Hematology Commons^™

A Phase 2 Study Of Nivolumab Combined With Ibrutinib In Patients With Diffuse Large B-Cell Richter Transformation Of Cll, Nitin Jain, Jayastu Senapati, Beenu Thakral, Alessandra Ferrajoli, Philip Thompson, Jan Burger, Sreyashi Basu, Tapan Kadia, Naval Daver, Gautam Borthakur, Marina Konopleva, Naveen Pemmaraju, Erin Parry, Catherine J Wu, Joseph Khoury, Carlos Bueso-Ramos, Naveen Garg, Xuemei Wang, Wanda Lopez, Ana Ayala, Susan O'Brien, Hagop Kantarjian, Michael Keating, James Allison, Padmanee Sharma, William Wierda

Faculty, Staff and Student Publications

Richter transformation (RT) is a rare complication of chronic lymphocytic leukemia (CLL) that has dismal outcomes. Upregulation of PD-1/PD-L1 drives immunological evasion in patients with RT. We hypothesized that combining nivolumab, a PD-1 blocking antibody, with the BTK inhibitor (BTKi) ibrutinib could potentiate tumor-cell killing. We conducted an investigator-initiated phase 2 clinical trial to assess the efficacy of combined nivolumab and ibrutinib in patients with diffuse large B-cell lymphoma (DLBCL) RT and CLL. Patients included were ≥18 years of age with adequate hepatic and renal function. Patients received nivolumab every 2 weeks of a 4-week cycle for a maximum of …

Functional Evaluation Of A Novel Rpl30 Mutation And Its Role In Diamond Blackfan Anemia (Dba), Alexandra Prosser, Alexandria Cockrell, Danny Miller, Chris Seidel, Tamara Potapova, John M. Perry, Midhat Farooqi, Erin M. Guest, Jennifer Gerton

Research Days

Background: Bone marrow failure is life-threatening and requires prompt, intensive treatment, which is dependent upon identification of genetic drivers. Although there has been investigation into associated genetic mutations, especially in Diamond Blackfan anemia (DBA), the relationship between genotype and phenotype remains unclear.DBA has been identified as a ribosomopathy, also known as a disease associated with defects in ribosome biogenesis. We identified a novel heterozygous variant (c.167+769C >T) in the noncoding region of RPL30 in a patient with clinical diagnosis of DBA. Clinical RNA sequencing (RNA-seq) suggests the variant generates a novel splice acceptor site resulting in truncated RPL30 transcripts. Elucidation …

Five-Year Follow-Up Of Zuma-1 Supports The Curative Potential Of Axicabtagene Ciloleucel In Refractory Large B-Cell Lymphoma, Sattva S Neelapu, Caron A Jacobson, Armin Ghobadi, David B Miklos, Lazaros J Lekakis, Olalekan O Oluwole, Yi Lin, Ira Braunschweig, Brian T Hill, John M Timmerman, Abhinav Deol, Patrick M Reagan, Patrick Stiff, Ian W Flinn, Umar Farooq, Andre H Goy, Peter A Mcsweeney, Javier Munoz, Tanya Siddiqi, Julio C Chavez, Alex F Herrera, Nancy L Bartlett, Adrian A Bot, Rhine R Shen, Jinghui Dong, Kanwarjit Singh, Harry Miao, Jenny J Kim, Yan Zheng, Frederick L Locke

Faculty, Staff and Student Publications

In phase 2 of ZUMA-1, a single-arm, multicenter, registrational trial, axicabtagene ciloleucel (axi-cel) autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy demonstrated durable responses at 2 years in patients with refractory large B-cell lymphoma (LBCL). Here, we assessed outcomes in ZUMA-1 after 5 years of follow-up. Eligible adults received lymphodepleting chemotherapy followed by axi-cel (2 × 106 cells per kg). Investigator-assessed response, survival, safety, and pharmacokinetics were assessed in patients who had received treatment. The objective response rate in these 101 patients was 83% (58% complete response rate); with a median follow-up of 63.1 months, responses were ongoing in 31% …

Sirolimus Versus Cyclosporine A In Patients With Primary Acquired Pure Red Cell Aplasia: A Prospective Cohort Study, Yuan Yang, Zengwei Tang, Yuzhou Huang, Qinglin Hu, Shuqing Wang, Jiang Ji, Yali Du, Chen Yang, Miao Chen, Shimin Hu, Bing Han

Faculty, Staff and Student Publications

No abstract provided.

