Neha Katanguri

1/8/17
Pd. 3
Interview
NK: Hi.

CT: Hi, this is Dr. Takemoto.

NK: Hi, nice to meet you.

CT: Hi, I’m not sure how to pronounce your name. Is it Neha?

NK: -Yes.

CT: How are you doing?

NK: I’m good, how are you?

CT: Good.

NK: So, first of all, thank you so much for accepting my research request.

CT: Mhm. Sure

NK: … and I hoped you enjoyed your holidays.

CT: I did. Thank you. How about yourself?

NK: Yeah, I really liked my holidays too.

CT: Good.

NK: So for my research, I am studying the ​effectiveness of bone marrow transplantation and how
treatments can prevent the recurrence of a condition multiple times in recovered patients. And
for my research class, I need to transcribe this interview, so is it okay with you if I record this
interview?

CT: Sure.
NK: Okay, thank you.

So, I have a few questions I’d like to ask you about this topic of bone marrow.

CT: Mhhm.

NK: So, what is the best way to diagnose cancers relating to bone marrow? In other words, how
would this diagnosis work in accurately measuring a patient's blood cells?

CT: So… um… can you repeat your question again?

NK: Yes, what is the best way to diagnose cancers relating to bone marrow? In other words, how
would this diagnosis work in accurately measuring a patient's blood cells?

CT: So, the most common type of malignancy or cancers that we see, um… in bone marrow is
Leukemia. Leukemia is a disorder that is from genetic changes in the blood stem cells, or blood
[?].

NK: mhhm.

CT: ...uh make up the normal cells in your, in your bloodstream. So an examination of the bone
marrow is the best way to make a diagnosis of Leukemia. Leukemia can present with the
abnormal cells in the, in the peripheral blood. So that means if you just did a regular blood test
you'd be able to see the Leukemic cells, and make a diagnosis. But sometimes the Leukemic
cells are just within the bone marrow, they don't not… your either uh um…um very few of them
come out or where you cant, you can’t easily detect them in the peripheral blood. So, that would
be the test that is done most commonly to make that diagnosis. The bone marrow is, the way the
bone marrow test is done is a needle placed into, usually the hip or the pelvic bone either in the
back part or the posterior area of the of the object what we call the iliac crest or the exterior iliac
crest, and the needle is placed inside the bone and then that's where the bone marrow is and then
the sample of bone marrow is taken out its looked under the microscope and you can, you should
be able to look at the cells and find that the bone marrow usually has a very high percentage of
these abnormal cells that you see in a bone marrow. There are specialized tests that are done
where the pathology doctors can look specifically at the proteins on the surface of the cell and
some of the different subsets of leukemia can be classified based on how proteins are expressed
and also the genetics are different for the different types of leukemia so there are, there are
genetic tests that are done on the cells. So that’s, that’s how, so basically the bone.. it's the bone
marrow, is how you diagnose cancers of the blood.
NK: Okay, thank you. And also are these tests performed in a child’s first few months, or does it
depend on when the patient’s symptoms are visible?

CT: Well, when a patient has symptoms or findings that are [rejective?] or suspicious for
Leukemia or cancers of the bone marrow, then that test is done immediately. We don't want to
wait to make that diagnose cause it needs to be treated urgently.

NK: Okay, thank you. And do you believe that bone marrow transplantation is the most efficient
procedure for conditions such as Leukemia? And how exactly would these procedures work in
trying to stimulate blood cells?

CT: So, the role of bone marrow transplantation for certain um types of leukemia and in certain
cases of leukemia when it doesn't respond to therapy so broadly, kinda basically talking about
Leukemia there’s, there’s two basic types that we see in children. Two common types. One is
called Acute Lymphoid Leukemia and the other type is called Acute Myeloid Leukemia. The
acronym for that or for Acute Lymphoid Leukemia is called ALL, and for Acute myeloid
Leukemia we call it AML. For ALL, for the majority of ALL, the treatments with chemotherapy-
and these are medications that for the most, the most are given IV, some are given by mouth, uh
some are given as a shot um an intramuscular shot. That treatment with chemotherapy alone for,
for some types of Leukemia can, will be curative in the majority of patients, and the best for
Leukemia can be over ninety percent. In Leukemias that are more resistant to therapy, -so an
AML it's also true that for- for some of the good [prognosis?] Leukemias that chemotherapy
could be curative. But for both ALL and for AML, for those that are higher risk, doing the bone
marrow transplantation would be the preferred treatment because the bone marrow
transplantation is much more intensive therapy.

