35 replies to this topic

[pammartin]

This question is directed at anyone and everyone.  After six months of reading I am still confused at what level of response is considered acceptable, and if a person can hover in the areas of 10-20% PCR (just an example number) and still be considered responding.  I have read about leveling out, holding at a lower number, and not reaching PCRU, but I have also ready that even the lowest test does not reveal all leukemic cells so the lowest PCR test although accurate is only as good as the level it is tested for.  If a person reaches a three log reduction but never goes below 11%, is this acceptable or are they still considered high risk and need to change drugs or once again speak of transplant.  I am not speaking about the possibility of mutations, I suppose that is a factor also, but for now I am trying to understand this part of the testing and positive results.  Is there a guideline for the lowest result a person should be achieving in a time period or can they hold at a low level and be as healthy as possible and continue the drug therapy.  I do understand changing labs makes a difference, but I am basing my questions on using the same lab and the same drug over a period of time.  The lines are probably very clear, but I continue to experience confusion on the over all process and what is considered positive continued results.  As I read and learn I admit to being less than inclined to be overall concerned with the PCR test, I realize it is important, but because each lab is different, the testing is not as precise as I previously believed.  On that note, another question, why is it the labs do not follow a baseline for testing, or would this be impossible from lab to lab.  Also, do the mutations exist from the beginning or do mutations develop throughout the length of the disease, or are both scenarios possible?

Thanks in advance for any responses, thoughts, or facts, some of these subjects continue to be Greek to me and I have this need to clarify things I do not understand.

Pam

[Tedsey]

Hi Pam,

The kids are still asleep and I saw your post.  I am post dx 2.5 years.  As like you, much of this is Greek to me, but clearly it is learnable since Greek is still a surviving language.  Thank goodness we have so many knowledgeable people on this board.  Anyway, from what I understand, and what others have been telling me, in terms of survival, having a complete cytogenic response, and to hold it, is acceptable.  If a patient's PCR does not go up steadily using one lab, then as long as a patient is stable, the disease is not progressing.  Loss of a CCR is a problem, or never attaining it while on drug therapy.  The rest is, as I understand it, deepness of response.  For example, MMR,(which seems to be a wide range depending on what you measure it from----your number from dx or a lab control gene), and PCRU status. 

As for the value (figuratively) of the PCR test, it is the least invasive way, once a person attains a CCR, to monitor residual disease, (I guess a BMB would work, but could not quantify the fusion protein, BCR-ABL, which denotes CML).  Again, as long as the PCR value is not going up consistently at one lab, stable = no disease progression.  As for the accuracy of the test, from what I have learned, it could have a margin of error from .5 to 1 whole log.  So, if a patient has a 1 log increase, the PCR should be run again to see if the same thing happens (errors happen, blood samples get degraded, etc.).  From that point on, the onc will decide, hopefully taking the patient's history with the disease into account, what to do (ex. wait, order a mutation test, switch drugs, etc.). 

You ask, "...why is it the labs do not follow a baseline for testing.."  Well, I understand labs all have a control gene they measure the PCR value against.  Why is this different from lab to lab?  Not really sure.  Probably political.  I believe people in the business of developing PCRs all want to push their bigger and better machine, or in the case of universities, they can develop their own cheaper (probably--but that is just my guess).  Maybe they put a few grad students on it.  Who knows?  Aren't the students, (undergrad included), the ones who run our PCRs?  Anyway, I do not understand when people report percents (like you did writing "10-20% PCR"--that is Greek to me).  And I have a scanty knowledge of the Int'l scale.  So, sorry there.

I have also been thinking lately about your question about the mutations.  After 2.5 years I have come to believe that the mutations are there from the beginning (but who knows, with more reading, I could change my mind next year).  I think that is really an unknown.  But it seems to me that if the TKI is effective clearing out the lower-level leukemic WBC, (from what I understand, there are more of the lower-level WBC proliferating since the LSC, leukemic stem cell, divides into two daughter cells, and so on), the cells that are left are higher-order leukemic WBC.  This is where the known mutations, if detected, will be found.  And that is when a patient will show signs of losing response (unless they progress overnight into Blast Crisis, which happens, but is rare).  So, as I understand, the TKI clears out the lower-order leukemic WBC first.  What is left is the higher-order ones.  If they have mutations, this is when they will be detected.  Sorry, that was probably redundant.  But this is what I have come to understand at present.  But I am always open to correction.

