Pediatric Cancers/Lymphoblastic Leukemia

July 06, 2020

Information

July 5, 2020

Yale Cancer Center

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00:00Support for Yale Cancer Answers
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00:14Welcome to Yale Cancer
00:15Answers with your host
00:17Doctor Anees Chagpar.
00:18Yale Cancer Answers features the
00:20latest information on cancer care by
00:23welcoming oncologists and specialists
00:24who are on the forefront of the
00:27battle to fight cancer. This week
00:28it's a conversation about pediatric
00:30cancers and lymphoblastic
00:31leukemia with doctor Aron Flagg.
00:33Doctor Flagg is an assistant professor
00:35of Pediatrics in hematology/oncology
00:37at the Yale School of Medicine,
00:39where doctor Chagpar is a
00:41professor of surgical oncology.
00:44Aron, maybe we can start off by
00:47you telling us a little bit about
00:49pediatric cancers in general.
00:51Nobody ever likes to think
00:53about cancer occurring in kids,
00:55but how common are pediatric cancers?
00:57Overall
00:57pediatric cancers are rare
00:58compared to adult cancers.
01:00The most common that we see is something
01:02called acute lymphoblastic leukemia or ALL,
01:04and we see several 1000 cases of ALL
01:07in the United States every year.
01:09Beyond that,
01:09the next most common types of cancers
01:12are brain tumors or brain cancers,
01:14of which there
01:15are a number of types and following
01:16that there are a number of different
01:18cancers we can see elsewhere
01:20throughout the body.
01:21So tell us a little bit more about ALL.
01:24How does it present?
01:25Because
01:26if you're a parent out there
01:27and you're listening to this,
01:29you're kind of thinking,
01:30I never want my kid to get cancer,
01:32but Gosh darn it if I ever
01:34find a sign or symptom,
01:36I want to know what that is so that
01:38I can take appropriate next steps.
01:40Sure, this can
01:41be tough sometimes because a lot
01:43of the symptoms are nonspecific,
01:44meaning they can happen
01:46for a variety of reasons,
01:47and many of them are not cancerous.
01:50So specifically with ALL or
01:52acute lymphoblastic leukemia,
01:53many children will be very tired or fatigued.
01:55They may look very pale.
01:56They may have bleeding or
01:58bruising for no reason,
01:59and then many children will also
02:01have pain in the bones or the joints,
02:03and so a limp is also a common
02:06symptom that patients can have.
02:07But for other types of cancers that
02:09can occur really throughout the body,
02:11the symptoms really depend on what type
02:13of cancer and where it's occurring,
02:15so it can be very hard to list
02:17off one specific symptom
02:19that might be a sign of cancer.
02:21So from my standpoint,
02:22if a parent is worried that
02:23something is going on,
02:24if symptoms are there and not
02:26getting better on their own,
02:27they should always talk with
02:28the pediatrician.
02:29So you know when we think about
02:31ALL and the symptoms that you
02:33mentioned are really non specific.
02:35I mean kids jump around they play,
02:38they get tired, they get bruised.
02:40They may have some pain.
02:41They get pale and
02:43a lot of people
02:45go into their pediatricians.
02:47I think it can be
02:49really tough and from my standpoint
02:52when patients finally come to
02:54see me they almost always have a
02:56diagnosis or they have a lab test
02:58that shows something is wrong.
03:00And so my job in some ways is simpler
03:02because I know there's a problem.
03:04I think it's much harder for an
03:06emergency room doctor or a pediatrician
03:08to take a child who's got these
03:11symptoms where 99 out of 100 may be
03:13fine and pick out the one in 100 who
03:15really does have a severe problem.
03:17How do they do that exactly?
03:19So through careful history, a
03:21physical exam and through taking
03:23lab tests to look for things is
03:25really the best way to do it.
03:27But far and wide,
03:28the most important thing is listening
03:30to parents and looking at the child.
03:33And what exactly are they listening
03:35for? And looking for?
03:37I think when they're listening,
03:38it's when symptoms don't get better.
03:40It's something that's been there
03:42that doesn't seem just like a virus,
03:44which is probably the most common
03:45reason for a lot of these complaints
03:48young kids will have,
03:49and so when that symptom is there over weeks,
03:51and instead of getting
03:53better is getting worse.
