Medical Specialties Commons^™

Tisagenlecleucel Immunogenicity In Relapsed/Refractory Acute Lymphoblastic Leukemia And Diffuse Large B-Cell Lymphoma., Karen Thudium Mueller, Stephan A. Grupp, Shannon L. Maude, John E. Levine, Michael A. Pulsipher, Michael W. Boyer, Keith August, Douglas Myers, Constantine S. Tam, Ulrich Jaeger, Stephen Ronan Foley, Peter Borchmann, Stephen J. Schuster, Edmund K. Waller, Rakesh Awasthi, Bernd Potthoff, Andy Warren, Edward R. Waldron, Fraser Mcblane, Andrea Chassot-Agostinho, Theodore W. Laetsch

Manuscripts, Articles, Book Chapters and Other Papers

Tisagenlecleucel is indicated for pediatric and young adult patients with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) and adult patients with r/r diffuse large B-cell lymphoma (DLBCL). The tisagenlecleucel chimeric antigen receptor (CAR) contains a murine single-chain variable fragment domain; we examined the effects of humoral and cellular immune responses to tisagenlecleucel on clinical outcomes using 2 validated assays. Data were pooled from the ELIANA (registered at www.clinicaltrials.gov as #NCT02435849) and ENSIGN (#NCT02228096) trials in r/r B-ALL (N = 143) and the JULIET trial (#NCT02445248) in r/r DLBCL (N = 115). Humoral responses were determined …

A Prospective Observational Study Of Antihemophilic Factor (Recombinant) Prophylaxis Related To Physical Activity Levels In Patients With Hemophilia A In The United States (Space)., Barbara A. Konkle, Doris V. Quon, Leslie Raffini, Michael Recht, Vlad C. Radulescu, Shannon L. Carpenter, Amy L. Dunn, Mei Lu, Maureen Watt

Manuscripts, Articles, Book Chapters and Other Papers

Introduction: High collision-risk physical activity can increase bleeding risk in people with hemophilia A, as can increasing the time between factor VIII (FVIII) administration and physical activity. FVIII prophylaxis may be tailored to planned activities to prevent activity-related bleeding.

Aim: To explore the relationship between physical activity levels, FVIII infusion timing, and occurrence of bleeding in patients with severe/moderately severe hemophilia A without FVIII inhibitors receiving antihemophilic factor (recombinant) (rAHF; ADVATE®; Baxalta US Inc., a Takeda company, Lexington, MA, USA).

Methods: SPACE was a 6-month, prospective, multicenter, observational outcomes study (NCT02190149). Enrolled patients received an eDiary application and …

Aberrantly Low Stat3 And Stat5 Responses Are Associated With Poor Outcome And An Inflammatory Gene Expression Signature In Pediatric Acute Myeloid Leukemia., P Narayanan, T-K Man, R B Gerbing, R Ries, A M Stevens, Y-C Wang, X Long, A S. Gamis, T Cooper, S Meshinchi, T A Alonzo, M S Redell

Manuscripts, Articles, Book Chapters and Other Papers

The relapse rate for children with acute myeloid leukemia is nearly 40% despite aggressive chemotherapy and often stem cell transplant. We sought to understand how environment-induced signaling responses are associated with clinical response to treatment. We previously reported that patients whose AML cells showed low G-CSF-induced STAT3 activation had inferior event-free survival compared to patients with stronger STAT3 responses. Here, we expanded the paradigm to evaluate multiple signaling parameters induced by a more physiological stimulus. We measured STAT3, STAT5 and ERK1/2 responses to G-CSF and to stromal cell-conditioned medium for 113 patients enrolled on COG trials AAML03P1 and AAML0531. Low …

Pooled Safety Analysis Of Tisagenlecleucel In Children And Young Adults With B Cell Acute Lymphoblastic Leukemia., John E. Levine, Stephan A. Grupp, Michael A. Pulsipher, Andrew C. Dietz, Susana Rives, Douglas Myers, Keith August, Michael R. Verneris, Jochen Buechner, Theodore W. Laetsch, Henrique Bittencourt, Andre Baruchel, Michael W. Boyer, Barbara De Moerloose, Muna Qayed, Stella M. Davies, Christine L. Phillips, Timothy A. Driscoll, Peter Bader, Krysta Schlis, Patricia A. Wood, Rajen Mody, Lan Yi, Mimi Leung, Lamis K. Eldjerou, Carl H. June, Shannon L. Maude

Manuscripts, Articles, Book Chapters and Other Papers

Background: Tisagenlecleucel, an anti-CD19 chimeric antigen receptor T cell therapy, has demonstrated efficacy in children and young adults with relapsed/refractory B cell acute lymphoblastic leukemia (B-ALL) in two multicenter phase 2 trials (ClinicalTrials.gov, NCT02435849 (ELIANA) and NCT02228096 (ENSIGN)), leading to commercialization of tisagenlecleucel for the treatment of patients up to age 25 years with B-ALL that is refractory or in second or greater relapse.

