Pressure in Chest when Standing

Ian,

Sprycel is known to cause pleural effusion (PE) which has the symptoms you describe. It is a build-up of fluid between the lining of the lung and chest. This excess fluid exerts pressure that can affect breathing when it gets severe.

You should have this checked right away (x-ray will show if it is PE) and if confirmed you will have to stop taking Sprycel until it clears up.

You have had a terrific response to Sprycel so far. At a pcr of 3.8% after only 3 months, you will be able to take time off drug for this issue to clear up without concern - and then resume Sprycel at a MUCH LOWER DOSE. In your case I would strongly urge your doctor to start back at 20 mg. and continue checking pcr. Given your dramatic response (and strangely the fact you may have a pleural effusion is associated with terrific CML response), you may very well never need a high dose of Sprycel to get complete remission. There is emerging strong evidence that patients shouldn't even be started at 100mg - 50 should be the starting dose. And some researchers even suggest 20 mg as starting dose with gradual increases if response is not sufficient (chronic phase only).

One more thing - you were diagnosed with 2% blasts - what are your blast counts now? Ideally they should be zero. Zero blast count is the most important indicator for stable CML such that you can stop drug and have time for a pleural effusion to clear up. Have your vitamin D level checked and if low (it probably is ....), supplement to get it above 50 ng/ml. Vitamin D induces blast cells to differentiate - even leukemic ones. It will help chronic phase CML stay chronic phase.

Hopefully you do not have a pleural effusion. But if you do, it can be managed, stopping drug will reverse it and re-starting at lower dose may help avoid future issues.

You are going to be fine.

RC Kirk and Scuba, thank you very much for the responses. It makes me much less worried to read this forum and the information you have provided. Regarding your questions Scuba, I don't think my Oncologist measured my blasts at 3 months or my vitamin D for that matter. If he did, he didn't provide me with this information. I will check with him before the next visit, which is unfortunately another 3 months from now. We were doing more frequent visits and weekly CBC's previously, but he said every three months should be okay now that it seems things are stabilizing (although my last ANC test seemed rather low at 1.0, but from what I've seen on this forum it is okay to go a little lower before getting overly worried?).

Also, I contacted the oncologist and I mentioned the pressure in my chest and inquired about PE and scheduling an x-ray soon. He said he didn't want to do an x-ray at this time because it is only discomfort and I am not having trouble breathing yet. I also asked about the potential for lowering the dosage in the future as you suggested Scuba, but he is against lowering dosage at any time unless there is concern for my health. I guess it is still early in my CML journey to look into lowering dosage, but it is a little concerning that he won't entertain the idea in the future.

Thanks again for all the great info!

Ian 

Hi Kat,

What is your current PCR level?

I have been reading a great deal how patients on Sprycel who develop P.E.'s often have tremendous response.

https://www.nature.com/articles/leu200946

Hi Ian,

" ... but he is against lowering dosage at any time unless there is concern for my health".

Tell him you have concern for your health! Give him the research papers from experts in the field that document lowering dosage.

Let him know you are not suggesting this out of thin air. He might learn something that can benefit his patients. If he refuses to read these papers, you need to find a new doctor.

https://www.sciencedirect.com/science/article/pii/S2152265016305687

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3018898/  (note - this paper published in 2010 - eight years ago we knew low dose works).

http://ascopubs.org/doi/abs/10.1200/JCO.2017.35.15_suppl.e18551

This last link might prove particularly useful. Ask him if he knows of Dr. Cortes at M.D. Anderson Cancer Center. It would also be interesting for you to learn if your doctor attends any of the blood cancer conferences (especially ASH).

Kirk,

I would not cut your dasatinib tablets. They crumble easily and you would not know what actual dose you are providing yourself. In addition, the distribution of active drug throughout the tablet is not assured so splitting them will not guarantee that one piece has the same amount as another piece.

It would be best if you could get 20 mg tablets and take two if you wanted a 40 mg dose.

Dr. Cortes told me that it is better to take a lower dose every day, then doubling the dose every other day given the fast clearance of Dasatinib from the body.

We would have to discover the half life of CML cells in connection with Dasatinib half-life. What I mean by that is CML cells divide very quickly being completely turned over in 13-20 days. Given that fast rate, taking Dasatinib every second or every third day means for a relatively long time, CML cells are dividing without any drug present. It's possible that the growth rate during this non-drug period is not faster than the destroy rate during drug presence. IN which case you might get away with it. But keep in mind that since Dasatnib is a threshold drug - doubling up every other day probably doesn't make a difference. The cells die when Dasatnib is present once the threshold dose is reached. More doesn't change anything (except increase toxicity).

