Neoplasms Commons^™

Outcomes Of Radiation Integrated With T-Cell-Engaging Bispecific Antibodies In Relapsed/Refractory Multiple Myeloma, Heta Patel, Harper Hubbeling, Kyle Yu, Maribel Carpenter, Michael Lariviere, John Plastaras, Adam Cohen, Shivani Kapur, Dan Vogl, Adam Waxman, Edward Stadtmauer, Alfred Garfall, Sandra Susanibar-Adaniya

Student Papers, Posters & Projects

No abstract provided.

Plasmacytoma As The Initial Presentation Of Multiple Myeloma: A Case Report, Chantelle Martin, Sidra Memon, Austin Kim, Saleha Asghar

Advances in Clinical Medical Research and Healthcare Delivery

We report an unusual case of a woman who presented with nonspecific symptoms of unilateral facial mass and bleeding from her lower lip over several weeks. The mass was found to be relatively fixed and irregular with destruction of facial bone as evidenced by imaging. Initial investigations indicated the possibility of multiple myeloma, which was later confirmed with serum protein electrophoresis and bone marrow biopsy. Cervical lymph node biopsy confirmed presence of plasmacytoid cells positive for CD 20.

Effect Of Valemetostat On The Pharmacokinetics Of Midazolam And Digoxin: A Phase 1 Drug-Drug Interaction Study In Patients With Non-Hodgkin Lymphoma, Masaya Tachibana, Steven Horwitz, Eric Jacobsen, Francine Foss, Pamela Allen, Pierluigi Porcu, Tatyana Feldman, Jia Ruan, Jonathan Brammer, Jie Wang, Shinichi Inaba, Yuka Iko, Keiko Nakajima, Yasuyuki Kakurai, Noriaki Kitami, Yang Chen, Yvonne Lau

Department of Medicine Faculty Papers

Valemetostat tosylate (valemetostat) is an oral, potent, dual inhibitor of enhancer of zeste homolog (EZH)2/1, under investigation in non-Hodgkin lymphomas (NHLs) and solid tumors. In vitro, it inhibits cytochrome P450 3A (CYP3A) and P-glycoprotein (P-gp) when combined with sensitive CYP3A or P-gp substrates. This drug–drug interaction (DDI) sub-study is part of the phase 1 trial of valemetostat monotherapy (DS3201-A-J101; NCT02732275), assessing the effect of valemetostat on the pharmacokinetics (PK) of sensitive CYP3A and P-gp substrates midazolam and digoxin, respectively, in patients with relapsed or refractory NHL, and its safety and efficacy. Patients received two simultaneous single doses of midazolam and …

Artificial Intelligence In The Management Of Leukemia, Stephanie Koo, Austin P. Runde, Melvin Speisman

School of Medicine

BACKGROUND: Recently, given the demonstrated ability of AI to accurately characterize complex pathologies, AI has been proposed to be of use in the diagnosis, treatment, and monitoring of leukemias given their genetic complexity and subtype heterogeneity, array of treatments, and need for relapse detection. AI has several potential applications in the management of leukemia. First, it can be used to detect leukemia; using AI to detect nuances in lab values can ensure these deadly cancers are never missed. Second, AI can be used to risk-stratify patients and personalize treatments; leukemias are among the most genetically complex cancers with well-characterized risk …

Radiologic Findings Of A Mediastinal Mass With Pleural Fluid Cytologic Analysis: A Case Report Of Recurrent Mantle-Cell Lymphoma, Mark Cwajna, Zaain Ahmad, Evan Basha, Emily Maggioncalda, Shehbaz Ahmad, Joel Thompson

Advances in Clinical Medical Research and Healthcare Delivery

This case report details a 69-year-old male who presented with a right-sided pleural effusion and a mediastinal mass that was ultimately identified as recurrent mantle-cell lymphoma, occurring over 20 years after his initial diagnosis. Imaging findings discussed include chest radiograph and chest, abdomen and pelvis computed tomography depicting the mass compressing on various neighboring structures.

