Hemic and Lymphatic Diseases Commons^™

Identifying Targetable Vulnerabilities To Circumvent Or Overcome Venetoclax Resistance In Diffuse Large B-Cell Lymphoma, Clare M. Adams, Amanda Mcbride, Peter Michener, Irina Shkundina, Ramkrishna Mitra, Hyun Hwan An, Pierluigi Porcu, Christine M. Eischen

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Clinical trials with single-agent venetoclax/ABT-199 (anti-apoptotic BCL2 inhibitor) revealed that diffuse large B-cell lymphoma (DLBCL) is not solely dependent on BCL2 for survival. Gaining insight into pathways/proteins that increase venetoclax sensitivity or unique vulnerabilities in venetoclax-resistant DLBCL would provide new potential treatment avenues. Therefore, we generated acquired venetoclax-resistant DLBCL cells and evaluated these together with intrinsically venetoclax-resistant and -sensitive DLBCL lines. We identified resistance mechanisms, including alterations in BCL2 family members that differed between intrinsic and acquired venetoclax resistance and increased dependencies on specific pathways. Although combination treatments with BCL2 family member inhibitors may overcome venetoclax resistance, RNA-sequencing and drug/compound …

A Phase 1/2 Study Of Pepinemab In Children, Adolescents, Or Young Adults With Recurrent Or Refractory Solid Tumors: A Children’S Oncology Group Consortium Report (Advl1614), Emily Greengard, Robin Williams, Branden Moriarity, Xiaowei Liu, Charles G Minard, Joel M Reid, Terrence Fisher, Elizabeth Evans, Desa Rae Pastore, Maurice Zauderer, Stephan Voss, Elizabeth Fox, Brenda J Weigel

Faculty, Staff and Students Publications

PURPOSE: Pepinemab, a humanized IgG4 monoclonal antibody, targets the SEMA4D (CD100) antigen to inhibit binding to its high-affinity receptors (plexin B1/PLXNB1, plexin B2/PLXNB2) and low-affinity receptor (CD72). SEMA4D blockade leads to increased cytotoxic T-cell infiltration, delayed tumor growth, and durable tumor rejection in murine tumor models. Pepinemab was well tolerated and improved T cell infiltration in clinical studies in adults with refractory tumors. SEMA4D was identified as a strong candidate proto-oncogene in a model of osteosarcoma. Based on these preclinical and clinical data, we conducted a phase 1/2 study to determine the recommended phase 2 dose (RP2D), pharmacokinetics, pharmacodynamics, and …

Clinical Features And Genomic Epidemiology Of Bloodstream Infections Due To Enterococcal Species Other Than Enterococcus Faecalis Or E Faecium In Patients With Cancer, Dierdre B Axell-House, Patrycja A Ashley, Stephanie L Egge, Truc T Tran, Claudia Pedroza, Meng Zhang, An Q Dinh, Shelby R Simar, Pranoti V Sahasrabhojane, William R Miller, Samuel A Shelburne, Blake M Hanson, Cesar A Arias

Faculty, Staff and Student Publications

BACKGROUND: Non–Enterococcus faecium, non–E. faecalis (NFF) enterococci are a heterogeneous group of clinically pathogenic enterococci that include species with intrinsic low-level vancomycin resistance. Patients with cancer are at increased risk for bacteremia with NFF enterococci, but their clinical and molecular epidemiology have not been extensively described.

METHODS: We conducted a retrospective review of all patients (n = 70) with NFF bacteremia from 2016 to 2022 at a major cancer center. The main outcomes assessed were 30-day mortality, microbiological failure (positive blood cultures for ≥4 days), and recurrence of bacteremia (positive blood cultureclearance). Whole-genome sequencing was performed on all …

Stat5b Mutations In Myeloid Neoplasms Differ By Disease Subtypes But Characterize A Subset Of Chronic Myeloid Neoplasms With Eosinophilia And/Or Basophilia, C Cameron Yin, Wayne Tam, Serena M Walker, Amandeep Kaur, Madhu M Ouseph, Wei Xie, Olga K Weinberg, Peng Li, Zhuang Zuo, Mark J Routbort, Simon Chen, L Jeffrey Medeiros, Tracy I George, Attilio Orazi, Daniel A Arber, Adam Bagg, Robert P Hasserjian, Sa A Wang

