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

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 accep...

Full description

Saved in:
Bibliographic Details
Published inCancer Vol. 126; no. 3; pp. 593 - 601
Main Authors Orgel, Etan, Alexander, Thomas B., Wood, Brent L., Kahwash, Samir B., Devidas, Meenakshi, Dai, Yunfeng, Alonzo, Todd A., Mullighan, Charles G., Inaba, Hiroto, Hunger, Stephen P., Raetz, Elizabeth A., Gamis, Alan S., Rabin, Karen R., Carroll, Andrew J., Heerema, Nyla A., Berman, Jason N., Woods, William G., Loh, Mignon L., Zweidler‐McKay, Patrick A., Horan, John T.
Format Journal Article
LanguageEnglish
Published United States Wiley Subscription Services, Inc 01.02.2020
Subjects
Online AccessGet full text

Cover

Loading…
More Information
Summary: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. Acute lymphoblastic leukemia–directed chemotherapy without hematopoietic stem cell transplantation may be sufficient therapy for most children with World Health Organization 2016 classification–defined mixed‐phenotype acute leukemia. A proposed prospective trial will investigate this approach and explore mixed‐phenotype acute leukemia genomics and correlative biology.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
PAZM and JTH should be considered joint senior authors.
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.
ISSN:0008-543X
1097-0142
DOI:10.1002/cncr.32552