Narrator: Coming up on Mayo Clinic Q&A.
Dr. William Hogan: So, what we do is we take out the stem
cells, put them in the freezer to protect them, and then give
higher doses of chemotherapy that can kill the cancer more
effectively, and then infuse the stem cells back into the patient
to allow them to repopulate the bone marrow after the
chemotherapy has been used. So that way, you get to use much
higher doses of chemotherapy and much more effective killing of
malignant cells, but at the same time, sparing the bone marrow
with the toxicities of the chemotherapy.
Narrator: Bone marrow transplants are lifesaving
treatments for patients with blood cancers and other
diseases. Thanks to advances in blood and marrow
transplantation, more patients can now benefit.
Dr. William Hogan: Things have really been transformed over the
last number of years. The advance in biomarkers for
detection of acute graft versus host disease as higher risk is
really transforming how we do things and the advances with
regard to reducing the risk of relapse with targeted agents. So
many of these advances are somewhat incremental, and there
are others that are more transformative like Car-T
therapy, but a combination of all these things together is
really kind of moving the field forward and allowing us to offer
more effective treatments with less toxicity for many patients.
Jason Howland: Hello, everyone, and welcome to the Mayo Clinic
Q&A podcast. I'm your host Jason Howland sitting in for Dr.
Halena Gazelka. Bone marrow transplant is used to treat
blood cancers and related disorders by infusing healthy
blood forming stem cells into your body to replace unhealthy
bone marrow. A bone marrow transplant is also called a stem
cell transplant. Recently, Mayo Clinic in Rochester, Minnesota
celebrated its 10,000th bone marrow transplant. Researchers
are now examining the potential for stem cell transplant to
treat other conditions, including multiple sclerosis.
Here with us today to discuss advances in bone marrow
transplant is Dr. William Hogan, Director of Mayo Clinic Blood
and Bone Marrow Transplant Program in Minnesota. Dr. Hogan,
welcome to the program.
Dr. William Hogan: Thank you very much, Jason. It's pleasure
to be here.
Jason Howland: So first off Dr. Hogan, what cancers can be
treated with bone marrow transplant?
Dr. William Hogan: Well, we can treat a lot of both cancerous
conditions and benign conditions with bone marrow transplant, but
the vast majority of what we treat currently are blood
cancers. So cancers such as lymphoma, multiple myeloma and
leukemias represent the vast majority of what we use
transplant as a treatment for. But there are a variety of other
things, including some solid tumors, such as germ cell
tumors, and then we use transplant to treat other
diseases that are not malignant, such as bone marrow failure
syndromes, and aplastic anemia, as well. And, rarely, some other
related disorders that are not related to hematology, such as
neurologic disorders, occasionally, such as multiple
sclerosis, as you mentioned.
Jason Howland: How is a bone marrow transplant performed?
Dr. William Hogan: So in general, there are two different
types of transplants that we do. One is called an autologous
transplant. And that means that we take the stem cells that we
use for the transplant from the patient themselves. The other
form of transplant that we consider is an allogeneic
transplant, and that's where we use a donor in order to provide
the stem cells. So for an autologous transplant, this is
usually for treating diseases such as multiple myeloma or
lymphoma. And that's where we collect the stem cells in
advance of the transplant from the patient and we freeze these.
And that allows us to get much higher doses of chemotherapy
than otherwise would be possible because the doses of
chemotherapy would injure the bone marrow permanently. So what
we do is we take out the stem cells, put them in the freezer
to protect them, and then give higher doses of chemotherapy
that can kill the cancer more effectively, and then infuse the
stem cells back into the patient to allow them to repopulate the
bone marrow after the chemotherapy has been used. So
that way, you get to use much higher doses of chemotherapy and
much more effective killing of malignant cells. But at the same
time, sparing the bone marrow with the toxicities of the
chemotherapy. The other type of transplant that we use is
allogeneic transplant, and that's where we use a donor. And
so that can be helpful if a patient has a bone marrow
failure syndrome. For instance, they got exposed to radiation or
they took a drug or there's a inherited problem with the bone
marrow that causes it to fail. And if that happens, then we can
use stem cells from somebody else because our own stem cells
are not going to be able to produce because they have the
underlying bone marrow failure syndrome. The other possibility
is for certain types of bone cancers and blood cancers, such
as leukemias, the bone marrow itself is not going to be great
if we take it from the original patient because that can have
the malignant cells present. And so we use donor bone marrow both
to replace the diseased bone marrow and also to provide what
we call a graft versus leukemia effect. So that's where the
donor bone marrow itself is involved in actually killing the
cancer cells in addition to the chemotherapy that we give, and
that can actually be a very effective strategy for treating
leukemias.