Faculty, Staff and Student Publications

STAT5B has been reported as a recurrent mutation in myeloid neoplasms with eosinophilia, but its overall frequency and importance across a spectrum of myeloid neoplasms are largely unknown. We conducted a multicenter study on a series of 82 myeloid neoplasms with STAT5B mutations detected by next-generation sequencing. The estimated frequency of STAT5B mutations in myeloid neoplasms was low, <0.5%, but mutations were detected in all categories of such neoplasms, including myelodysplastic syndrome (MDS, 28%), acute myeloid leukemia (AML, 26%), myelodysplastic/myeloproliferative neoplasm (MDS/MPN, 18%), Philadelphia chromosome-negative classic MPN (12%), systemic mastocytosis (1%), and, with a notably high frequency, chronic eosinophilic leukemia, not otherwise specified (CEL-NOS, 15%). STAT5B mutations occurred preferentially in the SH2 domain (95%), involved 12 different codons, with the N642H hotspot being the most common (78%). Co-mutations were present in all cases and clonal hierarchy analysis showed that STAT5B mutations tended to be subclonal in AML, MPN, and MDS, but frequently dominant/co-dominant in CEL-NOS (83%), followed by MDS/MPN (40%). Across the group, eosinophilia and/or basophilia were common (41%), frequently observed in cases in which STAT5B mutations were detected at initial diagnosis (P<0.0001), with a high variant allele frequency (median 42.5%, P=0.0001), as a dominant/ co-dominant clone (P<0.0001), involving the canonical N642H (P=0.0607), and associated with fewer co-mutations (P=0.0009). Our data show that the characteristics and importance of a STAT5B mutation differ among myeloid neoplasms, but if present as a dominant mutation and detected at initial diagnosis, it appears to be a driver mutation in a subgroup of chronic myeloid neoplasms, preferentially promoting a proliferation of eosinophils and basophils.

Immune Infiltration At The Primary Tumor Is Associated With Clinical Outcome Of Patients With Extranodal Extension Of Lymph Node Metastasis In Oral Cancer, Chieko Michikawa, Frederico O Gleber-Netto, Curtis R Pickering, Xiayu Rao, Jing Wang, Andrew G Sikora, Jeffrey N Myers, Mitchell J Frederick

Faculty, Staff and Student Publications

Background: Extranodal extension (ENE) of lymph node metastasis is one of the most reliable prognostic indicators for patients with locally advanced oral cancer. Although multiple reports have found a close relationship between immune infiltration of tumors and patient clinical outcomes, its association with ENE is unknown.

Methods: We identified 234 human papillomavirus-negative (HPV-) oral cavity squamous cell carcinoma (OSCC) patients in The Cancer Genome Atlas and investigated the immune infiltration profiles of primary tumors and their association with survival.

Results: Hierarchical clustering analysis clearly classified the overall immune infiltration status in OSCC into high immune or low immune groups. The …

Using Rapid Protein Degradation To Determine The Effect Of Runx1 Loss-Of- Function On Dna Damage Accumulation And Repair., Jackriel Pina Morales

Theses and Dissertations

Germline mutations in RUNX1 are associated with familial platelet disorder with a predisposition to myeloid malignancy (RUNX1-FPDMM), in which patients present with low platelet counts,excessive bleeding and bruising, and an increased risk of Acute Myeloid Leukemia (AML)/Myelodysplastic Syndrome (MDS) development throughout their lifetime. To understand how these loss-of-function mutations in RUNX1 drive predispose to malignancy, it is important to develop a detailed understanding of the molecular basis of RUNX1 function. While RUNX1 is a transcription factor, preliminary data from our group and work from others suggests that RUNX1 also interacts with proteins that are critical for DNA damage …

