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Author Notes:

Correspondence: Etan Orgel, M.D. M.S., Division of Hematology, Oncology, BMT, Children’s Hospital Los Angeles, 4650 Sunset Blvd, MS#54, Los Angeles, CA 90027, Fax: (323) 361-7128; Phone: (323) 361-2672, eorgel@chla.usc.edu

Author contributions: E.O: study conception & research design; M.J.O. and G.W. conducted the hematopathology central review; J.M. and R.S. performed the statistical analysis; M.J.O, S.S.R., and E.O. wrote the manuscript first draft; All authors contributed case data, interpreted the analysis, and reviewed/edited manuscript.

Disclosures: M.J.O. is currently employed at Caris Life Sciences. There are no other conflicts of interest to report.

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Research Funding:

Data was collated using the REDCAP database supported by NIH/NCATS UL1TR001855 and UL1TR000130.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Oncology
  • Hematology
  • Isolated myeloperoxidase expression
  • Acute lymphoblastic leukemia
  • World health organization
  • Prognostic value
  • Classification
  • Risk
  • Cell
  • Therapy

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

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Journal Title:

Leukemia

Volume:

Volume 34, Number 7

Publisher:

, Pages 1741-1750

Type of Work:

Article | Post-print: After Peer Review

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.

Copyright information:

© The Author(s), under exclusive licence to Springer Nature Limited 2020.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (https://creativecommons.org/licenses/by-nc/4.0/).
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