If the Leukemia is resistant, or if its harder to [or?] if its a higher risk Leukemia, then that's a
question of whether a bone marrow transplant should be, should be done. There are, there are
people that the other category because higher risk Leukemias, you would get bone marrow
transplantation or chemotherapy, would be those, those patients who relapse. So, there are people
who go into remission after getting chemotherapy alone. But the Leukemia comes back. And in
those cases, the question is whether bone marrow transplant should be done. The way bone
marrow transplant is done is, is there is, there are more toxicities, with bone marrow transplants,
it's much-much higher doses of chemotherapy. And that's why, if you don't need to do it then,
you would avoid doing bone marrow transplants cause of the potential toxicities. But the way,
the basic idea of a bone marrow transplant is that you give very high doses-very high doses of
chemotherapy, where you give such high doses that the bone-the person’s own bone marrow-it
doesn’t return, and that's one of the side effects of chemotherapy. Is that it will kill the Leukemic
cells, but it will also kill normal bone marrow cells. So you give very high doses of
chemotherapy-that is one of the side effects that your, your normal bone marrow cells will not
recover. And, in that case, the person needs new bone marrow. So, the bone marrow transplant,
high doses of chemotherapy, sometimes radiation is given. And then, bone marrow from another
person can be infused, and then a person would have, basically a new bone marrow.

The people that can donate bone marrow, the best, the best donors are people who match by what
they call HLA type. These are proteins, they are genes that are expressed proteins in your blood
cells and they differ between people. But if you are brother or sister, there is a 25% chance that
you will match, fully match. So, the best, the best donor, with the best chances of survival are the
donors who are a sibling who was matched at the HLA type. There are ways to see this with
people who are not matched, and these are people who are not relatives. But there are people
who can match and these are, I don't know you may have heard of bone marrow drives where
people get tested to see what their HLA type is.

NK: Yes…

CT: So you’ve heard of that. So that's, that’s the idea that there are people that didn't match at the
HLA type with the other people. They're not, it's usually not, it’s not as good as being a
brother/sister because genetically there are some differences, but that's another option for a
donor. It could be someone who is, who is unrelated, but matches. So that’s the treatment for
bone marrow transplant, and that’s, so its used in selective cases, but it’s much, its higher doses
and has higher-more toxicity than chemotherapy alone. So its not used for all treatments of
Leukemia.

NK: Okay, thank you. And as you were saying, like for bone marrow transplantation you would
need high doses of chemotherapy, what would after that? Like how exactly would you implant
the new bone marrow cells in a patient?

CT: Well it's very easy to see, the bone marrow basically, it’s infused-it looks like blood. It
comes in a plastic bag and it hangs and it goes to an IV, so it can go to you know like, if your
familiar with an IV, that they put into an arm…

NK: Yes…

CT: Usually people who have chemotherapy, they have intentionally [?] placed IV in their chest.
But it goes to the peripheral blood, and all the blood stem cells in the bone marrow actually will
find a home in the person's bone marrow. So thats how its given, its given like a basically like a
blood transfusion.
NK: Okay, thank you. And in your recent studies of bone marrow transplantation, what are the
advantages and disadvantages of the bone marrow transplant? How might this impact the success
of the transplantation?

