Acute myeloid leukemia complicated by post COVID-19 multi-system inflammatory syndrome-children

Corona Virus disease 2019 (COVID-19) pandemic has presented a huge challenge to the health care system in terms of magnitude of cases and to pediatric oncology units with varied clinical presentations. Acute myeloid leukemia(AML) is a rare heterogenous cancer of childhood with an induction mortality around 15% in our country due to neutropenic sepsis. Multisystem inflammatory syndrome in children(MIS-C) is an hyperinflammatory syndrome seen 4–6 weeks after COVID-19 infection. COVID infection in some of these children would have gone unnoticed. Here we report a two year eight months old boy diagnosed with AML on induction chemotherapy developed post COVID MIS-C. © 2022

Long-Term Efficacy and Safety of Zanubrutinib in Patients with Relapsed/Refractory (R/R) Marginal Zone Lymphoma (MZL): Final Analysis of the Magnolia (BGB-3111-214) Trial

Introduction: Advanced MZL is generally incurable, with periods of remission and relapse. Zanubrutinib (BGB-3111), a potent and highly specific next-generation Bruton tyrosine kinase (BTK) inhibitor, was approved in the US and Canada for R/R MZL based on the MAGNOLIA primary analysis (BGB- 3111-214;NCT03846427);here, the final MAGNOLIA analysis is presented. Method(s): This was a phase 2, multicenter, single-arm study of adult patients (pts) with R/R MZL (>=1 prior CD20-directed therapy). Zanubrutinib (160 mg twice daily) was given until disease progression or unacceptable toxicity. The primary endpoint was overall response rate (ORR) by independent review committee (IRC) per Lugano classification. Secondary endpoints were investigator-assessed ORR, duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Efficacy was assessed by positron emission tomography (PET)-based Lugano criteria for IRC-confirmed fluorodeoxyglucose (FDG)-avid disease at baseline;non-avid disease was assessed by computed tomography (CT)-based criteria. Result(s): As of May 4, 2022, 68 pts were treated (median age=70 y [range 37-95];>=75 y=27.9%). MZL subtypes included extranodal (38.2%), nodal (38.2%), splenic (17.6%), and unknown (5.9%). The median number of prior therapies was 2 (range 1-6);32.4% of pts had disease refractory to last therapy, most (89.7%) had prior chemoimmunotherapy, and 7 (10.3%) had rituximab monotherapy as their only prior treatment. Sixty-one pts (89.7%) had FDG-avid disease. After a median follow-up of 28.0 mos (range 1.6-32.9) and a median treatment duration of 24.2 mos (range 0.9-32.9), 66 pts were efficacy- evaluable. IRC-assessed ORR (complete response [CR]+partial response [PR]) was 68.2% (CR=25.8%). By subtype, (Figure Presented)(Figure Presented)ORR/CR rates were 64.0%/40.0% (extranodal), 76.0%/20.0% (nodal), 66.7%/8.3% (splenic), and 50.0%/25.0% (unknown). Median DOR, PFS, and OS were not reached. Over 70.0% of pts were alive or progression-free after 2 years (Figure). Sensitivity analysis using only CT-based criteria (n=66) showed an ORR of 66.7% and CR of 24.2%. The most common treatment-emergent AEs were bruising (23.5%), diarrhea (22.1%), and constipation (17.6%). Neutropenia (8.8%) and COVID-19 pneumonia (5.9%) were the most common Grade >=3 AEs. Five pts (7.4%) died due to unrelated AEs: COVID-19 pneumonia=2, acute myeloid leukemia=1, myocardial infarction=1, septic encephalopathy=1. Hypertension occurred in 3 pts (4.4%), atrial fibrillation and atrial flutter in 1 pt (1.5%) each;none led to treatment withdrawal. One pt (1.5%) had a Grade 3 gastrointestinal hemorrhage while receiving rivaroxaban. None of the pts required dose reduction. Conclusion(s): In this final analysis with over 2 years of median follow-up, zanubrutinib continues to demonstrate durable disease control and was generally well tolerated, with no new safety signals observedCopyright © 2023 American Society for Transplantation and Cellular Therapy

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

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

Diagnostic and Treatment Obstacles in Acute Myeloid Leukemia: Social, Operational, and Financial.

