ASH News Daily - Tuesday, December 13, 2011 - (Page A-6)
Page A–6
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MARROW FAILURE
Bone Marrow Failure: Success May Be on the Horizon
Diamond-Blackfan anemia (DBA)
By BaRBaRa pRo, Md
T
he Education Program session,
“Understanding and
Management of Inherited
Bone Marrow Failure Syndromes,”
included three presentations that
focused on dyskeratosis congenita
(DC), Diamond-Blackfan anemia,
and Fanconi anemia. We all had
to familiarize ourselves again with
these rare but very instructive disorders.
The first speaker, Dr. Inderjeet
Dokal, Barts and The London
School of Medicine and Dentistry,
also chair of this session, presented
an update on DC, a syndrome characterized
in the classic form by bone
marrow failure, mucocutaneous abnormalities,
and predisposition to
develop cancer, with the latter being
the most common cause of mortality.
“Clinical diagnosis of DC is
difficult as there are different faces
of DC,” said Dr. Dokal.
What do we know so far? Eight
genes have been found to be associated
with this disease and nearly
all of them (7 out of 8) are involved
in telomere maintenance (the DNA
tails). A number of other disorders
including aplastic anemia, myelodysplastic
syndromes, and leukemia
are also associated with defective
telomere maintainance. Dr. Dokal remarked,
“We need to increase physician
awareness and recognize that a
multidisciplinary approach is needed
to treat these patients.”
Multiple Myeloma
«« From Page A-3
#631) from the University of Michigan,
Ann Arbor, showed that carfilzomib
may be just as potent in the
front line setting with 100 percent of
patients achieving VGPR over time.
With a distinct toxicity profile, this
agent may be better tolerated over
the long term. Dr. Pieter Sonneveld
(abstract #633) from Erasmus Medical
Center, Rotterdam, Netherlands,
confirmed the significant activity
of the second-generation proteasome
inhibitor and its tolerance
when given as maintenance. In addition,
the preliminary clinical activity
and side effect profile of the
newest proteasome inhibitor, MLN
9708 (abstract #301), an oral agent,
was presented by Dr. Richardson,
who demonstrated 13 percent (>
PR) single-agent activity, although
the one complete response was in a
bortezomib naive patient. According
to Dr. Jesus G. Berdeja, from the
Sarah Cannan Research Institute,
Nashville, Tennessee, MLN9708 in
combination with lenalidomide and
is another rare but important congenital
disease, characterized among
physical abnormalities by red cell
aplasia and increased risk of cancer.
There is accumulating evidence
of abnormalities in ribosome biogenesis
in DBA. Dr. Sarah Ball, St.
George’s University of London,
summarized the clinical and genetic
features of this rare disease and concluded
that despite the “explosion of
knowledge” in this field, it has done
little thus far to effect change in clinical
management.
Lastly, Dr. Jean Soulier, Saint-
Louis Hospital and University Paris-Diderot,
France, gave a detailed
update on Fanconi anemia (FA). FA
is a rare genetic disorder characterized
by progressive bone marrow
failure during childhood. “Early
and accurate FA diagnosis is crucial,”
said Dr Soulier. As many as
15 genes (and counting) have been
identified to be associated with this
complex disease.
If you missed this education ses-
sion, plan to attend the Presidential
Symposium this morning at 9:45
a.m. in Hall AB, San Diego Convention
Center. It is chaired by ASH
President Dr. J. Evan Sadler. This
session will elucidate how analyses
of rare disorders can help our understanding
of the mechanisms that
control hematopiesis and their possible
implications in the diagnosis
and treatment of these diseases. Dr.
dexamethasone in newly diagnosed
patients again showed a 100 percent
response rate (abstract #479).
As an entirely oral regimen, this
combination may ultimately prove
most desirable.
Other innovative strategies to
treat relapsed patients that were
described include antibody therapy
directed against CD138 (abstract
#305) or CS1 (abstract #303), an
idotype-pulsed dendritic cell vaccine
(abstract #636), MEK ½ inhibition
(abstract #306), and inhibition
of kinesin spindle protein by a selective
inhibitor, ARRY-520 (abstract
#2935). Finally, Dr. David Siegel,
Hackensack University, New Jersey,
demonstrated promising results
with the HDAC inhibitor vorinostat
in combination with bortezomib
+/- dexamethasone (abstract #480).
Perhaps we can expect more than 31
flavors in the future?
Dr. Landau has served on a Mil-
lennium advisory board and currently
receives research support from Millennium.
