TY - JOUR
T1 - Persistent IDH1/2 mutations in remission can predict relapse in patients with acute myeloid leukemia
AU - Ok, Chi Young
AU - Loghavi, Sanam
AU - Sui, Dawen
AU - Wei, Peng
AU - Kanagal Shamanna, Rashmi
AU - Yin, Cheng Cameron
AU - Zuo, Zhuang
AU - Routbort, Mark J
AU - Tang, Guilin
AU - Tang, Zhenya
AU - Jorgensen, Jeffrey L
AU - Luthra, Rajyalakshmi
AU - Ravandi-Kashani, Farhad
AU - Kantarjian, Hagop M
AU - DiNardo, Courtney
AU - Medeiros, L Jeffrey
AU - Wang, Sa
AU - Patel, Keyur Pravinchandra
N1 - Publisher Copyright:
© 2019 Ferrata Storti Foundation.
PY - 2019/1/31
Y1 - 2019/1/31
N2 - Persistence of IDH1 or IDH2 mutations in remission bone marrow specimens of patients with acute myeloid leukemia has been observed, but the clinical impact of these mutations is not well known. In this study, we evaluated 80 acute myeloid leukemia patients with known IDH1 R132 or IDH2 R140/R172 mutations and assessed their bone marrow at the time of remission to determine the potential impact of persistent IDH1/2 mutations. Approximately 40% of acute myeloid leukemia patients given standard treatment in this cohort had persistent mutations in IDH1/2. Patients with an IDH1/2 mutation had an increased risk of relapse after 1 year of follow-up compared to patients without a detectable IDH1/2 mutation (59% versus 24%; P<0.01). However, a persistent mutation was not associated with a shorter time to relapse. High IDH1/2mutation burden (mutant allelic frequency =10%) did not correlate with relapse rate (77% versus 86% for patients with a low burden, i.e., mutant allelic frequency <10%; P=0.66). Persistent mutations were also observed in NPM1, DNMT3A and FLT3 during remission, but IDH1/2 mutations remained significant in predicting relapse by multivariate analysis. Flow cytometry was comparable and complementary to next-generation sequencing-based assay for predicting relapse. Monitoring for persistent IDH1/2 mutations in patients with acute myeloid leukemia in remission can provide information that could be used to justify early interventions, with the hope of facilitating longer remissions and better outcomes in these patients.
AB - Persistence of IDH1 or IDH2 mutations in remission bone marrow specimens of patients with acute myeloid leukemia has been observed, but the clinical impact of these mutations is not well known. In this study, we evaluated 80 acute myeloid leukemia patients with known IDH1 R132 or IDH2 R140/R172 mutations and assessed their bone marrow at the time of remission to determine the potential impact of persistent IDH1/2 mutations. Approximately 40% of acute myeloid leukemia patients given standard treatment in this cohort had persistent mutations in IDH1/2. Patients with an IDH1/2 mutation had an increased risk of relapse after 1 year of follow-up compared to patients without a detectable IDH1/2 mutation (59% versus 24%; P<0.01). However, a persistent mutation was not associated with a shorter time to relapse. High IDH1/2mutation burden (mutant allelic frequency =10%) did not correlate with relapse rate (77% versus 86% for patients with a low burden, i.e., mutant allelic frequency <10%; P=0.66). Persistent mutations were also observed in NPM1, DNMT3A and FLT3 during remission, but IDH1/2 mutations remained significant in predicting relapse by multivariate analysis. Flow cytometry was comparable and complementary to next-generation sequencing-based assay for predicting relapse. Monitoring for persistent IDH1/2 mutations in patients with acute myeloid leukemia in remission can provide information that could be used to justify early interventions, with the hope of facilitating longer remissions and better outcomes in these patients.
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U2 - 10.3324/haematol.2018.191148
DO - 10.3324/haematol.2018.191148
M3 - Article
C2 - 30171025
AN - SCOPUS:85060953696
SN - 0390-6078
VL - 104
SP - 305
EP - 311
JO - Haematologica
JF - Haematologica
IS - 2
ER -