Matched Targeted Therapy for Pediatric Patients with Relapsed, Refractory, or High-Risk Leukemias: A Report from the LEAP Consortium.


Journal

Cancer discovery
ISSN: 2159-8290
Titre abrégé: Cancer Discov
Pays: United States
ID NLM: 101561693

Informations de publication

Date de publication:
06 2021
Historique:
received: 04 05 2020
revised: 25 11 2020
accepted: 14 01 2021
pubmed: 11 2 2021
medline: 19 2 2022
entrez: 10 2 2021
Statut: ppublish

Résumé

Despite a remarkable increase in the genomic profiling of cancer, integration of genomic discoveries into clinical care has lagged behind. We report the feasibility of rapid identification of targetable mutations in 153 pediatric patients with relapsed/refractory or high-risk leukemias enrolled on a prospective clinical trial conducted by the LEAP Consortium. Eighteen percent of patients had a high confidence Tier 1 or 2 recommendation. We describe clinical responses in the 14% of patients with relapsed/refractory leukemia who received the matched targeted therapy. Further, in order to inform future targeted therapy for patients, we validated variants of uncertain significance, performed

Identifiants

pubmed: 33563661
pii: 2159-8290.CD-20-0564
doi: 10.1158/2159-8290.CD-20-0564
pmc: PMC8178162
mid: NIHMS1667659
doi:

Substances chimiques

Biomarkers, Tumor 0

Types de publication

Clinical Trial Journal Article Multicenter Study Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1424-1439

Subventions

Organisme : NCI NIH HHS
ID : P50 CA206963
Pays : United States
Organisme : NCI NIH HHS
ID : K08 CA184418
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA214428
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA210030
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA128583
Pays : United States
Organisme : NCI NIH HHS
ID : K08 CA222684
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA232486
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA046934
Pays : United States

Commentaires et corrections

Type : CommentIn

Informations de copyright

©2021 American Association for Cancer Research.

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Auteurs

Yana Pikman (Y)

Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. Kimberly_stegmaier@dfci.harvard.edu Yana_pikman@dfci.harvard.edu.
Division of Hematology/Oncology, Boston Children's Hospital, Boston, Massachusetts.

Sarah K Tasian (SK)

Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Department of Pediatrics and Abramson Cancer Center at the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.

Maria Luisa Sulis (ML)

Division of Pediatric Hematology/Oncology/Stem Cell Transplantation, Columbia University Irving Medical Center, New York, New York.
Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York.

Kristen Stevenson (K)

Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.

Traci M Blonquist (TM)

Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.

Beth Apsel Winger (B)

Department of Pediatrics, Division of Hematology/Oncology, Benioff Children's Hospital and the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California.

Todd M Cooper (TM)

Seattle Children's Hospital, Cancer and Blood Disorders Center, Seattle, Washington.

Melinda Pauly (M)

Division of Hematology/Oncology, Emory University, Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Atlanta, Georgia.

Kelly W Maloney (KW)

Children's Hospital Colorado, University of Colorado Cancer Center, Aurora, Colorado.

Michael J Burke (MJ)

Medical College of Wisconsin, Children's Hospital of Wisconsin, Milwaukee, Wisconsin.

Patrick A Brown (PA)

Johns Hopkins Kimmel Cancer Center, Baltimore, Maryland.

Nathan Gossai (N)

Center for Cancer and Blood Disorders, Children's Minnesota, Minneapolis, Minnesota.

Jennifer L McNeer (JL)

University of Chicago, Comer Children's Hospital, Chicago, Illinois.

Neerav N Shukla (NN)

Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York.

Peter D Cole (PD)

Children's Hospital at Montefiore, Bronx, New York.
Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey.

Justine M Kahn (JM)

Division of Pediatric Hematology/Oncology/Stem Cell Transplantation, Columbia University Irving Medical Center, New York, New York.

Jing Chen (J)

Division of Pediatric Hematology/Oncology/Stem Cell Transplantation, Columbia University Irving Medical Center, New York, New York.
Children's Cancer Institute, Joseph M. Sanzari Children's Hospital, Hackensack University Medical Center, Hackensack, New Jersey.

Matthew J Barth (MJ)

Roswell Park Comprehensive Cancer Center, Buffalo, New York.

Jeffrey A Magee (JA)

Division of Pediatric Hematology/Oncology, Washington University/St. Louis Children's Hospital, St. Louis, Missouri.

Lisa Gennarini (L)

Children's Hospital at Montefiore, Bronx, New York.

Asmani A Adhav (AA)

Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.

Catherine M Clinton (CM)

Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.

Nicole Ocasio-Martinez (N)

Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.

Giacomo Gotti (G)

Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.

Yuting Li (Y)

Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.

Shan Lin (S)

Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.

Alma Imamovic (A)

Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts.

Cristina E Tognon (CE)

Division of Hematology and Medical Oncology, Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon.

Tasleema Patel (T)

Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.

Haley L Faust (HL)

Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.

Cristina F Contreras (CF)

Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.

Anjali Cremer (A)

Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
University Hospital Frankfurt, Department of Hematology/Oncology, Frankfurt/Main, Germany.

Wilian A Cortopassi (WA)

Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, California.

Diego Garrido Ruiz (D)

Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, California.

Matthew P Jacobson (MP)

Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, California.

Neekesh V Dharia (NV)

Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Division of Hematology/Oncology, Boston Children's Hospital, Boston, Massachusetts.
Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts.

Angela Su (A)

INSERM UMR 944, IRSL, St Louis Hospital, Paris, France.

Amanda L Robichaud (AL)

Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.

Amy Saur Conway (A)

Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.

Katherine Tarlock (K)

Seattle Children's Hospital, Cancer and Blood Disorders Center, Seattle, Washington.

Elliot Stieglitz (E)

Department of Pediatrics, Division of Hematology/Oncology, Benioff Children's Hospital and the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California.

Andrew E Place (AE)

Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Division of Hematology/Oncology, Boston Children's Hospital, Boston, Massachusetts.

Alexandre Puissant (A)

INSERM UMR 944, IRSL, St Louis Hospital, Paris, France.

Stephen P Hunger (SP)

Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Department of Pediatrics and Abramson Cancer Center at the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.

Annette S Kim (AS)

Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.

Neal I Lindeman (NI)

Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.

Lia Gore (L)

Children's Hospital Colorado, University of Colorado Cancer Center, Aurora, Colorado.

Katherine A Janeway (KA)

Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Division of Hematology/Oncology, Boston Children's Hospital, Boston, Massachusetts.

Lewis B Silverman (LB)

Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Division of Hematology/Oncology, Boston Children's Hospital, Boston, Massachusetts.

Jeffrey W Tyner (JW)

Division of Hematology and Medical Oncology, Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon.

Marian H Harris (MH)

Department of Pathology, Boston Children's Hospital, Boston, Massachusetts.

Mignon L Loh (ML)

Department of Pediatrics, Division of Hematology/Oncology, Benioff Children's Hospital and the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California.

Kimberly Stegmaier (K)

Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. Kimberly_stegmaier@dfci.harvard.edu Yana_pikman@dfci.harvard.edu.
Division of Hematology/Oncology, Boston Children's Hospital, Boston, Massachusetts.
Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts.

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