Hematology Commons^™

Reduced Intensity Conditioning For Acute Myeloid Leukemia Using Melphalan- Vs Busulfan-Based Regimens: A Cibmtr Report, Zheng Zhou, Rajneesh Nath, Jan Cerny, Hai-Lin Wang, Mei-Jie Zhang, Hisham Abdel-Azim, Vaibhav Agrawal, Gulrayz Ahmed, A Samer Al-Homsi, Mahmoud Aljurf, Hassan B Alkhateeb, Amer Assal, Ulrike Bacher, Ashish Bajel, Qaiser Bashir, Minocher Battiwalla, Vijaya Raj Bhatt, Michael Byrne, Jean-Yves Cahn, Mitchell Cairo, Hannah Choe, Edward Copelan, Corey Cutler, Moussab B Damlaj, Zachariah Defilipp, Marcos De Lima, Miguel Angel Diaz, Nosha Farhadfar, James Foran, César O Freytes, Aaron T Gerds, Usama Gergis, Michael R Grunwald, Zartash Gul, Mehdi Hamadani, Shahrukh Hashmi, Mark Hertzberg, Gerhard C Hildebrandt, Nasheed Hossain, Yoshihiro Inamoto, Luis Isola, Tania Jain, Rammurti T Kamble, Muhammad Waqas Khan, Mohamed A Kharfan-Dabaja, Partow Kebriaei, Natasha Kekre, Nandita Khera, Hillard M Lazarus, Jane L Liesveld, Mark Litzow, Hongtao Liu, David I Marks, Rodrigo Martino, Vikram Mathews, Asmita Mishra, Hemant S Murthy, Arnon Nagler, Ryotaro Nakamura, Sunita Nathan, Taiga Nishihori, Rebecca Olin, Richard F Olsson, Neil Palmisiano, Sagar S Patel, Mrinal M Patnaik, Attaphol Pawarode, Miguel-Angel Perales, Ioannis Politikos, Uday Popat, David Rizzieri, Brenda M Sandmaier, Bipin N Savani, Sachiko Seo, Nirav N Shah, Geoffrey L Uy, David Valcárcel, Leo F Verdonck, Edmund K Waller, Youjin Wang, Daniel Weisdorf, Baldeep Wirk, Eric Wong, Jean A Yared, Wael Saber

Faculty, Staff and Students Publications

There is a lack of large comparative study on the outcomes of reduced intensity conditioning (RIC) in acute myeloid leukemia (AML) transplantation using fludarabine/busulfan (FB) and fludarabine/melphalan (FM) regimens. Adult AML patients from Center for International Blood and Marrow Transplant Research who received first RIC allo-transplant between 2001 and 2015 were studied. Patients were excluded if they received cord blood or identical twin transplant, total body irradiation in conditioning, or graft-versus-host disease (GVHD) prophylaxis with in vitro T-cell depletion. Primary outcome was overall survival (OS), secondary end points were leukemia-free survival (LFS), nonrelapse mortality (NRM), relapse, and GVHD. Multivariate survival …

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 …

Burden-Of-Illness Associated With Bleeding-Related Hospitalizations In Atrial Fibrillation Patients: Findings From The Nationwide Readmission Database, Benjamin Miao, Monique Miller, Belinda Lovelace, Anne Beaubrun, Kelly Mcneil-Posey, Mark J Alberts, William Frank Peacock, Olivia S Costa, Charles Michael White, Craig I Coleman

Faculty, Staff and Students Publications

Introduction  A paucity of contemporary data examining bleeding-related hospitalization outcomes in atrial fibrillation (AF) patients exists.

Methods  Adults in the Nationwide Readmissions Database (January 2016–November 2016) with AF and hospitalized for intracranial hemorrhage (ICH), gastrointestinal, genitourinary, or other bleeding were identified. Association between bleed types and outcomes were assessed using multivariable regression (gastrointestinal defined as referent) and reported as crude incidences and adjusted odds ratios (ORs) or mean differences with 95% confidence intervals (CIs).

Results  In total, 196,878 index bleeding-related hospitalizations were identified in this AF cohort (CHA2DS2VASc score ≥2 in 95.1%), with 70.8% classified as gastrointestinal. The overall incidences …

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 …

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’ …

Ubiquitination Of The Dna-Damage Checkpoint Kinase Chk1 By Traf4 Is Required For Chk1 Activation, Xinfang Yu, Wei Li, Haidan Liu, Qipan Deng, Xu Wang, Hui Hu, Zijun Y Xu-Monette, Wei Xiong, Zhongxin Lu, Ken H Young, Wei Wang, Yong Li

Faculty, Staff and Students Publications

BACKGROUND: Aberrant activation of DNA damage response (DDR) is a major cause of chemoresistance in colorectal cancer (CRC). CHK1 is upregulated in CRC and contributes to therapeutic resistance. We investigated the upstream signaling pathways governing CHK1 activation in CRC.

METHODS: We identified CHK1-binding proteins by mass spectrometry analysis. We analyzed the biologic consequences of knockout or overexpression of TRAF4 using immunoblotting, immunoprecipitation, and immunofluorescence. CHK1 and TRAF4 ubiquitination was studied in vitro and in vivo. We tested the functions of TRAF4 in CHK1 phosphorylation and CRC chemoresistance by measuring cell viability and proliferation, anchorage-dependent and -independent cell growth, and mouse …

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 …

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 …

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 …

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 …

Extra Medullar Granulocytic Sarcoma: A Case Report Of An Exceptional Localization, Bouhani Malek, Sakhri Saida, Jaidane Olfa, Adouni Olfa, Chargui Riadh, Rahal Khaled

Journal of Mind and Medical Sciences

Granulocytic sarcoma is a rare type of tumor composed of extramedullary immature cells. The breast location is very rare; it accounts for less than 8% of cases. The present study reports the case of a 36-year-old female with a medical history of myelodysplastic syndrome. She was referred because of a lump in the left breast. We have diagnosed a case of granulocytic sarcoma of the breast by core biopsy. Histology and immunohistochemistry showed hypercellular smears with immature myeloid cells. The blast cells were myeloperoxidase positive.

The patient underwent a lumpectomy. Five months later, she developed a contralateral recurrence, treated by …

An In Vivo Genome-Wide Crispr Screen Identifies The Rna-Binding Protein Staufen2 As A Key Regulator Of Myeloid Leukemia, Jeevisha Bajaj, Michael Hamilton, Yutaka Shima, Kendall Chambers, Kyle Spinler, Eric L Van Nostrand, Brian A Yee, Steven M Blue, Michael Chen, David Rizzeri, Charles Chuah, Vivian G Oehler, H Elizabeth Broome, Roman Sasik, James Scott-Browne, Anjana Rao, Gene W Yeo, Tannishtha Reya

Faculty, Staff and Students Publications

Aggressive myeloid leukemias such as blast crisis chronic myeloid leukemia and acute myeloid leukemia remain highly lethal. Here we report a genome-wide in vivo CRISPR screen to identify new dependencies in this disease. Among these, RNA-binding proteins (RBPs) in general, and the double-stranded RBP Staufen2 (Stau2) in particular, emerged as critical regulators of myeloid leukemia. In a newly developed knockout mouse, loss of Stau2 led to a profound decrease in leukemia growth and improved survival in mouse models of the disease. Further, Stau2 was required for growth of primary human blast crisis chronic myeloid leukemia and acute myeloid leukemia. Finally, …