Acute myeloid leukemia (AML) can affect individuals of all ages, but is more common in older adults. It has been estimated that AML accounted for 1% of all newly diagnosed cancers in the USA in 2022. The diagnostic process varies depending on the presenting symptoms and the healthcare facility that patients attend at diagnosis. The treatment process is long and prone to complications, requiring experienced medical professionals and appropriate infrastructure. Treatment of the disease did not change greatly over the years until 2017 when targeted therapies were licensed. The treatment of AML is associated with significant direct economic costs. A number of obstacles originating both from individual patients and the healthcare system may be encountered during the diagnosis and treatment of the disease, which may negatively impact the optimal management of the disease process. In this article, we focus primarily on the social, operational, and financial obstacles including the corona virus disease 2019 (COVID-19) pandemic experienced during the diagnosis and treatment of AML.

Giant Cellulitis-Like Sweet Syndrome Masquerading As Cellulitis and Shingles: A Case Report and Literature Review.

Sweet syndrome (SS) is also known as acute febrile neutrophilic dermatoses. Clinically, SS features fever, arthralgias, and the sudden onset of an erythematous rash. The morphologies of skin lesions in SS are heterogenous, varying from papules, plaques, and nodules to hemorrhagic bullae, which sometimes makes the diagnosis of SS more challenging. We report a 62-year-old obese male with a history of chronic myeloid leukemia in remission for 10 years who presented with a rash for five days. The patient reported prodromal flu-like symptoms with subjective fever, malaise, cough, and nasal congestion followed by a sudden onset, painful, non-pruritic rash. The rash was associated with bilateral hip arthralgias and abdominal pain. The patient denied any recent travel, exposure to sick contacts, or the use of any new medications. Physical examination showed a well-demarcated, non-blanching, confluent, erythematous plaque involving the bilateral buttocks and extending to the lower back and flanks with coalescent "juicy"-appearing plaques and flaccid bullae. No oral or mucosal involvement was noted. Laboratory investigations revealed mild leukocytosis, elevated inflammatory markers, and acute kidney injury. The patient was started on antibiotics given the cellulitis-like skin lesions, leukocytosis with neutrophilia, and elevated inflammatory markers. Dermatology was consulted, who attributed the patient's rash to shingles and recommended initiating acyclovir and obtaining a skin biopsy. However, the patient's rash and arthralgias worsened with anti-viral treatment while awaiting pathology results. Antinuclear antibodies, complement, human immunodeficiency virus, hepatitis panel, blood cultures, and tumor markers were all negative. Flow cytometry showed no evidence of hematopoietic neoplasms. The skin punch biopsy revealed dense neutrophilic infiltration in the dermis with no evidence of leukocytoclastic vasculitis, consistent with acute neutrophilic dermatoses. The diagnosis of giant cellulitis-like Sweet syndrome was established, and the patient was started on prednisone 60 milligrams daily. His symptoms improved promptly with steroid treatment. Our case suggests that SS can camouflage a wide spectrum of diseases, including cellulitis, shingles, vasculitis, drug eruptions, leukemia cutis, and sarcoidosis, which emphasizes the importance of keeping a high index of suspicion for SS when assessing the clinical constellations of fever, neutrophilia, and erythematous plaques suggesting atypical cellulitis. Approximately 21% of Sweet syndrome is associated with malignancy. Sweet syndrome can precede, concur with, or follow the onset of malignancy. Due to the lack of a systematic approach to patients with SS, under-investigation and diagnostic delays are common. Therefore, further screening and continuous monitoring in patients with SS becomes especially important in facilitating the early detection of a potential underlying malignancy and assists in initiating adequate therapy.

When it doesn't run in the blood(vessels) - events involved in vascular disorders.

