Hematology Commons^™

Dose-Dense Mini-Hyper-Cvd, Inotuzumab Ozogamicin And Blinatumomab Achieves Rapid Mrd-Negativity In Philadelphia Chromosome-Negative B-Cell Acute Lymphoblastic Leukemia, Nicholas J Short, Elias Jabbour, Trevor Jamison, Shilpa Paul, Branko Cuglievan, David Mccall, Amber Gibson, Nitin Jain, Fadi G Haddad, Lewis F Nasr, Kayleigh R Marx, Caitlin Rausch, J Michael Savoy, Rebecca Garris, Farhad Ravandi, Hagop Kantarjian

Faculty, Staff and Student Publications

Background: The combination of low-intensity chemotherapy and inotuzumab ozogamicin (INO), with sequential blinatumomab, is highly effective in older adults with newly diagnosed B-cell acute lymphoblastic leukemia (ALL) and in relapsed or refractory B-cell ALL. Earlier, "dose-dense" administration of blinatumomab could lead to earlier and deeper measurable residual disease (MRD) responses and better outcomes.

Patients and methods: We performed a retrospective analysis of the safety and efficacy of a dose-dense regimen of mini-hyper-CVD (mini-hyperfractionated cyclophosphamide, vincristine, and dexamethasone alternating with mini-methotrexate and cytarabine), INO, and blinatumomab in patients with B-cell ALL.

Results: Twenty-one patients were treated (frontline, n = 9; MRD …

Reduced Dose Azacitidine Plus Venetoclax As Maintenance Therapy In Acute Myeloid Leukaemia Following Intensive Or Low-Intensity Induction: A Single-Centre, Single-Arm, Phase 2 Trial, Alexandre Bazinet, Hagop Kantarjian, Alex Bataller, Naveen Pemmaraju, Gautam Borthakur, Kelly Chien, Yesid Alvarado, Prithviraj Bose, Elias Jabbour, Musa Yilmaz, Courtney Dinardo, Ghayas Issa, Guillermo Montalban-Bravo, Nicholas Short, Koji Sasaki, Debra Bull-Linderman, Naval Daver, Guillermo Garcia-Manero, Farhad Ravandi, Tapan Kadia

Faculty, Staff and Student Publications

Background: Patients with acute myeloid leukaemia have high rates of relapse, especially if they are unable to complete standard consolidation strategies or allogeneic haematopoietic stem-cell transplantation (HSCT). The phase 3 QUAZAR AML-001 study showed an overall survival benefit with oral azacitidine maintenance. The BCL2 inhibitor venetoclax is highly active in acute myeloid leukaemia and synergistic with azacitidine. We aimed to evaluate the efficacy and safety of low dose azacitidine plus venetoclax as maintenance therapy in acute myeloid leukaemia.

Methods: We performed a single-centre, single-arm, phase 2 study at the University of Texas MD Anderson Cancer Center in the USA. Eligible …

The Remission Status Of Aml Patients After Allo-Hct Is Associated With A Distinct Single-Cell Bone Marrow T-Cell Signature, Anna Mathioudaki, Xizhe Wang, David Sedloev, Richard Huth, Aryan Kamal, Michael Hundemer, Yi Liu, Spyridoula Vasileiou, Premal Lulla, Carsten Müller-Tidow, Peter Dreger, Thomas Luft, Tim Sauer, Michael Schmitt, Judith B Zaugg, Caroline Pabst

Faculty, Staff and Students Publications

Acute myeloid leukemia (AML) is a hematologic malignancy for which allogeneic hematopoietic cell transplantation (allo-HCT) often remains the only curative therapeutic approach. However, incapability of T cells to recognize and eliminate residual leukemia stem cells might lead to an insufficient graft-versus-leukemia (GVL) effect and relapse. Here, we performed single-cell RNA-sequencing (scRNA-seq) on bone marrow (BM) T lymphocytes and CD34+ cells of 6 patients with AML 100 days after allo-HCT to identify T-cell signatures associated with either imminent relapse (REL) or durable complete remission (CR). We observed a higher frequency of cytotoxic CD8+ effector and gamma delta (γδ) T cells in …

