Thursday, July 14, 2011

Some bone marrow results....

So our lovely trial nurse emailed us earlier this week to let us know that they had some partial test results!  Yes, early!  They completed part of the test in house and sent the other part to the Mayo Clinic to be processed, so we will have to wait on those a bit longer.

The news is GOOD!  Josh's PCR test came back with good results.  Obviously we are looking for a number of 0.  But that is going to take time to achieve if we ever hit it.   But until they see zero they are looking for a 3-log reduction as the goal.  So I was right in reading Josh's chart for his original PCR test - he had 91.43%.   So to lay out the numbers....
91.43     - 0 log reduction (base count)
9.143    - 1 log reduction
.9143   -  2 log reduction
.09143  - 3 log reduction

So this most recent test result came back with a result of 5.19.  So you can see we got a 1 log reduction, but we've got quite a ways to go to hit 3 log, if I am figuring this whole thing out correctly.  I know people see these results and think that means everything is completely hunky dory, but I just have to keep it in perspective that yes, things got better, but he has a long way to go. I found this transcript of Dr. Druker explaining the meaning of these tests.  I thought it might help others cause he explains it really well, so here is the important part (warning, this is long and the formatting copied poorly!)....

How do we monitor CML?
Clearly, we can monitor blood counts. We can also test for the presence of the abnormal chromosome that marks leukemia cells, the Philadelphia chromosome.
We can look for the Philadelphia chromosome either through cytogenetics, it can be done on bone marrow, or we’ll look at 20 dividing cells.
We can also use FISH (fluorescence in situ hybridization), either on blood or bone marrow, where we look at 200 cells, either dividing or non-dividing, or a polymerase chain reaction (PCR) where we can look for traces of leukemia in as many as a million cells.
So, let’s talk about this in a slightly different way, and let’s think about this in terms of numbers of leukemia cells. The ideal would be not to have any leukemia cells.
If you didn’t have any leukemia cells, you don’t have leukemia, and if we can ever get you to that point, we can say that you’re cured.
At diagnosis, most people with CML will have a white count of 50,000 to 500,000. A normal white count should be 5,000 to 10,000.
That’s anywhere between 5 to 50 times the upper limit of normal. In a normal bone marrow, there are 1 trillion cells.
Now that sounds like a big number, but that’s how many normal cells are in a normal bone marrow. If the bone marrow’s been taken over by leukemia, you have as many as 1 trillion leukemia cells. That may sound like a huge number, but that’s how many cells a normal bone marrow has, and now your bone marrow has leukemia.
The first goal of therapy is to get your white count down to normal. If you have a normal white count, we would call that a complete hematologic response. So a complete hematologic response simply means a normal white blood count.
Now the problem with that is that we really don’t know how much lower you’ve gone, how close you are to zero. We’ve only reduced the number of leukemia cells by maybe 10-fold, perhaps down only to 100 billion leukemia cells. So we’ve got to do much more sensitive testing, and this is where cytogenetics comes in.
This looks for the abnormal chromosome. This abnormal chromosome, which marks the leukemia cells, comes about because 2 chromosomes, chromosomes 9 and 22, exchange pieces, and you end up with a short chromosome 22, which is called the Philadelphia chromosome, and a longer chromosome 9.
It’s this short Philadelphia chromosome that we can look for in the bone marrow that marks leukemia cells and is actually what causes leukemia. This is what we look for in cytogenetics. We look for the presence of the Philadelphia chromosome.
As I mentioned, we look at 20 cells. Typically, when someone is diagnosed, all 20 of their bone marrow cells will have the Philadelphia chromosome. So it’ll be 20 out of 20 Philadelphia chromosome positive.
Now when somebody has a normal white blood count, what if they still were 20 out of 20 Philadelphia chromosome positive?
What that tells us is that most of their blood cells are still leukemic despite having a normal white blood count, and our estimates would be that that patient has 100 billion leukemia cells left.
Now, the reality is it’s better to have a normal white count than a white count of 500,000, but you could still be left with a lot of leukemia cells.
So the next goal of therapy would be to try to get somebody down to 0 out of 20 Philadelphia chromosome positive, also called Philadelphia chromosome negative, or a complete cytogenetic response. All those terms mean the same thing. It just means we’ve gotten you to Philadelphia chromosome negative.
In reality, we’ve only looked at 20 cells. A normal bone marrow has a trillion. We’ve just looked at a drop in the bucket. We’ve got to get much more sensitive tests if we’re going to figure out how well controlled somebody’s disease is.
Again, however, it’s far better to be Philadelphia chromosome negative than Philadelphia chromosome positive. So we need a more sensitive test known as PCR.
PCR testing is, for those of you that follow some of these crime scene dramas, the cops go to the scene of the crime, they scrape a piece of blood and figure out who did it. We can sort of do the same thing with a test tube, a vial of blood.
We can look for a trace of leukemia in that vial of blood. So with PCR testing, we can amplify a signal, and we can see 1 leukemia cell in between 1,000 to 1 million normal cells.
Now this PCR testing can be qualitative. It simply gives you a positive or negative. It tells you if this Philadelphia chromosome abnormality, which we’ll now call BCR-ABL, is present or not present. We can also do a quantitative test where it gives us an estimate of the number of leukemia cells.
So if we put this back on our graph, the reality is that we now can go from 1 trillion cells down to 1 million leukemia cells, but we have to make a couple of points here.
First, if you do an equivalence ratio, 1 in 1 million is equivalent to 1 million in 1 trillion. So PCR undetectable could still mean you have 1 million leukemia cells left. It doesn’t mean cured, and it also means that we can’t do anything more sensitive to look for lower levels of leukemia.
So PCR undetectable or PCR negative doesn’t mean cured. It just means the lowest level we can identify.
The second point is that about 80% of patients treated with imatinib will be between Philadelphia chromosome negative or complete cytogenetic response and PCR undetectable.
Most people will be there. The only way we can monitor patients in this range, where the majority of people are, is through PCR testing.
So let’s look at this graph, looking at PCR values, and here I’ve taken what’s now known, on the left-hand side, something called the International Scale where newly diagnosed patients arbitrarily would have a value of 100, and I’ve done 10-fold reductions, and you can see on the very far right we have a 3-log reduction. That just means 1,000-fold reduction in the number of leukemia cells, and that has some prognostic importance.
We can make a couple of other points.
First, I’ve shown this on a quantitative scale, meaning the quantitative PCR that gives us a number. If we did a qualitative PCRthat just said present or absent, all of these values would be positive. You couldn’t tell the difference between a newly diagnosed patient who would have a value of 100 and a very, very well-controlled patient, who would have a value of 1, which would likely be a complete cytogenetic response, 0.1 or even lower. So the reality is this quantitative PCR gives us a far better insight into how well controlled people’s leukemia is.
Second, clearly quantitative monitoring is preferred. It gives us an indication of where people are. The problem, though, is that different labs will give you different results. If you come to my hospital in Oregon or Dr. Neil Shah’s hospital in San Francisco, we’ll give you different results. We are working on standardization so that you can go anywhere in the world and have the same testing done and the same results done, but unfortunately we don’t yet have a standardized test. Until then, my
recommendation is that you send your samples to the same lab so that you can follow a trend.

