Hematology Commons^™

Evaluating The Market Withdrawal Of Andexanet Alfa, Jordyn Linfield, Addisyn Cooper, Alexander Defranco, Emma Gerding, Jessica Kelley, Tyler Henney, Connor Dains, Brenna Hissong, Brittany Bates

Pharmacy and Wellness Review

The coagulation cascade comprises intrinsic, extrinsic, and common pathways that converge when thrombin converts fibrinogen (factor I) into fibrin, leading to fibrin mesh formation, stabilization of the platelet plug, and ultimately thrombus formation. Inhibition of the coagulation cascade can be achieved with a variety of anticoagulant medications, including direct oral anticoagulants (DOACs). The mechanism of action of DOACs is to inhibit either factor Xa or thrombin. Reversal of anticoagulation remains an important clinical consideration when managing patients on DOACs who experience serious bleeding events. Andexanet alfa is a recombinant, modified human factor Xa protein previously indicated for patients receiving rivaroxaban …

Dupilumab In Chronic Rhinosinusitis Without Nasal Polyps: Randomized Phase 2 Trial (Orion), Stella E. Lee, Anju T. Peters, Philippe Gevaert, Joseph K. Han, Claus Bachert, Francisco Moreira Da Silva, Andrés Rosenblüt, Chih-Chi Hu, Jennifer Maloney, Paolo Caferra, Adrianna Michalak, Andrew P. Fontenot, Lacey B. Robinson, Neelam A. Phadke

Department of Otolaryngology (ENT) Faculty Publications

BACKGROUND: Chronic rhinosinusitis (CRS) is often driven by type 2 inflammation and is characterized by nasal obstruction/ discharge, facial pain/pressure, and/or reduced smell, either with or without nasal polyps (CRSwNP or CRSsNP).

OBJECTIVE: To test whether dupilumab improves radiographic features in CRSsNP. Methods: ORION (NCT04678856), a phase 2, randomized, multicenter, double blind, placebo-controlled study, assessed dupilumab efficacy and safety in adults with uncontrolled CRSsNP. Patients were randomized 1:1 to dupilumab or placebo for 24 to 52 weeks. Endpoints included changes from baseline at week 24 in Lund–Mackay computed tomography (LMK-CT) score (dupilumab only [primary] and vs placebo [secondary]), sinus Total …

Accidental Daily Dosing: Severe Methotrexate Toxicity In A Patient With Rheumatoid Arthritis, Sidra Memon, Kavitha Vemuri, Syed Uzair Mahmood, Darshit Patel

Advances in Clinical Medical Research and Healthcare Delivery

This case highlights a crucial complication of oral methotrexate therapy: toxicity due to dosing errors. A patient’s daily dosing regimen, instead of the intended weekly schedule, led to a significantly excessive cumulative dose of methotrexate over a short period, resulting in severe hematologic and mucosal toxicity. This underscores the importance of clear patient education and vigilant prescription practices to prevent such errors.

Upper Respiratory Tract Infection Leading To A New Diagnosis Of Sweet Syndrome And Monoclonal Gammopathy Of Unknown Significance, Nidhi Rawat, Meron Gebrehiwot, Jason Raw, Jeyaprakash Ramachandran

HCA Healthcare Journal of Medicine

Background

We present a rare case of Sweet syndrome with underlying monoclonal gammopathy of unknown significance (MGUS) which initially presented as upper respiratory tract infection.

Case Presentation

A 52-year-old woman presented with a complaint of sore throat for 6 days, productive cough and fever for 5 days, and red, pruritic, circular, tender rashes on face, arms and trunk for 2 days. There was a past history of similar self-limiting rashes presenting intermittently for 1.5 years. She also reported to be taking tablet ibuprofen, as required for the past 1-2 years, for cervical spondylosis. On integumentary examination, widespread, red, tender, annular …

