Pediatrics Commons^™

Lenvatinib Plus Ifosfamide And Etoposide In Children And Young Adults With Relapsed Osteosarcoma: A Phase 2 Randomized Clinical Trial, Nathalie Gaspar, Giun-Yi Hung, Sandra J Strauss, Quentin Campbell-Hewson, Filemon S Dela Cruz, Julia L Glade Bender, Kyung-Nam Koh, Sarah B Whittle, Godfrey Chi-Fung Chan, Nicolas U Gerber, Sauli Palmu, Daniel A Morgenstern, Alessandra Longhi, Fredrik Baecklund, Jun Ah Lee, Franco Locatelli, Catalina Márquez Vega, Katherine A Janeway, Geoffrey Mccowage, Martin G Mccabe, Behzad Bidadi, Jie Huang, Jodi Mckenzie, Chinyere E Okpara, Francisco Bautista, Olie Study Investigators

Faculty, Staff and Students Publications

IMPORTANCE: The combination of ifosfamide and etoposide (IE) is commonly used to treat relapsed or refractory osteosarcoma; however, second-line treatment recommendations vary across guidelines.

OBJECTIVE: To evaluate whether the addition of lenvatinib to IE (LEN-IE) improves outcomes in children and young adults with relapsed or refractory osteosarcoma.

DESIGN, SETTING, AND PARTICIPANTS: The OLIE phase II, open-label, randomized clinical trial was conducted globally across Europe, Asia and the Pacific, and North America. From March 22, 2020, through November 11, 2021, the trial enrolled patients aged 2 to 25 years with high-grade osteosarcoma, measurable or evaluable disease per Response Evaluation Criteria in …

Tumor-Promoted Changes In Pediatric Brain Histology Can Be Distinguished From Normal Parenchyma By Desorption Electrospray Ionization Mass Spectrometry Imaging, Ana L Seidinger, Felipe L T Silva, Mayara F Euzébio, Anna C Krieger, João Meidanis, Junier M Gutierrez, Thais M S Bezerra, Luciano Queiroz, Alex A Rosini Silva, Iva L Hoffmann, Camila M M Daiggi, Helder Tedeschi, Marcos N Eberlin, Livia S Eberlin, José A Yunes, Andreia M Porcari, Izilda A Cardinalli

Faculty, Staff and Students Publications

Background: Central nervous system (CNS) tumors are the second most frequent type of neoplasm in childhood and adolescence, after leukemia. Despite the incorporation of molecular classification and improvement of protocols combining chemotherapy, surgery, and radiotherapy, CNS tumors are still the most lethal neoplasm in this age group. Mass spectrometry imaging (MSI) is a powerful tool to map the distribution of molecular species in tissue sections. Among MSI techniques, desorption electrospray ionization (DESI-MSI) has been demonstrated to enable reliable agreement with the pathological evaluation of different adult cancer types, along with an acceptable time scale for intraoperative use.

Methods: In the …

Tumor-Associated Edema In Children With Kaposi Sarcoma: 14 Years' Experience At Kamuzu Central Hospital, Lilongwe, Malawi, Fatsani Rose Manase, Allison Silverstein, William Kamiyango, Jimmy Villiera, Clement Dziwe, Claudia Wallrauch, Tom Heller, Mark Zobeck, Tamiwe Tomoka, Michael E Scheurer, Carl E Allen, Nmazuo Ozuah, Rizine Mzikamanda, Nader Kim El-Mallawany, Casey L Mcatee

Center for Medical Ethics and Health Policy Staff Publications

Background/objectives: Kaposi sarcoma (KS) is a common lymphatic endothelial cancer among children with and without HIV in central and eastern Africa. Despite its clinical heterogeneity, its various clinical phenotypes are often grouped together in staging and treatment algorithms. Patients with KS tumor-associated edema, referring to hard, non-pitting lesions which often lead to chronic disability, represent a unique, understudied subgroup of children with KS. To continue our work defining the distinct phenotypes of pediatric KS, this study aimed to assess the clinical progression and outcomes of KS edema in children.

