery TG. Ibrutinib-associated bleeding: pathogenesis, management and risk reduction strategies. J Thromb Haemost. 2017;15(5):835-847. doi:10.1111/jth.13651 Reference #2: Burger JA, Tedeschi A, Barr PM, et al. Ibrutinib as Initial Therapy for Patients with Chronic Lymphocytic Leukemia. N Engl J Med. 2015;373(25):2425-2437. doi:10.1056/NEJMoa1509388 Reference #3: Paydas S. Management of adverse effects/toxicity of ibrutinib. Crit Rev Oncol Hematol. 2019;136:56-63. doi:10.1016/j.critrevonc.2019.02.001 DISCLOSURES: No relevant relationships by fatima ali No relevant relationships by Joan Wiley

PERSISTENT COVID-19 INFECTION IN A PATIENT WITH CASTLEMAN DISEASE

SESSION TITLE: Rare Pulmonary Infections SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 01:35 pm - 02:35 pm INTRODUCTION: Castleman's Disease (CD) includes a group of rare and heterogenous lymphoproliferative disorders that share characteristic histopathological features. The etiology of CD is unknown. The condition results in episodic regional lymphadenopathy. Symptoms are driven by episodic cytokine excess. Clinical presentation can include fevers, night sweats, weight loss and fatigue. Life expectancy is not affected, however patients are at risk of developing various other conditions including amyloidosis, cryptogenic organizing pneumonia and lymphoma. COVID-19 is known to have periods of cytokine excess. In severe instances in can lead to cytokine storm, characterized by bilateral pulmonary infiltrates, worsening hypoxemia, and organ failure. We present the case of a 48 year-old female with CD who endured prolonged COVID-19 and cytokine storm. CASE PRESENTATION: A 48-year-old female with CD presented to the emergency department for shortness of breath. Six months prior to admission she had received one dose of the mRNA-1273 (Moderna) vaccine against SARS-CoV-2. Unfortunately, she contracted COVID-19 prior to the second dose. At that time she was hospitalized at a separate institution for COVID-19 and hypoxemia. The patient was treated with systemic glucocorticoids and remdesivir, and subsequently discharged home on supplemental oxygen via nasal cannula at 2 l/min. Unfortunately her respiratory status progressively declined over the following two months. During this time PCR testing for SARS-CoV-2 was positive on multiple occasions. She subsequently presented to our ER for dyspnea and hypoxemia. She once again tested positive by PCR. Inflammatory markers including fibrin degradation products, c-reactive protein and fibrinogen were severely elevated. Chest radiograph revealed bilateral infiltrates. The patient was placed on high flow oxygen and admitted to the ICU. Treatment was initiated with remdesivir, systemic glucocorticoids, and tocilizumab. Unfortunately, she continued to decline and was eventually placed on mechanical ventilation. The patient was then transferred to another institution for evaluation of extracorporeal membrane oxygenation. DISCUSSION: Both CD and COVID-19 are characterized by cytokine excess. Our patient with CD presented with persistent COVID-19. She remained symptomatic for close to six months. Her course was waxing and waning for the first few months and then progressively declined. Multiple PCR tests for SARS-CoV-2 were positive during this interval. We postulate that the proclivity of CD to cytokine excess had a synergistic effect on the inflammatory components of COVID-19 infection. This may have contributed to the protracted infection. CONCLUSIONS: More research is needed in patients with lymphoproliferative disorders and the impact of COVID-19 infection on their outcomes. Reference #1: Van Rhee, Frits, et al. "International, Evidence-Based Consensus Treatment Guidelines for Idiopathic Multicentric Castleman Disease.” American Society of Hematology, American Society of Hematology, 15 Nov. 2018, https://ashpublications.org/blood/article/132/20/2115/39506/International-evidence-based-consensus-treatment. Reference #2: "Castleman Disease: Symptoms, Causes, Treatments and Tests.” Cleveland Clinic, https://my.clevelandclinic.org/health/diseases/17920-castleman-disease. Reference #3: "Castleman Disease.” NORD (National Organization for Rare Disorders), 10 July 2017, https://rarediseases.org/rare-diseases/castlemans-disease/. DISCLOSURES: No relevant relationships by Wajahat Khan No relevant relationships by Nashwa Yosry

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

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

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

PROTECTION OF PATIENTS WITH HEMATOLOGIC MALIGNANCY FROM SEVERE INFECTION DURING PANDEMIA: ESTONIAN TWO CENTRES EXPERIENCE