In the current issue of the Biomedical Journal the underlying pathology of hemodynamic compromise in acute small subcortical infarction are elucidated. A follow-up study in patients with childhood Kawasaki disease is presented, as well as an insight into the gradually decreasing antigen expression in cases of acute myeloid leukemia. Furthermore this issue provides an exciting update concerning COVID-19 and the use of CRISPR-Cas, a review about computational approaches in the research of kidney stone formation, factors connected to central precocious puberty, and why a rock star of paleogenetics recently received a Nobel Prize. Additionally, this issue contains an article proposing the repurposing of the lung cancer drug Capmatinib, a study of how the gut microbiome develops in neonates, an impulse about the role of the transmembrane protein TMED3 in esophageal carcinoma, and the revelation about how competing endogenous RNA influences ischemic stroke. Lastly, genetic reasons for male infertility are discussed, as well as the relation between non-alcoholic fatty liver disease and chronic kidney disease.

A case of aleukemic leukemia cutis after COVID-19 infection presenting as facial rash.

Aleukemic leukemia cutis (ALC) is a rare condition that is characterized by leukemic cells in the skin before presenting in the peripheral blood or bone marrow. We report a case of a 43-year-old woman who underwent assessment for bilateral facial nodules arising 1 month after COVID-19 infection. A punch biopsy specimen showed a malignant neoplasm primarily composed of immature blasts dissecting through the collagen in the dermis, concerning for myeloid sarcoma versus leukemia cutis. Bone marrow and blood specimens were negative for hematologic malignancy. The patient was appropriately treated with chemotherapy and is recovering well. This report highlights an interesting case of ALC following COVID-19 infection presenting as an isolated facial rash. Whether there is a true relationship between the patient's COVID-19 infection and her abrupt presentation of leukemia remains unclear, but we present this case regardless, in an effort to highlight a potentially unique association requiring further study.

Severe epidermolysis bullosa acquisita in a patient with graft-versus-host disease: causal or coincidental?

Graft-versus-host disease (GvHD) is common after haematopoietic cell transplantation (HCT). Mucocutaneous manifestations are variable and may simulate autoimmune bullous dermatoses. However, the association of GvHD with autoimmune disorders, including bullous dermatoses, is also well recognized. We describe a patient with GvHD in whom severe and relapsing epidermolysis bullosa acquisita (EBA) was diagnosed 3 years after transplant and propose a causal association with GvHD. A 66-year-old woman developed GvHD following allogeneic HCT for acute myeloid leukaemia in 2016. This affected her gastrointestinal tract and skin but improved with oral corticosteroids and ciclosporin. In 2019 she presented with a widespread rash consisting of large, tense, haemorrhagic blisters. Histological features were in keeping with EBA. Direct immunofluorescence was also consistent with EBA, demonstrating linear positivity for IgG and C3 confined to the blister base, as was detection of collagen VII antibodies on indirect immunofluorescence. She was admitted and treated with high-dose oral steroids, ciclosporin and intravenous immunoglobulin (IVIg) with eventual resolution of blistering. Although further IVIg administration was planned as an outpatient, this coincided with the start of the COVID-19 pandemic and she elected not to attend and also stopped all medication. Despite this, her EBA remained quiescent until September 2021 when she was readmitted with a severe deterioration in blistering and significant dysphagia due to an oesophageal stricture, with a weight of 31.7 kg. Once again, she responded rapidly to oral prednisolone and IVIg. Dapsone was considered but precluded by G6PD deficiency and there were clinical and adherence concerns about using mycophenolate mofetil. Upon discharge she was again nonadherent to medication and failed to attend for planned IVIg. She flared and was admitted for a third time in December 2021, requiring gastrostomy for nutritional support;her weight at this time was 26.4 kg. Her EBA is currently well controlled on prednisolone and IVIg. EBA is a rare, acquired blistering disorder secondary to autoantibodies targeting type VII collagen. Previous studies have found circulating basement membrane zone (BMZ) antibodies in 24% of chronic GvHD patients, possibly generated in response to chronic BMZ damage (Hofmann SC, Kopp G, Gall C et al. Basement membrane antibodies in sera of haematopoietic cell recipients are associated with graft-versushost disease. J Eur Acad Dermatol Venereol 2010;24: 587-94). Corresponding clinical manifestations are rare, with bullous pemphigoid the most frequently reported. EBA is much less common with four previously reported cases [Brassat S, Fleury J, Camus M, et al. (Epidermolysa bullosa acquisita and graftversus- host disease). Ann Dermatol Venereol 2014;141: 369-73 (in French)]. As a fifth case of EBA, our patient provides further evidence of a likely pathophysiological relationship between GvHD and autoimmune subepidermal bullous dermatoses, and highlights the significant challenges of managing these vulnerable patient groups during the COVID-19 pandemic.

