Hematology Commons^™

Targeting T Cell Metabolism To Ameliorate Graft-Versus-Host Disease, Karin Zikra

Honors Undergraduate Theses

Hematopoietic stem cell transplantation (HSCT) is an important form of therapy for hematological genetic disorders and malignancies, particularly hematological cancers. However, common usage of this procedure is obstructed by graft-versus-host disease (GvHD), in which transplanted donor T cells wage an attack on recipient antigens, causing severe tissue damage and mortality. GvHD prognosis remains poor, and current treatment methods continue to be insufficient, especially for patients with more advanced and severe GvHD. T cells have been identified as the fundamental force behind GvHD, and their cellular metabolism is deemed vital to their fate and function, especially in pathogenic environments. A hallmark …

Covid-19 Vaccine-Associated Thrombosis With Thrombocytopenia Syndrome (Tts): A Systematic Review And Post Hoc Analysis, Muhammad Usman Hafeez, Maha Ikram, Zunaira Shafiq, Azza Sarfraz, Zouina Sarfraz, Vikash Jaiswal, Muzna Sarfraz, Ivan Chérrez-Ojeda

Department of Paediatrics and Child Health

Background: A new clinical syndrome has been recognized following the COVID-19 vaccine, termed thrombosis with thrombocytopenia syndrome (TTS). The following systematic review focuses on extrapolating thrombotic risk factors, clinical manifestations, and outcomes of patients diagnosed with TTS following the COVID-19 vaccine.
Methods: We utilized the World Health Organization's criteria for a confirmed and probable case of TTS following COVID-19 vaccination and conducted a systematic review and posthoc analysis using the PRISMA 2020 statement. Data analysis was conducted using SPSS V25 for factors associated with mortality, including age, gender, anti-PF4/heparin antibodies, platelet nadir, D-dimer peak, time to event diagnosis, arterial or …

How Glucagon Impacts Type 1 Diabetes And Vice Versa, Sheri Colberg

Human Movement Studies & Special Education Faculty Publications

No abstract provided.

Effect Of He Plasma Jet Versus Surface Plasma On The Metabolites Of Acute Myeloid Leukemia Cells, Dehui Xu, Ning Ning, Yujing Xu, Wenjie Xia, Hai-Lan Chen, Michael G. Kong

Bioelectrics Publications

Cold atmospheric plasma, including plasma jet and surface plasma, can promote the apoptosis of cancer cells without causing significant damage to surrounding normal cells, which was hopeful to be applied to the clinical cancer therapy. However, experimental plasma devices used directly to clinical experiments has challenges in technology and methods, especially the difference in killing tumor cells efficiency of these two common plasma sources. Therefore, it is great necessity to explore the differences in treating tumors between different plasma sources. This paper achieved good killing efficiency by using two kinds of cold atmospheric plasma generating devices, namely plasma jet and …

Concomitant Essential Thrombocythemia And Mature B -Lymphoproliferative Disorder In A Patient, Ayesha Butt, Ruhul Quddus, Natasha Bahadur Ali

Section of Haematology/Oncology

A-64-year old male presented with cough, weight loss, and maculopapular rash for 15-20 days. On examination, he was found to have cervical lymphadenopathy and splenomegaly. His leukocyte count was 62.1x109/L, platelets were 1169x109/L and LDH was 816 IU/L. Peripheral blood film showed a leukoerythroblastic picture with thrombocytosis. He was started on hydroxyurea and allopurinol. Subsequently, bone marrow evaluation was done which depicted increased lymphoid cells with an M:E ratio of 4:1. Cellular areas exhibited an increase in myeloid precursors along with prominent lymphoid cells and abundant megakaryocytes. Immunohistochemistry showed an increase in B-lymphocytes. Grade MF-2 reticulin fibrosis was noted. Overall …

Tisagenlecleucel Infusion In Patients With Relapsed/Refractory All And Concurrent Serious Infection., Erin Hall, Dwight E. Yin, Rakesh K. Goyal, Atif Ahmed, Grace S. Mitchell, Shawn D. St Peter, Terrie Flatt, Ibrahim A. Ahmed, Weijie Li, Richard J. Hendrickson, Keith August, Douglas Myers

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Tisagenlecleucel, an anti-CD19 chimeric antigen receptor T (CAR-T) cell therapy, has demonstrated durable efficacy and a manageable safety profile in pediatric and young adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) in the ELIANA pivotal trial and real-world experience. Experience from investigator-led studies prior to ELIANA suggests that infections and inflammatory conditions may exacerbate the severity of cytokine release syndrome (CRS) associated with CAR-T cell therapy, leading to extreme caution and strong restrictions for on-study and commercial infusion of tisagenlecleucel in patients with active infection. CRS intervention with interleukin (IL)-6 blockade and/or steroid therapy was introduced late in …

