Pediatric Cancers/Lymphoblastic Leukemia

Transcript

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00:13 --> 00:15Welcome to Yale Cancer
00:15 --> 00:16Answers with your host
00:16 --> 00:18Doctor Anees Chagpar.
00:18 --> 00:20Yale Cancer Answers features the
00:20 --> 00:22latest information on cancer care by
00:22 --> 00:24welcoming oncologists and specialists
00:24 --> 00:26who are on the forefront of the
00:26 --> 00:28battle to fight cancer. This week
00:28 --> 00:30it's a conversation about pediatric
00:30 --> 00:31cancers and lymphoblastic
00:31 --> 00:32leukemia with doctor Aron Flagg.
00:33 --> 00:35Doctor Flagg is an assistant professor
00:35 --> 00:37of Pediatrics in hematology/oncology
00:37 --> 00:39at the Yale School of Medicine,
00:39 --> 00:41where doctor Chagpar is a
00:41 --> 00:42professor of surgical oncology.
00:44 --> 00:46Aron, maybe we can start off by
00:46 --> 00:49you telling us a little bit about
00:49 --> 00:50pediatric cancers in general.
00:50 --> 00:53Nobody ever likes to think
00:53 --> 00:54about cancer occurring in kids,
00:54 --> 00:56but how common are pediatric cancers?
00:56 --> 00:57Overall
00:57 --> 00:58pediatric cancers are rare
00:58 --> 00:59compared to adult cancers.
00:59 --> 01:02The most common that we see is something
01:02 --> 01:04called acute lymphoblastic leukemia or ALL,
01:04 --> 01:06and we see several 1000 cases of ALL
01:06 --> 01:08in the United States every year.
01:08 --> 01:09Beyond that,
01:09 --> 01:11the next most common types of cancers
01:11 --> 01:13are brain tumors or brain cancers,
01:13 --> 01:14of which there
01:14 --> 01:16are a number of types and following
01:16 --> 01:18that there are a number of different
01:18 --> 01:20cancers we can see elsewhere
01:20 --> 01:20throughout the body.
01:20 --> 01:23So tell us a little bit more about ALL.
01:23 --> 01:24How does it present?
01:24 --> 01:25Because
01:25 --> 01:27if you're a parent out there
01:27 --> 01:28and you're listening to this,
01:28 --> 01:29you're kind of thinking,
01:29 --> 01:32I never want my kid to get cancer,
01:32 --> 01:34but Gosh darn it if I ever
01:34 --> 01:35find a sign or symptom,
01:35 --> 01:37I want to know what that is so that
01:37 --> 01:40I can take appropriate next steps.
01:40 --> 01:41Sure, this can
01:41 --> 01:42be tough sometimes because a lot
01:42 --> 01:44of the symptoms are nonspecific,
01:44 --> 01:45meaning they can happen
01:45 --> 01:47for a variety of reasons,
01:47 --> 01:49and many of them are not cancerous.
01:49 --> 01:51So specifically with ALL or
01:51 --> 01:52acute lymphoblastic leukemia,
01:52 --> 01:54many children will be very tired or fatigued.
01:54 --> 01:56They may look very pale.
01:56 --> 01:57They may have bleeding or
01:57 --> 01:59bruising for no reason,
01:59 --> 02:00and then many children will also
02:00 --> 02:03have pain in the bones or the joints,
02:03 --> 02:05and so a limp is also a common
02:05 --> 02:07symptom that patients can have.
02:07 --> 02:09But for other types of cancers that
02:09 --> 02:11can occur really throughout the body,
02:11 --> 02:13the symptoms really depend on what type
02:13 --> 02:15of cancer and where it's occurring,
02:15 --> 02:16so it can be very hard to list
02:16 --> 02:18off one specific symptom
02:18 --> 02:21that might be a sign of cancer.
02:21 --> 02:22So from my standpoint,
02:22 --> 02:23if a parent is worried that
02:23 --> 02:24something is going on,
02:24 --> 02:25if symptoms are there and not
02:25 --> 02:26getting better on their own,
02:26 --> 02:27they should always talk with
02:27 --> 02:28the pediatrician.
02:28 --> 02:30So you know when we think about
02:30 --> 02:33ALL and the symptoms that you
02:33 --> 02:35mentioned are really non specific.
02:35 --> 02:37I mean kids jump around they play,
02:37 --> 02:39they get tired, they get bruised.
02:39 --> 02:41They may have some pain.
02:41 --> 02:43They get pale and
02:43 --> 02:45a lot of people
02:45 --> 02:47go into their pediatricians.
02:47 --> 02:49I think it can be
02:49 --> 02:51really tough and from my standpoint
02:51 --> 02:53when patients finally come to
02:53 --> 02:55see me they almost always have a
02:55 --> 02:57diagnosis or they have a lab test
02:57 --> 02:59that shows something is wrong.
02:59 --> 03:02And so my job in some ways is simpler
03:02 --> 03:04because I know there's a problem.
03:04 --> 03:06I think it's much harder for an
03:06 --> 03:08emergency room doctor or a pediatrician
03:08 --> 03:10to take a child who's got these
03:10 --> 03:12symptoms where 99 out of 100 may be
03:12 --> 03:15fine and pick out the one in 100 who
03:15 --> 03:17really does have a severe problem.
03:17 --> 03:19How do they do that exactly?
03:19 --> 03:20So through careful history, a
03:20 --> 03:22physical exam and through taking
03:22 --> 03:25lab tests to look for things is
03:25 --> 03:27really the best way to do it.
03:27 --> 03:28But far and wide,
03:28 --> 03:30the most important thing is listening
03:30 --> 03:32to parents and looking at the child.
03:33 --> 03:35And what exactly are they listening
03:35 --> 03:36for? And looking for?