For those of you who are interested, Novartis has set up a program called the CML Alliance™ and they currently use 2 labs. If you’re currently not being done at one of these labs, I would urge you to think about working with your physician through the CML Alliance, to have your testing done routinely at a standardized testing laboratory.
A third point about monitoring is that negative results also depend on the quality of the lab and the quality of the sample. The sensitivities vary from lab to lab, from 1 in 1,000 to 1 in 1 million, and so negative at 1 in 1,000 is not as good as negative at 1 in 1 million. Different labs, again, will have different results.
What do I consider a good response?
There’s a 3-log reduction. Any time you get it, it is a great place to be. (That’s me – Harvey)
Six months, 1 year, 2 years, that’s a great place to be.
The risk of relapse is a half percent per year, and it decreases over time. So at a half percent per year, that means that at 10 years, 5% of people in that category would relapse.
With a complete cytogenetic response to Philadelphia chromosome negative, there is a 2% risk of relapse per year, and by year 4 of maintaining that response, it declines to a half percent per year. So my view is that a stable complete cytogenetic response is equal to this 3-log reduction.

So if you are still reading this then I am way impressed.  It is pretty sad that I now find all this stuff interesting!  It feels good, though, to know what we are up against.  We are feeling encouraged with these results!  We will keep everyone updated when we get the rest of the results next week. We're still waiting on the cytogenetics to come back, which will tell us about those pesky chromosomes!