Hematopoietic Stem Cells With Granulo-Monocytic Differentiation State Overcome Venetoclax Sensitivity In Patients With Myelodysplastic Syndromes, Juan Jose Rodriguez-Sevilla, Irene Ganan-Gomez, Feiyang Ma, Kelly Chien, Monica Del Rey, Sanam Loghavi, Guillermo Montalban-Bravo, Vera Adema, Bethany Wildeman, Rashmi Kanagal-Shamanna, Alexandre Bazinet, Helen T Chifotides, Natthakan Thongon, Xavier Calvo, Jesús María Hernández-Rivas, Maria Díez-Campelo, Guillermo Garcia-Manero, Simona Colla

Faculty, Staff and Student Publications

The molecular mechanisms of venetoclax-based therapy failure in patients with acute myeloid leukemia were recently clarified, but the mechanisms by which patients with myelodysplastic syndromes (MDS) acquire secondary resistance to venetoclax after an initial response remain to be elucidated. Here, we show an expansion of MDS hematopoietic stem cells (HSCs) with a granulo-monocytic-biased transcriptional differentiation state in MDS patients who initially responded to venetoclax but eventually relapsed. While MDS HSCs in an undifferentiated cellular state are sensitive to venetoclax treatment, differentiation towards a granulo-monocytic-biased transcriptional state, through the acquisition or expansion of clones with STAG2 or RUNX1 mutations, affects HSCs' …

Most Recent Advances And Applications Of Extracellular Vesicles In Tackling Neurological Challenges, Mandeep Kaur, Salvatore Fusco, Bram Van Den Broek, Jaya Aseervatham, Abdolmohamad Rostami, Lorraine Iacovitti, Claudio Grassi, Barbara Lukomska, Amit K. Srivastava

Cardeza Foundation for Hematologic Research

Over the past few decades, there has been a notable increase in the global burden of central nervous system (CNS) diseases. Despite advances in technology and therapeutic options, neurological and neurodegenerative disorders persist as significant challenges in treatment and cure. Recently, there has been a remarkable surge of interest in extracellular vesicles (EVs) as pivotal mediators of intercellular communication. As carriers of molecular cargo, EVs demonstrate the ability to traverse the blood-brain barrier, enabling bidirectional communication. As a result, they have garnered attention as potential biomarkers and therapeutic agents, whether in their natural form or after being engineered for use …

Incidence And Risk Factors Of Early Onset Vod/Sos Differ In Younger Vs Older Adults After Stem Cell Transplantation, Curtis Marcoux, Rima M Saliba, Whitney Wallis, Sajad Khazal, Dristhi Ragoonanan, Gabriela Rondon, Priti Tewari, Uday Popat, Betul Oran, Amanda Olson, Qaiser Bashir, Muzaffar Qazilbash, Amin Alousi, Chitra Hosing, Yago Nieto, Gheath Alatrash, David Marin, Katayoun Rezvani, Issa Khouri, Samer Srour, Richard Champlin, Elizabeth Shpall, Partow Kebriaei

Faculty, Staff and Student Publications

Veno-occlusive disease (VOD) is a rare but potentially life-threatening complication after allogeneic hematopoietic stem cell transplantation (allo-SCT). Although increasing awareness and modern transplant techniques have mitigated risk, the interaction of historic risk factors in the current era with posttransplant cyclophosphamide (PTCy) is unknown. We performed a retrospective single-center analysis of adult patients aged ≥18 years undergoing allo-SCT (N = 1561) using predominately PTCy as graft-versus-host disease (GVHD) prophylaxis (72%). We found a higher rate of VOD at 16.8% (20 of 119) in those aged ≤25 years compared with 3.8% (55 of 1442) in those aged >25 years, with unique predictors …

Health Care Costs Among Patients With Hematologic Malignancies Receiving Allogeneic Transplants: A Us Payer Perspective, Richard Maziarz, Usama Gergis, Marie Louise Edwards, Yan Song, Qing Liu, Annika Anderson, James Signorovitch, Rocio Manghani, Ronit Simantov, Heayoung Shin, Smitha Sivaraman

