Hematology Commons^™

Fluorescent Peptide For Detecting Factor Xiiia Activity And Fibrin In Whole Blood Clots Forming Under Flow, Yue Liu, Jennifer Crossen, Timothy J. Stalker, Scott L. Diamond

Cardeza Foundation for Hematologic Research

Background

During clotting, thrombin generates fibrin monomers and activates plasma-derived transglutaminase factor (F) XIIIa; collagen and thrombin-activated platelets offer thrombin-independent cellular FXIIIa (cFXIIIa) for clotting. Detecting fibrin on collagen and tissue factor surfaces in whole blood clotting typically uses complex reagents like fluorescent fibrinogen or antifibrin antibody.

Objectives

We want to test whether the peptide using the α2- antiplasmin crosslinking mechanism by FXIIIa is a useful tool in both monitoring FXIIIa activity, and visualize and monitor fibrin formation, deposition, and extent of crosslinking within fibrin structures in whole blood clots formed under flow.

Methods

We tested a fluorescent peptide derived …

Single Cell Proteogenomics Analysis Of Aml Samples Treated With Decitabine And Venetoclax Reveals Divergent Treatment Escape Mechanisms, Yi June Kim

Dissertations and Theses (Open Access)

Venetoclax is a small molecule inhibitor targeting BCL-2. Since its approval, the combination therapy of hypomethylating agents and Venetoclax (HMA+Ven) has become a standard of care for acute myeloid leukemia (AML) patients unfit for intensive chemotherapy. Nonetheless, clinical challenges persist as patients either do not respond or eventually relapse, and the underlying mechanisms of these outcomes are not yet fully understood. Prior studies have identified genetic factors (TP53 and RTK/RAS pathway mutations) and phenotypic factors (monocytic differentiation) to be associated with resistance. In this light, we hypothesized that integrative assessment of genetic and phenotypic factors could further elucidate the unknown …

Influence Of Treatment Intensity And Medical Comorbidities In Older Adults With Peripheral T Cell Lymphoma, Max J Gordon, Zhigang Duan, Hui Zhao, Loretta Nastoupil, Samuel Ng, Alexey V Danilov, Swaminathan Iyer, Sharon H Giordano

Faculty, Staff and Student Publications

We conducted a population-based study of patients >65 years, diagnosed 2008-2017, with peripheral T-cell lymphoma (PTCL) using SEER-Medicare. Associations between PTCL subtype, treatment regimen, comorbidity, and mortality were assessed using the Kaplan-Meier method and multivariable Cox regression. Amongst the 2,546 patients, the median age was 77 years (interquartile range, 71-83). 5-year overall survival (OS) ranged from 22.2% to 37.3% depending on PTCL subtype. The most common frontline regimen was cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). 5-year OS rate was 47.0% for patients treated with etoposide + CHOP (N = 67; CHOEP), 33.7% for those treated with CHOP (N …

An Update On The Management Of Advanced Phase Chronic Myeloid Leukemia, Nicholas J Short, Jayastu Senapati, Elias Jabbour

Faculty, Staff and Student Publications

Purpose of review: While most patients with chronic myeloid leukemia (CML) present in a chronic phase and are expected to have a normal life expectancy, some patients present with or progress to a more aggressive accelerated phase (AP) or blast phase (BP) of CML. Herein, we discuss the diagnostic considerations of advanced phase CML and review its contemporary management.

Recent findings: Later-generation, more potent BCR::ABL1 tyrosine kinase inhibitors (TKIs) such as ponatinib may result in superior outcomes in patients with advanced phase CML. For CML-BP, combination approaches directed against the blast immunophenotype appear superior to TKI monotherapy. The role of …

Women, Power, And Cancer: A Lancet Commission, Ophira Ginsburg, Verna Vanderpuye, Ann Marie Beddoe, Nirmala Bhoo-Pathy, Freddie Bray, Carlo Caduf, Narjust Florez, Ibtihal Fadhil, Nazik Hammad, Miriam Mutebi

