Adult survivors of childhood Hodgkin lymphoma experience accelerated cognitive aging and decline, according to findings from St. Jude Children’s Research Hospital featured in the press program at the 64th annual American Society of Hematology (ASH) meeting. The conference will take place in person from December 10–13, at the Ernest N. Morial Convention Center in New Orleans, with a virtual viewing option. In addition to highlighting the survivorship research, ASH will also feature oral presentations, education sessions and posters shared by St. Jude scientists.
The Hodgkin lymphoma research from the St. Jude Lifetime cohort study (St. Jude LIFE) of childhood cancer survivors found that these individuals had the cognitive function equivalent to people much older than their chronological age, which was associated with signs of epigenetic age acceleration in their DNA.
“This study demonstrates for the first time that long-term survivors of childhood Hodgkin lymphoma are at heightened risk for cognitive impairment due to accelerated physiological aging,” said senior co-author Kevin Krull, Ph.D., St. Jude Department of Epidemiology and Cancer Control. “Understanding this mechanism will provide opportunities for targeted interventions to improve outcomes and promote a healthy lifespan in survivors.”
AnnaLynn Williams, Ph.D., a former research fellow who trained at St. Jude and who is now faculty at the University of Rochester, will present about the accelerated decline of neurocognitive function in long-term survivors of Hodgkin Lymphoma December 12.
St. Jude oral presentations at ASH:
St. Jude researchers will speak on topics including basic cell biology, clinical trials for sickle cell disease, acute lymphoblastic leukemia (ALL) and stem cell transplantation.
Up to 50% of patients with primary hemophagocytic lymphohistiocytosis (pHLH) die due to refractory disease or treatment-related complications. Therefore, finding new therapeutic strategies is a priority in the field. Camille Keenan, M.D., M.P.H., St. Jude Department of Oncology, will present a novel approach using immunoproteasome inhibition to treat patients with pHLH in her talk on December 10.
Children with sickle cell disease are treated with fixed-dose hydroxyurea safely and effectively. In older children and adults with sickle cell disease, intensifying the dose can improve clinical benefits of treatment, however, this must be balanced with the risk of causing harmful side effects. Meghna Dua, M.D., St. Jude Department of Global Pediatric Medicine, will present initial promising results of a clinical trial designed to find if doses could be safely intensified in very young children (6 - 18 months old) in her talk December 10.
Alterations in the gene IKZF1 are associated with poor outcomes for patients with B-cell ALL (B-ALL). Ruth Wang'ondu, M.D., Ph.D., St. Jude Department of Oncology, will present a deep analysis on the topic in her talk “IKZF1plus Confers a Strong Adverse Prognostic Effect in Total Therapy Studies (XV/XVI)” December 10.
Computational approaches, including machine learning, are showing promise in extracting more information from a diversity of studies and assembling actionable information. Yiwang Zhou, Ph.D., St. Jude Department of Biostatistics, will present how machine learning can integrate data from electronic health records and improve overall survival predictions of pediatric patients after undergoing allogeneic hematopoietic stem cell transplants in her talk December 10.
Certain genes are commonly mutated in B-ALL. One of these genes is TCF3, which is important for blood cell development. Carolin Escherich, Ph.D., St. Jude Department of Pharmacy and Pharmaceutical Sciences, will present on how a rare mutation in TCF3 predisposes children to ALL December 11.
Children with bone marrow failure and/or myelodysplastic syndrome cannot create healthy blood cell precursors. Charnise Goodings-Harris, Ph.D., St. Jude Department of Hematology, will present an analysis of how patient’s blood stem cells can acquire mutations in SAMD9 or SAMD9L genes to compensate, which drives their disease December 11.
HOXA9 is overexpressed in 50-70% of human acute myeloid leukemia (AML) and a subset of ALL patients. It also is correlated with poor outcomes, though the mechanism is unclear. Chunliang Li, Ph.D., St. Jude Department of Tumor Cell Biology, will present how they found the regulation mechanism via a systematic use of CRISPR to find the transcriptional network related to HOXA9 function December 11.
Certain genes are mutated in many cancers, indicating they are a critical part of preventing disease. Melvin Thomas, Ph.D., St. Jude Department of Pathology, will present how the Max-gene associated (MGA) gene contributes to normal blood stem cell growth and how its loss enhances cancer development in AML and potentially other tumors on December 11.
