Hematology Commons^™

Survival Benefit For Individuals With Constitutional Mismatch Repair Deficiency Undergoing Surveillance, Carol Durno, Ayse Bahar Ercan, Vanessa Bianchi, Melissa Edwards, Melyssa Aronson, Melissa Galati, Eshetu G. Atenafu, Gadi Abebe-Campino, Abeer Al-Battashi, Naureen Mushtaq

Section of Haematology/Oncology

Purpose: Constitutional mismatch repair deficiency syndrome (CMMRD) is a lethal cancer predisposition syndrome characterized by early-onset synchronous and metachronous multiorgan tumors. We designed a surveillance protocol for early tumor detection in these individuals.
Patients and methods: Data were collected from patients with confirmed CMMRD who were registered in the International Replication Repair Deficiency Consortium. Tumor spectrum, efficacy of the surveillance protocol, and malignant transformation of low-grade lesions were examined for the entire cohort. Survival outcomes were analyzed for patients followed prospectively from the time of surveillance implementation.
Results: A total of 193 malignant tumors in 110 patients were identified. Median …

Prospective Patient-Reported Symptom Profiles Associated With Pediatric Acute Lymphoblastic Leukemia Relapse, Austin L Brown, Kimberly P Raghubar, Olga A Taylor, Melanie Brooke Bernhardt, Lisa S Kahalley, Wei Pan, Philip J Lupo, Marilyn J Hockenberry, Michael E Scheurer

Faculty, Staff and Students Publications

PURPOSE: Despite improvements in frontline pediatric acute lymphoblastic leukemia (ALL) treatment, relapse remains a concern. Research in adult cancer patients suggests that patient-reported symptoms may predict survival, but the relationship between symptoms and relapse for pediatric ALL has received little attention.

METHODS: Pediatric patients with ALL (age 2-18 years) and/or their primary caregivers completed symptom surveys at the end of induction, start of delayed intensification (DI), start of maintenance cycle 1 (MC1), and start of maintenance cycle 2 (MC2). Symptom clusters for co-occurring fatigue, pain, sleep disruptions, and nausea were defined using latent profile analysis. Hazard ratios (HR) and 95% …

18f-Fluorothymidine Pet Is An Early And Superior Predictor Of Progression-Free Survival Following Chemoimmunotherapy Of Diffuse Large B Cell Lymphoma: A Multicenter Study, Ryogo Minamimoto, Luis Fayad, Julie M. Vose, Jane L. Meza, Ranjana Advani, Jordan Hankins, Felix Mottaghy, Homer Macapinlac, Alexander Heinzel, Malik E. Juweid, Andrew Quon

Journal Articles: Oncology and Hematology

PURPOSE: To determine whether interim 3'-deoxy-3'-[

METHODS: Ninety-two prospectively enrolled patients with DLBCL underwent both FLT-PET/CT and FDG-PET/CT 18-24 days after two cycles of R-CHOP/R-EPOCH. Deauville-criteria, PERCIST1.0, standardized uptake value (SUV), total lesion glycolysis (TLG), and metabolic tumor volume were used to interpret iFDG-PET/CT while dichotomous visual interpretation was used to interpret iFLT-PET/CT and the results were compared with the 3- and 5-year PFS.

RESULTS: iFLT-PET/CT was negative in 67 (73%) and positive in 25 (27%) patients. iFDG-PET/CT by Deauville criteria was negative (Deauville scores [DS] of 1-3) in 53 (58%) and positive (DS = 4-5) in 39 (42%) patients. …

Fall Prevention Using A Standardized K-Card Process, Falguni Shah Msn, Rn, Cms-Rn, Cnl, Anna Varghese Dnp, Msn, Rn, Ocn

