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CAR-T and pediatric

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https://www.readbyqxmd.com/read/30082906/management-guidelines-for-paediatric-patients-receiving-chimeric-antigen-receptor-t-cell-therapy
#1
REVIEW
Kris M Mahadeo, Sajad J Khazal, Hisham Abdel-Azim, Julie C Fitzgerald, Agne Taraseviciute, Catherine M Bollard, Priti Tewari, Christine Duncan, Chani Traube, David McCall, Marie E Steiner, Ira M Cheifetz, Leslie E Lehmann, Rodrigo Mejia, John M Slopis, Rajinder Bajwa, Partow Kebriaei, Paul L Martin, Jerelyn Moffet, Jennifer McArthur, Demetrios Petropoulos, Joan O'Hanlon Curry, Sarah Featherston, Jessica Foglesong, Basirat Shoberu, Alison Gulbis, Maria E Mireles, Lisa Hafemeister, Cathy Nguyen, Neena Kapoor, Katayoun Rezvani, Sattva S Neelapu, Elizabeth J Shpall
In 2017, an autologous chimeric antigen receptor (CAR) T cell therapy indicated for children and young adults with relapsed and/or refractory CD19+ acute lymphoblastic leukaemia became the first gene therapy to be approved in the USA. This innovative form of cellular immunotherapy has been associated with remarkable response rates but is also associated with unique and often severe toxicities, which can lead to rapid cardiorespiratory and/or neurological deterioration. Multidisciplinary medical vigilance and the requisite health-care infrastructure are imperative to ensuring optimal patient outcomes, especially as these therapies transition from research protocols to standard care...
August 6, 2018: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/29925499/non-viral-rna-chimeric-antigen-receptor-modified-t-cells-in-patients-with-hodgkin-lymphoma
#2
Jakub Svoboda, Susan R Rheingold, Saar I Gill, Stephan A Grupp, Simon F Lacey, Irina Kulikovskaya, Megan M Suhoski, J Joseph Melenhorst, Brandon Loudon, Anthony R Mato, Sunita Dwivedy Nasta, Daniel J Landsburg, Matthew R Youngman, Bruce L Levine, David L Porter, Carl H June, Stephen J Schuster
Chimeric antigen receptor (CAR) modified T cells are being investigated in many settings including classical Hodgkin lymphoma (cHL). The unique biology of cHL, characterized by scant Hodgkin and Reed-Sternberg (HRS) cells within an immunosuppressive tumor microenvironment (TME), may pose challenges for cellular therapies directly targeting antigens expressed on HRS. We hypothesized that eradicating CD19 positive (+) B cells within the TME and the putative circulating CD19+ HRS clonotypic cells using anti-CD19 directed CAR modified T cells (CART19) may indirectly affect HRS cells, which do not express CD19...
June 20, 2018: Blood
https://www.readbyqxmd.com/read/29797659/myeloid-lineage-switch-following-chimeric-antigen-receptor-t-cell-therapy-in-a-patient-with-tcf3-znf384-fusion-positive-b-lymphoblastic-leukemia
#3
Matthew J Oberley, Paul S Gaynon, Deepa Bhojwani, Michael A Pulsipher, Rebecca A Gardner, Matthew C Hiemenz, Jianling Ji, Jennifer Han, Maurice R G O'Gorman, Alan S Wayne, Gordana Raca
A pediatric patient diagnosed initially with B-lymphoblastic leukemia (B-ALL) relapsed with lineage switch to acute myeloid leukemia (AML) after chimeric antigen receptor T-cell (CAR-T) therapy and hematopoietic stem cell transplant . A TCF3-ZNF384 fusion was identified at diagnosis, persisted through B-ALL relapse, and was also present in the AML relapse cell population. ZNF384-rearrangements define a molecular subtype of B-ALL characterized by a pro-B-cell immunophenotype; furthermore, ZNF384-rearrangements are prevalent in mixed-phenotype acute leukemias...