Saturday, July 9, 2011

Twelve years!

It's so hard to imagine, but today is our twelve year anniversary!  Craziness, right?  I know without a doubt that twelve years ago we couldn't even imagine what was in store for us in the coming years.  But I do know that all my dreams came true when I married this man - the one and only person that God created for me to do life with. 

We did not have a wedding, cause there were no funds for it.  For a while we were engaged and just kind of thought that somehow, magically, a wedding would happen.  But when we realized that was out of the picture we picked a random day a few weeks away and made an appointment with the Justice of the Peace in College Station.  Not exactly the most romantic thing ever, but I am over it now! ;)  Back then I was pretty sad about missing out on the wedding hoopla.  We even had dreams of renewing our vows with an actual wedding 5 or 10 years down the road.  But when we hit those milestones it was already SO unimportant to me it didn't even cross my mind.  :)

Josh and I have never had the funds for extravagant gifts, and today is no exception to that.  I can honestly say the best gift I could have been given is the two months Josh was home with us after his diagnosis.  It was so amazingly nice to get to spend so much time with him.  All day, all night.  Every shopping trip, errand, and playdate.  As he was getting ready to go back to work last month we discussed that this was the most time we have spent together in the last 12 years.  It reminded me very much of the first few months after we started dating my freshman year at A&M.  We were so hopelessly head over heals we spent every single moment together, much to the detriment of our grades and other friendships.  It was an unexpected gift to get to have that much time together again, which we probably won't ever have again while we are young.

I have loved Josh since I was 16 years old and we met working at Oshman's Super Sports.  I got that job because I figured it was a good place to meet guys, and I was right!  I liked 2 guys there - Josh and the boy I dubbed "fine guy in bikes."  Luckily Josh won out!  I was pretty persistent - even though I told him I liked him the next year, he told me he didn't feel the same way.  But I wasn't to be turned away - I followed him to A&M.  Luckily I was able to convince Corrie to go with me so I didn't look like too much of a stalker! ;)  And I snared him and he didn't even know what happened!!  LOL

Anyways, I love thinking about how we fell in love and how wonderful it was, and it always makes me realize that it still is wonderful.  He is truly the only person that would put up with me for this long, and I am well aware that I am not an easy person to love.  He talks me down when I get worked up about things and knocks the sense into me that I almost always need.  He even makes me laugh when I'm furiously angry, and he's the only person who can get away with such shenanigans.  I got him a father's day card that explains exactly how I feel.  It reads, "I love you, I love us, I love our family."  Perfectly said.

Wednesday, July 6, 2011

More waiting!! (of course!)

So, after all our anticipation, we are still waiting on results.  And instead of getting them on Friday like we thought might happen they told us it will be 2-3 weeks!  Isn't that craziness!?!

When you have appointments at MDACC they schedule each little thing out for you and give you this printed schedule each day.  Cause you end up roaming all over the huge complex just to get everything done.  So you can print it at home or you can go to the front desk and have a nurse print it for you when you get there.  So I just figured we would have the nurse do it, cause I didn't want to mess with it last night.  And can you imagine that we were there so early there wasn't a single person at any of the desks yet?  So I had to call my mom and guide her through the process of finding it online just so we knew what floor and desk to go to!  I guess I learned my lesson about being prepared! :)

So Josh gave blood, which was nice and easy.  And then we made our way to the other side of the complex for the BMA.  If you remember Josh was REALLY worked up about this, even though it would be with sedation this time.  He couldn't eat after midnight, which if a big deal for Joshua - I have never met a person so intent on eating immediately when he wakes.  He drives me crazy with it at times!  So we go there at 7:00 and they told us that they had to change the times and he wouldn't be able to go in till 8:00.  So we waited and waited and finally they took us in and got him all hooked up to the IV and all the other gadgets.  So she tells us they will be giving him Propofol, and it seemed familiar but I was so intent on listening to her I didn't really think much about it till later in the waiting room.  Does it sound familiar to you?  If you are thinking Michael Jackson then give yourself a gold star cause you are right!  Josh now says he completely understands why MJ liked it so much!  LOL 

He said that the anesthesiologist told him "you'll feel some pain in your hand and then the next thing you'll remember is me saying Josh, Josh, wake up".  And sure enough he says that is exactly how it happened!  They wheeled him out in a wheelchair and I just wish I had my camera with me cause he just looked GONE!  So very confused and drunk looking!  And he just kept talking to me with slurred speech - it was really funny.  He kept talking about giving the thumbs up and then while we were waiting for the next appointment he likened himself to a robot in the wheelchair.  He was cracking me up!  And he wasn't the slightest bit concerned about eating for quite some time after the test.  I'm really tickled with his goofiness after the procedure! He says it was absolutely perfect and it is the only way he will do the bone marrow tests from now on.  I am so glad!  Especially since he will have to have another one in October.