CT: So, the, I think that the advantage for bone marrow transplant is that in some cases for blood
cancers, its you need a higher, you need high doses of chemotherapy to cure the disease. So
basically it's an option to try to cure the disease. It allows you- basically you can think of it as,
the bone marrow kind of rescues the side effects of chemotherapy. You give very high doses of
chemotherapy because you want to kill the Leukemia cells. But, the side effects of damaging the
normal cells, you have to rescue with bone marrow. So, the damages that in some cases where
the leukemia is very high risk, or its resistent, or its relapsed, this is an option that offers the
chance of cure. The downside is that it has potential, potential for very significant side effects.
There are people that will die-can die from the side effects, not from the cancer itself. So, the
major side effects that people can see are infection, because basically with the high doses of
chemotherapy, the immune system is basically gone until the new bone marrow comes out. So,
the infection is a major risk factor. The other risk is a condition called Graft vs Host disease
where the bone marrow actually recognizes- or thinks that the person who is getting the bone
marrow, it actually because the bone marrow it has immune cells in it, it thinks that the recipient
of the bone marrow is like a foreign, is a foreign object, it will react against the cancers-that the
donor. And so you'll get, you’ll can get symptoms of a rash, or sometimes the liver is infected.
And that’s a condition called Graft vs Host disease. So infection is the major, one of the major
side effects and Graft vs Host is another.

NK: Okay…

CT: Yeah, sometimes Leukemia comes back, but I would say those are the major toxicities.

NK: So as you were just saying, Leukemia does come back in some cases. So, why would there
be a possibility that it would occur a second time in recovered patients or that the patient
acquires a different form of the condition?

CT: So why, why does a person have relapses?

NK: Yes.

CT: Well, there are- you have chemother-that’s a question that many people have spent a lot of
interest in trying to understand why, why chemotherapy, or why cancers are resistant. And there
is a lot of, ideas and reasons why that might be-i mean in general the thought is that for some
cancers, chemotherapy there are many different types of chemotherapy, but the basic mechanism
of chemotherapy is that is inhibits cells from growing. The problem with chemotherapy is that it
is not 100% selective. It would mean that it affects all other normal tissues in addition to the, in
addition to the leukemic cells. So you can kind of think of it like, you know if you have a lawn
with weeds in it. And you give weed killer. You want to give weed killer that is selected to the
weed, but it also can have an effect on normal, the normal lawn. So, thats, thats kind of the
problem. So the chemotherapy is not 100% selective to the cancer cells. So there are cancer cells
that can survive chemotherapy and all you need is a few cancer cells to survive. And then they
can eventually grow. So, that's one mechanism.

The other way, there's a lot of research in trying to understand why cancer cells are protected. I
mean there may, there may be ways that cancer cells kind of disguise themselves from the
immune system-there's an idea that the immune system might have a normal role in trying to kill
cancer cells, you know low levels of cancer cells. Then there's also possibilities that with the
chemotherapy that there could be more damage to the DNA and you could have a new mutation
that comes out. That you get a cancer that’s new because you have damage to the DNA and you
have a new genetic mutation. So that's the- one of the limitations of chemotherapy- that is doesn't
always kill every single cancer cell.

NK: Okay, thank you so much. And in another article I read, I saw that the second time the
patient acquired cancer, they needed a bone marrow transplant. Do bone marrow transplants help
prevent the recurrence of Leukemia and cancers in a recuperated patient?

CT: Not- well again that's the idea, the basic idea is that bone marrow transplants allows- the
first the person got treated, they usually would get chemotherapy and its a dose where it kills the
cancer cells, but allows-is not high enough that it doesn't kills normal, the person's normal bone
marrow cells. So, the normal bone marrow cells recover. And the idea with the transplant is that
if you didn't give enough chemotherapy the first time, and the Leukemia came back that if you
gave a higher dose, with bone marrow transplant to you should be able to effectively eradicate
that the small amounts of Leukemia that you are able-not able to do with the-with the normal
amounts of chemotherapy. So that's the idea of Leukemia, its a common indication for bone
marrow transplant that if you relapse after chemotherapy alone.

NK: And as you were saying, chemotherapy makes sure that normal bone marrow cells recover.
To follow up on this, currently are there any new treatments or research being tested to prevent
these recurrences?