Methods: A retrospective cohort study was conducted at Kamuzu Central Hospital …

Diffuse Glioneuronal Tumor With Oligodendroglioma-Like Features And Nuclear Clusters Relapse In A Seven-Year-Old Boy: An Unusual Case Exhibiting Near-Tetraploidy And Chromosome 14 Diploidy, Francis M Torres, Thomas Denapoli, Ping-Sun Chen, Carrie Mohila, Kevin E Fisher, Kenneth Aldape, Mark R Lee, Timothy C Griffin

Faculty, Staff and Students Publications

Diffuse glioneuronal tumor with oligodendroglioma-like features and nuclear clusters (DGONC) is a rare brain tumor of the central nervous system (CNS). Although only a few cases of DGONC have been reported following the initial description of the tumor, they have a distinct DNA methylation pattern and share a recurrent chromosomal finding of monosomy 14. We encountered a seven-year-old boy who presented with seizures and was found to have a left frontal and suprasellar mass. The tumor was grossly totally resected; histopathologic evaluation showed a cellular glioneuronal tumor with brisk mitotic activity. A near-tetraploid chromosome complement was detected, with associated diploidy …

Microfluidic Affinity Selection Of B-Lineage Cells From Peripheral Blood For Minimal Residual Disease Monitoring In Pediatric B-Type Acute Lymphoblastic Leukemia Patients., Malgorzata A. Witek, Nicholas E. Larkey, Alena Bartakova, Mateusz L. Hupert, Shalee Mog, Jami K. Cronin, Judy Vun, Keith August, Steven A. Soper

Manuscripts, Articles, Book Chapters and Other Papers

Assessment of minimal residual disease (MRD) is the most powerful predictor of outcome in B-type acute lymphoblastic leukemia (B-ALL). MRD, defined as the presence of leukemic cells in the blood or bone marrow, is used for the evaluation of therapy efficacy. We report on a microfluidic-based MRD (MF-MRD) assay that allows for frequent evaluation of blood for the presence of circulating leukemia cells (CLCs). The microfluidic chip affinity selects B-lineage cells, including CLCs using anti-CD19 antibodies poised on the wall of the microfluidic chip. Affinity-selected cells are released from the capture surface and can be subjected to immunophenotyping to enumerate …

Transient Elastography And Diffusion-Weighted Magnetic Resonance Imaging For Assessment Of Liver Fibrosis In Children With Chronic Hepatitis C, Mohamed A El-Guindi, Alif A Allam, Ahmed A Abdel-Razek, Gihan A Sobhy, Menan E Salem, Mohamed A Abd-Allah, Mostafa M Sira

Faculty, Staff and Student Publications

BACKGROUND: Chronic hepatitis C (CHC) is a health burden with consequent morbidity and mortality. Liver biopsy is the gold standard for evaluating fibrosis and assessing disease severity and prognostic purposes post-treatment. Noninvasive alternatives for liver biopsy such as transient elastography (TE) and diffusion-weighted magnetic resonance imaging (DW-MRI) are critical needs.

AIM: To evaluate TE and DW-MRI as noninvasive tools for predicting liver fibrosis in children with CHC.

METHODS: This prospective cross-sectional study initially recruited 100 children with CHC virus infection. Sixty-four children completed the full set of investigations including liver stiffness measurement (LSM) using TE and measurement of apparent diffusion …

A Genomics Driven Human Induced Pluripotent Stem Cell Model Of Infant All – Updates On Hematopoietic Differentiation, Meagan Vacek, Jacqelyn Nemechek, Irina Pushel, Priyanka Kumar, Bradley Thornton, Molly Leyda, Midhat Farooqi, Erin Guest, Jay L. Vivian, John M. Perry

