Hematology Commons^™

Superior Vena Cava Syndrome Due To Germ Cell Tumor In A Young Adult: Case Report, Manlio F. Lara Duck, Netzahualcoyotl Mayek Pérez, Juan Rosales Martínez

Research Symposium

Background: In superior vena cava syndrome (SVCS), the superior vena cava becomes mechanically obstructed by venous thrombus formation or by compression caused by intrathoracic tumors. SVCS is most common in men over 45 years of age; 22.5% of patients with SVCS have stage IV lung cancer or lymphoma. SVCS may occur secondary to extrathoracic tumors (testicular, ovarian, kidney, intestinal).

Case presentation: Male (24 years old) with a history of cancer in his maternal grandmother; denied drug addiction. Factory worker who denied being in direct contact with any chemicals and/or toxins. He reported non-productive cough; paroxysmal unilateral left facial edema without …

Atypical Dengue Fever With Severe Hematological Manifestations: A Case From The Rio Grande Valley, Elias Arellano Villanueva, Alhasan Asaad, Jose Campo Maldonado

Research Symposium

Background: Dengue fever, a mosquito-borne viral illness, is endemic in tropical regions, including border regions like the Rio Grande Valley while often self-limited, severe presentations such as dengue hemorrhagic fever and dengue shock syndrome highlight its challenges and complexities. This report describes an atypical dengue case with severe hematological manifestations, underscoring the diagnostic challenges and the importance of early recognition, multidisciplinary evaluation, and evidence-based management.

Case Presentation: A 22-year-old Hispanic female with no significant past medical history presented to the ED with hematemesis and fever following her travel to Monterrey, Mexico. Initial symptoms included high fever (107.6°F), chills, diarrhea, vomiting, …

Overlap Of Pnh With Myelodysplastic Syndrome: Diagnostic Challenges And Management Approaches, Alyssa L. Sepulveda, Ronald A. Shaju, Yolanda V. Gutierrez

Research Symposium

Background: Paroxysmal Nocturnal Hemoglobinuria (PNH) and Myelodysplastic Syndrome (MDS) are both hematologic disorders that overlap, posing challenges in diagnosis and management. PNH involves complement-mediated hemolysis and clonal hematopoiesis, while MDS is characterized by ineffective hematopoiesis and cytopenias. Their shared features, such as clonal mutations and bone marrow failure, can complicate differentiation. Flow cytometry is essential for identifying PNH clones and guiding treatment. Understanding this overlap is key to improving outcomes through targeted therapies and advanced management strategies.

Methods: A systematic review of PubMed, Science Direct, and Cochrane was conducted for articles published between 2000 and 2025. Keywords included 'paroxysmal nocturnal …

Hyperleukocytosis In A Neuroblastoma Patient After Treatment With Natural Killer T Cells Expressing A Gd2-Specific Chimeric Antigen Receptor And Il-15, Gengwen Tian, Amy N Courtney, Hangjin Yu, Saleh Bhar, Xin Xu, Gabriel A Barragán, Claudia Martinez Amador, Nisha Ghatwai, Michael S Wood, Deborah Schady, Antonino Montalbano, Shantan Reddy, Aoife M Roche, David De La Cerda, Donald Williams Parsons, Erica J Di Pierro, Frederic D Bushman, Andras Heczey, Leonid S Metelitsa

Faculty, Staff and Students Publications

The ability of immune cells to expand numerically after infusion distinguishes adoptive immunotherapies from traditional drugs, providing unique therapeutic advantages as well as the potential for unmanageable toxicities. Here, we describe a case of lethal hyperleukocytosis in a patient with neuroblastoma treated on phase 1 clinical trial (NCT03294954) with autologous natural killer T cells (NKTs) expressing a GD2-specific chimeric antigen receptor and cytokine interleukin 15 (GD2-CAR.15). This patient was the first to be treated on dose level (DL) 5 and the first patient whose product was restimulated with K562-derived artificial antigen-presenting cells (aAPCs) instead of autologous peripheral blood mononuclear cells …

