Hematology Commons^™

Standardizing Ngs Testing For All Pediatric Oncology Patients: A Quality Improvement Approach, Casey Treuting Md, Zachary Leblanc Md

Quality Improvement & Patient Safety Forum

No abstract provided.

American Society Of Hematology/International Society On Thrombosis And Haemostasis 2024 Updated Guidelines For Treatment Of Venous Thromboembolism In Pediatric Patients, Paul Monagle, Muayad Azzam, Rachel Bercovitz, Marisol Betensky, Rukhmi Bhat, Tina Biss, Brian Branchford, Leonardo R. Brandão, Anthony K.C. Chan, Vincent E.S. Faustino, Julie Jaffray, Sophie Jones, Hassan Kawtharany, Bryce A. Kerlin, Nicole Kucine, Riten Kumar, Christoph Male, Marie Claude Pelland-Marcotte, Leslie Raffini, Chittalsinh Raulji, Sarah E. Sartain, Clifford M. Takemoto, Cristina Tarango, C. Heleen Van Ommen, Maria C. Velez, Sara K. Vesely, John Wiernikowski, Suzan Williams, Hope P. Wilson, Et Al

School of Medicine Faculty Publications

Background: The American Society of Hematology (ASH) guidelines on treatment of pediatric venous thromboembolism (VTE) were published in 2018. In the last 6 years, there has been a 10-fold increase in the number of children involved in VTE treatment trials. Objective: The ASH Committee on Quality and Guidelines agreed to update the pediatric guidelines in conjunction with the International Society on Thrombosis and Haemostasis (ISTH). These ASH/ISTH evidence-based guidelines are intended to support patients, clinicians, and other health care professionals in the management of pediatric patients with VTE. Methods: ASH/ISTH formed a multidisciplinary guideline panel to minimize potential bias from …

Multimodal Spatial Proteomic Profiling In Acute Myeloid Leukemia, Christopher P Ly, Ivo Veletic, Christopher D Pacheco, Enes Dasdemir, Fatima Z Jelloul, Sammy Ferri-Borgogno, Akshay V Basi, Javier A Gomez, Jessica L Root, Patrick K Reville, Sonali Jindal, Sreyashi Basu, Padmanee Sharma, Andres E Quesada, Carlos Bueso-Ramos, Taghi Manshouri, Branko Cuglievan, Miriam Garcia, Jared K Burks, Hussein A Abbas

Faculty, Staff and Student Publications

Acute myeloid leukemia (AML) resides in an immune-rich microenvironment, yet, immune-based therapies have faltered in eliciting durable responses. Bridging this paradox requires a comprehensive understanding of leukemic interactions within the bone marrow microenvironment. We optimized a high-throughput tissue-microarray-based pipeline for high-plex spatial immunofluorescence and mass cytometry imaging on a single slide, capturing immune, tumor, and structural components. Using unbiased clustering on the spatial K function, we unveiled the presence of tertiary lymphoid-like aggregates in bone marrow, which we validated using spatial transcriptomics and an independent proteomics approach. We then found validated TLS signatures predictive of outcomes in AML using an …

Novel Rpl30 Variant In Diamond Blackfan Anemia Demonstrates Early Impact On Erythroid Differentiation With Downregulated Gata1-Hsp70, Alexandra Prosser-Dombrowski, Irina Pushel, Jacqelyn Nemechek, Priyanka Kumar, Jay L. Vivian, Jennifer Gerton, John M. Perry

Research Days

Background: Diamond Blackfan anemia (DBA) is an inherited bone marrow failure syndrome caused by ribosomal protein gene mutations leading to apoptosis of erythroid progenitors. We identified a novel heterozygous variant (c.167+769C>T) in the noncoding region of RPL30 in a patient diagnosed with DBA.

Objectives/Goal: We hypothesized that this variant stunts erythroid differentiation at the proerythroblast stage and is pathogenic for DBA.

