ASH News Daily 2016 - Issue 3 - A-24

Page A-24

ASH News Daily

Monday, December 5, 2016

Symposium
«« From Page A-1

of SCD from Africa, to Europe, to
the United States.
The next three talks will highlight
state-of-the-art molecular pathways
that have hoisted SCD research to
new heights. In his talk, Dr. Gerd
Blobel will describe how chromatin
remodeling can affect globin-chain
synthesis. Using novel techniques,
Dr. Blobel's laboratory has demonstrated that chromatin looping plays
an important role in gene expression
and that this property can be exploited to reactivate dormant fetal globin
production in erythrocytes.
Continuing the theme of fetal
hemoglobin induction, Dr. Daniel
Bauer will then highlight gene editing as a method to regulate expression of BCL11A and hemoglobin F.
Genome-wide association studies
(GWASs) have led to the discovery
of several fetal hemoglobin modifying genes, and at the forefront is
BCL11A - a potent inhibitor of hemoglobin F. Variants of BCL11A are
associated with heredity of persistence of fetal hemoglobin, which,
in combination with SCD, results

Pediatric ALL
«« From Page A-1

treatment protocols: one with shortened chemotherapy (P-III) and one
with more extended chemotherapy
(P-II). The primary aim of the study
was to demonstrate noninferiority
of the patients who received less
therapy compared with those in the
standard/more extended treatment
group. Importantly, only those patients who met the criteria for standard-risk MRD (MRD negative at
both day 33 and day 78 from time
of induction chemotherapy) were
included in this analysis.
With a remarkably long period

Stem Cell
«« From Page A-2

"There is a growing body of literature that links stem cell function to
their metabolism, and in particular,
to the power engines of the stem cells:
the mitochondria," noted Dr. Tsvee
Lapidot, senior author on the abstract.
Dr. Dick added, "This is a remarkable finding, and one that extends
the support that hematopoietic stem
cells get from their niche cells beyond
cytokines and growth factors, to this
physical process." Dr. Golan went
on to emphasize that the clinical implications of this work reach beyond
cancer biology, to metabolic disorders
such as diabetes and osteoporosis.
In the third verse of The Police's
1979 hit, "Message in a Bottle," the
castaway realizes that he is not alone

in mild phenotype. Genome editing
provides a promising technique to
take advantage of these GWAS and
epidemiologic observations to enhance fetal hemoglobin production.
Lastly, Dr. Giuliana Ferrari will
explain how gene therapy can be
applied to hemoglobinopathies,
including SCD. Innovative work
by her laboratory and by other investigators has revolutionized the
concept of gene transfer as a means
of therapy for globin disorders. By
correcting a patient's own hematopoetic stem cells to produce normal adult hemoglobin, this exciting
therapy has the potential to lead to
a cure for all.
Don't miss this groundbreaking
2016 Presidential Symposium, tomorrow at 9:45 a.m. in Hall AB of
the San Diego Convention Center. "I
never thought that I would see this
day," Dr. Abrams stated. "It's an exciting time to be a part of sickle cell
research."
As this session is sure to reveal,
there truly is no ceiling when the
sky's the limit.
Dr. Naik indicated no relevant conflicts of interest.

ASH Sickle Cell Disease Initiative

SH is committed to addressing the burden of
sickle cell disease (SCD)
and is undertaking a multifaceted, global initiative to improve
outcomes for individuals with the
disease. ASH has engaged a broad
group of experts and stakeholders
to review the state of SCD and to
identify the greatest opportunities
for improvement. ASH continues
to invest in and explore the actions needed to make a significant
difference in SCD research, access
to care, and global issues. The
ASH-led Sickle Cell Disease Coalition (www.scdcoalition.org) helps
promote awareness, amplify the
voice of the SCD stakeholder community, and improve outcomes
for individuals with SCD.
The Society has also committed
to developing and implementing
up-to-date guidelines describing the management of acute and
chronic complications of SCD, as
well as educating hematologists
and other health-care providers in
all settings to recognize and properly respond to SCD complications

