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classification) to weighted scores. See TABLE 1 for a description of the components in each risk model.
“The strong impact of cytogenetic/molecular risks on mortality is not a surprise,” the authors commented,
but “why increasing age continues to have a significantly independent impact on mortality after accounting for
comorbidities is unclear.” They suggested that the acquisition of additional adverse molecular AML markers
with aging could explain this association.
In the validation set, the authors compared the
TABLE 1. Components of the AML-CM
prognostic ability of the novel AML-CM with the
and Their Corresponding Scores
AML-CI, the original hematopoietic cell transplanta-
tion comorbidity index (HCT-CI), and an augmented
Comorbidity
Score
HCT-CI (constructed from the 17 comorbidities in the
The HCT-CI
original HCT-CI plus hypoalbuminemia, thrombocy-
Arrhythmia
1
topenia, and high LDH values – predictive factors that
Cardiac dysfunction (coronary artery
1
were identified in multivariate analyses).
disease, congestive heart failure, myocardial
The prognostic models’ performances were com-
infarction, or EF ≤50%)
pared using C statistics for continuous outcomes and
Inflammatory bowel disease
1
area under the curve (AUC) for binary outcomes.
Diabetes
1
As seen in TABLE 2 , the augmented HCT-CI
Cerebrovascular
disease
(transient
ischemic
1
performed better than either AML-CI or the original
attack or cerebrovascular accident)
HCT-CI in predicting early and late mortality,
Psychiatric disturbance
1
“[validating] that comorbidities have a significant
Mild hepatic dysfunction
1
impact on early and one-year mortality [in this
Obesity
1
patient population],” the authors noted. And, when
comorbidities, age, and cytogenetic/molecular risks
Infection
1
were incorporated into the AML-CM, it performed
Rheumatologic comorbidity
2
better than any of the individual risk components
Peptic ulcer
2
alone (C statistic = 0.72 and AUC = 0.76 for 1-year
Moderate/severe renal dysfunction
2
mortality; AUC=0.78 for 8-week mortality).
Moderate pulmonary comorbidity
2
“Just as using the HCT-CI before allogeneic HCT
Prior malignancy
3
has had a major impact on the decision to proceed to
HCT, we believe use of the AML-CM could inform
Heart valve disease
3
decisions as to whether patients with newly diagnosed
Severe pulmonary comorbidity
3
AML should receive more intensive or less intensive
Moderate/severe hepatic dysfunction
3
therapies for their disease,” the researchers concluded.
The Augmented HCT-CI (all of the above, plus the
“This model could prove useful to the U.S. Food
following)
and Drug Administration when monitoring clinical
Hypoalbuminemia <3.5 g/dL
1
trials to ensure adequate representation of high-risk
Thrombocytopenia
1
patients in these trials and, hence, generalizability of
LDH >200-1,000 U/L
1
trial results to the whole AML population.”
The model did not incorporate treatment
LDH >1,000 U/L
2
intensity (though it was shown to predict mortal-
The AML-CM (all of the above, plus the following)
ity), because patients received therapies of differing
Age 50-59 years
1
intensities and because “this is the decision that we
Age ≥60 years
2
plan to improve based on the AML-CM scores,”
ELN intermediate cytogenetic/molecular
1
they added. The study also is limited by the retro-
risk
spective nature of data collection.
ELN adverse cytogenetic/molecular risk
2
The authors report no conflicts.
REFERENCE
Sorror ML, Storer BE, Fathi AT, et al. Development and validation of a novel acute
myeloid leukemia–composite model to estimate risks of mortality. JAMA Oncol. 2017
September 7. [Epub ahead of print]
HCT = hematopoietic cell transplantation; CI = comorbidity
index; EF = ejection fraction; AML = acute myeloid leukemia;
LDH = lactate dehydrogenase; ELN = European Leukemia Net
Comparisons of the Performance of Risk Factors and Indices in
the Validation Set
TABLE 2.
Risk factor
AML-CI
C-statistic for 1-year
mortality
True AUC for 1-year
mortality
True AUC for 8-week
mortality
n (SD) n (SD) n (SD)
314 0.596
(0.019) 297 0.606
(0.039) 305 0.659
(0.043)
Original HCT-CI 352 0.649
(0.025) 326 0.674
(0.028) 339 0.684
(0.042)
Augmented HCT-CI 305 0.664
(0.023) 289 0.687
(0.035) 296 0.721
(0.046)
Age (groups) 367 0.640
(0.020) 340 0.682
(0.029) 354 0.640
(0.040)
Cytogenetic/molecular risks
(groups) 350 0.614
(0.020) 324 0.654
(0.023) 337 0.597
(0.042)
AML-CM 292 0.719
(0.022) 277 0.758
(0.030) 283 0.776
(0.035)
KPS (groups) 291 0.619
(0.027) 266 0.646
(0.035) 279 0.676
(0.048)
AUC = area under the curve; SD = standard deviation; AML = acute myeloid leukemia; CI = comorbidity index; CM = composite model;
HCT-CI = hematopoietic cell transplantation comorbidity index; KPS = Karnofsky performance status
ASHClinicalNews.org
Luspatercept
Shows Activity
in Patients With
Lower-Risk MDS
and Anemia
Erythropoiesis-stimulating agents (ESAs) are a standard
treatment for patients with myelodysplastic syndromes
(MDS) and anemia; however, only around one-third of
patients have an erythroid response to ESAs, suggesting
that improving erythropoiesis in MDS might be best
achieved by targeting downstream processes indepen-
dent of erythropoietin regulation.
In the phase II, dose-finding PACE-MDS study with
long-term extension, Uwe Platzbecker, MD, from the
Department of Internal Medicine I at the University
Hospital Carl Gustav Carus in Dresden, Germany, and
co-authors evaluated whether the recombinant fusion
protein luspatercept could provide a new therapeutic
approach in anemic patients with lower-r