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You Make the Call: Readers’ Response
TRAINING
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ON
and EDUCATI
e program
Consult a Colleagu clinical
month’s
We asked, and
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Here are a few
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this month’s “You
Make the Call.”
ed
to next
question submitt in your response
e the Call we pick a challenging clinical
do. Send
You Mak
omatosis.
what you would print issue.
the Call,”
want to know
next
history of hemochr
“You Make
in
in the
a family
, but we also
Each month
mutation and
up to the expert’s
expert’s response
the C282Y
answer matches
and post the
a patient with
see how your
s managing
dilemma and
, MD, discusse
Susan F. Leitman
This month,
in the
showed ferritin le for
. The results
.
history is remarkab
ma:
by her primary-c liver function. Family for the C282Y mutation
performed
Clinical Dilem
red meat.
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homozygous
had iron studies
and eats no
38 percent,
that she is
are physician
of
ld woman
shows
method
mg/dL,
n saturation
A 19-year-o
iron of 208
genetic testing her oral contraceptive
range, transferri
of
matosis, and
showed a serum ng/mL. Would you
250 ng/mL
hemochro
301
iron studies
menses because
use
aunt with
and ferritin
She has no
however, her
told me to
a maternal
been pregnant.
liver function; n saturation of 78 percent, One hematologist
She has never labs showed normal
therapy?
mcg/dL, transferri on frequency of
Her most recent ing capacity of 268
decide
women.
you use to
pre-menopausal
total iron-bind y? And what would
as a goal in
start phlebotom
below 50 percent
saturation
transferrin
inion
Expert Op
Colleague
Consult a
ASH
Through is a service for ASH
Consult a Colleague facilitate the exchange
helps
members that between hematologists
on
can seek
of informati
ASH members
and their peers. clinical cases from qualified
on
consultation
:
11 categories
experts in
MD
Susan F. Leitman, Research Scholars
Director, Medical
Program
of Health
National Institutes
Bethesda, MD
for the HFE
homozygosity
frequent
matosis with
of the most
.
Genetic hemochro mutation is one
population
(C282Y)
in the Caucasian starts in
p.Cys282Tyr
recessive disorders ed iron absorption
autosomal
serum fer-
due to dysregulat
by an elevated
Iron loading
manifested
in this patient.
and may be
the teens, as
childhood
saturation in
in target organs,
30.
ritin and transferrin significant iron burden
levels.
until after age
use of
is below targeted
However, clinically
generally occur
women
liver, does not
in men than
when the ferritin level, to maximize effective ence, I would
19,
such as the
a faster pace
e that at age
On a practical
proceeds at
and inconveni
and
Iron loading
minimize costs
diet. It is remarkabl already has bio-
. The U.S. Food
affected by
resources and
for treatment
this patient
and can be
ng/mL
iron,
blood collection
301
a blood center
heme
of
a listing of
low in
y
ref er her to
with a ferritin
phlebotom
despite a diet
ation maintains
of excess iron,
Drug Administr deliver hemochromatosis meets blood
in women).
of
chemical evidence
that
150 ng/mL
1
the patient
with quality
of normal is
establishments
patient. If
(upper limit
made available
symptom interfering
charge to the
occurring
removed are
care without
find that
The most common
matosis is arthritis, be aggres-
the blood units
delighted to
can
with hemochro
donor criteria,
are usually
The arthritis
life in patients
n. Patients
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than discarded.
percent of subjects. severity is correlated
for transfusio
others rather
help
to
in 10 to 30
its
is used
to avoid alcohol
g; since
that early initiation
their blood
counseled
sive and debilitatin
it is assumed
should be
be vaccinated
The patient
at diagnosis,
She should
Elevated alanine s,
strongly
of her life.
arthropathy.
ferritin value
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for the rest
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y can prevent
to
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percent
her
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to
(if
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B
of
expose
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occurs in 10
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y prevents liver
counseled
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but advanced
Phlebotom
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testing.
of patients.
cancer.
hepatitis
ular
percent
genotype
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HFE
than
the risk of hepatocell
when the ferritin
vised to undergo
d treatment
and mitigates
a signif-
recommen
already has
for a Variance
Most experts
a.
Granted Approval
Since this patient age, female sex, and REFERENCE
“List of Establishments 20, 2018, from https://www.fd
300 ng/mL.
ariances/
her young
rapid
rises above
and Drug Administration. Accessed on March
eBloodSupply/V
1. U.S. Food
elevation despite to load iron at a more I
/Regulationofth
and 21CFR640.3(f).”
dBloodProducts
to 21CFR640.3(d)
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odVaccines/Bloo
diet, she appears hemochromatosis, and
gov/BiologicsBlo
.
low heme-iron
one 500-mL
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ucm164649.htm
typical
remove
the
pace than
y now. I would
phlebotom
until the ferritin
a:
would initiate
to four months
ce ferritin
every three
a maintenan
com-
’s Clinical Dilemm
unit of blood
and then target this to prevent
Next Month ld patient who presented had with
150 ng/mL,
a few atypi-
I would do
falls below
liver
months. He
and 200 ng/mL. arthropathy, as well as
(BM)
I have a 40-year-o
between 150
lasting three and his bone marrow
sociated
control at this
plaints of fever
l smear
aim for tighter
of acute pro-
hemochromatosis-as
e
to
reserves
periphera
his
iron
reason
in
suggestiv
with
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cal cells
gically
to leave her
to
injury. There
was not detected
was morpholo
and it is reasonable
aspiration
of bleeds necessary
PML-RAR alpha on all-trans retinoic
early stage,
leukemia.