Methods/Design: We developed an induced pluripotent stem cell (iPSC) model with a wild type (WT) and three CRISPR-Cas9 edited RPL30 mutant clones. iPSCs were differentiated into hematopoietic stem cells, which were assessed by flow cytometry and single cell …

Inpatient Thrombophilia Workup After Acute Vte: The Tests That Don’T Pay It Forward, Eliakim Munda, Bs, Ruben Rhoades, Md, Ms

Health Equity and Quality Improvement (HEQI) Summit

Background

• Venous thromboembolism is a complex multifactorial disease that is influenced by genetic, environmental and behavioral risk factors.
• Testing for inherited thrombophilia is commonly performed after a VTE event to help identify underlying genetic risk factors and assess the risk of recurrence.
• Despite clinical guidelines advising against thrombophilia testing in patients with acute VTE, these tests continue to be ordered even though lab results are unlikely to alter treatment decisions

Problem Statement

• At TJUH, activity and genetic assays are frequently ordered for patients with acute VTE during admission, increasing the likelihood of false- positive results that may lead to unnecessary …

Reducing Premedication Use With Intravenous Iron In The Outpatient Setting, Tara Rakiewicz, Liam Heneghan, Mark Attilio, Ruben Rhoades, Michael Zimmerman, Matthew Tucker, Brianna Costello, Adam Binder, Tanya Thomas

Health Equity and Quality Improvement (HEQI) Summit

Background

• Intravenous (IV) formulations of iron are safe, quick, easy to administer, and are indicated in patients with Iron Deficiency.
• Prior formulations of IV iron were associated with anaphylaxis and have since been removed from the market -- healthcare workers remain anxious about their potential for reactions
• Rate of anaphylactic reactions are about 1 in 200,000 infusions
• Current IV formulations available can be associated with a complement mediated, pseudo-allergy, that presents with flushing, myalgia/arthralgia, and chest pressure. Reactions are dependent on infusion rate and improve after stopping the infusion.
• Premedication with acetaminophen and diphenhydramine are often ordered for IV iron …

Time To Transfer - The Clock Is Ticking: A Quality Improvement Project, Tara Rakiewicz, Liam Heneghan, Brianna Costello, Matthew Tucker, Michael Zimmerman, Tanya Thomas, Jessica Sheridan, Adam Binder

Health Equity and Quality Improvement (HEQI) Summit

Background

• Thomas Jefferson University Hospital Center City (TJUH CC) campus is the predominant referral center for patients with hematologic malignancy in parts of PA, DE, and NJ
• Patients accepted for transfer to TJUH under Medical Oncology, often have longer than anticipated time to transfer (time from transfer acceptance to patient physical arrival)
• Long transfer times delay potentially lifesaving diagnostics and treatment; this can be most concerning for patients with aggressive hematologic malignancies given need for subspecialist management
• Data review from 2023-2024 showed patients with aggressive hematologic malignancy (defined as acute leukemia, chronic myeloid leukemia in blast crisis, diffuse large B …

Improving Recognition And Reporting Of Blood Transfusion Reactions In The Inpatient Setting, Tara Rakiewicz, Douglas Russ, Juliana Guarente, Katy Loos, Mary Harach, Jeffrey Riggio, Elizabeth Teixeira, Adam Binder

Health Equity and Quality Improvement (HEQI) Summit

Background

• Blood product transfusion reactions are associated with a spectrum of signs/ symptoms and can be challenging to identify. Transfusion reactions occur in about 1.1% of transfusions and constitute a significant source of iatrogenic morbidity and mortality.
• There is a nationwide under-reporting of transfusion reactions to blood transfusion Services.
• At TJUH, formally reported reactions comprised 0.24% of all blood product transfusions in 2024, similar to the national reporting average of 0.22%.
• Transfusion associated circulatory overload (TACO), and Transfusion related acute lung injury (TRALI) are two leading causes of mortality of blood transfusion reactions (Figure 1).
• Under-reporting leads to false data …

Are Hospital-Acquired Sepsis Cases Over-Reported Due To How Sepsis Is Coded In Electronic Health Records?, Michael Sakarya, Cooper Roslund, Spencer Foreman, David Gaieski, Md, Shruti Chandra, Md, Wayne Bond Lau

Health Equity and Quality Improvement (HEQI) Summit

Introduction

• Hospital-acquired sepsis (HAS) is a preventable cause of morbidity and mortality for hospitalized patients and is associated with greater cost and resource utilization compared to non-HAS.
• International Statistical Classification of Disease (ICD) coding system is used to identify HAS.
• Patients assigned HAS by ICD coding are presumed to have a nosocomial infection.
• Errors by ICD coding may cause misclassification of HAS cases.
• Unclear whether misclassified HAS have different outcomes than actual HAS

Resumption Of Anti-Platelet/Anticoagulation Therapy Following Lumbar Spine Surgery, Stephanie Serva, Md

