Adolescents and Young Adults with Sickle Cell Disease

August 30, 2021

Information

August 29, 2021

Yale Cancer Center

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00:00Funding for Yale Cancer Answers is provided
00:04by Smilow Cancer Hospital and AstraZeneca.
00:08Welcome to Yale Cancer Answers with
00:10your host doctor Anees Chagpar.
00:12Yale Cancer Answers features the latest
00:14information on cancer care by welcoming
00:17oncologists and specialists who are on the
00:19forefront of the battle to fight cancer.
00:21This week it's a conversation about the care
00:24of adolescents and young adults with sickle
00:27cell disease with Doctor Cece Calhoun.
00:29Dr Calhoun is an assistant professor of
00:32medicine and hematology and assistant
00:34professor of Pediatrics in hematology
00:36oncology at the Yale School of Medicine,
00:39where Doctor Chagpar is a
00:42professor of surgical oncology.
00:44Cece, maybe we could start off by
00:46you telling us a little bit about
00:48yourself and what you do.
00:50I like to call myself a lifespan
00:52hematologist, and both my clinical
00:55and research interests center around
00:57the care of young adults with sickle
01:00cell disease as they transition
01:02from pediatric to adult care.
01:04We know it's a really high
01:05risk time for them.
01:06And so all the work that I do both in
01:08the clinic and in the research setting
01:10is about making that process better.
01:13Is sickle cell disease a cancer?
01:15Tell us more about what
01:17exactly sickle cell disease is
01:18and why it's being seen
01:21by an oncologist?
01:23That's a great question, so actually sickle
01:26cell disease is an inherited condition
01:28of the red blood cells and so many
01:32people are familiar with anemia
01:34and conditions of that sort,
01:37which affect red blood
01:38cells and hemoglobin.
01:39And that's what sickle cell disease is
01:42a condition of, and it's genetic.
01:44So patients are born with it,
01:46and what it manifests as is a normal
01:48red blood cells are kind of squishy.
01:50I like to think of them as Jelly
01:52doughnuts because I like food.
01:54But when you have sickle cell disease
01:55because of a genetic mutation
01:57your red blood cells
01:59are not squishy and malleable,
02:00they can be really stiff
02:02and misshapen like a sickle.
02:04They can be shaped like a sickle or a banana,
02:06and so if you think of
02:08your blood cells as pipes,
02:10imagine if you had your Jelly doughnuts
02:12kind of going through those pipes,
02:14bouncing off the walls,
02:15taking oxygen to where it needs to go,
02:17and you replace those cells
02:19with sticky stuff,
02:20fragile misshapen red blood cells like
02:22sickle cells that are scratching up
02:24the red blood vessels sticking together,
02:27causing blockages, impeding flow,
02:28and then you can imagine all
02:31the complications that patients
02:33with sickle cell face.
02:34Most saliently or what patients have
02:39to really deal with is a lot of pain.
02:41That's the thing that brings
02:43them to the hospital.
02:44And acute meaning an unplanned basis,
02:46but any part of our body where
02:48there are blood vessels,
02:50those misshapen
02:50cells can get clogged up in those
02:53blood vessels and cause problems.
02:55It's important for patients
02:57with sickle cell disease to have
02:59regular care by an oncologist
03:01who also understands hematology,
03:02the blood, to make sure that all their
03:05organs are in tip top condition
03:06and that we treat anything before
03:08there's a problem.
03:10Now, I would think that if
03:12you're a pediatric patient and
03:15this is an inherited condition,
03:17you might have a sense of whether or
03:20not you have sickle cell disease
03:22based on whether your parents did.
03:24But somebody had to start with the
03:27genetic mutation to begin with.
03:29So how many of your patients
03:31actually know that they have sickle
03:33cell disease from the time that
03:35they were born
03:37and how many of them present to you acutely?
03:42In the United
03:44States we have the benefit of the newborn
03:47screen that all babies born in hospitals,
03:50when they
03:51get their heel poked and get that
03:53little spot of blood that can test
03:55for a variety of genetic conditions
03:56and sickle cell disease is
03:58included in those conditions.
04:00So if a child has an abnormal newborn screen,
04:03oftentimes the pediatrician will
04:05refer them to a hematologist for
04:08further evaluation and work up.
