28 replies to this topic

[CallMeLucky]

I was diagnosed in June 2010.  I started on gleevec and was a rapid responder I was Basically pcru in 11 months.  After a year of being undetectable I switched to Sprycel due to side effects.  I had significant muscle pain, fatigue, and brain fog.

I switched to Sprycel 100 mg and continued to be pcru.  I started having chest pains on Sprycel and asked dr to lower dose.  She said no so I went and found a dr who said yes. Went to 50 and was still pcru dr started to increase wanted to go to 80mg but I didn't want to so we stayed at 50 mg.  then I lost pcru.  My numbers started to climb.  I increased to 70 and they dropped to almost pcru. Then they started to climb again.  Last two PCR were increase from .0034 to .009.  I went back to 100mg two months ago and my PCR from the other day increased to .013.  I am now less than a 4 log reduction.  Despite increasing dose to 100 I have had a 1 log increase in 6 mo.  I have to repeat PCR I'm a few weeks and see what happens.  If it doesn't drop we are going to do another BMB

The last BMB from when I first lost pcru showed nothing on mutation analysis or cytogenetic changes.

I feel like such a fool.  I was doing so well and I heard about how so many people were lowering their dose and doing so well.  My first dr warned me about resistance and possible mutation with lower dose but I didn't listen.  Now I don't know what is going to happen if we can't stop this increase.

My wife made a comment last night when we talking about her friend who is going through testing for cancer very likely she has a serious one.  She made the comment that she shouldn't look at 5 year survival rates because for cml when she first looked it up it said I would only survive 3-5 years and that was old information and I was doing fine.  I hit 4 years in June not so sure about that 5 years anymore.

I hate this life, I hate this disease, and I hate that I am so stupid as to think I was going to out smart it.

How many times did I day cml is a dumb disease, it's so simple and predictable.  Now who's the dummy?  Clearly I am.

[simone4]

Lucky, I know you are beating yourself up about this, but I had a one log increase in April 2013,

after PCRU for a year.  We repeated it in July (PCRU) and again in Sept. (PCRU). However,

in Jan. 2014 it bumped up to .02. I am on 300mg Gleevec and have been on this low dosage

since 3 months after Dx.

My onc takes an attitude of "sensitivity of the PCR". Maybe so, but like you I don't understand

the coming in and out of PCRU.

Why not go back to Gleevec?  You were safe there.  It is the suckiest of all options.

And you didn't think you could out smart it.  You were just trying for a better QOL. 

You have not lost MMR, neither have I.  So if I have to increase my dosage, I will.

So will you, or go back to G.

I wish you peace through this ordeal. 

Take care,

Simone

[PhilB]

Hi Lucky,

I'm really sorry to hear you are having such a bad time.  It isn't worth beating yourself up over whether your lower dose has 'caused' the increase - and most people seem to think that your first Dr's ideas about taking too low a dose encouraging resistance don't apply in CML anyway.

Yes it is horribly stressful to see your numbers go up like that, but you are still in MMR so although you have every right to be concerned about which direction your numbers are moving in, you are still in a good place at the moment.  Lots of people on here have had 'blips' where the numbers go up and then come down again.  My personal theory is that a lot of these cases are quiescent stem cells deciding to come out and fight and therefore leading to higher numbers as they send a few waves of infantry to be mown down by your TKI machine guns.  Hopefully you also get to shoot the stem cell too in this scenario and end up with a more thorough response.

I doubt a BMB would how much at this level as they are unlikely to find a leukaemic cell in someone in MMR, but Trey is your man for techie things like that.

The one other thing I would say is that even if this is a genuine problem of resistance to Sprycel, you still have an increasing number of alternative drugs to try.  Hang in there.

Phil

[August1]

Hi Lucky,

Sorry to hear you're going through this. I can't blame you in the least for going for a better quality of life. There are treatment options with this disease and I would for sure in your shoes. You're still solid MMR at the four year mark and your readings seem to be moving up slowly in proportion to your decrease in dosage. So this doesn't necessarily mean resistance. Maybe your body is just getting back up to the therapeutic dose level to be effective or maybe Gleevac is just a better drug for you.

I am sure you will get a handle on this and things will be fine, and far beyond the 5 year mark.

