Hematology Commons^™

G-Csf And Gm-Csf Are Different. Which One Is Better For Covid-19?, Hillard M. Lazarus

Faculty Scholarship

No abstract provided.

Red Blood Cell Adhesion To Icam-1 Is Mediated By Fibrinogen And Is Associated With Right-To-Left Shunts In Sickle Cell Disease, Erdem Kucukal, Yuncheng Man, Erina Quinn, Neil Tewari, Ran An, Jane A. Little, Umut A. Gurkan

Faculty Scholarship

Sickle cell disease (SCD), which afflicts 100 000 Americans, as well as millions worldwide, is associated with anemia, lifelong morbidity, and early mortality. Abnormal adhesion of sickle red blood cells (RBCs) to activated vascular endothelium may contribute acutely to the initiation of painful vaso-occlusive crises and chronically to endothelial damage in SCD. Sickle RBCs adhere to activated endothelium through several adhesion mechanisms. In this study, using whole blood from 17 people with heterozygous SCD (HbS variant) and 55 people with homozygous SCD (HbSS) analyzed in an in vitro microfluidic assay, we present evidence for the adhesion of sickle RBCs to …

Menopause In Brazilian Women With Sickle Cell Anemia With And Without Hydroxyurea Therapy., Ana Mach Queiroz, Clarisse Lopes De Castro Lobo, Samir K. Ballas

Cardeza Foundation for Hematologic Research

Women with sickle cell anemia (SCA) require special attention for myriad obstetric and gynecologic issues associated with this complex hematologic disorder. These affect all aspects of female life from menarche through menopause. Information regarding obstetric and gynecologic complications of sickle cell disease (SCD), with a few exceptions, is based primarily on observational, anecdotal, retrospective, or cohort studies that may not reflect current aspects of obstetric care.¹ Similarly, there are no recent reports about menopause (also known as climacteric) in women with SCA. The fact that life expectancy of women with SCA was determined to be 46–48 years² delayed …

Guided Imagery And Deep Breathing: Minimizing Anxiety Experienced By Pediatric Cancer Patients, Bethany Grace Aney

Graduate Theses/Dissertations

This particular research study examined the impact of guided imagery and deep breathing as coping tools to reduce the anxiety levels experienced by pediatric cancer patients ages 6-12 years of age at a children’s hospital in Central Pennsylvania. This quantitative study utilized a pretest-posttest design, in addition to utilizing the State-Trait Anxiety Inventory for Children (STAIC™) as the baseline and post-test assessment. The STAIC™ is a questionnaire tool that assesses individuals’ state and trait anxiety through a total of 40 questions. This particular study had a total of five patients, two male and three female that consented to undergoing three …

The Roles Of Grks In Hemostasis And Thrombosis, Xi Chen, Xuefei Zhao, Matthew Cooper, Peisong Ma

Department of Medicine Faculty Papers

Along with cancer, cardiovascular and cerebrovascular diseases remain by far the most common causes of death. Heart attacks and strokes are diseases in which platelets play a role, through activation on ruptured plaques and subsequent thrombus formation. Most platelet agonists activate platelets via G protein-coupled receptors (GPCRs), which make these receptors ideal targets for many antiplatelet drugs. However, little is known about the mechanisms that provide feedback regulation on GPCRs to limit platelet activation. Emerging evidence from our group and others strongly suggests that GPCR kinases (GRKs) are critical negative regulators during platelet activation and thrombus formation. In this review, …

The Spectrum And Severity Of Bleeding In Adolescents With Low Von Willebrand Factor-Associated Heavy Menstrual Bleeding., Lakshmi Srivaths, Charles G. Minard, Sarah H. O'Brien, Allison P Wheeler, Eric Mullins, Mukta Sharma, Robert Sidonio, Shilpa Jain, Ayesha Zia, Margaret V. Ragni, Roshni Kulkarni, Jennifer E. Dietrich, Peter A. Kouides

