PMID- 31661160
OWN - NLM
STAT- MEDLINE
DCOM- 20200812
LR  - 20210201
IS  - 1097-0142 (Electronic)
IS  - 0008-543X (Print)
IS  - 0008-543X (Linking)
VI  - 126
IP  - 3
DP  - 2020 Feb 1
TI  - Mixed-phenotype acute leukemia: A cohort and consensus research strategy from the 
      Children's Oncology Group Acute Leukemia of Ambiguous Lineage Task Force.
PG  - 593-601
LID - 10.1002/cncr.32552 [doi]
AB  - 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.
CI  - (c) 2019 American Cancer Society.
FAU - Orgel, Etan
AU  - Orgel E
AUID- ORCID: 0000-0002-1487-6818
AD  - Department of Pediatrics, Children's Hospital Los Angeles, Los Angeles, 
      California.
AD  - Department of Pediatrics, University of Southern California, Los Angeles, 
      California.
FAU - Alexander, Thomas B
AU  - Alexander TB
AD  - Department of Pediatrics, University of North Carolina, Chapel Hill, North 
      Carolina.
FAU - Wood, Brent L
AU  - Wood BL
AD  - Departments of Laboratory Medicine and Pathology, University of Washington, 
      Seattle, Washington.
FAU - Kahwash, Samir B
AU  - Kahwash SB
AD  - Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, 
      Columbus, Ohio.
FAU - Devidas, Meenakshi
AU  - Devidas M
AD  - Department of Global Pediatric Medicine, St Jude Children's Research Hospital, 
      Memphis, Tennessee.
FAU - Dai, Yunfeng
AU  - Dai Y
AD  - Department of Biostatistics, University of Florida, Gainesville, Florida.
FAU - Alonzo, Todd A
AU  - Alonzo TA
AD  - Department of Preventive Medicine, University of Southern California, Los 
      Angeles, California.
FAU - Mullighan, Charles G
AU  - Mullighan CG
AD  - Department of Pathology, St Jude Children's Research Hospital, Memphis, 
      Tennessee.
FAU - Inaba, Hiroto
AU  - Inaba H
AUID- ORCID: 0000-0003-0605-7342
AD  - Department of Oncology, St Jude Children's Research Hospital, Memphis, Tennessee.
FAU - Hunger, Stephen P
AU  - Hunger SP
AD  - 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.
FAU - Raetz, Elizabeth A
AU  - Raetz EA
AD  - Department of Pediatrics, NYU Langone Health, New York, New York.
FAU - Gamis, Alan S
AU  - Gamis AS
AD  - Department of Pediatrics, Children's Mercy Cancer Center, Kansas City, Missouri.
FAU - Rabin, Karen R
AU  - Rabin KR
AD  - Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
FAU - Carroll, Andrew J 3rd
AU  - Carroll AJ 3rd
AD  - Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama.
FAU - Heerema, Nyla A
AU  - Heerema NA
AD  - Department of Pathology, College of Medicine, The Ohio State University Wexner 
      Medical Center, Columbus, Ohio.
FAU - Berman, Jason N
AU  - Berman JN
AD  - Department of Pediatrics and CHEO Research Institute, University of Ottawa, 
      Ottawa, Ontario, Canada.
FAU - Woods, William G
AU  - Woods WG
AD  - Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta/Emory 
      University, Atlanta, Georgia.
FAU - Loh, Mignon L
AU  - Loh ML
AD  - Department of Pediatrics, Benioff Children's Hospital and Helen Diller 
      Comprehensive Cancer Center, University of California, San Francisco, California.
FAU - Zweidler-McKay, Patrick A
AU  - Zweidler-McKay PA
AD  - ImmunoGen, Inc, Waltham, Massachusetts.
FAU - Horan, John T
AU  - Horan JT
AD  - Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta/Emory 
      University, Atlanta, Georgia.
CN  - Children's Oncology Group Acute Leukemia of Ambiguous Lineage Task Force
LA  - eng
GR  - U24 CA196173/CA/NCI NIH HHS/United States
GR  - U10 CA98543/CA/NCI NIH HHS/United States
GR  - R35 CA197695/CA/NCI NIH HHS/United States
GR  - U10 CA098543/CA/NCI NIH HHS/United States
GR  - U10 CA180899/CA/NCI NIH HHS/United States
GR  - U10 CA180886/CA/NCI NIH HHS/United States
GR  - U10 CA098413/CA/NCI NIH HHS/United States
GR  - U24 CA114766/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20191029
PL  - United States
TA  - Cancer
JT  - Cancer
JID - 0374236
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Child
MH  - Child, Preschool
MH  - Clinical Trials as Topic
MH  - Disease-Free Survival
MH  - Female
MH  - Hematopoietic Stem Cell Transplantation/*methods
MH  - Humans
MH  - Immunophenotyping/methods
MH  - Infant
MH  - Leukemia, Biphenotypic, Acute/*epidemiology/pathology/*therapy
MH  - Male
MH  - Pediatrics/trends
MH  - *Prognosis
MH  - World Health Organization
MH  - Young Adult
PMC - PMC7489437
MID - NIHMS1568225
OTO - NOTNLM
OT  - acute leukemia of ambiguous lineage
OT  - biphenotypic acute leukemia
OT  - hematopoietic stem cell transplantation
OT  - mixed-phenotype acute leukemia
OT  - pediatric leukemia
COIS- Potential conflicts of interest: SPH (Amgen [stock ownership], Merck [stock 
      ownership], Novartis [consulting fees]. PAZM (ImmunoGen [employment, stock 
      ownership]). The other authors report no potential competing interests.
EDAT- 2019/10/30 06:00
MHDA- 2020/08/13 06:00
PMCR- 2021/02/01
CRDT- 2019/10/30 06:00
PHST- 2019/03/26 00:00 [received]
PHST- 2019/08/29 00:00 [revised]
PHST- 2019/09/04 00:00 [accepted]
PHST- 2019/10/30 06:00 [pubmed]
PHST- 2020/08/13 06:00 [medline]
PHST- 2019/10/30 06:00 [entrez]
PHST- 2021/02/01 00:00 [pmc-release]
AID - 10.1002/cncr.32552 [doi]
PST - ppublish
SO  - Cancer. 2020 Feb 1;126(3):593-601. doi: 10.1002/cncr.32552. Epub 2019 Oct 29.