Hematology Commons^™

Reducing The Incidence Of Nosocomial Aspiration Pneumonia In Adult Oncology Patients Through Improved Compliance With Oral Hygiene Protocols, Rickey Maung

Master's Projects and Capstones

Objective: Oncology patients undergoing chemotherapy are at increased risk of mucosal barrier injuries and aspiration pneumonia, with current aspiration pneumonia rates exceeding target levels. Enhanced oral hygiene protocols and improved compliance have been shown to reduce these complications in this vulnerable population.

Context: The microsystem under review comprises six oncology units within Hospital A, a major medical center in California. Aspiration pneumonia, frequently linked to mucosal barrier injuries, poses a significant threat to patient safety and increases treatment costs and complications in oncology care. Recognizing the critical need to address this issue, an aspiration pneumonia task force has prioritized efforts …

Association Of Unmet Social Needs With Disease-Related Outcomes In Pediatric Patients With Sickle Cell Disease, Molly Sonenklar, Sarah Marks, Cerelia Donald, Cecelia Valrie, Wally Smith, India Sisler

School of Medicine Faculty Publications

Background: Social determinants of health (SDoH) are socioeconomic factors that influence health and well-being, though when unmet can greatly contribute to health disparities. Individuals with sickle cell disease (SCD) are at increased risk of mortality, disability, and healthcare utilization. However, there are limited data linking specific social needs with disease outcomes in this population. Therefore, we sought to identify the unmet needs in one institution and their association with healthcare utilization. Methods: Children with SCD and their guardians answered demographic and SDoH questionnaires during routine Sickle Cell Clinic appointments. We defined an unmet social need as any positive answer to …

Transplant-Associated Tma: The Conundrum Of Diagnosis And Treatment, Ang Li, Sarah E Sartain

Faculty, Staff and Students Publications

Transplant-associated thrombotic microangiopathy (TA-TMA) after hematopoietic cell transplantation is characterized by microangiopathic hemolytic anemia (MAHA) with persistent schistocytosis, elevated markers of hemolysis, thrombocytopenia, and microvascular thrombosis leading to ischemic injuries in the kidneys and other organs. The initial evaluation of the disease requires confirmation of non-immune MAHA and careful examination of known secondary causes of TMA. Due to increased likelihood of long-term renal failure and overall mortality, a rapid diagnosis and treatment of the underlying trigger is needed. However, the diagnostic criteria proposed to define TA-TMA remain insufficient. sC5b9, the soluble form of the membrane attack complex of the terminal …

Mutation- And Mrd-Informed Treatments For Transplant-Ineligible Patients, Curtis A Lachowiez, Courtney D Dinardo

Faculty, Staff and Student Publications

The ongoing development of molecularly targeted therapies in addition to the new standard of care combination of azacitidine and venetoclax (AZA-VEN) has transformed the prognostic outlook for older, transplant-ineligible patients with acute myeloid leukemia (AML). While conventional treatments, such as standard anthracycline and cytarabine- based chemotherapy or hypomethylating agent (HMA) monotherapy, are associated with a generally poor prognosis in this patient population, the use of these novel regimens can result in long-lasting, durable remissions in select patient subgroups. Furthermore, the simultaneous discovery of resistance mechanisms to targeted therapies and AZA-VEN has enabled the identification of patient subgroups with inferior outcomes, …

Clinical Effects Of Dexamethasone Among Patients With Sickle Cell Disease Hospitalized With Covid-19: Outcomes From A Single Academic Health System, William M. Garneau, Matthew J. Lankiewicz, Catherine R. Lesko, Ashley P. Lauriello, Kelly A. Gebo, Sophie M. Lanzkron

Department of Medicine Faculty Papers

BACKGROUND: Dexamethasone is a steroid used in the treatment of hospitalized patients with severe COVID-19. However, the effect of dexamethasone in patients with SCD remains unclear given that steroids may precipitate vaso-occlusive crisis (VOC) in patients with SCD.

