Sickle Cell Disease: Symptoms
and Benefits of Bone Marrow Transplant
Guest: Dr. Michelle Hudspeth – Pediatrics - Hematology/Oncology
Host: Dr. Linda Austin – Psychiatry
Linda Austin: I’m Dr. Linda Austin. I’m talking, today, with Dr. Michelle
Hudspeth who is Director of the Pediatric Blood and Marrow Transplant program
at the Children’s Hospital here at MUSC.
Dr. Hudspeth, one of your areas of interest is the treatment of children
with sickle cell disease. Just what is
sickle cell disease?
Michelle Hudspeth: Sickle cell disease
is really a devastating disease for a number of African-American patients in
the United States. What happens in sickle cell disease is
there’s actually just one small mutation change, but that change is significant
enough that it changes the makeup of hemoglobin. And hemoglobin, as you may know, is a major
component of red blood cells. That’s what
allows us to carry the oxygen in the body and have energy. Unfortunately, in these patients, this
abnormal hemoglobin causes an abnormal shape of the red blood cell.
to think that the was the main problem of the disease, you had an abnormal
shape of the red blood cell and it sort of jammed up in the blood vessels and that’s
what caused all the problems. We now
have learned so much more about sickle cell disease. It’s not simply just the shape of this red
blood cell but, really, this abnormal hemoglobin induces so many changes
throughout the body that there are just a lot of abnormal interactions between
the hemoglobin and the white blood cells in the blood vessels. It’s a very complex disease and,
unfortunately, really, has major complications for a number of patients. For instance, this was shown by the Cooperative
Study of Sickle Cell Disease (CSSCD),
these patients, unfortunately, have a greatly shortened life expectancy of
around only 42 to 48 years.
Dr. Linda Austin: And they
go into crises from time to time which are quite painful.
Dr. Michelle Hudspeth: That’s
right. There are a number of different
problems, and that’s the issue. This
abnormal hemoglobin causes the red blood cells to turn over very quickly and
break down. So, not only are the
patients anemic, they have kind of chronic problems with not delivering enough
oxygen and other needs to other tissues, so they really experience damage to
many other organs. They have lung
damage, kidney damage. Ten percent of
pediatric sickle cell patients will go on to have a stroke. It can be devastating. And what we’re also learning now is up to 20
percent of patients will have what we call a silent stroke, meaning, we don’t
see a change in their ability to talk and walk, but if you check their brain
MRIs, they most definitely have had an abnormality there. And if you do special testing, like you would
for school, they’re certainly being impaired in their ability to learn. So, really, this disease has consequences
throughout the body. And for many
patients, they’re frequently in the hospital with pain and other issues.
Dr. Linda Austin: So, let’s
talk about the treatment. What do you do
for these patients?
Dr. Michelle Hudspeth:
Well, a lot has been learned over the years in terms of supportive care,
very simple things, such as starting penicillin, because we know these patients
are prone to getting life-threatening infections. So, simple things, like starting penicillin
when they’re babies, can make a big impact.
We’ve learned other things over the years. If somebody is at a high risk for stroke, we
can predict that to some degree by using ultrasounds to look at their blood
flow. We can start them on transfusions,
and that can decrease their risk.
However, even with all these things that we’ve learned over the years,
there’s still a seven percent chance of dying by the age of 18 for patients
with sickle cell disease. That’s quite
The other counterpart is we certainly see a lot variability in
patients and we haven’t really learned that yet, why some patients with sickle
cell disease seem to have to be in the hospital all the time and have a very
severe course as children while other children may only be in the hospital
every so often. But what our adult
colleagues are coming back and telling us, even those kids who seem to have a
mild course of disease as children, by the time they come to us as adults, they
still have organ damage, and we’re seeing all the results of that. So, it’s quite a devastating disease.
Dr. Linda Austin: You
mentioned in another podcast that some of these patients actually get bone
marrow transplants, correct?
Dr. Michelle Hudspeth: That
is correct. And that’s an area I feel
quite passionate about because I think that, unfortunately, there’s a bit of a
health disparity here and that, probably, they’re not being referred for
transplant consultation as often as they should be. We’ve learned a lot about bone marrow
transplant for sickle cell disease. In
the setting where they have a matched brother or sister, who’s the donor, these
patients do quite well. They have
anywhere from an 85 to a 95 percent chance of overall survival, of being cured
for sickle cell disease. So, at this
point in time, bone marrow transplantation offers the only cure for sickle cell
I think people have often been scared about the risk of bone
marrow transplant and the things related to that. The most current data tells us that the risk
of dying from the transplant procedure itself is only seven percent. And, as I just told you, the chance of dying
from sickle cell disease by age 18 is also seven percent. So, really, we’re not increasing the chance
of a patient dying here, but what we are doing is offering the chance for cure,
for a lifetime, and making a significant difference.
Dr. Linda Austin: So, walk
us through the procedure of doing a bone marrow transplant for these
patients. What age, for example, would
you begin to think about this?