Small-Molecule Inhibitor Of Af9/Enl-Dot1l/Af4/Aff4 Interactions Suppresses Malignant Gene Expression And Tumor Grow, Fangrui Wu, Shenyou Nie, Yuan Yao, Tong Huo, Xin Li, Xiaowei Wu, Jidong Zhao, Yi-Lun Lin, Yinjie Zhang, Qianxing Mo, Yongcheng Song

Faculty, Staff and Students Publications

Chromosome translocations involving mixed lineage leukemia (MLL) gene cause acute leukemia with a poor prognosis. MLL is frequently fused with transcription cofactors AF4 (~35%), AF9 (25%) or its paralog ENL (10%). The AHD domain of AF9/ENL binds to AF4, its paralog AFF4, or histone-H3 lysine-79 (H3K79) methyltransferase DOT1L. Formation of AF9/ENL/AF4/AFF4-containing super elongation complexes (SEC) and the catalytic activity of DOT1L are essential for MLL-rearranged leukemia. Protein-protein interactions (PPI) between AF9/ENL and DOT1L/AF4/AFF4 are therefore a potential drug target.

Methods: Compound screening followed by medicinal chemistry was used to find inhibitors of such PPIs, which were examined for their biological …

Correlation Between Concentrations Of Four Heavy Metals In Cord Blood And Childhood Blood Of Jamaican Children, Mohammad H Rahbar, Maureen Samms-Vaughan, Manouchehr Hessabi, Jan Bressler, Shezeen Gillani, Megan L Grove, Sydonnie Shakspeare-Pellington, Katherine A Loveland

Faculty, Staff and Student Publications

This study investigated whether the concentrations of four metals [lead (Pb), mercury (Hg), manganese (Mn), and aluminum (Al)] are correlated in cord blood and childhood blood samples from Jamaican children. Cord blood samples were obtained from 21 pregnant women enrolled in the second Jamaican Birth Cohort Study from July 1, 2011 to September 30, 2011, and blood samples were drawn from their children who participated in a follow up study when the children were 4–8 years old. Correlations were assessed by the Pearson or the Spearman’s rank correlation coefficient. The mean ages of children at the childhood visit and their …

A Case Series Of Blastic Plasmacytoid Dendritic Cell Neoplasia, Valentina Giudice

Translational Medicine @ UniSa

lastic plasmacytoid dendritic cell neoplasm (BPDCN), an extremely rare and aggressive tumor, derives from plasmacytoid dendritic cell precursors and is characterized by CD4 and CD56 positivity accompanied by the expression of isolated myeloid, B- or T-cell lineage markers. Despite the recent introduction of specific targeted therapies, prognosis is still poor with a median overall survival of one year, and allogeneic bone marrow transplantation remains the only curative treatment in eligible patients. In this series, we described two cases of adult BPDCN treated with high dose cytarabine and methotrexate and autologous hematopoietic stem cell transplantation, or fludarabine, cytarabine, and idarubicin achieving …

Immature Platelet Dynamics In Immune-Mediated Thrombocytopenic States, Hollie M. Reeves, Robert W. Maitta

Faculty Scholarship

A major challenge encountered by clinicians is differentiating presentations characterized by significant thrombocytopenia due to overlapping clinical symptoms and signs in the setting of ambiguous laboratory results. Immature platelets represent the youngest platelets that can be measured in peripheral blood by current hematology analyzers. These young platelets are larger, with higher RNA content recently released from the bone marrow. Thrombocytopenic presentations caused directly or indirectly by immune responses can lead to compensatory bone marrow responses seeking to normalize the platelet count; thus obtaining absolute immature platelet counts may be informative while triaging patients. Over the last decade, their use has …

Does Breast Cancer Subtype Impact Margin Status In Patients Undergoing Partial Mastectomy?, Andrew Fenton, Elisabeth Dupont, Theodore Tsangaris, Carlos Garcia-Cantu, Marissa Howard-Mcnatt, Akiko Chiba, Adam Berger, Edward Levine, Jennifer Gass, Kristalyn Gallagher, Sharon Lum, Ricardo Martinez, Alliric Willis, Sonali Pandya, Eric A. Brown, Amanda Mendiola, Naveenraj Solomon, Maheswari Senthil, David Ollila, David Edmonson, Melissa Lazar, Jukes Namm, Fangyong Li, Meghan Butler, Noreen Mcgowan, Maria Herrera, Yoana Avitan, Brian Yoder, Laura L. Walters, Tara Mcpartland, Victor Haddad, Hongwei Ma, Ming Xie, Anees Chagpar

Conference Presentation Abstracts

BACKGROUND: Molecular subtype in invasive breast cancer guides systemic therapy. It is unknown whether molecular subtype should also be considered to tailor surgical therapy. The present investigation was designed to evaluate whether breast cancer subtype impacted surgical margins in patients with invasive breast cancer stage I through III undergoing breast-conserving therapy.