04:09And sometimes, even if it's abnormal
04:12to show sickle cell trait,
04:14which means that you don't have the disease,
04:16but you can be a carrier,
04:18and if your partner has the disease,
04:20you can have a child with sickle
04:21cell disease.
04:22We can figure that out from
04:24the newborn screen.
04:25So these days we know pretty early on
04:27which is critical to the survival
04:29of our young children or infants and
04:32toddlers and in other countries
04:34the newborn screen isn't quite as universal,
04:38and so sometimes children could present
04:39with swelling of the hands and feet.
04:42That's something called dactylitis,
04:44which is pretty rare these
04:46days as a presenting sign.
04:48And then there's some patients with more
04:51milder forms of sickle cell disease
04:53that don't know until they're older
04:56children or young adults,
04:57but most of the time we get them in
04:59our catchment when they are young
05:01because of their newborn screen and
05:03can really wrap our arms around them
05:05and give them the care they need.
05:06Let's suppose you're a newborn baby and
05:09you had your heel poked and they tell
05:11you that you have sickle cell disease.
05:14Well, presumably they don't tell you
05:16they tell your parents and you get
05:18referred to a pediatric oncologist.
05:20If that means that your red blood
05:22cells are now more
05:25like bananas than squishy Jelly
05:27Donuts, what can you do about that?
05:29I mean, is it reversible?
05:31At this time the only cure for sickle
05:34cell disease or way to reverse
05:36those cells is by replacing your
05:38bone marrow with another persons,
05:40but that's pretty rare.
05:42Later in the show, you get to talk
05:44a little bit more about therapies
05:45coming down the pipeline for patients,
05:47but right now that's the only
05:49way to reverse.
05:51However, if you are a little baby
05:53and your parents find out that
05:55you have sickle cell disease
05:57the benefit of coming and talking
05:59to a pediatric oncologist and
06:00hematologist who knows about this
06:02is that you now have a team member,
06:05somebody on your team that
06:06can help your baby,
06:07or you if you're the baby,
06:08stay healthy and safe.
06:10And what that looks like as a
06:13toddler is getting them started on
06:15penicillin prophylactically or in
06:17advance before there's any problems
06:19because we found that as
06:22recently as the late 70s,
06:25there was kind of a peak
06:27in infancy and toddlerhood of death,
06:29because patients with sickle cell
06:31were getting really bad infections,
06:33but we found that if we vaccinate them
06:35and give them prophylactic penicillin,
06:37they live well into adulthood.
06:39The challenge becomes,
06:39how do we help them when they
06:41go from infant to adults?
06:43And that's what I work on in my work.
06:44So just to back up a little bit when
06:47you say prophylactic penicillin,
06:49do you mean like every day for
06:51the rest of their life?
06:53So definitely every day for the
06:56first five years of their life.
06:58But what it does is it
07:01protects them against really bad
07:03infections like pneumococcus you know
07:05patients with sickle cell disease,
07:07their spleen doesn't really work
07:09as well as somebody without sickle
07:11cell and because of that they are
07:14susceptible to certain types of
07:16infections and that penicillin
07:17every day just like a vitamin helps
07:19them to stay healthy and safe.
07:22So why is there this transition then
07:24from childhood to young adulthood?
07:27What's the difference in terms of
07:29the disease and how it's managed
07:30that requires a specialist like you?
07:33Well, I think it's a variety of things.
07:36It's not just the disease,
07:38but it's becoming a young person
07:40and learning how to navigate the
07:41health care system on your own
07:43and earlier we talked
07:45about newborns and
07:46if you were a newborn and found out
07:48you had sickle cell disease that your parents
07:51would help you take you to the doctor.
07:53Manage your care,
07:54give you that prophylactic penicillin.
07:56But the beautiful part about being
07:58a young adult is you can start to
08:00assume some of that care for yourself,
08:02so it's pretty
08:03multi Factorial is a word I always
08:05like to use and I like to
08:08think that I was a pretty smart young
08:10adult like I made some good decisions.
08:12I'm a doctor now,
08:13but I still did some foolish things
08:15as a 16-17 eighteen year old and
08:18that's without a chronic disease.
08:19So in sickle cell disease,
08:21what we can do as lifespan hematologists
08:23and as health care providers is
08:26really help our patients as their
08:28disease complications may become
08:29a little more severe as they're
08:32learning to manage themselves.
