Hematology Commons^™

Treatment Outcomes For Newly Diagnosed, Treatment-Naïve Tp53-Mutated Acute Myeloid Leukemia: A Systematic Review And Meta-Analysis, Naval G Daver, Shahed Iqbal, Camille Renard, Rebecca J Chan, Ken Hasegawa, Hao Hu, Preston Tse, Jiajun Yan, Michael J Zoratti, Feng Xie, Giridharan Ramsingh

Faculty, Staff and Student Publications

Background: TP53 mutations, which are present in 5% to 10% of patients with acute myeloid leukemia (AML), are associated with treatment resistance and poor outcomes. First-line therapies for TP53-mutated (TP53m) AML consist of intensive chemotherapy (IC), hypomethylating agents (HMA), or venetoclax combined with HMA (VEN + HMA).

Methods: We conducted a systematic review and meta-analysis to describe and compare treatment outcomes in newly diagnosed treatment-naïve patients with TP53m AML. Randomized controlled trials, single-arm trials, prospective observational studies, and retrospective studies were included that reported on complete remission (CR), CR with incomplete hematologic recovery (CRi), overall survival (OS), event-free survival (EFS), …

Prevalence Of Iron Deficiency In Patients With Inherited Bleeding Disorders, Thomas Cochran, Brian Lee, Shannon Carpenter

Posters

Background: Synthesis of hemoglobin is one of several important roles iron plays in the human body. Approximately 50% of all anemia cases may be caused by iron deficiency which is frequently caused by chronic blood loss. Patients with bleeding disorders have greater propensity for blood loss and therefore may have a higher prevalence of iron deficiency when compared to the general population. However, few studies have assessed the prevalence of iron deficiency in children with inherited bleeding disorders. Objectives: This study aims to identify the prevalence of iron deficiency in children with an inherited bleeding disorder. Methods: A retrospective analysis …

Impact Of Time To Treatment On Endovascular Thrombectomy Outcomes In The Early Versus Late Treatment Time Windows, Negar Asdaghi, Kefeng Wang, Hannah Gardener, Angus Jameson, David Z Rose, Ayham Alkhachroum, Carolina M Gutierrez, Hao Ying, Nils Mueller-Kronast, Nicole B Sur, Chuanhui Dong, Gillian Gordon Perue, Marissa Lepain, Sebastian Koch, Nastajjia Krementz, Erika Marulanda-Londoño, Ricardo Hanel, Brijesh Mehta, Dileep R Yavagal, Tatjana Rundek, Ralph L Sacco, Jose G Romano

Faculty, Staff and Student Publications

BACKGROUND: The impact of time to treatment on outcomes of endovascular thrombectomy (EVT) especially in patients presenting after 6 hours from symptom onset is not well characterized. We studied the differences in characteristics and treatment timelines of EVT-treated patients participating in the Florida Stroke Registry and aimed to characterize the extent to which time impacts EVT outcomes in the early and late time windows.

METHODS: Prospectively collected data from Get With the Guidelines-Stroke hospitals participating in the Florida Stroke Registry from January 2010 to April 2020 were reviewed. Participants were EVT patients with onset-to-puncture time (OTP) of ≤24 hours and …

Building The Foundation For A Community-Generated National Research Blueprint For Inherited Bleeding Disorders: Research Priorities To Transform The Care Of People With Hemophilia, Duc Q Tran, Craig C Benson, Judith A Boice, Meera Chitlur, Amy L Dunn, Miguel A Escobar, Kalpna Gupta, Jill M Johnsen, James Jorgenson, Scott D Martin, Suzanne Martin, Shannon L Meeks, Alfredo A Narvaez, Doris V Quon, Mark T Reding, Ulrike M Reiss, Brittany Savage, Kim Schafer, Bruno Steiner, Courtney Thornburg, Lena M Volland, Annette Von Drygalski

Faculty, Staff and Student Publications

BACKGROUND: Decades of research have transformed hemophilia from severely limiting children's lives to a manageable disorder compatible with a full, active life, for many in high-income countries. The direction of future research will determine whether exciting developments truly advance health equity for all people with hemophilia (PWH). National Hemophilia Foundation (NHF) and American Thrombosis and Hemostasis Network conducted extensive inclusive all-stakeholder consultations to identify the priorities of people with inherited bleeding disorders and those who care for them.