03:54Maybe children are losing weight,
03:55maybe they are having fevers for no good reason,
03:58and then again on physical exam
03:59they may be able to find something
04:01that's abnormal that
04:03they might have
04:04swollen lymph nodes, their liver or
04:06spleen might be enlarged.
04:07Something that tips them off to
04:08something going on that isn't
04:09the run of the mill problem.
04:11And you mentioned lab tests.
04:12What kind of lab tests do
04:14they get?
04:16This can be difficult because depending
04:16on what type of cancer it is,
04:18certain lab tests may
04:19or may not be a good screening
04:21test to use for leukemia.
04:22The most common lab test we would look
04:24at is a complete blood count where we
04:26can look under the microscope with the blood,
04:28look at the white blood cells,
04:29red blood cells and platelets to
04:31see if they are normal and
04:33to see if there might be leukemia
04:35cells in the blood as well.
04:37So for ALL, and we will focus our
04:39discussion on ALL because that's
04:40the most common pediatric cancer
04:42and the one that you specialize in,
04:45what would you see in that
04:46complete blood count?
04:47So children are often anemic,
04:49meaning the red blood
04:50cell count is low.
04:53And red blood cells give your body the ability to carry oxygen.
04:56It makes the blood red and
04:58so when children are anemic,
04:59they're often very pale as well.
05:01So again, that physical exam might clue
05:04us into the low red blood cell count.
05:07Platelets are tiny cells in the blood that
05:09help to prevent bleeding and to form clots.
05:11When you get a cut and when
05:13there's a leukemia present,
05:15those platelets often become
05:16also very low and so we can see
05:19that very easily on a lab test.
05:21Finally, will look at the white blood
05:23cell count and leukemia cells are
05:25an early type of white blood cell,
05:27and so for many patients with leukemia,
05:29we might see that white blood cell
05:31count very elevated because of
05:33the leukemia cells in the blood,
05:34and if they see this trifecta,
05:37they get worried absolutely.
05:39And does that cinch the diagnosis of ALL?
05:41Sometimes it does
05:42so if we can see circulating
05:43leukemia cells in the blood,
05:45there's really nothing else that it could be,
05:47but sometimes it's not so easy.
05:48Some kids, when they present,
05:50especially early on in the course,
05:51may not have leukemia cells in the blood,
05:54and so if we're not able to make the
05:56diagnosis directly from a blood count,
05:58we might talk about doing a bone
05:59marrow biopsy to confirm a diagnosis.
06:01And what do you see on
06:03the bone marrow biopsy?
06:04So all of the blood is made
06:06within the bone marrow,
06:07and so when a leukemia comes on,
06:09it starts in the bone marrow.
06:11And when it's there very early
06:12before it's gotten into the blood,
06:14we might be able to see it
06:15in the bone marrow.
06:16So in a bone marrow biopsy,
06:18and we place a small needle
06:19into one of the bones,
06:20usually in the hip bones,
06:21they take a sample to
06:23look at under the microscope,
06:24and then you see leukemia cells and
06:25that would
06:26be the definitive test.
06:28And then they come to
06:30you, correct, with this diagnosis?
06:32And then what happens after they
06:34get over the shock of, Oh my God,
06:36my kid has cancer right?
06:38So a lot of that first meeting
06:40really is talking about,
06:41what is cancer?
06:44And where do we go from here?
06:47And really trying to get over
06:49that initial shock which can take
06:51us several days to let
06:53everything to sink in and many children,
06:55when their leukemias first are
06:56diagnosed are quite ill,
06:57and so this is usually happening
07:00in the hospital where we have time
07:02to sit down and talk outside of
07:04the constraints of an office visit.
07:06So how exactly is
07:09this treated?
07:11Is it treated through chemotherapy?
07:13It's given in several phases,
07:14some of them more intensive,
07:16especially at the beginning.
07:17Some of them later on in the course are much
07:20easier to tolerate the beginning course.
07:22We call induction chemotherapy some of
07:24that time is spent in the hospital,
07:26especially until the leukemia
07:27starts to go into remission.
07:28The majority of the rest of
07:30therapy is actually given in
07:31the office as an outpatient,
07:33where patients may have to come once
07:34or twice a week for several months
07:36in a row to get their therapy,
07:38and then it ends with the course of therapy
07:41that we call maintenance chemotherapy.
07:42Meaning leukemia is in remission,
07:44and we're trying to keep it that way.
07:46Maintenance therapy is usually
07:47given on a once a month basis.