Sorry for the long response.  However, it is not an easy subject to explain in a few words.  Hopefully someone else who understands more will also respond.

All the best and an excellent response to you!

Tedsey                

[pamsouth]

Tedsey,

Thank You so Much for your response to PamM.  I only had time to quickly skim thru your reply. When I get back from Physical Therapy.  I got some more question for you. 

PamM is really helping with these question. Sometimes hard for me to put in to words as it is sort of like putting a puzzle together.  I stayed up most of the night reading thru Treys stuff, you know the Genetics  and all and some other articles I think by Lucky or Scuba.  Seems the more I read the more question I have. I even google some words and how to pronounce them. I am getting there.  I want to be somewhat profient at the knowledge of CML from that first stem cell, on down, so that the questions I ask doc are not foolish and he knows I understand what I am saying.  I Don't go back to the Onc until June, but I really want to be up on this.

Got to run.

PamSouth

[pammartin]

Thanks Tedsey,

I agree with Pamsouth, the more I learn the more questions I seem to have.   I am under the same impression as you for the mutations, they are not usually created, but are present in some form from the beginning of the journey.  But as you stated, my opinion could change as I learn.  I am curious to what would be acceptable, most people I speak with share their docs want them to have fast hard results, even if a break is needed from the meds after the drop.  I am still questioning the idea falling steadily would be heathier for the patient than a slam dunk.  I am going to have to read your post again, and go through it piece by peice, so much information is hard to digest at one time because my mind keeps asking more questions and I confuse myself

I have a story to share; I had asked the dr's office to send me a hard copy of the PCR from April 13, to say the least today has been interesting.  Long ago I was told I was in the accelerated stage, but no blast cells were found in my results, I can't remember if it was Scuba, Phil, or someone else, but one of these guys said the doc needed his ears boxed for scaring me half out of my wits (easy to do because I have little some days).  Anyway I had a msg last Friday on my answering machine it stated my results for PCR this time were 0.010% a short jaunt from the 0.004% they were in January, a private message to Trey to make sure everything was ok and I posted my results.  So today when I grabbed the mail I noticed I had the letter from the doctor.  I had to open it, even though I knew the results.  The message is still on my answering machine from last week, I came back in and listened to it again after reading the test results, just to make sure I had not heard incorrectly last week; I did not, clearly states 0.010%.  The hard copy test reads,

The quantitative RT-PCR assay is negative for the b2as, b3a2, and e1a2 fusion gene transcripts found in chronic myelogenous leukemia and Philadelphia positive acute lymphocytic leukemia.  These results do not rule out the presence of low levels of BCR-ABL1 transcript below the level of detection, 0.001% of this assay, or the presence of rare BCR-ABL1 transcripts not detected by this assay.

Geez, I am undetectable according to my lab!  I am assuming the nurse who called just mixed up the numbers, but to someone who is waiting on these results, it could make a heck of a difference.  If I had not started asking for copies of test results I may not have known this until my next appointment if at all.  I continue my quest to learn all I can (even if it is written in Greek), thanks for the info, I am off to pick it apart and then probably ask a ton more questions!

[GerryL]

Hi Pam,

For me I figure you can't argue with what's in the report - Congratulations. Getting out of my chair at work and doing a happy dance for you as I walk to the kitchen at work for a cup of tea.

Originally when I mentioned to my doc about a possible dosage reduction if I could get to PCRU and maintain he told me "you've got to keep hitting the leukemia hard" - I was MMR at the time. When I got my PCRU he has come around to the idea of a maintenance dose - though we haven't really discussed when I could start. I have had my blood taken yesterday, so will see in two weeks if I am maintaining it, then I am going to have a conversation with him about starting a dosage reduction straight away if I have - down to 300mg Gleevec.

[ChrisC]

  U N D E T E C T A B L E ! Yay!  

[Lizzybee]

Congratulations on reaching pcru so fast!  Even .010% is an excellent result. On the IS, 0.1% is a 3 log reduction, so .01% would be a 4 log reduction.