08:33As they're learning to navigate a
08:35pretty complex health care system,
08:37and as they're just trying to be productive,
08:40happy young adults.
08:42What kinds of things do you
08:45talk about with your patients?
08:47It sounds like
08:48after their five years old,
08:49they're no longer on penicillin,
08:52but there's still no way to reverse
08:54the condition, so you're still
08:56at risk of all of those sticky,
08:58misshapen blood cells forming
09:00clots all over your body,
09:01which presumably can cause
09:03all kinds of problems.
09:05Is it just a matter
09:07of telling your patients what to
09:10watch for and when to seek help?
09:12Or are there things that they can do
09:15to reduce the risk of clots and
09:18other problems that it can cause?
09:22Absolutely, so I want to answer
09:24your question in two parts.
09:26First, what other parts of the
09:28body does sickle cell affect?
09:30How does that show up for
09:33patients across their lives?
09:35One of the things that our patients most
09:38deal with is pain every single day.
09:41So when those blood vessels get clogged
09:43up by those sickle cells and those juicy
09:45Jelly doughnut cells can't get through,
09:47that means oxygen isn't
09:48going to where it needs to
09:50in our bodies.
09:51And because of that,
09:52that can result in pretty bad bone pain
09:55for patients with sickle cell disease,
09:57and this is the thing that really affects
09:59their quality of life as young students
10:01trying to learn and keep up in school.
10:03If you have to be admitted to
10:05the hospital several times
10:06a year you can imagine how
10:08frustrating that can be as a scholar.
10:11Other parts of the body that are affected
10:13by sickle cell disease are numerous.
10:16Though patients with sickle
10:17cell disease can have something
10:18called acute chest syndrome,
10:20which is a really bad infection of the
10:22lungs that can be very challenging,
10:24they can even have strokes as young people,
10:27which is one of the reasons that
10:29compelled me as a Med student to
10:31pursue hematology was seeing a sickle
10:33cell patient eight years old who had
10:34a stroke in Pediatrics.
10:36And in order to kind of get a jump on these things,
10:38we do several things,
10:40we do screenings.
10:42Something called a transcranial Doppler,
10:43which is basically like an ultrasound
10:45of your head where you can look at the
10:47blood vessels and make sure you're
10:49not at risk for having a stroke.
10:51We always make sure that our patients
10:54have their eyes checked because
10:56sometimes in sickle cell disease
10:58you can have vision changes and a
11:00regular follow up with a hematologist
11:02can help you notice any changes
11:05before they cause problems.
11:07One of the biggest things and one
11:09of the things we know works and
11:11helps prolong life
11:11in sickle cell patients is a use of
11:14a medication called Hydroxyurea.
11:16Now, some of your listeners may be familiar,
11:18because sometimes this can be used in
11:21patients who have certain cancer diagnosis,
11:24but in sickle cell disease,
11:26the dose that we use is much lower and the
11:29way that we use it as a bit different.
11:31And we know that it kind of helps
11:33you have more juicy fat
11:35cells then bananas and so your body
11:38overall does better in the long term.
11:41So just to follow up on a few
11:44things that you just said.
11:45First off taking that last
11:48comment about Hydroxyurea making
11:50You have more fat and juicy like
11:52blood cells rather than sickling bananas,
11:55is it true that if you
11:57have sickle cell disease,
11:59not all of your blood cells are
12:01bananas and it is possible to
12:03increase the number of Jelly doughnut
12:05blood cells that you have instead
12:08of bananas?
12:11Absolutely, and that is up until
12:14recently, the only FDA
12:16approved medication that we have had
12:18for our patients is Hydroxyurea
12:20to increase the amount of non sickle cells,
12:23Jelly doughnut cells and ensure that
12:25you're pain complications are lower
12:28and that your organs can really get
12:30the oxygen they need to thrive.
12:33So an obvious question is why
12:35not use more and make
12:37all of your blood cells Jelly Donuts?
12:39But hold that thought.
12:41Because first we need to take a short
12:44break for medical minute. Stay tuned
12:46to learn more about adolescents and
12:48young adults with sickle cell disease
12:50with my guest doctor CeCe Calhoun.
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14:13listening to Connecticut
14:14Public Radio.
14:15Welcome back to Yale Cancer Answers.
