17 replies to this topic

[holygeez8]

I was diagnosed in May with WBC around 190K and platelets around 700K.  I went on Hydroxy Eurea for 2 weeks (low dose) and my WBC dropped to 150K but platelets went up to over 900K.  I went in the hospital under Dr. Khoury at Emory Winship Cancer Center for 4 days of high dose Hydrea and to start Sprycel.  After 4 days they dropped the dose of Hydrea and after a week stopped it.  I continued the Sprycel for about a month but then my WBC and platelets dropped drastically WBC around 500 and Platelets around 9k.  I had blood twice and platelets once, stopped Sprycel for a week and a half and then returned to a 50 mg dose.  My counts have all steadily dropped on the 50mg dose but never dropped significantly.  I had my first FISH and PCR last week and my FISH came back at 75%.  I don't have the PCR results yet.

Dr. Khoury wants to do mutation testing a week from tomorrow as he doesn't believe I am responding to Sprycel.  My question is, what is next and what can we expect?  How long does the mutation testing take?  What if it is not mutated, why would it not respond?  What are my options drug wise if it is or is not mutated?  When does a BMT become a real concern?

Thank you,

Craig

[CallMeLucky]

I wouldn't panic just yet.  You were only on Sprycel for a short time, you had to come off it and then you went on low dose so it is not like you were on it for 3 months straight at full dose and did not make any progress.  I don't get the new rush by so many doctors to get people to 0 so fast, it's like when all we had was Gleevec you got there when you got there and most did fine.  Now everyone has to get there within a few weeks or it is off to the next drug.  In your case if Sprycel is not the right drug for you there are three other approved drugs and one under review by FDA so there are options.  You could go to Tasigna, you could go to Gleevec, if those don't work you could try bosutinib, and then if that didn't work you could try ponatinib on compassionate use or maybe it will be approved before you ever need it.  You have a long way to go before thinking about BMT so give it time and work through the options.  Find out if there is a mutation and go from there.

[Trey]

The dosage has been too low to draw any conclusions.  Also, since the blood counts are very low, the percentages can be skewed.  Oddly, the percentage of leukemic cells can remain somewhat high for a while as total number of cells drops.  You have obviously killed off a lot of leukemic cells (lower level ones).

Sorry to say, this is another example of Oncs who use Hydroxyurea first for a newly diagnosed CML patient and crash the blood making system, instead of using TKI drugs from the start.  How I wish these Oncs would get a clue that this is improper procedure in the TKI era.  Your WBC was not that high in CML terms that HU was required for any reason.

So now you need to rebuild the blood making system while on low dosage.  But no harm is done by having a Kinase Mutation Test if you wish.

[scuba]

Craig wrote, "I had blood twice and platelets once, stopped Sprycel for a week and a half and then returned to a 50 mg dose.  My counts have all steadily dropped on the 50mg dose but never dropped significantly"

Craig - You almost certainly have had a great response with Sprycel. Myelosuppression is often associated with Sprycel effectiveness ... although it's tough to stay on Sprycel if you can't maintain sufficient levels of normal blood.

There is a good chance...better than good chance, that if you can keep taking Sprycel (50mg or even lower dose), your FISH levels will continue to drop and drop dramatically in the next 3 - 6 months. At this point you need regular CBC tests to monitor your blood levels (especially platelets & Neutrophils).

[mdszj]

Scuba

Is Sprycel regarded as the TKI that generally causes the greatest amount of platelet suppression, compared to Gleevec and Tasigna?

thx Mike

[scuba]

Mike,

All TKI's can cause myelosuppression. Sprycel does seem to have this affect more than the others.

It is not known if this is due to a faster depletion of Leukemic cells creating a "hole" in the normal blood which takes time to fill or if Sprycel actually impacts Ph- cells negatively until they increase reproduction through other - non-impacted- cell pathways. Trey may have more information on this.

I do know that getting the dose right for each patient is very important. And that the degree of myelosuppression is a guide on dose (Dr. Cortes).

I was able to go from 100% FISH to 0% FISH in seven months on 20mg. Sprycel*. Sprycel does lend itself very well to a wide range of dosing that can have very positive results.

My platelets went as low as 20 at one point and dose adjustment found a proper balance. My platelets now hover around 120 (just below normal).