Dr. Michelle Hudspeth:
Typically, patients with sickle cell disease don’t tend to have, really,
manifestations until after a year of age, and that’s because they have a high
proportion of this fetal hemoglobin that’s still in their bodies as
infants. Typically, we would look at a
patient who’s had some marker of a severe disease course, such as having a
stroke, having had silent stroke on MRI, some other concerning
complication. In general, we know it’s
much better to transplant these patients when they’re younger rather than when
they’re older. It seems to be, from the
transplants done across the world, that age 15 is an important age. Over the age of 15, you seem to increase your
chances of having complications related to the transplant. So, we certainly prefer to have children who
What typically would happen, we would have a patient who’s had
some marker of having a severe disease course referred to us. Then we would need to do what’s called HLA
(human leukocyte antigen) typing. This
is different than blood typing. We
actually don’t look at all to see what blood type someone is to be a bone
marrow match. This is more complicated
typing than that. So, we would want to
look at full siblings. Any full sibling
has a 25 percent chance of being a match with the patient that we’re looking
at, so that’s important testing that we would need to do. If you look overall at sickle cell patients,
close to 20 percent of sickle cell patients will have a full match.
Dr. Linda Austin: Does the
candidate donor have to be a full match?
Dr. Michelle Hudspeth: At
this point in time, that is recommended.
We know that you certainly increase your transplant-related mortality
the more mismatched the donor is. And,
right now, that would not be considered an indication for transplant in sickle
cell disease, so we would recommend, and really require, that you have a
matched sibling donor.
Dr. Linda Austin: Now, if
there is not a matched sibling donor, might you look outside the family?
Dr. Michelle Hudspeth: That
is a possibility. In the United States,
and actually throughout the world, there’s a registry of bone marrow donors that
can be searched. Unrelated donor
transplantation for sickle cell disease has a higher rate of complications and
morbidities and, right now, is mainly being looked at in the context of
Dr. Linda Austin: So let’s
assume, then, that there is a sibling and there is a perfect HLA match, what
Dr. Michelle Hudspeth: Then
we get the patient prepared for transplant.
For any of our patients that go through transplant, we do a number of
tests ahead of time to make sure that they have adequate organ function to
tolerate what’s needed for transplant.
So, they would undergo a series of tests, including an echocardiogram,
to look at their heart, lung function test, kidney function test, a number of
different blood tests, all to make sure that they would be suitable to handle
the complications and the treatment related to bone marrow transplant. Then begins, really, a long period of
conversation with the family to make sure that they fully understand what’s
involved and what’s required for transplant.
If everyone is in agreement to move forward then we schedule a date for
What transplant involves, for sickle cell disease, we use a
combination of three drugs ahead of time as part of what we call the
preparative regimen. This is really to
prepare the body to accept the new bone marrow.
We give a drug called Busulfan for four days. That’s a drug that we monitor very closely
and target the dose, especially for each person’s individualized
metabolism. The other drug is called Cyclophosomide. That’s also administered once a day for four
days. And then we give another drug
called ATG (anti- thymocyte globulin) and that’s just an immune suppressive
agent that helps prepare that body to receive the new bone marrow, and that’s
given over three days.
Then, on what we call
day 0, we sort of count down the negative days, the days that they get
chemotherapy, and on day 0, actually, we tell the patients it’s their new
birthday. That’s the day that they
receive the bone marrow. We would do a
bone marrow harvest on their sibling, and we could talk more about that in a
few minutes. Then the bone marrow comes
to them in a bag that looks, simply, like a bag of blood and they receive that
through a special IV line. And, again,
if you walked in the room, you wouldn’t think anything special was going on
that day other than a blood transfusion.
Then, from that time, they would need to be in the hospital generally
for about a month. They’re very
immunosuppressed at that time. We have
to wait for that new bone marrow to grow.
Austin: Immunosuppressed means?
Hudspeth: They’re immune system is
weakened, so they’re at a high risk for having an infection or other
complications. We have them in our
special bone marrow transplant rooms designed to filter out infections and
other concerns and we put them on special medicines to try to prevent
infections and watch them very closely.
Austin: Am I right in guessing that they
are pretty sick puppies during this, that they’re not feeling too well?
Hudspeth: During the time that they
receive the chemotherapy itself, it’s generally not so bad. It’s generally that week afterwards, when the
side effects of all the chemotherapy catches up with them. We certainly treat the nausea. If they have any pain, we treat that. If they have enough nausea and something we
call mucositis, which is mouth sores, that they can’t eat, we can give them
nutrition through their IV line. So, we
do a lot of supportive care in that time.
And, it is variable. The majority
of patients are able to stay on our unit, in our specialized bone marrow
transplant rooms, and we’re able to support them quite well.
Austin: So they stay in the hospital
Hudspeth: Generally about a month. And then it’s important because, really,
they’re resetting their whole immune system as this bone marrow is growing and
recovering. It’s very standard, across
the country, that we require them to be within close distance of the transplant
center for the first 100 days after transplant.
