Oncology Commons^™

Receptor Tyrosine Kinase (Rtk) Targeting In Pediatric High-Grade Glioma And Diffuse Midline Glioma: Pre-Clinical Models And Precision Medicine., Kallen Schwark, Dana Messinger, Jessica R. Cummings, Joshua Bradin, Abed Kawakibi, Clarissa M. Babila, Samantha Lyons, Sunjong Ji, Rodrigo T. Cartaxo, Seongbae Kong, Evan Cantor, Carl Koschmann, Viveka Nand Yadav

Manuscripts, Articles, Book Chapters and Other Papers

Pediatric high-grade glioma (pHGG), including both diffuse midline glioma (DMG) and non-midline tumors, continues to be one of the deadliest oncologic diagnoses (both henceforth referred to as "pHGG"). Targeted therapy options aimed at key oncogenic receptor tyrosine kinase (RTK) drivers using small-molecule RTK inhibitors has been extensively studied, but the absence of proper in vivo modeling that recapitulate pHGG biology has historically been a research challenge. Thankfully, there have been many recent advances in animal modeling, including Cre-inducible transgenic models, as well as intra-uterine electroporation (IUE) models, which closely recapitulate the salient features of human pHGG tumors. Over 20% of …

Real-World Use Of Tisagenlecleucel In Infant Acute Lymphoblastic Leukemia., Amy Moskop, Lauren Pommert, Christina Baggott, Snehit Prabhu, Holly L. Pacenta, Christine L. Phillips, Jenna Rossoff, Heather E. Stefanski, Julie-An Talano, Steve P. Margossian, Michael R. Verneris, Douglas Myers, Nicole A. Karras, Patrick A. Brown, Muna Qayed, Michelle L. Hermiston, Prakash Satwani, Christa Krupski, Amy K. Keating, Rachel Wilcox, Cara A. Rabik, Vanessa A. Fabrizio, Vasant Chinnabhandar, A Yasemin Goksenin, Kevin J. Curran, Crystal L. Mackall, Theodore W. Laetsch, Erin M. Guest, Erin H. Breese, Liora M. Schultz

Manuscripts, Articles, Book Chapters and Other Papers

Infants with B-cell acute lymphoblastic leukemia (B-ALL) have poor outcomes because of chemotherapy resistance leading to high relapse rates. Tisagenlecleucel, a CD19-directed chimeric antigen receptor T-cell (CART) therapy, is US Food and Drug Administration approved for relapsed or refractory B-ALL in patients ≤25 years; however, the safety and efficacy of this therapy in young patients is largely unknown because children(n = 14). Sixty-four percent of patients (n = 9) achieved minimal residual disease-negative remission after CART and 50% of patients remain in remission at last follow-up. All patients with high disease burden at time of CART infusion (>M1 marrow) …

Randomized Clinical Trial Of A Self-Care And Communication Intervention For Parents Of Adolescent/Young Adults Undergoing High-Risk Cancer Treatment: A Report From The Children's Oncology Group., Joan E. Haase, Kristin Stegenga, Sheri L. Robb, Mary C. Hooke, Debra S. Burns, Patrick O. Monahan, Timothy E. Stump, Amanda K. Henley, Paul R. Haut, Brooke Cherven, Lona Roll, Anne-Marie Langevin, Rita H. Pickler, Karen Albritton, Deanna Hawkins, Erin Osterkamp, Pauline Mitby, Jackie Smith, Virginia R. Diaz, Erica Garcia-Frausto, Margo Moore

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Parents of adolescents and young adults (AYAs) with cancer offer primary support to their children and often experience their own high levels of distress, affecting parent-AYA communication and quality of life.

OBJECTIVE: To reduce parent distress and improve communication during high-risk cancer treatment, we examined efficacy of a self-care and communication intervention for parents and indirect benefit for AYAs receiving a therapeutic music video (TMV) intervention.