Fractional Flow Reserve From Coronary Ct: Evidence, Applications, And Future Directions, Arta Kasaeian, Mohadese Ahmadzade, Taylor Hoffman, Mohammad Ghasemi-Rad, Anoop Padoor Ayyappan

Faculty, Staff and Students Publications

Coronary computed tomography angiography (CCTA) has emerged as the leading noninvasive imaging modality for the assessment of coronary artery disease (CAD), offering high-resolution visualization of the coronary anatomy and plaque characterization. The development of fractional flow reserve derived from CCTA (FFR-CT) has further transformed the diagnostic landscape by enabling the simultaneous evaluation of both anatomical stenosis and lesion-specific ischemia. FFR-CT has demonstrated diagnostic accuracy comparable to invasive FFR. The combined use of CCTA and FFR-CT is now pivotal in a broad range of clinical scenarios, including the evaluation of stable and acute chest pain, assessment of high-risk and complex plaque …

A Ticking Time Bomb: An Overview Of A Case Report Of Neutropenic Fever Secondary To Tick-Borne Illness, Yasemin Galiboglu, Danielle Thor, Joann Ha, Kristine Wong, Cindy Hou

Rowan-Virtua Research Day

The advent of immunomodulatory therapies and their ever-expanding number of treatment indications necessitates the understanding of their associated complications. Neutropenic fever serves as an example of these complications often encountered in clinical practice. Although neutropenic fever can result from virtually any pathogen, episodes of the syndrome secondary to tick-borne illness remain relatively undocumented in the scientific literature. In the case presented, a 77-year-old female with a pertinent past medical history of smoldering IgG multiple myeloma on active immunosuppressive therapy presented with a first-time episode of neutropenic fever likely secondary to tick-borne illness. Through this overview of a broader report, attention …

Case Report: Myeloid Neoplasms With The T(3;12)(Q26.2;P13.1)/ Mecom-Etv6 Translocation: Report Of Two New Cases And Review Of The Literature, Soumya Mikkilineni, Juan Pablo Pineda-Reyes, Lindsay Wilde, Andres Ferber, Zi-Xuan Wang, Stephen Peiper, Guldeep Uppal, Md, Jerald Gong, Jinglan Liu

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The MECOM (MDS1 and EVI1 complex locus) gene, located at 3q26.2, encodes an oncogenic transcription factor implicated in multiple signaling pathways. Rearrangements involving MECOM/3q26.2, including inversions, translocations, insertions and cryptic chromosomal changes, are observed in myeloid neoplasms and are associated with high-risk disease features and poor clinical outcomes. The translocation t(3;12)(q26.2;p13.1) is a rare genetic event, resulting in a fusion of the MECOM gene at 3q26.2 with the ETV6 gene at 12p13.1. To date, only 78 cases of hematologic neoplasms harboring t(3;12) have been reported in the English literature, primarily as case reports or case series. T(3;12) has …

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 …

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.

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 …

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 …

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 …

Central Nervous System Prophylaxis Utilization In Patients With Newly Diagnosed Diffuse Large B-Cell Lymphoma Within A Large Community Health System, Michael J. Williams, Sol D. Atienza, Renee H. Aranda, Kayleigh B. Flint, Sherjeel Sana, Stephen C. Medlin, Zartash Gul, Federico A. Sanchez, Michael A. Thompson

Journal of Patient-Centered Research and Reviews

Purpose: The impact of central nervous system (CNS) prophylaxis in diffuse large B-cell lymphoma (DLBCL) is contentious. The CNS International Prognostic Index (IPI) calculator offers prognostic guidance in identifying those patients who may be at highest risk of disease progression or relapse to the CNS. However, it is unclear whether this tool has guided clinician decision-making in a real-world setting. Studies have suggested that CNS prophylaxis may not offer clinically significant benefit in terms of preventing CNS disease progression. Given this, we investigated the utilization of CNS prophylaxis within our own population and documentation of the CNS-IPI score.