May 24, 2018: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29772353/cardiac-profile-of-chimeric-antigen-receptor-t-cell-therapy-in-children-a-single-institution-experience
#4
Danielle S Burstein, Shannon Maude, Stephen Grupp, Heather Griffis, Joseph Rossano, Kimberly Lin
Immunotherapy with chimeric antigen receptor (CAR)-modified T cells targeting CD19 for pediatric acute lymphoblastic leukemia (ALL) has demonstrated significant efficacy. The principle toxicity is cytokine release syndrome with resultant hypotension. However, the spectrum of cardiovascular effects associated with CAR T cell therapy has not been systematically evaluated. We reviewed all patients who received CD19-directed CAR T cells at the Children's Hospital of Philadelphia between April 2012 and September 2016...
May 14, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29764159/emerging-role-of-immunotherapy-for-childhood-cancers
#5
Rupert Handgretinger, Patrick Schlegel
Recent developments in cell and gene therapy have a great impact on the new therapeutic approaches in pediatric cancers. Monoclonal antibodies for neuroblastoma and bispecific antibodies for leukemia have induced significant clinical responses for otherwise chemorefractory patients. Moreover, cellular therapeutic approaches including chimeric antigen receptor (CAR) T-cells as well as natural killer (NK) cells have the potential to cure patients with so far incurable malignancies and are the basis for future new therapies for pediatric cancer...
April 2018: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/29746363/lower-extremity-fractures-in-hospitalized-pediatric-patients-following-road-traffic-accidents
#6
Shay Tenenbaum, Jason T Bariteau, Ofir Chechik, Adi Givon, Kobi Peleg, Ran Thein
Lower extremity fractures (LEFs) caused by road traffic accidents (RTAs) can result in significant morbidity and account for a substantial part of nonfatal injuries requiring hospitalization. This study investigated the epidemiology of RTA-associated LEFs in the pediatric population. Based on the National Trauma Registry, data of 28,924 RTA hospitalized pediatric patients were reviewed. Data were analyzed according to LEF mechanism of injury, age distribution, fracture types, associated injuries, surgical treatment, and their interrelations...
May 5, 2018: Pediatric Emergency Care
https://www.readbyqxmd.com/read/29731179/parents-adherence-to-pediatric-health-and-safety-guidelines-importance-of-patient-provider-relationships
#7
Lindsay N Fuzzell, A Scott LaJoie, Kyle T Smith, Sydney E Philpott, Katherine M Jones, Mary C Politi
OBJECTIVE: To examine 1) parent-provider communication about pediatric health/safety guidelines, 2) trust in child's provider, 3) comfort discussing guidelines, 4) agreement with guideline advice, 5) self-efficacy following guidelines, and their impact on guideline adherence. METHOD: 256 parents of children ages 0-6 completed an online survey about sunscreen use, newborn Vitamin K injections, influenza vaccination, routine vaccination, car seats, infant safe sleep, furniture anchoring, large trampoline use, and firearm safety...
September 2018: Patient Education and Counseling
https://www.readbyqxmd.com/read/29712574/durable-regression-of-medulloblastoma-after-regional-and-intravenous-delivery-of-anti-her2-chimeric-antigen-receptor-t-cells
#8
Anandani Nellan, Christopher Rota, Robbie Majzner, Cynthia M Lester-McCully, Andrea M Griesinger, Jean M Mulcahy Levy, Nicholas K Foreman, Katherine E Warren, Daniel W Lee
BACKGROUND: Standard-of-care therapies for treating pediatric medulloblastoma have long-term side effects, even in children who are cured. One emerging modality of cancer therapy that could be equally effective without such side effects would be chimeric antigen receptor (CAR) T cells. Knowing that human epidermal growth factor receptor 2 (HER2) is overexpressed in many medulloblastomas and has been used as a CAR T target before, we sought to evaluate the efficacy of more sophisticated anti-HER2 CAR T cells, as well as the feasibility and efficacy of different routes of delivering these cells, for the treatment of pediatric medulloblastoma...