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 …

Isatuximab Plus Bortezomib, Lenalidomide, And Dexamethasone For Transplant-Ineligible Newly Diagnosed Multiple Myeloma Patients: A Frailty Subgroup Analysis Of The Imroz Trial, Salomon Manier, Meletios-Athanasios Dimopoulos, Xavier P Leleu, Philippe Moreau, Michele Cavo, Hartmut Goldschmidt, Robert Z Orlowski, Muriel Tron, Christina Tekle, Marie-France Brégeault, Andrea T Shafer, Meral Beksac, Thierry Facon

Faculty, Staff and Student Publications

Patients with multiple myeloma (MM) meeting frailty criteria have worse outcomes than those identified as non-frail. Here, we present a post hoc subgroup analysis of IMROZ, a global, phase III, open-label study investigating isatuximab (Isa) with bortezomib, lenalidomide, and dexamethasone (VRd) followed by Isa-Rd (N=265) versus VRd followed by Rd (N=181) in newly diagnosed transplant-ineligible MM (Ti NDMM) patients using the simplified International Myeloma Working Group (sIMWG) frailty score. Although patients aged >80 years were excluded, there was no exclusion for patients meeting frailty criteria. All patients received standard VRd/Rd dosing; Isa-VRd patients received intravenous Isa (cycle 1, 10 mg/kg …

The Immunophenotypic And Genetic Characterization Of Pediatric T -L Ymphoblastic Leukemia With A Mature Immunophenotype, Mahsa Khanlari, Wei Wang, Parastou Tizro, Mohammad K Eldomery

Faculty, Staff and Student Publications

Not available.

Outcomes Of Patients With Newly Diagnosed Acute Myeloid Leukemia With Flt3-Tyrosine Kinase Domain Mutations: Prognostic Implications Of Npm1 Co-Mutation, Sankalp Arora, Wei-Ying Jen, Musa Yilmaz, Indraneel Deshmukh, Jayastu Senapati, Sanam Loghavi, Ghayas C Issa, Nicholas J Short, Tapan M Kadia, Courtney D Dinardo, Gautam Borthakur, Joseph Jabbour, Naveen Pemmaraju, Michael Andreeff, Koichi Takahashi, Kapil Bhalla, Uday Popat, Elizabeth J Shpall, Betul Oran, Hussein A Abbas, Guillermo Garcia-Manero, Farhad Ravandi, Hagop Kantarjian, Naval Daver

Faculty, Staff and Student Publications

Background: The prognostic impact of Fms-like tyrosine kinase 3 (FLT3)-tyrosine kinase domain (TKD) mutation in patients with acute myeloid leukemia (AML) is not well defined. The authors described outcomes of one of the largest cohorts of patients with FLT3-TKD mutated (FLT3-TKDmut) AML to date.

Methods: This retrospective study included patients with newly diagnosed AML who received frontline treatment at The University of Texas MD Anderson Cancer Center from January 2012 to March 2024 divided into two cohorts: FLT3-TKDmut AML and nucleophosmin-mutated (NPM1mut)/FLT3-TKD wild-type (FLT3-TKDwt) AML. Patients with FLT3 internal tandem duplication mutations were excluded.

Results: In total, 2922 patients were …

Cns And Retinal Radiologic Findings Of A Young Patient With Heterozygous Prothrombin G20210a Gene Mutation, Justina Kasteri, Timothy Ehmann, Bryan Scott

Advances in Clinical Medical Research and Healthcare Delivery

Stroke is one of the leading causes of death and acquired long-term disability in the world.¹ In United States stroke is the 5^th leading cause of death with a mortality rate of 49.1 deaths per 100,000 people.² Strokes can be ischemic or hemorrhagic in origin, of which 85% are ischemic strokes. Approximately 10--15% of ischemic strokes occur in patients 18-50 years of age, and inherited thrombophilia may be a contributing factor through induction of a hypercoagulable state. Prothrombin G20210A mutation has an overall prevalence of approximately 2% of the general population, with an association between young patients …

Incidence Of Cytogenetic Abnormalities Detected By Fish Analysis In Multiple Myeloma Cases: A Seven-Year Study From A Cytogenetic Laboratory In King Chulalongkorn Memorial Hospital, Thailand (2018–2024), Montakarn Tansatit, Nutcharee Jongpornchai, Suwannee Songchart, Kittipornpan Krajokpap, Hudadini Da-Oh

