Hematology Commons^™

Factors Associated With Pre-Donation Health-Related Quality-Of-Life Among Pediatric Sibling Hematopoietic Cell Donors: A Donorkids Ql Study., Galen E. Switzer, Jessica G. Bruce, Bronwen E. Shaw, Vidya Kuniyil, James W. Varni, Brandan J. Butler, Connor Erickson, Alisha Mussetter, Allison Neutzling, Hisham Abdel-Azim, Paibel Aguayo-Hiraldo, Eric J. Anderson, Victor M. Aquino, Karlie Boone, Farid Boulad, Joseph H. Chewning, Jessica Cooper, Ann Dahlberg, Christopher C. Dvorak, Jorge Galvez-Silva, Ann E. Haight, Jennifer A. Hoag, Michelle Hudspeth, David Jacobsohn, Kimberly A. Kasow, Carrie L. Kitko, Lakshmanan Krishnamurti, Lisa Madden, Holly K. Miller, Erin Morales, Timothy S. Olson, Anna B. Pawlowska, Vinod K. Prasad, Troy C. Quigg, Andromachi Scaradavou, Niketa C. Shah, Shalini Shenoy, Nancy Terwilliger, Lori Wiener, Gregory A. Yanik, Lolie C. Yu, Michael A. Pulsipher

Manuscripts, Articles, Book Chapters and Other Papers

Due to limited published data assessing pediatric hematopoietic cell donor experiences, we previously conducted one of the largest quantitative investigations of pediatric donor experiences and health-related quality-of-life (HRQoL) at the time (RDSafe). Findings from RDSafe demonstrated that a subset of pediatric HC donors experienced very poor HRQoL; unfortunately, that dataset addressed only a limited number of factors, and key associations explaining this poor HRQoL were not found. In this study, our goal was to address that deficit by describing pre-donation donor HRQoL in detail and identifying factors across five key domains that were associated with donor HRQoL. We conducted a …

High Concordance Of Physician-Attestation With Manual Data Abstraction For Sickle Cell Type: An Ash Rc Data Hub Study, Alexis Thompson, Ashima Singh, Donna Neuberg, Amanda Brandow, Allison King, Sophie Lanzkron, Emily Semmel, Sam Walters, Susan Rogers, Kathleen Torres, William Wood

Cardeza Foundation for Hematologic Research

Sickle cell disease (SCD) is the most common inherited blood disorder in the United States. The American Society of Hematology Research Collaborative (ASH RC) has built an SCD Data Hub (DH) to facilitate research and quality improvement using real-world data. To our knowledge, we report here the first analyses from the DH, focusing on cohort demographics and accurate identification of SCD diagnosis type. DH sites have data use agreements with ASH RC to extract and transfer electronic health record (EHR) data at least quarterly. Principal investigators (PI) provided additional attestation of SCD diagnosis based on existing local data sources deemed …

Trends In Hypertension Prevalance And Control In The United States Over 25 Years, Omar Saleh, Neda Rehan, Saleh Mostafa, Rehan Qayyum

Department of Medicine Faculty Publications

Despite sustained public health efforts, hypertension remains highly prevalent in the United States, with persistent disparities across demographic and socioeconomic groups. We examined 25-year trends in hypertension prevalence, undiagnosed hypertension, and on-treatment uncontrolled hypertension in the United States using nationally representative National Health and Nutrition Examination Survey (NHANES) data from adults aged ≥18 years. Hypertension was defined as systolic BP ≥130 mmHg, diastolic BP ≥80 mmHg, or current antihypertensive use. Undiagnosed hypertension was defined as elevated BP without prior diagnosis or treatment, while on-treatment uncontrolled hypertension was defined as diagnosed hypertension with BP ≥130/80 mmHg despite treatment. Survey-weighted generalized linear …

