18 replies to this topic

[JJR]

Hello,

It has been awhile since I have posted.  I am a 40 year-old male diagnosed with CML in 3/09.   I have had many ups and downs since my diagnosis in 3/09.  I just switched to Sprycel b/c Gleevec 400 never put me past hematologic remission, Gleevec 600 took my absolute neutrophil too low, 800/900, and Gleevec 500 had promise for only a month or so, then took me down below 1,000 again.  I did have the blood level test before going to the 600 mg b/c I was not getting maximum benefit.  The only good news from my Gleevec experiment was that despite the low absolute neutrophil counts, I did finally get to minor cyctogenic remission at 1.5 year mark.  My doctor who is in his 70s is quite conservative and didn't take to my eagerness to try Sprycel back in 3/09 but then the New England Journal of Medicine study came out this last summer and Sprycel became the way to go.  I  have now been on it for 1.5 months, have shortness of breath, teenage acne but no more cramping!  Despite taking a 1.5 month break before starting Sprycel and getting my WBC up to mid-normal, I now once again down to about the 1,000 mark for my absolute neutrophil count. 

Am I failing on Sprycel?  My doctor suggested I may just run low on TKIs and this is going to be my normal.  However, he is also willing to switch to the last of my medication options.  Any advice? How dangerous is it having a chronic low absolute neutrophil count?  How long should I experiment with Sprycel before I switch again?  Are there other medications I can take to boost my WBC and ANC so I can stay on Sprycel?

Thanks for any advice/feedback, I am continously amazed by the great info on this listserve.

JJR

[rct]

My wife has had consistently lower than the average bear WBC/ANC for 20 years.  Started Gleevec in 06 and had to have neulasta right away.  That worked, WBC/ANC remained consistently lower than the average bear, but nothing to be alarmed about.  So that woulda been 3000WBC/1500ANC, right around there.  Two years and PCRu later, WBC/ANC tanked, and without another long explanation, today still weekly shots of Neupogen to keep those two counts up.  For the official record, from our oncs here on the east coast, and from Druker to us in May of this year, it is not Failure, it is an unfortunate consequence of the TKI.  They seem to have no trouble with her being on Neupogen for years to come, as long as PCR stays good, which it has so far.

Interesting how these threads come up on the days they do.  We are off to the CancerSuperStore this afternoon, so this stuff is freshly gobbed into the front of my head.

I think of you all everyday.  Tedsey, I'm too grumpy to be a cheerleader, but Rah Rah Rah.

rct

[Trey]

As already mentioned, you will want to give your body time to adjust to Sprycel.  If Sprycel works well against the CML, then you may be able to reduce dosage to help with the low counts issue.  That is a balancing act that your current Onc does not seem well suited to accomplish.  If that turns out to be accurate, it were me, I would look at getting a new Onc who is more flexible.

[simone4]

rct, after reading your post, I noted for the first time your mentioning your

wife's WBC has been historically low. Mine as well. Even 20 years ago,

my WBC was around 3.0 -3.5. My ANC was generally low as well.

I'm almost two years from dx. and my counts are tanking even on 300mg.

of G. There were normal for six months or more, not now.  WBC 2.1

ANC  1.2. I remembered your 50% theory and it made me feel better.

No mention of Neut. shots yet, but I may be following the same pattern

as your wife. However, I am not PCRU. But my onc/hem will not up

my dosage for fear of  lowing them to dangerous levels.

I follow your posts and the info you bring to the board is relevant.

Let us know how the day at the Cancer Center goes today.

I wish only the best for your wife. She sounds like a trooper.

Simone

[rct]

Thank you Simone4.  I think especially her, and all of you, are Troopers.  I hope your counts stay right where they are, we would like to have a 2400/1200 without intervention.  And I hope you have continous low PCRs and a PCRu in there once in a while.

rct

[JJR]

RCT,

Thanks for the info, I hadn't heard of neupogen, I wonder if that is something us CML'ers could take to boost our counts.  I am sorry to hear that your wife has had such a long struggle but it is good to hear that one can trudge on with low counts.  Has your wife had to make any lifestyle changes to ward off infections that she might recommend? Cheers.

[rct]

The idea that low anc causes illness just isn't accurate.  My wife has had sub 600 ANC for years, and I've been sick way more than her.  Since the whole mess started she has had exactly 1(one) cold.  Our oncs and  Druker both have patients with way high normal WBC/ANC that get everything that comes down their streets, in fact, more patients like that than like my Mrs.

