Pediatric Cancers/Lymphoblastic Leukemia
July 06, 2020Information
July 5, 2020
Yale Cancer Center
visit: http://www.yalecancercenter.org
email: canceranswers@yale.edu
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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.