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Okay so now life after transplant and the future so I think it's fitting we go to
Sam. Sam what was your experience immediately after you've had the
transplant? Okay well I'm going to leave aside the pain of the surgery and the
recovery but just in terms of the immune system I started on a number of
different immunosuppressant medications straight away and it was a very intense
period of very close monitoring to make sure that the levels of immunosuppressant
were not too high that you open to infections and those sorts of problems
but not too low that you would have rejection of the organ so there was very
frequent blood tests and lots of lung function type tests and biopsies to make
sure that there was no rejection. How long were you in hospital for? I think I
set a record at the time I was in for 12 days which was pretty amazing at the
time yeah and so I was up sort of in intensive care for two days before I
went back onto the ward and then was down in the gym having physiotherapy and
walking on treadmills and stuff within about six days. How did you
feel physically? Well again leaving aside the pain of the surgery because I
had broken ribs and stuff from the surgery so that was pretty painful but
just in terms of being able to breathe and not coughing and gasping for air was
pretty amazing and to be down walking on a treadmill being able to walk further
than I'd been able to do for that say the past 10 years without oxygen without
needing to stop was pretty amazing. Yeah I can imagine and Toby from an
immunology point of view what was happening in Sam's body after she'd
received that organ? So as I said before when that organ was transplanted
that was taken and removed there are a whole lot of and we call them passenger
leukocytes, passenger white blood cells and they're literally that they're the
cells that as I said they're always streaming through your body all the
time so when you take an organ out to transplant it it's going to have a whole
lot of cells that are sitting in there that were just doing their job anyway so
you take them out and they've been stressed by the process of the person
dying and then you put them and you transport them and that further stresses
them and excites them and then transplant them and the first thing they do is
as I said before go looking for trouble and they're looking for trouble in the
lymphatic system to where so they can start fighting and then the body the
recipients body is doing exactly the same thing so the drugs that Sam was
talking about are designed to to stop that proliferation and we could get
her sure I hope she's going to tell you how many she takes in a minute let me
just add them up in my head while we're waiting. So she takes a large number of
drugs and the reason for that is that what we try to do is use you know three
or two or three drugs in small doses to avoid the side effects of using one
drug in a very large dose so that increases the total number of drugs
somebody takes to stop this process. They all work slightly differently as well.
And they're all working differently in slightly different aspects of the
immune system to try to block that block that response so that we hope that we
by using the combination that we get away with fewer side effects in the
short term and the long term and it's just as Sam was saying we're trying to
do is suppress the immune system enough so that it doesn't fight the
transplant but gives the the other side of the immune system enough strength to
fight infections and fight cancers and do all the other things it's supposed to do.
So Sam how many drugs? Well I take three different types of immunosuppressant
medications and then I take another ten or eleven types of medications partly
because of the side effects of the immunosuppressant medications and some of
them also for the cystic fibrosis my original condition as well. But that's
infinitely preferable. Yeah absolutely it's just another pill. I used to take
them before transplants so it's just a whole heap of different pills afterwards.