Department of Medical Oncology Faculty Papers

Patients with hematologic malignancies undergoing allogeneic hematopoietic cell transplant (allo-HCT) require extensive care. Using the Merative MarketScan Commercial Claims and Encounters database (2016 Q1-2020 Q2), we quantified the costs of care and assessed real-world complication rates among commercially insured US patients diagnosed with a hematologic malignancy and aged between 12 and 64 years undergoing inpatient allo-HCT. Health care resource use and costs were assessed from 100 days before HCT to 100 days after HCT. Primary hospitalization was defined as the time from HCT until first discharge date. Incidence of complications was assessed using medical billing codes from HCT date to …

Case Of Rosai Dorfman Disease In A Patient With Newly Diagnosed Hodgkin Lymphoma, Liza Salloum, Jennifer Rojas Huen, Ricardo Serna, Alisha Valdez

Research Symposium

Background: Rosai Dorfman Disease (RDD, also known as sinus histiocytosis with massive lymphadenopathy) is a rare non-Langerhans cell histiocytosis, classified into nodal (classic) and extranodal disease. Most patients present with non-tender cervical lymphadenopathy, although other sites including the inguinal and axillary regions have been reported. Extranodal disease (~43% of cases) can involve any organ system. RDD is more common in children, but cases have been reported in patients in their 70s. The prognosis of nodal RDD can correlate with the number of nodal groups involved. Many cases can be managed only with observation, although surgery, chemotherapy, corticosteroids, and immunomodulators have …

A True Bloody Emergency: An Unusual Case Of Thrombotic Thrombocytopenic Purpura, Joshua M. Ninan

Research Symposium

Background: Thrombotic thrombocytopenic purpura (TTP) is a primary thrombotic microangiopathy that is classically characterized by thrombocytopenia and microangiopathic hemolytic anemia (MAHA). Although rare with an annual incidence of 3.7 cases per one million adults, it is considered a true hematological emergency due to its fatality rate of almost 100% if appropriate treatment is not initiated immediately. This makes it vitally important to identify and treat patients with TTP, a task that becomes unusually challenging in the absence of the disorder’s other characteristically diagnostic clinical features such as mucosal bleeding, fever, or presence of schistocytes.

Case Presentation: A 30-year-old gentleman with …

The Development Of 2 Clonally And Histologically Distinct Subtypes Of Extranodal B-Cell Lymphomas In The Brain And Skin In 1 Individual, Daniel Joffe, Thomas Z. Rohan, Jenna Mandel, Jayson Suriano, Lauren Banner, Alexander Valiga, Pierluigi Porcu, Jerald Z. Gong, Jason B. Lee, Onder Alpdogan, Neda Nikbakht

Department of Dermatology and Cutaneous Biology Faculty Papers

No abstract provided.

The Utility Of Interventional Anesthesia, Kylie Daguio, Kiley Jackson, Samantha Boever, Andrew Chang, James Keane, Leonard B. Goldstein

SOMA Faculty Publications

no abstract

The Lymphoma Epidemiology Of Outcomes Cohort Study: Design, Baseline Characteristics, And Early Outcomes, James R Cerhan, Matthew J Maurer, Brian K Link, Andrew L Feldman, Thomas M Habermann, David L Jaye, W Richard Burack, Timothy J Mcdonnell, Francisco Vega, Jennifer R Chapman, Sergei Syrbu, Kiran R Vij, Giorgio Inghirami, John P Leonard, Leon Bernal-Mizrachi, Umar Farooq, Thomas E Witzig, George J Weiner, Yucai Wang, Juan P Alderuccio, Susan L Slager, Melissa C Larson, Shaun M Riska, Brianna J Gysbers, Julianne J Lunde, Tanner W Reicks, Amy A Ayers, Colin B O'Leary, Kathleen J Yost, Hongfang Liu, Grzegorz S Nowakowski, Jia Ruan, Dai Chihara, Jean L Koff, Carla Casulo, Carrie A Thompson, Jonathon B Cohen, Brad S Kahl, Loretta J Nastoupil, Izidore S Lossos, Jonathan W Friedberg, Peter Martin, Christopher R Flowers