03:36 --> 03:38I think when they're listening,
03:38 --> 03:40it's when symptoms don't get better.
03:40 --> 03:41It's something that's been there
03:41 --> 03:43that doesn't seem just like a virus,
03:43 --> 03:45which is probably the most common
03:45 --> 03:47reason for a lot of these complaints
03:47 --> 03:48young kids will have,
03:48 --> 03:51and so when that symptom is there over weeks,
03:51 --> 03:52and instead of getting
03:52 --> 03:53better is getting worse.
03:53 --> 03:55Maybe children are losing weight,
03:55 --> 03:57maybe they are having fevers for no good reason,
03:57 --> 03:59and then again on physical exam
03:59 --> 04:01they may be able to find something
04:01 --> 04:02that's abnormal that
04:02 --> 04:04they might have
04:04 --> 04:05swollen lymph nodes, their liver or
04:05 --> 04:06spleen might be enlarged.
04:06 --> 04:08Something that tips them off to
04:08 --> 04:09something going on that isn't
04:09 --> 04:10the run of the mill problem.
04:10 --> 04:12And you mentioned lab tests.
04:12 --> 04:14What kind of lab tests do
04:14 --> 04:15they get?
04:15 --> 04:16This can be difficult because depending
04:16 --> 04:17on what type of cancer it is,
04:17 --> 04:19certain lab tests may
04:19 --> 04:20or may not be a good screening
04:20 --> 04:22test to use for leukemia.
04:22 --> 04:23The most common lab test we would look
04:23 --> 04:25at is a complete blood count where we
04:25 --> 04:28can look under the microscope with the blood,
04:28 --> 04:29look at the white blood cells,
04:29 --> 04:30red blood cells and platelets to
04:30 --> 04:32see if they are normal and
04:32 --> 04:34to see if there might be leukemia
04:34 --> 04:35cells in the blood as well.
04:36 --> 04:38So for ALL, and we will focus our
04:38 --> 04:40discussion on ALL because that's
04:40 --> 04:42the most common pediatric cancer
04:42 --> 04:44and the one that you specialize in,
04:44 --> 04:46what would you see in that
04:46 --> 04:47complete blood count?
04:47 --> 04:48So children are often anemic,
04:48 --> 04:50meaning the red blood
04:50 --> 04:53cell count is low.
04:53 --> 04:55And red blood cells give your body the ability to carry oxygen.
04:55 --> 04:57It makes the blood red and
04:57 --> 04:59so when children are anemic,
04:59 --> 05:01they're often very pale as well.
05:01 --> 05:03So again, that physical exam might clue
05:03 --> 05:06us into the low red blood cell count.
05:06 --> 05:08Platelets are tiny cells in the blood that
05:08 --> 05:11help to prevent bleeding and to form clots.
05:11 --> 05:13When you get a cut and when
05:13 --> 05:14there's a leukemia present,
05:14 --> 05:16those platelets often become
05:16 --> 05:18also very low and so we can see
05:18 --> 05:20that very easily on a lab test.
05:20 --> 05:22Finally, will look at the white blood
05:22 --> 05:24cell count and leukemia cells are
05:24 --> 05:26an early type of white blood cell,
05:26 --> 05:28and so for many patients with leukemia,
05:28 --> 05:31we might see that white blood cell
05:31 --> 05:32count very elevated because of
05:32 --> 05:34the leukemia cells in the blood,
05:34 --> 05:37and if they see this trifecta,
05:37 --> 05:38they get worried absolutely.
05:38 --> 05:41And does that cinch the diagnosis of ALL?
05:41 --> 05:41Sometimes it does
05:41 --> 05:43so if we can see circulating
05:43 --> 05:44leukemia cells in the blood,
05:44 --> 05:46there's really nothing else that it could be,
05:46 --> 05:48but sometimes it's not so easy.
05:48 --> 05:49Some kids, when they present,
05:49 --> 05:51especially early on in the course,
05:51 --> 05:53may not have leukemia cells in the blood,
05:53 --> 05:55and so if we're not able to make the
05:55 --> 05:57diagnosis directly from a blood count,
05:57 --> 05:59we might talk about doing a bone
05:59 --> 06:01marrow biopsy to confirm a diagnosis.
06:01 --> 06:02And what do you see on
06:02 --> 06:03the bone marrow biopsy?
06:03 --> 06:05So all of the blood is made
06:05 --> 06:06within the bone marrow,
06:06 --> 06:08and so when a leukemia comes on,
06:08 --> 06:10it starts in the bone marrow.
06:10 --> 06:12And when it's there very early
06:12 --> 06:13before it's gotten into the blood,
06:13 --> 06:15we might be able to see it
06:15 --> 06:16in the bone marrow.
06:16 --> 06:17So in a bone marrow biopsy,
06:17 --> 06:19and we place a small needle
06:19 --> 06:20into one of the bones,
06:20 --> 06:21usually in the hip bones,
06:21 --> 06:22they take a sample to
06:22 --> 06:23look at under the microscope,
06:23 --> 06:25and then you see leukemia cells and
06:25 --> 06:26that would
06:26 --> 06:27be the definitive test.
06:27 --> 06:30And then they come to
06:30 --> 06:31you, correct, with this diagnosis?
06:31 --> 06:33And then what happens after they
06:33 --> 06:36get over the shock of, Oh my God,
06:36 --> 06:37my kid has cancer right?
06:37 --> 06:39So a lot of that first meeting
06:39 --> 06:40really is talking about,
06:40 --> 06:43what is cancer?
06:43 --> 06:46And where do we go from here?