METHODS AND FINDINGS: We performed a retrospective analysis of patients with SCD who were hospitalized at Johns Hopkins Health System between June 1, 2020 and June 26, 2022. We reviewed individual charts to assess severity of illness and eligibility for dexamethasone treatment. The exposure of interest was treatment with dexamethasone. Outcomes of interest included incident VTE, length of hospital stay, ICU admission, …

Antithrombotic Efficacy And Bleeding Risks Of Vaccine-Induced Immune Thrombotic Thrombocytopenia Treatments, Halina H.L. Leung, Zohra Ahmadi, Brendan Lee, John Casey, Sumita Ratnasingam, Steven E. Mckenzie, Jose Perdomo, Beng H. Chong

Cardeza Foundation for Hematologic Research

Current guidelines for treating vaccine-induced immune thrombotic thrombocytopenia (VITT) recommend nonheparin anticoagulants and IV immunoglobulin (IVIg). However, the efficacy of these treatments remains uncertain due to case studies involving small patient numbers, confounding factors (eg, concurrent treatments), and a lack of animal studies. A recent study proposed danaparoid and heparin as potential VITT therapies because of their ability to disrupt VITT IgG-platelet factor 4 (PF4) binding. Here, we examined the effects of various anticoagulants (including unfractionated [UF] heparin, danaparoid, bivalirudin, fondaparinux, and argatroban), IVIg, and the FcγRIIa receptor-blocking antibody, IV.3. Our investigation focused on VITT IgG-PF4 binding, platelet activation, thrombocytopenia, …

Real-World Impact Of Emicizumab And Immunosuppression On Acquired Hemophilia A: A Multicenter Us Cohort, Jacqueline N Poston, Cassandra Bryan, Annette Von Drygalski, Kadhim Al Banaa, Jenny Y Zhou, Aric Parnes, Evan C Chen, Osman Khan, Patrick Ellsworth, Lorraine Cafuir, Christopher Walsh, Miguel A Escobar, James F Wu, Lynn M Malec, Craig M Kessler, Maissaa Janbain, Rebecca Kruse-Jarres

Faculty, Staff and Student Publications

Acquired hemophilia A (AHA) is an autoimmune bleeding disorder that is caused by factor VIII (FVIII) autoantibodies with high morbidity and mortality due to bleeding and complications from immunosuppression (IST). To address the real-world implications of the FVIII mimetic antibody, emicizumab, and the role of IST, we retrospectively collected de-identified data on 62 patients with AHA who were treated off-label with emicizumab for a median of 10 weeks at 12 US-based hemophilia treatment centers. Most patients (95.2%) had acute bleeding at diagnosis, and 62.9% had partial or no control of bleeds despite the use of hemostatic agents at the time …

The Role Of Microrna-155 As A Biomarker In Diffuse Large B-Cell Lymphoma, Epameinondas Koumpis, Vasileios Georgoulis, Konstantina Papathanasiou, Alexandra Papoudou-Bai, Panagiotis Kanavaros, Evangelos Kolettas, Eleftheria Hatzimichael

Computational Medicine Center Faculty Papers

Diffuse Large B-cell Lymphoma (DLBCL) is the most common aggressive non-Hodgkin lymphoma (NHL). Despite the use of newer agents, such as polatuzumab vedotin, more than one-third of patients have ultimately relapsed or experienced refractory disease. MiRNAs are single-stranded, ~22-nucleotide-long RNAs that interact with their target RNA. They are significant regulators of post-transcriptional gene expression. One significant miRNA, miR-155, is involved in the pathophysiology of DLBCL and it is a critical modulator of hematopoiesis, inflammation, and immune responses. Targets of miR-155, such as histone deacetylase 4 (HDAC4), suppressor of cytokine signaling-1 (SOCS1) and immune cells, play a crucial role in DLBCL …

Genetic Risk Stratification And Outcomes Among Treatment-Naive Patients With Aml Treated With Venetoclax And Azacitidine, Hartmut Döhner, Keith W Pratz, Courtney D Dinardo, Andrew H Wei, Brian A Jonas, Vinod A Pullarkat, Michael J Thirman, Christian Récher, Andre C Schuh, Sunil Babu, Xiaotong Li, Grace Ku, Zihuan Liu, Yan Sun, Jalaja Potluri, Monique Dail, Brenda Chyla, Daniel A Pollyea