[LivingWellWithCML]

I see Dr. Khoury @ Emory as well - his quick conclusion re: response to Sprycel at a lower dosage surprises me, but he is a recognized CML specialist - so I wonder if there's more that he's assessing that we might not be aware of.  Did he do a bone marrow biopsy as part of your diagnosis?

Just comparing notes on our cases -- he did a BMB on me to confirm the diagnosis (my WBC was 155K at diagnosis, platelets were 355K), verified that I was Ph+ and in chronic phase (0.2% blasts), and started me on Gleevec 400mg daily.  This was 18 months ago - and his philosophy at the time was to start w/ Gleevec because it had been around the longest and had a well-known side effects profile, so I'm wondering if there was a specific reason he started you on Sprycel (which is totally fine BTW - it's a first line treatment as well).

[TeddyB]

Trey: All i got was 400mg Gleevec and allopurinol, and my wbc was 270k and it went down just fine in a few weeks time. I heard no mention of Hydroxyurea at all.

[mdszj]

thx Trey

WHen you mention that the degree of myelosuppression is a guide on dose, does this mean that the 2 are proportional, ie when dosage goes up, you can expect to have more myelosuppression?

thx Mike

[scuba]

Mike - It's not a proportional thing ... i.e. more dose = more myelosuppression. Some patients have little or no myelosuppression at all at full dose (100mg). Some patients have severe myelosuppression at low dose. But in general, there is some correlation that lower dose does lead to lower myelosuppression. That was certainly true in my case.

There are two schools of thought: Start out with full dose and adjust downward in response to myelosuppression - or start out with low dose and work up. I was never started at full dose. I started at 70mg. and that only lasted two weeks (due to severe myelosuppression). I was then off all treatment for 3 months and then re-started at 20mg. I have been on 20mg now for 16 months and I am at MMR (as of 3 months ago).

[holygeez8]

First, thank you all for your response.  Second, there is a little more detail I realize may help.

I was originally not under Dr. Khoury when the low dose Hydrea was started.  My bone marrow biopsy was actually done at a different hospital.  My blast percent put me in Chronic phase, but due to my platelets being over 900K I was having bleeding problems. Because of the symptoms (bleeding, spleen size, etc) and the platelet count, Dr. Khoury phased me at Accelerated.  The high platlet count was the reason for Hydrea and hospitalization by Dr. Khoury.  It was going up sigificantly and quickly and he was concerned about brain bleeds.

He did also start the Sprycel (better for Accelerated phase) immediately and stopped the Hydrea as soon as the platelets came down to a reasonalble number (around 500K from what I remember).

I am having regular CBCs done (weekly) and my counts continue to drop and I continue to take the Sprycel.  However, the nurse called yesterday and said that at 75% from 99% on FISH, it was not a response they considered success.  So, they want me to come in next friday for mutation testing.  There is also a concern because my counts have not stabilized and continue to drop slightly.

Thanks!

[scuba]

"However, the nurse called yesterday and said that at 75% from 99% on FISH, it was not a response they considered success"

I disagree with their conclusion. Your blood system was hit hard with Hydrea decimating your blood system. You have a lot of leukemic cells that as a percentage are high because a lot of normal blood was also affected. You are just now getting "normalized". I would expect your FISH count to keep dropping perhaps significantly from this point on. It's fine to do a mutation test (always good to have more data, but I would not stop taking the Sprycel (at whatever dose balances the myelosuppression). To go from 99% to 75% in 3 months is not bad and you could very well go from 75% to 5% in the next 3 months or even to zero. Dr. Cortes told me that he cares about trend and number of blasts. If Blasts are zero (or very very low), he just wants to see the numbers decrease test over test. Everyone is different in their rate.

Hydrea is nasty stuff: http://www.cancer.or...ugs/hydroxyurea

Your body has to recover from this - only then will the effectiveness of Sprycel be known.

I am curious if Trey concurs.

[Trey]

It may not be lightning fast, but you are responding so far, even on low dosage.  The liklihood of a Kinase Mutation is low (and would need to be the specific T315i mutation since you are on Sprycel).  What do they expect from low dosage?  Some do better than others on low dose, and we are all different. 

The 700K platelets is just average for CML at diagnosis (mine was 1 million), and a very enlarged spleen is also standard (nearly all of us).  That should not have prompted such actions.  And it definitely has nothing to do with calling it Accelerated Phase.  From what you are saying, my estimation of Dr Khoury is dropping precipitously -- using hydroxyurea to destroy your blood making system, saying you are in Accelerated Phase, suspecting a kinase mutation -- all what you would expect from a rank amateur.