Recombinant Factor Viia: New Insights Into The Mechanism Of Action Through Product Innovation, Miguel A Escobar, Maureane Hoffman, Giancarlo Castaman, Cedric Hermans, Johnny Mahlangu, Johannes Oldenburg, Charles L Percy, Mark T Reding, Amy D Shapiro, Steven W Pipe

Faculty, Staff and Student Publications

Management of bleeding in persons with hemophilia and inhibitors involves treatment with bypassing agents, including recombinant activated factor VII (rFVIIa). Two rFVIIa products are commercially approved for use in the United States and the European Union. Eptacog alfa and eptacog beta share the same amino acid sequence but differ in posttranslational modifications. Although rFVIIa has been used to manage bleeding in persons with hemophilia and inhibitors for over 30 years, its mechanisms of action is still being studied. In vitro and in vivo studies have suggested that rFVIIa could promote hemostasis by (1) increasing tissue factor-dependent activation of factor (F)X …

Management Of Hemolytic Transfusion Reactions In A Patient With Chronic Myelomonocytic Leukemia And Rare Antibodies: A Case Report, Grace S Park, Himachandana Atluri, Courtney D Dinardo, Bryan Guillroy, Jean Horak, Effrosyni Apostolidou, Maryam Buni, Guillermo Montalban Bravo, Naveen Pemmaraju

Faculty, Staff and Student Publications

Delayed hemolytic transfusion reaction (DHTR) poses a significant challenge in patients receiving blood transfusions. This case report highlights the complexities of managing DHTR in a newly diagnosed chronic myelomonocytic leukemia (CMML) patient with clinically significant JKa and little c antibodies during induction chemotherapy. A 46-year-old woman with CMML-2 who presented for induction chemotherapy was found to have hemolytic anemia. Due to presence of JKa and little c antibodies, she required intensive monitoring and supportive care measures. The coexistence of JKa and little c antibodies complicates transfusion management and chemotherapy tolerance in CMML patients.

High-Grade B-Cell Lymphoma Not Otherwise Specified, With Diffuse Large B-Cell Lymphoma Gene Expression Signatures: Genomic Analysis And Potential Therapeutics, Waseem Lone, Alyssa Bouska, Tyler A Herek, Catalina Amador, Joo Song, Alexander M Xu, Dylan Jochum, Issa Ismail Issa, Dennis D Weisenburger, Xuan Zhang, Sharath Kumar Bhagavathi, Tayla B Heavican-Foral, Sunandini Sharma, Ab Rauf Shah, Abdul Rouf Mir, Aisha Ahmad Alkhinji, Dalia El-Gamal, Bhavana J Dave, Keenan Hartert, Jiayu Yu, Mallick Saumyaranjan, Timothy C Greiner, Julie Vose, Timothy W Mckeithan, Kai Fu, Michael Green, Chengfeng Bi, Akil Merchant, Wing C Chan, Javeed Iqbal

Faculty, Staff and Student Publications

High-grade B-cell lymphoma not otherwise specified (HGBCL, NOS) has overlapping morphological and genetic features with diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL), leading to uncertainty in its diagnosis and clinical management. Using functional genomic approaches, we previously characterized HGBCL and NOS, that demonstrate gene expression profiling (GEP), and genetic signatures similar to BL. Herein, we characterize distinct HGBCL, NOS, cohort (n = 55) in adults (n = 45) and in children (n = 10), and compared the GEP, genomic DNA copy number (CN), and mutational spectrum with de novo DLBCL (n = 85) and BL (n = 52). …