Methods: We …

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 …

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.

Cerebral Venous Sinus Thrombosis (Cvst): A Retrospective Study, Nia Acharya

Theses/Capstones/Creative Projects

This retrospective study investigates the long-term management of Cerebral Venous Sinus Thrombosis (CVST) in 51 patients over a 3-month follow-up. The analysis covers demographics, risk factors, CVST presentation, associated diseases, thrombophilia, laboratory results, and antithrombotic treatments. CVST, a rare thrombosis of dural/cerebral sinuses, poses life-threatening risks with an annual incidence aligning with literature, notably affecting young individuals. Underlying causes range from rare disorders to common triggers, complicating diagnosis, especially during pregnancy. Imaging techniques aid diagnosis, with systemic anticoagulation preferred despite bleeding risks. Noteworthy findings include a higher incidence in women, predominantly presenting with headaches. Two cases of vaccine-induced immune thrombotic …

The Remission Status Of Aml Patients After Allo-Hct Is Associated With A Distinct Single-Cell Bone Marrow T-Cell Signature, Anna Mathioudaki, Xizhe Wang, David Sedloev, Richard Huth, Aryan Kamal, Michael Hundemer, Yi Liu, Spyridoula Vasileiou, Premal Lulla, Carsten Müller-Tidow, Peter Dreger, Thomas Luft, Tim Sauer, Michael Schmitt, Judith B Zaugg, Caroline Pabst

Faculty, Staff and Students Publications

Acute myeloid leukemia (AML) is a hematologic malignancy for which allogeneic hematopoietic cell transplantation (allo-HCT) often remains the only curative therapeutic approach. However, incapability of T cells to recognize and eliminate residual leukemia stem cells might lead to an insufficient graft-versus-leukemia (GVL) effect and relapse. Here, we performed single-cell RNA-sequencing (scRNA-seq) on bone marrow (BM) T lymphocytes and CD34+ cells of 6 patients with AML 100 days after allo-HCT to identify T-cell signatures associated with either imminent relapse (REL) or durable complete remission (CR). We observed a higher frequency of cytotoxic CD8+ effector and gamma delta (γδ) T cells in …

Case Of Rosai Dorfman Disease In A Patient With Newly Diagnosed Hodgkin Lymphoma, Liza Salloum, Jennifer Rojas Huen, Ricardo Serna, Alisha Valdez

Research Symposium

Background: Rosai Dorfman Disease (RDD, also known as sinus histiocytosis with massive lymphadenopathy) is a rare non-Langerhans cell histiocytosis, classified into nodal (classic) and extranodal disease. Most patients present with non-tender cervical lymphadenopathy, although other sites including the inguinal and axillary regions have been reported. Extranodal disease (~43% of cases) can involve any organ system. RDD is more common in children, but cases have been reported in patients in their 70s. The prognosis of nodal RDD can correlate with the number of nodal groups involved. Many cases can be managed only with observation, although surgery, chemotherapy, corticosteroids, and immunomodulators have …

Safety, Efficacy And Determinants Of Response Of Allogeneic Cd19-Specific Car-Nk Cells In Cd19+ B Cell Tumors: A Phase 1/2 Trial, David Marin, Ye Li, Rafet Basar, Hind Rafei, May Daher, Jinzhuang Dou, Vakul Mohanty, Merve Dede, Yago Nieto, Nadima Uprety, Sunil Acharya, Enli Liu, Jeffrey Wilson, Pinaki Banerjee, Homer A Macapinlac, Christina Ganesh, Peter F Thall, Roland Bassett, Mariam Ammari, Sheetal Rao, Kai Cao, Mayra Shanley, Mecit Kaplan, Chitra Hosing, Partow Kebriaei, Loretta J Nastoupil, Christopher R Flowers, Sadie Mae Moseley, Paul Lin, Sonny Ang, Uday R Popat, Muzaffar H Qazilbash, Richard E Champlin, Ken Chen, Elizabeth J Shpall, Katayoun Rezvani