07:49Also in the office,
07:50but goes on for many years, usually
07:53two to three years from diagnosis.
07:56So these children are essentially getting
07:57chemotherapy for potentially years?
07:59Yes, if it's a very long road and even
08:02in maintenance chemotherapy,
08:03or we think about a once a month visit to
08:06the oncology office when they're at home,
08:09they're often still taking chemotherapy
08:10by mouth every day or every week.
08:13And what are the effects of that?
08:15I mean, do they get sick and they
08:17still go to school?
08:20What happens to their friends and how
08:22does this affect their lives?
08:24That's a great question.
08:25Many of our patients can lead nearly
08:27normal lives going through this,
08:28although every patient is different.
08:30There certainly is a risk of infection,
08:32especially at the beginning when the
08:34chemotherapy is much more intensive.
08:35But really after that first month
08:37until the leukemia is in remission,
08:39after which we really advise children to
08:42try to have as normal a life as possible.
08:45We encourage kids to go to school.
08:47We encourage them to have normal
08:49relationships with friends and relatives.
08:50We really try to focus on
08:52keeping their quality of
08:53life as normal as possible.
08:55Tell me about the side effects of
08:57these chemotherapies because you know,
08:59I can imagine if you're a kid and
09:01you're trying to have a normal life,
09:04but you've lost your
09:06hair and your friends are calling
09:08you bald and you're feeling sick,
09:10and it might be easier said
09:12than done to have a normal life.
09:15Yeah, absolutely.
09:16And we're fortunate now that many children
09:18are able to be cured of their cancer.
09:21In fact, most children with ALL are
09:23able to be cured and so many years ago,
09:26our primary focus was curing the cancer.
09:28Now, because of the improvements in
09:30the chemotherapy that we can offer,
09:32we can focus on other issues like
09:35you mentioned quality of life,
09:37not just being able to get
09:38the cancer under control.
09:40We do work with psychologists to help with
09:43that transition back into normal life.
09:45You know, especially in teenagers
09:47body image is really important to be
09:49able to find ways to get through life.
09:51You know that may be different
09:54than it was before
09:56the chemotherapy in terms of side effects,
10:00Some patients may have a lot
10:02of nausea there may be infection.
10:05Many patients need transfusions because
10:07of side effects of chemotherapy.
10:10And we're not also focusing just
10:12on the side effects that we see
10:14right at the time of chemotherapy.
10:15We're also focusing now on the
10:17long term side effects.
10:18The late effects that might happen
10:20five years down the road, 10 years,
10:2220 years.
10:22Whether that's a problem with hormones
10:25affects on the heart or on bone development,
10:27really trying to find ways that we can
10:29improve upon those late outcomes and
10:31really give kids the best possible
10:33life after their therapy.
10:35So with chemotherapy, you
10:37tend to lose your hair, and I suppose
10:39that's the case with ALL as well.
10:42But you know, with other kinds of cancer,
10:44the therapies are much shorter and we
10:47always tell people don't worry your hair
10:49will grow back, but when they're
10:50getting years of therapy, I mean,
10:52do they ever grow their hair back?
10:55I mean, can they ever truly feel normal?
10:58Yeah, so the hair loss tends
10:59to be reasonably temporary,
11:00again we see it at the early parts of
11:02therapy with more intensive chemotherapy.
11:04Fortunately, by the time children
11:05are on maintenance chemotherapy,
11:06the low levels of medicines that we're
11:08giving do tend to allow hair to regrow,
11:10and so usually once you're in that
11:12maintenance cycle for a few months,
11:13we start to see the hair come back.
11:15And interestingly,
11:16a lot of the times it comes back
11:18thicker, it's curly,
11:19are so often it gives us something
11:21to talk about in the office in
11:22terms of comparing what their hair
11:24was before and what it is now.
11:26And one of
11:28the good things, I suppose,
11:30is that you know kids are living longer.
11:32Tell us about the prognosis with ALL.
11:35I mean, almost all patients
11:37you mentioned are cured.
11:40A very good proportion of them are.
11:41We are now able to identify for the most
11:44part which children are going to be cured
11:46by chemotherapy and cured
11:49of their ALL early on in their therapy.
11:51And then we can also predict which kids may
11:54have a harder time to achieve remission.
11:57How do we do that?
11:58Some of its based on very simple things
12:00like age, so we know that older kids,
12:03especially adolescents or young adults,
12:04have a harder time to be cured
12:07than younger kids.