National Alliance Of Sickle Cell Centers Consensus Recommendations On Sickle Cell Disease Health Maintenance: A Consensus Statement, Seethal A. Jacob, Melissa Frei-Jones, Sana Saif-Ur-Rehman, Monica L. Hulbert, Andrew R. W. O'Brien, Crawford Strunk, Anthony Villella, Ravi Talati, Amma Owusu-Ansah, Francis Coyne, Patrick T. Mcgann, Parul Rai, Robin Miller, Angeli Rampersad, Vishwas Sakhalkar, Neha Bhasin, Deepa Manwani, Sophie Lanzkron, Julie Kanter

Cardeza Foundation for Hematologic Research

IMPORTANCE: The most common inherited blood disorder in the world, sickle cell disease (SCD) is a known global health concern. While survival of children into adulthood has improved significantly over the last few decades in high-resource countries, substantial gaps in care standards and limited practice harmonization persist.

OBJECTIVE: To provide up-to-date recommendations for preventive care and treatment of all people living with SCD and its related comorbidities.

EVIDENCE REVIEW: As part of the National Alliance of Sickle Cell Centers (NASCC), 41 pediatric and adult sickle cell disease experts developed consensus standards and recommendations based on available evidence and expert consensus …

Outcomes Of Patients With Newly Diagnosed Acute Myeloid Leukemia With Flt3-Tyrosine Kinase Domain Mutations: Prognostic Implications Of Npm1 Co-Mutation, Sankalp Arora, Wei-Ying Jen, Musa Yilmaz, Indraneel Deshmukh, Jayastu Senapati, Sanam Loghavi, Ghayas C Issa, Nicholas J Short, Tapan M Kadia, Courtney D Dinardo, Gautam Borthakur, Joseph Jabbour, Naveen Pemmaraju, Michael Andreeff, Koichi Takahashi, Kapil Bhalla, Uday Popat, Elizabeth J Shpall, Betul Oran, Hussein A Abbas, Guillermo Garcia-Manero, Farhad Ravandi, Hagop Kantarjian, Naval Daver

Faculty, Staff and Student Publications

Background: The prognostic impact of Fms-like tyrosine kinase 3 (FLT3)-tyrosine kinase domain (TKD) mutation in patients with acute myeloid leukemia (AML) is not well defined. The authors described outcomes of one of the largest cohorts of patients with FLT3-TKD mutated (FLT3-TKDmut) AML to date.

Methods: This retrospective study included patients with newly diagnosed AML who received frontline treatment at The University of Texas MD Anderson Cancer Center from January 2012 to March 2024 divided into two cohorts: FLT3-TKDmut AML and nucleophosmin-mutated (NPM1mut)/FLT3-TKD wild-type (FLT3-TKDwt) AML. Patients with FLT3 internal tandem duplication mutations were excluded.

Results: In total, 2922 patients were …

Risk Of Early Death After Acute Leukemia Diagnosis Among Adolescents And Young Adults, Amy M Berkman, Clark R Andersen, Vidya Puthenpura, Nicholas J Short, Kelly Merriman, Mahesh Swaminathan, Branko Cuglievan, David Mccall, Courtney Dinardo, Cesar Nunez, Nitin Jain, Tapan Kadia, Ghayas Issa, Amber Gibson, Miriam B Garcia, J Andrew Livingston, Susan Parsons, Michelle A T Hildebrandt, Michael E Roth

Faculty, Staff and Student Publications

Background: Advances in care have led to improvements in survival for adolescents and young adults (AYAs) diagnosed with cancer; however, the risk of early death remains high for certain cancers, particularly acute leukemias. Risk factors for early death in AYAs diagnosed with acute leukemia have not been well studied.