Education Week Poster Showcase 2021

People's Choice winner in the 2021 Education Week Poster Competition

Department of Nursing

Department of Nursing Education

Genetic Correlates In Patients With Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Treated With Hyper-Cvad/Hyper-Cmad Plus Dasatinib Or Hyper-Cvad Plus Ponatinib, Yuya Sasaki Md, Phd, Hagop Kantarjian Md, Nicholas J. Short Md, Farhad Ravandi Md, Marina Konopleva Md, Phd, Guillermo Garcia-Manero Md, Andrew Futreal, Feng Wang, Koichi Takahashi Md, Phd, Elias Jabbour Md

Education Week Poster Showcase 2021

Department of Leukemia Research

Department of Leukemia

Department of Genomic Medicine

Supply, Demand, And Quality: A Three-Pronged Approach To Blood Product Management In Developing Countries, Kyle L. Gress, Karina Charipova, Ivan Urits, Omar Viswanath, Alan D. Kaye

Journal of Patient-Centered Research and Reviews

While transfusion of blood and blood products is instinctively linked to the provision of emergent care, blood and blood products are also routinely used for the treatment of subacute and chronic conditions. Despite the efforts of the World Health Organization and others, developing countries are faced with a three-part problem when it comes to access to and delivery of transfusions: insufficient supply, excessive demand, and inadequate quality of available supply. Developing countries rely heavily on replacement and remunerated donors rather than voluntary nonremunerated donors due to concerns regarding donation- and transfusion-transmitted infection as well as local and cultural beliefs. While …

D-Dimer Levels And Acute Pulmonary Embolism Development In Covid-19 Patients, Vural Ahmet, Kahraman Ahmet Nedim

Journal of Mind and Medical Sciences

Objective. To identify those who develop pulmonary embolism with Ddimer levels by evaluating pulmonary CT angiographies of patients who are followed up with suspicion of coronavirus disease 2019 (COVID-19). Methods. Patients who were followed up in a community hospital with suspicion of COVID-19 and underwent Pulmonary CT angiography examination were evaluated. Clinical and demographic parameters and DDimer values for patients with and without pulmonary embolism were evaluated in the pulmonary CT angiogram. Results. During the COVID-19 pandemic, Thorax CT examination was performed in our center for suspicion or follow-up of COVID-19 infection in 3396 patients. Pulmonary CT angiography was applied …

Structure, Function And Inhibition Of Critical Protein-Protein Interactions Involving Mixed Lineage Leukemia 1 And Its Fusion Oncoproteins, Xin Li, Yongcheng Song

Faculty, Staff and Students Publications

Mixed lineage leukemia 1 (MLL1, also known as MLL or KMT2A) is an important transcription factor and histone-H3 lysine-4 (H3K4) methyltransferase. It is a master regulator for transcription of important genes (e.g., Hox genes) for embryonic development and hematopoiesis. However, it is largely dispensable in matured cells. Dysregulation of MLL1 leads to overexpression of certain Hox genes and eventually leukemia initiation. Chromosome translocations involving MLL1 cause ~ 75% of acute leukemia in infants and 5-10% in children and adults with a poor prognosis. Targeted therapeutics against oncogenic fusion MLL1 (onco-MLL1) are therefore needed. Onco-MLL1 consists of the N-terminal DNA-interacting domains …

Goals-Of-Care & End-Of-Life Quality In Relapsed High-Risk Leukemia: Silent Conversations, Lacy Jo Graham

Doctor of Nursing Practice Scholarly Project

BACKGROUND: The distorted association of “end of life (EOL)” with “goals of care (GOC)” has “silenced” crucial goals discussions in patients with relapsed high-risk leukemia, which raises concerns for the provision of care that is inconsistent with patient’s values and preferences.

AIM: The two main goals of this study were to quantify hematologists rate of participation in a GOC pathway initiative during two separate months, then explore their definition and barriers to having/documenting GOC discussions.

DESIGN: Mixed-methods, explanatory sequential design (follow-up explanations variant).