RESEARCH DESIGN AND METHODS: Working group (WG) 1 of the NHF State of the Science Research Summit distilled the community-identified priorities for …

An Echogenic Clot Method For Thrombolysis Monitoring In Thrombotic Stroke Models, Dalton E Carter, Tao Peng, Melanie R Moody, Shao-Ling Huang, David D Mcpherson, Melvin E Klegerman

Faculty, Staff and Student Publications

To demonstrate thrombolytic efficacy of a tissue plasminogen activator (tPA)-loaded echogenic liposome (TELIP) formulation in a rabbit thrombotic stroke model (the most relevant animal model for evaluation of directed thrombolytic therapy for ischemic stroke), we sought to develop a means of monitoring thrombus dissolution quantitatively by ultrasound imaging methods. We hypothesized that a gas-free ultrasound contrast agent can be incorporated into blood clots at a concentration that does not affect the tPA-mediated clot dissolution rate, while enabling quantitative assessment of the clot dissolution rate. Clots were formed from a mixture of whole rabbit blood, 1 M calcium chloride, human thrombin …

Microfluidic Concurrent Assessment Of Red Blood Cell Adhesion And Microcapillary Occlusion: Potential Hemorheological Biomarkers In Sickle Cell Disease, Yuncheng Man, Douglas H. Wu, Ran An, Karamoja Monchamp, Utku Goreke, Zoe Sekyonda, William J. Wulftange, Chiara Federici, Allison Bode, Lalitha V. Nayak, Umut A. Gurkan

Faculty Scholarship

Deformability and non-adherence are two fundamental functional properties of red blood cells (RBCs), which allow them to move unimpeded through the microvasculature. In sickle cell disease (SCD), polymerization of abnormal sickle hemoglobin leads to decreased deformability and increased membrane adhesiveness in RBCs. This contributes to abnormal blood vessel occlusion, which is central to the underlying pathophysiology. RBC deformability and adhesiveness are, therefore key hemorheological biomarkers in characterizing disease states as well as in evaluating novel therapeutics. To date, these important interrelated biomarkers have been assessed in distinct laboratory assays, without integration or concurrent assessment in vitro. To this end, we …

The Immunomodulating Effects Of Morphine Dependence And Withdrawal In A Rat Model, Mark Stoll

Annual Research Symposium

Would you like to know what happens to the immune system during opioid drug withdrawal?

Exploiting Prmt5 As A Target For Combination Therapy In Mantle Cell Lymphoma Characterized By Frequent Atm And Tp53 Mutations, Yuxuan Che, Yang Liu, Yixin Yao, Holly A Hill, Yijing Li, Qingsong Cai, Fangfang Yan, Preetesh Jain, Wei Wang, Lixin Rui, Michael Wang

Faculty, Staff and Student Publications

Constant challenges for the treatment of mantle cell lymphoma (MCL) remain to be recurrent relapses and therapy resistance, especially in patients harboring somatic mutations in the tumor suppressors ATM and TP53, which are accumulated as therapy resistance emerges and the disease progresses, consistent with our OncoPrint results that ATM and TP53 alterations were most frequent in relapsed/refractory (R/R) MCL. We demonstrated that protein arginine methyltransferase-5 (PRMT5) was upregulated in R/R MCL, which predicted a poor prognosis. PRMT5 inhibitors displayed profound antitumor effects in the mouse models of MCL with mutated ATM and/or TP53, or refractory to CD19-targeted CAR T-cell therapy. …