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

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

"Inside out" - An exceptional intussusception

Introduction: We present the first case of appendiceal intussusception associated with myeloid sarcoma in a young patient. Minimally invasive techniques used along the clinical course are highlighted. Case description: A 2.5-year-old boy was admitted after three weeks of COVID-19 infection with ongoing symptoms of MIS-C. Due to constipation, distended belly and vomiting, US was done which showed ileocolic intussusception. After unsuccessful hydrostatic reduction laparoscopic exploration was performed, where the vermiform appendix was found to be thickened and partially intussuscepted into the coecum. The ileocecal region was exteriorized transumbilically. After manual reduction of the intussusception, a long, thickened, fragile appendix was removed. Histopathology revealed myeloid sarcoma. Bone marrow investigation identified acute myeloid leukemia. During the oncological treatment, laparoscopic cholecystectomy was necessary due to cholecystitis and cholelithiasis. The child recovered uneventfully in terms of surgical complications, with good cosmetic result. Conclusion(s): No similar case in childhood was found in the English literature. Unusual symptoms and radiological findings of intussusception can conceal unexpected disorders. Minimally invasive technique offered advantages in the treatment of the presented patient and can be recommended to treat intussusception or cholelithiasis, if applicable, during an ongoing oncological treatment as well.Copyright © 2023 The Authors

Comprehensive analysis of the novel omicron receptor AXL in cancers.

The SARS-CoV-2 is constantly mutating, and the new coronavirus such as Omicron has spread to many countries around the world. Anexelekto (AXL) is a transmembrane protein with biological functions such as promoting cell growth, migration, aggregation, metastasis and adhesion, and plays an important role in cancers and coronavirus disease 2019 (COVID-19). Unlike angiotensin-converting enzyme 2 (ACE2), AXL was highly expressed in respiratory system cells. In this study, we verified the AXL expression in cancer and normal tissues and found AXL expression was strongly correlated with cancer prognosis, tumor mutation burden (TMB), the microsatellite instability (MSI) in most tumor types. Immune infiltration analysis also demonstrated that there was an inextricable link between AXL expression and immune scores in cancer patients, especially in BLCA, BRCA and CESC. The NK-cells, plasmacytoid dendritic cells, myeloid dendritic cells, as one of the important components of the tumor microenvironment, were highly expressed AXL. In addition, AXL-related tumor neoantigens were identified and might provide the novel potential targets for tumor vaccines or SARS-Cov-2 vaccines research in cancer patients.

A Phase I Trial of Allogeneic γδ T Lymphocytes From Haploidentical Donors in Patients With Refractory or Relapsed Acute Myeloid Leukemia.

Introduction We report the results of a phase I clinical trial NCT03790072 of an adoptive transfer of γδ T lymphocytes from haploidentical donors in patients with refractory/relapsed acute myeloid leukemia after lymphodepletion regimen. Patients and methods Healthy donor mononuclear cells collected by leukapheresis were consistently expanded to generate products of 109 to 1010 γδ T cells. Seven patients received donor-derived T cell product at doses of 106/kg (n = 3), 107/kg (n = 3), and 108/kg (n = 1). Results Four patients had bone marrow evaluation at day 28. One patient had a complete remission, one was classified as morphologic leukemia-free state, one had stable disease and one had no evidence of response. In one patient, there was evidence of disease control with repeat infusions up to 100 days after first dosing. There were no treatment-related serious adverse events or treatment-related Common Terminology Criteria for Adverse Events grade 3 or greater toxicities at any dose level. Allogeneic Vγ9Vδ2 T cell infusion was shown to be safe and feasible up to a cell dose of 108/kg. Discussion In agreement with previously published studies, the infusion of allogeneic Vγ9Vδ2 cells was safe. The contribution of lymphodepleting chemotherapy to responses seen cannot be ruled out. Main limitation of the study is the low number of patients and interruption due to COVID-19 pandemic. Conclusion These positive Phase 1 results support progression to phase II clinical trials.