METHODS: Data from 2 randomized trials evaluating cavity shave margins (CSM) on margin status in patients undergoing partial mastectomy (PM) were used for this analysis. Patients were included if invasive carcinoma was present in the PM specimen and data for all 3 receptors (ER, PR, and HER2) were known. …

International Evidence-Based Consensus Diagnostic And Treatment Guidelines For Unicentric Castleman Disease., Frits Van Rhee, Eric Oksenhendler, Gordan Srkalovic, Peter Voorhees, Megan Lim, Angela Dispenzieri, Makoto Ide, Sophia Parente, Stephen Schey, Matthew Streetly, Raymond Wong, David Wu, Ivan Maillard, Joshua Brandstadter, Nikhil Munshi, Wilbur Bowne, Kojo S Elenitoba-Johnson, Alexander Fössa, Mary Jo Lechowicz, Shanmuganathan Chandrakasan, Sheila K Pierson, Amy Greenway, Sunita Nasta, Kazuyuki Yoshizaki, Razelle Kurzrock, Thomas S Uldrick, Corey Casper, Amy Chadburn, David C Fajgenbaum

Department of Surgery Faculty Papers

Castleman disease (CD) includes a group of rare and heterogeneous disorders with characteristic lymph node histopathological abnormalities. CD can occur in a single lymph node station, which is referred to as unicentric CD (UCD). CD can also involve multicentric lymphadenopathy and inflammatory symptoms (multicentric CD [MCD]). MCD includes human herpesvirus-8 (HHV-8)-associated MCD, POEMS-associated MCD, and HHV-8-/idiopathic MCD (iMCD). The first-ever diagnostic and treatment guidelines were recently developed for iMCD by an international expert consortium convened by the Castleman Disease Collaborative Network (CDCN). The focus of this report is to establish similar guidelines for the management of UCD. To this purpose, …

Case Series And Review Of Hematological And Non-Hematological Malignancies In Aging Patients With Sickle Cell Disease In The Hydroxyurea Era., Sanaa Rizk, David J. Axelrod, Rasaq Olaosebikan, Samir K. Ballas

Cardeza Foundation for Hematologic Research

Survival of adult patients with sickle cell disease has increased progressively since the 1970s. Aging patients with sickle cell disease are at risk of developing comorbidities that are not due to sickle cell disease itself, including malignancies. Many studies tried to assess the incidence of malignancy in patients with sickle cell disease. However, no studies have been done to evaluate cancer incidences in aging sickle cell patients, especially in the hydroxyurea (HU) era. In this review, we assessed the prevalence of malignancies in aging patients with sickle cell disease at our institution with or without HU therapy. Retrospective analysis of …

Pre-Transplant Marital Status And Hematopoietic Cell Transplantation Outcomes., J Tay, S Beattie, C Bredeson, R Brazauskas, N He, Ibrahim A. Ahmed, M Aljurf, M Askar, Y Atsuta, S Badawy, A Barata, A M Beitinjaneh, N S Bhatt, D Buchbinder, J Cerny, S Ciurea, A D'Souza, J Dalal, N Farhadfar, C O Freytes, S Ganguly, U Gergis, S Gerull, H M Lazarus, T Hahn, S Hong, Y Inamoto, N Khera, T Kindwall-Keller, R T Kamble, J M Knight, Y N Koleva, A Kumar, J Kwok, H S Murthy, R F Olsson, M Angel Diaz-Perez, D Rizzieri, S Seo, S Chhabra, H Schoemans, H C Schouten, A Steinberg, K M Sullivan, J Szer, D Szwajcer, M L Ulrickson, L F Verdonck, B Wirk, W A Wood, J A Yared, W Saber

Manuscripts, Articles, Book Chapters and Other Papers

Background: Evidence about the impact of marital status before hematopoietic cell transplantation (hct) on outcomes after hct is conflicting.

Methods: We identified patients 40 years of age and older within the Center for International Blood and Marrow Transplant Research registry who underwent hct between January 2008 and December 2015. Marital status before hct was declared as one of: married or living with a partner, single (never married), separated or divorced, and widowed. We performed a multivariable analysis to determine the association of marital status with outcomes after hct.

