ASH Clinical News Advances in Hematology Research & Patient Care: Hi | Page 10

INTERVIEWS

can improve the morbidity (including pain and other complications)
and overall survival in patients with SCD. But there is always room
for improvement, of course. Also, many providers and patients or
their family members are either unaware of or have limited access to
these therapies.
Hydroxyurea is currently the only drug approved by the U.S.
Food and Drug Administration for the treatment of SCD in adults,
but it is estimated that only about 30 percent of patients who
could benefit from the drug are actually taking it – and that is an
optimistic estimate. Getting the word out, to providers and patients
and their families, and educating them about hydroxyurea may help
increase this percentage.
Why is the percentage of SCD patients receiving hydroxyurea
so low?
That is a good question. The American Society of Hematology
has taken an aggressive, forward-looking stance to try to educate
providers – through regional activities and sessions like the one
I chaired at this year’s meeting. And, of course, at the National
Institutes of Health, we are continuing to use social media and other
outlets to educate the general public.
Hydroxyurea has been around for quite a while, though
not in the treatment of SCD; it has been used since the 1950s
for the treatment of leukemia and pre-leukemic conditions like
polycythemia vera. Because of this initial use, there are still
individuals who don’t think of using a form of chemotherapy to
treat what is considered a non-malignant disease; however, there are
other forms of chemotherapy that are being used to treat a variety
of other diseases. Methotrexate, for example, is being used to treat
psoriasis. We have to quash the notion that, because a drug was
developed for a particular indication, that approved indication is the
only use that should be considered.
What topics were addressed in the session on optimizing SCD
care?
One of the main topics we addressed in this session was the frequent
complications associated with SCD – specifically chronic pain. In
this setting, cumulative damage to the central nervous system via
this chronic pain can cause neurocognitive impairment. That has
implications for patients’ entire lives – for example, education in
young pediatric patients and their career choices as they age.
The session also dealt with issues related to clotting and the risk for
venous thromboembolism in SCD patients. There are still questions
about how to both diagnose and appropriately treat these events.
How does the future of SCD treatment look; are there new
therapies on the horizon?
Obviously, we need to increase the use of hydroxyurea, but
researchers are looking at other drugs that target some of the
downstream complications associated with a vaso-occlusive disease
like SCD, rather than drugs that directly treat the underlying
hemoglobin disorder and the sickling manifestations.
We know that SCD affects red blood cells and activates the
coagulation system and inflammatory pathways because of some
of its secondary complications. Targeting some of the coagulation
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2015 ASH Annual Meeting

phenomena associated with the disease, as well as the inflammatory
component, may be a way to either directly treat patients in acute
vaso-occlusive crisis, or to potentially prevent these crises from
happening in the first place.
Having been involved with clinical research in SCD, including the
research that eventually led to the approval of hydroxyurea, are
you optimistic about the future of SCD treatment?
I would characterize the future of SCD therapy by looking at the
past. Coined by Linus Pauling in 1949, SCD is the first genetic
disease to be understood at the molecular level, giving us an
understanding of not only the protein abnormality, but also the
genetic underpinnings of the disease. Now, we also have ready
access to the stem cells of SCD patients, so treating the upstream
complications is an area of active investigation.
At the moment, the most effective way to cure this disease is
to perform a bone marrow transplant. Sadly, though, only about
25 percent of patients who could benefit from transplant have
identical-matched sibling donors – leaving a vast number of patients
still ineligible. There are several approaches to transplantation,
and my colleagues at the National Institutes of Health are
currently working on developing a less myelosuppressive form of
transplantation. We are certainly hoping that approaches and others
like it will help make an increasing number of patients eligible for
transplantation.
Gene therapy also holds tremendous promise for the future.
For SCD patients, gene therapy involves taking a patient’s own
bone marrow or stem cells, modifying them in a way that would
counteract the effect of the sickle mutation.
Also, in terms of addressing some of the downstream
complications of the drugs, finding new therapies that target the
coagulation system, the adhesion system, and the inflammatory
system are other promising possibilities. New combinations of
therapies offered at different times in patients’ disease, as well, may
ultimately solve the problem in the vast majority of patients. ●

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