Hemic and Lymphatic Diseases Commons^™

Serological Evidence Of Severe Fever With Thrombocytopenia Syndrome Virus And Igm Positivity Were Identified In Healthy Residents In Vietnam, Xuan Chuong Tran, Sung Hye Kim, Jeong-Eun Lee, So-Hee Kim, Su Yeon Kang, Nguyen D Binh, Pham V Duc, Phan T K Phuong, Nguyen T P Thao, Wonwoo Lee, Joon-Yong Bae, Man-Seong Park, Misun Kim, Jeong Rae Yoo, Sang Taek Heo, Kyeong Ho An, Jung Mogg Kim, Nam-Hyuk Cho, Sun-Ho Kee, Keun Hwa Lee

Faculty, Staff and Student Publications

Severe fever with thrombocytopenia syndrome (SFTS), an emerging tick-borne viral disease, is prevalent in East Asia and has also been reported in Southeast Asia since 2019. SFTS patients in Vietnam were first reported in 2019. However, the seroprevalence of severe fever with thrombocytopenia syndrome virus (SFTSV) in Vietnam has not been reported. To investigate the seroprevalence of SFTSV in Vietnam, we collected serum samples from 714 healthy residents in Thua Thien Hue and Quang Nam Province, Vietnam, and the seroprevalence of SFTSV was assessed using immunofluorescence antibody assay (IFA), Enzyme-Linked Immunosorbent Assays (ELISAs) and the 50% focus reduction neutralization test …

Thromboembolism In Children With Multisystem Inflammatory Syndrome: A Literature Review, Neethu M Menon, Lakshmi V Srivaths

Faculty, Staff and Student Publications

Multisystem inflammatory syndrome in children (MIS-C) is a hyperinflammatory response observed in children several weeks to months after acute infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). On review of all published cases of thromboembolism (TE) as a complication of MIS-C, 33 cases of TE were found with incidence ranging from 1.4 to 6.5%. TE occurred mostly in children aged 12 years and above. One-third of the cases were cerebral infarcts and the remaining cases included intracardiac and radial arterial thromboses, upper and lower extremity deep vein thrombosis, pulmonary embolism, and splenic infarcts. Five were asymptomatic cases and 3/33 (9%) …

Metabolic, Physiological And Anatomical Responses Of Soybean Plants Under Water Deficit And High Temperature Condition, Roberto Gomes Vital, Caroline Müller, Francisco Bruno Silva Freire, Fábia Barbosa Silva, Priscila Ferreira Batista, David Fuentes, Arthur Almeida Rodrigues, Luciana Minervina Freitas Moura, Danilo Menezes Daloso, Adinan Alves Silva, Andrew Merchant, Alan Carlos Costa

Faculty, Staff and Student Publications

Water deficit (WD) combined with high temperature (HT) is the major factor limiting agriculture worldwide, and it is predicted to become worse according to the current climate change scenario. It is thus important to understand how current cultivated crops respond to these stress conditions. Here we investigated how four soybean cultivars respond to WD and HT isolated or in combination at metabolic, physiological, and anatomical levels. The WD + HT increased the level of stress in soybean plants when compared to plants under well-watered (WW), WD, or HT conditions. WD + HT exacerbates the increases in ascorbate peroxidase activity, which …

Clinical Relevance Of Proteomic Profiling In De Novo Pediatric Acute Myeloid Leukemia: A Children’S Oncology Group Study, Fieke W Hoff, Anneke D Van Dijk, Yihua Qiu, Chenyue W Hu, Rhonda E Ries, Andrew Ligeralde, Gaye N Jenkins, Robert B Gerbing, Alan S Gamis, Richard Aplenc, E Anders Kolb, Todd A Alonzo, Soheil Meshinchi, Amina A Qutub, Eveline S J M De Bont, Terzah M Horton, Steven M Kornblau

Faculty, Staff and Student Publications

Pediatric acute myeloid leukemia (AML) remains a fatal disease for at least 30% of patients, stressing the need for improved therapies and better risk stratification. As proteins are the unifying feature of (epi)genetic and environmental alterations, and are often targeted by novel chemotherapeutic agents, we studied the proteomic landscape of pediatric AML. Protein expression and activation levels were measured in 500 bulk leukemic patients' samples and 30 control CD34+ cell samples, using reverse phase protein arrays with 296 strictly validated antibodies. The multistep MetaGalaxy analysis methodology was applied and identified nine protein expression signatures (PrSIG), based on strong recurrent protein …