Manuscripts, Articles, Book Chapters and Other Papers

Low von Willebrand factor (VWF) in adults is associated with significant bleeding, most notably heavy menstrual bleeding (HMB) and postpartum hemorrhage, although this has not been characterized in adolescents. The objectives of this analysis of a multicenter single arm observational cohort study in adolescents with low VWF-associated HMB were to describe the bleeding phenotype, HMB severity, and related complications. Eligibility criteria included postmenarchal females(Pictorial Blood Assessment Chart [PBAC] score >100) and low VWF (2 values of VWF activity ≥30 and ≤50 IU/dL). Patients diagnosed with other bleeding disorders were ineligible. Clinical phenotype data, including PBAC and Bleeding Assessment Tool (BAT) …

Whole Blood Viscosity And Red Blood Cell Adhesion: Potential Biomarkers For Targeted And Curative Therapies In Sickle Cell Disease, Erdem Kucukal, Yuncheng Man, Ailis Hill, Shichen Liu, Allison Bode, Ran An, Jaikrishnan Kadambi, Jane A. Little, Umut A. Gurkan

Faculty Scholarship

Sickle cell disease (SCD) is a recessive genetic blood disorder exhibiting abnormal blood rheology. Polymerization of sickle hemoglobin, due to a point mutation in the β-globin gene of hemoglobin, results in aberrantly adhesive and stiff red blood cells (RBCs). Hemolysis, abnormal RBC adhesion, and abnormal blood rheology together impair endothelial health in people with SCD, which leads to cumulative systemic complications. Here, we describe a microfluidic assay combined with a micro particle image velocimetry technique for the integrated in vitro assessment of whole blood viscosity (WBV) and RBC adhesion. We examined WBV and RBC adhesion to laminin (LN) in microscale …

Convalescent Plasma In Covid-19, Ranjit S. Banwait, Joshua K. Salabei, Troy J. Fishman, Uma G. Iyer

HCA Healthcare Journal of Medicine

The recent pandemic of SARS-CoV-2, which causes novel coronavirus disease 2019 (Covid-19), has had devastating impact on a global and national scale. In order to overcome this outbreak it is imperative we find treatments that are safe and effective. To date, no definitive treatment is available that can curtail the spread of this viral syndrome. Convalescent plasma (CP) is one such option that has repeatedly served as an important tool in treatment of various bacterial and viral infections, especially in the setting of no specific antimicrobial or vaccination against an infectious disease. Herein, we review the history of CP, prior …

Bayesian Modelling Of High-Throughput Sequencing Assays With Malacoda., Andrew R Ghazi, Xianguo Kong, Ed S Chen, Leonard C Edelstein, Chad A Shaw

Cardeza Foundation for Hematologic Research

NGS studies have uncovered an ever-growing catalog of human variation while leaving an enormous gap between observed variation and experimental characterization of variant function. High-throughput screens powered by NGS have greatly increased the rate of variant functionalization, but the development of comprehensive statistical methods to analyze screen data has lagged. In the massively parallel reporter assay (MPRA), short barcodes are counted by sequencing DNA libraries transfected into cells and the cell's output RNA in order to simultaneously measure the shifts in transcription induced by thousands of genetic variants. These counts present many statistical challenges, including overdispersion, depth dependence, and uncertain …

Right Arm Pain, Color Change And Swelling In A 17-Year-Old Male Baseball Pitcher, Alvin Chi

Research Days

No abstract provided.

Safety And Activity Of Varlilumab, A Novel And First-In-Class Agonist Anti-Cd27 Antibody, For Hematologic Malignancies., Stephen M Ansell, Ian Flinn, Matthew H Taylor, Branimir I Sikic, Joshua Brody, John Nemunaitis, Andrew Feldman, Thomas R Hawthorne, Tracey Rawls, Tibor Keler, Michael J Yellin

Articles, Abstracts, and Reports

CD27, a costimulatory molecule on T cells, induces intracellular signals mediating cellular activation, proliferation, effector function, and cell survival on binding to its ligand, CD70. Varlilumab, a novel, first-in-class, agonist immunoglobulin G1 anti-CD27 antibody, mediates antitumor immunity and direct killing of CD27+ tumor cells in animal models. This first-in-human, dose-escalation, and expansion study evaluated varlilumab in patients with hematologic malignancies. Primary objectives were to assess safety and the maximum tolerated and optimal biologic doses of varlilumab. Secondary objectives were to evaluate pharmacokinetics, pharmacodynamics, immunogenicity, and antitumor activity. In a 3 + 3 dose-escalation design, 30 patients with B-cell (n = …