CT: There's a lot, yeah there's a lot of research, a lot of ideas about how, how you can treat
resistant leukemia. One of the newer therapies and ideas on how to treat cancer that come back is
to try to manipulate the immune system. To have the immune cells attack the cancer rather than
give chemotherapy which tends to be you know, tox-its directly poisonous to the cancer. So there
are, there are several types of therapies that are now-there are some that are approved for use in
different types of cancers where they stimulate a person's own immune [?], to attack the cancers.
Theres also Leukemia-there's a particular type of therapy that’s used-if you look on the internet
you may come across it- but it is using CAR T-cells and these are-this is a therapy where the
idea- the T cells are part of your immune system and the idea is to take a person's own T cells,
but to engineer them by putting in or to train them to recognize the proteins on the leukemia
cells, so that they will attack. The T cells usually attack infections and viruses but you basically
take these T cells and you train them to attack the cancer cells.So that's a therapy that was just
approved by the Federal Drug Administration. The Federal Drug Administration- the FDA and it
seems to be a promising way to treat resistant, rather than using chemotherapy.

NK: Okay, yeah that makes sense. Thank you. In another source I read, patients with congenital
neutropenia or Leukemia typically have promyelocyte cells in their bone marrow. How does this
impact the formation of white blood cells and the ability to protect the body from foreign
bacteria?

CT: So, the condition of neutropenia, so the article that I sent you really was focused on genetic
causes of neutropenia. So these are people that because they have a mutation in one of- in a
particular gene, they do not form mature neutrophils. So if you did a regular- if you just did a
blood count on either you or myself you would see that there are maybe two to five thousand
cubic millimeter neutrophils. And these patients they are born and they have, they may have
zero. The normal job of a neutrophil is to fight bacterial infections. So, patients that have no
neutrophils are risked to have bacterial infections. So these are infections that are, that
usually-for example there would be skin infections which we call cellulitis, there could be
obstacles [?] sometimes pneumonias, but these patients are at risk for severe infections. The-you
dont-the term that you used promyelocyte or myelocyte basically that's a term for one of the
stages of the neutrophils-their development. So, I always tell- to explain to medical students and
trainees like what cells develop [?], and you can kind of think of the neutrophil-all your blood
cells have to, have to kinda go through school to develop to be the mature neutrophil and you can
kind of think of it as the mature neutrophils are the people that have graduated college. And their
out and their working, they have a job, out in the bloodstream and they do their job and fight
infections. But the bone marrow is like a school. And you can start- you can see that they’re all
in different levels of development. They can be like really- babies or in kindergarden, or in junior
high or high school. And the promyelocyte is basically one of these stages they don't function as
well, but they have been trained to do the job of the person graduated college- out in the
peripheral blood. So a person that has the congenital neutropenia, basically that's what you'll see,
you'll see that if you get a blood test you'll see that there are very few mature neutrophils in the
bloodstream. If you looked at the bone marrow though, you could see- that's like looking at a
school, and you could see that they are very young neutrophils but then they kind of just stop-
nobody is going past- past elementary school basically. That’s, that's kind of the idea of what
you see. The promyelocyte or myelocyte is just a very early stage of the neutrophil during
development.

NK: Okay thank you. And lastly, does the success of a bone marrow transplant depend on the
severity of the mutation or the availability of a matching donor?

CT: For the, for the neutropenia condition?

NK: Yes.

CT: Its- I would say it's more dependent on the donor, so the success of the bone marrow
transplant basically the factors, the major factors are how well the donor is matched. That’s,
that’s a major factor. The type of mutation that gives you the neutropenia, probably doesn't
impact- as far as my understanding is, it does not impact the success of the transplantation, but
what it does do- you may have come across this, but- so there is a connection having the severe
congenital neutropenia and Leukemia. So, it does- depending on what type of mutation that you
have to give the neutropenia, there is-there may be a higher risk to develop Leukemia. Not
everybody with neutropenia develops Leukemia. So, the mutation of the genes that gives
neutropenia really is more risk effective [?] to say who develops Leukemia.

NK: Okay. Thank you so much for taking your time to answer my questions. I really appreciate
it.

CT: Okay, well good luck to you.

NK: Thank you, have a nice day.

CT: You too, bye.