Faculty, Staff and Student Publications

The European LeukemiaNet (ELN) acute myeloid leukemia (AML) genetic risk classification systems are based on response to intensive chemotherapy; their ability to discriminate outcomes in older patients treated with venetoclax-azacitidine may be suboptimal. This pooled analysis of the phase 3 VIALE-A trial (NCT02993523) and phase 1b study (NCT02203773) examined prognostic stratification according to the 2017 and 2022 ELN risk classifications and derived new molecular signatures differentiating venetoclax-azacitidine-treated patients based on overall survival (OS). Overall, 279 patients treated with venetoclax-azacitidine and 113 patients treated with placebo-azacitidine were analyzed. The ELN 2017 or 2022 prognostic criteria classified most …

Frontline Ph-Negative B-Cell Precursor Acute Lymphoblastic Leukemia Treatment And The Emerging Role Of Blinatumomab, Elias J Jabbour, Hagop M Kantarjian, Nicola Goekbuget, Bijal D Shah, Sabina Chiaretti, Jae H Park, Anita W Rijneveld, Lia Gore, Shaun Fleming, Aaron C Logan, Josep M Ribera, Tobias F Menne, Khalid Mezzi, Faraz Zaman, Kelly Velasco, Nicolas Boissel

Faculty, Staff and Student Publications

This narrative review seeks to summarize chemotherapeutic regimens commonly used for patients with newly diagnosed Philadelphia (Ph) chromosome-negative B-cell precursor acute lymphoblastic leukemia (BCP-ALL) in the frontline setting and to describe the latest clinical research using the bispecific T-cell-engaging immunotherapy blinatumomab in the first-line treatment setting. Current standard-of-care chemotherapeutic backbones for newly diagnosed Ph-negative BCP-ALL are based on the same overarching treatment principle: to reduce disease burden to undetectable levels and maintain lasting remission. The adult treatment landscape has progressively evolved following the adoption of pediatric-inspired regimens. However, these intense regimens are not tolerated by all, and high-risk patients still …

Assessing The Impact Of Obesity On Postoperative Outcomes In Rcc Using Machine Learning, Atulya A. Khosla, Manas Pustake, Sufal Chhabra, Yanjia Zhang, Mukesh Roy, Muni Rubens, Venkataraghavan Ramamoorthy, Anshul Saxena, Ishmael A. Jaiyesimi

Conference Presentation Abstracts

Introduction Obesity is associated with an increased risk of developing renal cell carcinoma (RCC) but paradoxically correlates with improved outcomes in metastatic cases. Moreover, the data on the relationship between obesity and postoperative outcomes following nephrectomy are inconsistent. Accurate prediction of postoperative outcomes, including complications, 30-day readmissions, and mortality, is essential for improving patient outcomes in surgical procedures. In this study, we utilized ML models to predict such outcomes in RCC patients undergoing nephroureterectomy, radical nephrectomy, partial nephrectomy, and other excision procedures on the kidney using data from the National Surgical Quality Improvement Program (NSQIP; 2016- 2021). Methods A gradient-boosted …

Nosebleed No More: Recognizing And Diagnosing Factor Viii Inhibitor, Salam Harb, Leidy Huie Martinez Md, Jose Alvarado Md, Ajit Koli Do, Hazem Nasef Ms4

HCA-NSU MD Research Day

Acquired hemophilia is a condition characterized by the unexpected onset of severe bleeding due to an issue with coagulation factors. Typically, this disorder results from the production of autoantibodies against the Factor VIII coagulation factor. Although acquired hemophilia is an extremely rare condition, with an annual incidence of just 1.5 cases per million, it is crucial to recognize and understand it. This is because diagnosing this disorder is intricate, and if left undiagnosed and untreated, it can lead to high levels of morbidity and mortality. This case stands out as the condition typically targets older adults, with around 80% of …