Posters

Acute lymphoblastic leukemia in infants (iALL) is a high-risk subtype of childhood leukemia, with poor survival outcomes despite intensive therapies. Rearrangement of KMT2A (KMT2A-r) occurs in 70% of cases and is associated with chemotherapy resistance, early relapse, and rapid leukemic progression, all of which contribute to poor survival outcomes. The most common KMT2A-r in iALL is KMT2A::AFF1 (MLL::AF4), derived from t(4;11)(q21;23). This KMT2A-r generates a driver fusion oncogene which leads to epigenetic dysregulation of target gene transcription. Infant ALL’s cell of origin is thought to be a very early hematopoietic precursor, with transcriptomic studies of iALL blasts showing similarities to …

Comparing The Diagnostic Yield Of Germline Exome Versus Panel Sequencing In The Diverse Population Of The Texas Kidscanseq Pediatric Cancer Study, Lauren R Desrosiers-Battu, Tao Wang, Jacquelyn Reuther, George Miles, Hongzheng Dai, Eunji Jo, Heidi Russell, Robin Raesz-Martinez, Alva Recinos, Stephanie Gutierrez, Amy Thomas, Emily Berenson, Jessica Corredor, Kimberly Nugent, Rachel Wyatt Castillo, Rebecca Althaus, Rebecca Littlejohn, Shawn Gessay, Gail Tomlinson, Jonathan Gill, Juan Carlos Bernini, Kelly Vallance, Timothy Griffin, Sarah Scollon, Frank Y Lin, Christine Eng, Shashikant Kulkarni, Susan G Hilsenbeck, Angshumoy Roy, Amy L Mcguire, D Williams Parsons, Sharon E Plon

Faculty, Staff and Student Publications

Purpose: To evaluate the relative diagnostic yield of clinical germline genomic tests in a diverse pediatric cancer population.

Patients and methods: The KidsCanSeq study enrolled pediatric cancer patients across six sites in Texas. Germline analysis included both exome sequencing and a therapy-focused pediatric cancer gene panel. The results were categorized by participants demographics, the presence of pathogenic or likely pathogenic (P/LP) variants, and variants of uncertain significance (VUS) in cancer predisposition genes (CPGs). Pediatric actionable CPGs were defined as those with cancer surveillance recommendations during childhood.

Results: Cancer P/LP variants were reported by at least one platform in 103 of …

The Impact Of Margins And Re-Resection In Pediatric Synovial Sarcoma, Andres F Espinoza, Priya B Shetty, Jillian C Jacobson, Hannah Todd, Kelley Harrell, Alfred F Trappey, John Doski, Eumenia C Castro, Nicole I Montgomery, M Fatih Okcu, Rajkumar Venkatramani, Dai H Chung, Sanjeev A Vasudevan

Faculty, Staff and Students Publications

INTRODUCTION: Synovial sarcoma is one of the most common soft tissue sarcomas in children. Guidelines regarding the adequate extent of resection margins and the role of re-resection are lacking. We sought to evaluate the adequate resection margin and the role of re-resection in predicting outcomes in children with synovial sarcomas.

METHODS: A cohort of 36 patients less than 18 years of age at diagnosis who were treated for localized synovial sarcoma at three tertiary pediatric hospitals between January 2004 and December 2020 were included in this study. Patient and tumor demographics, treatment information, and margin status after surgical resection were …

Evaluation Of Hi-C Sequencing For Detection Of Gene Fusions In Hematologic And Solid Tumor Pediatric Cancer Samples., Anthony D. Schmitt, Kristin Sikkink, Atif A. Ahmed, Shadi Melnyk, Derek Reid, Logan Van Meter, Erin M Guest, Lisa A. Lansdon, Tomi Pastinen, Irina Pushel, Byunggil Yoo, Midhat S. Farooqi

Manuscripts, Articles, Book Chapters and Other Papers

Hi-C sequencing is a DNA-based next-generation sequencing method that preserves the 3D genome conformation and has shown promise in detecting genomic rearrangements in translational research studies. To evaluate Hi-C as a potential clinical diagnostic platform, analytical concordance with routine laboratory testing was assessed using primary pediatric leukemia and sarcoma specimens. Archived viable and non-viable frozen leukemic cells and formalin-fixed paraffin-embedded (FFPE) tumor specimens were analyzed. Pediatric acute myeloid leukemia (AML) and alveolar rhabdomyosarcoma (A-RMS) specimens with known genomic rearrangements were subjected to Hi-C to assess analytical concordance. Subsequently, a discovery cohort consisting of AML and acute lymphoblastic leukemia (ALL) cases …