Faculty, Staff and Student Publications

To address the current and long-term unmet health needs of the growing population of non-Hodgkin lymphoma (NHL) patients, we established the Lymphoma Epidemiology of Outcomes (LEO) cohort study (NCT02736357; https://leocohort.org/). A total of 7735 newly diagnosed patients aged 18 years and older with NHL were prospectively enrolled from 7/1/2015 to 5/31/2020 at 8 academic centers in the United States. The median age at diagnosis was 62 years (range, 18-99). Participants came from 49 US states and included 538 Black/African-Americans (AA), 822 Hispanics (regardless of race), 3386 women, 716 age <40 >years, and 1513 rural residents. At study baseline, we abstracted clinical, …

Safety, Efficacy And Determinants Of Response Of Allogeneic Cd19-Specific Car-Nk Cells In Cd19+ B Cell Tumors: A Phase 1/2 Trial, David Marin, Ye Li, Rafet Basar, Hind Rafei, May Daher, Jinzhuang Dou, Vakul Mohanty, Merve Dede, Yago Nieto, Nadima Uprety, Sunil Acharya, Enli Liu, Jeffrey Wilson, Pinaki Banerjee, Homer A Macapinlac, Christina Ganesh, Peter F Thall, Roland Bassett, Mariam Ammari, Sheetal Rao, Kai Cao, Mayra Shanley, Mecit Kaplan, Chitra Hosing, Partow Kebriaei, Loretta J Nastoupil, Christopher R Flowers, Sadie Mae Moseley, Paul Lin, Sonny Ang, Uday R Popat, Muzaffar H Qazilbash, Richard E Champlin, Ken Chen, Elizabeth J Shpall, Katayoun Rezvani

Faculty, Staff and Student Publications

There is a pressing need for allogeneic chimeric antigen receptor (CAR)-immune cell therapies that are safe, effective and affordable. We conducted a phase 1/2 trial of cord blood-derived natural killer (NK) cells expressing anti-CD19 chimeric antigen receptor and interleukin-15 (CAR19/IL-15) in 37 patients with CD19+ B cell malignancies. The primary objectives were safety and efficacy, defined as day 30 overall response (OR). Secondary objectives included day 100 response, progression-free survival, overall survival and CAR19/IL-15 NK cell persistence. No notable toxicities such as cytokine release syndrome, neurotoxicity or graft-versus-host disease were observed. The day 30 and day 100 OR rates were …

Impact Of Electronic Cigarettes On Pediatric, Adolescent And Young Adult Leukemia Patients, Sanila Sarkar, Lea M Stitzlein, Joya Chandra

Faculty, Staff and Student Publications

Electronic cigarettes, which deliver an aerosolized, nicotine-containing product upon inhalation, are a public health issue that continue to gain popularity among adolescents and young adults in the United States. Use of electronic cigarettes is wide, and extends to pediatric patients with multiple comorbidities, including childhood cancer, leaving them vulnerable to further negative health outcomes. Acute leukemias are the most common type of cancer in pediatric populations, and treatment outcomes for these patients are improving; consequently, there is an increased emphasis on the effect of behavioral lifestyle factors on quality of life in survivorship. The rate of electronic cigarette use is …

A Phase 1/2 Study Of Mini-Hyper-Cvd Plus Venetoclax In Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia, Nicholas J Short, Elias Jabbour, Nitin Jain, Jayastu Senapati, Lewis Nasr, Fadi G Haddad, Zhenhua Li, Yu-Chih Hsiao, Jun J Yang, Naveen Pemmaraju, Maro Ohanian, William G Wierda, Guillermo Montalban-Bravo, Gautam Borthakur, Lina Han, Lianchun Xiao, Xuelin Huang, Regina Abramova, Min Zhao, Rebecca Garris, Marina Konopleva, Farhad Ravandi, Hagop Kantarjian

Faculty, Staff and Student Publications

Preclinical studies suggest that Bcl-2 inhibition with venetoclax has antileukemic activity in acute lymphoblastic leukemia (ALL) and may synergize with conventional chemotherapy. We designed a phase 1/2 clinical trial to evaluate the safety and efficacy of low-intensity chemotherapy in combination with venetoclax in adults with relapsed or refractory ALL. Patients received the mini-hyper-CVD regimen (dose-attenuated hyperfractionated cyclophosphamide, vincristine, and dexamethasone alternating with methotrexate and cytarabine) in combination with venetoclax (200 mg or 400 mg daily) on days 1 to 14 in cycle 1 and on days 1 to 7 in consolidation cycles. Twenty-two patients were treated. The median number of …