April 30, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29662203/potent-antitumor-efficacy-of-anti-gd2-car-t-cells-in-h3-k27m-diffuse-midline-gliomas
#9
Christopher W Mount, Robbie G Majzner, Shree Sundaresh, Evan P Arnold, Meena Kadapakkam, Samuel Haile, Louai Labanieh, Esther Hulleman, Pamelyn J Woo, Skyler P Rietberg, Hannes Vogel, Michelle Monje, Crystal L Mackall
Diffuse intrinsic pontine glioma (DIPG) and other diffuse midline gliomas (DMGs) with mutated histone H3 K27M (H3-K27M)1-5 are aggressive and universally fatal pediatric brain cancers 6 . Chimeric antigen receptor (CAR)-expressing T cells have mediated impressive clinical activity in B cell malignancies7-10 , and recent results suggest benefit in central nervous system malignancies11-13 . Here, we report that patient-derived H3-K27M-mutant glioma cell cultures exhibit uniform, high expression of the disialoganglioside GD2...
May 2018: Nature Medicine
https://www.readbyqxmd.com/read/29622697/fda-approval-summary-tocilizumab-for-treatment-of-chimeric-antigen-receptor-t-cell-induced-severe-or-life-threatening-cytokine-release-syndrome
#10
Robert Q Le, Liang Li, Weishi Yuan, Stacy S Shord, Lei Nie, Bahru A Habtemariam, Donna Przepiorka, Ann T Farrell, Richard Pazdur
On August 30, 2017, the U.S. Food and Drug Administration approved Actemra (tocilizumab, Genentech, Inc., South San Francisco, CA) for the treatment of severe or life-threatening chimeric antigen receptor (CAR) T cell-induced cytokine release syndrome (CRS) in adults and in pediatric patients 2 years of age and older. The approval was based on a retrospective analysis of data for patients who developed CRS after treatment with CTL019 and KTE-C19 on prospective clinical trials. Evaluable patients had been treated with intravenous tocilizumab 8 mg/kg (12 mg/kg for patients <30 kg) for severe or life-threatening CRS; only the first episode of CRS was included in the analysis...
April 5, 2018: Oncologist
https://www.readbyqxmd.com/read/29605883/induction-of-a-central-memory-and-stem-cell-memory-phenotype-in-functionally-active-cd4-and-cd8-car-t-cells-produced-in-an-automated-good-manufacturing-practice-system-for-the-treatment-of-cd19-acute-lymphoblastic-leukemia
#11
Franziska Blaeschke, Dana Stenger, Theresa Kaeuferle, Semjon Willier, Ramin Lotfi, Andrew Didier Kaiser, Mario Assenmacher, Michaela Döring, Judith Feucht, Tobias Feuchtinger
Relapsed/refractory B-precursor acute lymphoblastic leukemia (pre-B ALL) remains a major therapeutic challenge. Chimeric antigen receptor (CAR) T cells are promising treatment options. Central memory T cells (Tcm) and stem cell-like memory T cells (Tscm) are known to promote sustained proliferation and persistence after T-cell therapy, constituting essential preconditions for treatment efficacy. Therefore, we set up a protocol for anti-CD19 CAR T-cell generation aiming at high Tcm/Tscm numbers. 100 ml peripheral blood from pediatric pre-B ALL patients was processed including CD4+ /CD8+ -separation, T-cell activation with modified anti-CD3/-CD28 reagents and transduction with a 4-1BB-based second generation CAR lentiviral vector...