Bill

[scuba]

Hi Gary - I was saddened to see your note just now. But hang in there. You don't need me to tell you about the 1-log variation in PCR - it could be as simple as that, and I hope it is. But if there is a trend upward, there are other drugs to try - or even going back on Gleevec which seems to have worked well for you (side affects not withstanding). But I really believe it's a PCR variability issue. I was told by Dr. Zuo (M.D. Anderson), who does the PCR testing at M.D. Anderson's lab (and does research in PCR methods), that the third and fourth decimal places are meaningless and that variability can easily climb to the first and usually second decimal place. Dr. Cortes added that on any one blood sample - doing two PCR tests can easily vary 1 - log!

We're here with you. Stay positive - there is always much to be thankful for - you will beat this - you have beaten it. It's the last little bit that needs to be cleaned up.

By the way - what lab does your PCR and are the results reported using I.S. scale or Lab specific. It does seem (I don't recall completely from your earlier posts) that you PCRU from one lab and when you switched Dr's. the new lab never had you at PCRU?

[Marnie]

Lucky. . .you are being too hard on yourself, so cut yourself a break.  Susan has been here for well over 10 years, and so will we all be!  Whatever you end up doing, stop blaming yourself.  The docs don't know everything.  Neither do we.  We are all in this together and as we find things out we all know a little bit more. 

Life is too short to spend a ton of time and energy on the "what ifs."  If you hadn't lowered your dosage, you might be in just exactly the same place as you are right now.  Or you might be better off, or you might be worse off.  In any event, you are where you are. 

Find something else to occupy your mind, do something nice for yourself, and move forward.  That's the only direction worth moving into.

Marnie

[Susan61]

Hi Lucky:  I agree with everyone.  Do not beat yourself up over this.  I guess Marnie meant me.  I am on Gleevec 13 years this past Oct.  I have had side effects that just wiped me out in the very beginning.  Never thought I could stick it out, but I knew a BMT was not for me.

     These TKI drugs were a miracle in the treatment of CML, but they are not going to cure CML.  So I just made up my mind that I would continue t take these pills for as long as I can.  I would not rush into cutting the dose until you are pretty far ahead with a PCRU like Trey did.

    I have seen too many people who cut their dose, and did well for awhile only for this monster disease to take over again.

    Why don't you try the Gleevec again, and see how you do.  You might not experience the same side effects.

    My prayers are with you.  My Gary beat the Prostate Cancer, and now he is trying to beat the Bladder Cancer.  He does everything the doctor tells him to do, and the results have been amazing.

Susan

[mariebow]

  Well Lucky if you think you are a Dummy, well we must be Morons!  We are just trying to get through this CML diagnosis and life as we have it.  When you have worrisome side effects, it is a natural thing to seek help.  We cannot help what people say about our survival or anything else, there is so much cancer going around now, that no one is immune from the effects of cancer.  Someone told me one time, that you have to do what you got to do.

[mark1963]

still mmr. be thank full for that.

mark\

[CallMeLucky]

We are currently using Genoptix, which is the Novartis lab and supposedly the one they used for the IRIS trial.  It is supposed to be the "Gold Standard" for PCR testing.

The lab history is a bit of an issue.  When I was with the first hospital they did in house labs and they were not IS.  They also did not use ABL1 as the control gene.  When I switched Doctors I was PCRU with the first hospital.  Second Dr sent out to Qwest which was IS and used ABL1 as control gene and I was again PCRu.  That was the period we were playing with my dosage and I bounced around from 50 to 70 and back to 50.  I had 2 PCRu with Qwest and then all of a sudden my blood went to the new hospital's in-house lab.  Suddenly I was detectable and come to find out the lab was not IS.  A second test with the in-house lab showed a minor decrease but still detectable.  I was angry they switched lab and apparently Dr did not know hospital was going to do it.  When I went back they said they were switching to Genoptix which was IS and also used ABL1.  The first test showed I was a little less than 4 log reduction.  That was when they did BMB.  Nothing showed up, we increased dose to 70, got a little drop, then the next PCR was a big drop to barely detectable.  I thought I was ok, but the next two started to climb again, I then went back to 100 and was expecting a drop, but again there was a slight increase.