12:08That said, very young children,
12:10especially less than one year, may also
12:12have a problem getting into remission.
12:14So we can start with that.
12:16We also follow response to therapy,
12:18and
12:19what most people have been looking at the
12:21past few years is something called
12:23minimal residual disease or MRD analysis.
12:25It's a way for us,
12:26through a bone marrow test,
12:28to see how much of a remission
12:30somebody gets into,
12:31and we know that the deeper a
12:34remission the patient enters early on
12:35in their therapy predicts whether
12:37or not they'll be cured.
12:39And so with this information we can
12:41tell patients within a few months
12:42of their diagnosis whether or not
12:44we expect with a good certainty
12:46that they'll be cured,
12:47or whether or not we think there may
12:49be a challenge for patients who respond
12:51quickly who are in a favorable age range.
12:53More than 95% of those children
12:55can be cured through chemotherapy.
12:56For some older children,
12:58especially young adults or patients
12:59who don't quickly go into remission,
13:01there may be more of a struggle,
13:03and sometimes that may be more
13:0450 or 70% chance.
13:06I'd hate to be in that last group where you
13:09tell me that there's going to be a bit
13:11of a challenge for me to get a cure.
13:15What do you do about that?
13:17I would be like,
13:20well thank you for telling me
13:21that I might struggle,
13:23but what are you gonna do about
13:25it right now?
13:27These are very hard conversations to have and
13:29it's really through research that
13:31we're trying to find better ways,
13:32especially in these high risk groups
13:34to do better to get them in remission.
13:36So we participate in a large
13:38Children's Hospital Consortium called
13:39the children's oncology group
13:41that's really doing most of the
13:42research in the country to look at
13:44how we can achieve better outcomes.
13:46And that's using new medications that
13:48may work differently than the
13:50older types of chemotherapy,
13:51or even doing much more aggressive treatment,
13:53such as things like bone marrow transplant
13:55earlier on.
13:57We're going to pick up the conversation
13:59looking at those newer treatments and
14:01other treatments right after we take
14:03a short break for medical minute.
14:05Please stay tuned to learn more about
14:07pediatric cancers and lymphoblastic
14:08leukemia with my guest Doctor Aron Flagg.
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15:01at yalecancercenter.org.
15:02You're listening to Connecticut public radio.
15:05Welcome
15:06back to Yale Cancer Answers.
15:08This is doctor Anees Chagpar
15:10and I'm joined tonight
15:12by my guest Doctor Aron Flagg.
15:14We're talking about pediatric cancers,
15:16and in particular,
15:17acute lymphoblastic leukemia,
15:19which is the most common
15:21cancer affecting children.
15:22And right before the break
15:25Aron you said that
15:27we've done really well in
15:29terms of treating ALL and for a
15:32particular subgroup of patients,
15:34those who tend to be younger
15:37children but not too young who
15:39achieve remission with induction
15:41chemotherapy that
15:43those patients have a reasonably good shot,
15:4695% chance of achieving a cure.
15:48But then there's another group of patients,
15:51those who may not respond so well
15:54to initial chemotherapy who may be older
16:00who don't have as good of a shot of cure.
16:05And so you started to mention that
16:07in that group of patients there are
16:10other things besides traditional
16:12chemotherapy that you look at.
16:14Tell us more about that.
16:16Sure, I
16:17like to think of chemotherapy as
16:21very non specific medicine that
16:22attack cells in the body that are
16:25growing quickly, like cancer cells.
16:26They also cause a lot of side effects,
16:29but as we've kind of plateaued with how
16:32well those medicines work we're looking
16:34for other avenues and so we are now using
16:37many drugs called targeted agents,
16:39so not just to blindly kill off all
16:41the cancer cells but really to find
16:44specific targets on those cancer cells
16:46to hone in on that and make them
16:48much more effective than other drugs.
16:51We have used methods like pursuing
16:53a bone marrow transplant that allows
16:55us to give extraordinary doses of
16:57chemotherapy and give new bone
16:59marrow and then really in the past
17:01few years we've also used types of
17:03interventions called cellular therapies,
17:04so we're now able to take a patient's
17:06own immune system to engineer cells
17:08in a laboratory, put them back in,
17:11and allow those cells to attack
17:13the cancer itself.