Jason Howland: Who can donate bone marrow for use in bone
marrow transplants and how do they donate?
Dr. William Hogan: Sure. So there's a variety, maybe about
three quarters of the patients that we offer transplant to and
donate their own stem cells. And that's through a process called
leukapheresis. So generally we give a medication called growth
factor or gcsf, or filgrastim. And that releases the stem cells
from the bone marrow into the blood, and then we can collect
them through a machine called a leukapheresis machine. And that
allows us then to take the cells and freeze them. And so that's
what we normally do if we're doing an autologous transplant.
If we're doing an allogeneic transplant with a donor, options
might include a matched brother or sister sibling. Sometimes we
use half matched siblings or other family members. We use
unrelated donors sometimes if we don't have a family member
that's adequately matched. And then occasionally, we use cord
blood transplants that have been stored and that's becoming less
common, but that's still occasionally an option.
Jason Howland: So what do patients need to know about
recovery from bone marrow transplant? Will they need to
take any medications? Will they need to modify their diets or
other lifestyle factors?
Dr. William Hogan: Yes, it's quite variable. It depends on,
you know, how healthy the patient is going into transplant
and the type of transplant. Autologous transplants tend to
be shorter with regard to recovery period, maybe something
like four to six weeks in Rochester. But you know, after
that, even for many months, there can be some kind of
gradual recovery process of regaining stamina and strength
and all of that. After allogeneic transplant where
we're using a donor, it's a more complicated process. And
generally speaking, that person will be in Rochester for three
to four months. And that can be even a lifetime a follow up to
monitor for complications and treat afterwards. So it's quite
variable, depending on the situation.
Jason Howland: Are there any special considerations for
people of diverse backgrounds to consider if they are faced with
a cancer diagnosis that requires a bone marrow transplant?
Unknown: Sure, well, there are a lot of considerations, but one
area that particularly affects us is the ability to find a
matched donor. So in general, families don't always have a
matched donor within the family. And that's for a variety of
reasons. And these are smaller, and many diseases now are being
diagnosed at an older age. And then the brothers and sisters
are older with other medical problems. So it makes the
ability of a healthy donor in the family less common. So in
patients of diverse backgrounds, it can be harder to find a fully
matched donor in the unrelated donor registry, because there's
more diversity of the HLA, which is what we use for matching. So
there are some other options that we can consider in that
situation. And half-matched transplants have become much
more feasible in the last 10 or 15 years using a strategy called
post-transplant cyclophosphamide. And so that
has allowed us to consider less well-matched transplants for
patients that have diverse backgrounds, or even if they
don't. And then other possibilities include
mismatched, unrelated donor transplants, which is becoming
more possible as well. So we have a variety of options that
weren't available to us previously, that can now be a
good option for patients of diverse backgrounds. And cord
blood transplant may also be an option for patients that have no
matched donor, but that's becoming less common currently.
Jason Howland: All right, let's talk about advances in bone
marrow transplant and cell therapy. So you touched on it a
little bit there the use of mismatched donors, but also
treating older, more frail patients. Previously, bone
marrow transplant was limited to younger, healthier patients. But
that's changing now, isn't it?
Dr. William Hogan: Yeah, well, at the beginning of this when
transplant was really developed in the 1980s and 1970s, very
high doses of chemotherapy and radiation were essential in
order to prevent the transplant from being rejected. But with
the advent of drugs called purine analogues, this has
allowed much less intense regimens to be possible. And so
over the last 15, 20, 30 years, we've seen a trend towards using
much less intense regimens. And that's allowed us to consider
patients that are older and more frail. Also, the antibiotics and
the supportive care measures that we have are much better
than they were 15, 20 years ago. We've got a lot better
antibiotics, antifungal drugs, and other medications to help
people through. And so that has made a big difference with
regard to being able to consider patients that are a little
older, a bit more frail, compared to what was possible
even 10, 15 years ago.
Jason Howland: How about using biomarkers to recognize and
treat complications early? Can you explain graft versus host
disease.