Perspectives of caregivers of older adults with acute myeloid leukemia during initial hypomethylating agents and venetoclax chemotherapy.

BACKGROUND: Older adults with AML commonly receive a hypomethylating agent (HMA) as first-line therapy. The addition of venetoclax (VEN) to HMAs has been shown to improve remission rates and overall survival. The use of combination therapy (HMA + VEN) requires frequent follow-up, results in longer infusion times, and likely increases caregiver responsibility at home. We describe experiences of informal caregivers (family/friends) providing care to older adults with AML receiving HMA + VEN. METHODS: Fourteen caregivers of older adults with AML receiving HMA + VEN (September 2020 to September 2021) were recruited as part of a control group of an ongoing NIH-funded clinical trial. Semi-structured interviews were conducted to gain initial insight into caregiver experiences at the start of HMA + VEN treatment. Two researchers analyzed the data using thematic content analysis. Data saturation occurred when no new themes were found in subsequent interviews, but all interviews were coded and synthesized. RESULTS: Of the 14 caregivers interviewed, the majority were spouses (n = 10), female (n = 13), and aged 45 to 83 (median age 65). We identified five themes: (1) the impact of an AML diagnosis in older adulthood, (2) care recipient condition changes, (3) perspectives of caregiving roles and tasks, (4) factors influencing caregiving experiences, and (5) support system roles. CONCLUSIONS AND IMPLICATIONS: Caregivers for older adults with AML report a range of experiences navigating health systems, caregiving responsibilities, and resource needs. The risk for caregiver burden and unmet needs should be addressed to improve caregivers' abilities to provide care.

The impact of COVID-19 on acute myeloid leukemia patients undergoing allogeneic stem cell transplantation: a concise review.

This study aimed to delineate the possible impact of COVID-19 on acute myeloid leukemia (AML) patients in terms of diagnosis, chemotherapy, bone marrow transplant, and vaccination response. Allogeneic stem cell transplantation is markedly affected by the COVID-19 pandemic, as both donors and recipients must be healthy for transplantation to be feasible and successful. Delays in the identification of well-matched donors have been predicted, and represent a special challenge. Therefore, future donors should be tested for COVID-19. The outcome of delayed transplantation is vague and masked by variations in stem cell source along with disease subtype. However, if transplant delay results in recurrence of minimal residual disease, a negative impact on survival is anticipated.

Milrinone-induced platelet inhibition in patients supported on veno-aterial extracorporal membrane oxygenation: a case series