In the original post, you asked if it's okay if a person has a 3 log reduction but never goes below 11%.  It would be impossible to reach a 3 log reduction without going below 11%.  One log = 1/10.  If a person starts at 100%, a one log reduction is 10%, 2 log is 1%, and 3 log is .1%.  So I would think a person who never goes below 11% may not have a very good long term prognosis.

I was disappointed not to reach a 3 log reduction yet at my 9-month appt.  From my reading and watching videos online, it seems that the people who have the very best long term prognosis are those who reach a 3 log reduction within a year.  So I am hoping and praying to be there in July.

[pammartin]

You know GerryL, that is what I am going to do also, I have a time frame in mind and then a dosage in mind and although this is all new, and I will bide my time, I am also on a mission.  I know I will have to change docs to reduce, mine just does not know much beyond the basics and transplants, so I will be happy 'on hold'.  Thanks for the happy dance, I think I am still in a bit of shock, I mean I was happy with the 0.010% .

[pamsouth]

Hi Tedsey, Trey, or anyone, anwhere who would if up for the challenge, me.

Sorry I have no idea if I am on the right path, but I am making a stab at it.

it is 9:30pm and I am a bit tired from staying up into the wee hours this morning, reading some of these articles and charts.  I am 64 years and just a little slow at understanding all of this.  Will have to get to bed early tonight, got to start out early tomorrow and bright eyed and busy tail.

I had a list of questions in my mind yesterday but they have left. 

Anyhow I am looking at a chart by Call Me Lucky or maybe Scuba.  I also have an article I have printed out by Trey called Genetics of CML overview.

To bad we don't all have a projector or something to look at while someone explain all of this, right?

OKK... at the top of the Chart I am looking at is the,

1)        LT-HSC + Long Term Hematopietic Stem Cell, she would be the ancient mother stem cell, (don't know why I am calling her She.)  Anyhow She LT-HSC is freshly created from the bone marrow, the # 1 stem cell in hierarchy,  yes?   At this point there is no CML, or any kind of blood cancer, she is a good stem cell?  Correct?

2)    She LT-HSC produces two daughters called ;

ST-HSC = Short Term Hematopoietic Stem Cell, right?

3.  Now it would be these two daughter's of LT-HSC, the second generation, called the ST-HSC, that create an error of some kind, between her, St-HSC and the next level of MPP = Multipotent Projentiors. RIGHT?

Now I am looking at Trey article on Genetics.  quote "To expand on the subject, these blood stem cells are divided into categories such as CD7, CD34, CD34+ CD38 -, etc. WHICH INDICATE DIFFERENT TYPES OF BLOOD STEM CELLS BASED ON WHAT IS ON THE CELL SURFACE CLUSTERS OF DIFFERENTIATION — CD).""  OK I am trying to figure the pecking order here and where the first error occurs.  Are these compartments, CD7 Cd34 etc, of the LT-HSC and/OR THE ST-HSC or what??? 

While we are here at the top of genealogy  of the stem cells between the 2nd and 3rd generation.

2. Are these compartments such as CD7, Cd34, etc where the transcript error occurs before going down to the next level MPP??? or does the error occur in the case of CML would be at the next level, CMP side = Common Myeloid Projenitors. 

I hope I am making some sense I am trying to figure where or what level the transcript error occurs and if it is in these compartments, CD7 etc.

Also with the question above where does the PH+ begin?? Because first of all we have a transcript error that create the CML, then somewhere we have the start of PH+, right?  Common sense would tell me the PH+ has to at least start at the CMP Common Myeloid Projenitors because the Ph+ effects the red cells, the platelets and the white cells or granulocytes.

Now at the point of CMP = common myeloid projenitors these guys/ladies are nucleus, meaning they have the 23 pair of Chromosomes. So I would be assuming that again the PH+ is somewhere here at the CMP level? 

Now at the next level MEP (not sure what MEP stand for) The Erythorocytes, that makes the Red Blood Cells, and the Megakaryoctye that make the platelets. The red cells and platelets are no longer nucleus but the CML has affected them (as I had 2 million platelets at diagnosis). And the PH+ started at either the MPP or the CMP level, therefore the PH+ has effected the red cells, the platelets and of course the white cells (made of granulocytes basophil, neutrophil eosinophil) The white cells/granulocytes, which are nucleus, therefore they multiply and make copies with the PH+ BCR/ABL.  