The nurse that processed Josh for the BMA was so funny - the discharge instructions are pretty normal, like not operating heavy machinery or drinking alcohol.  But then they stress don't make any major purchases or important decisions.  She did clarify though, to ignore those instructions if he felt like buying me some jewelry today! :)

We waited for an hour for the five minute EKG and finally gave up and made our way upstairs to see Dr. Quintas.  And we were able to visit for a long time with the super sweet trial nurse, whom we love.  So that was really nice.  Only saw Dr. Quintas for a few minutes, but he said Josh is doing great.  Remember there are three responses they are looking for?  You can read about them here on this site.  The first response is a hematologic response, which he has achieved.  His platelets did fall some more in the last month, though.  They were at 99 today and normal is considered 140-440.  He said that his low count is from the nilotonib, and not from the leukemia, so they are not worried about it.  They did say they will keep an eye on it but that it is very normal for platelets to fall in the first few months and then level out as your body gets used to the drugs.

The next response is the cytogenetic response, and he is hoping that Josh has already hit that.  They won't know this until the results from the BMA are in.  You can see that they want this within 6 months, but he says that being on such a high dose of the stronger drug should bring that response already.  So we are very hopeful that is what he will get!  He did stress over and over that three months is extremely early into treatment, and that the treatment of CML takes time.  If he is doing over the top well he would already have a molecular response, so we will anxiously await those results as well.

So basically the responses are just a blood response, then a chromosomal response, and then finally a molecular response.  Of course these are all tied to the fact that he takes his chemo every single day.  If he were to stop taking it at any point, even ten years from now the leukemia would come back.  They did stress today that mutations are very rare which I think made Josh feel a lot better.  It is just scary, though, cause we know that it does happen.  I was asking Dr. Quintas about specific numbers that we should see with these results and he gave me some figures but then told me to not really worry about it.  I had to look at him straight in the eyes and inform him that I WOULD be worrying about it.  This is my man we're talking about!!  Dr. Quintas made us laugh cause he then made some sort of joke about how he didn't know how Josh could forget his pills with a wife like me!  ha ha ha  He has me all figured out in a few short visits!  I like it!

So all in all, today went well.  As crazy as MDACC makes me, I really love Josh's trial nurse and his doctor.  It is always nice to actually get to see them when we go in.  We did get a refill of meds, so we are good to go for the next three months.  Josh will go in monthly for blood tests until October when we will once again have bone marrow tests.  We will let everyone know when we get the test results back.  Isn't it just mean to make us wait that long??!  :)

Tuesday, July 5, 2011

Getting ready!!

So tomorrow is the big day!!!  Our first appointment is bright and early at 6:15!  Seriously already feel like crying just thinking about getting up early enough to get there on time!

Josh has a blood draw, bone marrow aspiration w/sedation, EKG, and a visit with the doctor.  So I'm fairly certain that will take ALL day, even though we are starting at the crack of dawn.

Hopefully he will get another prescription filled while we are there to restock his meds.  It is so strange to me but you have to keep the bottles for the trial and return them to the trial nurse.  Isn't that weird?  I snapped a pic of Josh's before we packed them up to go.  It is crazy to think that those few bottles of pills are what is keeping him alive!

And check out this other part - I think it is so funny that they treat it as though it is so very dangerous and you must dispose of properly.  So glad Josh is swallowing four of these daily! ;)  If we walk out with another bag of pills I will once again feel like we are stealing - I am still so amazed that they are giving them to us for free! 





And this is what the pills actually look like.  The NVR is for Novaris, the manufacturer.  And TKI is for tyrosine kinase inhibitor - the class of drug that Tasigna is. 






And the last thing we are returning is his medication diary, where he has recorded the time of every single pill he has taken over the last three months.  We keep it conveniently attached to the fridge!