A Multicenter Study Of Venetoclax-Based Treatment For Patients With Richter Transformation Of Chronic Lymphocytic Leukemia, Paul J Hampel, Mahesh Swaminathan, Kerry A Rogers, Erin M Parry, Jan A Burger, Matthew S Davids, Wei Ding, Alessandra Ferrajoli, Jonathan M Hyak, Nitin Jain, Saad S Kenderian, Yucai Wang, William G Wierda, Jennifer A Woyach, Sameer A Parikh, Philip A Thompson

Faculty, Staff and Student Publications

Patients with chronic lymphocytic leukemia (CLL) who develop Richter transformation (RT) have a poor prognosis when treated with chemoimmunotherapy regimens used for de novo diffuse large B-cell lymphoma. Venetoclax, a BCL2 inhibitor, has single-agent efficacy in patients with RT and is potentially synergistic with chemoimmunotherapy. In this multicenter, retrospective study, we evaluated 62 patients with RT who received venetoclax-based treatment outside of a clinical trial, in combination with a Bruton tyrosine kinase inhibitor (BTKi; n=28), rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) (n=13), or intensive chemoimmunotherapy other than R-CHOP (n=21). The best overall and complete response rates were 36%/25%, 54%/46%, and …

Astrocytic Slc4a4 Regulates Blood-Brain Barrier Integrity In Healthy And Stroke Brains Via A Ccl2-Ccr2 Pathway And No Dysregulation, Qi Ye, Juyeon Jo, Chih-Yen Wang, Heavin Oh, Jiangshan Zhan, Tiffany J Choy, Kyoung In Kim, Angelo D'Alessandro, Yana K Reshetnyak, Sung Yun Jung, Zheng Chen, Sean P Marrelli, Hyun Kyoung Lee

Faculty, Staff and Student Publications

Astrocytes play vital roles in blood-brain barrier (BBB) maintenance, yet how they support BBB integrity under normal or pathological conditions remains poorly defined. Recent evidence suggests that ion homeostasis is a cellular mechanism important for BBB integrity. In the current study, we investigated the function of an astrocyte-specific pH regulator, Slc4a4, in BBB maintenance and repair. We show that astrocytic Slc4a4 is required for normal astrocyte morphological complexity and BBB function. Multi-omics analyses identified increased astrocytic secretion of CCL2 coupled with dysregulated arginine-NO metabolism after Slc4a4 deletion. Using a model of ischemic stroke, we found that loss of Slc4a4 exacerbates …

Asymptomatic Covid-19-Associated Acquired Hemophilia A And Disseminated Intravascular Coagulation From A Bypassing Agent, Abraham Attah, Deanna Huffman, Palash Asawa, Vinay Edlukudige Keshava, Deep Shah

School of Medicine Faculty Publications

Acquired hemophilia A (AHA) is a clotting disorder characterized by the presence of neutralizing antibodies that inhibit factor VIII, resulting in increased bleeding risk. Known etiologies include malignancy, autoimmune conditions, graft-vs-host disease, and more recently coronavirus disease 2019 (COVID-19) infection. In this case report, we describe an 86-year-old female who was found to have AHA incidentally during preoperative workup for meningioma resection. She was subsequently found to have COVID-19 infection which was the likely cause of her development of AHA. She was treated with factor eight inhibitor bypassing agent (FEIBA) and recombinant factor VII (rVII) for a small hematoma on …

Implementation Of Lymphedema Education Toolkit For Nurse Coordinators, Heather Gee

Master's Projects and Capstones

Problem: Lymphedema is a chronic condition that develops secondary to cancer treatments such as chemotherapy, radiation, and surgical removal of affected lymph nodes. This swelling in patient’s limbs can cause discomfort and limit mobility, however lymphedema is often not detected until later stages, delaying treatment and patient education.

Context: This quality improvement project was conducted at Hospital S Women’s Cancer Center, an outpatient center specializing in advanced treatments for breast and gynecological cancers. This center has a multidisciplinary team focusing on both the medical and surgical aspects of oncology treatment.