Lp-118 Is A Novel B-Cell Lymphoma 2 / Extra-Large Inhibitor That Demonstrates Efficacy In Models Of Venetoclaxresistant Chronic Lymphocytic Leukemia, Janani Ravikrishnan, Daisy Y Diaz-Rohena, Elizabeth Muhowski, Xiaokui Mo, Tzung-Huei Lai, Shrilekha Misra, Charmelle D Williams, John Sanchez, Andrew Mitchell, Suresh Satpati, Elizabeth Perry, Tierney Kaufman, Chaomei Liu, Arletta Lozanski, Gerard Lozanski, Kerrya Rogers, Adam S Kittai, Seema A Bhat, Mary C Collins, Matthew S Davids, Nitin Jain, William G Wierda, Rosa Lapalombella, John C Byrd, Fenlai Tan, Yi Chen, Yu Chen, Yue Shen, Stephen P Anthony, Jennifer A Woyach, Deepa Sampath

Faculty, Staff and Student Publications

Patients with chronic lymphocytic leukemia (CLL) respond well to initial treatment with the B-cell lymphoma 2 (BCL2) inhibitor venetoclax. Upon relapse, they often retain sensitivity to BCL2 targeting, but durability of response remains a concern. We hypothesize that targeting both BCL2 and B-cell lymphoma-extra large (BCLXL) will be a successful strategy to treat CLL, including for patients who relapse on venetoclax. To test this hypothesis, we conducted a pre-clinical investigation of LP-118, a highly potent inhibitor of BCL2 with moderate BCLXL inhibition to minimize platelet toxicity. This study demonstrated that LP-118 induces efficient BAK activation, cytochrome C release, and apoptosis …

Association Between Neighborhood-Level Social Vulnerability And Hypertension Outcomes, John E. Brush Jr., Chungsoo Kim, Yuntian Liu, Xin Xin, Chenxi Huang, Iris J. Lundy, Jordan R. Asher, Mitsuaki Sawano, Patrick Young, Jacob Mcpadden, Mark Anderson, John S. Burrows, Harlan M. Krumholz, Yuan Lu

Department of Medicine Faculty Publications

Background

Neighborhood-level social vulnerability is associated with hypertension prevalence and severity and with cardiovascular complications in conditions other than hypertension, but its association with cardiovascular complications in patients with hypertension is understudied.

Objectives

The aim of the study was to examine how the neighborhood-level social vulnerability index (SVI) influences cardiovascular outcomes in a large, diverse cohort of patients with hypertension.

Methods

We used electronic health data to examine the association between census tract-level rankings for the SVI with a composite endpoint of incident myocardial infarction, congestive heart failure, or stroke.

Results

In a longitudinal cohort of 330,972 patients with hypertension …

Deep Dive Into Targeted Therapies: Understanding Idh1-Mutant Aml Treatments [Podcast], Amer M Zeidan, Courtney Dinardo

Faculty, Staff and Student Publications

This podcast episode reviews recent advances in the treatment of IDH1-mutant acute myeloid leukemia (AML), focusing on the mechanisms, efficacy, and safety profiles of approved IDH1 inhibitors. The purpose is to present expert insights and clinical data from key trials that underscore the clinical benefits of these targeted therapies. Through discussion of key findings from pivotal clinical trial studies, including data supporting the use of these agents in both newly diagnosed and relapsed or refractory (R/R) settings, the episode highlights significant outcomes such as increased overall response and prolonged duration of remission in patients treated with IDH1 inhibitors. The analysis …

Anemia In Pregnant Women: Findings From Kuwait Birth Cohort Study, Abdullah Al-Taiar, Ali H. Ziyab, Majeda S. Hammoud, Reem Al-Sabah, Saeed Akhtar

Epidemiology, Biostatistics, & Environmental Health Faculty Publications

Background Anemia is the most common hematologic disorder in pregnancy, affecting over one-third of pregnant women globally. This study aimed to assess the prevalence of anemia in pregnant women and its associated factors in the Kuwait Birth Cohort study.

Methods The Kuwait birth cohort (n = 1,108) was a prospective study in which pregnant women were recruited during their second or third trimester. Data were collected through personal interviews during antenatal care visits, including data on sociodemographic and lifestyle factors. Blood samples were analyzed under strict quality control to measure various laboratory indicators. Anemia was defined as hemoglobin (Hb) < 110 g/L. Predictors of anemia were categorized as underlying or direct factors, and logistic regression models were used to investigate their association with anemia.