Prospective Hemophilia Inhibitor Pup Study Reveals Distinct Antibody Signatures During Fviii Inhibitor Eradication, Helmut Paul, Verena Berg, Bagirath Gangadharan, Joel Bowen, Petra Lebeau, Jan Blatný, Christoph Male, Vlad C Radulescu, Rosa Diaz, Maria Elisa Mancuso, Deborah L Brown, Birgit M Reipert

Faculty, Staff and Student Publications

Factor VIII (FVIII) inhibitor formation is a major clinical concern during replacement therapy in patients with hemophilia A. Immune tolerance induction (ITI) is the only therapeutic approach to attempt inhibitor eradication and establishment of long-term immune tolerance to FVIII. Hemophilia Inhibitor Previously Untreated Patient (PUP) Study (HIPS) was a prospective clinical trial to investigate changes in the immune system of PUPs with severe hemophilia A. Five patients who developed persistent FVIII inhibitors during HIPS entered an ITI extension arm (HIPS-ITI). During HIPS-ITI, inhibitor patients received ITI with the same FVIII product (a single source of recombinant, human full-length FVIII) used …

Increasing Incentive Spirometry Use In Patients With Sickle Cell Disease: Longer Follow-Up Of Pdsa Cycle 1, Alexandra Prosser, Thomas Cochran

Research Days

Problem Statement/Question: Acute chest syndrome (ACS) is one of the leading causes of morbidity and mortality in patients with sickle cell disease. Patients are at higher risk for this complication during hospital admission due to limited mobility leading to decreased lung inflation. The National Heart, Lung, and Blood Institute (NHLBI) recommends providing ten breaths of incentive spirometry (IS) every two hours while awake for patients admitted to the hospital with sickle cell disease to help prevent development of acute chest syndrome. Without this intervention, patients are more likely to develop ACS requiring increased level of care, prolonged hospital stays, and …

Impact Of Early Relapse Within 24 Months After First-Line Systemic Therapy (Pod24) On Outcomes In Patients With Marginal Zone Lymphoma: A Us Multisite Study, Narendranath Epperla, Rina Li Welkie, Pallawi Torka, Geoffrey Shouse, Reem Karmali, Lauren Shea, Andrea Anampa-Guzmán, Timothy S Oh, Heather Reaves, Montreh Tavakkoli, Kathryn Lindsey, Irl Brian Greenwell, Emily Hansinger, Colin Thomas, Sayan Mullick Chowdhury, Kaitlin Annunzio, Beth Christian, Stefan K Barta, Praveen Ramakrishnan Geethakumari, Nancy L Bartlett, Alex F Herrera, Natalie S Grover, Adam J Olszewski

Department of Medicine Faculty Papers

Progression of disease within 24 months (POD24) from diagnosis in marginal zone lymphoma (MZL) was shown to portend poor outcomes in prior studies. However, many patients with MZL do not require immediate therapy, and the time from diagnosis-to-treatment interval can be highly variable with no universal criteria to initiate systemic therapy. Hence, we sought to evaluate the prognostic relevance of early relapse or progression within 24 months from systemic therapy initiation in a large US cohort. The primary objective was to evaluate the overall survival (OS) in the two groups. The secondary objective included the evaluation of factors predictive of …

Species Differences In Platelet Protease-Activated Receptors, Stephanie A Renna, Steven E. Mckenzie, James V. Michael

Cardeza Foundation for Hematologic Research

Protease-activated receptors (PARs) are a class of integral membrane proteins that are cleaved by a variety of proteases, most notably thrombin, to reveal a tethered ligand and promote activation. PARs are critical mediators of platelet function in hemostasis and thrombosis, and therefore are attractive targets for anti-platelet therapies. Animal models studying platelet PAR physiology have relied heavily on genetically modified mouse strains, which have provided ample insight but have some inherent limitations. The current review aims to summarize the notable PAR expression and functional differences between the mouse and human, in addition to highlighting some recently developed tools to further …

