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Gleevec causing Inflamed Liver

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Hi Folks,  What a wonderful forum, the most helpful wealth of CML info I have found for sure. Thank you for all the great advice I have read thus far.  I live in the Washington, DC area and see a local oncologist as well as Dr. Mauro at Sloan Kettering in NYC.   I started treatment for CML in December of 2018 with Gleevec and it was going great, I had achieved MMR in 7 months and then my Liver Enzymes (ALT and AST specifically) shot up above the 5x normal upper limits and I had to stop Gleevec.  I have tried Sprycel but have had 4 heart procedures with two Stents placed while being on Sprycel for 12 months so it seems that Sprycel is accelerating my pre-existing cardiovascular disease.  So we are going back to Gleevec as the other TKI's have an higher risk of Cardivascular events according to my docs.  

The plan is to restart Gleevec at a very low dose (100MG) with a healthy amount of steroids on board (either Prenisone or Budesonide).   I'd like to make the steroid course as short as possible as they have thier own risks.   I have researched on the forum some folks that have had the eleveated Liver enzymes and have taken Milk Thistle to help. 

My question is to those folks that have some experience with this issue to see if they had anything that really worked to keep the Liver enzymes in check while taking any of the TKIs?  Anything on specific brand and dosing of Milk Thistle?  Any other strategies such as diet?   I already drink an enormous amount of water daily and have recently switched to a plant based whole food diet.  No alcohol for me since diagnosis so that is not an issue.   Any tips or strategies folks have used would be greatly appreciated.  If this Gleevec attempt doesn't work they are looking at having to possbily abandon the TKIs and move to a more general Chemo called Omacetaxine (Synbrio) which I'd really like to avoid if possible.  Thx for the assistance and wishing you all the best in the fight against CML!

Bill R

 

Hi Bill,

Looks like you have a good CML team on your side.  I was just wondering if asciminib has been considered as an option?  I don't know, but maybe it's hard on the liver as well?

Kirk

Hi Kirk,  Thanks for the reply.  Asciminib has been mentioned by my oncology team but due to the fact that it is so new their is some hesitation due to the lack of clinical history to show its level of risk for cardiac events.  It may be the next option if the Gleevec spikes my Liver Enzymes again.  Hoping I can keep the Liver calm somehow.

Hi Bill,

it seems that milk thistle is not contraindicated with TKis

just a quick search indicates it is safe 

'Milk thistle is taken by mouth most often for liver disorders, including liver damage caused by chemicals, alcohol, and chemotherapy, as well as liver damage caused by Amanita mushroom poisoning, nonalcoholic fatty liver disease, chronic inflammatory liver disease, cirrhosis of the liver, and chronic hepatitis.

Some people apply milk thistle directly to the skin for skin damage caused by radiation.

In foods, milk thistle leaves and flowers are eaten as a vegetable for salads and a substitute for spinach. The seeds are roasted for use as a coffee substitute.

Don't confuse milk thistle with blessed thistle (Cnicus benedictus)...'

see here  for overview and interaction checker.

I remember quite a few people using M/thistle to counter raised liver enzymes possibly caused by additional stress on the liver of TKi therapy.  Acinimib is a new drug and your doctors are right to say there is no data as to its possible negative effects on the liver... however, in 2000 there was no data at all on imatinib side effects - serious or not! So maybe you have to take a view on this and try it. It would be a plus for you if it allowed you to restart imatinib - sounds like dasatinib is contra-indicated for you because of your pre-existing cardiac issues. You could also ask about bosutinib? 

To my knowledge clinical trials of Omacetaxine did not really pan out very well in controlling CML... however, I may not be up to date on that so I suggest you take a look at this study from 2015: 

Final Analysis of Efficacy and Safety of Omacetaxine Mepesuccinate in Patients With Chronic Phase (CP) or Accelerated Phase (AP) Chronic Myeloid Leukemia (CML): 24-Month Minimum Follow-Up Results

'In summary, the results of extended follow-up analyses are consistent with earlier results and suggest that long-term administration of omacetaxine is feasible and safe with dose adjustments to manage toxicities. Durable hematologic and cytogenetic responses may be achieved and sustained in a minority of patients.'

I would say trying Milk Thistle would be helpful as it may well get your liver enzymes down.

Sandy

Hi Bill,

I wonder if you are taking any other medications  such as pain killers like acetaminophen (paracetemol)  that will hammer the liver .

My consultant told me that the Gamma GT measure in the Liver bone test is a good indicator of inflammation-my last one was off range so no alcohol for  a while.

You mention diet as a possibility for liver health-I am always reticent to indicate this as a solution as there is a view even among medics that this is just fad:my practitioner nurse said to me it is up to you if you believe in this.

However if one looks at the entries on the internet one comes across benefits for the liver-coffee,greens especially broccoli,tofu,grains and nuts, fish (omega 3),sunflower,walnuts,avocado,olive oil,garlic ,green tea.No sugar,no fried except in olive oil,limited salt,no processed foods,,minimal red meat (it contains animal fats, saturated fats).

I am not vegan or vegetarian but my diet is very anti inflammatory-it might be worth further investigation ?I hope this helps.

With best wishes

John