General Surgery, East Africa

Women interact with cancer in complex ways, as healthy individuals participating in cancer prevention and screening activities, as individuals living with and beyond a cancer diagnosis, as caregivers for family members and friends, as patient advocates, as health workers and healthcare professionals, and as cancer researchers and policy makers. The topic of women and cancer spans broad terrain, beyond women’s cancers and the biomedical aspects of any type of cancer that women in all their diversities might experience. It is inclusive of the ways in which sex and gender influence exposures to cancer risk factors, interactions with the cancer health …

Sustained Remissions In Cll After Frontline Fcr Treatment With Very-Long-Term Follow-Up, Philip A Thompson, Alexandre Bazinet, William G Wierda, Constantine S Tam, Susan M O'Brien, Satabdi Saha, Christine B Peterson, William Plunkett, Michael J Keating

Faculty, Staff and Student Publications

Chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab (FCR) achieves durable remissions, with flattening of the progression-free survival (PFS) curve in patients with mutated immunoglobulin heavy chain variable gene (IGHV-M). We updated long-term follow-up results from the original 300-patient FCR study initiated at MD Anderson in 1999. The current median follow-up is 19.0 years. With this extended follow-up, the median PFS for patients with IGHV-M was 14.6 years vs 4.2 years for patients with unmutated IGHV (IGHV-UM). Disease progression beyond 10 years was uncommon. In total, 16 of 94 (17%) patients in remission at 10 years subsequently progressed with the additional follow-up …

Safety And Efficacy Of Direct Oral Anticoagulants In Stroke Prevention In Patients With Atrial Fibrillation Complicated With Anemia And/Or Thrombocytopenia: A Retrospective Cohort Study, Wenlin Xu, Jiana Chen, Shuyi Wu, Nianxu Huang, Xia Chen, Wang Zhang, Wei Hu, Jun Su, Hengfen Dai, Ping Gu, Xiaohong Huang, Xiaoming Du, Ruijuan Li, Qiaowei Zheng, Xiangsheng Lin, Yanxia Zhang, Lang Zou, Yuxin Liu, Min Zhang, Xiumei Liu, Zhu Zhu, Jinhua Zhang

Faculty, Staff and Student Publications

BACKGROUND: There are limited data about the clinical benefits and harm of direct oral anticoagulants (DOACs) in stroke prevention in patients with atrial fibrillation (AF) complicated with anemia or thrombocytopenia.

METHODS: This is a multi-center retrospective cohort study involving 5469 AF patients from 15 hospitals in China. Patients were divided into three groups according to hemoglobin and platelet levels: Group 1 (hemoglobin male ≥ 130 g/L; female ≥ 120 g/L and platelet ≥ 100 × 10

RESULTS: Higher hemoglobin levels were associated with a reduced risk of total bleeding and major bleeding, while platelet counts were not associated with any …

Allogeneic Hematopoietic Cell Transplantation For Blastic Plasmacytoid Dendritic Cell Neoplasm: A Cibmtr Analysis, Hemant S. Murthy, Mei-Jie Zhang, Karen Chen, Sairah Ahmed, Uday Deotare, Siddhartha Ganguly, Ankit Kansagra, Fotios V. Michelis, Taiga Nishihori, Mrinal Patnaik, Muhammad Bilal Abid, Mahmoud Aljurf, Yasuyuki Arai, Ulrike Bacher, Talha Badar, Sherif M. Badawy, Karen Ballen, Minoo Battiwalla, Amer Beitinjaneh, Nelli Bejanyan, Vijaya Raj Bhatt, Valerie I. Brown, Rodrigo Martino, Jean-Yves Cahn, Paul Castillo, Jan Cerny, Saurabh Chhabra, Edward Copelan, Andrew Daly, Bhagirathbhai Dholaria, Miguel Angel Diaz Perez, César O. Freytes, Michael R. Grunwald, Shahrukh Hashmi, Gerhard C. Hildebrandt, Omer Jamy, Jacinth Joseph, Christopher G. Kanakry, Nandita Khera, Maxwell M. Krem, Yachiyo Kuwatsuka, Hillard M. Lazarus, Lazaros J. Lekakis, Hongtao Liu, Dipenkumar Modi, Pashna N. Munshi, Alberto Mussetti, Neil D. Palmisiano, Sagar S. Patel, David A. Rizzieri, Sachiko Seo, Mithun Vinod Shah, Akshay Sharma, Melhm Sohl, Scott R. Solomon, Matthew Ulrickson, Celalettin Ustun, Marjolein Van Der Poel, Leo F. Verdonck, John L. Wagner, Trent Wang, Baldeep Wirk, Amer Zeidan, Mark Litzow, Partow Kebriaei, Christopher S. Hourigan, Daniel J. Weisdorf, Wael Saber, Mohamed A. Kharfan-Dabaja