Impact Of Clonal Plasma Cells In Autografts On Outcomes In High-Risk Multiple Myeloma Patients, Oren Pasvolsky, Denái R Milton, Mikael Rauf, Sassine Ghanem, Adeel Masood, Ali H Mohamedi, Mark R Tanner, Qaiser Bashir, Samer Srour, Neeraj Saini, Paul Lin, Jeremy Ramdial, Yago Nieto, Guilin Tang, Hans C Lee, Krina K Patel, Partow Kebriaei, Sheeba K Thomas, Donna M Weber, Robert Z Orlowski, Katy Rezvani, Richard Champlin, Elizabeth J Shpall, Pei Lin, Muzaffar H Qazilbash

Faculty, Staff and Student Publications

Most patients with multiple myeloma (MM) undergoing autologous hematopoietic stem cell transplantation (autoHCT) eventually relapse, perhaps due to the presence of clonal plasma cells (CPC) in the autograft. We conducted a retrospective analysis to evaluate the impact of CPC in the autograft on the outcomes of high-risk chromosomal abnormalities (HRMM) patients undergoing autoHCT between 2008 and 2018. Patients were divided into CPC+ or CPC- in the autograft by next-generation flow cytometry (NGF). There were 75 CPC + autografts (18%) and 341 CPC- (82%). The CPC + group was less likely to achieve MRD-negative complete remission post-transplant (11% vs. 42%; p < 0.001). Median progression free survival (PFS) and overall survival (OS) were (12.8 vs. 32.1 months) and (36.4 vs. 81.2 months) in the CPC + and CPC- groups, respectively (both p < 0.001). Also in the subset of patients with MRD-negative ≥VGPR prior to autoHCT, those with CPC + autografts had inferior PFS (HR 4.21, p = 0.006) and OS (HR 7.04, p = 0.002) compared to CPC-. In multivariable analysis, the degree of CPC positivity in the autograft was independently predictive of worse PFS (HR 1.50, p = 0.001) and OS (HR 1.37, p = 0.001). In conclusion, both the presence and degree of CPC in the autograft were highly predictive of inferior PFS and OS.

Effect Of Comorbidities And Choice Of Treatment On Overall Survival In Elderly Patients With Acute Myeloid Leukemia: A Beaumont Experience, Bilal M. Ali, Emma Herrman, James Huang Huang, Mohammad Muhsin Chisti

Posters

First line therapy for Acute Myeloid Leukemia (AML) is 7+3 regimen. It often cannot be used in elderly patients due to intensity. Venetoclax + hypomethylating agent (HMA) is approved for AML treatment in these patients. We investigate the efficacy of this treatment in a community setting where patients do not have the same resources available to them as a large academic center. Primary outcome was survival of patients greater than 60 years of age with a diagnosis of AML who received 7+3 therapy versus those who received venetoclax + HMA. Secondary outcomes included characteristics of those who received the two …

Impact Of Lyophilization On Porcine Hemoglobin Properties., Mustafa Almosawi

College of Arts & Sciences Senior Theses

Blood transfusion is the single most often performed lifesaving procedure in hospitals worldwide. Unfortunately, packed red blood cells (RBCs) used for transfusion can only be stored for 42 days at 4 °C before being discarded due to irreversible damage that occurs during storage. Any reduction in available RBCs for an extended period can lead to blood shortages. To increase the shelf-life of RBCs, we investigated freeze-drying (lyophilizing) in the presence of the non-toxic sugar trehalose as a method for long-term preservation. However, the oxidative stress of the lyophilization and storage processes can compromise the functionality of these cells, and the …

Outcomes Of Da R-Epoch Versus R-Chop In Treating Patients Diagnosed With Double-Expressor Lymphoma, Phat Duong, Ishmael Jaiyesimi

Posters

Double-expressor lymphoma (DEL) is a subtype of Diffuse Large B-cell lymphoma (DLBCL) that is associated with poor prognosis. The standard treatment for DLBCL is rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). It is hypothesized that the aggressive nature of DEL deserves a more intense regimen such as dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin plus rituximab (DA-R-EPOCH). A comparison of outcomes between those two treatments is needed to guide clinical decisions.