Tailored Approach To Participant Recruitment And Retention To Maximize Health Equity In Pediatric Cancer Research., Carolyn R. Bates, Renee M. Gilbert, Kelsey Dean, Keith August, Christie A. Befort, Shallyn Ward, Mary Gibson, Meredith Dreyer

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Lack of diversity in participants throughout the research process limits the generalizability of findings and may contribute to health disparities. There are unique challenges to recruitment of families to pediatric cancer research studies, especially for those from disadvantaged backgrounds. Thus, there is a need to evaluate the most effective recruitment and retention strategies to optimize equitable recruitment of diverse participants.

METHODS: The present study adapted and implemented methods outlined previously in the literature. These previous efforts were developed to address barriers to pediatric research, behavioral health intervention research and research with Black adolescents. Recruitment and retention strategies are described …

Characteristics And Treatment Of Acute Myeloid Neoplasms With Cutaneous Involvement In Infants Up To 6 Months Of Age: A Retrospective Study., Juliette Renaud, Bianca F. Goemans, Franco Locatelli, Martina Pigazzi, Shelagh Redmond, Claudia E. Kuehni, Alice Destaillats, Todd A. Alonzo, Robert B. Gerbing, Alan S. Gamis, Richard Aplenc, Raffaele Renella, Todd Cooper, Francesco Ceppi

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Myeloid neoplasms account for 50% of cases of pediatric leukemias in infants. Approximately 25%-50% of patients with newborn leukemia have cutaneous extramedullary disease (EMD). In less than 10% of patients, aleukemic leukemia cutis or isolated extramedullary disease with cutaneous involvement (cEMD) occurs when skin lesions appear prior to bone marrow involvement and systemic symptoms. Interestingly, in acute myeloid leukemia with cutaneous EMD (AML-cEMD) and cEMD, spontaneous remissions have been reported.

METHOD: This is a multicentric retrospective cohort study aiming to describe characteristics, treatment, and outcome of infants with either cEMD or presence of cutaneous disease with involvement of the …

Adaptive, Behavioral, And Emotional Outcomes Following Postoperative Pediatric Cerebellar Mutism Syndrome In Survivors Treated For Medulloblastoma, Kimberly P Raghubar, Andrew M Heitzer, Fatema Malbari, Jason Gill, Roy V Sillitoe, Livia Merrill, Johanna Escalante, M Fatih Okcu, Guillermo Aldave, Avner Meoded, Stephen Kralik, Kimberly Davis, Marina Ma, Emily A H Warren, Mark D Mccurdy, Howard L Weiner, William Whitehead, Michael E Scheurer, Lisa Rodriguez, Amy Daigle, Murali Chintagumpala, Lisa S Kahalley

Faculty, Staff and Students Publications

OBJECTIVE: Patients who experience postoperative pediatric cerebellar mutism syndrome (CMS) during treatment for medulloblastoma have long-term deficits in neurocognitive functioning; however, the consequences on functional or adaptive outcomes are unknown. The purpose of the present study was to compare adaptive, behavioral, and emotional functioning between survivors with and those without a history of CMS.

METHODS: The authors examined outcomes in 45 survivors (15 with CMS and 30 without CMS). Comprehensive neuropsychological evaluations, which included parent-report measures of adaptive, behavioral, and emotional functioning, were completed at a median of 2.90 years following craniospinal irradiation.