SAMPLE: Quan: Hematology inpatient admissions during the months of October 2020 and January …

Enhancing Medication Adherence Behaviors Among Ambulatory Pediatric Hematology & Oncology Patients: A Quality Improvement Project, Desiree Palmer

Doctoral Projects

Introduction: Researchers have found that pediatric patients with acute lymphoblastic leukemia and adolescent patients with sickle cell disease struggle to adhere to medication treatment requirements. Because of this trend, there is a clear need to address medication adherence. The purpose of this quality improvement project was to enhance medication adherence behaviors among pediatric hematology and oncology patients and their families within an ambulatory hematology and oncology clinic.

Methods: The project included a systematic literature review to identify evidence-based interventions, an organizational assessment, and a three-phase multifaceted quality improvement process. To increase patients bringing medications to appointments, 32 medication transportation bags …

Comorbidities And Complications In Adults With Pyruvate Kinase Deficiency., Audra N. Boscoe, Yan Yan, Elizabeth Hedgeman, Eduard J. Van Beers, Hanny Al-Samkari, Wilma Barcellini, Stefan W. Eber, Bertil Glader, Hassan M. Yaish, Satheesh Chonat, Mukta Sharma, Kevin H M Kuo, Ellis J. Neufeld, Heng Wang, Madeleine Verhovsek, Sujit Sheth, Rachael F. Grace

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVES: Pyruvate kinase (PK) deficiency is caused by PKLR gene mutations, leading to defective red blood cell glycolysis and hemolytic anemia. Rates of comorbidities and complications by transfusion history and relative to the general population remain poorly quantified.

METHODS: Data for patients aged ≥ 18 years with two confirmed PKLR mutations were obtained from the PK deficiency Natural History Study (NCT02053480). Frequencies of select conditions were compared with an age- and sex-matched cohort from a general insured US population without PK deficiency.

RESULTS: Compared with the matched population (n = 1220), patients with PK deficiency (n = 122) had significantly …

Severe Hyponatremia Following Cystoscopy And Urethral Dilation: An Unusual Late Complication, Mir Ibrahim Sajid, Shanila Ahmed, Noman Ali

Medical College Documents

No abstract provided.

Warm Autoimmune Hemolytic Anemia Associated With Asymptomatic Sars-Cov-2 Infection., Joseph R Liput, Kim Jordan, Rini Patadia, Elizabeth Kander

Ambulatory and Primary Care Articles

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the resultant coronavirus disease 2019 (COVID-19) are associated with several hematologic abnormalities, including immune thrombocytopenia, antiphospholipid syndrome, and autoimmune hemolytic anemia (AIHA). Initial case reports suggested immune dysregulation to be the underlying etiology of SARS-CoV-2-associated AIHA, as all reported cases involved patients with moderate to severe COVID-19, many of whom had underlying lymphoproliferative disorders. More recently, AIHA has been reported in patients with mildly symptomatic SARS-CoV-2 infection. Here, we detail a patient with asymptomatic SARS-CoV-2 infection who presented with severe, symptomatic anemia. Workup was consistent with warm autoimmune hemolytic anemia (WAIHA) secondary …

Opioids Are Not A Major Cause Of Death Of Patients With Sickle Cell Disease., Samir K. Ballas

Cardeza Foundation for Hematologic Research

According to the Center of Disease Control and Prevention (CDC) database, the total number of deaths due to opioid overdose from 1999 through 2018 was 840,629. Given the alarming nature of these statistics, patients who requested prescription for opioids became targets of suspicion and possible accusation of maladaptive behavior. Patients with sickle cell disease (SCD) were often not exempt from such accusations and became guilty by association. In order to clarify the effect of opioids on the mortality of patients with SCD, the mortality rates for children and adults with SCD were investigated using the CDC Wide-ranging Online Data for …

Retrospective Analysis Of Bleeding Events After Central Venous Catheter Placement In Thrombotic Thrombocytopenic Purpura, Waqas Haque, Maria A. Alvarenga, Suchith Vuppala, Manasa Reddy, Ravi Sarode

MEDI 9331 Scholarly Activities Clinical Years

Background

Thrombotic thrombocytopenic purpura (TTP) is a thrombotic disorder caused by severe deficiency of ADAMTS13. Platelets are transfused prophylactically in non-TTP patients for central venous catheter (CVC) with a count× 109/L to prevent bleeding. However, transfusing platelets in TTP prior to CVC placement remains controversial due to concern for arterial thrombosis and mortality. At our center, platelet transfusion is contraindicated in TTP, therefore, we analyzed data for bleeding complications following CVC placement.

