Significance of minimal residual disease in pediatric mixed phenotype acute leukemia: a multicenter cohort study

• Type of Material: Article
• Authors: Matthew J. Oberley, Childrens Hospital Los Angeles; Sunil Raikar, Emory University; Gerald B. Wertheim, University of Pennsylvania; Jemily Malvar, Childrens Hospital Los Angeles; Richard Sposto, Childrens Hospital Los Angeles; Karen R. Rabin, Baylor College of Medicine; Jyotinder N. Punia, Baylor College of Medicine; Alix E. Seif, Childrens Hospital of Philadelphia; Viviane C. Cahen, Childrens Hospital of Philadelphia; Reuven J. Schore, Childrens National Medical Center; Dragos C. Luca, Childrens National Medical Center; Terri Guinipero, Ohio State University; William Woods, Emory University; Maurice R. G. O'Gorman, Childrens Hospital Los Angeles; Etan Orgel, Childrens Hospital Los Angeles
• Language: English
• Date: 2020-02-14
• Publisher: Nature Publishing Group
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © The Author(s), under exclusive licence to Springer Nature Limited 2020.
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41375-020-0741-0
• Title of Journal or Parent Work: Leukemia
• Volume: 34
• Issue: 7
• Start Page: 1741
• End Page: 1750
• Grant/Funding Information: Data was collated using the REDCAP database supported by NIH/NCATS UL1TR001855 and UL1TR000130.
• Keywords: Prognostic value; Risk; Science & Technology; Cell; Classification; Oncology; Hematology; Isolated myeloperoxidase expression; Acute lymphoblastic leukemia; Life Sciences & Biomedicine; World health organization; Therapy
• Research Categories: Biology, Cell; Health Sciences, Pathology; Health Sciences, Oncology; Health Sciences, Immunology

Abstract

The rarity of mixed phenotype acute leukemia (MPAL) has precluded adequate data to incorporate minimal residual disease (MRD) monitoring into therapy. Fluidity in MPAL classification systems further complicates understanding its biology and outcomes; this includes uncertainty surrounding the impact of shifting diagnostic requirements even between iterations of the World Health Organization (WHO) classification. Our primary objective was to address these knowledge gaps. To do so, we analyzed clinicopathologic features, therapy, MRD, and survival in a centrally-reviewed, multicenter cohort of MPAL uniformly diagnosed by the WHO classification and treated with acute lymphoblastic leukemia (ALL) regimens. ALL induction therapy achieved an EOI MRD negative (<0.01%) remission in most patients (70%). EOI MRD positivity was predictive of 5-year EFS (HR = 6.00, p < 0.001) and OS (HR = 9.57, p = 0.003). Patients who cleared MRD by EOC had worse survival compared with those EOI MRD negative. In contrast to adults with MPAL, ALL therapy without transplantation was adequate to treat most pediatric patients. Earlier MRD clearance was associated with better treatment success and survival. Prospective trials are now necessary to validate and refine MRD thresholds within the pediatric MPAL population and to identify salvage strategies for those with poor predicted survival.