06:46 --> 06:48And really trying to get over
06:48 --> 06:50that initial shock which can take
06:50 --> 06:52us several days to let
06:52 --> 06:54everything to sink in and many children,
06:54 --> 06:55when their leukemias first are
06:55 --> 06:57diagnosed are quite ill,
06:57 --> 06:59and so this is usually happening
06:59 --> 07:01in the hospital where we have time
07:01 --> 07:04to sit down and talk outside of
07:04 --> 07:06the constraints of an office visit.
07:06 --> 07:09So how exactly is
07:09 --> 07:10this treated?
07:10 --> 07:12Is it treated through chemotherapy?
07:12 --> 07:14It's given in several phases,
07:14 --> 07:16some of them more intensive,
07:16 --> 07:17especially at the beginning.
07:17 --> 07:20Some of them later on in the course are much
07:20 --> 07:22easier to tolerate the beginning course.
07:22 --> 07:23We call induction chemotherapy some of
07:23 --> 07:25that time is spent in the hospital,
07:25 --> 07:26especially until the leukemia
07:26 --> 07:28starts to go into remission.
07:28 --> 07:29The majority of the rest of
07:29 --> 07:31therapy is actually given in
07:31 --> 07:32the office as an outpatient,
07:32 --> 07:34where patients may have to come once
07:34 --> 07:36or twice a week for several months
07:36 --> 07:38in a row to get their therapy,
07:38 --> 07:40and then it ends with the course of therapy
07:40 --> 07:41that we call maintenance chemotherapy.
07:41 --> 07:43Meaning leukemia is in remission,
07:43 --> 07:46and we're trying to keep it that way.
07:46 --> 07:47Maintenance therapy is usually
07:47 --> 07:49given on a once a month basis.
07:49 --> 07:50Also in the office,
07:50 --> 07:52but goes on for many years, usually
07:52 --> 07:54two to three years from diagnosis.
07:55 --> 07:57So these children are essentially getting
07:57 --> 07:58chemotherapy for potentially years?
07:58 --> 08:01Yes, if it's a very long road and even
08:01 --> 08:02in maintenance chemotherapy,
08:02 --> 08:06or we think about a once a month visit to
08:06 --> 08:08the oncology office when they're at home,
08:08 --> 08:10they're often still taking chemotherapy
08:10 --> 08:12by mouth every day or every week.
08:13 --> 08:15And what are the effects of that?
08:15 --> 08:17I mean, do they get sick and they
08:17 --> 08:19still go to school?
08:19 --> 08:21What happens to their friends and how
08:21 --> 08:23does this affect their lives?
08:23 --> 08:24That's a great question.
08:24 --> 08:26Many of our patients can lead nearly
08:26 --> 08:28normal lives going through this,
08:28 --> 08:29although every patient is different.
08:29 --> 08:31There certainly is a risk of infection,
08:31 --> 08:33especially at the beginning when the
08:33 --> 08:35chemotherapy is much more intensive.
08:35 --> 08:37But really after that first month
08:37 --> 08:39until the leukemia is in remission,
08:39 --> 08:41after which we really advise children to
08:41 --> 08:44try to have as normal a life as possible.
08:44 --> 08:46We encourage kids to go to school.
08:46 --> 08:48We encourage them to have normal
08:48 --> 08:50relationships with friends and relatives.
08:50 --> 08:52We really try to focus on
08:52 --> 08:53keeping their quality of
08:53 --> 08:55life as normal as possible.
08:55 --> 08:57Tell me about the side effects of
08:57 --> 08:58these chemotherapies because you know,
08:58 --> 09:01I can imagine if you're a kid and
09:01 --> 09:03you're trying to have a normal life,
09:03 --> 09:05but you've lost your
09:05 --> 09:07hair and your friends are calling
09:07 --> 09:09you bald and you're feeling sick,
09:09 --> 09:11and it might be easier said
09:11 --> 09:14than done to have a normal life.
09:14 --> 09:15Yeah, absolutely.
09:15 --> 09:18And we're fortunate now that many children
09:18 --> 09:20are able to be cured of their cancer.
09:20 --> 09:23In fact, most children with ALL are
09:23 --> 09:26able to be cured and so many years ago,
09:26 --> 09:28our primary focus was curing the cancer.
09:28 --> 09:30Now, because of the improvements in
09:30 --> 09:32the chemotherapy that we can offer,
09:32 --> 09:34we can focus on other issues like
09:34 --> 09:36you mentioned quality of life,
09:36 --> 09:38not just being able to get
09:38 --> 09:39the cancer under control.
09:39 --> 09:42We do work with psychologists to help with
09:42 --> 09:44that transition back into normal life.
09:44 --> 09:46You know, especially in teenagers
09:46 --> 09:49body image is really important to be
09:49 --> 09:51able to find ways to get through life.
09:51 --> 09:54You know that may be different
09:54 --> 09:56than it was before
09:56 --> 09:58the chemotherapy in terms of side effects,
10:00 --> 10:02Some patients may have a lot
10:02 --> 10:04of nausea there may be infection.
10:04 --> 10:07Many patients need transfusions because
10:07 --> 10:09of side effects of chemotherapy.
10:09 --> 10:11And we're not also focusing just
10:11 --> 10:13on the side effects that we see
10:13 --> 10:15right at the time of chemotherapy.
10:15 --> 10:16We're also focusing now on the
10:16 --> 10:17long term side effects.
10:17 --> 10:19The late effects that might happen
10:19 --> 10:21five years down the road, 10 years,
10:21 --> 10:2220 years.
10:22 --> 10:24Whether that's a problem with hormones
10:24 --> 10:26affects on the heart or on bone development,
10:26 --> 10:29really trying to find ways that we can
10:29 --> 10:31improve upon those late outcomes and
10:31 --> 10:33really give kids the best possible
10:33 --> 10:34life after their therapy.
10:34 --> 10:36So with chemotherapy, you
10:37 --> 10:39tend to lose your hair, and I suppose
10:39 --> 10:41that's the case with ALL as well.
