CLINICAL NEWS
Written in Blood
also had not taken mineral, vitamin, or
herbal supplements within two weeks
of the study’s start date and during the
entire duration of the study.
Dr. Moretti and co-authors actually
conducted three separate studies to
examine the iron-hepcidin relationship:
First, a dose-finding investigation in
which iron supplements were administered in four different concentrations
(40, 60, 80, 160, and 240 mg) at eight
hours fasting on one day (study 1,
n=25); second, in which supplements
were given on two consecutive days
(study 2, n=16); and third, a study
giving three 60 mg iron doses (twice-aday dosing) within 24 hours (study 3,
n=13).
In all three studies, participants
acted as their own controls. Iron
absorption was assessed by measuring
the amount of stable isotopic tracers
incorporated in red blood cells 14 days
post-administration.
Studies 1 and 2 indicated that 24
hours after doses of 60 mg of iron or
higher were administered, serum hepcidin was increased, while fractional
iron absorption was decreased by 35
to 45 percent (p<0.01 for both). With
each increased dose of iron, fractional
absorption decreased, while absolute
absorption increased (p<0.001 for
both). Also, a six-fold increase in iron
dose (from 40 mg to 240 mg) resulted
in just a three-fold increase in iron
absorbed: 6.7 mg to 18.1 mg.
Study 3 found that total iron
absorbed from three doses was not
significantly greater than the iron absorbed from two morning doses.
“Our data show that fractional
absorption in iron-depleted women is
highest at low iron doses (40-80 mg)
and that acute, consecutive-day dosing
results in decreased iron bioavailability,”
the authors concluded. “Providing 60
mg of iron twice-daily amplified the
plasma hepcidin increase and decreased
the fractional absorption of both the
afternoon dose and the next morning
dose, so that total iron absorbed from
the three doses [two mornings and one
afternoon] was not different to that
from two morning doses.”
“In the short-term in this population, iron at doses of 60 mg and
higher increases hepcidin, which has a
detrimental effect on iron absorption of
the subsequent dose on the next day,”
Dr. Moretti said. “In addition, our data
suggest that the common practice of
splitting doses to the morning and the
afternoon does not increase the bioavailability. On the contrary, it appears
that concentrating the supplementation
Novel Combination of ISS and EMC92 Gene Classifier Leads
to Better Risk Stratification in Multiple Myeloma
Patients with multiple myeloma have
variable survival rates and require
reliable prognostic and predictive scoring systems. Currently, the available
clinical and biologic risk markers are
used independently; but in a recent
study published in Blood, investigators found that the combination of
the International Staging System (ISS)
and biologic markers identified from
fluorescence in situ hybridization
(FISH)-based cytogenetics and geneexpression profiling (GEP) led to novel
risk classifications.
“Adequate prognostication of disease
outcome is important in order to make
treatment choices and to allocate highrisk patients to alternative treatment
options,” Rowan Kuiper, BSc, from the
Department of Hematology at Erasmus
MC Cancer Institute in Rotterdam,
Netherlands, and co-authors explained.
In the study, Dr. Kuiper and
colleagues systematically evaluated
all published risk markers used in
multiple myeloma, then compared
different combinations of FISH-, ISS-,
and GEP-based prognostic systems,
to find novel risk classifications in a
discovery/validation setting.
The researchers used data from the
following clinical studies:
• HOVON-65/GMMG-HD4 (newly
diagnosed patients)
• MRC-IX—intensive and nonintensive
(newly diagnosed patients)
• UAMS-TT2 (newly diagnosed
patients)
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ASH Clinical News
• UAMS-TT3 (newly diagnosed
patients)
• IFM-G (newly diagnosed patients)
• APEX (relapsed patients)
Data on overall survival (OS) or progression-free survival (PFS) and at least one
prognostic marker were available for all
patients. A total of 20 risk markers were
evaluated in 4,750 patients.
For OS, the following markers were
found to be significant:
• the FISH markers t(4;14), del17p,
gain1q, and del13q
• all GEP classifiers (EMC92, UAMS17,
UAMS70, UAMS80, MRCIX6,
IFM15, HM19, GPI50)
• ISS levels 1, 2, and 3
The data were split into discovery and
validation sets. The discovery set was
used to find meaningful combinations of
markers