So now Rhonda so after that transplant has occurred is that the end of the
association for you what happens then? Well like in Sam's case the
transplant unit will and especially for the kidneys will start sending the lab
regular serum samples if they think there's any hint of rejection occurring
they want to know what's happening and so the lab will receive a lot of cells
and serum from the patient and and then we'll retest them and see if the
antibody levels have gone up or if there's been a change in sort of different
types of antibodies that might be in there and so at some and that can go on
for a couple of weeks till it settles down again or it can be nothing you know
nothing's happening for a couple of weeks and then four or five weeks later
suddenly there's a bit of a reaction that can occur. So as we can measure the
antibody increases especially in the kidney transplants with the kidney not
doing very well and so that I will receive these samples and everything has
to be dropped and they have to be tested then because we need to know and
everybody needs to know what's happening in the patient post transplant what the
immune system is doing and which which bit of the fight is winning which bit
is losing and how we can then adjust drugs which Toby then uses that
information to address them adjust the medications to try and tone down so it's
been like an unruly class where you know the back corners misbehaving and then
the front bits playing up and you just try to kind of settle all down and get
them all in that nice even state and it's not that simple because there's so
many different aspects and each transplant each organ tissue expresses
the immune system differently and there's different drugs you know they
affect all the like Sam will tell you the side effects from some of the drugs
is quite different as well so you know not every individual has the same
outcome and can that you said a couple of weeks but I mean can it come back I
mean can it happen later yeah there can happen at any time when they where the
clinical unit think there's any hint of rejection of the graph the lab gets some
sample sense straight away and we might go back and read cross match or we might
you know so we actually store and freeze away donor cells from the organ
donor we store some for reference for later so that we can come back and
redo a cross match and that might be a couple of years it just depends on the
situation but yeah we just like to go back and the other thing that happens in
the meantime is the technology changes the assays get more and more sensitive
and we're able to do different testing and do it more extensively so we go back
and recheck sometimes so just it really depends on the reduction situations
happening in the patient some patients we don't receive any samples from some
patients we have a system depending on the clinical unit where we receive
regular samples that we don't test and we use them as a reference and we sort of
save them up we might get one at one week one month three months six months and
twelve months and we store them away there's a lot of different drug regimens
you know a lot of clinical trials and different drugs that we try and get this
unruly class to all settle down the same way that you know we have and we like to
go back and sort of check those serum samples each time and work out what's
happening with them so so this lab's still very involved in what's going on
with those transplants post graft as well so okay since those trays then you
said were there a really great step forward yeah what's been the biggest
leap since then the DNA sequencing has been the biggest change for us being
able to because in the past we could only sort of describe what we call the
the main part of the molecule on the surface of the cell if you bring that
picture up we've got the HLA molecules we can only really look at what color it
was in the part when I first started you know it was pretty cool we just look at
the color but another one with had the little forest yep so you know here
whether they're red or bling green or blue or whatever they might be but now
each of those little ribbons that not of the red and the blue bits there so
little curly bits every one of those is little amino acid and every one of those
amino acids has three nucleotides so we can actually walk along that and work
out now what those nucleotides are and describe them and work out where the
differences are so and that that's what makes a huge difference I'm in terms of
being able to understand better why we do get why we think it's match but it's
not exactly much because there are very small nucleotide differences that occur
so that would be one of the biggest developments I think in the HLA we now
have new antibody tests so this is to type this HLA type that we have
antibody tests that can equally describe the antibodies at that same degree of
nucleotide level and that's probably been the last five years that that would
have come in that we use routinely and so we now have what we call allele level
antibodies it's a really exquisite way of describing the antibodies a very
detailed level this is what gives us most of the grief on the night because
these guys kept ringing up saying you know that one you had was that was that
you know that I four or three is that the same as the I four or four is that a
different one you know that because it's been so much growth in that field in
this field and in that that system over the last five years it's been a really
exponential growth it's very hard to keep up given everything else you've got to
do it's a lot exactly so and Sam turning back to you what's your life like now
so it's 14 years on how has your life changed so I guess just from that
immediate recovery phase there was able to sort of relax some of the their
restrictions and the doses of medications came down a bit to a sort of a
new level but there's still a whole range of different monitoring and
maintenance things that I need to do as a result of having the transplant and
the immunosuppressant medications that I take so I still take all the medications
that I took at the beginning but just at slightly lower doses and I still have
regular follow-up appointments with my transplant specialist to monitor how my
lungs are going chest x-rays lung function tests still have those regular
blood tests to keep an eye on the level of immunosuppressant that's around and
because of the side effects the long-term side effects of those medications I now
have a range of other chronic conditions that I need to manage as well so for
instance one of the side effects of one of the immunosuppressants is risk of
osteoporosis so I have regular bone density scans and I take vitamin D and
calcium supplements to try to minimize that risk I have diabetes which is