Interventions: An evidence-based lymphedema education toolkit was created for nurse …

A Genomics Driven Induced Pluripotent Stem Cell Model Of Infant Acute Lymphoblastic Leukemia - Early Results, Meagan Vacek, Jacqelyn Nemechek, Irina Pushel, Bradley Thornton, Molly Leyda, Priyanka Prem Kumar, Midhat Farooqi, Jay L. Vivian, Erin M. Guest, John M. Perry

Research Days

While the cure rates for pediatric ALL have improved over the decades, infants with ALL (iALL) have not benefitted from these advances and continue to have a devastating prognosis. Unfortunately progress in treatment has also been slowed by inadequate research models. With this project, we address this unmet need by investigating a novel model to understand the cellular and molecular changes that occur during iALL onset and progression.

Increasing Palliative Care Team Involvement In Pediatric Hematopoietic Stem Cell Transplant Patients, Meagan Vacek, Lisa Tarbell, Melissa List, Erin Hall, Jennifer Linebarger, Kelstan Ellis, Gina Jones, Joel Thompson

Research Days

Early implementation of palliative care in pediatric oncology is well established but its role in pediatric hematopoietic stem cell transplant (HSCT) patients is yet to be fully determined. Multiple organizations encourage palliative care involvement in HSCT patients. Our aim was to increase palliative care team consults for patients receiving HSCT for our targeted diagnosis. Though we did not achieve this aim, we were able to increase the palliative care team's involvement in the total cohort of patients undergoing HSCT.

Zinc-Containing Over-The-Counter Product Causing Sideroblastic Anemia And Neutropenia, Marshall Patrick Stagg, Jennifer Miatech, Baseera Majid, Ravali Polala

School of Medicine Faculty Publications

Sideroblastic anemia is characterized by anemia, granulocytopenia, and bone marrow findings of vacuolated precursors and ringed sideroblasts. Zinc-induced copper deficiency can present as sideroblastic anemia and neutropenia. We report the case of a previously healthy 74-year-old female who presented with newly discovered sideroblastic anemia as a result of an over-the-counter oral vitamin and mineral supplement. Serum analysis revealed increased zinc levels, decreased copper levels, and a decrease in ceruloplasmin. Bone marrow evaluation revealed ringed sideroblasts and cytoplasmic vacuolization in myeloid precursors. She demonstrated improvement in her hematologic profile with discontinuation of the over-the-counter product and administration of oral copper supplementation. …

Novel Spirocyclic Dimer (Spid3) Displays Potent Preclinical Effects In Hematological Malignancies, Alexandria Eiken

Theses & Dissertations

Chronic lymphocytic leukemia (CLL) is a heterogeneous disease characterized by the accumulation of mature CD5⁺ B-cells in the peripheral blood, bone marrow, and secondary lymphoid tissues (e.g., spleen and lymph nodes).Despite the efficacy of front-line therapies, CLL is still an incurable disease, highlighting the need for development of novel therapeutics and further study of resistance mechanisms. Within the lymph node CLL tumor microenvironment (TME), there is an upregulation of gene signatures associated with B-cell receptor (BCR) and downstream nuclear factor kappa B (NF-κB) signaling compared to CLL cells found within the blood or bone marrow niches. Additionally, BCR signaling …

Therapeutic Effects Of Bet Protein Inhibition In B-Cell Malignancies And Beyond, Audrey L. Smith

Theses & Dissertations

Chronic lymphocytic leukemia (CLL) develops through a combination of intrinsic genetic defects, constitutively active survival/proliferation signaling pathways, and complex microenvironment interactions. Redundant tumor microenvironment (TME) immuno-suppressive mechanisms and epigenetic maintenance of terminal T-cell dysfunction also greatly hinder anti-tumor T-cell responses in CLL. Small-molecule agents targeting the B-cell receptor (BCR) pathway and anti-apoptotic proteins alone or in combination with chemo-immunotherapy have revolutionized the management of CLL, yet there is still a significant need for novel therapeutic strategies to yield durable tumor elimination. Bromodomain and extra-terminal domain (BET) proteins are epigenetic readers that bind to acetyl-lysine residues on histones to regulate gene …

Brief Review: Regional Anesthesia For Vaso-Occlusive Pain Crises, Oluwatomi Alade