10:41 --> 10:44But you know, with other kinds of cancer,
10:44 --> 10:46the therapies are much shorter and we
10:46 --> 10:48always tell people don't worry your hair
10:48 --> 10:50will grow back, but when they're
10:50 --> 10:52getting years of therapy, I mean,
10:52 --> 10:54do they ever grow their hair back?
10:54 --> 10:57I mean, can they ever truly feel normal?
10:57 --> 10:59Yeah, so the hair loss tends
10:59 --> 11:00to be reasonably temporary,
11:00 --> 11:01again we see it at the early parts of
11:02 --> 11:03therapy with more intensive chemotherapy.
11:03 --> 11:05Fortunately, by the time children
11:05 --> 11:05are on maintenance chemotherapy,
11:05 --> 11:07the low levels of medicines that we're
11:07 --> 11:09giving do tend to allow hair to regrow,
11:09 --> 11:11and so usually once you're in that
11:11 --> 11:13maintenance cycle for a few months,
11:13 --> 11:15we start to see the hair come back.
11:15 --> 11:15And interestingly,
11:15 --> 11:17a lot of the times it comes back
11:17 --> 11:18thicker, it's curly,
11:18 --> 11:20are so often it gives us something
11:20 --> 11:22to talk about in the office in
11:22 --> 11:23terms of comparing what their hair
11:23 --> 11:25was before and what it is now.
11:26 --> 11:28And one of
11:28 --> 11:29the good things, I suppose,
11:29 --> 11:32is that you know kids are living longer.
11:32 --> 11:35Tell us about the prognosis with ALL.
11:35 --> 11:36I mean, almost all patients
11:36 --> 11:37you mentioned are cured.
11:39 --> 11:41A very good proportion of them are.
11:41 --> 11:43We are now able to identify for the most
11:43 --> 11:46part which children are going to be cured
11:46 --> 11:48by chemotherapy and cured
11:48 --> 11:51of their ALL early on in their therapy.
11:51 --> 11:53And then we can also predict which kids may
11:53 --> 11:56have a harder time to achieve remission.
11:56 --> 11:58How do we do that?
11:58 --> 12:00Some of its based on very simple things
12:00 --> 12:02like age, so we know that older kids,
12:02 --> 12:03especially adolescents or young adults,
12:03 --> 12:06have a harder time to be cured
12:06 --> 12:08than younger kids.
12:08 --> 12:09That said, very young children,
12:09 --> 12:12especially less than one year, may also
12:12 --> 12:13have a problem getting into remission.
12:13 --> 12:15So we can start with that.
12:15 --> 12:17We also follow response to therapy,
12:17 --> 12:18and
12:18 --> 12:20what most people have been looking at the
12:20 --> 12:22past few years is something called
12:22 --> 12:24minimal residual disease or MRD analysis.
12:24 --> 12:26It's a way for us,
12:26 --> 12:28through a bone marrow test,
12:28 --> 12:30to see how much of a remission
12:30 --> 12:31somebody gets into,
12:31 --> 12:33and we know that the deeper a
12:33 --> 12:35remission the patient enters early on
12:35 --> 12:37in their therapy predicts whether
12:37 --> 12:38or not they'll be cured.
12:38 --> 12:40And so with this information we can
12:40 --> 12:42tell patients within a few months
12:42 --> 12:43of their diagnosis whether or not
12:43 --> 12:45we expect with a good certainty
12:45 --> 12:46that they'll be cured,
12:46 --> 12:48or whether or not we think there may
12:48 --> 12:50be a challenge for patients who respond
12:50 --> 12:53quickly who are in a favorable age range.
12:53 --> 12:54More than 95% of those children
12:54 --> 12:56can be cured through chemotherapy.
12:56 --> 12:57For some older children,
12:57 --> 12:58especially young adults or patients
12:58 --> 13:00who don't quickly go into remission,
13:00 --> 13:02there may be more of a struggle,
13:02 --> 13:04and sometimes that may be more
13:04 --> 13:0550 or 70% chance.
13:05 --> 13:08I'd hate to be in that last group where you
13:08 --> 13:11tell me that there's going to be a bit
13:11 --> 13:14of a challenge for me to get a cure.
13:14 --> 13:17What do you do about that?
13:17 --> 13:19I would be like,
13:19 --> 13:21well thank you for telling me
13:21 --> 13:23that I might struggle,
13:23 --> 13:25but what are you gonna do about
13:25 --> 13:26it right now?
13:26 --> 13:29These are very hard conversations to have and
13:29 --> 13:30it's really through research that
13:30 --> 13:32we're trying to find better ways,
13:32 --> 13:34especially in these high risk groups
13:34 --> 13:36to do better to get them in remission.
13:36 --> 13:38So we participate in a large
13:38 --> 13:39Children's Hospital Consortium called
13:39 --> 13:40the children's oncology group
13:40 --> 13:42that's really doing most of the
13:42 --> 13:44research in the country to look at
13:44 --> 13:46how we can achieve better outcomes.
13:46 --> 13:48And that's using new medications that
13:48 --> 13:49may work differently than the
13:49 --> 13:50older types of chemotherapy,
13:50 --> 13:53or even doing much more aggressive treatment,
13:53 --> 13:55such as things like bone marrow transplant
13:55 --> 13:56earlier on.
13:56 --> 13:58We're going to pick up the conversation
13:58 --> 14:00looking at those newer treatments and
14:00 --> 14:03other treatments right after we take
14:03 --> 14:04a short break for medical minute.
14:04 --> 14:06Please stay tuned to learn more about
14:06 --> 14:08pediatric cancers and lymphoblastic
14:08 --> 14:10leukemia with my guest Doctor Aron Flagg.