METHODS: In this study, we conducted a multisite, randomized controlled trial with AYAs and parents enrolled as dyads (n = 110). Parents were randomized to intervention or low-dose control; all AYAs received TMV. …

Variation In Thiopurine Metabolism In Hispanic Children, Kayeleigh Higgerson Do

Research Days

Background: Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Overall survival rate is > 90% in the United States. However, ethnic and racial disparities remain. Hispanic patients have an inferior overall survival compared to non-Hispanics. The reasons for these differences remain unclear. Mercaptopurine (6MP) is a crucial drug in ALL treatment. Variations in the TMPT and NUDT15 genes lead to altered 6MP metabolism and accumulation of toxic metabolites (6TGN or 6MMPN). Each metabolite is associated with specific dose-limiting toxicities. The accumulation of 6TGN causes myelosuppression, and increased 6MMPN causes GI toxicity. While variants in these genes have been identified …

Wilms Tumor Presenting With Spontaneous Necrosis And Clostridium Perfringens Co-Infection, Ronald Palmen, Abbey Elsbernd, Kristin Palmen

Research Days

Background: Wilm’s Tumor (WT) is the most common renal malignancy of childhood. The initial presentation of WT may mimic infection or other malignancies with nonspecific symptoms including fever, abdominal/flank pain, or hematuria. This poses a diagnostic challenge for providers, particularly when both infection and malignancy are observed. We describe a case of WT with spontaneous necrosis initially obscured by overlying Clostridium perfringens infection, making diagnosis of the cancer difficult.

Case Description: A previously healthy 5-year-old girl presented to the emergency department with a two-day history of left flank pain and fevers. In the emergency department, she was tachycardic (130 bpm), …

Primary Venous Thromboprophylaxis In Pediatric Oncology Patients, Kyra Mccarty

Research Days

Background: The Virchow’s Triad principles of venous stasis, endothelial damage, and hypercoagulability are all features of malignancy and contribute to the increased risk venous thromboembolism (VTE) seen in oncology patients. Additionally, certain chemotherapy treatments, presence of a central venous catheter and immobility are also intrinsically associated with malignancy diagnoses and exacerbate this risk. However, much debate exists over the use of thromboprophylaxis in the pediatric population, primarily due to lack of evidence regarding safety and efficacy, primarily the risk of major bleeding. Multiple retrospective studies have attempted to identify the primary risk factors for VTE in this pediatric oncology patient …

A Novel Approach To Triosephosphate Isomerase Deficiency, Kyra Mccarty

Research Days

Background: Triosephosphate isomerase deficiency (TPID) is a glycolytic pathway enzymopathy causing hemolytic anemia and neurologic dysfunction. TPID is caused by mutations in the TPI1 gene. These patients experience severe hemolytic anemia in infancy followed by progressive neurodegeneration. Diagnosis of TPID is made by measuring decreased TPI enzyme activity elevated dihydroxyacetone phosphate (DHAP) levels in the blood. The diagnosis is confirmed by molecular genetic testing. Neurological involvement typically manifests between 6 and 24 months of age, causing progressive motor dysfunction. Chronic axonal neuropathy is often present on nerve biopsy, and peripheral neuropathy is evident on electrophysiologic studies. Splenectomy and blood transfusions …

Treatment Of Recurrent Wilms Tumor With Irinotecan/Temozolomide, Meagan Vacek, Terrie Flatt

Posters

Background: Despite improvement in relapse free survival (RFS) in recurrent Wilms tumor, the 4-year RFS rate for patients treated with vincristine/dactinomycin/doxorubicin is approximately 40%. Ifosfamide, carboplatin and etoposide are commonly used in relapsed solid tumors, but have significant toxicities and require hospital admission for administration. Our patient focused on quality of life, and this led to exploration of other treatment options. Objective: Describe a case of multiply relapsed Wilms tumor with management on oral irinotecan/temozolomide for improved quality of life and remission for almost 1 year. Design/Method: Case Report Results: The patient is an 11-year-old female diagnosed with Wilms tumor …

Outstanding Outcomes In Infants With Kmt2a-Germline Acute Lymphoblastic Leukemia Treated With Chemotherapy Alone: Results Of The Children's Oncology Group Aall0631 Trial, Erin M. Guest, John A. Kairalla, Joanne M. Hilden, Zoann E. Dreyer, Andrew J. Carroll, Nyla A. Heerema, Cindy Y. Wang, Meenakshi Devidas, Lia Gore, Wanda L. Salzer, Naomi J. Winick, William L. Carroll, Elizabeth A. Raetz, Michael Borowitz, Mignon L. Loh, Stephen P. Hunger, Patrick A. Brown

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.