. The frequency weight, diet, and
was started
myelocytic
after
for future pregnancy will depend on her
six to
l blood. He
cytopenia
bleeds every
range
from periphera trioxide. He developed
this patient?
be
maintenance
maintain this
level should
I suspect that
PML-
acid plus arsenic ea. How should I manage
Her ferritin
other factors.
aspirate for
are
would be sufficient. bleeds.
and sent the
starting hydroxyur
12 months
for
a BM aspiration situ hybridization results
to any scheduled
sensitive test
I repeated
in
sample
reassessed prior saturation is a highly
its use
Fluorescence cyte count in the BM
variant, but
RAR alpha.
? ●
The transferrin
low promyelo
an HFE C282Y that, it has no
transcript detection
presence of
After
pending. Does
alpha
e
detecting the
diagnosis.
PML-RAR
It is susceptibl
screening and
influence the
to therapy.
is limited to
even
g response
be quite high
utility in monitorin variation and can
dietary
to diurnal and
• Anemias
oietic cell
• Hematop
transplantation
inopathies
• Hemoglob
sis/thrombosis
• Hemosta
as
• Lymphom
disorders
roliferative
• Lymphop
s
• Leukemia
Waldenström
myeloma &
• Multiple
macroglobulinemia
s
liferative neoplasm
• Myelopro
s
plastic syndrome
• Myelodys
cytopenias
• Thrombo
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For the full
description of the
clinical dilemma,
and to see how the expert responded, turn
to page 32.
32
ASH Clinical
d
not recommen ,
: ASH does
tests, physicians
any specific
and
or endorse
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or
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Reliance on
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n provided
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DISCLAIMER
Why not wait until the ferritin level
increases? Any data to support venesec-
tion (phlebotomy) just based on rising
transferrin saturation?
Glenn J. Shamdas, MD
Veterans Affairs Medical Center
Fargo, ND
April 2018
News
I would use quantitative phlebotomy
to assess mobilizable iron stores, then
decide on a course of action. Some
patients with that level of ferritin and
classical hemochromatosis can have
significantly increased iron stores. With
normal liver function, no hepatomegaly,
and ferritin less than 1,000 ng/mL, there
is no risk of occult cirrhosis.
Pradyumna D. Phatak, MBBS
Rochester Regional Health
Rochester, NY
I recommend periodic phlebotomy to main-
tain transferrin saturation below 50 percent.
Donald H. Mahoney Jr., MD
Texas Children’s Hospital Cancer and
Hematology Centers
Houston, TX
See more reader responses at ashclinicalnews.org/
you-make-the-call.
CMYK
Clinical Dilemma:
A 19-year-old woman’s iron studies
results showed ferritin in the 250 ng/mL
range, transferrin saturation of 38 per-
cent, and normal liver function. Family
history includes a maternal aunt with
hemochromatosis, and genetic test-
ing shows that she is homozygous for
the C282Y mutation. She has never
been pregnant. She has no menses
because of her ora l contraceptive
method and eats no red meat. Her
most recent labs showed normal liver
function; however, her iron studies
showed a serum iron of 208 mg/dL,
total iron-binding capacity of
268 mcg/dL, transferrin saturation
of 78 percent, and ferritin 301 ng/mL.
Would you start phlebotomy? And
what would you use to decide on
frequency of therapy?
Start phlebotomy, initially once
every two months, to keep transfer-
rin saturation below 50 percent.
Monitor iron parameters once every
three months.
Javid Gaziev, MD, PhD
Mediterranean Institute of Hematology
Rome, Italy
I would consider bringing her ferritin
below 50 ng/mL with weekly phle-
botomy, then check ferritin every
two to three months.
Nagesh H. Jayaram, MD
Southeastern Medical Oncology Center
Jacksonville, NC
We have had similar findings with
heterozygotes at our pediatric center
and have sent those with elevated
saturations to get liver imaging for
iron levels. If they have evidence of
liver iron overload, we start inter-
mittent phlebotomy.
Depending on the levels and
whether the patient is female and
premenarchal, we sometimes wait
until menarche to decide whether
phlebotomy is necessary.
Our understanding of multiple myeloma is evolving.
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MULTIPLE MYELOMA:
KEY STATISTICS RELAPSE AND
HETEROGENEITY THE ROLE OF
THE PROTEASOME
Second most common
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References: 1. American Cancer Society. Cancer Facts and Figures 2017. https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual
-cancer-facts-and-fi gures/2017/cancer-facts-and-fi gures-2017.pdf. Accessed December 21, 2017. 2. International Agency for Research on Cancer. GLOBOCAN 2012:
estimated cancer incidence, mortality and prevalence worldwide in 2012. http://globocan.iarc.fr/Pages/fact_sheets_population.aspx. Accessed December 8, 2017.
3. Paiva B, van Dongen JJM, Orfao A. Blood. 2015;125:3059-3068. 4. Crawford LJ, Walker B, Irvine AE. J Cell Commun Signal. 2011;5:101-110. 5. Fribley A, Wang CY.
Cancer Biol Ther. 2006;5:745-748. 6. Terpos E, Moulopoulos LA, Dimopoulos MA. J Clin Oncol. 2011;29:1907-1915.
Tiffany F. Lin, MD
University of California, San Francisco
ASHClinicalNews.org
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