17:14And so we have really many
17:15new ways to treat these,
17:17to provide options for patients
17:19who previously didn't have
17:20those.
17:21That sounds really interesting, so let's take
17:23each of those three in turn.
17:25Sure, so first, targeted therapies.
17:26I mean, we've spent a lot of time on
17:29this show talking about precision
17:31medicine and targeted therapy,
17:32and personalized medicine
17:34and so on and so forth
17:37where there's often a target on
17:39a cancer cell and we have a drug
17:43that will attack said target,
17:45essentially being more like a
17:47sniper rather than a machine gun
17:50at attacking these cancers.
17:52Tell us more about that approach in ALL.
17:55Yeah, so we
17:56know that mutations in the genetic
17:59code of these cancer cells is
18:01really what turns them from
18:03normal cells into cancer cells,
18:05and many of those changes,
18:07do have medicines that might
18:09affect those and slow down the
18:11growth of those cancer cells so we
18:13do have several of those available.
18:15In particular,
18:16there's a type of ALL called
18:17Philadelphia chromosome positive
18:18acute lymphoblastic leukemia,
18:19where there have been drugs on
18:21the market even since the 1990s,
18:23that specifically attack that
18:24Philadelphia chromosome,
18:25and so this was a disease that
18:27again 10-20 years ago,
18:28we might have recommended everybody
18:30have a bone marrow transplant,
18:32now most children don't need a
18:34bone marrow transplant because we
18:35can give a target before that.
18:37In that case,
18:39where we have targeted agents,
18:43do we give that instead of the induction
18:45chemotherapy and so on and so forth
18:47that you had mentioned before?
18:49Because it sounds like if
18:50you have a sniper, why
18:52use the machine gun, right?
18:53So right now these are really adjunctive,
18:56we give them in addition
18:58to traditional chemotherapy.
18:59It certainly may hit a point though that
19:01as these medicines improve or we find
19:03different ones that we might not have
19:05to give the same traditional
19:07chemotherapy anymore.
19:07But we're not there yet.
19:09OK, so if you have a particular kind
19:11of ALL that has a particular marker,
19:13for example the Philadelphia
19:15chromosome positive ALL,
19:17then targeted therapy is something
19:19that should certainly be
19:21part of the regimen absolutely,
19:22but then you mentioned the 2nd
19:25which was bone marrow transplant and
19:27you had mentioned before the break
19:30that the bone marrow is really the
19:32place where these cells are developed,
19:34and so in the factory that's making
19:37all of your red blood cells and white
19:40blood cells and platelets and so on.
19:43In that bone marrow,
19:44that's where the leukemias developed,
19:46and so with bone marrow transplant,
19:49you're really thinking about
19:50wiping out that bone marrow,
19:52and you mentioned that the purpose of
19:54that is to give really high doses of
19:57chemotherapy. Tell us more about how that works.
20:01So right now when you
20:03give regular doses of chemotherapy,
20:05it does attack the leukemia cells,
20:07but we can only give so much of it.
20:09And when you try to give very
20:11high doses of chemotherapy,
20:13we see so many side effects,
20:15especially to healthy bone marrow cells,
20:17that there's really a limit to how
20:19much we can give in the setting
20:21of bone marrow transplantation
20:22or stem cell transplantation for
20:24treating a cancer like leukemia.
20:26The idea is that we give astronomically
20:28high doses of chemotherapy,
20:29sometimes radiation therapy,
20:30to try to wipe out not just the leukemia,
20:34but we might also remove the healthy bone
20:37marrow as well by giving a transplant.
20:39It allows us to restore that
20:41normal bone marrow function.
20:43So two questions, first question,
20:45if you're going to give somebody an
20:47astronomical amount of chemotherapy,
20:49so much so that is going to wipe
20:52out their entire bone marrow,
20:54doesn't that give them a whole lot of
20:57side effects like why do that?
20:59I mean, unless we know that the
21:01response rate is better to that,
21:03but we're using it in people who
21:06aren't responding anyways, right?
21:07So the
21:08idea is that for some patients,
21:10if they have some resistance to
21:12the chemotherapy they're getting
21:13that if we give different types
21:15of chemotherapy, and especially
21:17very high doses of chemotherapy,
21:19that we can hopefully overcome some
21:21of that resistance that's there.
21:22But you're absolutely right,
21:24there's a lot of toxicity
21:26to this and one of the key areas of
21:29research right now is how can we
21:31provide similar rates of response,
21:34but without so much toxicity there.