partly due to having cystic fibrosis but also partly because of the side
effects of the immunosuppressant medications and so I need to take
medication for that I tend diabetes clinics and obviously have to pay
attention to my diet and manage that side of things I have hypertension so
high blood pressure and high cholesterol again the result of the side effects of
those medications that I take and so as a result I have to take other medications
to manage those conditions and I also have some renal impairment which was a
side effect of the immunosuppressant medication taken over a long period as
well in addition to that there's a whole range of precautions that I need to
take so one of the risks of being immunosuppressed is that you there's an
increased risk of cancer so there's a whole heap of surveillance things in
terms of pap smears and mammograms and dermatology skin checks annually as well
to check for skin cancers and need to take precautions when you go out in the
sun because you're more prone to skin cancers and so there's all those sort
of things to factor in and it's really just about minimizing your risk of
infection because you immunosuppress so activities like gardening when there's
lots of bacteria in the soil is a risky thing to do if you've got pets and you
have to be careful about scratches and cleaning kitty litter trays and things
like that so yeah there's a whole range of different things that you still need
to be really vigilant about and monitor quite closely so still quite a lot to do
our post transplant but I certainly don't mind not having to clean the kitty
litter tray and I don't really care that much about gardening so I'm perfectly
happy to delegate that to my husband and let him take care of that yeah so there's
some there's some upsides so Toby then in terms of research what's what's the
outlook in in what you're doing is there a likelihood at some point and Rhonda
might like to chime in on this one too in relation to the immune system maybe
one day being able to trick the itself or the antibodies to not actually you
know gather up going up on a new part of a body from somebody else
the answer of course is yes and I mean Rhonda talked about starting with 12
genes when you started as now 4,000 when I started in transplant we had three
drugs and and backs back in the 1890s we're now up to you know infinite
combinations probably got about 35 or 36 different combinations and every year
new drugs are coming on but they're not the drugs cause exactly the same we're
saying any drug we use would have side effect and if drug doesn't have a side
effect probably doesn't work so we're drugs are probably not going to be the
answer to this what's the real answer is something called tolerance and
tolerance is a state where where we we we think we can we can manipulate the
immune system into not recognizing the organ is foreign and that's been
achieved now it's been achieved in a number of patients in the United States
the tolerance trials just just starting so the total numbers of patients
treated around the world are very small the regimes are quite toxic but those
patients go on have an organ transplant and then all of their drugs get stopped
so that's real that's really where we want to be and I hope that we'll be
participating in some of those trials in the next in the next few years but
this point in time the best treatment is the immunosuppressive drugs which give
extraordinary outcomes like Sam's amazing as a doctor it's just there is
nothing better than seeing something like Sam nothing that it really works but
maybe in five years maybe in ten years we'll hopefully be having something that
won't work on the drugs probably got something I'll just talk about there is
some now that we understand at the nucleotide level the differences
between the HLA molecules and how the antibodies work that some there's an
opportunity for us and we're using this in very limited capacity at the moment
to identify what's an immunological match to look at that what we
call the immune epitope so we know that the immune system has some bits of this
that recognizes more keenly than other bits there are some parts like hot spots
that are more reactive and trying to match those by selection rather than
trying to match the whole lot might enable us to be able to target the
matching process a little better doesn't have to be an exact match but it can be
an immunological match so it's it's the cross match we do determines compatibility
as to whether the patient has an antibody it doesn't determine whether the
immune system is going to accept the graft all that readily but this is sort
of like a virtual matching process and it's being used in in the Netherlands at
the moment and they have some very good outcome looking at that data so I think
there's an opportunity with the combination of the new drug regimens
and tolerance and also the best thing is to put something in immunologically
compatible and to have a quieter system there's a lot of work that's being done
to not activate the cells when you're doing the transfer to harvest and when
we're collecting the organs to treat them well so that we can actually not
activate them so readily and and so to try and ship them in different ways so
that we're not faking too cold or you know freaking them out in any other ways
that we do with the cells that are in there but and as Toby was saying you
know the Alfred's got this Alfred hospital in Melbourne has this scaffold
where they're trying to actually keep the lungs perfused so that again they're
not going to activate all those cells lungs are very rich in cells like
neutrophils and and there's a very active and quite damaging cells so you
would you know you'd rather they all just stay in the corner and behave
themselves and not actually came out to play when you say perfused what do you
mean well where that's actually sorry yeah thank you where we try and keep the
lungs with fluid that's actually just keeping them happy keeping them at a
very comfortable state and like a bellows that sort of inflate them as well so
the lung will actually sit in a sit in a box with being perfused exactly as
Rhonda says and just letting the organ sort of calm down and and the outcomes
for transplanted lungs in that situation are actually dramatically better than
than transplanted in the conventional manner so I think that'll become the
standard in the future and that's what they've come out of the Alfred it's
true all right well it sounds like there's a really positive outlook there
so that some it's exciting to know and to know also that some of it's happening
in Australia because often we hear so much about all these advances overseas
it's good to know that we have people here working on it too