RESULTS: Adaptive functioning was significantly worse in …

The Kat Module Of The Saga Complex Maintains The Oncogenic Gene Expression Program In Mycn- Amplified Neuroblastoma, Clare F Malone, Nathaniel W Mabe, Alexandra B Forman, Gabriela Alexe, Kathleen L Engel, Ying-Jiun C Chen, Melinda Soeung, Silvi Salhotra, Allen Basanthakumar, Bin Liu, Sharon Y R Dent, Kimberly Stegmaier

Faculty, Staff and Student Publications

Pediatric cancers are frequently driven by genomic alterations that result in aberrant transcription factor activity. Here, we used functional genomic screens to identify multiple genes within the transcriptional coactivator Spt-Ada-Gcn5-acetyltransferase (SAGA) complex as selective dependencies for MYCN-amplified neuroblastoma, a disease of dysregulated development driven by an aberrant oncogenic transcriptional program. We characterized the DNA recruitment sites of the SAGA complex in neuroblastoma and the consequences of loss of SAGA complex lysine acetyltransferase (KAT) activity on histone acetylation and gene expression. We demonstrate that loss of SAGA complex KAT activity is associated with reduced MYCN binding on chromatin, suppression of …

Exploring The Role Of Pain On Physical Activity Among Youth With Acute Lymphoblastic Leukemia Using The Biopsychosocial Model, Anna E. Van Asselt, Renee Gilbert, Meghan Tokala, Jacee Weber, Meredith L. Dreyer Gillette, Robert C. Gibler, Carolyn R. Bates, Keith August

Research Days

The Role of Pain on Physical Activity in Pediatric ALL

Keywords: Biopsychosocial model, pediatric Acute Lymphoblastic Leukemia, pain, physical activity

Introduction: Engaging in physical activity (PA) during cancer treatment benefits a child’s physical and mental well-being (McLaughlin et al., 2021). However, engaging in PA may be challenging due to treatment and disease-related pain (Uhl et al., 2020). Pediatric cancer research has primarily focused on management of procedural and chronic pain, with fewer studies examining how pain may interfere with PA during treatment (Clews et al., 2022). The current study qualitatively investigated the impact of pain on PA using a …

A Genomics Driven Induced Pluripotent Stem Cell Model Of Infant Acute Lymphoblastic Leukemia - Early Results, Meagan Vacek, Jacqelyn Nemechek, Irina Pushel, Bradley Thornton, Molly Leyda, Priyanka Prem Kumar, Midhat Farooqi, Jay L. Vivian, Erin M. Guest, John M. Perry

Research Days

While the cure rates for pediatric ALL have improved over the decades, infants with ALL (iALL) have not benefitted from these advances and continue to have a devastating prognosis. Unfortunately progress in treatment has also been slowed by inadequate research models. With this project, we address this unmet need by investigating a novel model to understand the cellular and molecular changes that occur during iALL onset and progression.

Increasing Palliative Care Team Involvement In Pediatric Hematopoietic Stem Cell Transplant Patients, Meagan Vacek, Lisa Tarbell, Melissa List, Erin Hall, Jennifer Linebarger, Kelstan Ellis, Gina Jones, Joel Thompson

Research Days

Early implementation of palliative care in pediatric oncology is well established but its role in pediatric hematopoietic stem cell transplant (HSCT) patients is yet to be fully determined. Multiple organizations encourage palliative care involvement in HSCT patients. Our aim was to increase palliative care team consults for patients receiving HSCT for our targeted diagnosis. Though we did not achieve this aim, we were able to increase the palliative care team's involvement in the total cohort of patients undergoing HSCT.

Frailty In Children And Adolescents With Acute Lymphoblastic Leukemia Or Lymphoblastic Lymphoma Receiving Maintenance Chemotherapy – A Pilot Study, Thomas R. Cochran, Joy M. Fulbright, Samantha Butrous, Brian R. Lee, Keith J. August, David A. White

Research Days

The submitted study aims to identify children with acute lymphoblastic leukemia or lymphoblastic lymphoma that meet frailty criteria early to allow for prevention of chronic health conditions that lead to increased mortality as survivors age into adulthood. Prevention and/or reversal of frailty has the potential to improve quality of life, decrease burden of disease, and extend the lifespan of the growing population of childhood cancer survivors. Given that frailty has been accepted as a tool to identify elderly and chronically sick adults highly vulnerable to adverse health outcomes, better understanding of the relevance and applicability of frailty in pediatrics may …