I am debating whether to drop my 20 mg dose to 10 mg....and 5 mg. Unfortunately they don't make Sprycel tablets in less than 20 mg. dose. I want to do this so I can wean off Dasatinib when I go for cessation again.

The 100mg tablets can be split pretty easily to 50mg, but I don't think I would trust cutting them twice. The amount of dust when splitting them to 50 is pretty small, but I think the previously split edge would generate a lot more dust on the second split.

PS. I learned all of this from a friend who had a quick response to 100mg and disagreed with an onc that refused to lower the dose.  The end result was some extra pills lying around and no change in the PCR...

Okay, so the oncologist scheduled an ultrasound for in a couple months. My question to you all is (1) Is a couple months too long to wait if you suspect PE and (2) I keep reading about x-rays for determining PE, but not ultrasounds for PE. Does an ultrasound also work to determine PE?

The way PE is diagnosed is first by any symptoms (like shortness of breath or chest pain), second by listening with a stethoscope for a change or diminution (or dulling) of sound in the area where the fluid might be (and, NOTE, most physical exams stop short - literally - of listening far enough DOWN at the very bottom of the lung, and often can miss this), and thirdly by an ordinary chest x-ray, with lateral view included.  It would be unacceptable, with reported symptoms, to wait two months for any of this.  See your primary care doctor.  I still suspect your spleen, which will settle down.  But, you are not being unreasonable at all to ask for the three things above.  (Although you might not need the chest x-ray if the doc truly can't hear anything funny after a THOROUGH listen.)  Maybe the ultrasound was to look at the spleen?  Which, yes, you could wait two months for that.

Thanks, Scuba, but hardly!  Just a single voice of experience on the subject, no more or less.  I wondered if you had any comment on my reply to you that is a few posts above this, about my onc's umbrella analogy about resistance?

Hi Kat,

Regarding your Onc believing the Sprycel "umbrella" is not big enough to catch all of the CML if the dose is too low. He is correct and not correct in his analogy. He is correct that dose matters, but incorrect regarding resistance. Cancer is not bacteria. Cancer is about population dynamics.

Without going into too much "math" detail on population dynamics (https://en.wikipedia.org/wiki/Population_dynamics), drugs that are designed to kill cells (apoptosis) are modeled using population dynamic calculations. Most "doctors" are not schooled in these models so they use words like resistance which is incorrect. Cancer cells in the way they grow and multiply are not that different mathematically to the way roaches, fleas or bunny rabbit populations grow. These populations - barely noticeable - can suddenly explode in numbers.

Drugs like Sprcyel and Gleevec are population controllers - like flea traps, flea sprays or wolves that like eating rabbits. So in the scheme of things there are two competing forces in CML treatment that effect outcome. The rate of CML cell division and expansion and the rate of CML cell death caused by our TKI killing cml cells. If the rate of cell death is greater than the rate of cell expansion, our CML starts to fade away and ultimately go into remission. The fade away can be gradual or it can be sudden. Just like flea populations can also collapse after using a fogger. It doesn't mean all of the fleas are dead, just that enough of them are wiped out that re-establishing the "colony" is difficult - especially if a residual trap is left around.

TKI's work that way. They effect the population dynamics of CML.

When our CML is first diagnosed, the cell counts are explosive and out of control (for the most part - in reality our bodies are trying like crazy to keep it under control which is why the spleen enlarges among other things). When we take Gleevec (for some people), it binds imperfectly to the energy site of the CML cells and kills them. It does not kill all of the cells, but as long as it kills more cells than are being replaced, the overall CML population will go down and as it goes down, the CML population ultimately collapses to a new steady state condition. This is why some people remain at various levels of PCR.

Gleevec is a dose dependent drug. The more you take the better it works. Precisely because it doesn't kill every CML cell it comes into contact with. More drug is necessary to hit more cells more of the time. But of course more drug leads to toxicity and if a patient would need the equivalent of 2000 mg of Gleevec to be effective at controlling CML - the drug is impractical - 800 mg is pretty much the upper limit.

Sprycel on the other hand is a threshold drug. What makes Sprycel different is that it is more potent than Gleevec. When ever Sprycel comes into contact with CML cells they have no chance, they die - and they die at higher levels in the cell division hierarchy than Imatinib does (i.e. kill the fire ant queen, not just fire ants). So the amount of drug needed to cause a population collapse of CML cells is far lower and once crossed - more drug makes no difference - the CML population is already under collapse.

It is not quite correct to say that more Sprycel doesn't increase the rate of collapse, just that the increase is so small it's not important. So taking more drug just leads to toxicity. The key for patients therefore is to find the threshold that triggers CML collapse.