Genetically Determined Telomere Length In Monoclonal Gammopathy Of Undetermined Significance, Multiple Myeloma Risk And Outcome, Matteo Giaccherini, Alyssa I Clay-Gilmour, Romano Liotti, Angelica Macauda, Manuel Gentiluomo, Elizabeth E Brown, Mitchell J Machiela, Stephen J Chanock, Michelle A T Hildebrandt, Aaron D Norman, Elisabet Manasanch, S Vincent Rajkumar, Jonathan N Hofmann, Sonja I Berndt, Parveen Bhatti, Graham G Giles, Elad Ziv, Shaji K Kumar, Nicola J Camp, Wendy Cozen, Susan L Slager, Federico Canzian, Federica Gemignani, Celine M Vachon, Daniele Campa

Faculty, Staff and Student Publications

No abstract provided.

How Did Dat Happen? A Coombs Negative Delayed Hemolytic Transfusion Reaction In A Patient With Myelodysplastic Syndrome: A Case Report, Aniket Vijay Rao Dr, Aditya Sanjeevi, Daniel Jose Idoate, Nagesh Jadhav, Basil Verghese, Himal Kharel

Advances in Clinical Medical Research and Healthcare Delivery

Delayed hemolytic transfusion reactions (DHTRs) present significant challenges in diagnosis and management despite advancements in pre-transfusion testing. We report a case of a 76-year-old female with myelodysplastic syndrome (MDS) who developed severe hemolytic anemia following a seemingly compatible blood transfusion and appropriate pretransfusion testing. Evaluation revealed characteristics consistent with DHTR. Diagnostic uncertainty arose due to a negative Direct Antiglobulin Test (DAT) in the setting of a concomitant Vitamin B-12 deficiency. She was supported with prednisone and B12 supplementation. We discuss challenges in diagnosis, including the limitation of DAT, and propose strategies for comprehensive antibody identification. The case underscores the importance …

Recurrent Deep Vein Thrombosis In May Thurner Syndrome Precipitated By Heparin Induced Thrombocytopenia: A Case Report And Review Of Literature, Abhishek Bhandari, Chengu Niu

Advances in Clinical Medical Research and Healthcare Delivery

May Thurner Syndrome involves the extrinsic compression of the left common iliac vein by the right common iliac artery, which predisposes to venous thrombosis. This case report and review of literature details a complex instance of recurrent Deep Vein Thrombosis (DVT) in a 58-year-old female patient with May Thurner Syndrome (MTS), exacerbated by Heparin-Induced Thrombocytopenia (HIT). The patient, post Coronary Artery Bypass Graft surgery, developed leg symptoms leading to the discovery of an extensive DVT from the calf veins to the external iliac vein. She was initially treated with heparin, which was switched to bivalirudin following a significant drop in …

Tak1 Blockade Plus Azacitidine Induces Apoptosis, Augments Cytarabine, And Ablates Clonogenicity In Mll-Af9+ Human Aml Cell Lines, Austin P. Runde, Cameron Lewis, Peter Breslin Sj, Jiwang Zhang

School of Medicine

Acute myeloid leukemia (AML) encompasses a diverse group of cancers that originate in the blood-forming tissues of the bone marrow [1]. Aside from the PML-RARA⁺ subtype, AML carries a 5-year survival rate of 28% for patients 20+ years of age. AML is the most common cancer of the hematopoietic system and is slightly more common in biological males; the average age at diagnosis is 68 years. Standard frontline treatment for AML is a two-phase regimen of intensive chemotherapy (CTx) employing daunorubicin and cytarabine; etoposide may also be added in select regimens. Despite 60-70% of patients achieving complete remission (CR), …

Prognostic Stratification In Dlbcl Patients With Aberrant Myc Gene, Jian-Rong Li, Vikram R Shaw, Abi Parthasarathy, Yong Li, Christopher I Amos, Chao Cheng

Faculty, Staff and Students Publications

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease characterized by a subset of patients who exhibit treatment resistance and poor prognoses. Genomic assays have been widely employed to identify high-risk individuals characterized by rearrangements in the MYC, BCL2 and BCL6 genes. These patients typically undergo more aggressive therapeutic treatments; however, there remains a significant variation in their treatment outcomes. This study introduces an MYC signature score (MYCSS) derived from gene expression profiles, specifically designed to evaluate MYC overactivation in DLBCL patients. MYCSS was validated across several independent cohorts to assess its ability to stratify patients based on MYC-related genetic …