I have gone back and forth about the labs but when all is said and done, the reality is that my numbers keep trying to climb.  It would be one thing if they were bouncing up and down, but they are consistently increasing, albeit slowly, but then again CML is a slow disease isn't it?  So regardless of the lab and if I would be negative at another lab, there is this upward trend.  "Noise" in the test should show randomness, this doesn't show randomness, it shows a persistent increase, that dropped when more drug was introduced, then another persistent increase, which is now not showing an ease up even in face of full dose.  That appears to be resistance, that is getting stronger.

I know I have a real hard time with the stuff, while I tend to be fairly bright, I do not have a very good emotional anchor.  I worry a lot and take this stuff very hard.  I know what's done is done, and while I likely brought this on, I suppose at the time it made sense to me.  I think I did get myself into trouble with lowering the dose.  I don't really regret switching, I regret that I didn't figure out what the issue with Sprycel was and how to tolerate the higher dose.  I kept hearing about how everyone was lowering their dose and doing so well that I thought I could too, even though my doctors were advising against it.  I have to live with that decision now and deal with the consequences.  My hope is that if I did develop resistance that another drug will work, either going back to Gleevec or Tasigna.  Dr said he would want me to go to Tasigna so I guess we'll have to see what happens next.  I wasn't supposed to go back for three months but now I will be back in a few weeks for another test to see if there is any change after being on the 100mg for another couple of weeks.

Below is my PCR history.

Date	Months	PCR Percentage	Prior Test Var	Log Reduction	PCR Status	Scale	Drug	Dosage MG
7/7/10	0	1.20000%		0	No-MMR	Non-IS	Gleevec	400
10/25/10	3	0.25000%	-0.95000%	1	No-MMR	Non-IS	Gleevec	400
12/13/10	5	0.36700%	0.11700%	1	No-MMR	Non-IS	Gleevec	400
3/14/11	8	0.00810%	-0.35890%	3	MMR	Non-IS	Gleevec	400
6/13/11	11	0.00000%	-0.00810%	4+	MMR	Non-IS	Gleevec	400
9/19/11	14	0.00084%	0.00084%	3	MMR	Non-IS	Gleevec	400
12/5/11	16	0.00000%	-0.00084%	4+	MMR	Non-IS	Gleevec	400
3/12/12	20	0.00400%	0.00400%	3	MMR	Non-IS	Gleevec	400
6/11/12	23	0.00000%	-0.00400%	4+	MMR	Non-IS	Gleevec	400
9/17/12	26	0.00000%	0.00000%	4+	MMR	Non-IS	Gleevec	400
12/18/12	29	0.00000%	0.00000%	4+	MMR	Non-IS	Sprycel	100
1/11/13	30	0.00000%	0.00000%	4+	MMR	IS	Sprycel	50-60-70
3/18/13	32	0.00000%	0.00000%	4+	MMR	IS	Sprycel	60-70
4/15/13	33	0.03600%	0.03600%	4?	MMR	Non-IS	Sprycel	50
5/20/13	34	0.04600%	0.01000%	3 - 4	MMR	Non-IS	Sprycel	50
6/3/13	34	0.02390%	-0.02210%	3+	MMR	IS	Sprycel	50
7/1/13	35	0.01920%	-0.00470%	3+	MMR	IS	Sprycel	70
7/29/13	36	0.00340%	-0.01580%	4+	MMR	IS	Sprycel	70
10/7/13	39	0.00540%	0.00200%	4+	MMR	IS	Sprycel	70
1/6/14	41	0.00930%	0.00390%	4+	MMR	IS	Sprycel	70
3/24/14	44	0.01300%	0.00370%	3+	MMR	IS	Sprycel	100

[Tedsey]

Lucky,

You didn't do anything wrong.  You came at this with knowledge.  I think what happened could be coincidence.  It is quite possible that this would have happened despite the changing of doses (or meds--I still think what your first onc said was off the mark for CML).  But now you definitely know you need to be on something to control the CML and at a higher dose.  As we so disappointingly know, PCRU is only undetectable, not a cure, the CML is still there.  And it is probably OK if it a little "got out of control" if it did.  You and your doctor will figure out what dose and what med works best for you and your quality of life.  You cannot beat yourself up for trying.  You were and are brave (not in the meaningless cancer survivors are "brave" sense garbage).   From what I know of CML, and I second Phil, I do not think what you tried could adversely affect you.  I feel you will get back on track.  You steadily had the drug in you.  It is not like you skipped your pill.  Give the 100mg time to work.  It may take a while, but since you are still MMR, it will probably keep you there or better.  As long as your heart checks out, all is well. 

