Literature Scan
Presence of Minimal Residual Disease
Predicts Relapse and Survival in AML
For patients with acute myeloid leuke-
mia (AML), the detection of molecular
minimal residual disease (MRD) in
patients achieving morphologic complete
remission (CR) was associated with a
higher risk of relapse and a lower risk of
relapse-free survival, according to a study
published in The New England Journal of
Medicine. Recurrent mutations associated
with clonal hematopoiesis of indetermi-
nate potential (CHIP) during a four-year
follow-up period, however, did not pro-
vide this prognostic value.
“In this study, genetic sequencing
and multiparameter flow cytometry
each had independent and additive
prognostic value with respect to rates
of relapse and survival in patients with
AML,” the authors, led by Mojk Jongen-
Lavrencic, MD, PhD, from Erasmus
University Medical Center in Rotterdam,
Netherlands, wrote. “The detection of
residual leukemia with both methods is
associated with an excessively high prob-
ability of relapse (approximately 75%).”
Conversely, “the absence of [MRD] is
correlated with a relatively low probabil-
ity of relapse (approximately 25%).”
The trial enrolled 482 patients with
previously untreated AML or myelodys-
plastic syndromes involving refractory
anemia with excess blasts; all partici-
pants were in CR or CR with incomplete
hematologic recovery (CRi) and were
considered to be at high or very-high
risk of relapse (defined as a >4.5 score
on the Revised International Prognostic
Scoring System).
Patients underwent targeted next-
generation sequencing at diagnosis
and during CR to detect mutations in
54 genes associated with hematologic
malignancies. MRD also was detected
using multiparameter flow cytometry.
Nearly 90 percent of patients
(n=430) had at least one mutation at
diagnosis, and the average number of
mutations was 2.9 per patient. The most
common of these were mutations in
NPM1, DNMT3A, FLT3, and NRAS.
During CR, 51.4 percent of these
patients had persistent mutations and
“the rate at which mutations persisted
was highly variable across genes,”