72 replies to this topic

[scuba]

Hi Tedsey - thanks for the response.

My Anc last week was 0.7 and I find out tomorrow whether it is going up, down or the same.   I have been on Sprycel now for 3 weeks.  I feel absolutely fine - much better than with Gleevec.  I have a feeling that my Neutrophils are constant (not falling) since I don't have any symptoms of low Neutrophils.  My red blood has actually gone up since starting Sprycel and I am in the red zone (no pun intended).  On the Netrophils, when my level fell below 0.5, my mouth began to ulcer and tear.  The mucous lining became very poor.  This is the result of bacteria and low Neutrophils.  I am taking the lack of any problem right now a signal that my ANC numbers are at least not worse than last week.   If I can stay above 0.5 - then my body is starting to make normal cells.   That would be great.

Trey's point about the factory being out of whack (or was that RCT?) may be what's happening here and that it just takes time for the drug to keep the Leukemia at bay while the normal cells get going.  Again I won't know until tomorrow.

Sprycel is definitely more agreeable to me and seems to be working much faster than Gleevec.  I was told by Dr. Cortes that Sprycel is 325 times more potent than Gleevec and that it hits the CML very hard and he sees his patients getting to CCyR in 3 months or sooner.  Myelosuppression can also be just as hard because when the bad cells are whacked out - there's nothing to take their place.  He sees lower doses to start as a correction for that.

Keep your fingers crossed.

[scuba]

Bad news .... I am off Sprycel for now ...

CBC test today:

WBC: 1.2

ANC:  0.4

Platelets:  90

Seems that myelosuppression is a big problem for me.  Sprycel is doing the same thing as Gleevec - although faster.

Blast crisis is a real possibility if this on-again, off-again is not resolved soon.  The only thing the Oncologists seem to know how to do is suspend treatment.

I know my counts will recover, but with Leukemic cells.  According to Dr. Cortes I am in the 10% who have this problem.  I didn't ask him what happened to those 10% ... but Blast crisis is definitely in the mix.

Bummer ...k

(p.s. - Dr. Cortes did tell me it's not "panic" time yet.  We have time/room to keep 'finessing' ...)

[CallMeLucky]

That really sucks Michael.  Have they talked about stim shots?  Why can't you get the stim shot for white count and a transfusion for platelets (actually your platelets aren't dangerous low yet) go to a lower dose of Sprycel, like 50mg for a month or two and see what happens?  Tedsey did the shots and eventually things kicked in gear, rct's wife still does stim shots.  Have they even brought it up?  Hang in there, we are all pulling for you.

[scuba]

For whatever reason - Dr. Cortes does not want to do stim shots.  He rather do the on again/ off again.  He wants to start me on Sprycel again after I rise above 0.5 ANC.  Although I didn't ask him, I feel he wants to keep me around 0.5 and let the Sprycel work partially until he sees the counts rise and not fall.  Then I would be out of the woods and my therapy will be increased.  There is some data that suggests on again - off again can work.  As far as he's concerned I am early in this game and so there is time to try.

It's his call of course.

[CallMeLucky]

he's regarded as one of the best doctors, so it seems like you are in good hands and despite all our reading about stuff on the internet, he lives and breathes this stuff everyday so I guess you gotta have faith in the expert.  You are early in this and the fact is it is a slow moving disease.  He'll get you right, in the mean time enjoy the side effect free time.

[scuba]

Truth is - I have no side affects with Sprycel.  No difference at all.  With Gleevec I had minor issues (fatigue/ foggy feeling) and nausea if I didn't eat a proper mix with the pill.  With Sprycel - I take it at night (empty stomach) with some water and that's it.  No fatigue, or other side affects.  I am puzzled why my red blood is unaffected.

[Tedsey]

Dear Michael,

I am glad you are feeling well on Sprycel.  I think it was Dr Cortes who was part of a research study that supported GCSF as safe for CML patients.  I wonder what has changed?  Also, where does the blast crisis come in?  Has anything changed in your bloodwork recently?  It was Dr Druker that suggested the stim shot route for me a yr ago.  I wonder why Dr C does not want to do this for you?  Like Lucky said, I am sure he has a good reason, but I wonder why.  I understand that my case is different, but not sure how much so.