Endovascular Vs Medical Management For Late Anterior Large Vessel Occlusion With Prestroke Disability: Analysis Of Clear And Rescue-Japan, James E Siegler, Muhammad M Qureshi, Raul G Nogueira, Kanta Tanaka, Simon Nagel, Patrik Michel, Nicholas Vigilante, Marc Ribo, Hiroshi Yamagami, Shinichi Yoshimura, Mohamad Abdalkader, Diogo C Haussen, Mahmoud H Mohammaden, Stefania Nannoni, Markus A Möhlenbruch, Hilde Henon, Sunil A Sheth, Santiago Ortega-Gutierrez, Marta Olive-Gadea, Francois Caparros, Fatih Seker, Syed Zaidi, Alicia C Castonguay, Kazutaka Uchida, Nobuyuki Sakai, Ajit S Puri, Mudassir Farooqui, Kazunori Toyoda, Sergio Salazar-Marioni, Masataka Takeuchi, Behzad Farzin, Hesham E Masoud, Anna Luisa Kuhn, Ameena Rana, Masafumi Morimoto, Masunari Shibata, Tadashi Nonaka, Piers Klein, Anvitha Sathya, Nicole L Kiley, Charlotte Cordonnier, Davide Strambo, Jelle Demeestere, Peter A Ringleb, Daniel Roy, Osama O Zaidat, Tudor G Jovin, Johannes Kaesmacher, Urs Fischer, Jean Raymond, Thanh N Nguyen

Faculty, Staff and Student Publications

BACKGROUND AND OBJECTIVES: Current guidelines do not address recommendations for mechanical thrombectomy (MT) in the extended time window (>6 hours after time last seen well [TLSW]) for large vessel occlusion (LVO) patients with preexisting modified Rankin Scale (mRS) > 1. In this study, we evaluated the outcomes of MT vs medical management in patients with prestroke disability presenting in the 6- to 24-hour time window with acute LVO.

METHODS: We analyzed a multinational cohort (61 sites, 6 countries from 2014 to 2020) of patients with prestroke (or baseline) mRS 2 to 4 and anterior circulation LVO treated 6-24 hours from …

Cell-Membrane-Coated Nanoparticles For Targeted Drug Delivery To The Brain For The Treatment Of Neurological Diseases, Jianzhuang Li, Yanhao Wei, Chunlin Zhang, Rentang Bi, Yanmei Qiu, Yanan Li, Bo Hu

Faculty, Staff and Student Publications

Neurological diseases (NDs) are a significant cause of disability and death in the global population. However, effective treatments still need to be improved for most NDs. In recent years, cell-membrane-coated nanoparticles (CMCNPs) as drug-targeting delivery systems have become a research hotspot. Such a membrane-derived, nano drug-delivery system not only contributes to avoiding immune clearance but also endows nanoparticles (NPs) with various cellular and functional mimicries. This review article first provides an overview of the function and mechanism of single/hybrid cell-membrane-derived NPs. Then, we highlight the application and safety of CMCNPs in NDs. Finally, we discuss the challenges and opportunities in …

Effective Treatment Of Low-Risk Acute Gvhd With Itacitinib Monotherapy, Aaron Etra, Alexandra Capellini, Amin Alousi, Monzr M Al Malki, Hannah Choe, Zachariah Defilipp, William J Hogan, Carrie L Kitko, Francis Ayuk, Janna Baez, Isha Gandhi, Stelios Kasikis, Sigrun Gleich, Elizabeth Hexner, Matthias Hoepting, Urvi Kapoor, Steven Kowalyk, Deukwoo Kwon, Amelia Langston, Marco Mielcarek, George Morales, Umut Özbek, Muna Qayed, Ran Reshef, Wolf Rösler, Nikolaos Spyrou, Rachel Young, Yi-Bin Chen, James L M Ferrara, John E Levine

Faculty, Staff and Student Publications

The standard primary treatment for acute graft-versus-host disease (GVHD) requires prolonged, high-dose systemic corticosteroids (SCSs) that delay reconstitution of the immune system. We used validated clinical and biomarker staging criteria to identify a group of patients with low-risk (LR) GVHD that is very likely to respond to SCS. We hypothesized that itacitinib, a selective JAK1 inhibitor, would effectively treat LR GVHD without SCS. We treated 70 patients with LR GVHD in a multicenter, phase 2 trial (NCT03846479) with 28 days of itacitinib 200 mg/d (responders could receive a second 28-day cycle), and we compared their outcomes to those …