Neupogen is pretty well documented, it is used for hepatitis patients and also for chemo patients that need to get their counts back up.  It is its' own set of problems and we aren't happy at all that this is how it is, but this is how it is.

Good luck with it JJR. I hope your counts manage to stay above 1k and keep you off of any grower, while maintaining low PCR numbers.

rct

[JJR]

Thanks Trey,

I am Onc shopping b/c my Onc is semi-retired and always on vacation.  Good guy, experienced, but working in an overwhelmed managed care setting.  I am always so conflicted about my medical care b/c I have such a low co-pay, $15.00, for my meds, my testing (BMB, cytogenetics) is "free," and my results for my WBCs come back to me online in less than 24 hours but the doctors themselves are not really specialists nor have time to really become specialists in any one area.  Continued congrats on your sustained success with "G", that's got to feel encouraging.  By the way, have you seen the 44.4% 5 year survival rate for CML'ers posted on this website under questions and answers?  Seems to be a bit low for my taste, wondering if it is outdated?

JJR

[PhilB]

Oops.  That is seriously outdated and would be a pre-Gleevec figure let alone a current one.  Anyone (ie Trey) know how we get that sorted?

Current figures are more like 95% survival rather than 45% with 5 year rates virtually identical to 10 year rates and so on.

[JJR]

Thanks Phil,  I also just found this abstract, way more encouraging...

I have notified the LLS about these stats...not sure what they will report b/c of their protocols but they said they will make changes this week.

Jim

Bumbea et al. (2010) J. Med Life

Abstract:

Chronic Myeloid Leukemia is the first malignant disorder with a specific genetic abnormality in the background. Known as a disease with an inexorable progression to acute leukemia for many years, its natural history has been dramatically improved by the use of tyrosine kinase inhibitors (TKI). They represent the first molecular targeted therapy addressed to a neoplastic disorder. From these new classes of drugs, Imatinib was the first drug ever used, and it remains the standard therapy for patients in chronic phase with CML, having a global survival of 86%, for 7 years. The 2nd generation of TKI (Dasatinib, Nilotinib) is indicated for the patients who are refractory or intolerant to Imatinib. The other TKI have good promises to be efficient on the mutations of BCR-ABL transcript, especially to non-responsive T315I mutation.

[CallMeLucky]

This interview is a few years old, but I found the explanation by the doctor about "Survival statistics" informative.

http://www.cmlinfo.org/juckett.html

[PhilB]

The statistics are tricky little beasties and you can argue for various different numbers.  The key thing to bear in mind with that 86% 7 year survival figure is that it's very much a Glivec-or-transplant-only figure as 7 years ago they were the only games in town.  You therefore have to add on the fact that about half of those for whom Glivec doesn't work or isn't tolerated do well with Sprycel or Tasigna which bumps the 'real' survival numbers up markedly.  Then you have the trial drugs on top of that.

One thing I should have said earlier of course is that phase at diagnosis makes a big difference and the 95% figure I used was for chronic phase patients.

Phil

[Tedsey]

Dear JJR,

I was dx 11/09.  Since starting Gleevec, I have suffered low WBC counts.  So, I am still waiting for my WBC to get even close to normal and a complete cytogenic response (like you, I got near one and am a slug).  Lately, I hover around ANC .6 to .9.  I didn't receive GSFs (Granulocyte Stimulating Factor) shots until I was below ANC .5 (with my current onc).   I would not live so scared with .8 or .9.  As we are entering cold and flu season, it is always a good idea to keep your hands clean and to avoid touching your face (everyone should practice good hygene despite the season or a suppressed immune system) .  And like rct said, some people don't get sick even with low ANC, (which is a guess for how well your body can fight off bacteria).  For just about everyone, it is pure luck as to what we are exposed to, but staying away from actively sick people is a good idea (or anytime, really).  Especially if you are below ANC 1.0.  I get out of a lot of family events when I my ANC is low.  You can make it work for you.  Just kidding.

I had a hard time tolerating Gleevec, and it appeared that my numbers stayed flat after a few PCRs.  Like you, it was difficult to tell if Gleevec was really working well enough, but it was not certain I was failing it.  I switched to Sprycel last Aug. with the hope for a faster response and less side-effects.  My WBC is now around 1.2-1.4, but it started to become stable before I switched drugs.  My WBC have taken a couple of pretty low dips since Sprycel, but I have been able to fight off a few viruses in a normal time manner.  I have had no problems with bacterial infections so far (they actually have to test for a bacterial infection--viruses are harder to treat and generally go through their cycle while the body's immune system kills or incorporates them--most doctors don't do anything for a virus unless it lasts too long).  So, it appears my immune system is functional for "average" bacteria and viruses.  I hope you stay healthy.  Good luck finding a new onc.  If you feel uncomfortable, that is all the reason you need to change doctors.  It has to be a good fit.

