Mixed-phenotype acute leukemia: A cohort and consensus research strategy from the Children's Oncology Group Acute Leukemia of Ambiguous Lineage Task Force.


Journal

Cancer
ISSN: 1097-0142
Titre abrégé: Cancer
Pays: United States
ID NLM: 0374236

Informations de publication

Date de publication:
01 02 2020
Historique:
received: 26 03 2019
revised: 29 08 2019
accepted: 04 09 2019
pubmed: 30 10 2019
medline: 13 8 2020
entrez: 30 10 2019
Statut: ppublish

Résumé

Optimal chemotherapy for treating mixed-phenotype acute leukemia (MPAL) and the role of hematopoietic stem cell transplantation (HSCT) remain uncertain. Major limitations in interpreting available data are MPAL's rarity and the use of definitions other than the currently widely accepted criteria: the World Health Organization 2016 (WHO2016) classification. To assess the relative efficacy of chemotherapy types for treating pediatric MPAL, the Children's Oncology Group (COG) Acute Leukemia of Ambiguous Lineage Task Force assembled a retrospective cohort of centrally reviewed WHO2016 MPAL cases selected from banking studies for acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Patients were not treated in COG trials; treatment and outcome data were captured separately. The findings were then integrated with the available, mixed literature to develop a prospective trial in pediatric MPAL. The central review confirmed that 54 of 70 cases fulfilled WHO2016 criteria for MPAL. ALL induction regimens achieved remission in 72% of the cases (28 of 39), whereas AML regimens achieved remission in 69% (9 of 13). The 5-year event-free survival (EFS) and overall survival (OS) rates for the entire cohort were 72% ± 8% and 77% ± 7%, respectively. EFS and OS were 75% ± 13% and 84% ± 11%, respectively, for those receiving ALL chemotherapy alone without HSCT (n = 21). The results of the COG MPAL cohort and a literature review suggest that ALL chemotherapy without HSCT may be the preferred initial therapy. A prospective trial within the COG is proposed to investigate this approach; AML chemotherapy and/or HSCT will be reserved for those with treatment failure as assessed by minimal residual disease. Embedded biology studies will provide further insight into MPAL genomics.

Sections du résumé

BACKGROUND
Optimal chemotherapy for treating mixed-phenotype acute leukemia (MPAL) and the role of hematopoietic stem cell transplantation (HSCT) remain uncertain. Major limitations in interpreting available data are MPAL's rarity and the use of definitions other than the currently widely accepted criteria: the World Health Organization 2016 (WHO2016) classification.
METHODS
To assess the relative efficacy of chemotherapy types for treating pediatric MPAL, the Children's Oncology Group (COG) Acute Leukemia of Ambiguous Lineage Task Force assembled a retrospective cohort of centrally reviewed WHO2016 MPAL cases selected from banking studies for acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Patients were not treated in COG trials; treatment and outcome data were captured separately. The findings were then integrated with the available, mixed literature to develop a prospective trial in pediatric MPAL.
RESULTS
The central review confirmed that 54 of 70 cases fulfilled WHO2016 criteria for MPAL. ALL induction regimens achieved remission in 72% of the cases (28 of 39), whereas AML regimens achieved remission in 69% (9 of 13). The 5-year event-free survival (EFS) and overall survival (OS) rates for the entire cohort were 72% ± 8% and 77% ± 7%, respectively. EFS and OS were 75% ± 13% and 84% ± 11%, respectively, for those receiving ALL chemotherapy alone without HSCT (n = 21).
CONCLUSIONS
The results of the COG MPAL cohort and a literature review suggest that ALL chemotherapy without HSCT may be the preferred initial therapy. A prospective trial within the COG is proposed to investigate this approach; AML chemotherapy and/or HSCT will be reserved for those with treatment failure as assessed by minimal residual disease. Embedded biology studies will provide further insight into MPAL genomics.

Identifiants

pubmed: 31661160
doi: 10.1002/cncr.32552
pmc: PMC7489437
mid: NIHMS1568225
doi:

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

593-601

Subventions

Organisme : NCI NIH HHS
ID : U24 CA196173
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA98543
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA197695
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA098543
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA180899
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA180886
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA098413
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA114766
Pays : United States

Informations de copyright

© 2019 American Cancer Society.

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Auteurs

Etan Orgel (E)

Department of Pediatrics, Children's Hospital Los Angeles, Los Angeles, California.
Department of Pediatrics, University of Southern California, Los Angeles, California.

Thomas B Alexander (TB)

Department of Pediatrics, University of North Carolina, Chapel Hill, North Carolina.

Brent L Wood (BL)

Departments of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington.

Samir B Kahwash (SB)

Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, Ohio.

Meenakshi Devidas (M)

Department of Global Pediatric Medicine, St Jude Children's Research Hospital, Memphis, Tennessee.

Yunfeng Dai (Y)

Department of Biostatistics, University of Florida, Gainesville, Florida.

Todd A Alonzo (TA)

Department of Preventive Medicine, University of Southern California, Los Angeles, California.

Charles G Mullighan (CG)

Department of Pathology, St Jude Children's Research Hospital, Memphis, Tennessee.

Hiroto Inaba (H)

Department of Oncology, St Jude Children's Research Hospital, Memphis, Tennessee.

Stephen P Hunger (SP)

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

Elizabeth A Raetz (EA)

Department of Pediatrics, NYU Langone Health, New York, New York.

Alan S Gamis (AS)

Department of Pediatrics, Children's Mercy Cancer Center, Kansas City, Missouri.

Karen R Rabin (KR)

Department of Pediatrics, Baylor College of Medicine, Houston, Texas.

Andrew J Carroll (AJ)

Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama.

Nyla A Heerema (NA)

Department of Pathology, College of Medicine, The Ohio State University Wexner Medical Center, Columbus, Ohio.

Jason N Berman (JN)

Department of Pediatrics and CHEO Research Institute, University of Ottawa, Ottawa, Ontario, Canada.

William G Woods (WG)

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

Mignon L Loh (ML)

Department of Pediatrics, Benioff Children's Hospital and Helen Diller Comprehensive Cancer Center, University of California, San Francisco, California.

Patrick A Zweidler-McKay (PA)

ImmunoGen, Inc, Waltham, Massachusetts.

John T Horan (JT)

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

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