About this item:

69 Views | 23 Downloads

Author Notes:

Correspondence: Etan Orgel, MD, MS, Children’s Hospital Los Angeles, 4650 Sunset Blvd., MS #54, Los Angeles, CA 90027, Phone: (323) 361-2672, eorgel@chla.usc.edu

Author contributions: Etan Orgel & John T. Horan: Conceptualization, investigation, methodology, data curation, writing- original draft, writing- review/editing. Patrick A. Zweidler- McKay: Conceptualization, investigation, methodology, writing review/editing.

Meenakshi Devidas & Yunfeng Dai: Investigation, methodology, data curation, formal analysis, writing review/editing. All other authors: investigation, methodology, writing- review/editing.

Acknowledgements: MLL is the UCSF Benioff Chair of Children’s Health and Deborah and Arthur Ablin Endowed Chair in Pediatric Molecular Oncology. EAR is a KiDS of NYU Foundation Professor at NYU Langone Health.

SPH is the Jeffrey E. Perelman Distinguished Chair in the Department of Pediatrics at the Children’s Hospital of Philadelphia. C.G.M. is the William E. Evans Endowed Chair at St. Jude Children’s Research Hospital.

Disclosures: SPH (Amgen [stock ownership], Merck [stock ownership], Novartis [consulting fees]. PAZM (ImmunoGen [employment, stock ownership]). The other authors report no potential competing interests.


Research Funding:

Supported by the Children’s Oncology Group via the National Cancer Institute (NCI) awards U10 CA98543, U10 CA98413, U10 CA180886, U24 CA114766, U24 CA196173 and U10 CA180899, and an NCI outstanding Investigator Award R35-CA197695 (to C.G.M.).

Additional support was received from the St. Baldrick’s Foundation, The Henry Schueler 41&9 Foundation (to C.G.M.), and Cookies 4 Kids (to H.I.).


  • Science & Technology
  • Life Sciences & Biomedicine
  • Oncology
  • acute leukemia of ambiguous lineage
  • biphenotypic acute leukemia
  • hematopoietic stem cell transplantation
  • mixed-phenotype acute leukemia
  • pediatric leukemia
  • Isolated myeloperoxidase expression
  • Stem-cell transplantation
  • World health organization
  • Relapse risk
  • T-cells
  • Classification
  • Outcomes
  • Survival
  • Therapy

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

Show all authors Show less authors


Journal Title:



Volume 126, Number 3


, Pages 593-601

Type of Work:

Article | Post-print: After Peer Review


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.

Copyright information:

© American Cancer Society.

Export to EndNote