The lowest I think I got ever was ANC .2, but that was on Gleevec.  It took almost a year for things to get better for me (reaching at least .5-1.0).  And I had no more breaks after the initial two I had when I first started G.  It looks like Dr C and Dr D differ in their approach to myelosuppression (unless research at present supports off again on again as the best route).  I guess new findings come out daily that we are not privy to.  But it is kind of disappointing to think that the specialists may still be as baffled with the course of this disease in individuals as we are.  It appears that way.  I often wonder if many practioners just throw things at problems that arise to see what sticks.  Kinda makes me feel like a Guinea pig.  I guess we all are in some way.  And I guess it is still too soon to understand what reliable trends exist in individuals taking TKIs for CML (in all stages).  I really hope the best for you.   

Teds

[scuba]

Hi Tedsey - Yes ... I absolutely believe they guess and 'try' things.  It's why they call it a "clinic".

Because they feel every patient is unique (though we have the same genetic translocation), they try different approaches.  Although Dr. Cortes did not give me a reason for why he wants me to just stop and then start again; there appears to be evidence that since Sprycel (and Tasigna) works so much faster than G, they can do this on again / off again fairly quickly to see if response can be coaxed.  It is only taking a week for the levels to get impacted.  ON G it was months - it was a slow drop and then a break followed by another slow drop.  With Sprycel - I'm down in the low numbers in a week.  If I stayed on Sprycel - next week I am sure I would be down to about 0.2 or lower.

I do believe there is some 'experimenting' going on - though not a formal trial.  If I respond - then Dr. Cortes has another trick up his sleave for other patients.

He hasn't shared with me if he has had success doing this - but I have that impression.

Stim shots are probably a last resort.

As I try to internalize the biochemistry - I know that the body produces cytokines to message the bone marrow to produce more neutrophils when they get low.   And for whatever reason my normal blood stem cells are not responding.  It could be they are beginning to respond - just very slow.  But of course I don't really know.

I can tell you - I do not like being off a TKI - knowing that the CML will just start growing again.

[rct]

I'm sorry this is happening Michael.  I would say this to you:

I appreciate whom Cortes is, I know what he has done, haven't met him or anything, but I know who he is.  Our oncs here on the east coast, and the guy out in Oregon do not agree at all with the approach you are taking, and the one consistent theme through the last two, crap, nearly three years has been to stay on the TKI of choice as long as possible on as high a dose as possible.  The low counts is something to be dealt with alongside the leukemia, not something to drive the treatment of the leukemia.

You don't mention your PCR, so I can only guess there is either not one recently because of the stops and starts, or it is low enough to not cause alarm.

Our experience is getting better.  She is currently shooting less than 480 Neup every 14 days.  On that 14th day, that's when ANC matters, go to the blood draw, then go home and shoot Neupogen.  On that day she has been as high as 1200 lately, hooverin around a thousand.  After nearly three years, this is AWESOME to us.  Slowly, inexorably, it is coming up on it's own. To the point now that we don't even get a blood draw between monthly trips to the Cancer Emporium, we just time the shot and the appointment right, get it on the two weeks mark.  Only a year ago it would easily be below 700 after only a week.  Slow and steady change has come, because we found docs willing to work with her on it.  I don't know how it would go for you or anyone else, but shooting that stuff is not a picnic by any measure, so it is important to us that she get off it even without all of the other dangers of using it for too long.

Through all of this dumb stuff she has remained, on average, PCRU.  Last one was just couple weeks ago and we were again astounded to be no numbers at all.

Separate the treatment of the low counts from the treatment of the leukemia. View them as two entirely different things.  One has pretty straight forward treatment using the TKI of choice.  We only went off Gleevec to Tasigna for a very short time, it seemed fruitless once they had done it, and she went right back to Gleevec BECAUSE IT WORKS.  We'll save the Tasigna for someday should she ever need it, as it is she wasn't on it long enough to know if it works, but long enough to know that the low counts weren't going to change with the TKI.  Exactly, I'll add, as Druker predicted long before we did it.

Treat the low counts in the prescribed way, but work around them as much as possible.  The package says 480, or 300, whatever.  Don't have to take the dosing and the instructions as gospel, they can be tweaked to suit the individual, she is living proof of that.