Tigit Is The Central Player In T-Cell Suppression Associated With Car T-Cell Relapse In Mantle Cell Lymphoma, Vivian Changying Jiang, Dapeng Hao, Preetesh Jain, Yijing Li, Qingsong Cai, Yixin Yao, Lei Nie, Yang Liu, Jingling Jin, Wei Wang, Heng-Huan Lee, Yuxuan Che, Enyu Dai, Guangchun Han, Ruiping Wang, Kunal Rai, Andrew Futreal, Christopher Flowers, Linghua Wang, Michael Wang

Faculty, Staff and Student Publications

BACKGROUND: Chimeric antigen receptor (CAR) T-cell therapy using brexucabtagene autoleucel (BA) induces remission in many patients with mantle cell lymphoma (MCL), and BA is the only CAR T-cell therapy approved by the FDA for MCL. However, development of relapses to BA is recognized with poor patient outcomes. Multiple CAR T-cell therapies have been approved for other lymphomas and the resistance mechanisms have been investigated. However, the mechanisms underlying BA relapse in MCL have not been investigated and whether any previously reported resistance mechanisms apply to BA-relapsed patients with MCL is unknown.

METHODS: To interrogate BA resistance mechanisms in MCL, we …

Association Between Abnormal Lipid Profile And Inflammation And Progression Of Myelodysplastic Syndrome To Acute Leukemia, Wei Qiao, Elliana Young, Chun Feng, Suyu Liu, Jeff Jin, Laila Noor, Cristhiam M Rojas Hernandez, Gautam Borthakur, Olga Gorlova, Vahid Afshar-Kharghan

Faculty, Staff and Student Publications

Clonal hematopoiesis of indeterminate potential (CHIP) is associated with a small risk of developing hematologic malignancies and a higher risk of cardiovascular diseases (CVD). We asked whether the reverse correlation exists and cardiometabolic risk factors have an impact on the progression of myelodysplastic syndrome (MDS) to acute myeloid leukemia (AML). We investigated the association between abnormal lipid profiles and inflammation in MDS, which shares many genetic mutations with CHIP, and the risk of developing acute leukemia. We examined the medical records of 11071 MDS patients. Among them, 5422 had at least one lipid profile or C-reactive protein (CRP) measurement. In …

International Consensus Classification Of Myeloid Neoplasms And Acute Leukemias: Integrating Morphologic, Clinical, And Genomic Data, Daniel A Arber, Attilio Orazi, Robert P Hasserjian, Michael J Borowitz, Katherine R Calvo, Hans-Michael Kvasnicka, Sa A Wang, Adam Bagg, Tiziano Barbui, Susan Branford, Carlos E Bueso-Ramos, Jorge E Cortes, Paola Dal Cin, Courtney D Dinardo, Hervé Dombret, Eric J Duncavage, Benjamin L Ebert, Elihu H Estey, Fabio Facchetti, Kathryn Foucar, Naseema Gangat, Umberto Gianelli, Lucy A Godley, Nicola Gökbuget, Jason Gotlib, Eva Hellström-Lindberg, Gabriela S Hobbs, Ronald Hoffman, Elias J Jabbour, Jean-Jacques Kiladjian, Richard A Larson, Michelle M Le Beau, Mignon L-C Loh, Bob Löwenberg, Elizabeth Macintyre, Luca Malcovati, Charles G Mullighan, Charlotte Niemeyer, Olatoyosi M Odenike, Seishi Ogawa, Alberto Orfao, Elli Papaemmanuil, Francesco Passamonti, Kimmo Porkka, Ching-Hon Pui, Jerald P Radich, Andreas Reiter, Maria Rozman, Martina Rudelius, Michael R Savona, Charles A Schiffer, Annette Schmitt-Graeff, Akiko Shimamura, Jorge Sierra, Wendy A Stock, Richard M Stone, Martin S Tallman, Jürgen Thiele, Hwei-Fang Tien, Alexandar Tzankov, Alessandro M Vannucchi, Paresh Vyas, Andrew H Wei, Olga K Weinberg, Agnieszka Wierzbowska, Mario Cazzola, Hartmut Döhner, Ayalew Tefferi

Faculty, Staff and Student Publications

The classification of myeloid neoplasms and acute leukemias was last updated in 2016 within a collaboration between the World Health Organization (WHO), the Society for Hematopathology, and the European Association for Haematopathology. This collaboration was primarily based on input from a clinical advisory committees (CACs) composed of pathologists, hematologists, oncologists, geneticists, and bioinformaticians from around the world. The recent advances in our understanding of the biology of hematologic malignancies, the experience with the use of the 2016 WHO classification in clinical practice, and the results of clinical trials have indicated the need for further revising and updating the classification. As …