Gamma Delta T Cells In Acute Myeloid Leukemia: Biology And Emerging Therapeutic Strategies, Adishwar Rao, Akriti Agrawal, Gautam Borthakur, Venkata Lokesh Battula, Abhishek Maiti

Faculty, Staff and Student Publications

γδ T cells play an important role in disease control in acute myeloid leukemia (AML) and have become an emerging area of therapeutic interest. These cells represent a minor population of T lymphocytes with intrinsic abilities to recognize antigens in a major histocompatibility complex-independent manner and functionally straddle the innate and adaptive immunity interface. AML shows high expression of phosphoantigens and UL-16 binding proteins that activate the Vδ2 and Vδ1 subtypes of γδ T cells, respectively, leading to γδ T cell-mediated cytotoxicity. Insights from murine models and clinical data in humans show improved overall survival, leukemia-free survival, reduced risk of …

Distinguishing Leukemic Cells Using Fractal Chromatin Patterns And Machine Learning, Abigail Gordhamer, Paul Young, Ryan Cordner

Annual Research Symposium

One of the most important tests in the clinical laboratory is the Complete Blood Count, which involves identifying the white blood cells in a patient’s blood. The respective counts of the different white blood cell types correlate with various states of health and disease, and are critical to diagnosing diseases such as leukemia. Leukemic cells are considered especially difficult to distinguish, and it is of the upmost importance that these cells are identified correctly. To aid in the process of leukemic cell identification, we quantified fractal patterns in the chromatin of white blood cells and used the data to identify …

Chromatin Pattern Quantification For The Differentiation Of White Blood Cells, Paul Young, Ryan Cordner, Abigail Gordhamer

Annual Research Symposium

Nuclear chromatin patterns have been used historically to distinguish between different developmental stages and lineages of white blood cells. While it is common to characterize cells based on arbitrary ‘open’ or ‘closed’ chromatin patterns, quantification of chromatin data is lacking. By extracting nuclei from a database of white blood cells and running fractal analyses using TWOMBLI, we were able to produce meaningful data quantifying chromatin patterns. Our data were put through a random forest algorithm which grouped each point based on relationship probability. The algorithm compared immature and mature cell types as well as cells of similar maturity and differing …

Pain Screening In Youth With Sickle Cell Disease: A Quality Improvement Study, Dennis C. Vroom, Samuel N. Rodgers-Melnick, Amma Owusu-Ansah, Jeffery A. Dusek

Student Scholarship

Background: Youth with sickle cell disease (SCD) face several challenges as they age, including increased pain frequency, duration, and interference. The purpose of this study was to (i) determine the feasibility of routine pain screening; (ii) identify and describe various clinical pain presentations; and (iii) understand preferences/resources related to engaging in integrative health and medicine (IHM) modalities within an outpatient pediatric SCD clinic. Methods: During routine outpatient visits, patients aged 8–18 completed measures of pain frequency, duration, and chronic pain risk (Pediatric Pain Screening Tool [PPST]). Participants screening positive for (i) persistent or chronic pain or (ii) medium or high …

Most Deprived Louisiana Census Tracts Have Higher Hepatocellular Carcinoma Incidence And Worse Survival, Kendra L. Ratnapradipa, Tingting Li, Mei Chin Hsieh, Laura Tenner, Edward S. Peters

School of Public Health Faculty Publications

Background: Liver cancer incidence increased in the US from 1975 through 2015 with heterogeneous rates across subpopulations. Upstream or distal area-level factors impact liver cancer risks. Objective: The aim of this study was to examine the association between area-level deprivation and hepatocellular carcinoma (HCC) incidence and survival. We also explored the association between area deprivation and treatment modalities. Methods: Louisiana Tumor Registry identified 4,151 adult patients diagnosed with malignant HCC from 2011 to 2020 and linked residential address to census tract (CT)-level Area Deprivation Index (ADI) categorized into quartiles (Q1 = least deprived). ANOVA examined the association between ADI quartile …