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High NPM1 mutant allele burden at diagnosis correlates with minimal residual disease at first remission in de novo acute myeloid leukemia.

Author information

Affiliations

  • 1. Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
      Authors
    • Patel SS 1
    • Pinkus GS 1
    • Dal Cin P 1
    • Weinberg OK 1, 3
    (4 authors)
  • 2. Division of Genomic and Molecular Pathology, University of Chicago, Chicago, Illinois.
      Authors
    • Ritterhouse LL 2
    • Segal JP 2
    (2 authors)
  • 3. Department of Pathology, Boston Children's Hospital, Boston, Massachusetts.
      Authors
    • Restrepo T 3
    • Harris MH 3
    • Weinberg OK 1, 3
    (3 authors)
  • 4. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
      Authors
    • Stone RM 4
    (1 author)
  • 5. Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts.
      Authors
    • Hasserjian RP 5
    (1 author)

ORCIDs linked to this article

American Journal of Hematology, 17 Jun 2019, 94(8):921-928
https://doi.org/10.1002/ajh.25544 PMID: 31148220 

Abstract 

Acute myeloid leukemia (AML) with mutated NPM1 is a newly recognized separate entity in the revised 2016 WHO classification, and is associated with a favorable prognosis. While previous studies have evaluated NPM1 in a binary fashion, we recently demonstrated a significant independent negative prognostic effect of high NPM1 mutant allele burden (VAF) at diagnosis in a cohort of de novo AML patients. Although the importance of minimal residual disease (MRD) monitoring in NPM1-mutated AML has been well characterized, the potential relationship between diagnostic allele burden and MRD is unknown. We retrospectively evaluated for MRD at first remission (CR1). We used either next-generation sequencing (NGS) [n = 71], and/or immunohistochemistry (IHC) for mutant NPM1 (NPM1c) [n = 60], in a subset of patients from our recently examined cohort. We identified a statistically significant positive correlation between the VAF at diagnosis, and at CR1 (Spearman r = 0.4, P = .006), and enrichment for MRD in high diagnostic VAF patients (P = .05), as previously defined. IHC-positivity also correlated significantly with a higher median diagnostic NPM1 VAF (0.42 vs 0.39, P = .02), and with the VAF at CR1 (Spearman r = 0.7, P = .003). In multivariable analyses, both high diagnostic VAF (P = .003) and MRD (P = .02) were independent predictors of shorter event-free survival (EFS). Our findings suggest a relationship between the NPM1 mutant allele burden at diagnosis, and the presence of MRD at first remission. Our findings support IHC as a potentially useful adjunctive tool for disease monitoring.

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Read article at publisher's site: https://doi.org/10.1002/ajh.25544

Read article for free, from open access legal sources, via Unpaywall: https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ajh.25544Unpaywall

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