I can relate deeply to what you are thinking and going through.  For me, magical thoughts creep in in times of great anxiety (please be mindful of the stress this is causing you--I am certain excess stress effects us in the worst way possible, if not by raising our PCR) .  Maybe there is some kind of magic in the universe, or at least things we cannot yet understand that seem magical, but I do not believe by temping fate you screwed yourself and lost any chance at longevity.  There is nothing out there thumbing its nose at you (I know you know this, but it can so feel like this).  Just spit on that kind of thinking!  It defeats us.  Allow yourself to continue forward, do not look back, and carry on.

Ironically, at almost 4.5 years, I lost PCRU (which I had suddenly and for only 6 months).  Similar to you, I immediately thought I was just shy of my "five" years (meaning this was the beginning of the end for me).  So, I totally get what you are saying.  I think the truth is that we may see some more ups and downs with the numbers just like Scuba mentioned.  Please pay attention to what he says.  It is true about the PCR.  We have heard this over and over!  We need to let this sink in (I am saying "we" because I too fall victim to having my emotions weighed down heavily with my PCR values no matter how small--I begin to die with every rise and get a new lease on life with every fall--it is such a hard way to live, I know).  A log is a log is a log, yada, yada.  I like how Trey once told someone to ask their onc to "prove" that there was a problem (or something like that).  But that is not where you are at present.  I just like to keep that in mind.  If we were all being tested on the very same PCR machine at the same lab, the status of CML would be clearer.  Variation is the devil.  Until that is sorted out...let us live that long.  And by then, there may be a cure, or we will have already died of old age.

Take care.  Be well.  And for whatever it is worth, I am sending good vibes, wishes and such out into the universe for you, to you.

Peace brother,

Tedsey

[Tedsey]

I am not convinced you are losing response.  I assume you started on 100mg just after your Jan. PCR.  That is only about 2 1/2 months on 100mg.  It is possible that you need more time on the dose.  Your BMB also showed nothing.  Give it some more time.

[mariebow]

I agree

[PhilB]

Lucky, in 5 years of this disease one thing I have definitely learnt is just how random PCR results are, both in terms of testing 'error' and in and of themselves.  We have seen so many people's numbers go up and down like a clumsy mountaineer that one thing I am sure of is that it is way too early to call a persistent upward based trend on your numbers.  I  think you clearly have to look at the last year separately from the earlier numbers.  The early numbers look like 'your' Glivec response level.  The last year is your Sprycel response level.  Yes it isn't as deep as Glivec, but it's still absolutely fine.  Within the Sprycel period you are looking at a pretty small number of data points.  You are pessimistically ignoring the initial drop, or attributing it (very dodgily in my view) to dosage changes.  I read it as basically stable for the last year with a dip in the middle. I freely admit that if they were my own numbers I'd be panicking just as much as you, but that would be because you always read your own numbers with your hind brain and can only use your normal logical faculties on other people's.

You need more data before you can call any kind of trend and the only thing that will give that is more time and more tests.  There is nothing to be gained from worrying about it in the meantime so get back into those spangly tights and go have some fun.  If you do find yourself thinking that the glass if half empty, grab the bottle and top it up!

[thomaskk]

Hi Lucky

I spoke to my Onc about your numbers . He has few questions

1. What was your first PCR , 3 months on Gleevec ?

2. Did your FISH ever conformed with 0 ?

3. Are you taking any antacid tab along with your TKI ?

He does not  believing on anything between 3 long and 4.5 log ( he say all the same ) . But anything above 4.5 long is first step towards cure......