Study Design and Methods

95 acute episodes of TTP were identified. Twenty-six episodes were excluded for insufficient documentation or no CVC placement. The charts of 69 remaining episodes …

Platelets As Drivers Of Ischemia/Reperfusion Injury After Stroke., Noor F Shaik, Raymond F Regan, Ulhas P Naik

Cardeza Foundation for Hematologic Research

Ischemic stroke is a leading cause of morbidity and mortality worldwide and, despite reperfusion either via thrombolysis or thrombectomy, stroke patients often suffer from lifelong disabilities. These persistent neurological deficits may be improved by treating the ischemia/reperfusion (I/R) injury that occurs following ischemic stroke. There are currently no approved therapies to treat I/R injury, and thus it is imperative to find new targets to decrease the burden of ischemic stroke and related diseases. Platelets, cell fragments from megakaryocytes, are primarily known for their role in hemostasis. More recently, investigators have studied the nonhemostatic role of platelets in inflammatory pathologies, such …

Pctp Contributes To Human Platelet Activation By Enhancing Dense Granule Secretion, Shaji Abraham, Lin Ma, Xianguo Kong, Shayan Askari, Leonard Edelstein, Steven Mckenzie

Cardeza Foundation for Hematologic Research

PCTP (phosphatidylcholine transfer protein) was discovered recently to regulate aggregation of human platelets stimulated with PAR4 activating peptide (PAR4AP). However, the role of PCTP following thrombin stimulation, the mechanisms by which PCTP contributes to platelet activation, and the role of PCTP with other receptors remained unknown. As mouse platelets do not express PCTP, we treated human platelets with various agonists in the presence of the specific PCTP inhibitor A1. We observed that PCTP inhibition significantly reduced dense granule secretion in response to thrombin, PAR1AP, PAR4AP, convulxin (GPVI agonist) and FcγRIIA crosslinking. In contrast, among these agonists, PCTP inhibition reduced aggregation …

Prolonged Activated Partial Thromboplastin Time Secondary To Factor Xii Deficiency In Two Surgical Patients, Bushra Moiz, Muhammed Wahhaab Sadiq, Muhammad Abdullah Javed, Baqir Hasan Jafry, Muhammad Anees

Section of Haematology/Oncology

Factor XII (FXII) plays a pivotal role in hemostasis, inflammation and complement system. Its deficiency is usually an incidental finding in an otherwise asymptomatic patient who is identified during his/her routine preoperative blood work. This study aimed in evaluating the clinical course of the surgical patients having FXII deficiency. Information regarding demographics, laboratory tests and management of patients was obtained through medical chart and in-house integrated laboratory management system whereas the medical literature was searched through PubMed®. During the study period, two patients were consulted for FXII deficiency prior to the various surgical procedures. Both patients had uneventful surgeries without …

Role Of Gene Therapy In Fanconi Anemia: A Systematic And Literature Review With Future Directions, Shameel Shafqat, Eleze Tariq, Aric D. Parnes, Majed J. Dasouki, Syed O. Ahmed, Shahrukh K. Hashmi

Medical College Documents

Gene therapy (GT) has been reported to improve bone marrow function in individuals with Fanconi anemia (FA); however, its clinical application is still in the initial stages. We conducted this systematic review, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, to assess the long-term safety and clinical outcomes of GT in FA patients. Electronic searches from PubMed, Web of Science, Cochrane Library, and Google Scholar were conducted and full texts of articles meeting our inclusion criteria were reviewed. Three clinical trials were included, with a total of nine patients and mean age of 10.7 ± 5.7 …

Covid-19 And Adult Acute Lymphoblastic Leukemia: Presentation And Management, Ayesha Butt, Natasha Bahadur Ali

Medical College Documents

No abstract provided.