Health Equity and Quality Improvement (HEQI) Summit

Background

• Problem: There is data on AC/AP use in perioperative period for patients undergoing spine surgery and no formal established guidelines on when to resume AC/AP medications after surgery
• Aim: To determine standardized protocol for resuming antiplatelet/anticoagulation therapy following lumbar surgery and to reduce combined post-operative cardiac/cerebrovascular/thrombotic events, and post- operative hematomas by 10% in 5 years
• Population: Patients undergoing elective lumbar spine surgery who take AC/AP at home

Identifying Distinct Subgroups With Severe Pain In Sickle Cell Disease: A Cluster Analysis Of The Grndad Multi-Center Registry, Martha O. Kenney, Samuel Wilson, Morgan Rosser, Sophie Lanzkron, Julie Kanter, Susan Padrino, Payal Desai, Deepa Manwani, Alice Cohen, Stephanie Guarino, Ward Hagar, Joshua Field, Jane Little

Department of Medicine Faculty Papers

Sickle cell disease (SCD) affects millions of individuals worldwide, and is characterized by both acute, episodic pain and chronic, persistent pain. Despite the significant burden of the disease, clinicians continue to face significant challenges in treating SCD pain due to variability in pain experiences. The objectives of this study were (1) to identify distinct pain subgroups based on demographic and biopsychosocial characteristics and (2) to evaluate the relationship between the subgroups and pain impact - a SCD-disease specific measure of pain interference. To achieve these objectives, we performed a hierarchical cluster analysis on a cross-sectional sample of adults with SCD …

A Century Of Hypomethylating Agent: A Remarkable Response To Azacitidine Monotherapy For Relapsed Acute Myeloid Leukemia - A Case Report, Chetan Jeurkar, Amry Majeed, Lindsay Wilde, Gina Keiffer, Margaret Kasner

Department of Medical Oncology Faculty Papers

INTRODUCTION: Acute myeloid leukemia (AML) is a disease of the elderly with a median age at diagnosis of 68 and with a very poor prognosis outside of those patients who have cytogenetic and/or molecular findings which confer a better prognosis. Most fit patients are treated with chemotherapy and then allogeneic hematopoietic stem cell transplant if they are intermediate or poor risk by ELN 2022 criteria (aSCT). aSCT is the mainstay of curative treatment although many patients are not candidates due to age, performance status, and comorbidities. In patients who are not candidates for curative treatment, low-intensity chemotherapy regimens, including monotherapy …

Ubiquitin-Conjugating Enzyme Ube2n Modulates Proteostasis In Immunoproteasome-Positive Acute Myeloid Leukemia, Chiharu Ishikawa, Laura Barreyro, Avery M Sampson, Kathleen M Hueneman, Kwangmin Choi, Sophia Y Philbrook, Issac Choi, Lyndsey C Bolanos, Mark Wunderlich, Andrew G Volk, Stephanie S Watowich, Kenneth D Greis, Daniel T Starczynowski

Faculty, Staff and Student Publications

Altered protein homeostasis through proteasomal degradation of ubiquitinated proteins is a hallmark of many cancers. Ubiquitination, coordinated by E1, E2, and E3 enzymes, involves up to 40 E2-conjugating enzymes in humans to specify substrates and ubiquitin linkages. In a screen for E2 dependencies in acute myeloid leukemia (AML), ubiquitin conjugating enzyme E2 N (UBE2N) emerged as the top candidate. To investigate UBE2N's role in AML, we characterized an enzymatically defective mouse model of UBE2N, revealing UBE2N's requirement in AML without an impact on normal hematopoiesis. Unlike other E2s, which mediate lysine-48 (K48) polyubiquitination and degradation of proteins, UBE2N primarily synthesizes …

Effect Of Social Determinants Of Health On Clinic Visit Attendance In Patients With Hemophilia, Shailly Gaur Md, Brian Lee Phd, Mph, James Anderst Md, Msci, Katie Foote Lscsw, Lcsw, Osw-C, Andrea Bradley-Ewing Mpa, Ma, Shannon Carpenter Md

Research Days

Background

Social determinants of health (SDOH) create barriers to seeking care regularly, especially for patients with chronic disease. Patients with moderate-severe hemophilia A and B (factor 8 and 9 deficiencies respectively) have a life-long higher risk of bleeding and require chronic therapies. Specialized care is offered through hemophilia treatment centers (HTCs); however, these can be difficult to access for some individuals. Previous SDOH research in this patient population has been limited; therefore, it can be difficult to identify the barriers to care that exist. There is a need to examine SDOH more thoroughly to create patient-directed interventions to improve access …

Phase I Study Of Pomalidomide In Relapsed Or Refractory Waldenström Macroglobulinaemia, Karan L Chohan, Donna M Weber, Lei Feng, L Michael Wang, Sattva S Neelapu, Jasper Olsem, Ralph J Johnson, Claudia Morales De Partovi, Robert Z Orlowski, Sheeba K Thomas

Faculty, Staff and Student Publications

No abstract provided.