Case Report: Purpose: Milrinone is an inodilator that is used in the treatment of cardiogenic dysfunction and shock. It causes increased cardiac output by stimulating myocardial contractility, enhancing cardiac relaxation, and reducing afterload via phosphodiesterase III inhibition, preventing cyclic adenosine monophosphate (cAMP) degradation. Increased cAMP concentrations are known to inhibit platelet aggregation. Veno-arterial-extracorporeal membrane oxygenation (VA-ECMO) is an extracorporeal treatment option for inotrope-refractory cardiogenic shock and is often used in conjunction with inodilators. Often, patients supported on ECMO require systemic anticoagulation to prevent clotting complications. Therefore, thromboelastography (TEG) with platelet mapping is used to help gauge a patient's clotting status and gives clinicians information about the degree of platelet inhibition present. We present the case of two patients, both supported on VA-ECMO, who developed platelet inhibition with clinically significant bleeding while on milrinone, requiring the cessation of the milrinone infusion. Cases: First, we present an adult female in her fourth decade of life who required VA-ECMO for Covid-19 ARDS and cardiogenic shock. TEG platelet mapping was obtained for clinically significant bleeding from her trachea and gastrointestinal tract. Ten days after starting milrinone, adenosine-5'-diphosphate (ADP) inhibition was elevated at 67.4% and arachidonic acid (AA) inhibition normal at 1.8%. Twenty days after starting milrinone, ADP inhibition was 93.3% and AA inhibition was 76.4%. Milrinone discontinued and repeat TEG platelet mapping (10 days after discontinuation) showed ADP inhibition of 76.8% and AA inhibition of 0%. Her lowest ADP inhibition was 41.9%, approximately 1 month after milrinone discontinuation. Milrinone again attempted and ADP inhibition was 87.9% and AA inhibition 89.2% within 24 hours of initiation. No data available for platelet inhibition prior to starting milrinone. Next, we present a 9 year old female with acute myeloid leukemia who required VA-ECMO for septic shock. Initial TEG platelet mapping, obtained 2 days after milrinone initiation, showed ADP inhibition of 43.6% and AA inhibition of 98.7%. Two days after discontinuation of milrinone, her ADP inhibition was 19.6% but AA inhibition remained elevated at 91.9%. However, after 4 days off milrinone, her ADP inhibition was normal at 15.5% and AA inhibition mildly elevated at 33.6%. No data available for platelet inhibition prior to starting milrinone. Conclusion(s): Milrinone is a known platelet inhibitor due to increased intracellular cAMP concentrations. For patients on ECMO and milrinone, care should be given to the degree of platelet inhibition and potential risk of clinically significant bleeding. Further studies are needed to further investigate the correlation between milrinone, platelet inhibition, and clinically significant bleeding in ECMO patients. Copyright © 2023 Southern Society for Clinical Investigation.

GATA2 deficiency presenting as fever and rash

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

Respiratory virus infections in cancer patients in a tertiary care hospital-characteristics and outcome of the seasons 2016-2 018

Introduction: Respiratory virus infections may entail a vital threat to immunocompromised patients sufering from hematological/oncological malignancies. We become aware within the scope of COVID-19 pan-demia that specific data on respiratory viral epidemiology and outcome in these patients are rare but essential for high risk patient Management. Method(s): We performed a retrospective single-center study analyzing clinical and laboratory parameters as well as outcome of cancer patients with respiratory virus infections during the seasons 2016-2018. Result(s): We identifed 615 hematological patients with first diagnosis of respiratory virus infections. Tese patients were mainly male with a median age of 55 and mainly sufered from Acute Myeloid Leukemia as underlying disease followed by Non-Hodgkin-Lymphomas and Multiple Myelomas. 50% of patients had undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT). Mainly, respiratory virus infections were detected by multiplex PCRs derived from naso-pharyngeal swabs (97%), sputum (2%) or bronchoalveolar lavage (1%). The biggest fraction sufered from Parainfuenzaviruses (PIV;n=186), followed by 122 patients with first diagnosis of Respiratory Syncytial Virus (RSV), 113 patients with Rhinoviruses (RV), 81 patients with Infuenzaviruses, 58 patients with Metapneumoviruses (MPV) and 55 patients with Coronaviruses (none of them SARS-CoV-2). Signifcant changes in overall survival between the different respiratory virus infections could not be observed. 27% of all patients had to be treated in hospital for a mean of 20 days, with an equal proportion of patients afer allo-HSCT (50%). Hospitalized patients showed a substantial mortality of 30%. Interestingly, mortality in the subgroup of hospitalized patients afer allo-HSCT was slightly lower (22%). Deceased hospitalized patients with respiratory viral infection had higher levels of C-reactive protein for Infuenzaviruses (p=0.027), PIV (p=0.017) and RSV (p=0.013) than survivors whereas levels of Leukocytes, Lactatdehydrogenase, and Creatinin were not signifcantly changed. Conclusion(s): Despite preventive strategies and increased awareness, we observed still a substantial mortality of respiratory viral infections in cancer patients. Preemptive treatment strategies might have the potential to afect overall survival indicated by the lower mortality in patients afer allo-HSCT. However, overall survival was not infuenced by type of respiratory virus infection.