Results …

Approved Car-T Therapies Have Reproducible Efficacy And Safety In Clinical Practice, Daniel Goyco Vera, Hiral Waghela, Mohamed Nuh, Jonathan Pan, Premal Lulla

Faculty, Staff and Students Publications

CAR-T cell therapy has established itself as a highly effective treatment for hematological malignancies. There are currently six commercial CAR-T products that have been FDA approved for diseases such as B-ALL, LBCL, MCL, FL, MM, and CLL/SLL. "Real-world" studies allow us to evaluate outcomes from the general population to determine their efficacy and safety compared to those who were included in the original trials. Based on several well conducted "Real-world" studies that represent diverse populations, we report that outcomes from the original trials that led to the approval of these therapies are comparable to those in practice.

Digital Cognitive Behavioral Therapy Vs Education For Pain In Adults With Sickle Cell Disease, Charles R. Jonassaint, Christina M. Lalama, C. Patrick Carroll, Sherif M. Badawy, Megan E. Hamm, Jennifer N. Stinson, Chitra Lalloo, Santosh L. Saraf, Victor R. Gordeuk, Robert M. Cronin, Nirmish Shah, Sophie M. Lanzkron, Darla Liles, Julia A. O'Brien, Cassandra Trimnell, Lakiea Bailey, Raymona H. Lawrence, Leshana Saint Jean, Michael Debaun, Laura M. De Castro, Tonya M. Palermo, Kaleab Z. Abebe

Department of Medicine Faculty Papers

Despite the burden of chronic pain in sickle cell disease (SCD), nonpharmacological approaches remain limited. This multisite, randomized trial compared digital cognitive behavioral therapy (CBT) with a digital pain/SCD education program ("Education") for managing pain and related symptoms. Participants were recruited virtually from seven SCD centers and community organizations in the United States. Adults (aged ≥18 years) with SCD-related chronic pain and/or daily opioid use were assigned to receive either CBT or Education for 12 weeks. Both groups used an app with interactive chatbot lessons and received personalized health coach support. The primary outcome was the change in pain interference …

The Revised Cdc Chronic Pain Guidelines And Payer Opioid Analgesic Policies In Michigan, Victoria Tutag Lehr, Cynthia L. Arfken

Michigan Journal of Public Health

Abstract

The 2016 publication of A Guideline for Prescribing Opioids for Chronic Pain by the Centers for Disease Control and Prevention motivated commercial and Medicaid payers to restrict their opioid prescribing policies including the imposition of hard limits on opioid daily dosages and duration. One result of these policies was an increase in abrupt opioid discontinuation and rapid tapering events for patients receiving long-term opioid therapy. Responding to this misapplication of the 2016 guideline, the 2022 revised guidelines emphasized individualized opioid therapy and exclusion of certain chronic diseases. However, it is not known if the payers changed their policies to …

Venous Thromboembolism Prophylaxis In Orthopedic Surgery: A Narrative Review, Jacob Lahti, Sarah Gallitto, Thomas C. Varkey

Annual Research Symposium

This poster highlights current and updated guidelines for chemical and mechanical prophylaxis for venous thromboembolism in patients undergoing major and minor orthopedic surgery. Existing and new potential therapies were reviewed, as well as an analysis into the lack of high-quality risk-prediction score calculators to improve personalization of prophylaxis regimens. Alongside a summary of existing and potential new prophylaxis protocols, a call to action to improve validity of said risk score calculators so as to improve patient outcomes and personalized medicine is made.