Integrating Geriatric Assessment And Genetic Profiling To Personalize Therapy Selection In Older Adults With Acute Myeloid, Vijaya R. Bhatt

Theses & Dissertations

Integrating geriatric assessment for patient profiling and genetic profiling of leukemic cells represents an innovative approach to personalize therapy selection in older adults with acute myeloid leukemia (AML). We report results of a pre-planned interim analysis of a pragmatic phase II trial that utilized this strategy to personalize therapy. Patients ≥60 years with a new diagnosis of AML underwent geriatric assessment prior to initiation of treatment. Geriatric assessment of physical function, cognitive function and comorbidity burden were used to determine fitness for chemotherapy. Patients with good or intermediate-risk AML received intensive chemotherapy such as anthracycline and cytarabine (7+3) if determined …

Equivalency Testing For Two Formulations Of A Clinical Laboratory Control Material, Jessica M. Hart

Capstone Experience: Master of Public Health

Clinical laboratory control materials are an integral part of legally-mandated and highly regulated quality control protocols in all clinical laboratories. These controls ensure accurate performance of the laboratory testing and instrumentation used to produce medical test results for millions of patients. It is of clinical and public health interest to ensure the diagnostic test results which affect so many people are regulated by the most accurate and precise controls.

Formulation changes in control materials have the potential to impact laboratory quality control. In this study, data from two formulations of a hematology control were compared to assess equivalency of the …

Cytopenia Among Cml Patients On Imatinib In Kenya: Types, Grades, And Time Course, Angela Mcligeyo, Jamilla Rajab, Mohammed Ezzi, Peter Oyiro, Yatich Bett, Andrew Odhiambo, Matilda Ong’Ondi, Sitna Mwanzi, Mercy Gatua, Naothieno Abinya

Internal Medicine, East Africa

Background: Imatinib mesylate is the gold standard for the treatment of all phases of Philadelphia-positive chronic myeloid leukemia. Patients on imatinib treatment may develop cytopenia due to drug toxicity. This study aimed to determine the types, grades, and time course of cytopenia in CML patients on imatinib at a Nairobi hospital.

Methods: This was a cross-sectional descriptive study of adult patients aged ≥18 years followed up at the Glivec International Patient Access Program (GIPAP) clinic from 2007 to 2015. Patients who developed cytopenia within 12 months of initiating imatinib were eligible. Clinical and hematologic data were retrieved from the patients’ …

Cortisol As An Acute Stress Biomarker In Young Hematopoietic Cell Transplant Patients/Caregivers: Active Music Engagement Protocol., Kristen A. Russ, Steven J. Holochwost, Susan M. Perkins, Kristin Stegenga, Seethal A. Jacob, David Delgado, Amanda K. Henley, Joan E. Haase, Sheri L. Robb

Manuscripts, Articles, Book Chapters and Other Papers

Objective: Primary aims of the proposed protocol are to determine the feasibility/acceptability of the active music engagement intervention protocol during hematopoietic stem cell transplantation (HSCT) and clinical feasibility/acceptability of the biological sample collection schedule.

Design: The authors propose a single-case, alternating treatment design to compare levels of child and caregiver cortisol in blood and saliva collected on alternating days, when the dyad receives and does not receive AME sessions. Included are the scientific rationale for this design and detailed intervention and sample collection schedules based on transplant type.

Setting/Location: Pediatric inpatient HSCT unit.

Subjects: Eligible participants are dyads of children …

Preclinical Studies Of A Novel Idh1 Inhibitor In Acute Myeloid Leukemia (Aml), Vivian Salama

Dissertations and Theses (Open Access)

LY3410738, a novel covalent Isocitrate Dehydrogenase 1 (IDH1) inhibitor in Acute Myeloid Leukemia, it is more effective than Ivosidenib (AG120) and has a potent anti-leukemic effect against IDH1 mutant acute myeloid leukemia in combination with Venetoclax (ABT-199).