Methods: A pooled analysis of 137 patients from these trials (ELIANA: n=79; ENSIGN: n=58) was performed to provide a comprehensive safety profile for tisagenlecleucel.

Results: Grade 3/4 tisagenlecleucel-related adverse events (AEs) were reported in 77% of …

Longitudinal Analysis Of Myocardial Function Using Strain In Patients Receiving Cardiotoxic Chemotherapy, Anmol Goyal, Amulya Buddhavarapu, Kayla Simpson, Nataliya Kibiryeva, Wendy Hein, Joy M. Fulbright, Sanket Shah

Posters

Background:

Chemotherapy-related cardiotoxicity (CTRC) is associated with significant morbidity and mortality in long-term cancer survivors. Left ventricular [LV] Global longitudinal strain (GLS) is a sensitive parameter that can be used for earlier detection of contractile function changes in these patients. Recent literature suggested certain genotypes may influence CTRC. Our goal was to assess longitudinal myocardial function and identify any correlation between certain genetic variations and LV function regarding CTRC in our pediatric population.

Methods:

50 subjects ≥10 years of age who have survived >2 years after completion of cancer treatment were enrolled out of which 29 subjects agreed for genetic …

Next-Generation Sequencing In The Diagnosis Of Rare Pediatric Sinonasal Tumors., Atif A. Ahmed, Divya Vundamati, Midhat Farooqi, Elena Repnikova, Timothy Zinkus, Maxine Hetherington, Lorien Paulson

Manuscripts, Articles, Book Chapters and Other Papers

The diagnosis of desmoid fibromatosis or other spindle cell tumors in the sinonasal region is very rare in children and needs to be thoroughly confirmed with immunohistochemical and/or molecular tests. We report 2 patients with such rare tumors and describe the use of next-generation sequencing in their evaluation. A 3-year-old female had a 4.4-cm midline nasal cavity mass involving the bony septum and extending into the base of the skull bilaterally. The moderate cellular fibroblastic proliferation revealed areas of thick keloid-like collagen bands and other areas with myxoid edematous stroma. Deep targeted sequencing identified a novel G34V mutation in the

A New Paradigm: Ecmo Therapy In Pediatric Hematology/Oncology Patients, Igor Areinamo

Research Days

Background: The use of extracorporeal membrane oxygenation (ECMO) for support of pediatric patients has significantly increased in the past years. Patients with known oncologic diseases, immunodeficiencies, or bone marrow transplants (BMT) have traditionally not been considered candidates for Extracorporeal membrane oxygenation (ECMO) due to perceived high risk for mortality. Ongoing advances have continued to push the boundaries of ECMO use and we report our recent experience with this patient population

Objectives/Goal: To evaluate survival to discharge of pediatric patients who require ECMO support and who also have an underlying hematologic or oncologic disease process. To determine specific patient characteristics that …

Changes In Family Functioning During The First Year Of Pediatric Cancer Treatment: A Mixed-Method Pilot Study, Carolyn Bates

Research Days

Background: A new diagnosis of pediatric cancer presents a sudden and tremendous stressor for families of all backgrounds and circumstances (Long & Marsland, 2011; Bemis et al., 2015). Although many families are resilient in the context of new cancer diagnosis, approximately 33% are at risk for negative outcomes due to psychosocial distress and difficulties with effective coping (Kazak et al., 2020; Pai et al., 2008), supporting the need for systematic assessment of psychosocial health as a standard of care in pediatric oncology (Kazak et al., 2015). Alongside heightened stress within the first year of diagnosis, parents may relax family rules …

A Pediatric Case Of Treatment-Related Myelodysplastic Syndrome While On Therapy For Pre-B All, Sara Mcelroy

Research Days

Background: Treatment-related myelodysplastic syndrome (t-MDS) is a known, but rare, late effect of cancer therapy, specifically radiation, alkylating agents or topoisomerase II inhibitors. When secondary to treatment with alkylating agents, t-MDS typically occurs 4 to 7 years after therapy, and common cytogenetics include chromosomes 5 and 7 abnormalities. Treatment in children with t-MDS is typically allogeneic stem cell transplant, but the prognosis remains poor.

Objectives/Goal: To describe a rare case of a pediatric patient who developed t-MDS while receiving treatment for Pre-B Cell Acute Lymphoblastic Leukemia (pre-B ALL) and to outline the treatment regimen that he received.