Our current oncs are ok with the idea that should she get to the more-than-three-weeks-between-shots point they will consider 300 Gleevec if it means NO NEUPOGEN, even if there appears a number in the PCR.  That is working with the patient, because she knows by now that PCRU is nothing if you have to do this crap, it is better to have three zeros and any number if yer counts stay ok.  And we think they would on 300, once she gets stable enough for long enough.

I think of you every day and wonder how it is going.  It is not easy being one of the 10%, and it is hard to know what to do.  We only knew that early on when it started, our oncs refusal to even discuss lowering the Gleevec or maybe less Neup and trying it or anything outside of 480 weekly for the rest of your life as far as they knew was a very good reason to go find someone else, and we were immediately glad we did.  I hope you find the right combination soon.

rct

[CallMeLucky]

rct,

which "East Coast" facility does your wife go to?  I'm at Sloan Kettering, was just curious if that was the center you refer to.

Regards

[rct]

Fox Chase.

I don't write the names much because there may, and has, come a time to say something slightly less than glowing about these places.  Our hosts are not down wit dat.

rct

[CallMeLucky]

I understand

[scuba]

Thanks RCT for the reply: 

I asked Dr. Cortes about his recommendation that I stop/start, stop/start rather than shooting up with stim shots.  And he replied that he has been successful getting patients to remission (CCyR) doing it this way.  He commented that each patient is unique and that it is mostly a balancing act between response (including myelosuppression) and dose.  He told me that I am far from the "panic" stage and that he has room to work and finesse the transition.  He wants to get me to a point where the dose just matches the myelosuppression and then over time as the body gets going (your factory analogy), he increases the dose.  This has worked for him with other patients.   Essentially he wants to see my counts come back up to about 1.0 ANC. then resume Sprycel at the current dose...he expects that I will have myelosuppression again but it may take longer to fall below 0.5 ANC- but when it gets there, he stops the treatment - lets the counts rise to 1.0, then resume treatment at a lower dose.  He expects the counts to fall again, but may not fall as far or take longer.  And then - hopefully - I stay on treatment while the counts hover around 0.5.  His goal is to get me stable at 0.5 while still taking Sprycel.  Then we start increasing the dose again.  When he can increase the dose and I don't have a fall in counts,  I am over the "hump"...and my counts should start to rise slowly while still on Sprycel.  In this way my body has been coaxed back to creating normal cells unaffected by Sprycel.  I could spend the rest of this year getting to this point.  Meanwhile the CML should be dropping steadily or kept in check.  The PCR work will tell him if other things are going on during this "custom" adaptation.

Sprycel is good for this (Tasigna also) because it produces quicker response so he can see if it is working.

We'll see.  I have to go with his judgement on this.

Thanks for your prayers.

[rct]

You do have to go with his judgement, and I respect that judgement with all props n stuff.

Stay with it.  We have learned that it can be a pretty long road.

We have learned that the system is probably, MIGHT be developing new paths of indication of need.  The grower works, so we know that the factory can make them.  We also know that she has been historically low on whites and anc because we are lucky enough to have copious medical records because of some other health issues in her life.  So it may be a combination of Gleevec interrupting the usual route taken to deliver the messages in a system that it typically lower than what they normally see.  If that is the case, slowly but surely, we think, right now, that the system is developing alternatives.

We have also learned that Gleevec works and it works very well for her.  The side effects after five years now are pretty rough.  But if we could remove the Carousel Of Neupogen she would at least have a stable set of sides to cope with.  So above all, they want to keep on the Gleevec no matter what we have to do.

What we have to do is somehow live around it.  So work is becoming a significant issue and will have to stop in the future, probably near future.  At least, the current 10 hours a day 4 days a week grind we do.  I'd say that she'd have a better chance of getting a few years closer to retirement if she lives long enough, and the Gleevec can do that, if she could get the counts up to not need coercion.  Coerrshun.  Kourshin.  Whatever.

The following is not conspiracy theory tin foil helmeted ranting, it is just the way it is.

We have also learned that it is in the best interests of the docs to try not to have to use Neupogen.  If myelosuppresion becomes an official side effect and not an unfortunate consequence, there would be very much work to do in order to make Neupogen an acceptable way of dealing with that side effect.  That drug requires more than yer GP to monitor, requires the patient to learn how to inject themself, and it has very serious potential consequences of its' own.  It is not, as far as we know, approved for the use we are using its uses in use of.  Something.  It causes leukemia.  Thats a problem.