[mdszj]

Scuba - Seems like starting out again at a lower dose, letting platelets, etc stabilize, and then going up stepwise as needed is preferable to starting out again at a higher dose and going down.  I am thinking that the key is to allow enough time to let it stabilize before changing the dosage again, then you are constantly playing catch up.  But that is just my opinion...

Mike

[mdszj]

sorry, I meant to say "otherwise you are constantly playing catch up."

[scuba]

In my case, when I was ready, Dr. Cortes started me at 70mg. - that lasted two weeks before I had to stop. Instead of stepping me down to 50mg, he re-started me at 20mg. What he was trying to do is find what dose I could tolerate without having severe myelosuppression. He told me that since I did not have a blast issue (blasts were at a normal low), I had time on my side and he could focus on the myelosuppression first - CML later. He monitored my CBC response over the next 3 months with weekly blood tests.  And each week my blood counts (platelets and Neutrophils) dropped. Even on 20mg., I still had myelosuppression. The good news is it wasn't as bad or as fast a drop as what 70mg. did to me, but it still dropped....but only to a point. After several weeks of dropping, but still staying high enough that I could stay on the 20mg. dose, my counts bottomed out and started to recover. This was the first time in my treatment since diagnosis that I was able to measure an increase in cell count while at the same time taking 20mg every day.

I was then tested for FISH and PCR and it was noted that my FISH had dropped to zero and my PCR had dropped one or two logs. It was at that point I asked Dr. Cortes to increase my dose to 40mg. I was pretty adamant about it - and he said NO. He was equally adamant. I told him that since my blood seems to have recovered and that I am responding to 20mg, I want to test that I can go higher and potentially get a deeper response. He said NO again. He explained that I have achieved a balance between drug, and CML response that is very good. He did not want me to increase the "toxicity" for no good reason. I have been at 20mg. ever since. And since that time, my PCR's have kept dropping except for a blip up which he attributed to "margin of error" (and I asked to increase my dose because of the blip up and he said NO again) which was re-tested and shown to be an outlier ... my dropping trend was re-confirmed. In fact, it was 1.5 log lower from the blip. (In other words, if I took out the blip up and plotted the other data, it all fell on a straight line down).

I just had a PCR blood draw taken a few days ago. I am waiting for the results. My last PCR was 0.009 (Intl. Scale). I'm shooting for 0.000x . I had the impression (not confirmed) from his staff that I was his only patient at 20mg. who reached PCRU. I asked him if he had any patients at 20mg who are PCRU and all he would say is he had many patients on 20mg who are doing well, me being one of them.

It's one big guessing game in my opinion, and I have learned that in the treatment of CML with TKI's, it is very important that treatment be customized. One shoe does not fit all, and the NCCN guidelines are called 'guidelines' and not "rules" for a reason. Experimenting with dose in order to get a good balance between side affects and response should be the norm and not the exception. Dr. Cortes said something that is very key here. "As long as my blasts were normal", he felt he had room to try different doses. I think that is very important. And when given the chance to increase dose to increase response, he chose to keep my dose low. He believes each and every patient is unique. And deserves unique treatment.

[mdszj]

Scuba

I am just rereading this thread again.  It is very interesting what you said that Dr Cortes mentioned about having some time if the marrow blasts are in the normal range.  I did some searching on the internet and saw several references indicating some slightly different values such as 0-2%, 3-4%, 0-5%, etc.  Generally looked like 5% is the high end and seemed like most references had the lower numbers, say 0-2%.  So I just compared this with my bone marrow biopsy results when I was first diagnosed back in July - my BMB report said "There is no increase in CD34 positive blasts, and they comprise 2% of the total cells."   ALso when I went to get a consult with a second hematologist (David Porter at U Penn) his assistant doctor who I also spoke with, mentioned that normal marrow has up to about 2% blasts.

Did Dr Cortes indicate to you what he considered a normal range of marrow blasts to be?

thx Mike

[holygeez8]

Update:  Dr. increased my dosage of Sprycel from 50 mg to 100 mg and is checking my CBC every week to see where my numbers are.  If I don't respond well to the increase within a month then he wants to do a BMB and move me to ponatanib. My first blood test since the increase will be tomorrow.  Hopefully, my numbers won't have dropped too much.