Dnp Final Report: Breaking The Cycle: Care Coordination Interventions And Sickle Cell Readmissions, Naphtali Edge

DNP Final Reports

Background

Approximately 100,000 people in the United States are affected by Sickle Cell Disease (SCD). Sickle Cell Disease represents the second highest readmitting diagnosis at Houston Methodist Hospital. The purpose of this study is to determine the impact of implementing care coordination interventions to reduce hospital readmissions of patients with SCD.

PICOT

In adult patients with SCD in the acute care hospital setting, how does care coordination intervention compared to no care coordination intervention affect the readmission rate for patients with SCD over a 3 – 6-month period?

Body of Evidence

Eleven studies were critical appraised and included in the …

A Case Of Rare Subtype Of Multiple Myeloma: Secondary Plasma Cell Leukemia, Chandra Sanwal, Aftab Mahmood, Michael Bailey, Krutika Patel, Antonio Guzman

HCA Healthcare Journal of Medicine

Plasma cell leukemia is a rare, aggressive form of multiple myeloma with the presence of circulating plasma cells in the peripheral blood. There are two types of plasma cell leukemia, primary and secondary, depending on if there was previous evidence of multiple myeloma. The diagnostic criterion of plasma cell leukemia is based on a percentage (>20%) or an absolute number of (≥2 x 109/L) plasma cells in the peripheral circulation. We present the clinical course of a rare case of secondary plasma cell leukemia in a patient from the time of initial diagnosis of multiple myeloma, its remission period …

Lack Of Association Of The Abo Blood Group With Covid-19 Risk And Severity In Hospitalized Patients In Louisville, Ky, Rafael Fernandez-Botran, Meredith Cahill, Raghava S. Ambadapoodi, Evelyn Exposito Gonzalez, Stephen P. Furmanek, Ruth Carrico, Jose Bordon, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

Background: The potential association of the ABO blood group with the risk of COVID-19 and its severity has attracted a lot of interest since the start of the pandemic. While a number of studies have reported an increased risk associated with blood type A and a reduced risk with type O, other studies have did not found a significant effect. This study aimed to define the prevalence of different ABO blood groups in hospitalized COVID-19 patients in the Louisville, KY area and to investigate whether an association exists between the blood group and disease severity.

Methods: This was a retrospective …

Determinants Of The Outcome Of The Transition Of Children With Sickle Cell Disease To Adult Programs., Samir K. Ballas, Gaye Riddick-Burden, Elisabeth Congdon-Martin

Cardeza Foundation for Hematologic Research

Transition of adolescents with sickle cell disease to adult programs is associated with increased morbidity and mortality. The reasons for this poor outcome are not well known. This report describes the various factors that affect the outcome of the transition process. These include four inter-personal factors: country of residence, region within the country of residence, the health care system and intra-personal factors. Each factor is described in some detail. Understanding these factors and the establishment of guidelines or recommendations could improve the outcome of this critical transition in the life of patients with sickle cell disease.

Targeting Nsd2-Mediated Src-3 Liquid-Liquid Phase Separation Sensitizes Bortezomib Treatment In Multiple Myeloma, Jing Liu, Ying Xie, Jing Guo, Xin Li, Jingjing Wang, Hongmei Jiang, Ziyi Peng, Jingya Wang, Sheng Wang, Qian Li, Linquan Ye, Yuping Zhong, Qiguo Zhang, Xiaozhi Liu, David M Lonard, Jin Wang, Bert W O'Malley, Zhiqiang Liu