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15:01 --> 15:05You're listening to Connecticut public radio.
15:05 --> 15:05Welcome
15:05 --> 15:07back to Yale Cancer Answers.
15:07 --> 15:09This is doctor Anees Chagpar
15:09 --> 15:11and I'm joined tonight
15:11 --> 15:14by my guest Doctor Aron Flagg.
15:14 --> 15:16We're talking about pediatric cancers,
15:16 --> 15:17and in particular,
15:17 --> 15:18acute lymphoblastic leukemia,
15:18 --> 15:20which is the most common
15:20 --> 15:22cancer affecting children.
15:22 --> 15:24And right before the break
15:24 --> 15:27Aron you said that
15:27 --> 15:29we've done really well in
15:29 --> 15:32terms of treating ALL and for a
15:32 --> 15:34particular subgroup of patients,
15:34 --> 15:36those who tend to be younger
15:36 --> 15:39children but not too young who
15:39 --> 15:41achieve remission with induction
15:41 --> 15:42chemotherapy that
15:42 --> 15:45those patients have a reasonably good shot,
15:45 --> 15:4895% chance of achieving a cure.
15:48 --> 15:51But then there's another group of patients,
15:51 --> 15:54those who may not respond so well
15:54 --> 15:57to initial chemotherapy who may be older
15:59 --> 16:04who don't have as good of a shot of cure.
16:04 --> 16:06And so you started to mention that
16:06 --> 16:09in that group of patients there are
16:09 --> 16:11other things besides traditional
16:11 --> 16:13chemotherapy that you look at.
16:13 --> 16:15Tell us more about that.
16:15 --> 16:16Sure, I
16:16 --> 16:20like to think of chemotherapy as
16:20 --> 16:22very non specific medicine that
16:22 --> 16:24attack cells in the body that are
16:24 --> 16:26growing quickly, like cancer cells.
16:26 --> 16:29They also cause a lot of side effects,
16:29 --> 16:31but as we've kind of plateaued with how
16:31 --> 16:34well those medicines work we're looking
16:34 --> 16:36for other avenues and so we are now using
16:36 --> 16:38many drugs called targeted agents,
16:38 --> 16:41so not just to blindly kill off all
16:41 --> 16:43the cancer cells but really to find
16:43 --> 16:45specific targets on those cancer cells
16:45 --> 16:48to hone in on that and make them
16:48 --> 16:51much more effective than other drugs.
16:51 --> 16:53We have used methods like pursuing
16:53 --> 16:55a bone marrow transplant that allows
16:55 --> 16:57us to give extraordinary doses of
16:57 --> 16:58chemotherapy and give new bone
16:58 --> 17:00marrow and then really in the past
17:00 --> 17:02few years we've also used types of
17:02 --> 17:03interventions called cellular therapies,
17:03 --> 17:06so we're now able to take a patient's
17:06 --> 17:08own immune system to engineer cells
17:08 --> 17:10in a laboratory, put them back in,
17:10 --> 17:12and allow those cells to attack
17:12 --> 17:13the cancer itself.
17:13 --> 17:15And so we have really many
17:15 --> 17:17new ways to treat these,
17:17 --> 17:18to provide options for patients
17:18 --> 17:19who previously didn't have
17:19 --> 17:21those.
17:21 --> 17:22That sounds really interesting, so let's take
17:22 --> 17:24each of those three in turn.
17:24 --> 17:26Sure, so first, targeted therapies.
17:26 --> 17:28I mean, we've spent a lot of time on
17:28 --> 17:30this show talking about precision
17:30 --> 17:32medicine and targeted therapy,
17:32 --> 17:33and personalized medicine
17:33 --> 17:37and so on and so forth
17:37 --> 17:39where there's often a target on
17:39 --> 17:42a cancer cell and we have a drug
17:42 --> 17:44that will attack said target,
17:44 --> 17:47essentially being more like a
17:47 --> 17:49sniper rather than a machine gun
17:49 --> 17:52at attacking these cancers.
17:52 --> 17:54Tell us more about that approach in ALL.
17:54 --> 17:56Yeah, so we
17:56 --> 17:58know that mutations in the genetic
17:58 --> 18:01code of these cancer cells is
18:01 --> 18:03really what turns them from
18:03 --> 18:05normal cells into cancer cells,
18:05 --> 18:07and many of those changes,
18:07 --> 18:09do have medicines that might
18:09 --> 18:11affect those and slow down the
18:11 --> 18:12growth of those cancer cells so we
18:12 --> 18:15do have several of those available.
18:15 --> 18:15In particular,
18:15 --> 18:17there's a type of ALL called
18:17 --> 18:18Philadelphia chromosome positive
18:18 --> 18:19acute lymphoblastic leukemia,
18:19 --> 18:21where there have been drugs on
18:21 --> 18:23the market even since the 1990s,
18:23 --> 18:24that specifically attack that
18:24 --> 18:25Philadelphia chromosome,
18:25 --> 18:27and so this was a disease that
18:27 --> 18:28again 10-20 years ago,
18:28 --> 18:29we might have recommended everybody
18:29 --> 18:31have a bone marrow transplant,
18:31 --> 18:33now most children don't need a
18:33 --> 18:35bone marrow transplant because we
18:35 --> 18:37can give a target before that.
18:37 --> 18:38In that case,
18:38 --> 18:42where we have targeted agents,
18:42 --> 18:45do we give that instead of the induction
18:45 --> 18:47chemotherapy and so on and so forth
18:47 --> 18:48that you had mentioned before?
18:48 --> 18:50Because it sounds like if
18:50 --> 18:51you have a sniper, why
18:51 --> 18:53use the machine gun, right?
18:53 --> 18:55So right now these are really adjunctive,
18:55 --> 18:57we give them in addition
18:57 --> 18:58to traditional chemotherapy.
