Advised to start chelation

[Mseth]

My mother has been advised to start chelation therapy. From dx, she has received 20 units, and is doing fine as of now, being able to care for herself, has decent appetite and so on..Her recent ferritin levels are 2600 at one lab and 3600 at another, within the same week.
The chelation drug prescibed is Assunra(made by Novartis), same as Exjade.It is used extensively by Thalassemia patients(mostly children), who are transfusion dependent from birth due to a genetic disorder.

I am extremely worried about if and how she will tolerate this medicine. She is 77 years. I understand the iron overload and associated toxicity, but would be gratfeul if i could get some advice on the following:
1. How long(months/years) does the iron overload take to cause damage?
2. The iron overload may create damage at a later stage, but the chelation drug will start its renal & hepatic damage almost immediately, is it better to not take the chelation drug?
3. If the kidney & liver get affected, will the affects reverse on stopping the drug?
4. Will normal anti-nausea/anti-diarhea medicines help control these symptoms?
5.What are the factors that one should consider before starting on this? Is it advisable to get heart & liver MRI done to see if there is already an overload happening?
Thanks in advance for any suggestions and experience.

[Birgitta-A]

Hi Mseth,
It takes years for iron overload to cause serious damage in the liver (we manage well with 33% of the liver) and the heart.

If the creatinin or liver tests will increase too much the drug will be stopped. We manage well with one kidney which means that we have much reserve capacity.

I don't think we will get new liver cells or that the kidneys are repaired but that will not be a problem if these organs are OK initially.

It is important to start slowly with the drug and look out for adverse effects. I could only tolerate 500mg Exjade/day but according to my weight I should have had 1250mg. My WBC decreased when I took 1000mg. I had no other adverse effects.

I think it will be OK to control lever and kidney blood tests and follow them closely.

I had MRI of heart and liver done after about 50 units of blood. There was not a trace of iron overload. I had started with Desferal after 40 units of blood. Now I have received 186 units of blood with Desferal during 4 Days with trsfusions. My ferritin is about 1900. My liver tests are OK.
Kind regards
Birgitta-A

[Mseth]

Hi Mseth,
It takes years for iron overload to cause serious damage in the liver (we manage well with 33% of the liver) and the heart.


Hi Birgitta-A,

Thanks for the reply. My next question is if there is an answer as to how many years can one manage without chelation, if getting regular transfusions. How does one decide whether or not to take the drug and risk the adverse effects. The mixed reports on whether or not chelation is an advantage for older MDS patients confuses the issue further.

[Birgitta-A]

Hi Mseth,
Yes, this question is complicated. I don't think anybody knows how long we can manage with txs without chelation. Some doctors mention that patients who are supposed to live more than two years should start chelation when the ferritin level is more than 1000.

If your mother's liver and kidney tests are OK she could start to take 250 mg Exjade per day. The tests could be controlled every week. If they are OK the Exjade dose could be increased slowly.

You know all iron chelators can decrease the frequency of txs. Eventually the chelators decrease the oxidative stress in the bone marrow.
Kind regards
Birgitta-A

[Mseth]

Hi Birgitta-A, thanks for the suggestion, i agree that a low dose may be the best way to start. Always very anxious with any new drug. I hope and pray that she is able to tolerate it and has good response in bringing down the ferritin.

[Birgitta-A]

Hi Mseth,
Here is an abstract from the Hematology Conference about MRI examinarion of MDS patients. In short they show that they often don't find iron in heart (cor) though many patients had iron in the liver.

This finding is not new - I have read it several times before.

http://www.mdsbeacon.com/resources/mtgs/ash2013/abs/2819/
Kind regards
Birgitta-A

[Mseth]

Hi Birgitta-A,

Thanks for the link, is it that the tests are not accurate for seeing iron in the heart, or that iron overload does not happen in the heart and mainly affects liver.
The drug insert(it is made in switzerland, and marketed in India under name Asunra), mentions increased creatinine levels as a very common affect. As you have suggested, weekly monitoring will be important, my mother will start with 100 mg(1 tab), and increase gradually over next few weeks.
Thanks for sharing your experience and information.

[Birgitta-A]

Hi Mseth,
In this abstract they write that the method perhaps isn't OK for measuring iron in the heart. Otherwise they write that MDS patients are different from Thalassemia patients who start with txs when they are children and that in MDS the liver often manage to protect the heart and other organs during several years.
Kind regards
Birgitta-A

[Mseth]

in MDS the liver often manage to protect the heart and other organs during several years.