Factors And Behaviors Related To Successful Transition Of Care After Hospitalization For Ischemic Stroke, Chuanhui Dong, Hannah Gardener, Tatjana Rundek, Erika Marulanda, Carolina M Gutierrez, Iszet Campo-Bustillo, Gillian Gordon Perue, Karlon H Johnson, Ralph L Sacco, Jose G Romano, Transitions Of Care Stroke Disparities Study (Tcsd-S) Investigators

Faculty, Staff and Student Publications

BACKGROUND: Our objective is to describe adoption of the posthospitalization behaviors associated with successful transition of care and related baseline characteristics.

METHODS: This study includes 550 participants in the Transition of Care Stroke Disparities Study, a prospective observational cohort derived from the Florida Stroke Registry. Participants had an ischemic stroke (2018-2021), discharged home or to rehabilitation, with modified Rankin Scale score=0-3 (44% women, 24% Black, 48% White, 26% Hispanic, 35% foreign-born). We collected baseline sociodemographic and clinical characteristics. A structured telephone interview at 30-day postdischarge evaluated outcomes including medication adherence, medical appointment attendance, outpatient therapy, exercise, diet modification, toxic habit …

Massage Therapy For Children, Adolescents, And Young Adults: Clinical Delivery And Effectiveness In Hematology And Oncology, Samuel N. Rodgers-Melnick, Mandy Bartolovich, Neha J. Desai, Smitha Hosahalli Vasanna, Amma Owusu-Ansah, Sanjay P. Ahuja, Jeffery A. Dusek, David W. Miller

Student Scholarship

Background: Children, adolescents, and young adults with hematologic and/or oncologic conditions experience multiple, significant symptoms (e.g., pain, stress, and anxiety), which may be addressed by nonpharmacologic approaches such as massage therapy (MT). The purpose of this study was to describe the clinical delivery of MT provided by a certified pediatric massage therapist and assess effectiveness in two patient groups: those with sickle cell disease (SCD) or hematologic and/or oncologic conditions excluding SCD (HemOnc). Methods: Investigators conducted a retrospective review of MT sessions provided to patients 0–39 years with hematologic and/or oncologic conditions at a large pediatric academic medical center. Results: …

Zone 1 Endovascular Balloon Occlusion Of The Aorta Vs Resuscitative Thoracotomy For Patient Resuscitation After Severe Hemorrhagic Shock, Alexis L Cralley, Navin Vigneshwar, Ernest E Moore, Joseph Dubose, Megan L Brenner, Angela Sauaia, Aast Aorta Study Group

Faculty, Staff and Student Publications

IMPORTANCE: Aortic occlusion (AO) is a lifesaving therapy for the treatment of severe traumatic hemorrhagic shock; however, there remains controversy whether AO should be accomplished via resuscitative thoracotomy (RT) or via endovascular balloon occlusion of the aorta (REBOA) in zone 1.

OBJECTIVE: To compare outcomes of AO via RT vs REBOA zone 1.

DESIGN, SETTING, AND PARTICIPANTS: This was a comparative effectiveness research study using a multicenter registry of postinjury AO from October 2013 to September 2021. AO via REBOA zone 1 (above celiac artery) was compared with RT performed in the emergency department of facilities experienced in both procedures …