18:58 --> 19:00It certainly may hit a point though that
19:00 --> 19:03as these medicines improve or we find
19:03 --> 19:05different ones that we might not have
19:05 --> 19:06to give the same traditional
19:06 --> 19:07chemotherapy anymore.
19:07 --> 19:08But we're not there yet.
19:08 --> 19:11OK, so if you have a particular kind
19:11 --> 19:13of ALL that has a particular marker,
19:13 --> 19:15for example the Philadelphia
19:15 --> 19:16chromosome positive ALL,
19:16 --> 19:18then targeted therapy is something
19:18 --> 19:20that should certainly be
19:20 --> 19:22part of the regimen absolutely,
19:22 --> 19:24but then you mentioned the 2nd
19:24 --> 19:27which was bone marrow transplant and
19:27 --> 19:29you had mentioned before the break
19:29 --> 19:32that the bone marrow is really the
19:32 --> 19:34place where these cells are developed,
19:34 --> 19:37and so in the factory that's making
19:37 --> 19:40all of your red blood cells and white
19:40 --> 19:42blood cells and platelets and so on.
19:42 --> 19:44In that bone marrow,
19:44 --> 19:46that's where the leukemias developed,
19:46 --> 19:48and so with bone marrow transplant,
19:48 --> 19:50you're really thinking about
19:50 --> 19:51wiping out that bone marrow,
19:51 --> 19:54and you mentioned that the purpose of
19:54 --> 19:57that is to give really high doses of
19:57 --> 20:00chemotherapy. Tell us more about how that works.
20:00 --> 20:02So right now when you
20:02 --> 20:04give regular doses of chemotherapy,
20:04 --> 20:06it does attack the leukemia cells,
20:06 --> 20:09but we can only give so much of it.
20:09 --> 20:11And when you try to give very
20:11 --> 20:12high doses of chemotherapy,
20:12 --> 20:14we see so many side effects,
20:14 --> 20:16especially to healthy bone marrow cells,
20:16 --> 20:18that there's really a limit to how
20:18 --> 20:20much we can give in the setting
20:20 --> 20:21of bone marrow transplantation
20:21 --> 20:23or stem cell transplantation for
20:23 --> 20:25treating a cancer like leukemia.
20:25 --> 20:27The idea is that we give astronomically
20:27 --> 20:29high doses of chemotherapy,
20:29 --> 20:30sometimes radiation therapy,
20:30 --> 20:34to try to wipe out not just the leukemia,
20:34 --> 20:36but we might also remove the healthy bone
20:36 --> 20:39marrow as well by giving a transplant.
20:39 --> 20:41It allows us to restore that
20:41 --> 20:42normal bone marrow function.
20:42 --> 20:44So two questions, first question,
20:44 --> 20:46if you're going to give somebody an
20:46 --> 20:48astronomical amount of chemotherapy,
20:48 --> 20:51so much so that is going to wipe
20:51 --> 20:54out their entire bone marrow,
20:54 --> 20:56doesn't that give them a whole lot of
20:56 --> 20:58side effects like why do that?
20:58 --> 21:01I mean, unless we know that the
21:01 --> 21:03response rate is better to that,
21:03 --> 21:05but we're using it in people who
21:05 --> 21:07aren't responding anyways, right?
21:07 --> 21:07So the
21:07 --> 21:09idea is that for some patients,
21:09 --> 21:11if they have some resistance to
21:11 --> 21:13the chemotherapy they're getting
21:13 --> 21:15that if we give different types
21:15 --> 21:16of chemotherapy, and especially
21:16 --> 21:18very high doses of chemotherapy,
21:18 --> 21:20that we can hopefully overcome some
21:20 --> 21:22of that resistance that's there.
21:22 --> 21:23But you're absolutely right,
21:23 --> 21:25there's a lot of toxicity
21:25 --> 21:28to this and one of the key areas of
21:28 --> 21:31research right now is how can we
21:31 --> 21:33provide similar rates of response,
21:33 --> 21:36but without so much toxicity there.
21:36 --> 21:38There's definitely favorable
21:38 --> 21:40studies on the horizon, again,
21:40 --> 21:42some of this is targeted therapies.
21:42 --> 21:44There's even newer chemotherapies
21:44 --> 21:47that are out there that can still
21:47 --> 21:48provide we call myeloablation
21:48 --> 21:51a strong dose of chemotherapy,
21:51 --> 21:54but without so many side effects to the
21:54 --> 21:55other organs.
21:55 --> 21:57Who exactly would need a
21:57 --> 21:58bone marrow transplant?
21:58 --> 22:00Because it sounds right now
22:00 --> 22:01the way you've described it, pretty scary.
22:06 --> 22:07It's absolutely something that
22:07 --> 22:10I think should be taken with caution.
22:10 --> 22:12We use bone marrow transplant really
22:12 --> 22:14for patients who really need it,
22:14 --> 22:16so we wouldn't want to give a
22:16 --> 22:18transplant to somebody who we
22:18 --> 22:20think is likely to be cured
22:20 --> 22:21through traditional chemotherapy.
22:21 --> 22:24So for a patient with leukemia again,
22:24 --> 22:26these are patients we anticipate
22:26 --> 22:27to be at very high risk,
22:27 --> 22:29maybe their cancer has
22:29 --> 22:30already come back and we're trying
22:30 --> 22:32to cure it for a second time.
22:34 --> 22:37We can use this also for a lot of other
22:37 --> 22:40cancers that aren't just leukemias.
22:40 --> 22:41Sometimes we use chemotherapy
22:41 --> 22:43and high dose chemotherapy with
22:43 --> 22:45a rescue transplant or rescue the
22:45 --> 22:48bone marrow for other solid tumors.