July 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29555644/biological-impact-of-%C3%AE-genes-%C3%AE-haplotypes-and-g6pd-activity-in-sickle-cell-anemia-at-baseline-and-with-hydroxyurea
#12
Françoise Bernaudin, Cécile Arnaud, Annie Kamdem, Isabelle Hau, Françoise Lelong, Ralph Epaud, Corinne Pondarré, Serge Pissard
Sickle cell anemia (SCA), albeit monogenic, has heterogeneous phenotypic expression, mainly related to the level of hemoglobin F (HbF). No large cohort studies have ever compared biological parameters in patients with major β-globin haplotypes; ie, Senegal (SEN), Benin (BEN), and Bantu/Central African Republic (CAR). The aim of this study was to evaluate the biological impact of α genes, β haplotypes, and glucose-6-phosphate dehydrogenase (G6PD) activity at baseline and with hydroxyurea (HU). Homozygous HbS patients from the Créteil pediatric cohort with available α-gene and β-haplotype data were included (n = 580; 301 females and 279 males) in this retrospective study...
March 27, 2018: Blood Advances
https://www.readbyqxmd.com/read/29501911/approved-car-t-cell-therapies-ice-bucket-challenges-on-glaring-safety-risks-and-long-term-impacts
#13
Ping-Pin Zheng, Johan M Kros, Jin Li
Two autologous chimeric antigen receptor (CAR) T cell therapies (Kymriah™ and Yescarta™) were recently approved by the FDA. Kymriah™ is for the treatment of pediatric patients and young adults with refractory or relapse (R/R) B cell precursor acute lymphoblastic leukemia and Yescarta™ is for the treatment of adult patients with R/R large B cell lymphoma. In common, both are CD19-specific CAR T cell therapies lysing CD19-positive targets. Their dramatic efficacy in the short term has been highlighted by many media reports...
June 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/29499750/grading-of-cytokine-release-syndrome-associated-with-the-car-t-cell-therapy-tisagenlecleucel
#14
REVIEW
David Porter, Noelle Frey, Patricia A Wood, Yanqiu Weng, Stephan A Grupp
BACKGROUND: Anti-CD19 CAR T cell therapy has demonstrated high response rates in patients with relapsed or refractory (r/r) B cell malignancies but is associated with significant toxicity. Cytokine release syndrome (CRS) is the most significant complication associated with CAR T cell therapy, and it is critical to have a reproducible and easy method to grade CRS after CAR T cell infusions. DISCUSSION: The Common Terminology Criteria for Adverse Events scale is inadequate for grading CRS associated with cellular therapy...
March 2, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29442287/recent-developments-in-adolescent-and-young-adult-aya-acute-lymphoblastic-leukemia
#15
REVIEW
Victor M Orellana-Noia, Michael G Douvas
PURPOSE OF REVIEW: Adolescent and Young Adult (AYA) Oncology is a relatively new field encompassing research in the unique pathophysiology, clinical care, and psychosocial issues facing patients between the ages of 15 and 40 with cancer. About 100,000 of the approximately 1.5 million people diagnosed annually with cancer in the USA are in this age range. This chapter will review notable new developments in the care of adolescents and young adults with acute lymphoblastic leukemia (ALL) within the last 3 years...
April 2018: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/29419431/sequential-loss-of-tumor-surface-antigens-following-chimeric-antigen-receptor-t-cell-therapies-in-diffuse-large-b-cell-lymphoma
#16
LETTER
Haneen Shalabi, Ira L Kraft, Hao-Wei Wang, Constance M Yuan, Bonnie Yates, Cindy Delbrook, Julie D Zimbelman, Roger Giller, Maryalice Stetler-Stevenson, Elaine S Jaffe, Daniel W Lee, Jack F Shern, Terry J Fry, Nirali N Shah
No abstract text is available yet for this article.