Outcomes And Genetic Dynamics Of Acute Myeloid Leukemia At First Relapse, Alex Bataller, Hagop Kantarjian, Alexandre Bazinet, Tapan Kadia, Naval Daver, Courtney D Dinardo, Gautam Borthakur, Sanam Loghavi, Keyur Patel, Guilin Tang, Koji Sasaki, Nicholas J Short, Musa Yilmaz, Ghayas C Issa, Yesid Alvarado, Guillermo Montalban-Bravo, Abhishek Maiti, Hussein A Abbas, Koichi Takahashi, Sherry Pierce, Elias Jabbour, Guillermo Garcia-Manero, Farhad Ravandi

Faculty, Staff and Student Publications

Patients with relapsed acute myeloid leukemia (AML) experience dismal outcomes. We performed a comprehensive analysis of patients with relapsed AML to determine the genetic dynamics and factors predicting survival. We analyzed 875 patients with newly diagnosed AML who received intensive treatment or low-intensity treatment. Of these patients, 197 subsequently relapsed. Data were available for 164 of these patients, with a median time from complete remission/complete remission with incomplete blood count recovery to relapse of 6.5 months. Thirty-five of the 164 patients (21%) experienced relapse after allogeneic hematopoietic stem cell transplantation. At relapse, mutations in genes involved in pathway signaling tended …

Vertical Targeting Of The Pi3k/Akt Pathway At Multiple Points Is Synergistic And Effective For Non-Hodgkin Lymphoma, Kristyna Kupcova, Jana Senavova, Filip Jura, Vaclav Herman, Anezka Rajmonova, Mariana Pacheco-Blanco, Tereza Chrbolkova, Iva Hamova, R Eric Davis, Ondrej Havranek

Faculty, Staff and Student Publications

The phosphatidylinositol 3‑kinase/protein kinase B (PI3K/AKT) signaling pathway is critically active in many cell types, both normal and neoplastic. Many small-molecule inhibitors targeting different levels of the PI3K/AKT pathway have been developed for cancer therapy, but their efficacy is reduced by compensatory pathway re-activation mechanisms, and their tolerability by toxic side effects. We studied this problem using cell lines representing diffuse large B-cell lymphoma (SUDHL-4 and OCI-Ly7), a genetically-encoded live-cell reporter of AKT activity, and 3 small-molecule inhibitors targeting different levels of the pathway: idelalisib (PI3Kδ), GSK2334470 (PDPK1), and ipatasertib (AKT). Half-maximal (IC50) concentrations of these inhibitors for AKT activity …

Optimal Infused Cd34+ Cell Dose In Multiple Myeloma Patients Undergoing Upfront Autologous Hematopoietic Stem Cell Transplantation, Oren Pasvolsky, Curtis Marcoux, Denái R Milton, Babar Pal, Mark R Tanner, Qaiser Bashir, Samer Srour, Jaehyun Lee, Neeraj Saini, Paul Lin, Jeremy Ramdial, Yago Nieto, Guilin Tang, Yosra Aljawai, Partow Kebriaei, Melody R Becnel, Hans C Lee, Krina K Patel, Sheeba K Thomas, Robert Z Orlowski, Elizabeth J Shpall, Richard E Champlin, Muzaffar H Qazilbash

Faculty, Staff and Student Publications

Autologous transplantation remains the standard of care for eligible multiple myeloma (MM) patients, yet optimal CD34+ cell dose remains unclear. We conducted a retrospective study on MM patients undergoing upfront transplant between 2005 and 2021 and divided them into low (≤2.5 × 106 cells/kg) and high (>2.5 × 106 cells/kg) CD34+ dose groups. We included 2479 patients, 95 in the low CD34+ group and 2384 in the high CD34+ group. Patients in the low CD34+ group were older (63.2 vs 61.1 years, p = 0.013), more often had R-ISS III (19% vs 9%, p = 0.014), received plerixafor (60% …