In mathematical terms, Gleevec impact on CML is mostly linear, where Sprycels impact on CML is logarithmic.

The key - is  - if it works. If Sprycel works, it tends to work very well. When it doesn't work - it doesn't work, more drug usually (there are always exceptions) makes no difference. Gleevec, when it works, usually works even better with more drug - so its threshold of effectiveness is not as sharp as Sprycels.

As we are all slightly different, finding the right drug, the right dose and even the right other things (like Curcumin, or vitamin D) requires individual testing.

Hope this helps answer the 'umbrella' question.

Hi Davide,

I'm curious as to the differences between symptoms of pleural effusion and pericardial effusion.  Did you have both at the same time? If so, do you have an idea which one caused the sensation of pressure?

Thanks, Kirk

Hello Kirk.

I had absolutely no symptoms of pericardial effusion. It was discovered during a routine echocardio (heart ultrasound). My hematologist prescribed an echocardio before I started the Sprycel treatment, for baseline I believe; and another after one year. Its main purpose is to check for pulmonary hypertension I think. 

Anyway, at the first year checkpoint PE had come back; the pericardial effusion was quite apparent in the echocardio screen, you can really see it. It was rated as moderate. I was quite scared, but my doctors assured that it is quite common when PE happens. It is just the same mechanism, cell membranes become more permeable, and so water passes through these membranes.

As I said, no symptoms at all for me, although some of the potential symptoms overlap with those of PE: fatigue, a persistent cough. My hematologist mentioned that cough appearing in certain positions might be related more to pericardial than to pleural effusion, but that is all. 

As far as consequences/therapy, the approach is the exact same of PE: drug holiday or, if not advisable, anti-inflammatory (ie: prednisone) and diuteric (furosemide). The only extra cautionary step was a cardiologic exam: an electrocardiogram and a general exam with a cardiologist who made sure that my heart was generally in good shape. 

For me it has been a source of anxiety, but on the practical side it really had no consequences. PE was more annoying when peaking, because you can really feel it (when doing heavy gardening, for example).

Cheers,
Davide

Hi, ipmaki! Thought I would add my two cents worth to the discussion. In 2012 I had been on 100 mg. Sprycel for 2.5 years. I had experienced a very strange rash on my toes only for the previous 6 months. I started feeling a vague sense of shortness of breath (SOB) in February with discomfort (not pain, per se) when I took a deep breath.

I ignored it (denied it, really) for a couple of weeks and finally went to my onc for an X-ray. It was found that the effusion was very small, hardly even blunting the tip on my right side. He felt it was so small I shouldn't even be experiencing symptoms. No mention was made of stopping Sprycel. Fast forward two weeks and I was quite SOB. Back to clinic where they ordered a CT and found by then I had a fairly large effusion and I had a thoracentisis to relieve the discomfort. I stopped Sprycel on the findings of the CT and was off for almost three months while the effusion totally resolved. Very important!

I also found that a couple of courses of prednisolone was the turning point in resolution, diuretics did nothing. 

Two things I learned from this experience: 1. Don't ignore the symptoms, if it is an effusion it will NOT go away on it's own and will very likely increase to an uncomfortable, if not dangerous, level, and, 2. It is very important that the effusion totally resolve before restarting Sprycel at a lower level.

I've been on 50 mg. since that time and it is working quite nicely for me. I lost MMR and almost lost CCyR, but I regained them at the lower dose within 15 months.

Your onc should be able to hear normal breath sounds all the way down to the bottom of your lung. Don't settle if he/she says they hear "nothing". If they hear nothing, fluid may be pushing your lung up and reducing oxygen capacity.

Don't mess around, effusions can be very uncomfortable at the least. Good luck!

I just wanted to follow-up on my CT scan for those interested. Turns out I don't have a pleural effusion. The results say "No CT evidence of acute cardiopulmonary process. No suspicious pulmonary nodules, masses, or pleural effusions." This is good news I guess, but also a little disheartening because I still don't know the cause. Recently I've also noticed an enlarged lymph node (assuming it's a lymph node) on my left chest that I was hoping the CT scan would also catch. I guess it didn't and will likely try to have a follow-up with my doctor on the enlarged lymph node. Has anyone else experienced this with Sprycel? I read about it happening in previous forums at the arm pits, but not the chest. It's been about two weeks now.

My husband hasn’t experienced swollen lymph nodes in the chest but he did in his neck. It came and then went away after a few days. Then the swelling focused around his eyes  and that was much more persistent. Much better now on 50 mg and no more swelling anywhere else. He is also taking Curcumin eases inflammation. 

Sorry for the worry. You are never sure now when something is wrong if it’s the leukemia or the TKI or something else. 

Best wishes Louise