Results: We identified 10,226 allogeneic and 5714 autologous hct cases with, respectively, …

Acute Ischemic Stroke As The Presenting Feature Of Covid-19 In The Young And Pregnant, Nermila A. Ballmick, Jiri F. Kubac, Hossein Akhondi

HCA Healthcare Journal of Medicine

Introduction: Coronavirus disease (COVID-19) is an emerging and rapidly evolving public health issue that has become globally widespread and an overwhelming pandemic. Clinical manifestations of the disease include asymptomatic carrier states, acute respiratory distress syndrome, and even multiorgan dysfunction. Here, we present a unique and rare case of an acute ischemic stroke (AIS) in an asymptomatic pregnant woman with no predisposing medical illnesses.

Discussion: An 18-year-old G2P1 African American woman at 7 weeks gestational age with no significant medical or family history presenting to the Emergency Department during the initial phases of the pandemic with complaints of new onset left …

Is G-Csf Dangerous In Covid-19: Why Not Use Gm-Csf?, Hillard M. Lazarus

Faculty Scholarship

No abstract provided.

Active Music Engagement And Cortisol As An Acute Stress Biomarker In Young Hematopoietic Stem Cell Transplant Patients And Caregivers: Results Of A Single Case Design Pilot Study., Steven J. Holochwost, Sheri L. Robb, Amanda K. Henley, Kristin Stegenga, Susan M. Perkins, Kristen A. Russ, Seethal A. Jacob, David Delgado, Joan E. Haase, Caitlin M. Krater

Manuscripts, Articles, Book Chapters and Other Papers

This paper reports the results of a single case design pilot study of a music therapy intervention [the Active Music Engagement (AME)] for young children (age 3.51 to 4.53 years) undergoing hematopoietic stem cell transplantation (HCST) and their caregivers. The primary aims of the study were to determine feasibility/acceptability of the AME intervention protocol and data collection in the context of HCST. Secondary aims were to examine caregivers' perceptions of the benefit of AME and whether there were changes in child and caregiver cortisol levels relative to the AME intervention. Results indicated that the AME could be implemented in this …

Stroke Preventive In African American Women Ages 20-40 That Are Using Or Have Used Oral Contraceptives, Ashanti L. N. Coleman

Electronic Theses and Dissertations

This Doctor of Nursing Practice project will inform the audience of stroke awareness as it pertains to oral contraceptives. The study’s focus was to enhance the knowledge of African American women ages 20–40 that have used or are currently using an oral contraceptive. It has been identified that this patient population lacked the knowledge regarding stroke and oral contraceptives, and African American women continue to have the highest incidence of stroke. African American women also make up more than half of the consumers utilizing oral contraceptives. An oral contraceptive knowledge questionnaire was utilized from previous research to determine if any …

Karachi Cancer Registry (Kcr): Age-Standardized Incidence Rate By Age-Group And Gender In A Mega City Of Pakistan, Shahid Pervez, Adnan Jabbar, Ghulam Haider, Shamvil Ashraf, Muhammad Asif Qureshi, Fouzia Lateef, Imtiaz Bashir, Manzoor Zaidi, Mohammad Khurshid, Mohammad Saeed Quraishy

Department of Pathology and Laboratory Medicine

Objectives: To estimate the cancer incidence by age group and gender for the population of Karachi Division by analyzing the Karachi Cancer Registry data of 2017-19.
Settings: The population of Karachi division is 16.1 million according to national census 2017. 'Karachi Cancer Registry' which is a part of 'National Cancer Registry' is collecting data from eight major hospitals in Karachi since 2017. For outcome measures, cancer counts and the age standardized incidence rates (ASIR) per 100,000 population were computed for age groups (0-14, 15-19 and ≥20 years), in both genders and all cancer site/type.
Methods: The population denominators were based …

Childhood Medulloblastoma, Naureen Mushtaq, Shahzadi Resham, Muhammad Shahzad Shamim, Bilal Mazhar Qureshi, Quratulain Riaz, Eric Bouffet

Section of Haematology/Oncology

Medulloblastoma is the most common malignant brain tumour in children and is a major cause of mortality and morbidity, particularly in low- and middle-income countries. It has been risk-stratified on the basis of clinical (age, metastasis and extent of resection) and histological subtypes (classic, desmoplastic and anaplastic). However, recently medulloblastoma has been sub-grouped by using a variety of different genomic approaches, such as gene expression profiling, micro-ribonucleic acid profiling and methylation array into 4 groups, namely Wingless, Sonic hedgehog, Group 3 and Group 4. This new sub-grouping has important therapeutic and prognostic implications. After acute leukaemia, brain tumour is the …