Oh, myelosuppression (low WBC) likely does not indicate TKI failure.  I guess that for many of us, it is a side-effect of the drugs we are on, but like I always say, it beats the alternative (too many WBC--which was our problem at the beginning of this mess).

[Trey]

JJR,

The 44.6% figure you refer to was not survival, it was an attempt by a so-called medical professional to sell another drug to the FDA by saying that 44.6% of those who took Gleevec became "resistant and/or intolerant" and lableled these as "unmet needs".  Any time I do not have ice cream during a meal, that is an "unmet need" to me.  I am surprised PhilB did not recall this one, since he watched with glee from the sidelines and chortled as I defended our TKI drugs from statistical gerrymandering, as stated by that so-called medical professional:

"44.6% were IM resistant and/or intolerant (as reported in the medical  chart if resistance/toxicity led to a change in or discontinuation of IM  use) at some time since IM initiation. 20%  stopped and did not restart  IM during the study period. 23% stopped IM temporarily due to toxicity (median duration 22 days), of  whom ~30% had >1 such interruption. The most common increase was 400 to 600 mg (33%); most common decrease was 400 to 300 mg (39%)."

So anyone who decreased Gleevec dosage was counted.  Anyone who ever increased Gleevec dosage was counted.  Anyone who ever took a Gleevec break was counted.  Get the drift -- statistical gerrymandering.  Useless data.

Did you find that as a posting or on something you called "questions and answers" -- what's that?

[PhilB]

Hi Trey,

I'm pleading not guilty on this one - although I wouldn't have been surpised if I had messed up as I was posting in the wee small hours of the morning whilst having a rough night with my friend Mr Glivec.  This is from question 5 in the Questions and Answers section of the LLS home page:

"What are the statistics for the survival of leukemia, lymphoma and myeloma?

Survival is measured in several ways so it is important to define each measure. The survival statistics are often presented as five-year survival, that is, the percentage of people who survive five years from the date of diagnosis. The five-year survival rates for the blood cancers (for all age groups) are: leukemia 50%; Hodgkin lymphoma 86%; non-Hodgkin lymphoma 64% and myeloma 34%. Leukemia rates by type of disease(for all age groups)are: ALL 65.3%; CLL 74.8%; AML 20.7% and CML is 44.4%. These figures differ for children ages 0-19 and people over 75. "

I do indeed remember the barny about the 'failure' rate, but I think the 44% is just a coincidence here.  This looks like just another case of a web page not being updated and lurking in the undergrowth to frighten the unwary.

Phil

[rct]

I would add to Tedsey here that our oncs always remind The Mrs that the cells needed to "fight" whatever we may think it is they "fight" are found in the tissue, not circulating in peripheral blood.  The blood draw is a nice number to use for comparison to the last draw and the next draw, but it doesn't tell us anything about the particular human being that it was drawn from.  There is not a known way to figure out ones tissue levels, so that will remain a mystery.

Since yesterdays draw was 3.1WBC/1.3ANC they have moved the neupogen out to every 9 days instead of every 7.  This is good.  PCR up, but still two zeros to the right of the decimal point before the numbers even start, so we are very happy with that considering all the stopping/starting/new drug/old drug of the last few months.

rct

[Trey]

Phil,

OK, I now see that this is a different issue.  I sent the following email to the L&LS folks today:

QUOTE:

The following L&LS website page has very bad info on it.  The 5 year  survival stats for CML are listed as 44.4%.  That is very wrong since  it was the figure before Gleevec and other drugs came along.

http://www.leukemia-lymphoma.org/all_faq.adp?item_id=9454
QUOTE:
"5.What are the statistics for the survival of leukemia, lymphoma and myeloma?