14:17This is Doctor Anees Chagpar and I'm
14:20joined tonight by my guest Dr. Cece Calhoun.
14:23We're talking about the care of adolescents
14:25and young adults with sickle cell
14:27disease and bright before the break
14:29CeCe was mentioning that while sickle cell
14:33disease is completely
14:35irreversible,
14:38that actually using a drug called
14:40Hydroxyurea can help your body to
14:43create more of these quote juicy
14:46cells which are normal red blood cells
14:49and less of these quote banana like
14:52cells which are the sickle cells.
14:54So my question to you was.
14:57before we had the break, is why
15:01not just give more Hydroxyurea?
15:04I mean if it helps your body to produce
15:07more normal cells and less sickle cells,
15:09wouldn't that be a way to kind
15:11of reverse it?
15:14I would love if it could be
15:16totally reversed by Hydroxyurea
15:18but we know that when our
15:20patients are awesome, take their
15:22medications every day as prescribed,
15:24there's still an upper limit to
15:26how many of those juicy fat
15:29cells they can replace.
15:31They can produce to replace the banana cells,
15:34so there's a threshold of how
15:37effective the drug can be,
15:39but it can really,
15:40really help enough to help
15:42your organs stay healthy.
15:44So this Hydroxyurea is something
15:46that you're taking every day?
15:48For your whole life?
15:50And the other thing
15:53that you mentioned before the break
15:56and I wanted to pick up on as well
15:59was this concept of pain and the fact
16:02that many of these patients they present
16:05with pain and they have pain every day
16:08which impairs their ability to
16:12concentrate at school or maybe place
16:15boards so what do you do about that?
16:19I mean, are these patients
16:21treated with daily painkillers?
16:22Or do you tell them to simply
16:24wait until they have pain and
16:27then prescribe pain medication?
16:29I mean how do they get through their day
16:31to day life if they're in pain everyday?
16:35Yeah, so sickle cell patients are warriors
16:38and you'll often see that described because
16:42despite having pain of variable severity,
16:45they managed to live life and be productive.
16:48That's one of the most awesome things
16:50about working with sickle cell patients.
16:53So in terms of pain prevention,
16:55what can we do?
16:56Number one Hydroxyurea and get more juicy
16:59cells around so you have less pain.
17:01And recently there are a couple
17:03of medications on the market
17:05that help with pain prevention.
17:08Also just keeping yourself well hydrated.
17:11My patients are so wonderful in
17:12that they often know their bodies.
17:14They know their triggers.
17:16And what situations make their pain worse.
17:18And what kind of things can
17:19make their pain better.
17:20So really being attuned to those things
17:23in terms of addressing pain acutely
17:25when it happens and it's not planned,
17:28we have a couple of things in our toolkit.
17:32Yes, pain medication is something
17:34that we give frequently for pain,
17:37but we can also use red
17:39blood cell transfusions if we need to.
17:41If somebody is having pain often,
17:43but many times we can't predict
17:46when the pain will come,
17:47or how severe it will be,
17:49and so because of that our patients
17:51have to get care in the ED sometimes
17:53to get treatment for their pain.
17:56You mentioned something
17:57that I found kind of intriguing.
17:59You said that we have medications
18:01for pain prevention, like what?
18:04Hot off the press I know,
18:07so recently there's been
18:10an FDA approved medication,
18:12Adakveo or crizanlizumab
18:16but I try not to say
18:19that because crizanlizumab,
18:21but that can be used to prevent pain
18:24as an infusion given once monthly.
18:32And another medication that's recently been
18:34approved is something called Oxbryta
18:36and really, what that does is increase
18:39patients with sickle cell disease,
18:41their hemoglobin,
18:42and so the thought is if their
18:45hemoglobin is better they
18:47may in turn have less pain,
18:49but the primary medication that
18:52is out there for pain
18:55prevention is Adakveo.
18:57That sounds like a
18:59pretty good deal, right?
19:01If instead of having pain everyday,
19:03if you had an infusion once a month,
19:05does that infusion kind of really get
19:07rid of the chances of having pain?
19:09Or not really?
19:12I think that the medication is pretty
19:15new and patients themselves are
19:18are individuals,
19:19and so I've had some patients
19:21who it's worked great for.
19:22I've had some patients that we
19:23just have to try other things.
