TY - JOUR
T1 - High NPM1 mutant allele burden at diagnosis correlates with minimal residual disease at first remission in de novo acute myeloid leukemia
AU - Patel, Sanjay S.
AU - Pinkus, Geraldine S.
AU - Ritterhouse, Lauren L.
AU - Segal, Jeremy P.
AU - Dal Cin, Paola
AU - Restrepo, Tamara
AU - Harris, Marian H.
AU - Stone, Richard M.
AU - Hasserjian, Robert P.
AU - Weinberg, Olga K.
N1 - Funding Information:
The authors would like to thank the European Association for Haematopathology for its monetary support via the David Y. Mason Award (S.S.P.).
Publisher Copyright:
© 2019 Wiley Periodicals, Inc.
PY - 2019/8
Y1 - 2019/8
N2 - 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.
AB - 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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U2 - 10.1002/ajh.25544
DO - 10.1002/ajh.25544
M3 - Article
C2 - 31148220
AN - SCOPUS:85067494111
SN - 0361-8609
VL - 94
SP - 921
EP - 928
JO - American Journal of Hematology
JF - American Journal of Hematology
IS - 8
ER -