21:36There's definitely favorable
21:38studies on the horizon, again,
21:40some of this is targeted therapies.
21:43There's even newer chemotherapies
21:44that are out there that can still
21:47provide we call myeloablation
21:49a strong dose of chemotherapy,
21:51but without so many side effects to the
21:54other organs.
21:56Who exactly would need a
21:57bone marrow transplant?
21:58Because it sounds right now
22:00the way you've described it, pretty scary.
22:06It's absolutely something that
22:08I think should be taken with caution.
22:10We use bone marrow transplant really
22:12for patients who really need it,
22:15so we wouldn't want to give a
22:17transplant to somebody who we
22:19think is likely to be cured
22:21through traditional chemotherapy.
22:22So for a patient with leukemia again,
22:24these are patients we anticipate
22:26to be at very high risk,
22:28maybe their cancer has
22:29already come back and we're trying
22:31to cure it for a second time.
22:34We can use this also for a lot of other
22:37cancers that aren't just leukemias.
22:40Sometimes we use chemotherapy
22:42and high dose chemotherapy with
22:44a rescue transplant or rescue the
22:46bone marrow for other solid tumors.
22:48So sometimes for lymphomas or lymph node
22:51cancers for a common abdominal tumor,
22:53and young children with neuroblastoma
22:55we will give chemotherapy as a way to maximize
22:59how much treatment we can give them.
23:01We also use stem cell transplant
23:04for diseases that aren't cancer.
23:06We can use them to treat a
23:08variety of blood diseases,
23:09especially sickle cell
23:10disease or thalassemia.
23:10We can also use them to
23:12replace an immune system,
23:13so for a child that has a
23:15severe immunodeficiency,
23:15but you can use this to restore
23:17their normal immune function,
23:18and then lastly,
23:19we can also use transplant as a way
23:21to treat certain genetic diseases
23:22or metabolic diseases where,
23:23say,
23:24a patient is missing an enzyme and
23:25we can give them a new bone marrow
23:27that can then make that enzyme
23:29from which they're deficient so
23:31it can be used for a lot of things,
23:33but it still has a lot of side effects.
23:36And so again we are
23:38always very careful to make sure when
23:39we recommend a transplant for a patient,
23:41that we really think that is the best
23:43option compared to what else might be
23:44available for them.
23:45My second question is,
23:47you talk about wiping out the bone marrow,
23:50but people need bone marrow to survive.
23:52because that's where all of our cells are
23:55and the blood cells don't last forever.
23:57So you need a factory continuing
23:59to make these blood cells.
24:01Where do you get the bone marrow from?
24:03So there's a
24:04lot of places we can get it.
24:06For some diseases we can actually
24:08use the patients own bone marrow,
24:10so again, for certain solid tumors,
24:12we might collect their bone marrow,
24:13keep it stored,
24:14and then after a high dose of chemotherapy,
24:17give it back to them
24:18to replenish their own healthy bone marrow.
24:21But for most patients,
24:22when they hear transplant,
24:23we're really talking about somebody who's
24:25donating a bone marrow to that patient,
24:27so that could be from a variety of people.
24:30Traditionally it's from a sibling,
24:32so a brother or a sister whose immune
24:34system is a match to the patient,
24:36but we may also use parents.
24:38We can now use even more distant relatives,
24:41and when those people aren't available,
24:43we can take volunteer donors
24:44from an unrelated bone
24:45marrow donor registry.
24:46And so when you do that,
24:48I mean when we think about transplant,
24:51you think it has
24:52to be a match because otherwise
24:54your immune system is going
24:56to attack that foreign stuff.
24:58Now granted, your immune system is
25:00part of your blood cells and you
25:02kind of wiped out your bone marrow,
25:04but don't you have the risk of still
25:07attacking the new bone marrow?
25:08If it's not your own right?
25:10So we definitely do need a match, and
25:13we match based on the immune system,
25:15so it's not the same as the blood type,
25:18which a lot of people think about.
25:22A sibling has about a 25% chance of being
25:24a match, and so if you have multiple
25:27siblings your chance of one of them
25:29being a match continues to go up
25:31the more siblings you have,
25:32but with even several siblings,
25:34many patients still don't have
25:36a donor within the family
25:37that's a good match,
25:38and that's where we go to these
25:41unrelated donor registries where
25:42right now across the world
25:43there are more than 30 million
25:45people who have volunteered to
25:47potentially donate bone marrow or
25:49stem cells to patients who need it.