Mutation- And Mrd-Informed Treatments For Transplant-Ineligible Patients, Curtis A Lachowiez, Courtney D Dinardo

Faculty, Staff and Student Publications

The ongoing development of molecularly targeted therapies in addition to the new standard of care combination of azacitidine and venetoclax (AZA-VEN) has transformed the prognostic outlook for older, transplant-ineligible patients with acute myeloid leukemia (AML). While conventional treatments, such as standard anthracycline and cytarabine- based chemotherapy or hypomethylating agent (HMA) monotherapy, are associated with a generally poor prognosis in this patient population, the use of these novel regimens can result in long-lasting, durable remissions in select patient subgroups. Furthermore, the simultaneous discovery of resistance mechanisms to targeted therapies and AZA-VEN has enabled the identification of patient subgroups with inferior outcomes, …

Transplant-Associated Tma: The Conundrum Of Diagnosis And Treatment, Ang Li, Sarah E Sartain

Faculty, Staff and Students Publications

Transplant-associated thrombotic microangiopathy (TA-TMA) after hematopoietic cell transplantation is characterized by microangiopathic hemolytic anemia (MAHA) with persistent schistocytosis, elevated markers of hemolysis, thrombocytopenia, and microvascular thrombosis leading to ischemic injuries in the kidneys and other organs. The initial evaluation of the disease requires confirmation of non-immune MAHA and careful examination of known secondary causes of TMA. Due to increased likelihood of long-term renal failure and overall mortality, a rapid diagnosis and treatment of the underlying trigger is needed. However, the diagnostic criteria proposed to define TA-TMA remain insufficient. sC5b9, the soluble form of the membrane attack complex of the terminal …

Antithrombotic Efficacy And Bleeding Risks Of Vaccine-Induced Immune Thrombotic Thrombocytopenia Treatments, Halina H.L. Leung, Zohra Ahmadi, Brendan Lee, John Casey, Sumita Ratnasingam, Steven E. Mckenzie, Jose Perdomo, Beng H. Chong

Cardeza Foundation for Hematologic Research

Current guidelines for treating vaccine-induced immune thrombotic thrombocytopenia (VITT) recommend nonheparin anticoagulants and IV immunoglobulin (IVIg). However, the efficacy of these treatments remains uncertain due to case studies involving small patient numbers, confounding factors (eg, concurrent treatments), and a lack of animal studies. A recent study proposed danaparoid and heparin as potential VITT therapies because of their ability to disrupt VITT IgG-platelet factor 4 (PF4) binding. Here, we examined the effects of various anticoagulants (including unfractionated [UF] heparin, danaparoid, bivalirudin, fondaparinux, and argatroban), IVIg, and the FcγRIIa receptor-blocking antibody, IV.3. Our investigation focused on VITT IgG-PF4 binding, platelet activation, thrombocytopenia, …

Real-World Impact Of Emicizumab And Immunosuppression On Acquired Hemophilia A: A Multicenter Us Cohort, Jacqueline N Poston, Cassandra Bryan, Annette Von Drygalski, Kadhim Al Banaa, Jenny Y Zhou, Aric Parnes, Evan C Chen, Osman Khan, Patrick Ellsworth, Lorraine Cafuir, Christopher Walsh, Miguel A Escobar, James F Wu, Lynn M Malec, Craig M Kessler, Maissaa Janbain, Rebecca Kruse-Jarres

Faculty, Staff and Student Publications

Acquired hemophilia A (AHA) is an autoimmune bleeding disorder that is caused by factor VIII (FVIII) autoantibodies with high morbidity and mortality due to bleeding and complications from immunosuppression (IST). To address the real-world implications of the FVIII mimetic antibody, emicizumab, and the role of IST, we retrospectively collected de-identified data on 62 patients with AHA who were treated off-label with emicizumab for a median of 10 weeks at 12 US-based hemophilia treatment centers. Most patients (95.2%) had acute bleeding at diagnosis, and 62.9% had partial or no control of bleeds despite the use of hemostatic agents at the time …

Nosebleed No More: Recognizing And Diagnosing Factor Viii Inhibitor, Salam Harb, Leidy Huie Martinez Md, Jose Alvarado Md, Ajit Koli Do, Hazem Nasef Ms4

