The inside of the Couric Cancer Center is not unlike the WFBH Cancer Center; maybe a few years older and in need of some structural TLC. Everyone is super friendly and the place is decorated festively in an attempt to take your mind off your malady. Thanksgiving and Christmas provide an even more festive occasion to decorate and provide visual stimulation to distract patients from the real purpose behind the visit.
Registration was easy enough. Take a number, sit and wait until your number is called, give the nice gentleman at the kiosk your insurance information, confirm your identity, confirm the purpose of your visit and then off for blood work. The wait wasn't long for either registration or the blood draw. After I was called back to Hotel Transylvania where the vampires performed their hematologic withdrawal Holly Davis appeared and introduced herself. What a nice surprise that was. She is my primary contact for the LGLL Registry and my visit to see Dr. Loughran. Holly is awesome - a young, petite brunette with dark eyes and a sparkling personality. Her smile is genuine and inviting, like she really wants to let you in her personal space and make you feel welcome. After I was down a quart, she personally escorted us to the hematology clinic on the third floor and checked me in. She did so with authority and alacrity. After Holly escorted us to the examination room we waited in eager anticipation to see the Great Oz himself. Deep breath!
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| If Dr. Loughran is Oz, Holly Davis is Glenda, the good witch. |
Dr. Loughran is warm and affable, not prone to verbosity but quite capable of explaining things in terms that are relatively easy to understand. He listens well and answers questions with a clear understanding of the underlying motive. He's definitely an introvert and I can easily picture him pouring over hematologic reports in a lab rather than interacting with patients. Regardless, his easy-going manner, incredibly deep wisdom and expansive experience with LGLL qualifies him for any honorific titles that may be bestowed upon him, including guru and wizard.
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| The Great and Powerful Oz, aka Dr. Thomas Loughran. |
Dr. Loughran: Lymphocytes are increased in reaction to viruses but if they are chronically
elevated persistently for a long time we think of chronic leukemia. The most common one is
leukemia of the B cells, so when people say CLL, chronic lymphocytic leukemia, they generally
are referring to B cells, which is 95% of cases. The other cases are probably LGL leukemia which
are either T cells or NK (natural killer) cells. In terms of the workup that you’ve done in the past,
you had this done (referring to TCR test) which was positive. So that raises a suspicion that the
T cells are clonal and it could be LGL leukemia. So this being positive, it’s suspicious it is LGL
leukemia.
This one (referring to the previous flow cytometry test) is the one done not really well
anywhere else other than maybe here; we have this special panel. The previous study was done
but it suggested two things. One that there is a clonal population of B cells as well as a small
population of LGL which probably wasn’t high enough to meet this criteria, but this is not really
very accurate. I think, based on this atypical lymphocyte (referring to the atypical lymphocyte
count from the CBC performed there at UVA), it’s kind of almost, whenever I see this this is
underestimated. LGL are atypical. So they’re probably in here (referring to atypical LGL). We’ll
take a look at this. But it is suspicious that you probably have LGL leukemia now that I have this
result back (CBC from UVA).
How do we determine the number? The normal number is… So about 10% of a person’s normal
lymphocytes are LGL and that comes out to a total number of 200 plus or minus a hundred as a
standard deviation. These are normal cells in your system. Three standard deviations above
normal is 500 so just for definition more than 500 we say is an increase. So, just to prove the
illness more than 500 LGL clonal. So, how do we figure that out?
The way we figure this out is, it’s another derived number. Let’s just say these are 6,000
(referring to absolute lymphocyte count), these are your lymphocytes. So LGL are going to be in
here. If they’re 10%, which is normal percentage, this is 600 or so, that’s a little bit higher than
normal. Generally our patients have 50%, 80%, 95% so we’re going to figure that out and get
the actual number based on the flow.
The conclusion I’m making is based on this one test that is positive; sometimes it’s a false
positive. That’s why we like to repeat it. Also in the context of your case, the flow wasn’t
definitive before so I’ll repeat this. But I’d say it’s suspicious that you probably have LGL
leukemia based on the atypical lymphocytes and this (flow test) being positive.
