16 replies to this topic

[Tedsey]

My logic says, the higher the WBC at dx, the higher the leukemic burden.  However, this does not always appear to be so.  I just read about a patient dx with WBC around 450K, on hydroxyurea for 3 months, and was PCRU within 4 months on Gleevec, (so this person reports).  Aside from other variables, like undetectable mutations, one's biological response and synthesis of said TKI, I have read about people who had WBC and are not even at MMR years later.  So why does this happen?  It also seems that people dx with lower WBC have a faster response (especially on Gleevec).  Thus, continued success on G = success overall (so it appears). 

From what I read, people who respond fairly quickly generally do the best overall (but G has been around longer than the other drugs, thus studied more).  And Sprycel seems to produce a speedy MMR in many as a first line therapy and also for those who have a slow response to Gleevec, (esp. on this site).

So, is it possible that a high WBC at dx does not mean a high PCR?

My PCR at six months was 13.something %.  Since I have no dx number, I assume my leukemic burden was much higher than most CMLers at dx.  Perhaps higher even than those dx with much higher WBC?  A higher leukemic burden at dx, possible mutations, or my body just does not synthesize the TKIs with great efficiency, are the only things I can come up with as to why some people with higher WBC at dx sailed to MMR or PCRU as opposed to moi.  Any thoughts?

So confused,

Teds

P.S.  Of course, this is all about me, but I was just wondering what the current thoughts are (if there are any).  I was dx at 180K, given hydroxyurea for about 3 weeks, then given G, 400mg.  My PCR stopped moving at 9 months, so I was switched to Sprycel.  I reached CCyR at 1 year (after 3 months on Sprycel), but things are going very slowly, (I have been dx with CML for 19 months now).  Just cannot help but wonder why others on this site, who were dx with higher WBC are now MMR or PCRU (and at least 1 person is at less than the standard dose of Spycel and having success in less than a year----I am a slug at the average dose of 100mg).  

[jjg]

Hi Teds,

Yup it is perfectly understandable that you would like to know why you are a slug. You've heard this before but as long as you are moving forward in the right direction....blah ba blah

I was dx with almost normal WBC 13,000 and because I did 2 IVF cycles (to preserve youngish embryos) it took 2 months to start treatment. During that two months my WBC dropped back into the normal range. I had a 2.2 log reduction at 3 months so at this stage I fit the low leukemic burden good response curve. My hem told me that catching it so early meant that I had a lower chance of further mutations but that that was all it meant and that everything else was drug response. I guess that makes sense in that nearly everybody reaches CHR within weeks. I had a few weeks head start so it will be interesting to see if I still have a good reduction between 3 & 6 months.

I was interested when you said that you may not synthesize the TKIs efficiently. Have you ever had a drug concentration test? I had one with my 3 month PCR.  It was not a standard test and it had to go off to a research lab to be  processed. Unlike all my other tests it wasn't covered by medicare  (Australia) but it was not too expensive ($60) especially as they seem  to have forgotten to send me the bill. Anyway it might be interesting to  know if you have lower than average blood levels. I did actually have slightly  lower than expected levels but my response was good so the  conversation moved on. We did the concentration test to see if I could drop from 600mg gleevec to 400 - the result being that I'm on 600 for now. When I see my hem in two weeks I'm going to ask  if I might be eating the wrong stuff with gleevec. I guess in terms of your anemia you are maxed out on the dose so knowing concentration would just be of interest.

The question you have asked does have a statistical answer. I expect that the person with WBC of 450 with PCRU at 4 months is about 3 standard deviations outside the mean. You also might be on the other edge of the bell curve. Anyway thanks for posing this quesion - be interesting to hear what the experts say.

J

[Trey]

Generally, a lower WBC at diagnosis is considered better.  But my WBC was 100K and my diagnostic BMB and FISH were both 100%.  Those with a 450K WBC were also 100%.  What does that mean?  Dunno.  Some with low WBC respond quickly, and some with high WBC also respond quickly.  Others in both categories do not.