Next Very Important Question, it is at the level of either the CMP or down a level at MEP AND GMP that the TKI works???  Which ever level CMP OR MEP / GMP THE TKI never reach the transcript error at MPP OR ST-HSC WHICH EVER IT IS, because at this point I am not sure at what level these thing happen at.

Next very important question!!!!!  At which level do mutations occur???  Are these mutations that doctors speak of on the PH+ like are we talking about the P210 breaking point, etc or another chromosome?  Or are the doctors referring to mutations at the higher level of ST-HSC OR MPP??

I Think if I could understand the above it would answer a lot of my question about the TKI and decisions I need to make going forward.  I mean really I have that sometimes when you or doc make a bad decision sometimes there is no fixing and a lot of needless suffering and consequence.  Doctors after different theories, but I am the patient and I would like to undestand it enough to make some intelligent decsions.

Does this make any sense? 

PamSouth

[pammartin]

Lizzybee,

I see what you are saying about the 3 log reduction, I was just pulling a few numbers out of my hat to try to wrap my brain around the entire process.  I understand your disappointment, but I am a believer is slow and steady also, so as long as the numbers are going down, it is a positive.  I have read many stories of people who go up before they start down, and then slowly creep toward PCRU.  Don't give up, I am a firm believer in positive thinking!

[pammartin]

Thanks ChrisC!

[GerryL]

Hi Pam,

I think it helps to have a plan, makes you feel a bit more in contol of things, when a lot of it is out of our control.

[pammartin]

GerryL,

A plan is never a negative thing, even my plans (I fear my husband might disagree at times)

[pamsouth]

pammartin wrote:
Thanks Tedsey,
I agree with Pamsouth, the more I learn the more questions I seem to have.   I am under the same impression as you for the mutations, they are not usually created, but are present in some form from the beginning of the journey.  But as you stated, my opinion could change as I learn.  I am curious to what would be acceptable, most people I speak with share their docs want them to have fast hard results, even if a break is needed from the meds after the drop.  I am still questioning the idea falling steadily would be heathier for the patient than a slam dunk.  I am going to have to read your post again, and go through it piece by peice, so much information is hard to digest at one time because my mind keeps asking more questions and I confuse myself
I have a story to share; I had asked the dr's office to send me a hard copy of the PCR from April 13, to say the least today has been interesting.  Long ago I was told I was in the accelerated stage, but no blast cells were found in my results, I can't remember if it was Scuba, Phil, or someone else, but one of these guys said the doc needed his ears boxed for scaring me half out of my wits (easy to do because I have little some days).  Anyway I had a msg last Friday on my answering machine it stated my results for PCR this time were 0.010% a short jaunt from the 0.004% they were in January, a private message to Trey to make sure everything was ok and I posted my results.  So today when I grabbed the mail I noticed I had the letter from the doctor.  I had to open it, even though I knew the results.  The message is still on my answering machine from last week, I came back in and listened to it again after reading the test results, just to make sure I had not heard incorrectly last week; I did not, clearly states 0.010%.  The hard copy test reads, 
The quantitative RT-PCR assay is negative for the b2as, b3a2, and e1a2 fusion gene transcripts found in chronic myelogenous leukemia and Philadelphia positive acute lymphocytic leukemia.  These results do not rule out the presence of low levels of BCR-ABL1 transcript below the level of detection, 0.001% of this assay, or the presence of rare BCR-ABL1 transcripts not detected by this assay.
Geez, I am undetectable according to my lab!  I am assuming the nurse who called just mixed up the numbers, but to someone who is waiting on these results, it could make a heck of a difference.  If I had not started asking for copies of test results I may not have known this until my next appointment if at all.  I continue my quest to learn all I can (even if it is written in Greek), thanks for the info, I am off to pick it apart and then probably ask a ton more questions!

Wow PamM from the msg of .01 to a .001%,  I would say a toast in order with a little celebration!!