Chulalongkorn Medical Journal

Background: Multiple myeloma (MM) is a genetically heterogeneous plasma cell malignancy with cytogenetic abnormalities influencing prognosis and treatment outcomes. Fluorescence in situ hybridization (FISH) is crucial for detecting clinically significant abnormalities, including IGH translocations and deletions (e.g., del(17p)), particularly in non-dividing plasma cells. However, cost and accessibility challenges limit comprehensive testing in resource-constrained settings like Thailand. Objectives: To investigate the incidence of cytogenetic abnormalities detected by FISH in MM cases over seven years in a Thai population, highlighting regional trends and barriers to comprehensive testing. Methods: A retrospective analysis was conducted on 360 bone marrow samples from MM patients between …

Mitophagy’S Impacts On Cancer And Neurodegenerative Diseases: Implications For Future Therapies, Jason Huang, Vincent Truong Pham, Shaozi Fu, Gang Huang, Ya-Guang Liu, Lei Zheng

Faculty, Staff and Student Publications

Substantial evidence supports an inverse relationship between cancer and neurodegenerative diseases (NDDs), but few studies investigate the biological mechanisms underlying this phenomenon. While previous explanations-such as inflammation, reactive oxygen species (ROS), genetic mutations, and cell death-remain significant, they ultimately converge on mitophagy. This review identifies mitophagy as a pivotal factor in the development of both cancer and NDDs, while also evaluating specific mechanisms and processes to clarify how mitophagy connects these opposing disease trajectories. By examining these factors, we aim to uncover the underlying mechanisms that explain the inverse relationship between cancer and NDDs, which will help develop therapeutic strategies …

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 …

Ptpn11 Mutations Define A Rare But Highly Adverse Subset Of Myelodysplastic Syndromes, Alexandre Bazinet, Alex Bataller, Guillermo Montalban-Bravo, Kelly Chien, Koji Sasaki, Wei Ying Jen, Mahesh Swaminathan, Tapan Kadia, Courtney Dinardo, Farhad Ravandi, Guillermo Garcia-Manero, Hagop Kantarjian

Faculty, Staff and Student Publications

No abstract provided.

Risk Of Early Death After Acute Leukemia Diagnosis Among Adolescents And Young Adults, Amy M Berkman, Clark R Andersen, Vidya Puthenpura, Nicholas J Short, Kelly Merriman, Mahesh Swaminathan, Branko Cuglievan, David Mccall, Courtney Dinardo, Cesar Nunez, Nitin Jain, Tapan Kadia, Ghayas Issa, Amber Gibson, Miriam B Garcia, J Andrew Livingston, Susan Parsons, Michelle A T Hildebrandt, Michael E Roth

Faculty, Staff and Student Publications

Background: Advances in care have led to improvements in survival for adolescents and young adults (AYAs) diagnosed with cancer; however, the risk of early death remains high for certain cancers, particularly acute leukemias. Risk factors for early death in AYAs diagnosed with acute leukemia have not been well studied.

Methods: The Surveillance, Epidemiology, and End Results registry was used to assess risk of early death (within 2 months of diagnosis) in AYAs diagnosed with acute leukemia (n = 16 153). Early death proportion, by year, for AYAs diagnosed between 2006 and 2020 was described. Associations between incidence of early death …

Complications And Management Of Idiopathic Multicentric Castleman Disease, Kavanya Feustel, Jacob W. Keeling, Olivia Makos, Dmitriy Scherbak

HCA Healthcare Journal of Medicine

Background

The pathophysiology of idiopathic multicentric Castleman disease (iMCD) is poorly understood compared to the other subtypes of MCD, which has contributed to limited treatment options and poor prognosis for iMCD patients. The pathogenesis of iMCD is thought to be mediated in part by dysregulation of interleukin (IL)-6.