Prognostic Impact Of Cooccurring Mutations In Flt3-Itd Pediatric Acute Myeloid Leukemia., Katherine Tarlock, Robert B. Gerbing, Rhonda E. Ries, Jenny L. Smith, Amanda Leonti, Benjamin J. Huang, Danielle Kirkey, Leila Robinson, Jack H. Peplinksi, Beverly Lange, Todd M. Cooper, Alan S. Gamis, E Anders Kolb, Richard Aplenc, Jessica A. Pollard, Todd A. Alonzo, Soheil Meshinchi

Manuscripts, Articles, Book Chapters and Other Papers

We sought to define the cooccurring mutational profile of FLT3-ITD-positive (ITDpos) acute myeloid leukemia (AML) in pediatric and young adult patients and to define the prognostic impact of cooperating mutations. We identified 464 patients with FLT3-ITD mutations treated on Children's Oncology Group trials with available sequencing and outcome data. Overall survival, event-free survival (EFS), and relapse risk were determined according to the presence of cooccurring risk stratifying mutations. Among the cohort, 79% of patients had cooccurring alterations across 239 different genes that were altered through mutations or fusions. Evaluation of the prognostic impact of the cooccurring mutations demonstrated that patients …

Assessment Of In-Vitro And In-Vivo Pre-Clinical Pharmacokinetics Of Epz015666; A Novel Small Molecule For Medulloblastoma Treatment, Pratiksha U. Kshirsagar

Theses & Dissertations

Group 3 medulloblastoma (MB) has the worst prognosis of the MB subgroups associated with elevated MYC expression and a 5-year survival rate of

Quantitation of EPZ was performed on a Shimadzu LC-MS/MS system utilizing electrospray ionization operated in positive mode. The validated assay was linear from 0.2 to 500 ng/mL. Metabolic stability studies demonstrated slow intrinsic clearance of EPZ in mouse and human liver microsomes, suggesting no CYP-mediated metabolism. Additionally, EPZ exhibited low binding affinity to plasma and brain proteins and high apparent permeability across artificial membranes, indicating efficient membrane penetration. Drug transporter studies identified EPZ as a substrate of …

Resection And Reconstruction Of Ewing Sarcoma Of The Cuboid Utilizing Vascularized Fibular Autograft: A Case Report, Brandon Cunha, Alexandre Arkader

Rowan-Virtua Research Day

Ewing Sarcoma (EWS) rarely presents in the bones of the foot, and particularly in the cuboid, making it an exceedingly rare occurrence. We present the case of a 7-year-old female diagnosed with EWS of the right cuboid, detailing the management and outcomes of this rare presentation. The patient, now almost 5 years post-initial local control, exhibits restored foot function, a normalized gait, and no evidence of disease recurrence. This case underscores the potential for preserving lower extremity function and improving postoperative quality of life in rare presentations of EWS through innovative reconstruction strategies.

Cost-Effectiveness And Outcomes Of Utilizing Tisagenlecleucel Therapy (Car T-Cell) In Pediatric Acute Lymphoblastic Leukemia In Comparison To Standard Of Care (Soc) Therapies: A Scoping Review, Andrew Atschinow, Evangeline Attota, Warren Chan, Pooja Kasarapu, Priyal Shah, Karina Vizzoni

Rowan-Virtua Research Day

Aims

This review aims to assess the correlations between outcomes and cost of treatment methods for pediatric acute lymphoblastic leukemia patients, specifically comparing CAR T-cell therapy and Standard-of-Care (SoC) therapy. The socioeconomic background of patients will also be taken into consideration to see if there are differences in their outcomes.

Methods

Peer-reviewed publications were collected from PubMed and Web of Science. The keyword strings used were “acute lymphoblastic leukemia,” “pediatric acute lymphoblastic leukemia,” “pediatric,” “CAR T-cell therapy,” and “cost-effectiveness.” 27 citations were obtained. Titles were screened by 6 authors. Articles met the inclusion criteria including potential Quality-Adjusted Life Year (QALY) …

The Evidence Is Mounting: Insurance Coverage Disruptions Lead To Worse Outcomes Among Children Diagnosed With Cancer, Philip J Lupo, Christina L Magyar

Faculty, Staff and Students Publications

No abstract provided.