Hi Birgitta-A,
While this finding is encouraging it also confuses the issue on whether using chelating drugs is an advantage or not in elderly MDS patients, the drug may lead to a deterioration in quality of life and other adverse effects quicker than what they may experience without chelating agents.

[Birgitta-A]

You know many patients can take Exjade - perhaps not the full dose - for years without adverse effects.

In Sweden Desferal that is given intavenously in a port during four days in connection with txs is the first drug. I have received 75 doses of Desferal in a small home pump without any complications or adverse effects.

I don't really think txs and Deferal make my quality of life lower but I have been tx dependent since dx 2006 except for almost 3 years 2010-2013 when I had Thalidomide.
Kind regards
Birgitta-A

[Mseth]

Hi Birgitta-A,

It is the positive experience that some like you have, which encourages us to even think about giving it a try.
I will post the response once she starts.

Many thanks.

[Birgitta-A]

Good luck!
Kind regards
Birgitta-A

[Mseth]

Hi Birgitta-A,

Thanks for your good wishes. First week of 100 mg/day of Asunra(exjade equivalent) has gone off fine, now increased to 2X100 mg/day. Hematology doc will be unhappy with this low dose as he wanted to start with 800 mg/day. But gradual increase seems safer to do.

Thankyou.

[Birgitta-A]

Hi Mseyh,
Very good that you managed to make the doctor increase Asunra slowly. There is no hurry when your mother probably will take the drug during a very long time.

Do you follow your mother's counts and creatinine (a kidney test)?
Kind regards
Birgitta-A

[Mseth]

Hi Birgitta-A,

Yes, i follow the counts which are done every 2 weeks. Following the creatinine levels as well now, after 1 week of 100 mg asunra, creatinine is still same at 0.7 (ref range 0.5 - 1.5).
Thanks for taking the time to read my posts.
Regards.

[Birgitta-A]

Hi Mseth,
Good that your mother is OK this far and that you can support her:)!
Kind regards
Birgitta-A

[Mseth]

Hi Birgitta-A,

Is there a way to calculate how much the Ferritin should reduce with chelation and over what period of time? And the additional burden that comes with each transfusion?

Thanks.

[Marlene]

John was on lower doses of Exjade and it really took a long for the FE to come down. And at the time, he was not transfusion dependent. FE fluctuates too much to be a used as a reliable indicator of iron excretion.

If I am remembering correctly, each unit of packed red cells has 200 - 250 mg of iron.

This is from the RXlist.com http://www.rxlist.com/exjade-drug/clinical-pharmacology.htm

"Pharmacodynamic effects tested in an iron balance metabolic study showed that deferasirox (10, 20, and 40 mg per kg per day) was able to induce a mean net iron excretion (0.119, 0.329, and 0.445 mg Fe/kg body weight per day, respectively) within the clinically relevant range (0.1-0.5 mg per kg per day). Iron excretion was predominantly fecal."

It's very difficult to reduce iron while still transfusion dependent. Sometime all you can do is stop or slow down further accumulation. A lot depend on the dosage you are taking. We knew of one person who did IV desferal 24/7 in order to get his FE lowered. That was a very aggressive approach.

[Mseth]

Marlene, thanks for responding. I now know not to expect a great reduction in ferritin, my mother is currently on 10 g per/kg dose, gradually increasing and keeping a watch on kidney & liver function.
Each unit adds in about 250 mg of iron, but not sure how much it directly adds to ferritin. I read sometime back that its 100 ferritin points per unit, but have not found that article again.

[Marlene]

Sorry....thought you meant iron when asking about the FE.

I don't think you can actually depend on FE to be an accurate indicator. Once it's elevated over 1000, pretty much anything can cause it to rise. John's would bounce around all the time. We'd see jumps of 1500 points and then drop the next week. So many things can effect it. It seems it would stabilize for months within a specific range and then all of a sudden drop only to hold at that level for a while. The closer we got to 1500 the less erratic it behaved.

Once it gets below 1000, it seems to behave better. But our doc said that even then, you need to look at the entire iron profile.

John had to stop it eventually because his kidneys were being effected. He never got to full dose so it was very slow going for him.

[Mseth]

Hi Marlene,

Thanks for sharing the experience.Did you find any specific foods or remedies that helped the side effects & tolerbality even a little bit? I have read some posts emphasising on keeping well hydrated which helps to some extent.