Methods/Design: Case Report …

Impact Of Covid-19 On Families With A Child In Cancer Treatment, Mirae J. Fornander

Research Days

Background: A new diagnosis of pediatric cancer diagnosis is a sudden and tremendous stressor to families (Long & Marsland, 2011). The COVID-19 pandemic presented an acute, universal stressor that impacted daily life around the world (Brooks et al., 2020). The impact of the COVID-19 pandemic on children with cancer and their families is not yet known.

Objectives/Goal: The current study is a pilot investigation of COVID-19 exposure and impact among a sample of families with a child being treated for cancer.

Methods/Design: Primary caregivers (N=22) of a child (M age=7.4, SD=4.6) who was diagnosed with cancer within the last 18 …

Levofloxacin Versus Ciprofloxacin Prophylaxis In Pediatric Cancer Patients At High Risk Of Infection, Chandni Dargan Md, Amy Johnson Md, Mba

Research Days

Background: Patients with cancer and those undergoing chemotherapy are at risk of developing bacterial infections due to myelosuppression. Patients undergoing the most intensive chemotherapy regimens are at a higher risk for morbidity and mortality due to profound neutropenia. Antibacterial prophylaxis is given to reduce the incidence of infection in those at highest risk. Starting March 1, 2016 our institution used ciprofloxacin for antibacterial prophylaxis however recent literature, including the COG trial ACCL0934, supports using levofloxacin in certain high risk (HR) populations due to greater efficacy in reducing neutropenic fever (NF) and bacteremia. Therefore, we switched to this April 1, 2019. …

Survival Following Relapse In Children With Acute Myeloid Leukemia: A Report From Aml-Bfm And Cog., Mareike Rasche, Martin Zimmermann, Emma Steidel, Todd Alonzo, Richard Aplenc, Jean-Pierre Bourquin, Heidrun Boztug, Todd Cooper, A S. Gamis, Robert B. Gerbing, Iveta Janotova, Jan-Henning Klusmann, Thomas Lehrnbecher, Nora Mühlegger, Nils V. Neuhoff, Naghmeh Niktoreh, Lucie Sramkova, Jan Stary, Katharina Waack, Christiane Walter, Ursula Creutzig, Michael Dworzak, Gertjan Kaspers, Edward Anders Kolb, Dirk Reinhardt

Manuscripts, Articles, Book Chapters and Other Papers

Post-relapse therapy remains critical for survival in children with acute myeloid leukemia (AML). We evaluated survival, response and prognostic variables following relapse in independent cooperative group studies conducted by COG and the population-based AML-BFM study group. BFM included 197 patients who relapsed after closure of the last I-BFM relapse trial until 2017, while COG included 852 patients who relapsed on the last Phase 3 trials (AAML0531, AAML1031). Overall survival at 5 years (OS) was 42 ± 4% (BFM) and 35 ± 2% (COG). Initial high-risk features (BFM 32 ± 6%, COG 26 ± 4%) and short time to relapse (BFM …

Standardization Of Fertility Preservation Discussion Amongst Pediatric Oncology And Bone Marrow Transplant Patients: A Single Institution Experience, Chandni Dargan, Sarah E. Mc Dermott, Shelby Chesbro

Research Days

Background/Project Intent (Aim Statement): As treatment for pediatric malignancies improves long term survival, physicians are shifting focus to late effects of therapy such as infertility. Currently, options for fertility preservation include cryopreservation of mature oocytes, sperm, and gonadal tissue, although barriers remain present. Within our division, we lacked a standard approach to discussing fertility preservation options prior to initiation of treatment.

Methods (include PDSA cycles): Records from 474 pediatric patients with new oncologic diagnoses at CMH from 2014- 2020 were retrospectively reviewed. We evaluated the frequency that reproductive health discussions were documented in pubertal males and females requiring chemotherapy or …

Tisagenlecleucel Infusion In Patients With Relapsed/Refractory All And Concurrent Serious Infection., Erin Hall, Dwight E. Yin, Rakesh K. Goyal, Atif Ahmed, Grace S. Mitchell, Shawn D. St Peter, Terrie Flatt, Ibrahim A. Ahmed, Weijie Li, Richard J. Hendrickson, Keith August, Douglas Myers

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Tisagenlecleucel, an anti-CD19 chimeric antigen receptor T (CAR-T) cell therapy, has demonstrated durable efficacy and a manageable safety profile in pediatric and young adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) in the ELIANA pivotal trial and real-world experience. Experience from investigator-led studies prior to ELIANA suggests that infections and inflammatory conditions may exacerbate the severity of cytokine release syndrome (CRS) associated with CAR-T cell therapy, leading to extreme caution and strong restrictions for on-study and commercial infusion of tisagenlecleucel in patients with active infection. CRS intervention with interleukin (IL)-6 blockade and/or steroid therapy was introduced late in …