Mir4435-2hg As A Possible Novel Predictive Biomarker Of Chemotherapy Response And Death In Pediatric B-Cell All, Yulieth Torres-Llanos, Jovanny Zabaleta, Nataly Cruz-Rodriguez, Sandra Quijano, Paula Carolina Guzmán, Iliana De Los Reyes, Nathaly Poveda-Garavito, Ana Infante, Liliana Lopez-Kleine, Alba Lucía Combita

School of Medicine Faculty Publications

Introduction: Although B-cell acute lymphoblastic leukemia (B-cell ALL) survival rates have improved in recent years, Hispanic children continue to have poorer survival rates. There are few tools available to identify at the time of diagnosis whether the patient will respond to induction therapy. Our goal was to identify predictive biomarkers of treatment response, which could also serve as prognostic biomarkers of death, by identifying methylated and differentially expressed genes between patients with positive minimal residual disease (MRD+) and negative minimal residual disease (MRD-). Methods: DNA and RNA were extracted from tumor blasts separated by immunomagnetic columns. Illumina MethlationEPIC and mRNA …

Structural Variants Involving Mllt10 Fusion Are Associated With Adverse Outcomes In Pediatric Acute Myeloid Leukemia., Oussama Abla, Rhonda E. Ries, Tim Triche, Robert B. Gerbing, Betsy Hirsch, Susana Raimondi, Todd Cooper, Jason E. Farrar, Nathaniel Buteyn, Lauren M. Harmon, Hong Wen, Aniruddha J. Deshpande, E Anders Kolb, Alan S. Gamis, Richard Aplenc, Todd Alonzo, Soheil Meshinchi

Manuscripts, Articles, Book Chapters and Other Papers

MLLT10 gene rearrangements with KMT2A occur in pediatric acute myeloid leukemia (AML) and confer poor prognosis, but the prognostic impact of MLLT10 in partnership with other genes is unknown. We conducted a retrospective study with 2080 children and young adults with AML registered on the Children's Oncology Group AAML0531 (NCT00372593) and AAML1031 trials (NCT01371981). Transcriptome profiling and/or karyotyping were performed to identify leukemia-associated fusions associated with prognosis. Collectively, 127 patients (6.1%) were identified with MLLT10 fusions: 104 (81.9%) with KMT2A::MLLT10, 13 (10.2%) with PICALM::MLLT10, and 10 (7.9%) X::MLLT10: (2 each of DDX3X and TEC), with 6 partners (DDX3Y, CEP164, SCN2B, …

Assessing Social Vulnerabilities Of Salivary Gland Cancer Care, Prognosis, And Treatment In The United States, Govind S. Bindra, David J. Fei-Zhang, Atharva Desai, John Maddalozzo, Stephanie S. Smith, Urjeet A. Patel, Daniel C. Chelius, Jill N. D'Souza, Jeffrey C. Rastatter, M. Boyd Gillespie, Anthony M. Sheyn

School of Medicine Faculty Publications

Background: Salivary gland cancers (SGC)-social determinants of health (SDoH) investigations are limited by narrow scopes of SGC-types and SDoH. This Social Vulnerability Index (SVI)-study hypothesized that socioeconomic status (SES) most contributed to SDoH-associated SGC-disparities. Methods: Retrospective cohort of 24 775 SGCs assessed SES, minority-language status (ML), household composition (HH), housing-transportation (HT), and composite-SDoH measured by the SVI via regressions with surveillance and survival length, late-staging presentation, and treatment (surgery, radio-, chemotherapy) receipt. Results: Increasing social vulnerability showed decreases in surveillance/survival; increased odds of advanced-presenting-stage (OR: 1.12, 95% CI: 1.07, 1.17), chemotherapy receipt (OR: 1.13, 95% CI: 1.03, 1.23); decreased odds …