The next I want to do is talk about something you mentioned about our research and also
treatment options – do we treat patients all the time. The big point to emphasize is it’s a very
chronic illness. The three prominent clinical problems patients get is one is anemia, which you
really don’t have, it’s really mild if it’s… I wouldn’t even call it anemia. The second one is
neutropenia which is a low neutrophil count, which yours is totally normal. (Low neutrophil
counts result in frequent and recurrent infections.) These (neutrophils) are the white blood cells
that fight infection and we have patients without any of these cells with the disease and they
get recurrent episodes of pneumonia, skin infections, and sinus infections. The number that
turns out to be key there is as long as it’s over 500, patients are free of serious infection. In your
case it’s probably normal so you don’t have to worry about this range. The third thing is our
patients do get, not infrequently, rheumatoid arthritis. In your case, you don’t have any of
these three prominent problems. Generally I tell patients that it’s a very chronic illness, it’s
probably not going to have any impact on longevity, whatever that might be. In your case, I’m
even more confident stating that because you don’t have any significant of these three
problems. Just kind of discovered as an accident really…incidentally we call it.
So, let’s talk a little bit about our research…
Me: Before you go on, you said it won’t have any effect on my longevity. I told you that my dad
lived until he was 98. What I had heard previously was that a life expectancy…these things
don’t progress to the stage where you require treatment until maybe 10 years or so.
Dr. Loughran: Ten years was one of the first statistics we had 30 years ago or something. That’s totally changed.
Really, frankly, the only patients that die of this illness are these people I mentioned who have a neutrophil count of zero and they get a big overwhelming infection. Because it’s normal today and has been normal throughout the last five years, I don’t think it will ever go significantly low enough that you’ll ever need treatment.
Our lab, and thanks for participating with our research program... This is a rare disease. We
think there’s maybe a thousand new patients diagnosed with it every year in the United States.
It’s seen all around the world. We have the registry that allows us to collect clinical information
from patients. If you have any questions email us. We have a lab and basically we’re trying to
figure out the biology of these cells; how are they different than the normal cells. The main
point that you’ve already mentioned is they’re unlike normal cells they’re never resting; they
are always activated. We can measure in the blood the high levels of these pro-inflammatory
cytokines we call them and the reason they’re turned on or activated is also they’re not dying
like the normal cells should be doing if they respond to a virus. We’ve been looking at the
20,000 genes we all have and coming up with a network at how they all interact with one
another so it turns out that there are 15 key hubs of something we call the survival network.
These genes are abnormally turned on, they keep themselves alive all the time. The most
important one is probably in the central hub of the network which actually was a computational
model that we did in collaboration with the physics department. It’s been really very important
in validating in our lab as much as we can. But the central hub is this gene we call stat3.
Way back in 2001 we showed that it was abnormally on in all our patients. Stat3 is a
transcription factor; its job is to turn on other genes. It literally turns on probably hundreds if
not a thousand of the 20,000 genes we have. We discovered this in 2001. In 2012, we showed
the reason it was turned on in about a third of the patients is that there’s a mutation in this
gene and it’s acquired and somatic.
Me: I know what acquired means, what does somatic mean?
Dr. Loughran: Somatic means that it’s occurring only in the blood tissue in this case, not in any
of your other normal cells so it’s not inherited. So as a consequence of the disease there’s this
mutation of the stat3 occurring only in the LGL cells.
Mari Jo: This also shows that it’s not something that can be passed on?
Dr. Loughran: It’s not inherited, it’s acquired. Yeah.
So in the research we’ll be testing in the lab to see if you have the mutation or not. It doesn’t
seem to have any, right now, impact as far as we know on any feature of the disease but that’s
our research question we’re trying to figure out. Trying to connect them more often to any of
these three particular symptoms (referring to anemia, neutropenia and RA), is it associated
with response to treatment; these are all unanswered questions. We’re doing that as our
research test. That’s the reason we’re asking you to do the saliva because saliva is the source of
normal cells. We’re basically sequencing all 20,000 genes and we get sequence information
which is like four letters of the alphabet (referring to DNA molecular bases made up of guanine
(G), cytosine (C), adenine (A), thymine (T) and uracil (U)) in different orders from 100 to 200 of
these letters strung together and it’s a giant jigsaw puzzle because we have thousands or
hundreds of thousands of these little pieces and we have to put them all together. What we
found was that we compared the blood to the saliva we found one letter was changed and that
letter was stat3. That mutation actually turns this gene on even at a higher level than the other
patients where it’s already abnormally turned on.