Rowan-Virtua Research Day

Vaso-occlusive pain crisis occurs with obstruction of blood vessels from sickled red blood cells. This results in ischemic injury causing in pain. Acute vasoocclusive pain crisis is one of the most common reasons for patients with sickle cell disease to present to the hospital for medical attention. Acute treatment involves IV opioid therapy, non-opioid therapy, and IV hydration. There is a known lack of trust between a patient in acute pain and a provider in the emergency department (ED) and hospital secondary to stereotypes regarding pain seeking behavior. Here we discuss a case of vasoocclusive pain crisis refractory to opioid …

Case Report: A Case Of Ttp In The Ed, Brian F. Lim, Andrew Caravello, James A. Espinosa, Alan Lucerna

Rowan-Virtua Research Day

We report a case of a 54-year-old female who presented with mild shortness of breath, lower chest discomfort, fatigue, and weakness ongoing for several days and was diagnosed with thrombotic thrombocytopenic purpura (TTP). TTP is characterized by microangiopathic hemolytic anemia and thrombocytopenia due to either an inherited or immune-mediated reduction in von Willebrand Factor (VWF) cleaving protease ADAMTS13.

Patients presenting with non-specific symptoms is becoming increasingly common and initial bias could be to attribute symptoms to viral syndrome or upper respiratory tract infection. However, the differential for non-specific complaints is extensive and thorough review of labs and re-evaluations of patients …

Morel Lavallee Lesion: A Shear Fascia-Nating Soft Tissue Injury, Isaac F. Su, James A. Espinosa, Alan A. Lucerna

Rowan-Virtua Research Day

Morel-Lavallée lesions (MLLs), first described by their namesake, French physician Victor-Auguste-François Morel-Lavallée, in 1863, represent a distinct category of soft-tissue degloving injuries. These injuries occur when a shearing force disrupts the connection between subcutaneous tissue and fascia, severing lymphatic vessels and capillaries, and leading to an encapsulated collection of lymph, blood, and necrotic fat. Because this space is deep and enclosed, the fluid accumulation cannot easily drain or resolve spontaneously and often an inflammatory capsule develops, further inhibiting resorption. Undiagnosed, patients go on to develop chronic pain, infection, skin necrosis, progressive neurovascular deficits, and, in severe cases, potential loss of …

Efficacy Of Mcl-1 Inhibitors In Multiple Myeloma Cells Resistant To Bortezomib, Emily Nelson, Omar S. Al-Odat, Sabrina M. Paparo, Daniel A. Guirguis, Gabriella Yao, Manoj Pandey, Subash Jonnalagadda, Tulin Budak-Alpdogan

Rowan-Virtua Research Day

Multiple myeloma (MM) is a type of cancer that affects plasma B cells. Patients with MM often experience frequent relapses and can develop resistance to drugs. As a medical researcher, it is important to understand the role of Mcl-1 in preventing intrinsic apoptosis and drug resistance. Mcl-1 belongs to the anti-apoptotic subgroup of Bcl-2 family proteins and plays a crucial role in these processes. Mcl-1 plays a crucial role in driving disease progression and contributing to drug resistance in MM. It has been observed that there is an increased expression of Mcl-1 in 52% of patients with MM during diagnosis, …

Investigating The Therapeutic Potential Of Soursop In Treating Hematologic Malignancies, Sabrina Marie Paparo, Rebeca Mendoza, Robert Chitren, Omar Al-Odat, Emily Nelson, Subash Jonnalagadda, Roger Strair, Manoj Pandey

Rowan-Virtua Research Day

Acute Myeloid Leukemia (AML) and Multiple Myeloma (MM) are hematologic malignancies that originate in the bone marrow and account for approximately 1.3% and 2% of cancer cases, respectively. AML is characterized by an accumulation of myeloblasts, or immature myeloid cells, that have the potential to spread to the peripheral blood. There is an uncontrolled proliferation of plasma cells in the bone marrow in MM. While the current treatment options for both AML and MM show promise in achieving initial remission, it is unfortunately common for patients to experience relapse and develop drug resistance. There is a theory that relapse and …