22:48 --> 22:50So sometimes for lymphomas or lymph node
22:50 --> 22:53cancers for a common abdominal tumor,
22:53 --> 22:55and young children with neuroblastoma
22:55 --> 22:58we will give chemotherapy as a way to maximize
22:58 --> 23:01how much treatment we can give them.
23:01 --> 23:03We also use stem cell transplant
23:03 --> 23:05for diseases that aren't cancer.
23:05 --> 23:07We can use them to treat a
23:07 --> 23:08variety of blood diseases,
23:08 --> 23:09especially sickle cell
23:09 --> 23:10disease or thalassemia.
23:10 --> 23:11We can also use them to
23:11 --> 23:12replace an immune system,
23:12 --> 23:14so for a child that has a
23:14 --> 23:15severe immunodeficiency,
23:15 --> 23:17but you can use this to restore
23:17 --> 23:18their normal immune function,
23:18 --> 23:18and then lastly,
23:18 --> 23:20we can also use transplant as a way
23:20 --> 23:22to treat certain genetic diseases
23:22 --> 23:23or metabolic diseases where,
23:23 --> 23:23say,
23:23 --> 23:25a patient is missing an enzyme and
23:25 --> 23:27we can give them a new bone marrow
23:27 --> 23:29that can then make that enzyme
23:29 --> 23:30from which they're deficient so
23:30 --> 23:32it can be used for a lot of things,
23:32 --> 23:35but it still has a lot of side effects.
23:35 --> 23:37And so again we are
23:37 --> 23:39always very careful to make sure when
23:39 --> 23:40we recommend a transplant for a patient,
23:40 --> 23:42that we really think that is the best
23:42 --> 23:44option compared to what else might be
23:44 --> 23:45available for them.
23:45 --> 23:47My second question is,
23:47 --> 23:49you talk about wiping out the bone marrow,
23:49 --> 23:51but people need bone marrow to survive.
23:51 --> 23:54because that's where all of our cells are
23:55 --> 23:57and the blood cells don't last forever.
23:57 --> 23:59So you need a factory continuing
23:59 --> 24:00to make these blood cells.
24:00 --> 24:02Where do you get the bone marrow from?
24:03 --> 24:04So there's a
24:04 --> 24:06lot of places we can get it.
24:06 --> 24:08For some diseases we can actually
24:08 --> 24:09use the patients own bone marrow,
24:09 --> 24:11so again, for certain solid tumors,
24:11 --> 24:13we might collect their bone marrow,
24:13 --> 24:14keep it stored,
24:14 --> 24:16and then after a high dose of chemotherapy,
24:16 --> 24:18give it back to them
24:18 --> 24:20to replenish their own healthy bone marrow.
24:20 --> 24:21But for most patients,
24:21 --> 24:23when they hear transplant,
24:23 --> 24:25we're really talking about somebody who's
24:25 --> 24:27donating a bone marrow to that patient,
24:27 --> 24:30so that could be from a variety of people.
24:30 --> 24:31Traditionally it's from a sibling,
24:31 --> 24:34so a brother or a sister whose immune
24:34 --> 24:36system is a match to the patient,
24:36 --> 24:38but we may also use parents.
24:38 --> 24:40We can now use even more distant relatives,
24:40 --> 24:42and when those people aren't available,
24:42 --> 24:44we can take volunteer donors
24:44 --> 24:45from an unrelated bone
24:45 --> 24:46marrow donor registry.
24:46 --> 24:48And so when you do that,
24:48 --> 24:50I mean when we think about transplant,
24:50 --> 24:52you think it has
24:52 --> 24:54to be a match because otherwise
24:54 --> 24:55your immune system is going
24:55 --> 24:57to attack that foreign stuff.
24:57 --> 24:59Now granted, your immune system is
24:59 --> 25:02part of your blood cells and you
25:02 --> 25:04kind of wiped out your bone marrow,
25:04 --> 25:06but don't you have the risk of still
25:06 --> 25:08attacking the new bone marrow?
25:08 --> 25:10If it's not your own right?
25:10 --> 25:12So we definitely do need a match, and
25:12 --> 25:15we match based on the immune system,
25:15 --> 25:17so it's not the same as the blood type,
25:17 --> 25:21which a lot of people think about.
25:21 --> 25:24A sibling has about a 25% chance of being
25:24 --> 25:26a match, and so if you have multiple
25:26 --> 25:28siblings your chance of one of them
25:28 --> 25:30being a match continues to go up
25:30 --> 25:32the more siblings you have,
25:32 --> 25:34but with even several siblings,
25:34 --> 25:35many patients still don't have
25:35 --> 25:37a donor within the family
25:37 --> 25:38that's a good match,
25:38 --> 25:40and that's where we go to these
25:40 --> 25:41unrelated donor registries where
25:41 --> 25:43right now across the world
25:43 --> 25:45there are more than 30 million
25:45 --> 25:46people who have volunteered to
25:46 --> 25:48potentially donate bone marrow or
25:48 --> 25:50stem cells to patients who need it.
25:50 --> 25:51The most recent advance
25:51 --> 25:54in the field is that we know
25:54 --> 25:56that parents are 1/2 match,
25:56 --> 25:58so their immune system will be 50% the
25:58 --> 26:01same as their children and 10 years ago
26:01 --> 26:03that wasn't good enough.
26:03 --> 26:05We now have technology that allows
26:05 --> 26:07us to use a parent or a half match,
26:07 --> 26:09or we call Haploidentical
26:09 --> 26:11relative as a bone marrow donor,
26:11 --> 26:14and so this has hugely opened up
26:14 --> 26:16the availability of finding a donor.