Methods: The Surveillance, Epidemiology, and End Results registry was used to assess risk of early death (within 2 months of diagnosis) in AYAs diagnosed with acute leukemia (n = 16 153). Early death proportion, by year, for AYAs diagnosed between 2006 and 2020 was described. Associations between incidence of early death …

Long Term Results Of Venetoclax Combined With Flag-Ida Induction And Consolidation For Newly Diagnosed And Relapsed Or Refractory Acute Myeloid Leukemia, Courtney D Dinardo, Wei-Ying Jen, Koichi Takahashi, Tapan M Kadia, Sanam Loghavi, Naval G Daver, Lianchun Xiao, Patrick K Reville, Ghayas C Issa, Nicholas J Short, Koji Sasaki, Sa A Wang, Jillian K Mullin, Sherry Pierce, Corey Bradley, Gautam Borthakur, Abhishek Maiti, Yesid Alvarado, Naveen Pemmaraju, Alessandra Ferrajoli, Mahesh Swaminathan, Maro Ohanian, Hussein A Abbas, Danielle Hammond, Jan Burger, Fadi Haddad, Guillermo Montalban-Bravo, Kelly Chien, Lucia Masarova, Musa Yilmaz, Nitin Jain, Michael Andreeff, Guillermo Garcia-Manero, Steven Kornblau, Farhad Ravandi, Elias Jabbour, Marina Y Konopleva, Hagop M Kantarjian

Faculty, Staff and Student Publications

Intensive chemotherapy remains the standard for newly diagnosed (ND) acute myeloid leukemia (AML); however, relapse risk remains high. Additionally, most patients with relapsed/refractory (RR) AML have poor outcomes. We report the long-term experience of 138 patients, 77 ND and 61 RR, treated with FLAG-IDA in combination with venetoclax. In the ND cohort, the overall response rate (ORR) was 97%, with a composite complete remission (CRc) rate of 95% and undetectable measurable residual disease (MRD) status by flow cytometry in 90%. The 3-year OS and EFS rates were 66 and 64%, respectively. Outcomes were similar across European LeukemiaNet (ELN) 2022 risk …

Impact Of Measurable Residual Disease Clearance Kinetics In Patients With Aml Undergoing Intensive Chemotherapy, Wei-Ying Jen, Koji Sasaki, Farhad Ravandi, Tapan M Kadia, Sa A Wang, Wei Wang, Sanam Loghavi, Naval G Daver, Courtney D Dinardo, Ghayas C Issa, Hussein A Abbas, Cedric Nasnas, Alex Bataller, Samuel Urrutia, Omer S Karrar, Sherry Pierce, Hagop M Kantarjian, Nicholas J Short

Faculty, Staff and Student Publications

The prognostic impact of measurable residual disease (MRD) in acute myeloid leukemia (AML) is unequivocal; however, the optimal time point for achieving undetectable MRD is unclear. We retrospectively studied patients with newly diagnosed (ND) AML who achieved remission with frontline intensive chemotherapy and had MRD assessed by flow cytometry after induction (time point 1 [TP1]) and after cycles 2 or 3 (TP2). Cases were grouped into MRD negative (Neg)/Neg, positive (Pos)/Neg, or Pos/Pos at TP1 and TP2, respectively. Of 1980 patients with ND AML, 277 met the inclusion criteria and were included in this analysis. The median relapse-free survival (RFS) …

High-Grade B-Cell Lymphoma Not Otherwise Specified, With Diffuse Large B-Cell Lymphoma Gene Expression Signatures: Genomic Analysis And Potential Therapeutics, Waseem Lone, Alyssa Bouska, Tyler A Herek, Catalina Amador, Joo Song, Alexander M Xu, Dylan Jochum, Issa Ismail Issa, Dennis D Weisenburger, Xuan Zhang, Sharath Kumar Bhagavathi, Tayla B Heavican-Foral, Sunandini Sharma, Ab Rauf Shah, Abdul Rouf Mir, Aisha Ahmad Alkhinji, Dalia El-Gamal, Bhavana J Dave, Keenan Hartert, Jiayu Yu, Mallick Saumyaranjan, Timothy C Greiner, Julie Vose, Timothy W Mckeithan, Kai Fu, Michael Green, Chengfeng Bi, Akil Merchant, Wing C Chan, Javeed Iqbal