19:25I think the wonderful thing
19:27about being a physician
19:29scientist and sickle cell,
19:30or even being a patient right now
19:32who has sickle cell is that it is
19:34such a fertile time for discovery.
19:36In terms of sickle cell disease,
19:38how to prevent complications
19:39and how to cure it.
19:41So you just have to work with
19:43your hematologist to find
19:44the right regimen for you.
19:46So I want to pick up on
19:48that discovery and some of the
19:51new advances that are going on
19:53in terms of sickle cell research.
19:54But before that I had one other question
19:57about the complications
19:59you had mentioned before the break.
20:01One of the impetuses for you to
20:04become a pediatric climatologist
20:06was an 8 year old who had a stroke,
20:09which just I mean is heartbreaking to me.
20:12But clearly if you think about these
20:15sickle cells, it makes sense, right?
20:17These sickle cells kind of glom
20:19together and they cut off blood
20:20supply to a part of your brain
20:22that's called the stroke.
20:23Now when we think about
20:25older patients who
20:27may be at risk of stroke or who may
20:29be at risk of heart attack or who
20:31may be at risk of other clotting,
20:33whether it's in their lungs or
20:35in their legs or whatever,
20:37we often use blood thinners,
20:40so are sickle cell patients put
20:42on blood thinners to
20:44prevent these complications?
20:45Since we know that they're
20:47at risk of getting clots.
20:48So the blockages that occur in sickle
20:51cell disease are a little bit different
20:54than your normal blood clot, which is
20:57caused by a different series of events,
21:00and so for patients with sickle cell disease,
21:02though they are at an increased
21:04risk to have those
21:05traditionally, what we think of blood clots,
21:07we don't put them on blood thinners
21:09to try to prevent complications
21:11with sickle cell disease.
21:13We know those blockages can be stuck
21:15like a clot, or they can be transient,
21:17they come and go because of the
21:18cells sticking together.
21:19It's not like the other proteins in
21:21your body are swimming over there,
21:23making a huge clot.
21:24What we do in our young people
21:27to maximize stroke prevention
21:28is we do screenings like the
21:30Transcranial Doppler I mentioned.
21:32And if we notice any kind
21:34of abnormality at all,
21:36we have a couple of options.
21:38One we can start them on chronic
21:41transfusion to decrease the
21:43amount of sickle cells circulating in their
21:46blood and give them more normal cells.
21:48Or if somebody has been
21:50on transfusions,
21:52their transcranial dopplers looks fine,
21:54we can switch them to again Hydroxyurea
21:57put more Jelly Donuts around,
21:59have less sickle cells,
22:01decrease the risk of complications,
22:03and that's again why it's important
22:05to connect with your
22:06friendly hematologist so we
22:07can help you on that journey.
22:09Yeah, but presumably you would have
22:11already been on the Hydroxyurea
22:13so if that transcranial Doppler finds
22:16that you're at increased risk
22:20I guess the transfusion
22:22is your only alternative,
22:23but the issue there is if you keep
22:26getting transfusions on a regular basis,
22:29doesn't that increase your risk of
22:32transfusion reactions and potentially
22:33ultimately developing antibodies such
22:35that there are fewer and fewer blood
22:38types that you can actually take?
22:42Absolutely.
22:44For patients who have chronic transfusions,
22:47they're a variety of risks that
22:49come along with that.
22:50There's obviously a clear benefit
22:52in that it keeps you safe
22:53and protects you against stroke
22:55and may decrease your pain.
22:56But you're absolutely right,
22:57our bodies recognize
22:59things that aren't foreign,
23:00and that's why we really work in tandem
23:03and together with our transfusion
23:05medicine colleagues to do extended
23:07typing in patients with sickle cell
23:09disease to prevent that risk of
23:11developing antibodies.
23:14Another big risk is something
23:16called iron overload,
23:17where excess iron from the blood deposits
23:20in different organs like your liver,
23:22your heart, or your eyes.
23:24So we measure that regularly and again,
23:26medicine is so cool because we're
23:29always ideally moving forward and
23:31there's also a procedure
23:34called Erythrocytosis
23:35which I don't too much mind
23:37saying five times fast,
23:38but I like it, which can help
23:40decrease that risk of iron overload.
23:49Let's talk a little bit
23:51about some of the exciting advances
23:53in terms of sickle cell disease.
23:55Tell us about what you think are the
23:57most exciting things that are on the
23:59forefront that you think are really going
24:00to make a difference for your patients.