  So I am not surprised at the variety of responses to the low whites/anc problem.  Our first oncologist never saw it bad enough to respond, our second onc wanted her to shoot the Neupogen once a week forever without any discussion of anything else, our third and current oncs want her to use it as little as possible as infrequently as possible because they can talk about the dangers of it with us, and Druker wants her to use it as needed, no matter how often that need, because he believes that her system will makes its' own way and not need it.  Eventually.  He gave us his pretty classic shrug and said "I don't know...5 years?"  Carol agreed that they had patients using it at least three years and still using it as needed, some even weekly.  He also felt that if we would like to drive out to Oregon every year to see him he was pretty sure we'd get tired of it, because based on her response to the TKI he expects to be seeing her for a long time.

Good luck with it Michael, do what they say, it may take time.  For me, I don't have CML, I can relay that none of our oncs have expressed grave concerns about it, they don't think it is too major a deal-y-0.  But I don't have CML, so I can take that from them.  The patient sees it differently, especially from about 6 hours after the shot through about the 5th day after the shot.  At least my patient, that is.  If you have to use it, it may not effect you the same way, that is definitely a possibility, we know others not nearly as knocked down as her, and we know of others that have it even worse when they shoot.

"effect you" may need to be "affect you", I just don't feel like finding an online encyclothesarusionary.

rct

[Paula]

Was the Gleevec working on the CML? I've been on Gleevec now for approx. 21 months

and do not have a CCR. MY onc has talked about switching to Sprycel but wants me to try

another month on Gleevec at 500mg. How long were you on Gleevec and what was the results

of your PCR tests?

[Marnie]

HI, Paula. . .

I was on Gleevec for about 20 months.  The Gleevec was working, but I had hit a plateau.  My PCR numbers were:

.200

.059

.054

.100

.027

.147

My onc wanted to wait for another 3 months before switching to see if the count went down again, but I told him that I wanted to switch.  He wanted me to try Tasigna, because he has 3 other patients who are currently doing well on Tasigna, and he had no patients on Sprycel.  But with my active lifestyle, I just didn't want to have to work around the schedule of Tasigna.  Also, Trey gave some pretty good reasoning for trying Sprycel.  Right now, I'm thrilled with it. . .as I said, side effects are way, way less invasive, and I just generally feel better, though the fatigue is still there.  I'm concerned about the QT interval issue, but I guess I'll deal with that if my doc sees it as a problem.   I'm very impatient for my next PCR test.

Marnie

[cherylannes]

Michael,

We have patients here in Montreal and close by (geographically speaking) who have had the same problem as you.  Their doctors have reduced their dosage of Sprycel down to 40mg once daily in order to keep them on the drug.  After time they can bump up the dosage if needed....

Would Dr. Cortes consider trying an even lower dosage on you in order to keep you on the drug....I should add that these patients have been doing this for close to five years, and from what we can see no mutations have developed.  I think this is somewhat unique to Sprycel as it is a SRC Kinase inhibitor....

Hope some of this helps.

Cheers!

[scuba]

Hi Cherylannes,

Dr. Cortes wants to wait for my counts to increase from 0.14 to over 1.0 ANC.  And then he will put me back on the 70 mg. Spyrcel I was taking before. No dose reduction.

I'll ask him again why not just a lower dose ... His past responses to my questions on treatment are, "We can certainly do that ...." variety.  He is not definitive, but more experimental.  He believes that every patient is unique (subtle differences in proteins - which is why we all look different even though functionally similar) and requires "tuning".  So he makes his best guess on what to do next.

He likes the idea of higher doseage with breaks rather than lower dosage with no breaks.  A higher "die off" of the CML cells is believed to be 'stimulative' to the bone marrow in general and should coax my normal system.  That's the theory anyway.  A chronic lower dose with no breaks could coax the body into coexistence with both normal and abnormal cells living side by side.  He very much believes that getting to the higher dose with normal blood is what he wants to achieve.  He also told me that the new TKI's (sprycel/Tasigna) allow him to do this because they are so potent. Hit hard, back off, hit hard, back off.  I suppose it makes sense.