Stones, Bones, And Groans With Cancerous Overtones - A Rare Case Of Diffuse Large B Cell Lymphoma Presenting As Hypercalcemia, Evan Becker, Caitlyn Moss, Steve Chung

Advances in Clinical Medical Research and Healthcare Delivery

Diffuse large B cell lymphoma (DLBCL) is a type of non-Hodgkin lymphoma that can present in a variety of ways including fever, weight loss, weakness, and drenching night sweats. Uncommonly, hypercalcemia of malignancy can be associated with DLBCL through multiple mechanisms that include synthesis of parathyroid hormone related peptide (PTHrP) or elevated calcitriol levels. It is estimated that hypercalcemia in the setting of DLBCL is present in 18% of newly diagnosed cases. This report details a case of an 80-year-old man with history of chronic anemia and CKD stage 3b that presented with weakness, decreased oral intake, and self-reported weight …

Covid-19 And Blood Clots: A Report Of Massive Pulmonary Embolism In Covid-19 Patient Supported On Veno-Venous Ecmo And The Utility Of Thrombolysis, Bindu Akkanti, Joseph Zwischenberger, Mark T Warner, Kha Dinh, Rahat Hussain, Farah Kazzaz, Pascal Kingah, Lisa M Janowiak, Biswajit Kar, Igor D Gregoric

Faculty, Staff and Student Publications

COVID-19 morbidity and mortality are not equivalent to other etiologies of acute respiratory distress syndrome (ARDS) as fulminant activation of coagulation can occur, thereby resulting in widespread microvascular thrombosis and consumption of coagulation factors. A 53-year-old female presented to an emergency center on two occasions with progressive gastrointestinal and respiratory symptoms. She was diagnosed with COVID-19 pneumonia and admitted to a satellite intensive care unit with hypoxemic respiratory failure. She was intubated and mechanically ventilated, but her ARDS progressed over the next 48 hours. The patient was emergently cannulated for veno-venous extracorporeal membrane oxygenation (V-V ECMO) and transferred to our …

Primary Sjögren's Syndrome Presenting As Cerebral Venous Thrombosis: A Rare Case, Mohan Sonu Chandra, Monisha G A, Ravi Kiran M

Faculty, Staff and Student Publications

Sjogren's syndrome is a late-onset, slowly progressing autoimmune disease characterized by the destruction of the exocrine glands by lymphocytic infiltration, resulting in dry mouth (xerostomia) and dry eyes (keratoconjunctivitis sicca). Sjögren's syndrome may be associated with various autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, and systemic sclerosis. We report a case of a 34-year-old female who delivered a live baby 20 days ago. She presented in a postictal state after two episodes of tonic-clonic movements of limbs with altered sensorium with a history of headache for seven days. Further evaluation revealed that the subject had a history of multiple …

Pure Erythroid Leukemia Is Characterized By Biallelic Tp53 Inactivation And Abnormal P53 Expression Patterns In De Novo And Secondary Cases, Hong Fang, Sa A Wang, Joseph D Khoury, Siba El Hussein, Do Hwan Kim, Mehrnoosh Tashakori, Zhenya Tang, Shaoying Li, Zhihong Hu, Fatima Zahra Jelloul, Keyur P Patel, Timothy J Mcdonnell, Tapan Kadia, L Jeffrey Medeiros, Wei Wang

Faculty, Staff and Student Publications

No abstract provided.

Supporting Self-Management For Patients With Interstitial Lung Diseases: Utility And Acceptability Of Digital Devices, Shima Aran, Orest O Kayder, Teena Chopra, Hani Abujudeh

Faculty, Staff and Student Publications

On December 2020, the US Food and Drug Administration issued the first emergency use authorization for a vaccine for the prevention of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report development of superficial thrombophlebitis in the ipsilateral breast of a 43-year-old female 7 days after receiving the first dose of the Pfizer-BioNTech COVID-19 vaccine. Given that this is the first case of superficial thrombophlebitis in the breast shortly after mRNA vaccination for COVID-19 reported to our knowledge, we suggest that this may be a rare vaccine-related event.