Drug resistance developing in B-ALL patients is a major cause of relapse. Xiaotu Ma, Ph.D., St. Jude Department of Computational Biology, will present an analysis of how different subtypes of B-ALL develop drug resistance December 11.
Relapsed childhood cancers, including ALL, continue to have a poor long-term prognosis. Sometimes the anti-cancer drug cures some patients but leaves small amounts of cancer cells unaffected in other patient. Yizhen Li, St. Jude Department of Pharmacy and Pharmaceutical Sciences, will present an explanation for why this happens in ALL patients treated with chemotherapy blinatumomab December 11.
Human chromosomes are often modified in cancers, including AML. Akshay Sharma, M.D., M.B.B.S., St. Jude Department of Bone Marrow Transplantation and Cellular Therapy, will present on how certain abnormalities of chromosomes predict survival in pediatric patients with AML after transplant. Increasing expression of fetal hemoglobin in patients with sickle cell disease protects against complications from the disease. Sharma will also present on a successful preliminary treatment of severe sickle cell disease using CRISPR/Cas9-edited hematopoietic stem cells induced to generate fetal hemoglobin. Both presentations will be held December 12.
Children with sickle cell disease at risk for stroke often have elevated blood velocity within their heads. If caught early enough, physicians can begin chronic blood transfusion to reduce primary stroke. However, performing transcranial doppler screening is expensive and time-consuming, indicating a need to identify which patients are most likely to benefit. As a first step in that process, Ayo Olanrewaju, M.D., St. Jude Department of Hematology, will present an approach to optimize how often children with sickle cell disease receive transcranial doppler frequency December 12.
Children with relapsed T-cell ALL (T-ALL) have dismal long-term outcomes. If physicians can identify the types of T-ALL most likely to relapse, they can focus on finding ways to prevent relapse during frontline therapy. Petri Pölönen, Ph.D., St. Jude Department of Pathology, will present St. Jude research that defined the genomic landscape of T-ALL with whole genome sequencing and RNAseq data from 1,313 T-ALL patients December 12.
Different subtypes of childhood ALL respond differently to the same drug. Shawn Lee, M.D., formerly of the St. Jude Department of Pharmacy and Pharmaceutical Sciences, will present which subtypes of ALL are sensitive to different drugs in his talk December 12.
Bone marrow failure disorders are a group of diseases in which a patient’s body does not make enough healthy blood cells. These disorders are difficult to study, as model systems, such as cell cultures and mice, do not perfectly mimic human disease. To provide insights to researchers in the field about what to expect from the differences between models and human disease, Sushree Sahoo, Ph.D., St. Jude Department of Hematology, will present how a single mutation acts differently in human, mice and cells with bone marrow failure disorder December 12.
St. Jude researchers will present during multiple ASH scientific workshops:
Carolin Escherich, M.D., St. Jude Department of Pharmaceutical Sciences, will present “Targeted Sequencing in Pediatric ALL Identifies Lineage-Specific Enrichment of TCF3 Germline Variants,” Mackenzie Bloom, Ph.D., St. Jude Department of Oncology, will present “Mouse Model of Pathogenic ETV6 Germline Variant Reveals Loss of HSC Self Renewal and Increased Production of TNF,” Sherif Abdelhamed, Ph.D., St. Jude Department of Pathology will present “In Vivo Expression of Samd9l Mutation Impairs Hematopoiesis to Induce Bone Marrow Failure” and Trent Hall, St. Department of Hematology, will present “Aberrant T-Cell Development in Children with Down Syndrome” December 9 during the workshop on “Germline Predisposition to Hematopoietic Malignancies and Bone Marrow Failure,” moderated by Sushree Sahoo, Ph.D., St. Jude Department of Hematology.
Relapsed childhood cancers, including ALL, continue to have a poor long-term prognosis. One approach is to treat relapsed disease with chimeric antigen receptor (CAR) T cells. However, this approach has failed to deliver its theoretical promise in many cancer types. Giedre Krenciute, Ph.D., St. Jude Department of Bone Marrow Transplantation and Cellular Therapy, will present “CAR-T Cell Dysfunction: Revitalizing the Living Drug” December 10 in the scientific session on “Overcoming T-cell Burnout and Exhaustion.”