May 2018: Haematologica
https://www.readbyqxmd.com/read/29385370/tisagenlecleucel-in-children-and-young-adults-with-b-cell-lymphoblastic-leukemia
#17
MULTICENTER STUDY
Shannon L Maude, Theodore W Laetsch, Jochen Buechner, Susana Rives, Michael Boyer, Henrique Bittencourt, Peter Bader, Michael R Verneris, Heather E Stefanski, Gary D Myers, Muna Qayed, Barbara De Moerloose, Hidefumi Hiramatsu, Krysta Schlis, Kara L Davis, Paul L Martin, Eneida R Nemecek, Gregory A Yanik, Christina Peters, Andre Baruchel, Nicolas Boissel, Francoise Mechinaud, Adriana Balduzzi, Joerg Krueger, Carl H June, Bruce L Levine, Patricia Wood, Tetiana Taran, Mimi Leung, Karen T Mueller, Yiyun Zhang, Kapildeb Sen, David Lebwohl, Michael A Pulsipher, Stephan A Grupp
BACKGROUND: In a single-center phase 1-2a study, the anti-CD19 chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel produced high rates of complete remission and was associated with serious but mainly reversible toxic effects in children and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL). METHODS: We conducted a phase 2, single-cohort, 25-center, global study of tisagenlecleucel in pediatric and young adult patients with CD19+ relapsed or refractory B-cell ALL...
February 1, 2018: New England Journal of Medicine
https://www.readbyqxmd.com/read/29370379/glycan-directed-car-t-cells
#18
Catharina Steentoft, Denis Migliorini, Tiffany R King, Ulla Mandel, Carl H June, Avery D Posey
Cancer immunotherapy is rapidly advancing in the treatment of a variety of hematopoietic cancers, including pediatric acute lymphoblastic leukemia and diffuse large B cell lymphoma, with chimeric antigen receptor (CAR)-T cells. CARs are genetically encoded artificial T cell receptors that combine the antigen specificity of an antibody with the machinery of T cell activation. However, implementation of CAR technology in the treatment of solid tumors has been progressing much slower. Solid tumors are characterized by a number of challenges that need to be overcome, including cellular heterogeneity, immunosuppressive tumor microenvironment (TME), and, in particular, few known cancer-specific targets...
January 23, 2018: Glycobiology
https://www.readbyqxmd.com/read/29262471/-correlation-between-serum-25-hydroxyvitamin-d-level-and-core-symptoms-of-autism-spectrum-disorder-in-children
#19
RANDOMIZED CONTROLLED TRIAL
H Y Dong, B Wang, H H Li, L Shan, F Y Jia
Objective: To explore the relationship between serum 25-hydroxyvitamin D levels and core symptoms of autism spectrum disorder (ASD) in children. Method: In this cross-sectional study, ASD children 4 to 6 years of age who were diagnosed in Department of Developmental and Behavioral Pediatrics, First Hospital of Jilin university from January to May 2017 were assigned to ASD group, and children for routine growth and development assessment in Jilin province were assigned to control group. The two groups were well matched for age and sex, and none of them had received vitamin D supplementation...
December 2, 2017: Zhonghua Er Ke za Zhi. Chinese Journal of Pediatrics
https://www.readbyqxmd.com/read/29213269/safety-and-immunogenicity-of-malaria-vectored-vaccines-given-with-routine-expanded-program-on-immunization-vaccines-in-gambian-infants-and-neonates-a-randomized-controlled-trial
#20
Victorine A Mensah, Sophie Roetynck, Ebrima K Kanteh, Georgina Bowyer, Amy Ndaw, Francis Oko, Carly M Bliss, Ya Jankey Jagne, Riccardo Cortese, Alfredo Nicosia, Rachel Roberts, Flavia D'Alessio, Odile Leroy, Babacar Faye, Beate Kampmann, Badara Cisse, Kalifa Bojang, Stephen Gerry, Nicola K Viebig, Alison M Lawrie, Ed Clarke, Egeruan B Imoukhuede, Katie J Ewer, Adrian V S Hill, Muhammed O Afolabi
Background: Heterologous prime-boost vaccination with chimpanzee adenovirus 63 (ChAd63) and modified vaccinia virus Ankara (MVA) encoding multiple epitope string thrombospondin-related adhesion protein (ME-TRAP) has shown acceptable safety and promising immunogenicity in African adult and pediatric populations. If licensed, this vaccine could be given to infants receiving routine childhood immunizations. We therefore evaluated responses to ChAd63 MVA ME-TRAP when co-administered with routine Expanded Program on Immunization (EPI) vaccines...
2017: Frontiers in Immunology
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