Cost-Effectiveness And Outcomes Of Utilizing Tisagenlecleucel Therapy (Car T-Cell) In Pediatric Acute Lymphoblastic Leukemia In Comparison To Standard Of Care (Soc) Therapies: A Scoping Review, Andrew Atschinow, Evangeline Attota, Warren Chan, Pooja Kasarapu, Priyal Shah, Karina Vizzoni

Rowan-Virtua Research Day

Aims

This review aims to assess the correlations between outcomes and cost of treatment methods for pediatric acute lymphoblastic leukemia patients, specifically comparing CAR T-cell therapy and Standard-of-Care (SoC) therapy. The socioeconomic background of patients will also be taken into consideration to see if there are differences in their outcomes.

Methods

Peer-reviewed publications were collected from PubMed and Web of Science. The keyword strings used were “acute lymphoblastic leukemia,” “pediatric acute lymphoblastic leukemia,” “pediatric,” “CAR T-cell therapy,” and “cost-effectiveness.” 27 citations were obtained. Titles were screened by 6 authors. Articles met the inclusion criteria including potential Quality-Adjusted Life Year (QALY) …

Chilling Complications: A Case Of Covid-Associated Cold Autoimmune Hemolytic Anemia (Aiha), Julian Coz, Kishan B. Patel

Rowan-Virtua Research Day

Cold Agglutinin disease (CAD) also known as Cold Autoimmune Hemolytic Anemia (AIHA) is a form of autoimmune hemolytic anemia wherein cold agglutinins (IgM autoantibodies against red blood cell (RBC) antigens) bind during cold temperatures causing clinical symptoms related to RBC agglutination resulting to hemolytic anemia. Clinicians should recognize that Cold Agglutinin disease can be secondary to an underlying pathology such as COVID-19. Here we describe an unusual case of Cold Agglutinin Autoimmune Hemolytic Anemia which was diagnosed in the Emergency Department with the presence of COVID-19 and with a hospital course complicated by acute deep vein thrombosis (DVT) and bilateral …

A Rare Presentation: Intracranial Hemorrhage As A Symptom Of Acute Leukemic Transformation In A 23-Year Old Male, Kelsey M. Murray, Kishan B. Patel

Rowan-Virtua Research Day

This case highlights the urgency of considering acute leukemic transformation in young patients presenting with neurological deficits, emphasizing the importance of prompt evaluation and management to optimize patient outcomes. The case depicted is a tragic complication of Chronic Myeloid Leukemia (CML) and its acute blast crisis. Remarkably, the patient exhibited none of the typical constitutional symptoms associated with CML.

Profiling The Activity Of The Para-Caspase Malt1 In B-Cell Acute Lymphoblastic Leukemia For Potential Targeted Therapeutic Application, Firas M Safa, Terri Rasmussen, Lorena Fontan, Min Xia, Ari Melnick, Adrian Wiestner, Patricia Lobelle-Rich, Jan A Burger, Yara Mouawad, Hana Safah, Erik K Flemington, Nakhle S Saba

Faculty, Staff and Student Publications

B-cell acute lymphoblastic leukemia (B-ALL) remains a hard-to-treat disease with a poor prognosis in adults. Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is a para-caspase required for B-cell receptor (BCR)-mediated NF-κB activation. Inhibition of MALT1 in preclinical models has proven efficacious in many B-cell malignancies including chronic lymphocytic leukemia, mantle cell lymphoma and diffuse large B-cell lymphoma. We sought to examine the role of MALT1 in B-ALL and determine the biological consequences of its inhibition. Targeting MALT1 with both Z-VRPR-fmk and MI-2 efficiently kills B-ALL cells independent of the cell-of-origin (pro, pre, mature) or the presence of the Philadelphia …

Stat3 Protects Hematopoietic Stem Cells By Preventing Activation Of A Deleterious Autocrine Type-I Interferon Response, Bhakti Patel, Yifan Zhou, Rachel L Babcock, Feiyang Ma, M Anna Zal, Dhiraj Kumar, Yusra B Medik, Laura M Kahn, Josué E Pineda, Elizabeth M Park, Sarah M Schneider, Ximing Tang, Maria Gabriela Raso, Collene R Jeter, Tomasz Zal, Karen Clise-Dwyer, Khandan Keyomarsi, Filippo G Giancotti, Simona Colla, Stephanie S Watowich