Faculty, Staff and Student Publications

There is a pressing need for allogeneic chimeric antigen receptor (CAR)-immune cell therapies that are safe, effective and affordable. We conducted a phase 1/2 trial of cord blood-derived natural killer (NK) cells expressing anti-CD19 chimeric antigen receptor and interleukin-15 (CAR19/IL-15) in 37 patients with CD19+ B cell malignancies. The primary objectives were safety and efficacy, defined as day 30 overall response (OR). Secondary objectives included day 100 response, progression-free survival, overall survival and CAR19/IL-15 NK cell persistence. No notable toxicities such as cytokine release syndrome, neurotoxicity or graft-versus-host disease were observed. The day 30 and day 100 OR rates were …

Gamma Delta T Cells In Acute Myeloid Leukemia: Biology And Emerging Therapeutic Strategies, Adishwar Rao, Akriti Agrawal, Gautam Borthakur, Venkata Lokesh Battula, Abhishek Maiti

Faculty, Staff and Student Publications

γδ T cells play an important role in disease control in acute myeloid leukemia (AML) and have become an emerging area of therapeutic interest. These cells represent a minor population of T lymphocytes with intrinsic abilities to recognize antigens in a major histocompatibility complex-independent manner and functionally straddle the innate and adaptive immunity interface. AML shows high expression of phosphoantigens and UL-16 binding proteins that activate the Vδ2 and Vδ1 subtypes of γδ T cells, respectively, leading to γδ T cell-mediated cytotoxicity. Insights from murine models and clinical data in humans show improved overall survival, leukemia-free survival, reduced risk of …

Anesthetic Management Of A Patient With Renal Cell Carcinoma-Associated Venous Thrombosis And Massive Transfusion, Gary Zhang, Ryan Palacios, Jamal Hasoon, Christopher L Robinson, Anvinh Nguyen

Faculty, Staff and Students Publications

A 53-year-old male with a history of multiple deep venous thromboses (DVTs) underwent a right open radical nephrectomy with inferior vena cava (IVC) thrombectomy in the context of renal cell carcinoma (RCC)-associated venous thrombosis. Imaging and renal biopsy revealed a diagnosis of RCC with non-occlusive thrombosis of the left renal vein and occlusive thrombosis of the infrarenal IVC. The major risks of concern for the procedure included thrombus embolization from surgical manipulation and massive bleeding. Intraoperatively, the patient experienced significant hemorrhage requiring massive transfusion protocol. The purpose of this case report is to emphasize the importance of multidisciplinary involvement, intraoperative …

Discovery, Structure-Activity Relationship And In Vitro Anticancer Activity Of Small-Molecule Inhibitors Of The Protein-Protein Interactions Between Af9/Enl And Af4 Or Dot1l, Xin Li, Xiaowei Wu, Shenyou Nie, Jidong Zhao, Yuan Yao, Fangrui Wu, Chandra Bhushan Mishra, Md Ashraf-Uz-Zaman, Bala Krishna Moku, Yongcheng Song

Faculty, Staff and Students Publications

Simple Summary

Chromosomal translocations involving the mixed lineage leukemia (MLL) gene generate potent fusion oncogenes and cause acute myeloid leukemia or lymphocytic leukemia, which account for ~75% infant and 5–10% child/adult acute leukemia cases with a poor prognosis (5-year survival rates < 45%). Protein–protein interactions between the most frequent MLL fusion partner proteins AF9/ENL and AF4 or histone methyltransferase DOT1L are critical to malignant gene expression and are therefore a potential drug target for cancer. Compound screening followed by medicinal chemistry studies identified several novel small-molecule inhibitors showing strong inhibition of these protein–protein interactions, significant suppression of characteristic gene expression, and robust cellular anticancer activities with negligible cytotoxicity. These compounds are useful chemical probes for biological studies of these protein–protein interactions, as well as pharmacological leads for further drug development against MLL-rearranged and other leukemias.

