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Chylous Ascites as a TKI side-effect? Specifically Sprycel?

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I have had CML for 8 year and obtained MMR, however I developed severe ascites and mild to moderate pleural effusions.  The lung problem was never tested but I had several paracentesis done and the fluid that came out (on average about 6 liters each time) was "chylous"; high triglycerides [~4000], hi protien, high neutrophils, and even came out with a BCRABL reading that was slightly different than that which was in my blood (2.6 vs 3 in the blood).

In 2016 since I was in MMR, I stopped the Spycel (I was taking 50 mg daily and holding MMR no problem).  When I stopped the sprycell the fluid problem stopped and the pleural effusions went away as well.

Seemed pretty indicative that it was related to the Sprycel.  Unfortunately the CML came rushing back and 3 months after stopping I was back at the top of the BCRABL graph.  So the doctor put me BACK on Sprycel.

Slowly, over months, the ascites returned but wasn't localized enough for effective paracentesis removal.  Then, somehow, last year, the ascites came back with a vengence and I was getting more and more taken out at shorter and shorter intervals.  First it was 6 liters in 6 months, then 6 liters in 3 months, then 6 liters in two weeks, then 8 liters in 10 days, now it's six liters every six days.

This is NUTS. I've been hospitalized at one of the top research hospitals in the US and nobody can figure out what the heck it is.  They've tested for:

  • TB, liver failure (two different liver MRI's), heart failure 
  • Spontaneous bacterial peritonitis
  • Every type of hepatitis
  • Other malignancies haven't shown up
  • Lymph system anomalies -- I had a Lymphoscintigraphy where they injected radionuclides between the toes of each foot and followed it around my lymph system but found no leaks and no malignancies

So here's the think, in August 2018 I stopped the sprycel again expecting the ascites to go away (again), but it didn't.  didn't even slow down.

So once again I lost MMR pretty much immediately and 3 months later, I was approaching the top of the BCRABL graph again so my oncologist started me on Bosutinib... that drug started impacting my CML but not the ascites.

I swtiched oncology teams and am now with this top hospital with a top researcher involved in the development of Gleevec.

He has not started me back on a TKI and is considering options.  He didn't like the bosutinib option for me.

I have had (for 18 years) a mild to moderate cardiomyopathy and have been on cardiac drugs for 18 years.  Because of these drugs I have super-low blood pressure.  I can barely get my systolic above 100 but at least it keeps my constant afib at bay a little bit.

These doctors (many many doctors) have scoured the research trying to find a connection between the TKI and the abdominal ascites (i.e. 1 liter of chylous fluid every single day) but so far they found some data on Sprycel and Pleural Effusions but that's about it.  And those effusions stopped with the discontinuing of the sprycel, like it did for me in 2016 but not now.

The oncologist told me two days ago that he really expected after my week of hospitalization that they would have uncovered the cause, I've probably had a hundred blood tests and other labs and MRI's and CT Scan.  I asked him what he was thinking it might have been and he said, heart failure, liver failure or some malignancy.

So while he's talking to some of his colleagues around the country, I thought I would post my very first message in here... i know this is a long one.  I am happy to reciprocate with my 7 years experience on Sprycel but I don't know much about CML except that Sprycel worked.  When I was diagnosed, accidentally, I was approaching blast crisis with 30% blast cells (i think); they gave my hydroxyurea to knock it down and then started me on 100 mg of Sprycel and quickly moving to 50 mg for several years.  Then 20 mg (which worked fine) until discontinuing it in August because of the suspected connection with the ascites.

Thank you everyone.

Jim

 

 

Jim, I sure hope they can get those ascites under control.  I did find a mention of ascites in the Sprycel prescribing information.

6.2 Additional Pooled Data from Clinical Trials
The following additional adverse reactions were reported in adult and pediatric patients
(n=2809) in SPRYCEL CML and Ph+ ALL clinical studies at a frequency of ≥10%, 1%–
<10%, 0.1%–<1%, or <0.1%. These adverse reactions are included based on clinical
relevance.
Gastrointestinal Disorders: 1%–<10% – mucosal inflammation (including mucositis/
stomatitis), dyspepsia, abdominal distension, constipation, gastritis, colitis (including
neutropenic colitis), oral soft tissue disorder; 0.1%–<1% – ascites, dysphagia, anal
fissure, upper gastrointestinal ulcer, esophagitis, pancreatitis, gastroesophageal reflux
disease; <0.1% – protein losing gastroenteropathy, ileus, acute pancreatitis, anal fistula.

I guess the good news is you have more TKIs to try - imatinib, nilotinib, ponatinib, radotinib.  Perhaps asciminib will be the answer for you.

I hope you can get out of the hospital soon.

Kirk

Hi Kirk,

Yeah, that percentage is in the literature but from what I've learned is pretty skewed (low).  I talked to four different parmacists over the years who said it's a lot higher than that (maybe as much as 37%) but that the doctors don't always go through the process of reporting it back to the pharmaceutical companies.  My own oncologist as a case in point -- he never did it because his patient load is so high that it just wasn't feasible.