HCA-NSU MD Research Day

Acquired hemophilia is a condition characterized by the unexpected onset of severe bleeding due to an issue with coagulation factors. Typically, this disorder results from the production of autoantibodies against the Factor VIII coagulation factor. Although acquired hemophilia is an extremely rare condition, with an annual incidence of just 1.5 cases per million, it is crucial to recognize and understand it. This is because diagnosing this disorder is intricate, and if left undiagnosed and untreated, it can lead to high levels of morbidity and mortality. This case stands out as the condition typically targets older adults, with around 80% of …

Genetically Determined Telomere Length In Monoclonal Gammopathy Of Undetermined Significance, Multiple Myeloma Risk And Outcome, Matteo Giaccherini, Alyssa I Clay-Gilmour, Romano Liotti, Angelica Macauda, Manuel Gentiluomo, Elizabeth E Brown, Mitchell J Machiela, Stephen J Chanock, Michelle A T Hildebrandt, Aaron D Norman, Elisabet Manasanch, S Vincent Rajkumar, Jonathan N Hofmann, Sonja I Berndt, Parveen Bhatti, Graham G Giles, Elad Ziv, Shaji K Kumar, Nicola J Camp, Wendy Cozen, Susan L Slager, Federico Canzian, Federica Gemignani, Celine M Vachon, Daniele Campa

Faculty, Staff and Student Publications

No abstract provided.

Outcomes And Genetic Dynamics Of Acute Myeloid Leukemia At First Relapse, Alex Bataller, Hagop Kantarjian, Alexandre Bazinet, Tapan Kadia, Naval Daver, Courtney D Dinardo, Gautam Borthakur, Sanam Loghavi, Keyur Patel, Guilin Tang, Koji Sasaki, Nicholas J Short, Musa Yilmaz, Ghayas C Issa, Yesid Alvarado, Guillermo Montalban-Bravo, Abhishek Maiti, Hussein A Abbas, Koichi Takahashi, Sherry Pierce, Elias Jabbour, Guillermo Garcia-Manero, Farhad Ravandi

Faculty, Staff and Student Publications

Patients with relapsed acute myeloid leukemia (AML) experience dismal outcomes. We performed a comprehensive analysis of patients with relapsed AML to determine the genetic dynamics and factors predicting survival. We analyzed 875 patients with newly diagnosed AML who received intensive treatment or low-intensity treatment. Of these patients, 197 subsequently relapsed. Data were available for 164 of these patients, with a median time from complete remission/complete remission with incomplete blood count recovery to relapse of 6.5 months. Thirty-five of the 164 patients (21%) experienced relapse after allogeneic hematopoietic stem cell transplantation. At relapse, mutations in genes involved in pathway signaling tended …

The Dleu2/Mir-15a/Mir-16-1 Cluster Shapes The Immune Microenvironment Of Chronic Lymphocytic Leukemia, Ronghua Zhang, Priyanka Khare, Priyanka Banerjee, Cristina Ivan, Sarah Schneider, Federica Barbaglio, Karen Clise-Dwyer, Vanessa Behrana Jensen, Erika Thompson, Marisela Mendoza, Nicholas Chiorazzi, Shih-Shih Chen, Xiao-Jie Joy Yan, Nitin Jain, Paolo Ghia, Federico Caligaris-Cappio, Rima Mendonsa, Sashi Kasimsetty, Ryan Swoboda, Recep Bayraktar, William Wierda, Varsha Gandhi, George A Calin, Michael J Keating, Maria Teresa Sabrina Bertilaccio

Faculty, Staff and Student Publications

The development and progression of chronic lymphocytic leukemia (CLL) depend on genetic abnormalities and on the immunosuppressive microenvironment. We have explored the possibility that genetic drivers might be responsible for the immune cell dysregulation that shapes the protumor microenvironment. We performed a transcriptome analysis of coding and non-coding RNAs (ncRNAs) during leukemia progression in the Rag2-/-γc-/- MEC1-based xenotransplantation model. The DLEU2/miR-16 locus was found downmodulated in monocytes/macrophages of leukemic mice. To validate the role of this cluster in the tumor immune microenvironment, we generated a mouse model that simultaneously mimics the overexpression of hTCL1 and the germline deletion of the …