I am in for a long haul.  So far my bone marrow has not been wanting to make many normal cells.  But I am impressed with how fast Sprycel works.  A week or two and my counts plummet.  With Gleevec it took months.  One final thing - he told me that once I start to stay above critical for WBC's - he expects the Sprycel to bring me into CCyR in 8 weeks.  Very fast drop.  The rules are being re-written on time lines and other markers for long term prognosis.

[cherylannes]

Michael,

I would be curious to know why he wouldn't consider lowering you to 40mgs for a while and seeing what happens....I would also wonder what data he would have to worry about abnormal and normal cells learning to co-exist.  I do not think that can happen, but I could be wrong.  I think that if you can be stable on a drug, then do all that you can to help your immune system to recover, such as eat the right things (Veggies, fruits, etc) exercise, rest, stay away from stress for a while, my feeling is that both these things contribute to keeping the bad cells in check....The theory about higher kill off of CML cells being stimulative is also interesting.  Exercise is very stimulating, but not always possible due to fatigue.  I find that when I run or snow shoe often my Hgb shoots up.  It isn't always easy to maintain the pace though.  Sometimes I try to time my exercises to match the peak of the half life of the drug in the hopes that I pushed more CML cells out in circulation to be exposed to the TKI....Amazing what we can bring ourselves to visualize when we are busy focusing on being well and listening to the scary "wake up call" from our bodies.  I also have this running dialogue with myself, something like this..Body to Cheryl's brain:  "You see what we were trying to tell you?  We would love to do all the things you think about, but we are the physical aspect of you, sometimes we just can't keep up with your creativity"  Cheryl's brain: "I hear what you are saying, but I have one more big account to win, then I get to the bonus level, come on we can do this, sleeping and eating is so over-rated, if I cut back on both, I can spend more time focusing on the account."  The scenario goes on and on, actually it makes a good story that I am writing - so stay tuned.  But it is along the lines of the body telling the brain that it needs to take a break before something goes wrong, like cancer......

Indeed the rules are being re-written and more so with the 2nd generation TKI's.

I couldn't agree more with Dr. Cortes, in fact we are not a "one size fits all" group of patients and our doctors need the freedom to work with us directly on what might be the best thing for us. Uninhibited by  financial constraints, insurance programs, or even underfunded government programs....

Here's hoping your counts come up quicker!

Cheers,

Cheryl-Anne

[scuba]

I am a biochemistry kind of guy.  Chemical equilibria and such.  The body makes Neutrophils.  It knows how many to make (cytokines feedback) to keep us in balance.  When too many are produced, the body shuts down the 'signaling'.  When TKI's (Sprycel in my case) wipe out the Leukemic Neutrophils, the body, in a chemical reaction, starts the signalling to make more.  As long as TKI's are present, the Leukemic system can't make more (a good thing), so the only path left is the normal system which has been largely shut down.  It has to ramp up and that takes time - apparently a lot of time.  Meanwhile the body has to have neutrophils so the TKI's are withdrawn and the Leukemic cells start filling the void.  By keeping the counts low (around 1.0 ANC), but sufficient to stay alive (no killing infection), the signals are still produced to make more cells.  Both leukemic and normal cells respond.  But the leukemic cells keep experiencing a TKI to keep the numbers low.  Eventually the normal system starts to over populate relative to the leukemic one.  And it is at that point that much increased TKI pressure can be brought to bear to lower the CML cells dramatically and cross over into remission.

Until I get a balance between normal and leukemic where normal is increasing enough to maintain health - I have to live with some CML in a steady-state with a slight favor to the normal system and disfavor to CML.  The way I think about is - my marrow needs to be cleared so that there is biochemical pressure to make more cells - assuming I have normal cells left ! (I am sure there are some).  It took years for CML to grow and take root.  It could take years to reverse it.

It's all guessing.  In a perfect world, my ANC would be monitored continuously (every day?) and the drug administered to just keep my ANC steady - until such time that my ANC starts to rise even with Sprycel.  Then they do a test to see if ANC is rising due to lack of response or due to normal function (bone marrow test).

At least that's the plan.  Exercise is always a good thing.  It stimulates the blood.