Abstract

Chromosomal translocations involving the mixed lineage leukemia (MLL) gene cause 5–10% acute leukemias with poor clinical outcomes. Protein–protein interactions (PPI) between the most frequent MLL fusion partner proteins AF9/ENL and AF4 or histone methyltransferase DOT1L are drug targets for MLL-rearranged (MLL-r) leukemia. Several benzothiophene-carboxamide compounds were identified as novel inhibitors of these PPIs with IC₅₀ values as …

Prospective Clinical And Biomarker Validation Of The American Society For Transplantation And Cellular Therapy Consensus Definition For Transplantation-Associated Thrombotic Microangiopathy, Shengling Ma, Saleh Bhar, Danielle Guffey, Rock Bum Kim, Mahrukh Jamil, Christopher I Amos, Stephanie J Lee, Sangeeta R Hingorani, Sarah E Sartain, Ang Li

Faculty, Staff and Students Publications

Transplantation-associated thrombotic microangiography (TA-TMA) is a disorder that causes severe complications after allogeneic hematopoietic cell transplantation (allo-HCT). Diagnosing TA-TMA is challenging because of the lack of standardized criteria. In this study, we aimed to evaluate the new TA-TMA consensus definition from the American Society for Transplantation and Cellular Therapy (ASTCT) panel as part of an ongoing prospective pediatric cohort study, and also to compare the impact and outcomes of using the current definition of clinical TMA (cTMA) versus the new consensus definition. We included patients age 0 to 18 years who underwent their first allo-HCT between May 2021 and January …

Characteristics And Clinical Outcomes Of Patients With Acute Myeloid Leukemia With Inv(3)(Q21q262) Or T(3; 3)(Q21; Q262), Guillaume Richard-Carpentier, Caitlin R Rausch, Koji Sasaki, Danielle Hammond, Kiyomi Morita, Koichi Takahashi, Guilin Tang, Rashmi Kanagal-Shamanna, Kapil Bhalla, Courtney D Dinardo, Gautam Borthakur, Naveen Pemmaraju, Elizabeth J Shpall, Amin Alousi, Naval G Daver, Guillermo Garcia-Manero, Marina Y Konopleva, Farhad Ravandi, Hagop M Kantarjian, Tapan M Kadia

Faculty, Staff and Student Publications

Acute myeloid leukemia (AML) with inv(3)(q21q26.2)/t(3;3)(q21;q26.2) has a very poor prognosis. Determinants of clinical outcomes and optimal treatment remain uncertain. We retrospectively reviewed 108 cases of AML with inv(3)/t(3;3) and evaluated clinicopathological characteristics and clinical outcomes: 53 newly diagnosed (ND) AML and 55 relapsed/refractory (R/R) AML. Median age was 55 years. White blood cell (WBC) count ≥20x109/L and platelet count ≥140x109/L was observed in 25% and 32% of ND patients, respectively. Anomalies involving chromosome 7 were identified in 56% of patients. The most frequently mutated genes were SF3B1, PTPN11, NRAS, KRAS and ASXL1. In ND patients, the composite complete remission …

Risks Factors And Outcomes For Isolated Catheter-Related Deep Venous Thrombosis In Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation, Jonathan Avery, Danielle Guffey, Shengling Ma, Ryan Basom, Stephanie J Lee, David Garcia, Cristhiam M Rojas Hernandez, Ang Li, Kylee L Martens

Faculty, Staff and Students Publications

INTRODUCTION: Patients undergoing allogenic hematopoietic stem cell transplantation (allo-HSCT) require indwelling central venous catheters. The comparative incidence, risk, and outcome of isolated catheter-related deep venous thrombosis (CR-DVT) versus pulmonary embolism/lower-extremity DVT (PE/LE-DVT) remains unclear.