Memory T Cell Populations In Human Leukemia, Sara Mcelroy, Fang Tao, John Szarejko, John M. Perry

Posters

Background Incorporating the immune system into cancer management is an area of robust research. Treatment modalities aimed at activating cytotoxic T cells against malignancies include immune checkpoint inhibitors, bispecific T-cell engagers, and chimeric antigen receptor (CAR) tumor-specific T cells. Most anti-cancer T cell research is narrowly focused, but knowledge about the nature of diverse sub-populations of T cells in cancer, particularly memory T cells, is vital prior to potential incorporation into therapies. T memory stem cells (Tscm) are of interest due to their longevity and powerful abilities of self-renewal and creating the full spectrum of memory CD8+ T cells, including …

Blood Count Recovery Following Induction Therapy For Acute Myeloid Leukemia In Children Does Not Predict Survival, Lauren Pommert, Todd M. Cooper, Robert B. Gerbing, Lisa Brodersen, Michael Loken, Alan S. Gamis, Richard Aplenc, Todd A. Alonzo, Edwards Anders Kolb

Manuscripts, Articles, Book Chapters and Other Papers

International Working Group (IWG) and European LeukemiaNet (ELN) response definitions are utilized to evaluate the efficacy of new agents for childhood acute myeloid leukemia (AML) for regulatory purposes. However, these criteria are not consistent with definitions used in pediatric AML trials or with standard pediatric practice to proceed with subsequent therapy cycles prior to IWG/ELN-defined count recovery. We retrospectively analyzed data from the two most recent Phase 3 pediatric AML clinical trials conducted by the Children’s Oncology Group (COG) to assess the incidence, timing, and prognostic significance of count recovery following induction chemotherapy. Of the patients with fewer than 5% …

Next-Generation Sequencing Of Minimal Residual Disease For Predicting Relapse After Tisagenlecleucel In Children And Young Adults With Acute Lymphoblastic Leukemia., Michael A. Pulsipher, Xia Han, Shannon L. Maude, Theodore W. Laetsch, Muna Qayed, Susana Rives, Michael W. Boyer, Hidefumi Hiramatsu, Gregory A. Yanik, Tim Driscoll, Douglas Myers, Peter Bader, Andre Baruchel, Jochen Buechner, Heather E. Stefanski, Creton Kalfoglou, Kevin Nguyen, Edward R. Waldron, Karen Thudium Mueller, Harald J. Maier, Gabor Kari, Stephan A. Grupp

Manuscripts, Articles, Book Chapters and Other Papers

We assessed minimal residual disease (MRD) detection and B-cell aplasia after tisagenlecleucel therapy for acute lymphoblastic leukemia (ALL) to define biomarkers predictive of relapse (N = 143). Next-generation sequencing (NGS) MRD detection >0 in bone marrow (BM) was highly associated with relapse. B-cell recovery [signifying loss of functional chimeric antigen receptor (CAR) T cells] within the first year of treatment was associated with a hazard ratio (HR) for relapse of 4.5 [95% confidence interval (CI), 2.03-9.97; P < 0.001]. Multivariate analysis at day 28 showed independent associations of BMNGS-MRD >0 (HR = 4.87; 95% CI, 2.18-10.8; P < 0.001) and B-cell recovery (HR = 3.33; 95% CI, 1.44-7.69; P = 0.005) with relapse. By 3 months, the BMNGS-MRD HR increased to 12 …

Cancer Care Annual Report 2020-2021, Children's Mercy Kansas City

Cancer Center Annual Reports

Annual report of cancer care and oncology services at the Children's Mercy Kansas City, a pediatric medical center. This year’s report focuses on Hodgkin Lymphoma.

Implementing Nih Behavior Change Consortium Treatment Fidelity Recommendations In A Multi-Site Randomized Controlled Trial Of An Active Music Engagement Intervention For Young Children With Cancer And Parents., Jessica A. Maclean, Kristin Stegenga, Amanda K. Henley, Sheri L. Robb

Manuscripts, Articles, Book Chapters and Other Papers

Treatment fidelity is the use of methodological strategies to monitor and enhance reliability and validity of behavioral intervention trials. Despite availability of guidelines and checklists, treatment fidelity remains underreported, hindering evaluation, interpretation, and cross-study comparisons. Treatment fidelity is particularly important for music interventions given the inherent complexity of musical stimuli and flexibility required for tailored delivery. The purpose of this paper is to define and describe treatment fidelity strategies for our trial of a music-based play intervention for young children with cancer and parents grounded in the NIH Behavior Change Consortium Treatment Fidelity Recommendations. We report strategies for all 5 …