Faculty, Staff and Students Publications

Development of chemoresistance is the main reason for failure of clinical management of multiple myeloma (MM), but the genetic and epigenetic aberrations that interact to confer such chemoresistance remains unknown. In the present study, we find that high steroid receptor coactivator-3 (SRC-3) expression is correlated with relapse/refractory and poor outcomes in MM patients treated with bortezomib (BTZ)-based regimens. Furthermore, in immortalized cell lines, high SRC-3 enhances resistance to proteasome inhibitor (PI)-induced apoptosis. Overexpressed histone methyltransferase NSD2 in patients bearing a t(4;14) translocation or in BTZ-resistant MM cells coordinates elevated SRC-3 by enhancing its liquid-liquid phase separation to supranormally modify histone …

Current Practice Of Oral Care For Hematopoietic Stem Cell Transplant Patients: A Survey Of The Eastern Mediterranean Blood And Marrow Transplantation Group, Hani Mawardi, Nathaniel Treister, Osama Felemban, Waleed Alamoudi, Ghada Algohary, Abdulrahman Alsultan, Nawal Alshehri, Illias Tazi, Marwan Shaheen, Natasha Bahadur Ali

Section of Haematology/Oncology

Introduction: The oral cavity is one of the most common sites impacted by hematopoietic stem cell transplantation (HSCT) with acute complications including mucositis, bleeding, salivary gland dysfunction, infection, and taste alteration. These complications may result in significant morbidity and can negatively impact outcomes such as length of stay and overall costs. As such, oral care during HSCT for prevention and management of oral toxicities is a standard component of transplant protocols at all centers. The objective of this study was to evaluate the current oral care practices for patients during HSCT at different transplant centers within the Eastern Mediterranean region. …

Bax 335 Hemophilia B Gene Therapy Clinical Trial Results: Potential Impact Of Cpg Sequences On Gene Expression, Barbara A Konkle, Christopher E Walsh, Miguel A Escobar, Neil C Josephson, Guy Young, Annette Von Drygalski, Scott W J Mcphee, R Jude Samulski, Ivan Bilic, Maurus De La Rosa, Birgit M Reipert, Hanspeter Rottensteiner, Friedrich Scheiflinger, John C Chapin, Bruce Ewenstein, Paul E Monahan

Faculty, Staff and Student Publications

Gene therapy has the potential to maintain therapeutic blood clotting factor IX (FIX) levels in patients with hemophilia B by delivering a functional human F9 gene into liver cells. This phase 1/2, open-label dose-escalation study investigated BAX 335 (AskBio009, AAV8.sc-TTR-FIXR338Lopt), an adeno-associated virus serotype 8 (AAV8)-based FIX Padua gene therapy, in patients with hemophilia B. This report focuses on 12-month interim analyses of safety, pharmacokinetic variables, effects on FIX activity, and immune responses for dosed participants. Eight adult male participants (aged 20-69 years; range FIX activity, 0.5% to 2.0%) received 1 of 3 BAX 335 IV doses: 2.0 × 1011; …

Sickle Haemoglobin: How Critical Are Laboratory Quality Measures For Accurate Identification?, Nazish Sana, Muhammad Shariq Shaikh

Department of Pathology and Laboratory Medicine

No abstract provided.

Voxelotor Modulates The Analgesic Effect Of Certain Opioids., Samir K. Ballas

Cardeza Foundation for Hematologic Research

No abstract provided.

Links Between Thrombosis And Inflammation In Traumatic Brain Injury, W Brad Hubbard, Jing-Fei Dong, Miguel A Cruz, Rolando E Rumbaut

Faculty, Staff and Students Publications

Traumatic brain injury (TBI) continues to be a major healthcare problem and there is much to be explored regarding the secondary pathobiology to identify early predictive markers and new therapeutic targets. While documented changes in thrombosis and inflammation in major trauma have been well described, growing evidence suggests that isolated TBI also results in systemic alterations in these mechanisms. Here, we review recent experimental and clinical findings that demonstrate how blood-brain barrier dysfunction, systemic immune response, inflammation, platelet activation, and thrombosis contribute significantly to the pathogenesis of TBI. Despite advances in the links between thrombosis and inflammation, there is a …