Josh just got out of the shower since he won't be able to bathe for 2 days after his BMA and we're packing up the bag for the hospital right now.  We're feeling quite anxious about tomorrow - Josh mostly for the bone marrow test itself, and me mostly for the outcome.  We never got the situation with the nurses worked out about when we will get the results, so we're not even certain we will have anything to report tomorrow at all.  Josh's job allowed him to take a vacation day Thursday night, so we are pleased with that.  He didn't want to have to sit up in an uncomfortable chair all night with the pain he will have in his back from the tests.  That also allows us to meet with the doctors again on Friday if need be.

It seems that the way that they measure your success with the meds is through a test called a PCR.  If I am reading his test results correctly from the first test, he had 91.43% as his PCR results.  The goal is to get as close to 0% as possible.  Want to see why we are a bit confused?  Here is a copy of just the top quarter of this test result page....
REAL TIME BCR INTERP PB                          
BCR-ABL qRT-PCR:

Coexpression of b3a2 and b2a2 BCR-ABL fusion transcripts is detected by
real-time PCR.

The percentage of BCR-ABL to ABL transcripts is 91.43.

COMMENT: Quantitative real-time PCR analysis performed on RNA from this
sample for the BCR-ABL fusion transcript resulting from the t(9;22) in
leukemia. BCR-ABL and ABL transcript levels are detected simultaneously
and quantitative results expressed as the ratio of BCR-ABL to ABL levels.
This ratio may vary up to one-log because of methodological reasons.  As
of 8/2/07, the assay has shifted to a new platform.
And the font is half as large as the one here, and then there are about 40 more pages of test results from that same day.  See why we are confused?  I will be glad to see the doctor tomorrow and get to talk to someone about all this!

We'll post again tomorrow night after we have time to process everything that happens tomorrows.  Prayers are appreciated - especially for Josh to be calm for his procedure.  Thanks guys!

Sunday, July 3, 2011

Sunday Scripture!

I am a dreamer.  Nearly every single night I have long, detailed dreams.  About once a month I dream that I did not actually graduate from A&M and my degree is taken away from me.  And it seriously takes me 2-3 minutes when I wake up to realize that it is not true.  And I feel such a sense of relief.  Now I also have GREAT dreams that take me a few minutes to realize are not true.  And when it hits me I feel so horribly sad.  But last night I had an amazing dream - all about my sweet Joshua.  And I can't remember the details, but it was just this overwhelming, wonderful feeling that he loves me and I love him.  Just pure joy.  And when I woke up I laid there and realized I was dreaming and started to feel sad for a second, and then it hit me that my dream was true!!!  I know it sounds so silly but it was really just the most fantastic feeling in the world.  And it just made me feel so thankful, before my feet ever touched the floor.  God has just lavished me with His love through this man. So thankful!!

Ephesians 5:19-20

19 speaking to one another with psalms, hymns, and songs from the Spirit. Sing and make music from your heart to the Lord, 20 always giving thanks to God the Father for everything, in the name of our Lord Jesus Christ.



And amazingly this verse lead right into the other thing I wanted to share today - a song Josh and I are loving right now.  It is an old hymn that Casting Crowns has on their newest album.  It is AMAZING!!!  I could just listen to it over and over again, and I suggest you do too! :)  I love how it shows Christ's whole life - living, dying, buried, rising, and the glorious day when He comes again. I'm so thankful for this amazing plan God has for saving us!




GLORIOUS DAY
Artist: CASTING CROWNS.
Album: Until the Whole World Hears


One day when Heaven was filled with His praises
One day when sin was as black as could be
Jesus came forth to be born of a virgin
Dwelt among men, my example is He
Word became flesh and the light shined among us
His glory revealed

Living, He loved me
Dying, He saved me
Buried, He carried my sins far away
Rising, He justified freely forever
One day He’s coming
Oh glorious day, oh glorious day

One day they led Him up Calvary’s mountain
One day they nailed Him to die on a tree
Suffering anguish, despised and rejected
Bearing our sins, my Redeemer is He
Hands that healed nations, stretched out on a tree
And took the nails for me

One day the grave could conceal Him no longer
One day the stone rolled away from the door
Then He arose, over death He had conquered
Now He’s ascended, my Lord evermore
Death could not hold Him, the grave could not keep Him
From rising again

One day the trumpet will sound for His coming
One day the skies with His glories will shine
Wonderful day, my Beloved One, bringing
My Savior, Jesus, is mine

Oh, glorious day