Journal ArticleDOI
Molecular-based and antibody-based targeted pharmacological approaches in childhood acute lymphoblastic leukemia.
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In this article, the authors provide an overview of the genomic landscape of childhood acute lymphoblastic leukemia and highlight recent advances in molecular-based and antibody-based pharmacological approaches in the treatment of childhood ALL, from emerging preclinical evidence to published results of completed clinical trials.Abstract:
Introduction: Despite the significant survival improvement in childhood acutelymphoblastic leukemia (ALL), 15-20% of patients continue to relapse; outcomes following relapse remain suboptimal and have room for further improvement. Advances in genomics have shed new insights on the biology of ALL, led to the discovery of novel genomically defined ALL subtypes, refined prognostic significance and revealed new therapeutic vulnerabilities.Areas covered: In this review, the authors provide an overview of the genomic landscape of childhood ALL and highlight recent advances in molecular-based and antibody-based pharmacological approaches in the treatment of childhood ALL, from emerging preclinical evidence to published results of completed clinical trials.Expert opinion: Molecularly targeted therapies and immunotherapies have expanded the horizons of ALL therapy and represent promising therapeutic avenues for high-risk and relapsed/refractory ALL. These novel therapies are now moving into frontline ALL therapy and may define new treatment paradigms that aim to further improve survival and reduce chemotherapy-related toxicities in the management of pediatric ALL.read more
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Oncogene-Induced Reprogramming in Acute Lymphoblastic Leukemia: Towards Targeted Therapy of Leukemia-Initiating Cells
TL;DR: A review of the previous and current concepts exploring the phenotypic, genetic and functional heterogeneity in patients with acute lymphoblastic leukemia can be found in this article, where the benefits of using engineered mouse models to explore the early steps of leukemia development and to identify the biological mechanisms driving the emergence of leukemia-initiating cells are discussed.
References
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Journal ArticleDOI
Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia
Shannon L. Maude,Theodore W. Laetsch,Jochen Buechner,S. Rives,Michael Boyer,Henrique Bittencourt,Peter Bader,Michael R. Verneris,Heather E. Stefanski,G.D. Myers,Muna Qayed,B. De Moerloose,Hidefumi Hiramatsu,Krysta Schlis,Kara L. Davis,Paul L. Martin,Eneida R. Nemecek,Gregory A. Yanik,Christina Peters,André Baruchel,Nicolas Boissel,Francoise Mechinaud,Adriana Balduzzi,Joerg Krueger,Carl H. June,Bruce L. Levine,Patricia A. Wood,Tanya Taran,Mimi Leung,Karen Thudium Mueller,Yiyun Zhang,Kapildeb Sen,David Lebwohl,Michael A. Pulsipher,Stephan A. Grupp +34 more
TL;DR: In this global study of CAR T‐cell therapy, a single infusion of tisagenlecleucel provided durable remission with long‐term persistence in pediatric and young adult patients with relapsed or refractory B‐cell ALL, with transient high‐grade toxic effects.
Journal ArticleDOI
T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial
Daniel W. Lee,James N. Kochenderfer,Maryalice Stetler-Stevenson,Yongzhi K Cui,Cindy Delbrook,Steven A. Feldman,Terry J. Fry,Rimas J. Orentas,Marianna Sabatino,Nirali N. Shah,Seth M. Steinberg,Dave Stroncek,Nick Tschernia,Constance M. Yuan,Hua Zhang,Ling Zhang,Steven A. Rosenberg,Alan S. Wayne,Crystal L. Mackall +18 more
TL;DR: CD19-CAR T cell therapy is feasible, safe, and mediates potent anti-leukaemic activity in children and young adults with chemotherapy-resistant B-precursor acute lymphoblastic leukaemia and non-Hodgkin lymphoma.
Journal ArticleDOI
Chimeric antigen receptor T-cell therapy — assessment and management of toxicities
Sattva S. Neelapu,Sudhakar Tummala,Partow Kebriaei,William G. Wierda,Cristina Gutierrez,Frederick L. Locke,Krishna V. Komanduri,Yi Lin,Nitin Jain,Naval Daver,Jason R. Westin,Alison M. Gulbis,Monica Loghin,John de Groot,Sherry Adkins,Suzanne E. Davis,Katayoun Rezvani,Patrick Hwu,Elizabeth J. Shpall +18 more
TL;DR: The multidisciplinary approach adopted at institutions is described, and recommendations for monitoring, grading, and managing the acute toxicities that can occur in patients treated with CAR-T-cell therapy are provided.
Journal ArticleDOI
The genetic basis of early T-cell precursor acute lymphoblastic leukaemia
Jinghui Zhang,Li Ding,Linda Holmfeldt,Gang Wu,Susan L. Heatley,Susan L. Heatley,Debbie Payne-Turner,John Easton,Xiang Chen,Jianmin Wang,Michael Rusch,Charles Lu,Shann Ching Chen,Lei Wei,J. Racquel Collins-Underwood,Jing Ma,Kathryn G. Roberts,Stanley Pounds,Anatoly Ulyanov,Jared Becksfort,Pankaj Gupta,Robert Huether,Richard W. Kriwacki,Matthew Parker,Daniel J. McGoldrick,David Zhao,Daniel Alford,Stephen Espy,Kiran Chand Bobba,Guangchun Song,Deqing Pei,Cheng Cheng,Stefan Roberts,Michael I. Barbato,Michael I. Barbato,Dario Campana,Dario Campana,Elaine Coustan-Smith,Elaine Coustan-Smith,Sheila A. Shurtleff,Susana C. Raimondi,Maria Kleppe,Maria Kleppe,Jan Cools,Kristin A. Shimano,Michelle L. Hermiston,Sergei Doulatov,Kolja Eppert,Elisa Laurenti,Faiyaz Notta,John E. Dick,Giuseppe Basso,Stephen P. Hunger,Mignon L. Loh,Meenakshi Devidas,Brent L. Wood,Stuart S. Winter,Kimberley P. Dunsmore,Robert S. Fulton,Lucinda Fulton,Xin Hong,Chris Harris,David J. Dooling,Kerri Ochoa,Kimberly J. Johnson,John C. Obenauer,William E. Evans,Ching-Hon Pui,Clayton W. Naeve,Timothy J. Ley,Elaine R. Mardis,Richard K. Wilson,James R. Downing,Charles G. Mullighan +73 more
TL;DR: The mutational spectrum is similar to myeloid tumours, and moreover, the global transcriptional profile of ETP ALL was similar to that of normal andMyeloid leukaemia haematopoietic stem cells, suggesting that addition of myeloids-directed therapies might improve the poor outcome of E TP ALL.
Journal ArticleDOI
ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells
Daniel W. Lee,Bianca Santomasso,Frederick L. Locke,Armin Ghobadi,Cameron J. Turtle,Jennifer N. Brudno,Marcela V. Maus,Jae H. Park,Elena Mead,Steven Z. Pavletic,William Y. Go,Lamis K. Eldjerou,Rebecca Gardner,Noelle V. Frey,Kevin J. Curran,Karl S. Peggs,Marcelo C. Pasquini,John F. DiPersio,Marcel R.M. van den Brink,Krishna V. Komanduri,Stephan A. Grupp,Sattva S. Neelapu +21 more
TL;DR: The goal is to provide a uniform consensus grading system for CRS and neurotoxicity associated with immune effector cell therapies, for use across clinical trials and in the postapproval clinical setting.