MATERIALS AND METHODS: We conducted a retrospective cohort study for patients undergoing allo-HSCT from 2006 to 2019. CR-DVT and PE/LE-DVT outcomes were screened using ICD codes and radiology reports and confirmed by medical record reviews. Cox regression models were used to assess the association between thrombotic outcomes and pertinent baseline and time-varying covariates. The impact of thrombotic events within 1-year post-transplant (time-varying) on overall mortality was …

Venous Thromboembolism Risk In Cancer Patients Receiving First-Line Immune Checkpoint Inhibitor Versus Chemotherapy, Ang Li, Sarah B May, Jennifer La, Kylee L Martens, Christopher I Amos, Christopher R Flowers, Nhan V Do, Mary T Brophy, Vipul Chitalia, Katya Ravid, John Michael Gaziano, Nathanael R Fillmore

Faculty, Staff and Students Publications

It remains unclear if immune checkpoint inhibitor (ICI) therapy is associated with higher rate of venous thromboembolism (VTE) compared with cytotoxic chemotherapy (chemo) in patients with comparable cancer type, staging, and comorbidities. Using the national Veterans Affairs healthcare system database from 2016 to 2021, we performed a propensity score (PS)-weighted retrospective cohort study to compare the incidence of VTE in patients with selected stage III/IV cancer receiving first-line ICI versus chemo. The PS model utilized overlap weights to balance age, sex, race, treatment year, VTE history, paralysis/immobilization, prolonged hospitalization, cancer type, staging, time between diagnosis and treatment, and National Cancer …

External Validation Of A Novel Electronic Risk Score For Cancer-Associated Thrombosis In A Comprehensive Cancer Center, Ang Li, Giordana De Las Pozas, Clark R Andersen, Chijioke C Nze, Katy M Toale, Emily M Milner, Nathanael R Fillmore, Elizabeth Yu Chiao, Cristhiam Rojas Hernandez, Michael H Kroll, Kelly W Merriman, Christopher R Flowers

Faculty, Staff and Students Publications

Venous thromboembolism (VTE) is a significant complication for cancer patients undergoing systemic therapy. We performed an independent external validation for a recently derived and validated a novel electronic health record (EHR) VTE risk score in a comprehensive cancer center. Adult patients with incident cancer diagnoses were identified from MD Anderson Cancer Center Tumor Registry 1/2017-1/2021. Baseline covariates extracted at the time of first-line systemic therapy included demographics, cancer site/histology, stage, treatment, complete blood count, body mass index, recent prolonged hospitalization, and history of VTE or paralysis. VTE was ascertained using an institution-specific natural language processing radiology algorithm (positive predictive value …

Targeting Glutaminase Is Therapeutically Effective In Ibrutinib-Resistant Mantle Cell Lymphoma, Lingzhi Li, Lei Nie, Alexa Jordan, Qingsong Cai, Yang Liu, Yijing Li, Yuxuan Che, Jovanny Vargas, Zhihong Chen, Angela Leeming, Wei Wang, Yixin Yao, Michael Wang, Vivian Changying Jiang

Faculty, Staff and Student Publications

Mantle cell lymphoma (MCL) is an incurable B-cell non-Hodgkin lymphoma characterized by frequent relapses. The development of resistance to ibrutinib therapy remains a major challenge in MCL. We previously showed that glutaminolysis is associated with resistance to ibrutinib. In this study, we confirmed that glutaminase (GLS), the first enzyme in glutaminolysis, is overexpressed in ibrutinib-resistant MCL cells, and that its expression correlates well with elevated glutamine dependency and glutaminolysis. Furthermore, we discovered that GLS expression correlates with MYC expression and the functioning of the glutamine transporter ASCT2. Depletion of glutamine or GLS significantly reduced cell growth, while GLS overexpression enhanced …