Tp53-Altered Chronic Lymphocytic Leukemia Treated With Firstline Bruton’S Tyrosine Kinase Inhibitor-Based Therapy: A Retrospective Analysis, Hua-Jay J Cherng, Raamis Khwaja, Rashmi Kanagal-Shamanna, Guilin Tang, Jan Burger, Philip Thompson, Alessandra Ferrajoli, Zeev Estrov, Koji Sasaki, Deepa Sampath, Xuemei Wang, Hagop Kantarjian, Michael Keating, William G Wierda, Nitin Jain

Faculty, Staff and Student Publications

Long-term follow up of prospective studies has shown that continuous Bruton's tyrosine kinase inhibitor (BTKi) therapy leads to durable remissions in previously untreated patients with TP53-altered chronic lymphocytic leukemia (CLL); however, it is unknown how variant allele frequency (VAF) of TP53 mutation (TP53-m) or percentage of cells with deletion of chromosome 17p [del(17p)] influences efficacy of firstline BTKi. We performed a retrospective analysis of 130 patients with CLL with baseline del(17p) and/or TP53-m treated with BTKi with or without the BCL2 inhibitor venetoclax (VEN) and with or without CD20 antibody in the firstline setting. A total of 104/130 (80%) patients …

Real-World Third Covid-19 Vaccine Dosing And Antibody Response In Patients With Hematologic Malignancies, Michael A. Thompson, Sigrun Hallmeyer, Veronica E. Fitzpatrick, Yunqi Liao, Michael P. Mullane, Stephen C. Medlin, Kenneth Copeland, James L. Weese

Journal of Patient-Centered Research and Reviews

Purpose: This study sought to describe the changes in immune response to a third dose of either Pfizer’s or Moderna’s COVID-19 mRNA vaccine (3V) among patients with hematologic malignancies, as well as associated characteristics

Methods: This retrospective cohort study analyzed pre-3V and post-3V data on 493 patients diagnosed with hematologic malignancies across a large Midwestern health system between August 28, 2021, and November 1, 2021. For antibody testing, S1 spike antigen of the SARS-CoV-2 virus titer was used to determine serostatus.

Results: Among 493 participants, 274 (55.6%) were seropositive both pre- and post-3V (+/+) while 115 (23.3%) seroconverted to positive …

Pneumonitis After Immune Checkpoint Inhibitor Therapies In Patients With Acute Myeloid Leukemia: A Retrospective Cohort Study, Ajay Sheshadri, Alberto A Goizueta, Vickie R Shannon, David London, Guillermo Garcia-Manero, Hagop M Kantarjian, Farhad Ravandi-Kashani, Tapan M Kadia, Marina Y Konopleva, Courtney D Dinardo, Sherry Pierce, Abdulrazzak Zarifa, Aya A Albittar, Linda L Zhong, Fechukwu O Akhmedzhanov, Muhammad H Arain, Mansour Alfayez, Ahmad Alotaibi, Mehmet Altan, Aung Naing, Tito R Mendoza, Myrna C B Godoy, Girish Shroff, Sang T Kim, Saadia A Faiz, Dimitrios P Kontoyiannis, Fareed Khawaja, Kristofer Jennings, Naval G Daver

Faculty, Staff and Student Publications

Background: Immune checkpoint inhibitors (ICI), combined with hypomethylating agents, can be used to treat acute myeloid leukemia (AML), but this strategy results in a high rate of pneumonitis. The authors sought to determine risk factors for pneumonitis development and whether pneumonitis increased mortality.

Methods: The authors conducted a retrospective review of 258 AML patients who received ICI-containing regimens from 2016 to 2018. A multidisciplinary adjudication committee diagnosed pneumonia and pneumonitis by reviewing symptoms, imaging, microbiology, and response to therapies. To measure risk factors for pneumonitis and mortality, multivariate Cox proportional hazards models were constructed. Pneumonia, pneumonitis, and disease progression were …

Antiphospholipid Antibodies And Vitamin D Deficiency In Covid-19 Infection With And Without Venous Or Arterial Thrombosis: A Pilot Case-Control Study, Ruchi Shah, Yaqub Nadeem Mohammed, Tracy J Koehler, Jasmeet Kaur, Margarita Toufeili, Priyanjali Pulipati, Ahmed Alqaysi, Ali Khan, Mahrukh Khalid, Yi Lee, Parveen Dhillon, Anna Thao Dan, Nicholas Kumar, Monica Bowen, Anupam A Sule, Geetha Krishnamoorthy

Faculty, Staff and Student Publications

BACKGROUND: Coronavirus disease-2019 (COVID-19) is associated with thromboembolism. Antiphospholipid antibody (APLa) formation is one of the mechanisms. Vitamin D deficiency has been associated with thrombosis in antiphospholipid antibody syndrome.

OBJECTIVE: Measure APLa and vitamin D in hospitalized COVID-19 patients with and without thrombosis to evaluate if thromboembolism is associated with concomitant APLa and vitamin D deficiency.

