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

Sanjay S. Patel, Geraldine S. Pinkus, Lauren L. Ritterhouse, Jeremy P. Segal, Paola Dal Cin, Tamara Restrepo, Marian H. Harris, Richard M. Stone, Robert P. Hasserjian, Olga K. Weinberg

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)921-928
Number of pages8
JournalAmerican Journal of Hematology
Volume94
Issue number8
DOIs
StatePublished - Aug 2019
Externally publishedYes

ASJC Scopus subject areas

  • Hematology

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