Case Presentation

We present a case report of a 39-year-old Caucasian man with siltuximab-refractory iMCD. He presented with severe lower extremity lymphedema and wounds. His disease progressed through standard-of-care siltuximab. Due to his severe disease-related morbidity, he contracted recurrent infections, often complicated by sepsis. Ultimately, he required a left lower extremity amputation. …

Emerging Technologies Of Single-Cell Multi-Omics, Yi June Kim, Koichi Takahashi

Faculty, Staff and Student Publications

The heterogeneity of the hematopoietic system was largely veiled by traditional bulk sequencing methods, which measure the averaged signals from mixed cellular populations. In contrast, single-cell sequencing has enabled the direct measurement of individual signals from each cell, significantly enhancing our ability to unveil such heterogeneity. Building on these advances, numerous single-cell multi-omics techniques have been developed into high-throughput, routinely accessible platforms, delineating the precise relationships among different layers of the central dogma in molecular biology. These technologies have uncovered the intricate landscape of genetic clonality and transcriptional heterogeneity in both normal and malignant hematopoietic systems, highlighting their roles in …

Clinical Interrogation Of Tp53 Aberrations And Its Impact On Survival In Patients With Myeloid Neoplasms, Jayastu Senapati, Sanam Loghavi, Guillermo Garcia-Manero, Guillin Tang, Tapan Kadia, Nicholas J Short, Hussein A Abbas, Naszrin Arani, Courtney D Dinardo, Gautam Borthakur, Naveen Pemmaraju, Betul Oran, Elizabeth Shpall, Uday Popat, Richard Champlin, Sherry Pierce, Sankalp Arora, Ghayas Issa, Musa Yilmaz, Keyur Patel, Koichi Takahashi, Guillermo Montalban-Bravo, Danielle Hammond, Fadi G Haddad, Farhad Ravandi, Hagop M Kantarjian, Naval G Daver

Faculty, Staff and Student Publications

In myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) with TP53 aberrations, dissecting the interaction amongst patient, disease and treatment factors are important for therapeutic decisions and prognostication. This retrospective analysis included patients with newly diagnosed MDS (>5% blasts) and AML with TP53 mutation(s) treated at MD Anderson Cancer Center. We factored patient age, TP53 aberration burden, therapy intensity and use of venetoclax in the AML subgroup, and allogeneic hematopoietic stem cell transplantation (HSCT) to interrogate outcomes. TP53 was annotated as high-risk (TP53HR) if >1 mutation, one mutation plus allelic deletion or a single mutation with variant allele frequency …

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 …

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 …

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 …

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 …

Clonal Dynamics And Somatic Evolution Of Haematopoiesis In Mouse, Chiraag D Kapadia, Nicholas Williams, Kevin J Dawson, Caroline Watson, Matthew J Yousefzadeh, Duy Le, Kudzai Nyamondo, Sreeya Kodavali, Alex Cagan, Sarah Waldvogel, Xiaoyan Zhang, Josephine De La Fuente, Daniel Leongamornlert, Emily Mitchell, Marcus A Florez, Krzysztof Sosnowski, Rogelio Aguilar, Alejandra Martell, Anna Guzman, David Harrison, Laura J Niedernhofer, Katherine Y King, Peter J Campbell, Jamie Blundell, Margaret A Goodell, Jyoti Nangalia

Center on Aging Staff Publications

Haematopoietic stem cells maintain blood production throughout life1. Although extensively characterized using the laboratory mouse, little is known about clonal selection and population dynamics of the haematopoietic stem cell pool during murine ageing. We isolated stem cells and progenitors from young and old mice, identifying 221,890 somatic mutations genome-wide in 1,845 single-cell-derived colonies. Mouse stem cells and progenitors accrue approximately 45 somatic mutations per year, a rate only approximately threefold greater than human progenitors despite the vastly different organismal sizes and lifespans. Phylogenetic patterns show that stem and multipotent progenitor cell pools are established during embryogenesis, after which …

Prospective Clinical Trials Of Venetoclax And Hypomethylating Agents For Relapsed Bpdcn, Naveen Pemmaraju, Luan Hai Phan, Geoffrey Fell, Marlise R Luskin, Mahesh Swaminathan, Sherry Pierce, Courtney Dinardo, Abhishek Maiti, Marina Konopleva, Andrew A Lane

Faculty, Staff and Student Publications

No abstract provided.