METHODS: Case-control study. Hospitalized COVID-19 patients with a thromboembolic event (ischemic stroke, myocardial infarction, deep venous thrombosis/pulmonary embolism, Cases n = 20). Controls (n = 20): Age, sex-matched without thromboembolic events. Patients with autoimmune disorders, antiphospholipid antibody syndrome, thrombophilia, anticoagulation therapy, prior thromboembolism, chronic …

Platelet Function In Trauma: Is Current Technology In Function Testing Missing The Mark In Injured Patients?, Jacob B Schriner, Mitchell J George, Jessica C Cardenas, Scott D Olson, Kimberly A Mankiewicz, Charles S Cox, Brijesh S Gill, Charles E Wade

Faculty, Staff and Student Publications

Platelets are subcellular anucleate components of blood primarily responsible for initiating and maintaining hemostasis. Following injury to a blood vessel, platelets can be activated via several pathways, resulting in changed shape, adherence to the injury site, aggregation to form a plug, degranulation to initiate activation in other nearby platelets, and acceleration of thrombin formation to convert fibrinogen to fibrin before contracting to strengthen the clot. Platelet function assays use agonists to induce and measure 1 or more of these processes to identify alterations in platelet function that increase the likelihood of bleeding or thrombotic events. In severe trauma, these assays …

Lenalidomide Enhances Cd23car T Cell Therapy In Chronic Lymphocytic Leukemia, Sarah Tettamanti, Maria Caterina Rotiroti, Greta Maria Paola Giordano Attianese, Silvia Arcangeli, Ronghua Zhang, Priyanka Banerjee, Giovanni Galletti, Sheighlah Mcmanus, Massimiliano Mazza, Fabio Nicolini, Giovanni Martinelli, Cristina Ivan, Tania Veliz Rodriguez, Federica Barbaglio, Lydia Scarfò, Maurilio Ponzoni, William Wierda, Varsha Gandhi, Michael Keating, Andrea Biondi, Federico Caligaris-Cappio, Ettore Biagi, Paolo Ghia, Maria Teresa Sabrina Bertilaccio

Faculty, Staff and Student Publications

Chimeric antigen receptors (CAR)-modified T cells are an emerging therapeutic tool for chronic lymphocytic leukemia (CLL). However, in patients with CLL, well-known T-cell defects and the inhibitory properties of the tumor microenvironment (TME) hinder the efficacy of CAR T cells. We explored a novel approach combining CARs with lenalidomide, an immunomodulatory drug that tempers the immunosuppressive activity of the CLL TME. T cells from patients with CLL were engineered to express a CAR specific for CD23, a promising target antigen. Lenalidomide maintained the in vitro effector functions of CD23.CAR+ T cells effector functions in terms of antigen-specific cytotoxicity, cytokine release …

Prediction Of Survival With Intensive Chemotherapy In Acute Myeloid Leukemia, Koji Sasaki, Farhad Ravandi, Tapan Kadia, Courtney Dinardo, Gautam Borthakur, Nicholas Short, Nitin Jain, Naval Daver, Elias Jabbour, Guillermo Garcia-Manero, Joseph Khoury, Sergej Konoplev, Sanam Loghavi, Keyur Patel, Guillermo Montalban-Bravo, Lucia Masarova, Marina Konopleva, Hagop Kantarjian

Faculty, Staff and Student Publications

Progress with intensive chemotherapy and supportive care measures has improved survival in newly diagnosed acute myeloid leukemia (AML). Predicting outcome helps in treatment decision making. We analyzed survival as the treatment endpoint in 3728 patients with newly diagnosed AML treated with intensive chemotherapy from 1980 to 2021. We divided the total study group (3:1 basis) into a training (n = 2790) and a validation group (n = 938). The associations between survival and 27 characteristics were investigated. In the training cohort, the multivariate analysis identified 12 consistent adverse prognostic variables independently associated with worse survival: older age, therapy-related myeloid neoplasm, …

Thromboelastography Profiles Of Hemophilia A Patients On Emicizumab, Daniel J. Vanzweden, Meera Chitlur, Charity J. Stadler

Medical Student Research Symposium

Emicizumab is a new monoclonal antibody developed to dtreat people with Hemophilia A, especially those with antibodies. However, breakthrough bleeding can still occur in patients taking Emicizumab. TEG is a global coagulation assay which measures coagulability through viscosity. This study describes the use of tissue factor activated TEG in measuring bleeding profiles in patients taking Emicizumab. The goal of this prospective study is to determine if TEG can be used, which variables of TEG might be useful, and how much more useful it is than the current standard, aPtt. Findings include a 25% increased R time and 24% increased K …