Department of Medical Oncology Faculty Papers

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy with a poor prognosis and considered incurable with conventional chemotherapy. Small observational studies reported allogeneic hematopoietic cell transplantation (allo-HCT) offers durable remissions in patients with BPDCN. We report an analysis of patients with BPDCN who received an allo-HCT, using data reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). We identified 164 patients with BPDCN from 78 centers who underwent allo-HCT between 2007 and 2018. The 5-year overall survival (OS), disease-free survival (DFS), relapse, and nonrelapse mortality (NRM) rates were 51.2% (95% confidence interval [CI], 42.5-59.8), …

Cigarette Smoke Exposure Accelerates Aml Progression In Flt3-Itd Models, Mary Figueroa, Huaxian Ma, Mansour Alfayez, Daniel Enrique Morales-Mantilla, Fei Wang, Yue Lu, Marcos R Estecio, Katherine Y King, Eugenie Kleinerman, Seyed Javad Moghaddam, Naval Daver, Michael Andreeff, Marina Konopleva, Courtney Dinardo, Joya Chandra

Faculty, Staff and Student Publications

No abstract provided.

Dhodh: A Promising Target In The Treatment Of T-Cell Acute Lymphoblastic Leukemia, Amy N Sexauer, Gabriela Alexe, Karin Gustafsson, Elizabeth Zanetakos, Jelena Milosevic, Mary Ayres, Varsha Gandhi, Yana Pikman, Kimberly Stegmaier, David B Sykes

Faculty, Staff and Student Publications

Patients with relapsed or refractory T-cell acute lymphoblastic leukemia (T-ALL) have a poor prognosis with few therapeutic options. With the goal of identifying novel therapeutic targets, we used data from the Dependency Map project to identify dihydroorotate dehydrogenase (DHODH) as one of the top metabolic dependencies in T-ALL. DHODH catalyzes the fourth step of de novo pyrimidine nucleotide synthesis. Small molecule inhibition of DHODH rapidly leads to the depletion of intracellular pyrimidine pools and forces cells to rely on extracellular salvage. In the absence of sufficient salvage, this intracellular nucleotide starvation results in the inhibition of DNA and RNA synthesis, …

Association Of Anemia With Mortality In Young Adult Patients With Intracerebral Hemorrhage, Yixin Tian, Yu Zhang, Jialing He, Pengfei Hao, Tiangui Li, Yangchun Xiao, Liyuan Peng, Yuning Feng, Xin Cheng, Haidong Deng, Peng Wang, Weelic Chong, Yang Hai, Lvlin Chen, Chao You, Fang Fang

Student Papers, Posters & Projects

This study aimed to examine the association of hemoglobin concentration with a 90-day mortality of young adult patients with ICH in a large retrospective cohort. A retrospective observational study was conducted between December 2013 and June 2019 in two tertiary academic medical centers in China. We defined patients with hemoglobin concentration < 80 g/L as severe anemia and 80-120/130 g/L as mild to moderate anemia. We also defined patients with hemoglobin concentration > 160 g/L as high hemoglobin. Associations of hemoglobin and outcomes were evaluated in multivariable regression analyses. The primary outcome was mortality at 90 days. We identified 4098 patients with ICH who met the inclusion criteria. After adjusting primary confounding variables, the 90-day mortality rate was significantly higher in young …

A Randomized Phase Iii Study Of Standard Versus High-Dose Cytarabine With Or Without Vorinostat For Aml, Guillermo Garcia-Manero, Nikolai A Podoltsev, Megan Othus, John M Pagel, Jerald P Radich, Min Fang, David A Rizzieri, Guido Marcucci, Stephen A Strickland, Mark R Litzow, M Lynn Savoie, Bruno C Medeiros, Mikkael A Sekeres, Tara L Lin, Geoffrey L Uy, Bayard L Powell, Jonathan E Kolitz, Richard A Larson, Richard M Stone, David Claxton, James Essell, Selina M Luger, Sanjay R Mohan, Anna Moseley, Frederick R Appelbaum, Harry P Erba