[Marlene]

There was nothing that seemed to help him with the exjade side effects. And we tried many things. Homeopathy helps a tiny bit but Exjade always won out in the end. Nausea was the most troubling. He would just have to take a break from it for about a week or two and then start up again. He had the same problem with desferal.

John was on a low dose for about two years. He started at 500 and worked up to 750 mg. 1000mg was too much for him. It wasn't until the last couple of months that his kidney panel was off. Even 250 mg would cause the creatinine to rise.

[Lbrown]

I'm taking exjade, but I really don't understand why the dose is based on your weight, when the blood transfusions aren't. I'm supposed to take 2000 mg a day but I usually take 1500 mg.

Deb

[Mseth]

Hi Deb,

Its good you are able to tolerate 1500 mg/day, how long have you been on chelation and are you able to have lesser side effects than when you started?
Do you monitor your kidney & liver functions regularly?
The heme doc says that with Asunra(the exjade equivalent in India), most tolerate well and if there is an issue, it normally happens within 1st week or so, after which the body begins to adapt to it.

Thanks for sharing your experience.

[Lbrown]

I guess I've been taking exjade for 3 years or more. I wish it was as cheap here (Canada) as it is in India though. I really hate taking it and sometimes I am able to get away without taking it for awhile. I get my counts done every 2 weeks, creatinine and ferritin too.

Deb

[Mseth]

Hi Deb,

Thanks for the reply. Does this dose keep ferritin under control, while still getting transfusions?
Yes, fortunately the drug is better priced in India, else Novartis would have missed out on the large number of thalassemia patients who would not be able to afford a higher price. Still, for us it is expensive, as everything has to be managed privately - no govt subsidy or insurance.

Merry Xmas and best wishes for the New Year!!

[Lbrown]

Yeah, I guess it keeps it under control.

Deb

[Mseth]

Hi all,

Just to update this thread, and for those who may be starting out on chelation - After starting out with 100 mg then 200 mg and now 400 mg/day of asunra(exjade equiv) for last 5 weeks, my mother is able to tolerate it well, creatinine is normal at 0.73 (range 0.5 - 1.3), Ferritin down from 3600+ to just below 3000. She has also received 4 units(2 units twice) pRBC in this period.

[Birgitta-A]

Hi Mseth,
Very positive that your mother tolerates Asunra (Exjade) and that the drug has a positive effect on the ferritin level. All iron chelators can lead to higher HGB eventually by reducing the free radicals in the bone marrow. Hopefully your mothe will see this effect too.
Kind regards
Birgitta-A

[Mseth]

Hi Birgitta-A,

Thanks for responding.

Is there any study or information on drop in ferritin levels and HGB increase, at what level of ferritin can we expect any improvement in HGB? Ferritin at diagnosis was 980. The doctor also is of this opinion that there have been hematopoeisis improvement in people after start of chelation, but for that he said she should be on minimum dose of 800 mg/day.

She has increased the dose now to 600 mg/day. Will update with next reading.

Thankyou.

[Marlene]

Glad your mom is responding well to the chelation.

[Birgitta-A]

Hi Mseth,
I wonder how your doctor knows how much Exjade that is needed to increase the HGB? I have never read anything about that and we know that everybody reacts different when we take drugs depending for example on liver and kidney function.

Here is a study about Exjade and HGB: http://www.mdsbeacon.com/news/2012/05/03/exjade-deferasirox-may-improve-blood-cell-counts-and-reduce-transfusion-needs-in-mds-patients/
Kind regards
Birgitta-A

[Mseth]

Hi Birgitta-A,

I think doctor may have meant that 400 mg is too low a dose to expect an improvement. My mother is approx 43 kg, so starting dose had been put at 800 mg/day to be increased further. Maybe at this dose the iron chelation would be higher/faster. I don't know, just guessing.
If she does fine on 600 mg/day, it can be further increased after few weeks.

Thankyou for the link, I hope we too see some response and HGB increase over a period of time, the study was done after a year on exjade.

[Mseth]

Glad your mom is responding well to the chelation.

Thanks Marlene,hope that it continues fine and there is some HGB response as well.

[Mseth]

Hi all,

Ferritin level has come down from 3600 in Dec2013 at start of chelation to 2300 in Feb 2014. :) No increase in HGB levels though. :(
Creatinine increased slightly to 0.86 (from 0.73 to 0.83 to 0.86). Though this is still within normal values of 0.5-1.3, it seems to show an increasing trend. At what creatinine level should the asunra(exjade) dose be stopped or atleast reduced? The dose has been increased to 800 mg/day which is the prescribed starting dose for her.