Faculty, Staff and Student Publications

High-grade B-cell lymphoma not otherwise specified (HGBCL, NOS) has overlapping morphological and genetic features with diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL), leading to uncertainty in its diagnosis and clinical management. Using functional genomic approaches, we previously characterized HGBCL and NOS, that demonstrate gene expression profiling (GEP), and genetic signatures similar to BL. Herein, we characterize distinct HGBCL, NOS, cohort (n = 55) in adults (n = 45) and in children (n = 10), and compared the GEP, genomic DNA copy number (CN), and mutational spectrum with de novo DLBCL (n = 85) and BL (n = 52). …

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 …

Eculizumab For Management Of Hyperhemolysis Syndrome In Pediatric Patients With Sickle Cell Disease: A Single-Center Case Series, Ajibike Lapite, Saleh Bhar, Titilope Fasipe

Faculty, Staff and Students Publications

Chronic hemolytic anemia and vascular occlusion are hallmarks of sickle cell disease (SCD). Blood transfusions are critical for supportive and preventive management of SCD complications. Patients with SCD are at risk for hyperhemolysis syndrome (HHS), a subtype of delayed hemolytic transfusion reactions. HHS management includes intravenous immunoglobulin, corticosteroids, and avoidance of further transfusions. Not all patients respond to first-line agents. Eculizumab, which blocks terminal complement activation, has been proposed as second-line management of HHS. We describe two patients who received eculizumab for refractory HHS. In our experience, eculizumab is a safe and effective option for refractory pediatric HHS.

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 …

Recurrent Nontraumatic Subgaleal Hematomas In A Pediatric Patient With Sickle Cell Disease, Irtiza N Sheikh, Olayinka Okeleji, Rabya Afzal, Eliana Bonfante, Monica Kodakandla, Neethu M Menon

Faculty, Staff and Student Publications

Spontaneous subgaleal hematoma in pediatric patients with sickle cell disease (SCD) is a rare occurrence that can present with symptoms mimicking ischemic stroke, a known complication of SCD. However, unlike ischemic stroke, subgaleal hematoma is nonlethal and can be managed conservatively without major sequelae. Here, we present the case of an adolescent with SCD who presented with 2 episodes of subgaleal and epidural hematomas, 2 years apart. The latter episode occurred while on crizanlizumab, an anti-P-selectin antibody, approved for use in SCD in 2019 to reduce the number of acute pain crises. We demonstrate the diagnosis of subgaleal hematoma and …

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 …

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 …

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, …

Prospective Clinical And Biomarker Validation Of The American Society For Transplantation And Cellular Therapy Consensus Definition For Transplantation-Associated Thrombotic Microangiopathy, Shengling Ma, Saleh Bhar, Danielle Guffey, Rock Bum Kim, Mahrukh Jamil, Christopher I Amos, Stephanie J Lee, Sangeeta R Hingorani, Sarah E Sartain, Ang Li

Faculty, Staff and Students Publications

Transplantation-associated thrombotic microangiography (TA-TMA) is a disorder that causes severe complications after allogeneic hematopoietic cell transplantation (allo-HCT). Diagnosing TA-TMA is challenging because of the lack of standardized criteria. In this study, we aimed to evaluate the new TA-TMA consensus definition from the American Society for Transplantation and Cellular Therapy (ASTCT) panel as part of an ongoing prospective pediatric cohort study, and also to compare the impact and outcomes of using the current definition of clinical TMA (cTMA) versus the new consensus definition. We included patients age 0 to 18 years who underwent their first allo-HCT between May 2021 and January …

Pediatric Traumatic Hemorrhagic Shock Consensus Conference Research Priorities, Robert T Russell, Melania M Bembea, Matthew A Borgman, Randall S Burd, Barbara A Gaines, Mubeen Jafri, Cassandra D Josephson, Christine M Leeper, Julie C Leonard, Jennifer A Muszynski, Kathleen K Nicol, Daniel K Nishijima, Paul A Stricker, Adam M Vogel, Trisha E Wong, Philip C Spinella

Faculty, Staff and Students Publications

BACKGROUND: Traumatic injury is the leading cause of death in children and adolescents. Hemorrhagic shock remains a common and preventable cause of death in the pediatric trauma patients. A paucity of high-quality evidence is available to guide specific aspects of hemorrhage control in this population. We sought to identify high-priority research topics for the care of pediatric trauma patients in hemorrhagic shock.