Faculty, Staff and Student Publications

Prior experience indicated that use of higher doses of cytarabine during induction for acute myeloid leukemia (AML) with a histone deacetylase inhibitor resulted in high response rates. S1203 was a randomized multicenter trial for previously untreated patients aged 18-60 with AML which compared daunorubicin and cytarabine (DA), idarubicin with higher dose cytarabine (IA) and IA with vorinostat (IA + V). The primary endpoint was event free survival (EFS). 738 patients were randomized: 261 to each DA and IA arms and 216 to the IA + V arm. 96, 456, and 150 patients had favorable-, intermediate-, and unfavorable-risk cytogenetics, respectively. 152 …

Glutamate Receptor Dysregulation And Platelet Glutamate Dynamics In Alzheimer's And Parkinson's Diseases: Insights Into Current Medications, Deepa Gautam, Ulhas Naik, Meghna Naik, Santosh Yadav, Rameshwar Nath Chaurasia, Debabrata Dash

Cardeza Foundation for Hematologic Research

Two of the most prevalent neurodegenerative disorders (NDDs), Alzheimer's disease (AD) and Parkinson's disease (PD), present significant challenges to healthcare systems worldwide. While the etiologies of AD and PD differ, both diseases share commonalities in synaptic dysfunction, thereby focusing attention on the role of neurotransmitters. The possible functions that platelets may play in neurodegenerative illnesses including PD and AD are becoming more acknowledged. In AD, platelets have been investigated for their ability to generate amyloid-ß (Aß) peptides, contributing to the formation of neurotoxic plaques. Moreover, platelets are considered biomarkers for early AD diagnosis. In PD, platelets have been studied for …

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 …

Virtual Delivery Of Stress Management And Resiliency Training (Smart) During The Covid-19 Pandemic To Hematology/Oncology Fellows: A Pilot Study, Colt Williams, Sherry Chesak, Deirdre R. Pachman, Ross Dierkhising, Laura Rhee, Konstantinos Leventakos

Journal of Wellness

Introduction: Medical trainees experience a high degree of stress that predisposes them to burnout. This pilot study tested a scalable approach to deliver a validated resilience program (Stress Management and Resiliency Training (SMART)) among Hematology/Oncology fellows at an academic medical center.

Methods: This was a mixed-methods, prospective, single-arm clinical trial involving Hematology/Oncology fellows at Mayo Clinic in Rochester, MN, USA. Four one-hour training sessions were conducted virtually with 26 fellows. Stress, burnout, and emotional resilience were measured at baseline, three months, and six months post-intervention using the Perceived Stress Scale (PSS-10), Maslach Burnout Inventory (MBI-HSS), and Connor-Davidson Resilience …

Hypofibrinogenemia Following Injury In 186 Children And Adolescents: Identification Of The Phenotype, Current Outcomes, And Potential For Intervention, Justin Gerard, Jan-Michael Van Gent, Jessica Cardenas, Christian Gage, David E Meyer, Charles Cox, Charles E Wade, Bryan A Cotton

Faculty, Staff and Student Publications

OBJECTIVES: Recent studies evaluating fibrinogen replacement in trauma, along with newly available fibrinogen-based products, has led to an increase in debate on where products such as cryoprecipitate belong in our resuscitation strategies. We set out to define the phenotype and outcomes of those with hypofibrinogenemia and evaluate whether fibrinogen replacement should have a role in the initial administration of massive transfusion.