We know that, in particular, that first 100 days, you need to be watched
very carefully for complications or other concerns. We have special transplant housing here at
our Ronald McDonald House for patients that don’t live locally. Then, once they’re discharged from the
hospital, which is generally after about a month’s time, we generally see them
two to three times in clinic each week and take care of any needs that they
Austin: You mentioned that you’re
observing for complications, what might those be?
Hudspeth: There are a number of
complications. You can imagine, it’s
sort of a balancing act. We have the
immune system of the recipient and the immune system of the new bone
marrow. As I mentioned, we do something
called HLA typing to see that they’re matched.
However, we’re able to test for many things, but we, obviously, can’t
test for every possible difference between people. We know that even if you’re a perfect match
on paper, there are still going to be some small differences. Those are the small differences that can
sometimes create a problem.
One problem is
rejection. That’s what happens when the
new bone marrow comes in and the person receiving it, the sickle cell patient,
their bone marrow sees that bone marrow and says, hey, how’re you doing, you know, we’re a lot alike, aren’t we? But then says, wait a minute, we’re not completely alike, you’re a little different over
here. So, sometimes the recipient’s
immune system can mount a reaction to the new bone marrow coming in because
they see those small
differences and can reject the bone marrow.
In sickle cell disease, that can happen up to 10 percent of the
time. But, thankfully, most of the time,
their own bone marrow actually comes back and the patients survive and do
fine. Unfortunately, we haven’t cured
their sickle cell disease, but many of those patients go on to have a
successful second transplant.
So, rejection is one
of the major complications. The flip
side of that, in thinking about this balancing of immune systems, is something
called graft-versus-host disease. Graft
is a funny word that we use to refer to this new bone marrow coming in. It’s called a graft. And this is sort of the flip side. Host is the patient
receiving the bone marrow graft. As this
bone marrow graft comes in, it’s typed for all the things we can type for. But it can come in and see that recipient and
say, oh, we’re a lot
alike, but wait a minute, there are still some small differences between us. And, the immune system in the new bone marrow
can start attacking the recipient and that can cause the graft-versus-host
disease. We give medications to prevent
this, but we’re not always successful.
So, we generally see graft-versus-host disease in this setting about 15
to 20 percent of the time.
Austin: Now, at what point are you able
to say, it worked, you’re
fine, no more problems?
Hudspeth: We do testing along the way to
see how much of that bone marrow is the recipient and how much is the
donor. If by 100 days we’ve seen very
steady, what we call ingraftments, we have close to 100 percent of donor cells
in there, we feel quite comfortable, and we’ll have a huge party at one
year. If we’ve made it to 100 days,
we’ve made it past the major point of rejection.
Austin: That must be so thrilling.
Hudspeth: Oh, it is thrilling. And what’s clear is, we’ve looked at these
sickle cell disease patients over time, one of the problems of sickle cell
disease is that their spleen, which is an organ that filters the blood, doesn’t
work well. And this is the basis of
their risk for infections. And after
transplant, a number of patients actually regain complete function of their
spleen, which is very exciting. Another
problem in sickle cell patients is they don’t grow very well because of this
chronic disease they have. After
transplant, what we’ve seen is that teenagers have improved growth.
Austin: Now, you started to talk about
the process of harvesting the bone marrow from the sibling. What does that process consist of?
Hudspeth: That day is a little bit
harder for the sibling than the person receiving the bone marrow. The sibling undergoes general anesthesia so
they don’t feel anything during the procedure.
We then remove bone marrow from their hip bones. The hip bones are where most of the bone
marrow in the body lives. While the
patient is asleep, we insert needles and pull out the bone marrow. The bone, really, just kind of looks like
blood when it comes out. And the
pediatric oncologist doing the procedure has the ability to check the bone
marrow as it’s coming out. We need a
certain number of cells in order for it to be successful. We’re able to monitor that number of cells
during the procedure such that we don’t take more than we need from the donor,
but we want to make sure we have enough for the recipient.
It’s and outpatient
procedure. They, generally, are
discharged that same day. They’re
generally a little bit sore afterwards.
We usually tell them to take it easy for a couple of days. It’s very rare for them to need a blood
transfusion or any other support. I’m
constantly amazed that the children actually bounce back very quickly. I had one donor who actually did cheerleading
tryout two days later. So, the children
actually recover quite well.
Dr. Linda Austin:
Something to cheer about.
Dr. Linda Austin: How many transplants do we do a year for
Hudspeth: It varies greatly. So far, this year, we’ll be up to two
Dr. Linda Austin: In the first three months of 2008?
Dr. Michelle Hudspeth: That’s right.
Dr. Linda Austin: So, maybe, roughly, one per month, or so?
Dr. Michelle Hudspeth: It really was increased for a time and has
sort of dropped off. And this is sort of
an area of interest for me because I think that, again, with this being the
only curative therapy for the disease and with the overall complication rate
being very low, I think we simply aren’t having enough patients referred to us
that could really benefit from this therapy.
Dr. Linda Austin: Important to get the word out.
Dr. Michelle Hudspeth: Absolutely.
Dr. Linda Austin: Dr. Hudspeth, thank you so much for talking
Dr. Michelle Hudspeth: Thank you.
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