METHODS: A panel of 16 consensus multidisciplinary committee members from the Pediatric Traumatic Hemorrhagic Shock Consensus Conference developed research priorities for addressing knowledge gaps in the care of injured children and adolescents in hemorrhagic shock. These ideas were …

Urgent Cytoreduction For Newly Diagnosed Acute Myeloid Leukemia Patients Allows Acquisition Of Pretreatment Genomic Data And Enrollment On Investigational Clinical Trials, Kunhwa Kim, Marina Konopleva, Courtney D Dinardo, Gautam Borthakur, Sanam Loghavi, Guilin Tang, Naval Daver, Naveen Pemmaraju, Elias Jabbour, Caitlin R Rausch, Musa Yilmaz, Koji Sasaki, Nicholas J Short, Nitin Jain, Mark Brandt, Sherry Pierce, Guillermo Garcia-Manero, Farhad Ravandi, Hagop Kantarjian, Tapan M Kadia

Faculty, Staff and Student Publications

Newly diagnosed acute myeloid leukemia is often deemed a medical emergency, requiring urgent treatment. This is in contradiction with the need for accurate cytogenetic and molecular data, which is not immediately available, to select optimal therapy. We hypothesized that cytoreduction with hydroxyurea or cytarabine would enable urgent disease control and provide a bridge to clinical trial enrollment. We analyzed three prospective frontline clinical trials that allowed the use of cytoreduction before treatment initiation. Among 274 patients with a median age of 62 (range, 18-89), there was no significant difference in short- and long-term outcome and safety among patients who did …

Symptom Clusters, Physical Activity, And Quality Of Life: A Latent Class Analysis Of Children During Maintenance Therapy For Leukemia, Mary C Hooke, Michelle A Mathiason, Audrey Blommer, Jessica Hutter, Pauline Mitby, Olga Taylor, Michael E Scheurer, Alicia S Kunin-Batson, Wei Pan, Marilyn J Hockenberry

Faculty, Staff and Students Publications

BACKGROUND: Children undergoing treatment for acute lymphocytic leukemia (ALL) report co-occurring symptoms of fatigue, sleep disturbances, and depression as a symptom cluster. Physical activity (PA) may influence symptom severity and quality of life (QOL).

OBJECTIVES: This study examined changes in symptoms and QOL during ALL maintenance in children categorized by symptom cluster and explored the influence of PA and symptoms on QOL.

METHODS: Self-report of fatigue, sleep disturbance, and depression; QOL; and PA were measured at the beginning and end of maintenance in 42 children aged 3 to 18 years with ALL. Children were categorized into symptom cluster groups based …

Randomized Phase Iii Bmt Ctn Trial Of Calcineurin Inhibitor-Free Chronic Graft-Versus-Host Disease Interventions In Myeloablative Hematopoietic Cell Transplantation For Hematologic Malignancies, Leo Luznik, Marcelo C Pasquini, Brent Logan, Robert J Soiffer, Juan Wu, Steven M Devine, Nancy Geller, Sergio Giralt, Helen E Heslop, Mary M Horowitz, Richard J Jones, Mark R Litzow, Adam Mendizabal, Lori Muffly, Eneida R Nemecek, Lynn O'Donnell, Richard J O'Reilly, Raquel Palencia, Johannes Schetelig, Leyla Shune, Scott R Solomon, Sumithira Vasu, Vincent T Ho, Miguel-Angel Perales

Faculty, Staff and Students Publications

PURPOSE: Calcineurin inhibitors (CNI) are standard components of graft-versus-host disease (GVHD) prophylaxis after hematopoietic cell transplantation (HCT). Prior data suggested that CNI-free approaches using donor T-cell depletion, either by ex vivo CD34 selection or in vivo post-transplant cyclophosphamide (PTCy) as a single agent, are associated with lower rates of chronic GVHD (cGVHD).