I don’t think you’re ever going to need any treatment so I’m not really going too focus too much
on this but I’m going to let you know a category and maybe mention some drugs. We don’t use
chemotherapy for this illness. The main problem is these LGL cells, being a part of the immune
system, are too active, they’re making these poisons and they’re clonal so we need to turn
them off or suppress them, which is what these medicines are. The most common medicine we
use is methotrexate which is the most commonly used medicine for treatment of rheumatoid
arthritis. And it does work well for LGL leukemia. There are a bunch of connections we’re
seeing; you asked about the connection between RA and LGL. We don’t exactly why they’re
connected but we’re thinking that the biology would be similar in terms of that mutation
perhaps and the LGLs proliferating.
So the bottom line is that it is suspicious that you have this illness. We’ll work this (tests) up. If
you have it I just want to reassure you it’s a chronic illness and I don’t think you’re ever going to
need any treatment for it. The secondary point is that they (previous pathologist) did comment,
and we’re going to check this out too, that there was a small component of B cells that were
clonal. Now, if there’s enough of these cells there then that could classify you as B cell CLL. I
probably think if we validate that it’s probably going to be a very small proportion. It turns out
that LGL leukemia is also connected to abnormally…. So the disease involves T cells or NK cells
but the B cells are also abnormal in our patients. It’s not uncommon as we follow patients over
20 years that some of the B cells become clonal. Sometimes they actually get a disease like B
cell CLL. That’s an entirely different discussion but I don’t anticipate that there would be
enough of those cells around that we’d actually call it B cell CLL. Basically B cell CLL is the same
thing but 4,000 of these cells are B cells which would be pretty impossible that most of them
are the LGLs.
The bottom line is it’s very suspicious that you have the T cell form of LGL leukemia. We’re
going to work that up. There may a minor component of clonal B cells but it’s not the CLL
disease. The B cell CLL is a big expansion of these cells. I’m thinking there’s a small proportion.
We don’t know if it’s true; it’s suggested from the other studies (previous pathologist report).
Even if it were true though, it’s not going to be sufficient to be enough of these to be B cell CLL.
It’s just something we would watch over time with your other doctors.
Mari Jo: Is anemia or feeling fatigued usually one of the first symptoms we’d see?
Dr. Loughran: Yeah, one of the three things we mentioned. Tiredness, fatigue, shortness of breath are symptoms of anemia. Symptoms of neutropenia or consequences are basically infections and
then arthritis. Neutropenia and RA are linked together. RA is usually seen in conjunction with
neutropenia. Often times you see RA plus neutropenia but you can either of them alone.
Me: Even if I definitely have LGLL, since it’s such a chronic disease, it won’t affect my longevity.
Currently I’m being asked to have blood draws every 3 months and visits to the doctor every six
months. Is this schedule still true?
Dr. Loughran: It’s up to your doc at home. With these counts…. They go up and down but
they’re really unchanged for the last couple of years. At some point your doc may want to see
you only once a year but right now that’s a good schedule.
Me: How will the results of these tests (referring to the ones that Dr. Loughran ordered) be
communicated to me?
Dr. Loughran: Once you get all these results back going to be a week at least. They’re coming
back in 8 or 9 days right now. I’ll write a letter and a summary. Everything goes to your doc and
I’ll give him a call.
Mari Jo: Can we get a copy of that also?
Dr. Loughran: Yeah we can send you a copy. Holly can send you a copy.
Mari Jo: Not that we’re anywhere near that, when it came to blood transfusions…is there a
time line on that?
Dr. Loughran: I don’t think you’ll ever get to that point. That’s really severe anemia. He would
have like 8 or less (referring to red blood cells or hemoglobin). People vary in terms of their
transfusions needs. All those patients need to be treated and hopefully the treatment would
work so they don’t need transfusions any more.
"The Great Oz has spoken (ummm, pay no attention to that man behind the curtain!) and decreed that LGLL will not be the cause of your demise! Further, I am confident that your LGLL will never reach the stage requiring treatment much less blood transfusions."
"Holy shit Toto, we're not in Kansas anymore!"
Unlike the tin man, I did not receive a heart or emotional enlightenment. But I was also not called a clinking, clanking, clattering collection of caliginous junk. Unlike the scarecrow, I did not receive a brain or wisdom. Too bad on that count. I'll add it to my bucket list. And, unlike the cowardly lion, I did not receive courage or fortitude. If my fear was palpable, it was well hidden from outsiders anyway. However, like Dorothy, I have been awakened from a terribly disturbing dream that threatened my very existence, albeit for a short time.
Click, click, click. "There's no place like home. There's no place like home. There's no place like home!"
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