Childhood Cancer Survivorship: Navigating A New Normal In Middle Tennessee, Karli M. Beaumont

OTD Capstone Projects

Monroe Carell Jr. Children’s Hospital at Vanderbilt in partnership with Vanderbilt-Ingram Cancer Center offers REACH for Cancer Survivorship, a pediatric cancer survivorship clinic. REACH provides a full range of follow-up care designed to meet the physical, emotional, and practical needs of survivors and continuous surveillance of deleterious effects of cancer and its treatments. The purpose of this project was to meet population and agency needs through research of long- and late-term sequela while advocating for occupational therapy’s role in the oncology population through the proactive therapy and prospective surveillance models. The process of creating this project included synthesizing the literature, …

Chromatin Profiles Are Prognostic Of Clinical Response To Bortezomib-Containing Chemotherapy In Pediatric Acute Myeloid Leukemia: Results From The Cog Aaml1031 Trial., Anneke D. Van Dijk, Fieke W. Hoff, Yihua Qiu, Stefan E. Hubner, Robin L. Go, Vivian R. Ruvolo, Amanda R. Leonti, Robert B. Gerbing, Alan S. Gamis, Richard Aplenc, Edward A. Kolb, Todd A. Alonzo, Soheil Meshinchi, Eveline S J M De Bont, Terzah M. Horton, Steven M. Kornblau

Manuscripts, Articles, Book Chapters and Other Papers

The addition of the proteasome inhibitor bortezomib to standard chemotherapy did not improve survival in pediatric acute myeloid leukemia (AML) when all patients were analyzed as a group in the Children's Oncology Group phase 3 trial AAML1031 (NCT01371981). Proteasome inhibition influences the chromatin landscape and proteostasis, and we hypothesized that baseline proteomic analysis of histone- and chromatin-modifying enzymes (HMEs) would identify AML subgroups that benefitted from bortezomib addition. A proteomic profile of 483 patients treated with AAML1031 chemotherapy was generated using a reverse-phase protein array. A relatively high expression of 16 HME was associated with lower EFS and higher 3-year …

Chromatin Profiles Are Prognostic Of Clinical Response To Bortezomib-Containing Chemotherapy In Pediatric Acute Myeloid Leukemia: Results From The Cog Aaml1031 Trial, Anneke D Van Dijk, Fieke W Hoff, Yihua Qiu, Stefan E Hubner, Robin L Go, Vivian R Ruvolo, Amanda R Leonti, Robert B Gerbing, Alan S Gamis, Richard Aplenc, Edward A Kolb, Todd A Alonzo, Soheil Meshinchi, Eveline S J M De Bont, Terzah M Horton, Steven M Kornblau

Faculty, Staff and Student Publications

The addition of the proteasome inhibitor bortezomib to standard chemotherapy did not improve survival in pediatric acute myeloid leukemia (AML) when all patients were analyzed as a group in the Children's Oncology Group phase 3 trial AAML1031 (NCT01371981). Proteasome inhibition influences the chromatin landscape and proteostasis, and we hypothesized that baseline proteomic analysis of histone- and chromatin-modifying enzymes (HMEs) would identify AML subgroups that benefitted from bortezomib addition. A proteomic profile of 483 patients treated with AAML1031 chemotherapy was generated using a reverse-phase protein array. A relatively high expression of 16 HME was associated with lower EFS and …

"Fueling For A Healthy Life:" A Cooking Class For Adolescent And Young Adult Childhood Cancer Survivors, Hope Dominique

Senior Theses

Following cancer treatment, childhood cancer survivors (CCS) are at an increased risk of developing chronic diseases and face an increased risk of health-related death during adulthood. Recent literature demonstrates that modifying lifestyle factors such as nutrition can reduce the risk of late mortality in survivors, suggesting that interventions promoting a healthy lifestyle may improve quality and quantity of life for CCS. However, many adolescent and young adult (AYA) CCS do not adhere to national dietary guidelines and face both real and perceived barriers to adopting healthier eating habits while in a critical period for establishing behaviors that contribute to lifelong …