METHODS: This multicenter phase III trial randomly assigned patients with acute leukemia or myelodysplasia and an HLA-matched donor to receive CD34-selected peripheral blood stem cell, PTCy after a bone marrow (BM) graft, or tacrolimus and methotrexate after BM graft (control). The primary end point was cGVHD (moderate or …

Utility Of Blood As The Clinical Specimen For The Diagnosis Of Ocular Toxoplasmosis Using Uracil Dna Glycosylase-Supplemented Loop-Mediated Isothermal Amplification And Real-Time Polymerase Chain Reaction Assays Based On Rep-529 Sequence And B1 Gene, Bahman Rahimi Esboei, Shirzad Fallahi, Mohammad Zarei, Bahram Kazemi, Mehdi Mohebali, Saeedeh Shojaee, Parisa Mousavi, Aref Teimouri, Raziyeh Mahmoudzadeh, Mirataollah Salabati, Hossein Keshavarz Valian

Wills Eye Hospital Papers

Background: Ocular infection with Toxoplasma gondii is a major preventable cause of blindness, especially in young people. The aim of the present study was to assess detection rate of T. gondii DNA in blood samples of clinically diagnosed of ocular toxoplasmosis using uracil DNA glycosylase-supplemented loop-mediated isothermal amplification (UDG-LAMP) and real-time quantitative PCR (qPCR) based on REP-529 and B1.

Methods: One hundred and seventeen patients with clinically diagnosed ocular toxoplasmosis (OT) were participated in the study as well as 200 control patients. Peripheral blood samples were assessed using UDG-LAMP and qPCR techniques targeting REP-529 and B1.

Results: Detection limits of …

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% …

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 …

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; …

The Longitudinal Parallel Process Analysis Of Biomarkers Of Oxidative Stress, Symptom Clusters, And Cognitive Function In Children With Leukemia, Mary C Hooke, Daniel Hatch, Marilyn J Hockenberry, Susan Whitman, Ida Moore, David Montgomery, Kari Marano, Pauline Mitby, Michael E Scheurer, Olga Taylor, Wei Pan

Faculty, Staff and Students Publications

Background: During treatment for acute lymphoblastic leukemia (ALL), children report co-occurring symptoms of fatigue, sleep disturbance, pain, nausea, and depression as a symptom cluster. Central nervous system–directed ALL therapies also put children at risk for cognitive impairments. Cancer therapies can cause an increase in oxidative stress, which may contribute to treatment-related symptoms. This study examined the longitudinal relationships between biomarkers of oxidative stress in the cerebrospinal fluid, the Childhood Cancer Symptom Cluster–Leukemia (CCSC-L), and cognition, in children over the first year of ALL treatment. Methods: Glutathione (GSH) biomarkers of oxidative stress were measured in cerebrospinal fluid collected during treatment lumbar …

The Concentration Of Total Nucleated Cells In Harvested Bone Marrow For Transplantation Has Decreased Over Time., Nicole L. Prokopishyn, Brent R. Logan, Deidre M. Kiefer, Jennifer A. Sees, Pintip Chitphakdithai, Ibrahim A. Ahmed, Paolo N. Anderlini, Amer M. Beitinjaneh, Christopher Bredeson, Jan Cerny, Saurabh Chhabra, Andrew Daly, Miguel Angel Diaz, Nosha Farhadfar, Haydar A. Frangoul, Siddhartha Ganguly, Dennis A. Gastineau, Usama Gergis, Gregory A. Hale, Peiman Hematti, Rammurti T. Kamble, Kimberly A. Kasow, Hillard M. Lazarus, Jane L. Liesveld, Hemant S. Murthy, Maxim Norkin, Richard F. Olsson, Mona Papari, Bipin N. Savani, Jeffrey Szer, Edmund K. Waller, Baldeep Wirk, Jean A. Yared, Michael A. Pulsipher, Nirali N. Shah, Galen E. Switzer, Paul V. O'Donnell, Dennis L. Confer, Bronwen E. Shaw