Demographics And Survival In Aml Patients Over 60 Years Of Age. A Single Institutional Analysi, Damilola Gbadebo, Nwabundo Anusim, Ishmael Jaiyesimi

Posters

Acute Myeloid Leukemia (AML) is a malignancy of the myeloid cell line. Patients diagnosed with AML, typically exhibit symptoms of neutropenia, anemia and thrombocytopenia. The diagnosis of AML is based on greater than 20 percent of myeloid cells in the bone marrow (1). Some risk factors for acquiring the disease include, but not limited to age, sex, smoking, exposure to certain chemicals, radiation, genetic predisposition and being treated with certain chemotherapeutic agents (2).
AML is frequently diagnosed among people between ages 65-74, with a current relative survival rate for AML being 28.7%. Men account for majority of these cases, at …

Dna Methylation Analysis Is Used To Identify Novel Genetic Loci Associated With Circulating Fibrinogen Levels In Blood, Julie Hahn, Jan Bressler, Arce Domingo-Relloso, Ming-Huei Chen, Daniel L Mccartney, Alexander Teumer, Jenny Van Dongen, Marcus E Kleber, Dylan Aïssi, Brenton R Swenson, Jie Yao, Wei Zhao, Jian Huang, Yujing Xia, Michael R Brown, Ricardo Costeira, Eco J C De Geus, Graciela E Delgado, Dre'von A Dobson, Paul Elliott, Hans J Grabe, Xiuqing Guo, Sarah E Harris, Jennifer E Huffman, Sharon L R Kardia, Yongmei Liu, Stefan Lorkowski, Riccardo E Marioni, Matthias Nauck, Scott M Ratliff, Maria Sabater-Lleal, Tim D Spector, Pierre Suchon, Kent D Taylor, Florian Thibord, David-Alexandre Trégouët, Kerri L Wiggins, Gonneke Willemsen, Jordana T Bell, Dorret I Boomsma, Shelley A Cole, Simon R Cox, Abbas Dehghan, Andreas Greinacher, Karin Haack, Winfried März, Pierre-Emmanuel Morange, Jerome I Rotter, Nona Sotoodehnia, Maria Tellez-Plaza, Ana Navas-Acien, Jennifer A Smith, Andrew D Johnson, Myriam Fornage, Nicholas L Smith, Alisa S Wolberg, Alanna C Morrison, Paul S De Vries

Faculty, Staff and Student Publications

Background:

Fibrinogen plays an essential role in blood coagulation and inflammation. Circulating fibrinogen levels may be determined by inter-individual differences in DNA methylation at CpG sites, and vice versa.

Methods:

We performed an epigenome-wide association study (EWAS) of circulating fibrinogen levels in 18,037 White, Black, American Indian, and Hispanic participants representing 14 studies from the CHARGE consortium. Circulating leukocyte DNA methylation was measured in 12,904 participants using the Illumina 450K array, and in 5,133 participants using the EPIC array. Each study performed an EWAS of fibrinogen using linear mixed models adjusted for potential confounders. Study-specific results were combined using array-specific …

Mastro I: Meta-Analysis And Systematic Review Of Thrombectomy Stent Retriever Outcomes: Comparing Functional, Safety And Recanalization Outcomes Between Embotrap, Solitaire And Trevo In Acute Ischemic Stroke, Osama O Zaidat, Shelly Ikeme, Sunil A Sheth, Shinichi Yoshimura, Xin-Guang Yang, Waleed Brinjikji, David F Kallmes, Patrick Brouwer, John Pederson, Ranita Tarchand, Annie Steffenson, Kevin M Kallmes, Jillienne Touchette, Tommy Andersson

Faculty, Staff and Student Publications

Aims:

Stent-retriever (SR) thrombectomy has demonstrated superior outcomes in patients with acute ischemic stroke compared with medical management alone, but differences among SRs remain unexplored. We conducted a Systematic Review/Meta-Analysis to compare outcomes between three SRs: EmboTrap^®, Solitaire™, and Trevo^®.

Methods:

We conducted a PRISMA-compliant Systematic Review among English-language studies published after 2014 in PubMed/MEDLINE that reported SRs in ≥25 patients. Functional and safety outcomes included 90-day modified Rankin scale (mRS 0-2), mortality, symptomatic intracranial hemorrhage (sICH), and embolization to new territory (ENT). Recanalization outcomes included modified thrombolysis in cerebral infarction (mTICI) and first-pass recanalization (FPR). …

Development And Validation Of A Patient-Reported Outcome Measure To Assess Symptom Burden After Chimeric Antigen Receptor T-Cell Therapy, Xin Shelley Wang, Samer A Srour, Tito Mendoza, Meagan Whisenant, Ishwaria Subbiah, Elizabeth Gonzalez, Mona Kamal, Shu-En Shen, Charles Cleeland, Partow Kebriaei, Katayoun Rezvani, Sattva Neelapu, Sairah Ahmed, Elizabeth Shpall