Kras Mutation Detection By Liquid Biopsy For Pancreatic Ductal Adenocarcinoma, Mahmoud Yousef, Abdelrahman Yousef, Mark W Hurd, Ashwathy Pillai, Saikat Chowdhury, Rebecca Snyder, Mark Knafl, Ryan L Lewis, Paul M Roy, Mohammad Fanaeian, Sali Albarouki, Luca F Castelnovo, Jennifer Peterson, Brandon G Smaglo, Robert A Wolff, Shubham Pant, Jason Willis, Ryan Huey, Michael Overman, Ching-Wei Tzeng, Michael P Kim, Naruhiko Ikoma, Jess E Maxwell, Matthew H G Katz, Huamin Wang, Anirban Maitra, Eugene Koay, Ethan B Ludmir, Anthony Chen, Camila Lopez, Haoqiang Ying, John Paul Shen, Dan Zhao

Faculty, Staff and Student Publications

The clinical utility of liquid biopsy (LB) for pancreatic ductal adenocarcinoma (PDAC) remain understudied. Our single-institution cohort of 311 PDAC patients with non-tumor tissues informed LB found 81.2% positivity (N = 186) in metastatic cases and in 52.4% (N = 43) of localized disease. KRAS mutations were detected in 64.6% (N = 148) of metastatic cases and 16% (N = 13) for localized disease. Positive LB, especially KRAS mutation detection, is associated with worse overall survival (OS) in metastatic PDAC (median 14.5 vs. 31.3 months, HR = 2.7, 95%CI = 1.7-4.3, P <  0.0001). The positive concordance rates of KRAS and TP53 mutations were 63% and 68% in metastatic disease but only 7% (KRAS) and 33% (TP53) in localized disease, respectively. Among the 41 patients who underwent serial liquid biopsy testing, 25% tested positive after an initial negative result. LB detects therapeutically targetable mutations in 58.5% of PDAC patients and is associated with OS.

Phase 2 Trial Of Ibrutinib And Nivolumab In Patients With Relapsed Cns Lymphomas, Dai Chihara, Raphael E Steiner, Ranjit Nair, Lei Feng, Sairah Ahmed, Paolo Strati, Luis Malpica, Donna P Griffith, Shivon A Mathew, Wirt Montinez, Gita Masand, Felipe Samaniego, Maria A Rodriguez, Fredrick B Hagemeister, Luis E Fayad, Swaminathan P Iyer, Loretta J Nastoupil, Sattva S Neelapu, Christopher R Flowers, Jason R Westin

Faculty, Staff and Student Publications

Treatment options are limited for both relapsed/refractory primary and secondary central nervous system (CNS) lymphoma and the prognosis remains poor. Previous studies have shown the activity of Bruton tyrosine kinase inhibitors and programmed death-1-targeted therapies in CNS lymphoma, and studies suggested potential synergy. Therefore, we conducted a phase 2 trial that combined ibrutinib with nivolumab for patients with relapsed/refractory CNS lymphoma. Patients received 560 mg oral ibrutinib daily with 240 mg IV nivolumab every 14 days (28 days per cycle). Patients who had partial or complete response after 6 cycles of treatment could continue therapy for up to 2 years …

Ven In Combination With 10-Day Dec In Newly Diagnosed Elderly Or Relapsed/Refractory Acute Myeloid Leukemia, And High-Risk Myelodysplastic Syndrome: Long Term Follow-Up Of A Phase 2 Trial, Mahesh Swaminathan, Courtney D Dinardo, Abhishek Maiti, Naveen Pemmaraju, Maro Ohanian, Navel G Daver, Guillermo Garcia-Manero, Ghayas C Issa, Gautam Borthakur, Farhad Ravandi, Guillermo Montalban-Bravo, Tapan M Kadia, Yesid Alvarado, Elias J Jabbour, Nicholas J Short, William G Wierda, Nitin Jain, Steven M Kornblau, Lucia Masarova, Sherry A Pierce, Wei Qiao, Jing Ning, Hagop Kantarjian, Marina Y Konopleva

Faculty, Staff and Student Publications

No abstract provided.