Association Of Endovascular Thrombectomy Vs Medical Management With Functional And Safety Outcomes In Patients Treated Beyond 24 Hours Of Last Known Well, Amrou Sarraj, Timothy J Kleinig, Ameer E Hassan, Pere Cardona Portela, Santiago Ortega-Gutierrez, Michael G Abraham, Nathan W Manning, James E Siegler, Nitin Goyal, Laith Maali, Spiros Blackburn, Teddy Y Wu, Jordi Blasco, Arturu Renú, Navdeep S Sangha, Juan F Arenillas, Margy E Mccullough-Hicks, Adam Wallace, Daniel Gibson, Deep K Pujara, Faris Shaker, Mercedes De Lera Alfonso, Marta Olivé-Gadea, Mudassir Farooqui, Juan S Vivanco Suarez, Zachary Iezzi, Jane Khalife, Colleen G Lechtenberg, Syed K Qadri, Rami B Moussa, Mohammad A Abdulrazzak, Tareq S Almaghrabi, Osman Mir, James Beharry, Balaji Krishnaiah, Megan Miller, Najwa Khalil, Gagan J Sharma, Aristeidis H Katsanos, Ali Fadhil, Kelsey R Duncan, Yin Hu, Sheryl B Martin-Schild, Georgios K Tsivgoulis, Dennis Cordato, Anthony Furlan, Leonid Churilov, Peter J Mitchell, Adam S Arthur, Mark W Parsons, James C Grotta, Clark W Sitton, Marc Ribo, Gregory W Albers, Bruce C V Campbell

Faculty, Staff and Student Publications

IMPORTANCE: The role of endovascular thrombectomy is uncertain for patients presenting beyond 24 hours of the time they were last known well.

OBJECTIVE: To evaluate functional and safety outcomes for endovascular thrombectomy (EVT) vs medical management in patients with large-vessel occlusion beyond 24 hours of last known well.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective observational cohort study enrolled patients between July 2012 and December 2021 at 17 centers across the United States, Spain, Australia, and New Zealand. Eligible patients had occlusions in the internal carotid artery or middle cerebral artery (M1 or M2 segment) and were treated with EVT or …

Association Of Endovascular Thrombectomy Vs Medical Management With Functional And Safety Outcomes In Patients Treated Beyond 24 Hours Of Last Known Well, Amrou Sarraj, Timothy J Kleinig, Ameer E Hassan, Pere Cardona Portela, Santiago Ortega-Gutierrez, Michael G Abraham, Nathan W Manning, James E Siegler, Nitin Goyal, Laith Maali, Spiros Blackburn, Teddy Y Wu, Jordi Blasco, Arturu Renú, Navdeep S Sangha, Juan F Arenillas, Margy E Mccullough-Hicks, Adam Wallace, Daniel Gibson, Deep K Pujara, Faris Shaker, Mercedes De Lera Alfonso, Marta Olivé-Gadea, Mudassir Farooqui, Juan S Vivanco Suarez, Zachary Iezzi, Jane Khalife, Colleen G Lechtenberg, Syed K Qadri, Rami B Moussa, Mohammad A Abdulrazzak, Tareq S Almaghrabi, Osman Mir, James Beharry, Balaji Krishnaiah, Megan Miller, Najwa Khalil, Gagan J Sharma, Aristeidis H Katsanos, Ali Fadhil, Kelsey R Duncan, Yin Hu, Sheryl B Martin-Schild, Georgios K Tsivgoulis, Dennis Cordato, Anthony Furlan, Leonid Churilov, Peter J Mitchell, Adam S Arthur, Mark W Parsons, James C Grotta, Clark W Sitton, Marc Ribo, Gregory W Albers, Bruce C V Campbell

Faculty, Staff and Student Publications

IMPORTANCE: The role of endovascular thrombectomy is uncertain for patients presenting beyond 24 hours of the time they were last known well.

OBJECTIVE: To evaluate functional and safety outcomes for endovascular thrombectomy (EVT) vs medical management in patients with large-vessel occlusion beyond 24 hours of last known well.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective observational cohort study enrolled patients between July 2012 and December 2021 at 17 centers across the United States, Spain, Australia, and New Zealand. Eligible patients had occlusions in the internal carotid artery or middle cerebral artery (M1 or M2 segment) and were treated with EVT or …

Hetrombopag Plus Porcine Atg And Cyclosporine For The Treatment Of Aplastic Anaemia: Early Outcomes Of A Prospective Pilot Study, Wenrui Yang, Xin Zhao, Xu Liu, Youzhen Xiong, Huihui Fan, Li Zhang, Jianping Li, Lei Ye, Kang Zhou, Yuan Li, Yang Yang, Guangxin Peng, Liping Jing, Fengkui Zhang

