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

• Authors: Etan Orgel, Childrens Hospital Los Angeles; Thomas B. Alexander, University of North Carolina; Brent L. Wood, University of Washington; Samir B. Kahwash, Nationwide Childrens Hospital; Meenakshi Devidas, St Jude Childrens Research Hospital; Yunfeng Dai, University of Florida; Todd A. Alonzo, University of Southern California; Charles G. Mullighan, St Jude Childrens Research Hospital; Hiroto Inaba, St Jude Childrens Research Hospital; Stephen P. Hunger, Childrens Hospital of Philadelphia; Elizabeth A. Raetz, NYU Langone Health; Alan S. Gamis, Childrens Mercy Cancer Center; Karen R. Rabin, Baylor College of Medicine; Andrew J. Carroll, University of Alabama Birmingham; Nyla Heerema, Ohio State University; Jason N. Berman, University of Ottawa; William Woods, Emory University; Mignon L. Loh, University of California San Francisco; Patrick A. Zweidler-McKay, ImmunoGen, Inc.; John Horan, Emory University
• Journal Title: Cancer
• Volume: Volume 126, Number 3
• Publisher: Wiley | 2019-10-29, Pages 593-601
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1002/cncr.32552
• Subjects: Health Sciences, Rehabilitation and Therapy; Health Sciences, Oncology; Biology, Cell; Health Sciences, Immunology
• Keywords: 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

Abstract

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.