METHODS: All patients/17-4/21 were reviewed. We then evaluated all patients who received emergency-release and massive transfusion protocol (MTP) products. Patients were defined as hypofibrinogenemic (HYPOFIB) if admission fibrinogen(r-TEG) angleHYPOFIB, the impact on outcomes, and whether early replacement improved mortality. …

Α-Synuclein Is The Major Platelet Isoform But Is Dispensable For Activation, Secretion, And Thrombosis, Alexis N. Smith, Smita Joshi, Harry Chanzu, Hammodah Rawhi Hammodah Alfar, Kanakanagavalli Shravani Prakhya, Sidney W. Whiteheart

Saha Cardiovascular Research Center Faculty Publications

Platelets play many roles in the vasculature ensuring proper hemostasis and maintaining integrity. These roles are facilitated, in part, by cargo molecules released from platelet granules via Soluble NSF Attachment Protein Receptor (SNARE) mediated membrane fusion, which is controlled by several protein-protein interactions. Chaperones have been characterized for t-SNAREs (i.e. Munc18b for Syntaxin-11), but none have been clearly identified for v-SNAREs. α- Synuclein has been proposed as a v-SNARE chaperone which may affect SNARE-complex assembly, fusion pore opening, and thus secretion. Despite its abundance and that it is the only isoform present, α-synuclein’s role in platelet secretion is uncharacterized. In …

Automated Large Vessel Occlusion Detection Software And Thrombectomy Treatment Times: A Cluster Randomized Clinical Trial, Juan Carlos Martinez-Gutierrez, Youngran Kim, Sergio Salazar-Marioni, Muhammad Bilal Tariq, Rania Abdelkhaleq, Arash Niktabe, Anjan N Ballekere, Ananya S Iyyangar, Mai Le, Hussain Azeem, Charles C Miller, Jon E Tyson, Sandi Shaw, Peri Smith, Mallory Cowan, Isabel Gonzales, Louise D Mccullough, Andrew D Barreto, Luca Giancardo, Sunil A Sheth

Faculty, Staff and Student Publications

Importance

The benefit of endovascular stroke therapy (EVT) in large vessel occlusion (LVO) ischemic stroke is highly time dependent. Process improvements to accelerate in-hospital workflows are critical.

Objective

To determine whether automated computed tomography (CT) angiogram interpretation coupled with secure group messaging can improve in-hospital EVT workflows.

Design, Setting, and Participants

This cluster randomized stepped-wedge clinical trial took place from January 1, 2021, through February 27, 2022, at 4 comprehensive stroke centers (CSCs) in the greater Houston, Texas, area. All 443 participants with LVO stroke who presented through the emergency department were treated with EVT at the 4 CSCs. Exclusion …

The Use Of Viatorr Stent At The Thoracic Outlet To Maintain Hemodialysis Access Function, Mohammad Ghasemi-Rad, Lauren Do, Michael Collard, Jai Cui, Zubin Irani

Faculty, Staff and Students Publications

PURPOSE: Venous steno-occlusive disease at the thoracic outlet affects up to 30% of the hemodialysis population [1] causing arm swelling and hemodialysis access dysfunction. Balloon angioplasty in this region can be of limited utility given the rigid compressive effect of surrounding musculoskeletal (MSK) structures. Outcomes of using the Viatorr endoprosthesis (Gore Viatorr TIPS Endoprosthesis, Gore, Flagstaff AR, USA, Viatorr ®) within this region to salvage the HD access in patients who presented with dialysis access dysfunction is presented.

METHODS: A retrospective chart review was performed of our tertiary and quaternary care hospital system. Hemodialysis patients were included in the study …

Market Competition And Anemia Management In The United States Following Dialysis Payment Reform, Anshul Bhatnagar, Vishnupriyadevi Parvathareddy, Wolfgang C Winkelmayer, Glenn M Chertow, Kevin F Erickson

Faculty, Staff and Students Publications

BACKGROUND: Whether market competition influences health care provider responses to national reimbursement reforms is unknown.

OBJECTIVES: We examined whether changes in anemia management after the expansion of Medicare's dialysis payment bundle varied with market competition.

RESEARCH DESIGN: With data from the US dialysis registry, we used a difference-in-differences (DID) design to estimate the independent associations of market competition with changes in anemia management after dialysis reimbursement reform.

SUBJECTS: A total of 326,150 patients underwent in-center hemodialysis in 2009 and 2012, representing periods before and after reimbursement reform.

MEASURES: Outcomes were erythropoiesis-stimulating agent (ESA) and intravenous iron dosage, the probability of …