Literature Scan
All 86 patients had banked bone
marrow samples available, and 58 had
pretransplant samples available. Bone
marrow samples at 30 days post-
transplant were available for all 86
patients, and samples at 100 days post-
transplant were available for 58 of them.
Skin samples from all participants also
were sequenced and analyzed. In this
study, samples were considered to be
positive for a mutation if the maximum
variant allele frequency (VAF) was
≥0.5 percent.
The investigators used enhanced
exome sequencing, which included
probes for 285 genes that are fre-
quently mutated in MDS and acute
myeloid leukemia, to detect muta-
tions in pre-AHCT samples, then
evaluated mutation clearance by
using error-corrected sequencing to
genotype mutations in post-AHCT
bone marrow samples.
During a median follow-up of
356 days (range = 45-2,786 days),
35 of the 86 patients had disease
progression after transplant. The
median time to progression was 141
days (range = 27-1,308 days).
Nearly all enrolled patients
(n=86/90; 96%) had at least one
somatic mutation detected on
pretransplantation sequencing.
Of these, 32 patients (37%) had at
least one mutation with a VAF ≥0.5
percent at 30-day follow-up.
Patients whose disease pro-
gressed had mutations with a high-
er VAF at 30 days, compared with
those who did not have progressive
disease (median maximum VAF =
0.9% vs. 0%; p<0.001).
After adjusting for pre-AHCT
conditioning regimens (either
myeloablative [n=50] or reduced-
intensity [n=36]), the investiga-
tors also found that the presence
of at least one high VAF mutation
conferred a higher risk of disease
progression and a lower likelihood
of PFS at one year, compared with
no mutation:
• disease progression: 53.1% vs.
13.0% (conditioning regimen-
adjusted hazard ratio [HR]
= 3.86; 95% CI 1.96-7.62;
p<0.001)
• PFS: 31.3% vs. 59.3%
(conditioning regimen-
adjusted HR=2.22; 95% CI
1.32-3.73; p=0.005)
Type of conditioning regimen
also was associated with disease
progression, with patients who
received reduced-intensity condi-
tioning at a greater risk for dis-
ease progression, compared with
those who received myeloablative
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ASH Clinical News
conditioning (HR=0.40; 95% 0.21-0.78;
p=0.007).
“The rate of [PFS] was lower among
patients who had received a reduced-
intensity conditioning regimen and had
at least one persistent mutation with a
[VAF] of at least 0.5 percent at day 30 than
among patients with other combinations
of conditioning regimen and mutation
status (p≤0.001),” the authors added.
When the authors further adjusted
“We hope these findings lead to
post-transplant mutation testing
being incorporated into routine
clinical care.”
—MEAGAN JACOBY, MD, PhD
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INDICATIONS
Jivi antihemophilic factor (recombinant), PEGylated-aucl, is a recombinant DNA-derived, Factor VIII
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Monitor patients for hypersensitivity symptoms.
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