Faculty, Staff and Student Publications

Hematopoietic stem and progenitor cells (HSPCs) maintain blood-forming and immune activity, yet intrinsic regulators of HSPCs remain elusive. STAT3 function in HSPCs has been difficult to dissect as Stat3-deficiency in the hematopoietic compartment induces systemic inflammation, which can impact HSPC activity. Here, we developed mixed bone marrow (BM) chimeric mice with inducible Stat3 deletion in 20% of the hematopoietic compartment to avoid systemic inflammation. Stat3-deficient HSPCs were significantly impaired in reconstitution ability following primary or secondary bone marrow transplantation, indicating hematopoietic stem cell (HSC) defects. Single-cell RNA sequencing of Lin-ckit+Sca1+ BM cells (LSKs) revealed aberrant activation of cell cycle, p53, …

Proteomics For Optimizing Therapy In Acute Myeloid Leukemia: Venetoclax Plus Hypomethylating Agents Versus Conventional Chemotherapy, Eduardo Sabino De Camargo Magalhães, Stefan Edward Hubner, Brandon Douglas Brown, Yihua Qiu, Steven Mitchell Kornblau

Faculty, Staff and Student Publications

The use of Hypomethylating agents combined with Venetoclax (VH) for the treatment of Acute Myeloid Leukemia (AML) has greatly improved outcomes in recent years. However not all patients benefit from the VH regimen and a way to rationally select between VH and Conventional Chemotherapy (CC) for individual AML patients is needed. Here, we developed a proteomic-based triaging strategy using Reverse-phase Protein Arrays (RPPA) to optimize therapy selection. We evaluated the expression of 411 proteins in 810 newly diagnosed adult AML patients, identifying 109 prognostic proteins, that divided into five patient expression profiles, which are useful for optimizing therapy selection. Furthermore, …

Retrospective Analysis Of Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome In Paediatric Patients Undergoing Hematopoietic Cell Transplantation -A Multicentre Study, Dristhi Ragoonanan, Hisham Abdel-Azim, Aditya Sharma, Saleh Bhar, Jennifer Mcarthur, Renee Madden, April Rahrig, Rajinder Bajwa, Jian Wang, Victoria Sun, Mariah Wright, Rebekah Lassiter, Basirat Shoberu, Jitesh Kawedia, Sajad Jawad Khazal, Kris Michael Mahadeo, Pediatric Acute Lung Injury And Sepsis Investigators (Palisi) Network

Faculty, Staff and Students Publications

BACKGROUND: Sinusoidal obstruction syndrome is a potentially fatal complication following hematopoietic cell transplantation, high-intensity chemotherapies and increasingly seen with calicheamicin based leukemia therapies. Paediatric specific European Society for Blood and Marrow Transplantation (pEBMT) diagnostic criteria have demonstrated benefit in single center studies compared to historic criteria. Yet, the extent to which they have been universally implemented remains unclear.

METHODS: We conducted a retrospective multi-centre study to examine the potential impact of the Baltimore, modified Seattle and pEBMT criteria on the incidence, severity, and outcomes of sinusoidal obstruction syndrome among paediatric hematopoietic cell transplantation patients.

FINDINGS: The incidence of sinusoidal obstruction …

Sickle-Cell Trait As A Risk Factor For Unprovoked Venous Thromboembolism: A Case Report, James Cross, Brendan Mackey, Umme Yasmin

Tower Health Research Day

No abstract provided.

Lymphoma Revealed: Exploring Stroke-Like Patterns, Mohammad Abu Tineh, Tan Tran, Mahmood Danishwar, Raesham Bukhari, Andrew Rettew

Tower Health Research Day

No abstract provided.

The Silent Culprit: Factor V Leiden’S Covert Role In Recurrent Miscarriages And First-Time Thromboembolism, Tanner Aldous, Sarah Almarzooqi, Mingran Yu, Jeremy Ellis

Tower Health Research Day

No abstract provided.