Acute myeloid Leukemia (AML) is an aggressive neoplastic blood disorder characterized by proliferation of poorly differentiated cells of myeloid lineage. IDH1 is a cytoplasmic enzyme that catalyze the oxidative decarboxylation of isocitrate to α-ketoglutarate (α-KG) in the citric acid cycle. Somatic gain-of-function mutations in IDH1 occur in ~10% of the newly diagnosed AML patients. The neo-enzymatic activity of mutant IDH1 results in accumulation …

Assessing Patient Attitudes To Ward Genetic Testing For Hereditary Hematologic Malignancy, Addison Johnson

Dissertations and Theses (Open Access)

Since 2003, more than 15 genes have been identified to predispose to hereditary hematologic malignancy (HHM). Although the diagnostic yield of germline analysis for leukemia is similar to solid tumors, referral for genetic evaluation in adults with leukemia is underperformed. Identifying HHM is important for prognostication, treatment, and donor selection for hematopoietic stem cell transplant. No studies have examined leukemia patients’ attitudes toward genetic testing for HHM. This study aimed to assess leukemia patients’ attitudes toward genetic testing and elicit current perceived distress due to a leukemia diagnosis. Data were elicited through an electronic survey sent to 5,513 patients diagnosed …

A Phase 1/2 Study Of The Oral Flt3 Inhibitor Pexidartinib In Relapsed/Refractory Flt3-Itd-Mutant Acute Myeloid Leukemia., Catherine C Smith, Mark J Levis, Olga Frankfurt, John M Pagel, Gail J Roboz, Richard M Stone, Eunice S Wang, Paul L Severson, Brian L West, Mai H Le, Sabine Kayser, Bao Lam, Henry H Hsu, Chao Zhang, Gideon Bollag, Alexander E Perl

Articles, Abstracts, and Reports

FMS-like tyrosine kinase 3 (FLT3) tyrosine kinase inhibitors (TKIs) have activity in acute myeloid leukemia (AML) patients with FLT3 internal tandem duplication (ITD) mutations, but efficacy is limited by resistance-conferring kinase domain mutations. This phase 1/2 study evaluated the safety, tolerability, and efficacy of the oral FLT3 inhibitor PLX3397 (pexidartinib), which has activity against the FLT3 TKI-resistant F691L gatekeeper mutation in relapsed/refractory FLT3-ITD-mutant AML. Ninety patients were treated: 34 in dose escalation (part 1) and 56 in dose expansion (part 2). Doses of 800 to 5000 mg per day in divided doses were tested. No maximally tolerated dose was reached. …

Iron Deficiency Anemia: An Unexpected Cause Of An Acute Occipital Lobe Stroke In An Otherwise Healthy Young Woman, Qian Zhang, Khine S. Shan, Conor O'Sullivan, Travis C. Nace

Abington Jefferson Health Papers

A 29-year-old caucasian woman who presented to the hospital with an acute onset of right eye visual disturbance and headache was found to have an acute left occipital lobe infarction. Past medical history was significant for iron deficiency anemia (IDA) secondary to menorrhagia. Her initial hemoglobin level was 7.8 G/DL, and her symptoms improved after iron and blood transfusions. Hypercoagulable studies were completed in the outpatient setting, and the results were unremarkable. Her acute stroke was most likely related to IDA as she had low cardiovascular risk factors along with a negative complete stroke workup.

A Validated Composite Organ And Hematologic Response Model For Early Assessment Of Treatment Outcomes In Light Chain Amyloidosis, Surbhi Sidana, Paolo Milani, Moritz Binder, Marco Basset, Nidhi Tandon, Andrea Foli, Angela Dispenzieri, Morie A Gertz, Suzanne R Hayman, Francis K Buadi, Martha Q Lacy, Prashant Kapoor, Nelson Leung, S Vincent Rajkumar, Giampaolo Merlini, Giovanni Palladini, Shaji K Kumar

Faculty, Staff and Student Publications

Newly diagnosed AL amyloidosis patients were evaluated to develop a model for early assessment of treatment benefit at 6 months, integrating both hematologic (HR) and organ response (OR) assessment (testing cohort, Mayo: n = 473; validation cohort, Pavia: n = 575). Multiple OR were assessed as follows: All OR (AOR): response in all organs, mixed OR (MOR): response in some organs, no OR (NOR)]. AOR rates at 6 months improved with deepening HR; complete response (CR; 38%, 35%), very good partial response (VGPR; 30%, 26%), and partial response (PR; 16%, 21%), respectively. A composite HR/OR (CHOR) model was developed using …