Survival  is measured in several ways so it is important to define each measure.  The survival statistics are often presented as five-year survival, that  is, the percentage of people who survive five years from the date of  diagnosis. The five-year survival rates for the blood cancers (for all  age groups) are: leukemia 50%; Hodgkin lymphoma 86%; non-Hodgkin  lymphoma 64% and myeloma 34%. Leukemia rates by type of disease(for all  age groups)are: ALL 65.3%; CLL 74.8%; AML 20.7% and CML is 44.4%. These figures differ for children ages 0-19 and people over 75."
END QUOTE

Another L&LS page says the CML 5 year survival stat is 54.6%, but this is also very low. 
http://www.leukemia-...dp?item_id=9346

Actual current survival stats for CML at 5 years are about double what  you show.  Dr Brian Druker, who is sometimes called the "Father of  Gleevec" says "Today, the average five-year survival for CML patients who take Gleevec is close to 90 percent."
http://www.hhmi.org/...druker_bio.html

The CML IRIS Trials showed the following at 5 years:
"The 12 months and 60 months complete cytogenetic response (CCR) rates were 69% and 87% respectively.  Only 7% of patients on Gleevec
progressed into advanced phases in 5 years time.  The overall survival was 89% and when censored for transplant deaths and deaths unrelated to
CML, the overall survival for newly diagnosed Gleevec patients on 400mg is 95% at 5 years.  Due to the excellent response rates and 5-year
survival data, Gleevec is now the first-line therapy treatment in CML even for young patients with suitable donors. "
http://www.cmlinfo.org/fiveyrim.html

MD Anderson confirms that the survival rate is 90%:
"Imatinib, a targeted therapy that blocks the activity of a fusion  protein called BCR-ABL that is created by the aberrant Philadelphia  chromosome, was a breakthrough drug for CML, nearly doubling the median  five-year survival rate for the disease from 50 to 90 percent."
http://www.mdanderso...remissions.html

So I would request that you change this very misleading information on  the L&LS website.  It is needlessly scaring people who are newly  diagnosed with CML.

Thanks for the great work you all do.

--Trey

[Tedsey]

Thanks Trey.  Those stats give me hope.  Although I felt absolutely horrible yesterday, I am so happy to be alive every day.  And grateful to have such support on this board.

rct, what do you mean by "...our oncs always remind The Mrs that the cells needed to "fight" whatever we may think it is they "fight" are found in the tissue, not circulating in peripheral blood.  The blood draw is a nice number to use for comparison to the last draw and the next draw, but it doesn't tell us anything about the particular human being that it was drawn from.  There is not a known way to figure out ones tissue levels, so that will remain a mystery." 

Still got much to learn.  I am not sure what your oncs are saying.  Do you mean the bone marrow when you refer to tissue?  I assumed with CML, not all tissues are affected (except what are unknown side-effects from TKIs, ESAs or GSFs, and other treatments--if those relationships could be considered).  I can sorta understand because our tissues are supported by our blood.  And everything is interconnected because everything in our bodies relies on everything else for homeostasis.  And all cells (tissue too--which I think are globs of cells that serve some function) originate from the same highest order stem cell.  I understand that peripheral blood just tells a bit of the story.  But the WBC do carry DNA, which identifies the particular human being (but it does not show you, as of yet or what we know how to read in genetic material, all that goes on outwardly and how the human describes how he or she feels--which is probably needed to complete the puzzle).  I think I am misunderstanding something.  Guess I am having a hard time on the larger level.  I am locked into seeing everything as cells and molecules.

Glad to hear the WBC are up.  I keep on hoping and wishing she can lay off the shots soon.  You guys are still in my thoughts.  Thanks for the "rah", despite your bad mood.  I understand.  Spending the day at the cancer center is not a mood lifter.  And although I always deprive myself, I could use a very stiff drink afterwards--minus the minerals.

I am reading the book you brought up long ago called, Stem Cell Now by Christopher Thomas Scott.  I am thinking that it may just depress me more, but I gotta know.  I so believe this is the cornerstone for a cure.  Maybe we can do a little more cookin' in my lab than PCRs.  

Trey, the basement is still available.  We have not accumulated enough junk yet to fill the empty space.  We can work around the baby paraphernalia and new washer and dryer.  The machines both have a nifty sanitizing feature, which may come in handy for washing beakers, test tubes, lab coats and such.

Teds  

[rct]

Tedsey, what our oncs have been telling us is that the blood draw gives them targets to shoot for.  If your body needs to fight infection it will draw from the muscles and connective tissue as well as circulating blood in order to get the cells it needs.  So the count doesn't tell them anything at all about getting sick, because the people prove the rules wrong all the time.  My wife has been rarely sick since diagnosis, and we've been around the sick little kidz and the sick adults here at the office and raw vegetables and everything else.  She's had less colds and stuff than most people we know, if not all.  So they can't really tell anyone what is a good number, because they have leukemics with 4000WBC/2200ANC that get sick all the time.  Just doesn't work the way we would like it to I guess.  Doesn't make it any easier to hear that your counts are way too low though.

rct