25:51The most recent advance
25:52in the field is that we know
25:54that parents are 1/2 match,
25:56so their immune system will be 50% the
25:59same as their children and 10 years ago
26:02that wasn't good enough.
26:03We now have technology that allows
26:06us to use a parent or a half match,
26:08or we call Haploidentical
26:10relative as a bone marrow donor,
26:12and so this has hugely opened up
26:14the availability of finding a donor.
26:16Now for patients who previously
26:18didn't have a sibling match or
26:20didn't have a registry match,
26:22almost everybody has a family member
26:24who may be 1/2 identical
26:26match to use and so do these kids
26:28who get bone marrow transplants.
26:30Do they need to be on some
26:32sort of immuno suppression
26:33for the rest of their life?
26:35Like you would be if you had a
26:38liver transplant for example?
26:39Or kidney transplant?
26:40Yeah, that's a great question.
26:41So at least at first we do need to use
26:44immune suppression so the donor immune
26:46system does run the risk of attacking
26:49the patient and we want to quiet that
26:51donor immune system down for awhile.
26:53The really unique thing about doing a bone
26:55marrow or a stem cell transplant is
26:57because we're giving a new immune
26:59system, that new immune system overtime
27:01actually becomes tolerant to the patient,
27:03and so with a liver transplant,
27:05patients need to remain on immuno
27:07suppression, really lifelong,
27:08to quiet the immune system, but with
27:10a bone marrow transplant
27:11we really just need it for
27:13a brief period of time.
27:15So for many patients they are on
27:17immune suppression for three to six
27:19months after their transplants and
27:21most patients are off of immune
27:22suppression by one year after.
27:25Interesting and then the third
27:27bucket of therapies that you mentioned
27:30as something that you would consider
27:33in people who did not respond or
27:36aren't responding well to chemotherapy,
27:37was this whole bucket of therapies
27:40you called cellular therapies?
27:41Tell us more about that.
27:44So cellular therapies
27:45are a way to leverage a patient's
27:48immune system to recognize the
27:50cancer in their body and attack it.
27:53So really, the first licensed cellular
27:55therapy was for acute lymphoblastic leukemia.
27:58And the way this works is we can
28:01actually collect lymphocytes or the
28:02immune system cells from our patient
28:04in the laboratory we can teach them
28:06to recognize markers on their leukemia
28:08and then re infuse those cells back
28:11into the patient to allow their own
28:13immune system cells that have been
28:15modified to attack their cancer.
28:16This has been really an incredible
28:18breakthrough therapy over the past
28:20several years in almost 100% of
28:22patients who receive this therapy
28:23will go into remission within the
28:25first 30 days after receiving it.
28:27It's really miraculous.
28:28Wow, so a few questions. First question,
28:31when you said you harvest a patients
28:36lymphocytes, but your leukemia cells are
28:38part of your immune system aren't they?
28:41They are, but
28:43we're able to differentiate
28:45them in the laboratory,
28:46and so really we're able to isolate
28:48mature kind of healthy lymphocytes
28:50to be able to re infuse back.
28:52But they made
28:53it possible that there may
28:55be leukemia cells in these
28:57cell therapy products,
28:58but the engineered cells can
29:00actually still recognize those
29:01leukemia cells to attack them, and
29:03the engineered cells will continue
29:05to attack the cancer cells
29:07and everybody gets a response.
29:09So almost everybody responds.
29:10One of the big questions is what
29:12happens to these patients long term.
29:14So there are some patients where these
29:16engineered lymphocytes persist long term,
29:18but for many patients the
29:20lymphocytes actually disappear
29:21over a period of about six months,
29:23and so one of the questions is how
29:25do we maintain that remission and
29:27what do we do after the cell therapy?
29:30And for many patients,
29:31that might mean still doing a bone
29:33marrow transplant once they're in
29:35remission.
29:36doctor Aron Flagg is an assistant
29:38professor of Pediatrics and hematology
29:40oncology at the Yale School of Medicine.
29:42If you have questions,
29:43the address is canceranswers@yale.edu
29:45and past editions of the program
29:47are available in audio and written
29:49form at Yalecancercenter.org.
29:50We hope you'll join us next week to
29:53learn more about the fight against
29:55cancer here on Connecticut public radio.