Faculty, Staff and Student Publications

This cross-sectional study aimed to develop and validate a patient-reported outcomes (PROs) assessment tool to assess symptom burden and daily functioning in patients after chimeric antigen receptor (CAR) T-cell therapy, the MD Anderson Symptom Inventory (MDASI-CAR). The items were generated based on literature review, content elicitation interviews with patients, and clinician's review. The patients completed the MDASI core and module, single-item quality-of-life (QoL) measure and Patient-Reported Outcomes Measurement Information System-29 (PROMIS-29). The psychometric validation analysis was based on the acceptability after item reduction process. The final 10 MDASI-CAR module items included tremors, fever/chills, headache, balance, dizziness, attention, difficulty speaking, coughing, …

Rapid Hepatomegaly From Ruxolitinib Discontinuation Syndrome, Ryan Jansen Van Rensburg, Shayna Hale, Anna Calara, Kulveer Dabb, Uday Dandamudi, Parth Desai

HCA Healthcare Journal of Medicine

Introduction

Ruxolitinib (RUX) is a Food and Drug Administration-approved Janus Kinase (JAK) inhibitor shown to be effective in improving hypercatabolic symptoms and splenomegaly in patients with myelofibrosis (MF). RUX therapy provides symptomatic benefits for MF patients but is often discontinued for various reasons including worsening cytopenias. Ruxolitinib Discontinuation Syndrome (RDS) involves an acute cytokine-storm rebound phenomenon that can manifest as an acute relapse of symptoms, worsening splenomegaly, respiratory distress, systemic inflammatory response syndrome, or disseminated intravascular coagulopathy.

Case Presentation

We present the case of a patient with JAK2-positive post-polycythemia vera MF, whose RUX therapy was discontinued due to an active …

Anti-Factor Xa Level Monitoring For Enoxaparin Prophylaxis And Treatment In High-Risk Patient Groups, Lucie Sikes, Kipson Charles, Abigail Antigua, Rima Patel, Selina Imboywa, Pheba Cherian

HCA Healthcare Journal of Medicine

Monitoring anti-factor Xa levels is a controversial topic in the inpatient setting due to resource utilization and unclear conditional guideline recommendations regarding this practice. Enoxaparin dosing in certain high-risk patient populations such as those with low body weight, obesity, renal insufficiency, and pregnancy has not been determined. The objective of this review was to assess the safety and efficacy of enoxaparin monitoring via anti-factor Xa levels in high-risk patient populations.

The PubMed database was searched for articles related to low-molecular-weight heparin monitoring. Randomized controlled trials and meta-analyses that evaluated the safety and efficacy of enoxaparin prophylaxis and treatment in patients …

Blastic Plasmacytoid Dendritic Cell Neoplasm, Jacquelyn Medina, Adam Chahine, Courtney Bernett, Karthik Krishnamurthy

South Atlantic Division GME Research Day 2023

No abstract provided.

Kindlin-3 Deficiency Leads To Impaired Erythropoiesis And Erythrocyte Cytoskeleton, Chloe Turpin, Utku Goreke, Utku Goreke, Katarzyna Bialkowska, Kamila M. Bledzka, Dmitriy Verbovetskiy, Umut A. Gurkan, Jun Qin, Edward F. Plow, Elzbieta Pluskota

Faculty Scholarship

Kindlin-3 (K3) is critical for the activation of integrin adhesion receptors in hematopoietic cells. In humans and mice, K3 deficiency is associated with impaired immunity and bone development, bleeding, and aberrant erythrocyte shape. To delineate how K3 deficiency (K3KO) contributes to anemia and misshaped erythrocytes, mice deficient in erythroid (K3KO\EpoR-cre) or myeloid cell K3 (K3KO\Lyz2cre), knockin mice expressing mutant K3 (Q597W598 to AA) with reduced integrin-activation function (K3KI), and control wild-type (WT) K3 mice were studied. Both K3-deficient strains and K3KI mice showed anemia at baseline, reduced response to erythropoietin stimulation, and compromised recovery after phenylhydrazine (PHZ)-induced hemolytic anemia as …