A Pharmacokinetic And Safety Study Of Oral Arsenic Trioxide In Patients With Acute Promyelocytic Leukemia, Farhad Ravandi, Sravanti Rangaraju, Hagop Kantarjian, Guillermo Garcia-Manero, Musa Yilmaz, Kristen Baker, Terence Hall, Joy Grabenstein, Pourab Roy, Beth A Zamboni, William C Zamboni, Erica Warlick, Michael Kelly, David A Roth, Gabriel Ghiaur

Faculty, Staff and Student Publications

SY-2101 is a novel oral formulation of arsenic trioxide (ATO). Although IV ATO in combination with all trans retinoic acid is highly efficacious in treating acute promyelocytic leukemia (APL), there remains a significant unmet need due to the treatment burden associated with receiving daily ATO infusions for nearly a year and the risk of complications associated with indwelling central catheters. The pharmacokinetics (PK), safety, and tolerability of SY-2101 and ATO IV after single- and multiple-dose administration and the impact of food on PK for SY-2101 were evaluated in this phase 1 study in 15 participants with APL. SY-2101 in the …

Respiratory Failure In Pediatric Hematology And Oncology Patients On Extracorporeal Membrane Oxygenation: A Comparative Analysis, Michelle Brown Do, Jenna Miller, Asdis Finnsdottir Wagner, Erin Hall, Maya Dewan Md, Christopher Dandoy Md, Kalee Grassia Md, Bin Zhang Phd

Research Days

This project was a retrospective comparative analysis between two tertiary care pediatric institutions. The primary objective entailed examining survival outcomes in the oncologic and hematopoetic stem cell transplant patient populations with respiratory failure in the presence and absence of ECMO support.

Relationships Between Health Behaviors And Markers Of Oxidative Stress And Inflammation On Blood Pressure, Alison M. Godfrey

Honors Scholar Theses

Background. Young adulthood is a period when cardiometabolic risk factors begin to emerge. Developing cardiometabolic risk early can increase the risk and severity of chronic illness across the lifespan. Despite this, young adults are often understudied particularly as it relates to major cardiometabolic risk factors such as blood pressure (BP) and risk of hypertension. Hypertension is a public health crisis and early indicators of hypertension risk should be more thoroughly researched. Therefore, the purpose of the presented thesis is to examine BP in young adults and two potential pathways by which risk may emerge in young adults; inflammation (C-Reactive …

Evaluating The Therapeutic Potential Of Geranylgeranyl Diphosphate Synthase Inhibitor, Ram2061, In Myeloma Bone Disease, Molly Muehlebach

Theses & Dissertations

Multiple myeloma (MM) is a hematological malignancy of the plasma cells which often results in lytic bone disease. Myeloma bone disease (MBD), characterized by diffuse osteopenia, bone lesions, or pathological fracture, results from MM mediated promotion of osteoclast resorption and dual inhibition of bone formation, drastically reducing bone strength and integrity. Development of MBD is known to significantly impact patient quality of life and increase risk of mortality. Considering that up to 80-95% of MM patients are expected to develop bone disease post-initial MM diagnosis, there is a significant need within this population for therapeutics which address both MM disease …

Can Anemia Be A Prognostic Indicator To Scope For Gastroesophageal Junction Adenocarcinoma?, Ryan Tam, Neha Narayanan, Evan Basha, Joel Thompson

Advances in Clinical Medical Research and Healthcare Delivery

Gastroesophageal junction adenocarcinoma is a rapidly progressive disease that has a poor prognosis with a 5-year survival rate of 20%. It commonly presents with major symptoms of dysphagia and weight loss in addition to a long-standing history of reflux. As of now, screening for esophageal adenocarcinoma (EAC) is dependent on identifying risk factors which include a family history of Barrett’s esophagus and esophageal adenocarcinoma or patients with gastroesophageal reflux disease and at least one other risk factory for EAC such as age greater than 50 years, obesity or central adiposity, history of smoking, or male gender. Here, we present a …