Physician Perspectives About The Diagnosis And Management Of Acute Chest Syndrome, Neha Bhasin, Dana Marie Leblanc, Sean Yates, Quentin Eichbaum, An Pham, Deva Sharma, Li Zhang, Elliott P. Vichinsky, Ravi Sarode

School of Medicine Faculty Publications

Background: Acute chest syndrome (ACS) is the leading cause of mortality, accounting for 25% of all deaths among individuals with sickle cell disease (SCD). There is a lack of evidence-based laboratory and clinical risk stratification guidelines for the diagnosis and management of ACS. Study Design and Methods: To better understand physician practices for the management of ACS in the United States, we created an ACS Working Group including hematology and transfusion medicine physicians from four different SCD treatment centers in the United States. The working group created a physician survey that included physician demographics and ACS diagnostic criteria that they …

Menin Inhibitors In Pediatric Acute Leukemia: A Comprehensive Review And Recommendations To Accelerate Progress In Collaboration With Adult Leukemia And The International Community, Branko Cuglievan, Hagop Kantarjian, Jeffrey E Rubnitz, Todd M Cooper, C Michel Zwaan, Jessica A Pollard, Courtney D Dinardo, Tapan M Kadia, Erin Guest, Nicholas J Short, David Mccall, Naval Daver, Cesar Nunez, Fadi G Haddad, Miriam Garcia, Kapil N Bhalla, Abhishek Maiti, Samanta Catueno, Warren Fiskus, Bing Z Carter, Amber Gibson, Michael Roth, Sajad Khazal, Priti Tewari, Hussein A Abbas, Wallace Bourgeois, Michael Andreeff, Neerav N Shukla, Danh D Truong, Jeremy Connors, Joseph A Ludwig, Janine Stutterheim, Elisabeth Salzer, Kristian L Juul-Dam, Koji Sasaki, Kris M Mahadeo, Sarah K Tasian, Gautam Borthakur, Samantha Dickson, Nitin Jain, Elias Jabbour, Soheil Meshinchi, Guillermo Garcia-Manero, Farhad Ravandi, Eytan M Stein, E Anders Kolb, Ghayas C Issa

Faculty, Staff and Student Publications

Aberrant expression of HOX and MEIS1 family genes, as seen in KMT2A-rearranged, NUP98-rearranged, or NPM1-mutated leukemias leads to arrested differentiation and leukemia development. HOX family genes are essential gatekeepers of physiologic hematopoiesis, and their expression is regulated by the interaction between KMT2A and menin. Menin inhibitors block this interaction, downregulate the abnormal expression of MEIS1 and other transcription factors and thereby release the differentiation block. Menin inhibitors show significant clinical efficacy against KMT2A-rearranged and NPM1-mutated acute leukemias, with promising potential to address unmet needs in various pediatric leukemia subtypes. In this collaborative initiative, pediatric and adult hematologists/oncologists, and stem cell …

Discordance Between Aptt And Anti-Xa In Monitoring Heparin Anticoagulation In Mechanical Circulatory Support, Song Li, Ang Li, Jennifer A Beckman, Christopher Kim, Marian A Granich, John Mondin, Daniel E Sabath, David A Garcia, Claudius Mahr

Faculty, Staff and Students Publications

AIMS: It is unclear whether activated partial thromboplastin time (aPTT) or anti-Xa is more accurate for monitoring heparin anticoagulation in mechanical circulatory support (MCS) patients. This study investigates the relationship between aPTT and anti-Xa in MCS patients and identifies predictors of discordance.