Faculty, Staff and Student Publications

Hetrombopag, a small molecular thrombopoietin-receptor agonist, has shown encouraging efficiency in immunosuppressive therapy refractory or relapsed severe aplastic anaemia. To investigate the response rate of hetrombopag combined with IST as first-line treatment, we designed a prospective pilot study including 32 patients with SAA treated with anti-human T lymphocyte porcine immunoglobulin (p-ATG), cyclosporine, and hetrombopag. In addition, 96 patients with SAA treated with p-ATG and cyclosporine alone were matched as controls. In total, 21.9% of patients treated with hetrombopag achieved complete response (CR) at 3 months, while 5.2% of patients achieved CR in the control group (P = 0.005). At …

Vip152 Is A Selective Cdk9 Inhibitor With Pre-Clinical In Vitro And In Vivo Efficacy In Chronic Lymphocytic Leukemia, Steven Sher, Ethan Whipp, Janek Walker, Pu Zhang, Larry Beaver, Katie Williams, Shelley Orwick, Janani Ravikrishnan, Brandi Walker, Elizabeth Perry, Charles Gregory, Matthew Purcell, Alexander Pan, Pearlly Yan, Lapo Alinari, Amy J Johnson, Melanie M Frigault, Joy M Greer, Ahmed Hamdy, Raquel Izumi, Xiaokui Mo, Deepa Sampath, Jennifer Woyach, James Blachly, John C Byrd, Rosa Lapalombella

Faculty, Staff and Student Publications

Chronic lymphocytic leukemia (CLL) is effectively treated with targeted therapies including Bruton tyrosine kinase inhibitors and BCL2 antagonists. When these become ineffective, treatment options are limited. Positive transcription elongation factor complex (P-TEFb), a heterodimeric protein complex composed of cyclin dependent kinase 9 (CDK9) and cyclin T1, functions to regulate short half-life transcripts by phosphorylation of RNA Polymerase II (POLII). These transcripts are frequently dysregulated in hematologic malignancies; however, therapies targeting inhibition of P-TEFb have not yet achieved approval for cancer treatment. VIP152 kinome profiling revealed CDK9 as the main enzyme inhibited at 100 nM, with over a 10-fold increase in …

Pyridoxamine Treatment Ameliorates Large Artery Stiffening And Cerebral Artery Endothelial Dysfunction In Old Mice, Emily H Reeve, Elise K Kronquist, Julia R Wolf, Byron Lee, Aleena Khurana, Hanson Pham, Abigail E Cullen, Jessica A Peterson, Antonio Meza, R Colton Bramwell, Laura Villasana, Daniel R Machin, Grant D Henson, Ashley E Walker

Faculty, Staff and Student Publications

Age-related increases in large artery stiffness are associated with cerebrovascular dysfunction and cognitive impairment. Pyridoxamine treatment prevents large artery stiffening with advancing age, but the effects of pyridoxamine treatment on the cerebral vasculature or cognition is unknown. The purpose of this study was to investigate the effects of pyridoxamine on blood pressure, large artery stiffness, cerebral artery function, and cognitive function in old mice. Old male C57BL/6 mice consumed either pyridoxamine (2 g/L) or vehicle control in drinking water for ∼7.5 months and were compared with young male C57BL/6 mice. From pre- to post-treatment, systolic blood pressure increased in old …

Frequency Of Von Willebrand Disease And Its Types: Data From A Tertiary Care Hospital Of Karachi, Pakistan, Jyoti Mohan Lal, Anila Rashid, Natasha Ali

Department of Pathology and Laboratory Medicine

Introduction: von Willebrand disease is the most common inherited bleeding disorder. It is classified into 3 main types, type I and III are quantitative defects whereas type II is qualitative defect which is further sub-classified in to II-A, II-B, II-M, II-N. The aim of the present study is to see frequency and types of von Willebrand disease in a tertiary care hospital of Karachi, Pakistan.
Materials and methods: This retrospective cross-sectional study was conducted in the section of Hematology and Transfusion Medicine, Department of Pathology and Laboratory Medicine, the Aga Khan University hospital, Karachi, from May 2020 to April 2021 …