Dr. William Hogan: Graft versus host disease generally occurs in
patients that have had a allogeneic transplant from a
donor. And this is where the donor immune system doesn't just
recognize the leukemia that we're trying to treat, which is
what we want, but also recognizes the patient's normal
tissues. For instance, their gut or liver or their lung. And so
this can be anything from a relatively mild to a very
devastating problem that can occur after transplant. And one
of the challenges was that, by the time that has been fully
developed, then it's harder to treat. So one of the goals of
research in the last few years, has been to develop markers that
will tell us which patients are at risk of having the most
severe graft versus host disease, and allowing us to
target more effective treatment towards those patients. Whereas
sparing patients that are less likely to develop more severe
GVHD from the side effects of medications to treat graft
versus host disease. And there's been a lot of very useful
research that has been developed in the last 10 years that has
really advanced the role of biomarkers or acute graft versus
host disease. And we've participated and developed many
of the trials that have been evaluating this further. And I
think it's really making a significant difference with
regard to the management of these patients and potentially
very devastating complications getting a little bit easier to
manage.
Jason Howland: What about Car-T cell therapy? Is this considered
a bone marrow transplant? Or is that something different? And
and what are the advantages of this newer form of cell therapy?
Dr. William Hogan: Yeah, so car-T therapy is a very
interesting therapy. It has been developed after many decades of
research, and it's really come to fruition in the last five to
10 years. This is similar to bone marrow transplant, but not
quite the same. But there are many principles that are
similar. It's a cellular-based therapy, so not a drug, but
using cells that are modified in order to try and treat leukemias
and other cancers. And basically what it does is it takes our
native immune system, and then the T cells specifically, and
modifies them so that they are much more effective at
recognizing targets that are on leukemia cells or other
malignant cells. And that really kind of allows us to use the
native immune system in a much more effective way of trying to
kill leukemias. Sometimes, when we develop leukemia, our own
immune system tends to be suppressed somewhat by the
cancer. But this gets around that for many patients. It's a
very effective strategy for many diseases. And it's really
transformed the management of some of the diseases that we've
run into. It's not without some risks, and it's got some
limitations, but it has been an extremely valuable advance in
the treatment of certain cancers.
Jason Howland: Can you tell us a little bit about research into
using bone marrow transplant to treat other non-cancerous
conditions.
Dr. William Hogan: So there are a variety of different projects.
So looking at car-T for instance, that is also being
developed for many different malignant diseases. But from the
standpoint of benign diseases, we routinely use bone marrow
transplant for treating conditions such as bone marrow
failure syndromes, like aplastic anemia, and inherited bone
marrow failure syndromes. There are also a number of diseases
that are outside of the realm of blood disorders. So for
instance, multiple sclerosis that we mentioned earlier, and
it can also be potentially treated by an autologous
transplant. Now this is a very well defined or subset of
patients with multiple sclerosis. It's not,
unfortunately for everybody with multiple sclerosis, but it's
those patients that have a particular form that is very
inflammatory. And the intense immunosuppression or suppression
of the immune system that comes with the transplant can be
helpful for some of those patients. So Dr. Keegan here in
neurology, who's a part of our multiple sclerosis unit, and I
are working together to try and identify which patients would be
good candidates for this and consider doing an autologous
transplant as part of a national trial looking at treatment for
multiple sclerosis. This is not really a standard treatment at
this time. It's an experimental trial. But for selected
patients, that could be an option.
Jason Howland: So it seems like there's been a lot of
advancements in this field in recent years. I would imagine
that it's something that you're pretty excited about.
Dr. William Hogan: Things have really been transformed over the
last number of years. I think, you know, I think in the last
five to 10 years with the advent of car-T therapy that has been
really kind of groundbreaking. The advance in biomarkers for
detection of acute graft versus host disease as higher risk is
really transforming how we do things, and the advances with
regard to reducing the risk of relapse with targeted agents. So
small molecule drugs to try and prevent relapses of acute
leukemias is also making a significant impact into the
reduction in risk of relapse after transplant. So many of
these advances are somewhat incremental. And there are
others that are more transformative like car-T
therapy, but the combination of all these things together is
really kind of moving the field forward, and allowing us to
offer more effective treatments with less toxicity for many
patients.
Jason Howland: Well, unfortunately, we are all out of
time, but I'd like to thank our guest, Dr. William Hogan, who is
director of Mayo Clinic's Blood and Bone Marrow Transplant
Program in Minnesota. Thank you Dr. Hogan, for joining us today.
Dr. William Hogan: Thank you very much, Jason. It's been a
privilege. Thank you.
Jason Howland: And thank you for watching and listening here on
the Mayo Clinic Q&A Podcast. I'm Jason Howland, and thanks for
joining.
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