Manuscripts, Articles, Book Chapters and Other Papers

Bone marrow (BM) is an essential source of hematopoietic stem cell grafts for many allogeneic hematopoietic cell transplant (HCT) recipients, including adult patients (for specific diseases and transplantation strategies) and the majority of pediatric recipient. However, since the advent of granulocyte colony-stimulating factor-mobilized peripheral blood stem cell (PBSC) grafts, there has been a significant decrease in the use of BM in HCT, thought to be due mainly to the increased logistical challenges in harvesting BM compared with PBSCs, as well as generally no significant survival advantage of BM over PBSCs. The decreased frequency of collection has the potential to impact …

Clinical Pharmacology Of Tisagenlecleucel In B-Cell Acute Lymphoblastic Leukemia., Karen Thudium Mueller, Edward Waldron, Stephan A. Grupp, John E. Levine, Theodore W. Laetsch, Michael A. Pulsipher, Michael W. Boyer, Keith August, Jason Hamilton, Rakesh Awasthi, Andrew M. Stein, Denise Sickert, Abhijit Chakraborty, Bruce L. Levine, Carl H. June, Lori Tomassian, Sweta S. Shah, Mimi Leung, Tetiana Taran, Patricia A. Wood, Shannon L. Maude

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE: Tisagenlecleucel is an anti-CD19 chimeric antigen receptor (CAR19) T-cell therapy approved for the treatment of children and young adults with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL).

PATIENTS AND METHODS: We evaluated the cellular kinetics of tisagenlecleucel, the effect of patient factors, humoral immunogenicity, and manufacturing attributes on its kinetics, and exposure-response analysis for efficacy, safety and pharmacodynamic endpoints in 79 patients across two studies in pediatric B-ALL (ELIANA and ENSIGN).

RESULTS: Using quantitative polymerase chain reaction to quantify levels of tisagenlecleucel transgene, responders (N = 62) had ≈2-fold higher tisagenlecleucel expansion in peripheral blood than nonresponders ( …

Novel Hla-Dp Region Susceptibility Loci Associated With Severe Acute Gvhd., Rakesh K. Goyal, S J. Lee, T Wang, M Trucco, M Haagenson, S R. Spellman, M Verneris, R E. Ferrell

Manuscripts, Articles, Book Chapters and Other Papers

Despite HLA allele matching, significant acute GvHD remains a major barrier to successful unrelated donor BMT. We conducted a genome-wide association study (GWAS) to identify recipient and donor genes associated with the risk of acute GvHD. A case-control design (grade III-IV versus no acute GvHD) and pooled GWA approach was used to study European-American recipients with hematological malignancies who received myeloablative conditioning non-T-cell-depleted first transplantation from HLA-A, -B, -C, -DRB1, -DQB1 allele level (10/10) matched unrelated donors. DNA samples were divided into three pools and tested in triplicate using the Affymetrix Genome-wide SNP Array 6.0. We identified three novel susceptibility …

Health-Related Quality Of Life (Hr-Qol) And Chronic Health Conditions In Survivors Of Childhood Acute Myeloid Leukemia (Aml) With Down Syndrome (Ds): A Report From The Children's Oncology Group., Kris Ann P. Schultz, Lu Chen, Alicia Kunin-Batson, Zhengjia Chen, William G. Woods, A S. Gamis, Toana Kawashima, Kevin C. Oeffinger, H Stacy Stacy Nicholson, Joseph P. Neglia

Manuscripts, Articles, Book Chapters and Other Papers

Survival rates for children with Down syndrome (DS) and acute myeloid leukemia (AML) are high; however, little is known regarding the health-related quality of life (HR-QOL) of these survivors. Individuals who survived ≥5 years following diagnosis of childhood AML were invited to complete parent or patient-report surveys measuring HR-QOL and chronic health conditions. In total, 26 individuals with DS had a median age at diagnosis of 1.8 years (range, 0.77 to 10.9 y) and median age at interview of 15 years (range, 8.3 to 27.6 y). Participants with DS and AML were compared with AML survivors without DS whose caregiver …