There is supposed to be a "new" Tki that works differently? something called bcrzero or something like that?  I guess I should google it. I must have he name wrong... I'll ask my doctor about it again.

If this problem IS caused by the TKI drug I wonder if it's just TKI's in general.  And it may not even be related, we don't now, it was odd that the first time I stopped sprycel the problem stopped immediately and stayed stopped until I started back 4 months later... that's pretty damning anecdotal evidence.

But that didn't work this past year.  I stopped spycell for four months and nothing changed.  Started Bosutinib and nothing changed.  Stopped bosutinib 2 weeks ago and so far, nothing's changed.

thanks
Jim

 

PS - EDIT

Just looked up one of the drugs you mentioned -- that's it https://medkoo.com/products/7317  it's called ABL001.

Thanks again for the reference -- that was the one. I'm going to read up on it.

Jim - This is just awful.  I feel just tremendously sorry for you to be going through this.  Bad enough to have the trouble itself, but to not know what the hell is going on - terrible.  The only good thing here is that you are at a research institution with CML specialists of the highest order.  In the US, there is a place under the National Institutes of Health umbrella for diagnostic "stumpers" - when all else has failed to uncover the answer - maybe the UK also has such a place.  I hope there will be others here who can comment and help, but I also would suggest you re-post your tale on the US forum, because there is a guy there - Trey - who might have something helpful to say.  Please keep us apprised, and good luck to you.

Thanks for posting Jim and so sorry to hear you are going through this. I really hope you get some relief soon.

I shouldn't comment as I'm not qualified to do so, but it strikes me that there could well be some interplay between your cardiac meds (and low blood pressure) and these ascites. Do you mind me asking what cardiac meds you are on?

I've been on enalapril (an ACE inhibitor, blood pressure medication) for 25 years as a prophylactic (to protect my kidneys from diabetic nephropathy) and I've had low blood pressure since starting Sprycel two and a half years ago, with even the very smallest dose of enalapril. I took myself off the enalapril six weeks ago (not recommending this to anyone else!) and my blood pressure is now fine. Now just need to make sure my kidneys are ok.

Only mentioning because I feel as though there is an interaction between Sprycel and enalapril and I also believe I have had mild ascites since very early  in the Sprycel treatment. 

Not sure this helps whatsoever. Thank you again for posting and all the very best in your quest for answers and relief.

It's funny you should mention this -- I had this thought the other day.  The cardiac meds keep my blood pressure so low (typically 95/70).

Metroprolol 75 mg x 2
Digoxin 250 mcg
Spironolactone 100 mg daily
Lovastatin 40 mg

 

Also Allopurinol (gout)

Was taking Sprycel for 7 years 100 mg then 50 then 20. now waiting to swtich to new TKI

Every time they take all this fluid out of me (typically 6 liters or better) my pressure gets even worse... obviuosly.

I have wondered about a BP connection in all this.

Hey, I really appreciate you folks chiming in.

Jim

 

Can find no references to TKI drugs in this main article https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5863006/ from NIH

 

Every new thread of information is helpful.... I'm trying to connect the dots.  I'm flabbergaseted (or I guess you guys across the pond would say Gobsmacked... (?) that my previous oncologist would have treated this so matter-of-factly that three years ago we/they should have dug into this -- deeply, instead nothing was done other than get me paracentesis once in a while.

Now I'm reading articles of a mortality of 40 to 70% (probably because of the preponderence of undiscovered malignancies) for Atraumatic chylous ascites.  I've been just going and getting my peritoneal cavity drained and it wasn't until I switched doctors to this major hospital here in AZ, that the hematologist/oncologist asked me the question: "What's the cause of the chylous fluid in your belly?"

And I'm like, uh, I don't know, nobody told me.  So that's when they started the investigation.  then I read articles like this https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5863006/ from NIH and it scares the crap out of me that nobody has been working on this all this time until just last month.

Anyway, they're checking with other cancer institutions in the US and perhaps in the UK to see if they can find anything.  In the meantime my CML still has to be dealt with so I'm going to have to go on SOME form of drug, soon.  Just nuts.

But thank you everyone... maybe we'll hit on something.

Jim, didn't realize you were an American!  I reiterate you should additionally post on the LLS Forum, because of Trey.  Obviously, I can't guarantee that he can/will add anything to the discussion.

This is just appalling.  I, too, had to do my own digging, but that's another story.  I well remember the frustration and agony of having to be my own medical and scientific sleuth - something I had no training for whatsoever!  I think, unfortunately, that many doctors function like medicine is just another job, and they stay in their lanes.  I was always so sad that there was no intellectual curiosity, let alone the much vaunted compassion they were supposed to have.  Nope.  Just another day at the office.

SOME doctors.  I am hoping and praying that you land in the hands of doctors and at an institution that truly cares to get to the bottom of your case and get you some relief.