I forget what dosage of Sprycel you are on and when you started? Just wondering how the side effects have settled in?   I see you are already spinning your wheels as to your next step.  Good for you!! You have got my curiosity up at to your mission and what doc you decide on choosing?  I will be anxiously awaiting to hear....  Hum.... not so boring anymore! Stir up a little dust, and don't look back at that doc!

PamSouth

[pammartin]

Yeah, the nurse just made a mistake, but what if it were a higher number, I will mention this when I speak to the office about the idea the doctor will actually be present when I come for next appointment.  I still fight the side effects, I am doing well on the Ritalin, but I have learned it does not work when I am having a slow day(s).  It seems like the Ritalin just tries to get me moving and instead just makes me anxious.  I am going to use it in moderation, this way I can try to regulate my response.  My side effects honestly come and go.  I went for a few months without almost any symptoms but they are beginning to rear their ugly head again.  Small Sprycel headaches, the dreaded red rash on my face, and for some reason my left ear sometimes seems like it is on fire, looks like it also, the heat is apparent even to others.  The interesting thing about these side effects is they occur about 2-4 hours before my next pill is due.  I usually take the Sprycel around 5 to 7 every evening.  I still battle the tired and fatigue, but I have decided it is something that is going to be a part of my new life with CML.  My mission is simple, if I continue this trend, I am going to reduce to 75 mg of Sprycel, and if that works for a period of time, (yet undetermined) I am going to try to reduce to 50 mg and if it works, I am hoping I will be comfortable with that dosage for long term.  Everything is very new and I have a way to go, but a goal is always a good start, and I am looking forward to more milestones and reaching my goals.    (And continuing to be very very boring to all doctors)

[pamsouth]

PamM

Isn't it Scuba that is down to 20 mg on Sprycel?   Now that would be cool 20mg!!  I don't remember if he has any  side effects or if his CBC are all normal.  I am sure that he mentioned taking the Curcumin and I believe Scuba said he takes the Curcumin with the Sprycel and it helped him to get him low counts.  I think his doctor agreed with him, too.

esterday I bought 2 bottles, (nataure's Way) Tumeric, each bottle has 60 tablets.

The label on the back says, 95 % Curcuminoids & Tumeric root 50 %.

Do you really need the Ritalan? I mean that is another chemical with the Sprycel. Regarding the side effects, I know it is different for everyone, but on Gleevec it was pretty much that way for me for about 2 years, up and down, and in and out of the hospital. Gleevec was all that was out in 2005 and now I have pretty much gotten use to it, me and Gleevec have made friends since them days!   Seem like after I had my Gall Bladder out things started to get better. The surgeon said my gall bladder looked normal but according to the test it wasn't working, I don't know if that was due to the Gleevec or just fluke. 

Anyhow maybe you can lower your dose now, and see how your labs level out and you will feel better!

Hope your doctor will work with you on your plan and all.

Blessing and may things be looking up for now on.  Hopefully they will find a cure, soon.

PamSouth

[Judy2]

PCRU!!!

Hugs,

Judy

[Pin]

Ye-es!

I believe some congratulations are in order! That is such awesome news and I have to say, it makes so much more sense in the context of your previous results.

Pam M - You have come so far in such a short time, wonderful - enjoy!

[Tedsey]

Dear PamSouth,

If we could answer all those questions, I think we would have a cure on our hands.  Thanks for putting my name beside Trey's, but I am afraid my knowledge is too limited.  Nevertheless, I think you are headed in the right direction, aside from getting a degree in cellular biology and genetics .  What I mean, is by trying to understand this CML animal the best you can.  You seem pretty darn educable (smart), so don't use your age as an excuse.  This is complex stuff for anyone.  

Sadly, some oncs, in real life, do not know how to treat this disease, but play the part on TV.  For us, I think it is a delicate balance of education and "feeling right".  Don't get too bogged down in cellular details.  I don't  think anyone has really been able to identify the highest order stem cell with certainty yet.  Lots of conjecture, but good and educated guesses, (I hope).  Anyway, it is kind of like astrophysics and the string theory.  Strings may be the smallest pieces of matter (we will leave the God particle aside for now).  A few scientists worked out the same equation in different parts of the world at different times that support their existence.  But no one has yet to "see" one. 

Good luck!

Teds

[Tedsey]

Yessss!  Congrats on a great response. 

Take care!