of follow-up (median, 8.6 years),
the investigators showed that the
four-year disease-free survival rate
was 91.8 percent for those in the PIII group versus 95.8 percent in the
P-II group, respectively (p=0.04).
However, there was no statistically significant difference noted
in terms of four-year cumulative
incidence of relapse. Notably, there
was a trend for higher relapse rate
in the P-III group compared with
the P-II group (6.3 percent vs. 3.2
percent, respectively). There was
no significant difference found between the two treatment groups
for eight-year overall survival. The
investigators noted that the pattern

of relapse incidence was similar between both treatment groups, and
the incidence of death in remission showed no statistically significant differences. Dr. Schrappe
concluded that even among pediatric patients with ALL who have
more favorable prognosis (as demonstrated by MRD negativity), an
attempt to decrease the amount of
chemotherapy needed for cure by
instituting a reduced amount of delayed intensification chemotherapy
was ultimately not able to show
better outcomes, as evidenced by
the increased number of relapsed
patients in the shortened chemotherapy arm of this large random-

when innumerable bottles wash up
on his shore. Likewise, the authors
of this abstract, although distant,
were not alone. Their collaboration
spanned oceans and time zones. Dr.
Lapidot highlighted the key role
played by long-distance partnerships with Drs. Toshio Suda and Jose
Cancellas, "After we invoked [Dr.
Concellas] to consider mitochondria
transfer, he made many critical contributions, and has independently
confirmed our results."
The story of the castaway in "Message in a Bottle" comes full circle in
the end. In a similar fashion, the story
of this abstract came full circle with
Dr. Dick's introduction. As a postdoctoral fellow in Dr. Dick's laboratory, Dr. Lapidot worked on mouse
models that laid the foundation on
which Dr. Lapidot's postdoctoral fel-

low, Dr. Golan, built the experiments
presented in yesterday's Plenary
Session. Commenting on having his
mentor set the stage, Dr. Lapidot said,
"It's like a Hollywood movie." Dr.
Dick echoed that sentiment: "There is
a special pleasure that a mentor has
when they open a journal and they
see a beautiful piece of work coming
from one of their trainees. I got such
a warm feeling when I was invited to
introduce the work of Tsvee's postdoc, and that there was a thin, golden
thread that extended back to the original work that Tsvee did when he was
in my lab." A clear example of just
how impactful a mentor can be when
he opens up a trainee's message in a
bottle and answers the call.
Dr. Gerds indicated no relevant conflicts of interest.

in their everyday practices. ASH
is exploring the development of
a consortium of African countries to institute a populationbased registry study for newborn
screening and early intervention.
The Society continues to encourage the study of critical, unaddressed research questions, and
to work with Congress and federal agencies to enhance and expand federal SCD programs. For
more about this initiative, please
visit www.hematology.org/scd.
Lastly, Blood has issued a compendium of SCD articles published in 2016, premiering here
at the ASH annual meeting. This
series includes original research
articles and reviews on the pathophysiology, diagnosis, and treatment of SCD, and highlights the
coalition and State of Sickle Cell
Disease Report. We encourage
attendees to visit the ASH Booth
(#2715) or the ASH Store in the
Sails Pavilion to obtain a copy
and to learn more about the Society's SCD-related resources and
programs.
ized study. "Indeed, the value of a
robust randomized study can again
be demonstrated in our study... it
has been another attempt to decrease treatment intensity but it
did not succeed (again, as shown in
previous studies by this and other
study groups). Had we not randomized, we would have missed
this point, as the difference is not
dramatic," concluded Dr. Schrappe.
Dr. Hunger summed up by saying, "In my opinion, the underlying principle is correct: There are
patients who can be cured with
less therapy, including perhaps a
much more dramatic reduction in
therapy than was attempted here.
However, we need a different strategy to identify those patients."
Dr. Hunger believes that strategy
might also incorporate clinical
risk factors such as age and initial
WBC count, tumor genetics (presence or absence of specific sentinel
genetic alterations), and even more
sensitive measures of MRD. "This
study is important and shows us
that randomized trials are critically
important when we try to reduce
treatment for a highly curable cancer," he concludes. So, in the end,
while we want the ultimate answer
to be "less is more," for now, we are
reminded that less is not always
more, and instead that sometimes,
less is indeed ... less.
Dr. Pemmaraju indicated no relevant conflicts of interest.

Table of Contents for the Digital Edition of ASH News Daily 2016 - Issue 3