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

Authors
  • Orgel, Etan1, 2
  • Alexander, Thomas B3
  • Wood, Brent L4
  • Kahwash, Samir B5
  • Devidas, Meenakshi6
  • Dai, Yunfeng7
  • Alonzo, Todd A8
  • Mullighan, Charles G9
  • Inaba, Hiroto10
  • Hunger, Stephen P11
  • Raetz, Elizabeth A12
  • Gamis, Alan S13
  • Rabin, Karen R14
  • Carroll, Andrew J 3rd15
  • Heerema, Nyla A16
  • Berman, Jason N17
  • Woods, William G18
  • Loh, Mignon L19
  • Zweidler-McKay, Patrick A20
  • Horan, John T18
  • 1 Department of Pediatrics, Children's Hospital Los Angeles, Los Angeles, California.
  • 2 Department of Pediatrics, University of Southern California, Los Angeles, California.
  • 3 Department of Pediatrics, University of North Carolina, Chapel Hill, North Carolina.
  • 4 Departments of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington.
  • 5 Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, Ohio.
  • 6 Department of Global Pediatric Medicine, St Jude Children's Research Hospital, Memphis, Tennessee.
  • 7 Department of Biostatistics, University of Florida, Gainesville, Florida.
  • 8 Department of Preventive Medicine, University of Southern California, Los Angeles, California.
  • 9 Department of Pathology, St Jude Children's Research Hospital, Memphis, Tennessee.
  • 10 Department of Oncology, St Jude Children's Research Hospital, Memphis, Tennessee.
  • 11 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.
  • 12 Department of Pediatrics, NYU Langone Health, New York, New York.
  • 13 Department of Pediatrics, Children's Mercy Cancer Center, Kansas City, Missouri.
  • 14 Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
  • 15 Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama.
  • 16 Department of Pathology, College of Medicine, The Ohio State University Wexner Medical Center, Columbus, Ohio.
  • 17 Department of Pediatrics and CHEO Research Institute, University of Ottawa, Ottawa, Ontario, Canada. , (Canada)
  • 18 Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta/Emory University, Atlanta, Georgia. , (Georgia)
  • 19 Department of Pediatrics, Benioff Children's Hospital and Helen Diller Comprehensive Cancer Center, University of California, San Francisco, California.
  • 20 ImmunoGen, Inc, Waltham, Massachusetts.
Type
Published Article
Journal
Cancer
Publisher
Wiley (John Wiley & Sons)
Publication Date
Feb 01, 2020
Volume
126
Issue
3
Pages
593–601
Identifiers
DOI: 10.1002/cncr.32552
PMID: 31661160
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

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. © 2019 American Cancer Society.

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