METHODS AND RESULTS: aPTT and anti-Xa were simultaneously measured in a prospective cohort of MCS patients receiving unfractionated heparin at a tertiary academic medical centre. Therapeutic aPTT and anti-Xa levels were 60-100 s and 0.3-0.7 IU/mL, respectively, and concordance was defined as both levels being subtherapeutic, therapeutic, or supratherapeutic. To identify predictors of discordance, both a machine learning …

Mutant Npm1 Marginally Impacts Ribosome Footprint In Acute Myeloid Leukemia Cells, Lorenzo Brunetti, Giulia Pianigiani, Michael C Gundry, Margaret A Goodell, Brunangelo Falini

Faculty, Staff and Students Publications

BACKGROUND:NPM1‐mutated acute myeloid leukemia (AML) is the most frequent AML subtype. As wild‐type NPM1 is known to orchestrate ribosome biogenesis, it has been hypothesized that altered translation may contribute to leukemogenesis and leukemia maintenance in NPM1‐mutated AML. However, this hypothesis has never been investigated. We reasoned that if mutant NPM1 (NPM1c) directly impacts translation in leukemic cells, loss of NPM1c would result in acute changes in the ribosome footprint.

METHODS: Here, we performed ribosome footprint profiling (Ribo-seq) and bulk messenger RNA (mRNA) sequencing in two

RESULTS AND DISCUSSION: Incubation of degron cells with the small compound dTAG-13 …

Current Status And Research Directions In Acute Myeloid Leukemia, Hagop Kantarjian, Gautam Borthakur, Naval Daver, Courtney D Dinardo, Ghayas Issa, Elias Jabbour, Tapan Kadia, Koji Sasaki, Nicholas J Short, Musa Yilmaz, Farhad Ravandi

Faculty, Staff and Student Publications

The understanding of the molecular pathobiology of acute myeloid leukemia (AML) has spurred the identification of therapeutic targets and the development of corresponding novel targeted therapies. Since 2017, twelve agents have been approved for the treatment of AML subsets: the BCL2 inhibitor venetoclax; the CD33 antibody drug conjugate gemtuzumab ozogamicin; three FLT3 inhibitors (midostaurin, gilteritinib, quizartinib); three IDH inhibitors (ivosidenib and olutasidenib targeting IDH1 mutations; enasidenib targeting IDH2 mutations); two oral hypomethylating agents (oral poorly absorbable azacitidine; fully absorbable decitabine-cedazuridine [latter approved as an alternative to parenteral hypomethylating agents in myelodysplastic syndrome and chronic myelomonocytic leukemia but commonly used in …

Sotatercept For Anemia Of Myelofibrosis: A Phase Ii Investigator-Initiated Study, Prithviraj Bose, Lucia Masarova, Naveen Pemmaraju, Sharon D Bledsoe, Naval G Daver, Elias J Jabbour, Tapan M Kadia, Zeev Estrov, Steven M Kornblau, Michael Andreeff, Nitin Jain, Jorge E Cortes, Gautam Borthakur, Yesid Alvarado, Mary Ann Richie, Mackenzie H Dobbins, Selene A Mccrackin, Lingsha Zhou, Sherry A Pierce, Xuemei Wang, Allison M Pike, Guillermo Garcia-Manero, Hagop M Kantarjian, Srdan Verstovsek

Faculty, Staff and Student Publications

No abstract provided.

Association Between Intravenous Fluids During Labor And Primary Postpartum Hemorrhage: A Retrospective Cohort Study, Belinda R Bruce, Heather L Shepherd, Saleem Ahmed Khan, Charlotte R Haunton, Julie Leask, Bradley S De Vries

Faculty, Staff and Student Publications

INTRODUCTION: There is a major research gap relating to the impact of intravenous (IV) fluids administration during labor on maternal and neonatal outcomes. It is biologically plausible that a relationship between volume of IV fluids and primary postpartum hemorrhage (PPH) exists. The primary objective of this study was to evaluate whether the administration of high-volume IV fluids during labor (≥ 2500 mL) increases the risk of primary PPH and other adverse outcomes for women with a term, singleton pregnancy, in comparison to low-volume IV fluids during labor (<2500 >mL).

MATERIAL AND METHODS: A retrospective cohort study was conducted at a …