Background: In the course of lymphoproliferative diseases, an immunodeficiency of humoral or cellular origin has been described. Infectious complications of common or atypical origin alter patients' lifestyles or result in severe, life-threatening hospitalizations. Hematology patients are prone to opportunistic infections after viral infection. In Estonia, chemotherapy for haematological patients is mainly covered in two regional centers in Tartu (University Hospital) and in Tallinn. The outpatient consultations are also covered in other parts of Estonia. In times of pandemic, when lockdowns are changing the situation and it has been difficult to travel to large centers, local hematology care needs for high-risk hematology elderly patients are growing. Aims: In the case of lymphoproliferative diseases, a secondary immune deficiency with severe infections can develop during the course of therapy, which is objectively discovered by immunoglobulin testing (IgG), and replased by immunoglobulin substitution. According to Kreuth IV, the value for prophylactic IgG replacement therapy is below 4g/l Methods: Review of the 20 case records of the two hospitals in Estonia, in Pärnu and in Kuressaare. Results: There are in regulare treatment or watching in Pärnu center and in Kuressaare center about 80 patients with lymphoproliferative disease. From them needed according to IgG status below 7(ref 7-16) 20 patients. The mean age of patisents is 70.8 ( range 38-89). The mean basic IgG (ref 7-16) in patients in Immunoglobulin treatment is 4,49 (range 3.3-6) .The intervall for prophylactic replasment was 4.6 or 8 weeks in 20 patients. From those 8 patients had SARS-Cov2 during this period, no patient was dying because of SARS-Cov2 infection and in 4 patients there was SARS-COV2 IgG pos later, in one patients SARS-COV2 IgG was negative afther the severe infection, in 3 patients is SARS-COV2 IgG not known afther frecovery from disease. Two patents died: one of secondary Pulm tumor related infection and one of sigmoidal ca, who had 6 months earlyer COVID19 severe infection. From 20 patients 9 diceided to have vaccination and 6 got no SARS-COVIgG antibodyes afther that. All patients had during 01.06.2019-01.02. 2022 years in some period immunosupressive treatment. Summary/Conclusion: We recommend the individualized protection of vulnerable hematologyc diseases patients with long-term illness. Secondary immunodeficient patients need during pandemic when hospital beds are overgrown immunoglobulin replasmenttherapy to prevent their unneccesary hospitalization.

SIGNIFICANT INCREASE IN NEWLY DIAGNOSED HEMATOLOGICAL MALIGNANCIES FOLLOWING LOCKDOWN EASE IN CROATIA

Background: Special epidemiological measures aimed at suppressing SARS-CoV-2 outbreak were introduced in Croatia in March 2020, thus reducing regular work capacity in hematological outpatient and inpatient care. In our hospital, this included relocating the entire Hematology Department to a remote location, reduction of hospital beds in the Hematology Inpatient Unit by approximately 60%, Day Clinic operating at a reduced capacity, and a complete suspension of Hematology Polyclinic during first lockdown. Aims: Herein we report our observation of unusually high incidence of newly diagnosed malignant hematological diseases following first lockdown ease in May/June 2020. Methods: We collected data of patients hospitalized in Hematology Department for 4 periods: May 1 - June 15, 2020 for the test arm, and the same calendar period during previous 3 years (May 1 - June 15 of each of the calendar years 2017, 2018 and 2019), for the control arm. The rationale for such design was that a phenomenon of re-establishing regular work capacity, following temporary restriction, was only observed in the test arm. The study included patients of both sexes older than 18 who were diagnosed with either: Hodgkin lymphoma (C81.0 -C81.9 according to the 10th ICD Revision), different types of non-Hodgkin lymphoma (subsections C82.0 - C83.9 and C85.1-C85), as well as multiple myeloma and malignant plasma cell neoplasms (C90.0 - C90.3). Excluded from our study were diagnoses of T/NK cell lymphoma (C84.0- C84.9;C86.0 - C86.6), malignant immunoproliferative diseases (C88.0 - C88.9), leukemias and other specified malignant neoplasms of lymphatic, hematopoietic and related tissues (C91.0 - C96.9) as well as polycythemia vera and non-malignant hematological diseases (D45 and D50 - D89 in ICD-10). Results: In years 2017-2019, similar numbers of patients were diagnosed with a hematological malignancy in our Department (n=4 for 2017, n=8 for 2018, n=4 for 2019) whereas in 2020, a total of 28 patients were diagnosed during the same calendar period (Hodgkin lymphoma: n=5, NHL n=12, multiple myeloma n=7, CLL/SLL n=4). Statistical analysis revealed a significant increase (p ≤0.05) of newly diagnosed hematological malignancies in May and first half of June 2020, when compared to the same calendar periods during previous three years. Further statistical analysis has not established significant differences in outcome (difference in EFS statistically insignificant, p=0.86), as we had expected in the short follow-up period. (Table Presented) Summary/Conclusion: Facilitating treatment of patients affected by the novel coronavirus represented a welcome change in healthcare system in early 2020, in our country and abroad. At the same time, however, the reduction of tertiary health care capacity aimed at population with hematological diseases presented serious risks for successful diagnosis and treatment outcome, a subject that gained wide attention in literature. It has been reported that, also due to psychological reasons, a fraction of patients delayed seeking medical attention after noticing symptoms. In our study we aimed at analyzing the effects of lockdown ease on the number of newly diagnosed hematological malignancies. We were able to demonstrate the effect of pandemic-related measures on detecting new disease cases. It remains to be clarified if a sudden surge in new diagnoses was due to delayed first physician's appointments/hospitalizations, as is suggested by available literature. The results of our study suggest that longer follow-up period will be required in order to clarify the effects of possible late diagnoses on the treatment outcome.