26:16 --> 26:18Now for patients who previously
26:18 --> 26:20didn't have a sibling match or
26:20 --> 26:22didn't have a registry match,
26:22 --> 26:24almost everybody has a family member
26:24 --> 26:26who may be 1/2 identical
26:26 --> 26:28match to use and so do these kids
26:28 --> 26:29who get bone marrow transplants.
26:29 --> 26:31Do they need to be on some
26:31 --> 26:32sort of immuno suppression
26:32 --> 26:35for the rest of their life?
26:35 --> 26:37Like you would be if you had a
26:37 --> 26:38liver transplant for example?
26:38 --> 26:39Or kidney transplant?
26:39 --> 26:41Yeah, that's a great question.
26:41 --> 26:43So at least at first we do need to use
26:43 --> 26:46immune suppression so the donor immune
26:46 --> 26:48system does run the risk of attacking
26:48 --> 26:51the patient and we want to quiet that
26:51 --> 26:53donor immune system down for awhile.
26:53 --> 26:55The really unique thing about doing a bone
26:55 --> 26:57marrow or a stem cell transplant is
26:57 --> 26:58because we're giving a new immune
26:59 --> 27:01system, that new immune system overtime
27:01 --> 27:03actually becomes tolerant to the patient,
27:03 --> 27:05and so with a liver transplant,
27:05 --> 27:07patients need to remain on immuno
27:07 --> 27:08suppression, really lifelong,
27:08 --> 27:09to quiet the immune system, but with
27:09 --> 27:11a bone marrow transplant
27:11 --> 27:13we really just need it for
27:13 --> 27:14a brief period of time.
27:14 --> 27:16So for many patients they are on
27:16 --> 27:18immune suppression for three to six
27:18 --> 27:20months after their transplants and
27:20 --> 27:22most patients are off of immune
27:22 --> 27:23suppression by one year after.
27:24 --> 27:27Interesting and then the third
27:27 --> 27:29bucket of therapies that you mentioned
27:29 --> 27:32as something that you would consider
27:32 --> 27:35in people who did not respond or
27:35 --> 27:37aren't responding well to chemotherapy,
27:37 --> 27:39was this whole bucket of therapies
27:39 --> 27:41you called cellular therapies?
27:41 --> 27:43Tell us more about that.
27:43 --> 27:45So cellular therapies
27:45 --> 27:47are a way to leverage a patient's
27:47 --> 27:49immune system to recognize the
27:49 --> 27:52cancer in their body and attack it.
27:52 --> 27:55So really, the first licensed cellular
27:55 --> 27:58therapy was for acute lymphoblastic leukemia.
27:58 --> 28:00And the way this works is we can
28:00 --> 28:02actually collect lymphocytes or the
28:02 --> 28:04immune system cells from our patient
28:04 --> 28:06in the laboratory we can teach them
28:06 --> 28:08to recognize markers on their leukemia
28:08 --> 28:10and then re infuse those cells back
28:10 --> 28:12into the patient to allow their own
28:12 --> 28:14immune system cells that have been
28:14 --> 28:16modified to attack their cancer.
28:16 --> 28:18This has been really an incredible
28:18 --> 28:19breakthrough therapy over the past
28:19 --> 28:21several years in almost 100% of
28:21 --> 28:23patients who receive this therapy
28:23 --> 28:25will go into remission within the
28:25 --> 28:27first 30 days after receiving it.
28:27 --> 28:27It's really miraculous.
28:28 --> 28:31Wow, so a few questions. First question,
28:31 --> 28:36when you said you harvest a patients
28:36 --> 28:38lymphocytes, but your leukemia cells are
28:38 --> 28:40part of your immune system aren't they?
28:40 --> 28:43They are, but
28:43 --> 28:44we're able to differentiate
28:44 --> 28:45them in the laboratory,
28:45 --> 28:48and so really we're able to isolate
28:48 --> 28:49mature kind of healthy lymphocytes
28:49 --> 28:52to be able to re infuse back.
28:52 --> 28:53But they made
28:53 --> 28:54it possible that there may
28:54 --> 28:56be leukemia cells in these
28:56 --> 28:57cell therapy products,
28:57 --> 28:59but the engineered cells can
28:59 --> 29:01actually still recognize those
29:01 --> 29:02leukemia cells to attack them, and
29:02 --> 29:04the engineered cells will continue
29:04 --> 29:06to attack the cancer cells
29:06 --> 29:08and everybody gets a response.
29:08 --> 29:09So almost everybody responds.
29:09 --> 29:12One of the big questions is what
29:12 --> 29:14happens to these patients long term.
29:14 --> 29:16So there are some patients where these
29:16 --> 29:18engineered lymphocytes persist long term,
29:18 --> 29:19but for many patients the
29:19 --> 29:20lymphocytes actually disappear
29:20 --> 29:22over a period of about six months,
29:22 --> 29:25and so one of the questions is how
29:25 --> 29:27do we maintain that remission and
29:27 --> 29:29what do we do after the cell therapy?
29:30 --> 29:31And for many patients,
29:31 --> 29:33that might mean still doing a bone
29:33 --> 29:35marrow transplant once they're in
29:35 --> 29:35remission.
29:35 --> 29:37doctor Aron Flagg is an assistant
29:37 --> 29:39professor of Pediatrics and hematology
29:39 --> 29:41oncology at the Yale School of Medicine.
29:41 --> 29:43If you have questions,
29:43 --> 29:44the address is canceranswers@yale.edu
29:44 --> 29:46and past editions of the program
29:46 --> 29:48are available in audio and written
29:48 --> 29:50form at Yalecancercenter.org.
29:50 --> 29:52We hope you'll join us next week to
29:52 --> 29:55learn more about the fight against
29:55 --> 29:58cancer here on Connecticut public radio.

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July 5, 2020

Yale Cancer Center

visit: http://www.yalecancercenter.org

email: canceranswers@yale.edu

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