Response to TKI drug therapy is an inexact science.  The reasons for such a wide variation in response rates is not well understood.  There is uptake from the GI tract into the blood plasma, then there is uptake from the plasma into the WBCs.  Both must be efficient.  Then the cellular processes come into play.  JJG mentioned the plasma testing, but the more important issue is getting the TKI into the progenitor WBCs, which is where it does its work.  TKIs in the plasma are useless unless they get inside the WBCs.

Some people who were in the original IRIS trials starting in 2001 are just now reaching PCRU after 10 years on Gleevec.  Some might conclude that such an outcome, although not alacritous, does not suck.

[GerryL]

alacritous - I had to double check that I had the correct meaning for this, in the dictionary; now I've just got to remember it and throw it into a conversation occasionally.

[Trey]

Don't try this at home.  Especially if you are Australian, and prone to...how did PhilB put it....a distinct lack of tactfulness.  Oh, you are Australian.  Oops.

Those who like "alacritous" (speedy, quickly) may also like:

Sanguine (Tedsey): having blood as the predominating humor and consequently being ruddy-faced, cheerful, etc.*

Circumambulate (PhilB):  to walk or go about or around, especially ceremoniously.

Polyseme (?): a word or phrase with different, but related senses.

* See, it really is all about Tedsey.....

[GerryL]

I blame it on our colonial background.

Here's my word

Epignosis (Trey): full and complete knowledge - or should that just be "full of it".  

[PhilB]

If it's sesquipedalian words you're after, then I would suggest 'Valetudinarian' - a person excessively concerned with their health - which covers just about all of us!

[Trey]

So as you can see, Tedsey, it really is all about you.

[CallMeLucky]

I would only add that you should take individual's statuses posted online (along with how they do with side effects) with a grain of salt.

[Tedsey]

Aw shucks Billie, thanks for the support.  The guys are just being supportive in their own way.  I am used to it and they often make me smile.  I have to admit, it looks like I am a 1/2 log away from MMR (I think, looks that way from the graph).  So, I am not so bad off unless things go north by this August.  Got a BMB coming up.  I am feeling well, despite a slight cold.  Hoping it is not West Nile.  I was just eaten alive by the most ferocious mosquitoes in the garden.  They bit me on my eye-lids because I had bug spray on (so much for the Gleevec puffiness, this was way worse).  When one gets in the house, it feasts on me.  I look like a leper because I have such a bad reaction to the bites (no, not because of the TKI, I have always had this reaction, so does my 2 yr old).

Funny you mention chin hairs.  I am fair and naturally blond.  However, every once in a while, I get a spiky white hair on my chin.  I also rush to pluck it out.  In the position we will be placed in the coffin, it does not bode well for excess facial hair, (I would like a closed casket ceremony anyway).  But I think I would really like to donate my body to CML research.  So, who cares if the med students, et.al. see some spikes.  When I worked on cadavers, we always covered up their faces and genitals out of respect.  Not so worried what people think of my body once I am dead.  You could always threaten to haunt your sister if she forgets.  Kicking the bucket aside, may you and I have many decades ahead of plucking out our own chin hairs before we ever have to worry about this.  By then, we will be too old to care.

Teds

P.S. I had no symptoms before dx. BUUUUUT, I had extreme weightloss just after my first baby.  Went to my doc and specialists for 3 years.  No one could find anything wrong.  Sooo, right before I was due for my yearly check up in 2009, my abdomen swelled up, so I was able to get an earlier appt.  Good thing.  It was my spleen.  The rest is history.  And I know this is baaaaaaad, but I have not made an appt. for a yearly checkup since I was dx.  I used to be so militant about my health.  So much for preventative medicine...  Didn't work for me.  My internist actually said to me that "This shouldn't be happening!"  "You were one of my healthiest patients."  She is really big on preventative medicine and we talked so much about it in all the years I had seen her.  She told me that she was soooo sorry.  Whatever...  Now I am scared to know what else might be wrong with me.  But I am sure I will eventually get up enough courage to go. 