24:03I think there are a lot of
24:06medications in the works to address pain
24:10and complications of sickle cell disease.
24:13But one of the things I think that is
24:16most exciting is the idea of a cure
24:20through gene therapy,
24:22and that's pretty awesome.
24:24There's been some media, the
24:30New York Times has published about it
24:32and the Washington Post as
24:34well about how we can use different
24:37scientific technologies like CRISPR
24:39technology or use different vectors
24:41like viral vectors to take somebody's
24:44stem cells and correct that defect
24:46in their DNA that caused them to
24:49be making sickle cells and then
24:52give it back to them in a safe way,
24:54and then when those new and
24:56improved cells from their bodies
24:58replicate
24:59they are no longer affected
25:01by sickle cell disease.
25:02They may still make some sickle cells,
25:05but will effectively be cured or
25:06be like somebody who just has the
25:09trait and that's one of the things
25:10I think that's most exciting.
25:12The possibility of a cure
25:13in our future.
25:18And is that 10-15, 30-50 years from now?
25:21No, the time is totally now,
25:24so there are clinical,
25:25active clinical trials going on
25:28to better understand the safety
25:30and efficacy of this process
25:32for patients and so
25:34that's happening now.
25:36Wow, that's
25:39super exciting. What else is going on?
25:42So I think the other main things are
25:45the development of oral medications
25:47to improve pain and to decrease
25:50complications from sickle cell disease.
25:52That one medication,
25:53Adakveo, the way that it works,
25:56it's something called
25:58a B selection inhibitor.
25:59And so they're more medications
26:01coming around that look at that.
26:03And there's some additional
26:07oral medications coming that target
26:10different mechanisms and other blood
26:12problems like thalassemia and
26:14they want to see if those medications
26:17can work well in
26:18patients with sickle cell disease.
26:20So I think that fact that we are shining
26:22a light on this community of people
26:25with sickle cell disease and that we as
26:27a scientific community have committed
26:29to making their quality of life better,
26:31that's the thing that's most exciting to me,
26:34because oftentimes I think my
26:36patients feel unseen and unheard,
26:38and so it's great to see so many people,
26:43brilliant people standing up for them
26:44and helping to make their lives better.
26:46That's awesome.
26:47I guess the last question that I have is
26:50really with regards to clinical trials.
26:52I mean, it sounds like there's so
26:56many great things on the horizon.
26:58Do you find that young people
27:01adolescents are interested in clinical
27:04trials and willing to participate?
27:08Are there barriers to participation?
27:10How has that been going along?
27:13Yeah, so anybody who has lived
27:15with sickle cell or chronic pain,
27:17I think is enthusiastic about
27:19finding a way to have a better
27:21life and to come have a better
27:23quality of life and to find a cure.
27:26When it comes to clinical trials,
27:28there's a careful balance
27:32between understanding clinical
27:34studies and not wanting to feel like
27:36an experiment and understanding
27:38how the medical system can wrap
27:40around you to keep you safe.
27:42As we understand more about
27:44how to help you have a cure.
27:47And so when I think about
27:49my young people,
27:50are they interested in clinical trials?
27:52I think that they have a lot of excellent
27:55questions about the benefits and
27:57risks of participating in clinical trials.
28:00But many of them ultimately,
28:01when we sit and talk and take the time,
28:04they understand that it is their
28:06contribution to not only their health,
28:08but the community of sickle cell patients.
28:10And that's the beauty of having providers
28:12that have known you through the lifespan.
28:14You have a relationship.
28:15They know that I care for them.
28:17They can trust me.
28:18And so when I offer them this option,
28:23then there's a little bit
28:25more willingness to enroll.
28:27Dr Cece Calhoun is an assistant
28:29professor of medicine in hematology
28:31and assistant professor of
28:33Pediatrics in hematology,
28:34oncology at the Yale School of Medicine.
28:37If you have questions,
28:38the address is canceranswers@yale.edu
28:40and past editions of
28:42the program are available in audio and
28:45written form at yalecancercenter.org.
28:48We hope you'll join us next week to
28:50learn more about the fight against
28:52cancer here on Connecticut Public
28:54radio funding for Yale Cancer
28:56Answers is provided by Smilow
28:57Cancer Hospital and Astra Zeneca.