According to him you are still on solid grounds

Thomas

[Skittles]

Lucky,  You have had many ups and downs in the years we have been in this group but every single time you manage to come through it ok.  This will be another one of those times.  Listen to Phil and the others in regards to not beating yourself up.  You are still in a safe zone with results so allow the doctors to  figure this out for you.  I find all too often that I am trying to figure out a way to make things better when in reality I do not have the expertise to that to begin with.  I am on several support groups for CML and will tell you that quite honestly there  are far too may folks that lose their responses after being PCRU for several years even in light of taking the full dose of the medication that had kept them there all that time.  It may have absolutely nothing to do with changing drugs or lowering dose or it may.  It is what it is....time to let someone who knows fix a potential problem and trust they will. You did nothing wrong.  We are in a time of folks lowering, changing and even coming off TKI treatment for a better life with CML. Some succeed and that encourages us and some fail and that scares us.  You were brave to at least try to better the situation of  dealing with side effects. 

Take care Lucky, Skittles

[ChrisC]

Hi Lucky,

So wonderful that you can turn to this forum for understanding and care: you know we all do; however we express it we wish you the very best of ease in dealing with CML and all other challenges in life.

For what it's worth, here is something that I find helpful. May it be of some inspiration to you in letting go of fear and anything else that might be an obstacle in your path . . .

ChrisC

http://redwoodcity-w...01&newsRef=true

[0vercast]

A PCR of 0.013% is MINISCULE. That's a deep, deep response that many of us would love to see in ourselves.

[gark]

     Dear Lucky, I feel for you.  My new oncologist reduced my GLEEVEC dosage from 800 to 400 mg in August, my PCR went from weak positive and sometimes undectable to quantifiable we are retesting again this Tuesday, and, like you I am nervousness and worried.  I was diagnosed in 2005, it took me almost two years on 800 mg of GLEEVEC to get into a safe range, and my first onc was very strict about keeping me on a high dose despite bad side effects...my new onc is very confident that experimenting will not be risky, and that I can go up to 800 again if it looks like things are trending in a bad direction.  Like you I worry about resistance, mutTion, etc.  DO NOT beat yourself up!  I feel so much better on a lower dosage.  My wife and I are finally trying to start a family, I can work full time, and I just ran my first half marathon since being diagnosed in '05!  It has been worth it to me just to feel a little bit better, less malaise, and pain, fatigue, and brain fog.  If I have to go back, that is fine, at least we have options and the possibility of cure. A friend of mine with melanoma just passed away, after brutal trials.  She ran out of options in three years, and suffered immensely through them all.

     I pray you will find stability soon!

-Gark

[CallMeLucky]

Thank you all for the reassuring messages.  As you can see I do not handle this stuff very well.  There are reasons why I don't, some I am aware of and understand, others not so much.  I know that I don't do well with uncertainty and I have trouble keeping my emotions under control.  This is a trying experience.  I don't like to think there is a reason why any of us got this illness, but sometimes I wonder if there is a reason, if it is to somehow teach me how to deal with myself better. 

The feedback I have gotten from all of you over the past few days has been comforting and I appreciate it very much.  It helps knowing there are others out there who share the same concerns, frustrations and set backs, though I do wish none of you had to experience this in your lives.

When I think about it I still get unsettled.  I know my response overall has been very good, but these test results have made me nervous.  Like all of you, I know I just have to wait for that next test result.  Although I believe it is that state of mind that contributes to the overall problem, aside from the CML that is.  This state of living from test to test, it kind of obscures the "living" part.  I spend so much time worrying about living, that I can hardly even recall the past almost four years since I was diagnosed.  So much time spent worrying, so much wasted time that made no difference to the outcome.  You'd think I would learn something from that.  Apparently I am quite stubborn, or at least habitual.

Supposedly my great-grandfather had leukemia.  No one recalls the exact type, but given his age and how many years he lived after he was diagnosed, I surmised it was likely CLL.  I was told that he was an older man when he was diagnosed and no one really told him what was wrong with him.  They just let him be, told him to take some medication each day and he went about his life.  When I found out I had CML I devoted myself to learning as much as I could about the illness.  I've read so many studies, books, and articles.  I've spoken to so many experts and attended many events on the topic.  Sometimes I wonder if no one had told me anything and just got me to take a pill each day what a difference it would be.  I've become the embodiment of this disease and when I'm not worried about this, there is something else usually in its place for me to fret over.  Perhaps I need to meditate on that for a while ......

Thank you all, I wish each of you peace and good health.......