[GerryL]

Our little turtle is slowly making her way to an MMR, hopefully that will be the outcome at your next BMB, or at the very least closer to it.

[acb]

It all doesn't make a lot of sense to me either. My WBC at official diagnosis at the cancer center was 149 and my platelets were 1300. However, the day before at my doctor's office, my WBC was around 123, and then it was around 134 at the ER (where they sent me) 3-4 hours later. Even with WBC at 149k, my FISH showed only 85.5% leukemic cells (from PB though, not BMB). I have no idea why it wasn't 100%. I was very fortunate to respond very quickly to hydroxurea and also to Sprycel. I have no idea why I responded so quickly.

My side effects are not too bad, but they do go in cycles. What I find interesting is that I felt my best in a long time while we were traveling and while we were at Disney World. I was dreading going, because I was worried about muscle pain and fatigue. It was a 15+ hour car ride one way, and we were on the go non-stop for 7 days while we were there. I felt fine the entire time, luckily. I am not sure if I felt so good because of all of the exercise or because of the change in environment/climate. Sorry to go off topic -- but my point is that it all seems so unpredictable to me and there appears to be no rhyme or reason for some things.

I hope you continue on a successful path to MMR, Tedsey!

[GerryL]

I think mind set has a bit to do with it. I took an overseas trip to San Francisco 3 months after starting Gleevec - spent 12 hour days walking most places.  So having your mind busy elswhere and falling into bed at night too tired to think about your CML all add up to having a good holiday with CML.

[Tedsey]

Thanks acb!

I got another question, but it might be best addressed on another thread.  Is there any info out there regarding PLT count at dx?  I had above normal PLT at dx, but they were closer to normal than a million.  However, my WBC were high (180,000).  My PLT seemed to be very low compared to what is usually found with high WBC.  I always thought this was unusual.  The combos of low WBC and high PLT or high WBC and lower PLT, etc... is baffling.  What does it all mean?  Ahhhhhhhhhh!

Teds

[CallMeLucky]

I'm not so sure it means anything.  Blood counts fluctuate, and they do not appear to be directly tied to CML burden.  The molecular tests seem to be the definitive there.  If we think about the mechanics of it.  CML cells produce BCR/ABL, an oncogene that tells the body to keep producing white blood cells.  Reason suggests the more BCR/ABL the higher the WBC, but I am not so sure that is the case.  It could just be that your body was more sensitive to BCR/ABL and produced more cells.  I don't know enough about molecular biology to really discuss this, but it seems to me that the simplified model of higher counts means more leukemia may not hold up.  I'm guessing it is more complicated than that with various factors that influence the situation.  Some may be known, others may not be known.

I think it is important to understand the past, but at the same time it is important not to get caught up in the past for the purpose of trying to predict the future.  Unfortunately it doesn't seem you can predict how it is going to play out.  Some people respond well and some don't.  Some appear to do well then suddenly go bad, some drag along, some have a really hard time and then eventually persevere.  On one hand I wish I could predict how its going to turn out, but on the other maybe I don't .  I think all that matter is how you're doing today.  Are your counts acceptable?  Are the drugs keeping your disease under control?  Are you able to live your life with reasonable quality?  If the answer is yes, then I think we just have to accept that and make the best of it.

But I do understand the desire to dwell on it..........

[Trey]

When blood counts get "leukemic high", the body fights hard to lower them.  The spleen "eats" as many as it can (which is why it gets so large -- kind of like when PhilB finds Bon Bons...).  Anyway, this frantic action causes wild swings in blood counts.  The WBC and platelets could have large swings in a few hours.

It is also worthwhile to remember that PCRs fluctuate in a similar fashion, and there are also more variables in the PCR numbers (more ways the sample can become degraded due to shipping time, and more errors that can be made in the lab, besides what is going on in the body).