Ilaria Iacobucci, Ph.D., St. Jude Department of Pathology, will present “Contemporary Guidelines for Diagnosis and Genomic Classification of Acute Lymphoblastic Leukemia (ALL),” Jeffery Klco, M.D., Ph.D., St. Jude Department of Pathology, will present “Ubtf Tandem Duplications As a Novel Sutype of Pediatric Acute Myeloid Leukemia” and Lu Wang, M.D., Ph.D., St. Jude Department of Pathology will present “Integrating Whole-Genome and Whole-Transcriptome Sequencing for Molecular Diagnosis, Classification and Risk Stratification of Pediatric and Adolescent AML” December 9 during the workshop “Translational Molecular Diagnostics: Genomic Reclassification of Blood Cancer.”
Ruth Wang'ondu, M.D., Ph.D., St. Jude Department of Oncology, will present “The Role of Ikaros (IKZF1) Alterations in B-Acute Lymphoblastic Leukemia” December 10, during the Promoting Minorities in Hematology Session.
St. Jude researchers will host ASH educational and career developmental sessions:
St. Jude researchers and clinicians are taking on the task of training and guiding the next generation in hematology care and research at ASH.
Jane Hankins, M.D., St. Jude Department of Hematology, will present “Sickle Cell Disease” during the training session “Blood Drop: Sickle Cell Disease” December 9.
Sara Lewis, St. Jude Department of Hematology, will present “Genetic Counseling: Ethical Considerations during the Diagnostic Process and How to Avoid Confusing Situations” December 11.
Shannon McKinney-Freeman, Ph.D., St. Jude Department of Hematology, will present “Writing a Good CV, Portfolio, and Biosketch” December 11.
Kevin Krull, Ph.D., St. Jude Department of Epidemiology and Cancer Control, will present “Risk Factors and Screening for Neurocognitive Impacts of Therapy” December 12.
Posters presenting original research
St. Jude researchers will present posters on a variety of topics, including ALL genetics, CAR T-cell therapy development, hemoglobin alterations for sickle cell disease and more.
Poster abstracts available online.
Multiple St. Jude faculty will moderate oral sessions at the conference:
Aimee Talleur, M.D., St. Jude Department of Bone Marrow Transplantation and Cellular Therapy, will co-moderate the “Cellular Immunotherapies: Novel Predictors of Response or Toxicity to Cellular Therapies” session December 10.
Akshay Sharma, M.D., St. Jude Department of Bone Marrow Transplantation and Cellular Therapy, will moderate the “Gene Therapies: Addressing Challenges & Opportunities in Pre-clinical Settings” session December 10.
Hiroto Inaba, M.D., Ph.D., St. Jude Department of Oncology, will moderate the “Acute Lymphoblastic Leukemias: Clinical and Epidemiological: Management of Novel ALL Subsets in Different Age Groups” session December 10.
Paulina Velasquez, M.D., St. Jude Department of Bone Marrow Transplantation and Cellular Therapy, will co-moderate the “Cellular Immunotherapies: Basic and Translational II” session December 10.
Jeffery Klco, M.D., Ph.D., St. Jude Department of Pathology, will moderate the “Bone Marrow Failure Syndromes: Diagnostic Principles in 2022” session December 11.
Ilaria Iacobucci, Ph.D., St. Jude Department of Pathology, will moderate “Emerging Tools, Techniques and Artificial Intelligence in Hematology: New Molecular Tools for Precision Diagnostics in Hematology” session on December 11.
Marta Derecka, Ph.D., St. Jude Department of Hematology, will co-moderate the “Bone Marrow Microenvironment: Extrinsic Regulators of Hematopoiesis” session December 12.
Rebecca Epperly, M.D., St. Jude Department of Bone Marrow Transplantation and Cellular Therapy, will co-moderate the “Cellular Immunotherapies: Early Phase and Investigational Therapies: Acute Leukemia and Hodgkin Lymphoma” session December 12.
St. Jude Children's Research Hospital
St. Jude Children's Research Hospital is leading the way the world understands, treats and cures childhood cancer, sickle cell disease, and other life-threatening disorders. It is the only National Cancer Institute-designated Comprehensive Cancer Center devoted solely to children. Treatments developed at St. Jude have helped push the overall childhood cancer survival rate from 20% to 80% since the hospital opened more than 60 years ago. St. Jude shares the breakthroughs it makes to help doctors and researchers at local hospitals and cancer centers around the world improve the quality of treatment and care for even more children. To learn more, visit stjude.org, read St. Jude Progress blog, and follow St. Jude on social media at @stjuderesearch.