Dr. Rosenzweig indicated no relevant
conflicts of interest.
Monica Bessler, The Children’s Hospital
of Philadelphia, will begin the
session with an update on the role
of telomereses in the pathogenesis
of bone marrow failure. Short
tails can be a sign of age but can
also be present in the very young
and cause a number of problems.
Dr. Benjamin Ebert, Brigham and
Women’s Hospital, will give an
update on ribosomopathies and
THROMBOSIS
All Things Anti-Thrombotic
By david GaRcia, Md,
and ShaRi Ghanny, Md
terday was a busy one. In “New
Anticoagulants,” an Education
Spotlight session chaired by Dr.
Elaine Hylek, Boston Medical Center,
and Dr. John Heit, Mayo Clinic,
Minnesota, attendees heard details
from three different landmark clinical
trials that have compared warfarin
to a novel anticoagulant agent
(dabigatran etexilate, rivaroxaban
or apixaban, respectively) for the
prevention of stroke in patients
with non-valvular atrial fibrillation.
The presenters provided suggestions
regarding the assessment of
their dabigatran-associated bleeding
and provided insight about how
and under what circumstances one
might assess dabigatran’s anticoagulant
effect. “Dabigatran etexilate
and rivaroxaban represent the next
generation of oral antithrombotics
that have been eagerly awaited
since the first reports on vitamin
K antagonists (dicoumarol) for the
prevention and treatment of thrombosis
in 1942. However, these novel
antithrombotics have important
strengths and weaknesses that clinicians
must understand in order to
provide optimal management of the
individual patient,” said Dr. Heit.
Later Monday, several clinically
I
important papers were presented in
a session on antithrombotic therapy
and VTE. Dr. Cecilia Becattini, University
of Perugia, Italy, shared the
results of the Warfasa study, a randomized,
double-blinded trial of
aspirin as a secondary prevention
method for patients with idiopathic
VTE. In the trial, 403 patients with
unprovoked venous thrombosis
were, after 6-18 months of standard
anticoagulation, randomly assigned
to receive 100 mg of daily aspirin or
matching placebo during a median
study period of 24.6 months. Not
surprisingly, during the first two
f you’re interested in the treatment
of patients with (or at risk
for) clotting disorders, then yes-
years of follow-up, the annualized
recurrent thrombosis rate was 11.2
percent for the patients taking placebo.
However, the rate of recurrent
DVT/PE was about 40 percent lower
(6.6%) among patients who received
aspirin (hazard ratio = 0.57; 95% CI
0.35 to 0.93). There was no difference
between the groups in the proportion
of patients who experienced
bleeding.
Two papers, one presented by Dr.
Jovana Yudin, McMaster University,
and one by Dr. Leslie Skeith, University
of Western Ontario, raised
new questions about the benefits
of peri-procedural anticoagulant
(“bridging”) therapy. Dr. Yudin described
a meta-analysis of 32 (mostly
observational) studies that included
data from more than 6,700 patients
who interrupted anticoagulation for
a procedure. Patients who received
bridging treatment had a more than
five-fold increased risk for major
bleeding. Interestingly, the overall
rate of thrombosis was quite low
and no difference was seen based on
whether patients were “bridged” or
not (0.87 vs. 0.77%, respectively).
The rates of thrombosis were sim-
ilarly low in a study presented by
Dr. Leslie Skeith. In this single-institution,
observational study more
than 400 patients interrupted warfarin
more than 600 hundred times
to undergo procedures. All patients
were taking warfarin to prevent
VTE and none had experienced VTE
less than three months prior to warfarin
interruption. Although bridging
therapy was used in only about
one-quarter of the patients, the 90day
rate of thrombosis was very
low at 0.63 percent. Taken together,
these studies highlight the need for
prospective, randomized controlled
trials that will better define the benefits
(and risks) of bridging therapy
for warfarin-treated patients.
Dr. Garcia has served on the advisory
boards of Boehringer Ingelheim, Janssen,
and Daiichi Sankyo. Dr. Ghanny indicated
no relevant conflicts of interest.
genetic abnormalities leading to
ribosome dysfunction. Lastly, Dr.
Alan D’Andrea, Dana-Farber Cancer
Institute, will give an overview
of Fanconi anemia with special
emphasis in the genetic alterations
found in this disease and present
in other types of cancer.
Dr. Pro indicated no relevant conflicts
of interest.
ASH NEWS DAILY
Tuesday, December 13, 2011
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