Many thanks in advance for reading my post and any advice.

[Birgitta-A]

Hi Mseth,
Very good decrease in ferritin level! There are many patients without an increase in HGB though the ferritin level is lower.

I think the Exjade dose should be reduced if/when the creatinine is 1.3 or higher.

Tell your mother to drink as much as possible. That makes the kidneys work better. In fact dietists in reports from conferences tell us to try to drink 2 L extra per day when we have MDS or similar diseases. I like to drink much and have done that since dx.
Kind regards
Birgitta-A

[Mseth]

Hi Birgitta-A,

Thanks for responding. I always look forward to your opinion.

I read another thread where you had mentioned neck pain, i hope you are well now and managing the pain well.

The ferritin drop is positive, this response has happened with a dose of 600 mg/day, I wonder if it is better to keep the drug at that dose and therefore maintain the creatinine levels than to increase the dose of the drug and put additional work for the kidneys. The worry is if the creatinine levels will not return to normal once it increases beyond the normal range. Even at 600 mg/day, the creatinine is showing a gradually increasing trend, but as the doctor had prescribed 800 mg/day, my mother has increased to this dose for last 2 weeks. We will see what the next blood draw shows.

[Birgitta-A]

Hi Mseth,
Yes thanks, after 4 weeks my neck pains at last disappeared.

Very good that you are following the creatinine. If the doctor gives your mother a lower dose of Exjade her creatinine should decrease.

As I probably have written before we manage well with one kidney - they have much reserv capacity.
Kind regards
Birgitta-A

[Caregive]

Husband on Exjade for a month. The place we get it from found a way to reduce our cost from $175 a month to $75 a month. Quite a difference. With other ailments to deal with I am not sure what this drug will do to him. And I don't know if he will notice anything about his health with the ferritin hopefully lowered. I have been following this site and this is the first time I posted here. I wish you all well. Gets lonely with no one to help us locally and hard to explain to people what's it's all about. But we really focus on vegs and fruits and low dairy intake and low meat intake and low gluten intake. Other docs are happy with his cholesterol and such so I think I'll keep doing what I am doing which is all I can do. Cook from scratch, walk the mall, dr appts, transfusions. Contribute to this organization and ask others to do that. We are no where near a support organization so this site helps.

[Mseth]

Hi Caregive,

Does your husband have a MDS diagnosis or some other bonemarrow ailment? Since he is on exjade I presume he is getting regular transfusions. As you can read from this thread I was very wary and anxious of how my mother would tolerate chelation drug, but starting out with a low dose has helped and she is doing ok. Have you been monitoring the ferritin and creatinine as well, exjade will increase the creatinine(a kidney related function) so its important to keep a watch.
As you can see from the numerous posts and threads on this forum, there are many here who will be happy to help you with advice and suggestions whenever you need, so post and ask questions freely.
You may find someone in your area and/or with the same issues you have.
I found an MDS patient in Delhi, India through this forum. Coincidentally, his and my mothers case is almost identical and we now connect and share information regularly.
Wish you and your husband well!!

[Mseth]

Hi Birgitta-A,

Very good that your neck pain disappeared. Was it related to the MDS?

The lab results after 2 weeks of 800 mg asunra(exjade) show creatinine at 0.98(increased from 0.86, 2 weeks earlier). Range 0.5 - 1.3. Ferritin now 2086. I hope the doctor will decrease the dose to 600 mg/day as with this dose, the ferritin was reducing and creatinine increasing very slowly.

[Birgitta-A]

Hi Mseth,
No, I have had problems with my back the latest 50 years but only 4 - 5 days - never one month.

Perhaps you are right and the Exjade dose should be lower.
Kind regards
Birgitta-A

[Caregive]

Thank you to the two of you who seem to be the ones quite knowledgeable about these illnesses. Husband has B12 anemia, IgG kappa MGUS, low grade MDS. And other health situations. He was on aranesp but that didn't help him. Now on Exjade and we have an appt next week to check blood levels. He gets transfused about monthly. His red cells don't mature. His platelets and white cell levels are normal. He is doing well going about his life doing outside activities, yard and garden, farm equipment repair, walking and all. I am so focused on what I can do but feel like I'm swimming in phone calls and paperwork. Also I make our meals super-healthful and encourage him to drink lots of water.

It's fascinating to me that this site includes people from all over the world. I was on another MDS site where a man in Iran was asking questions and I feel for people who live where there is simply less medical care available. Which makes me think conditions of the blood and other things are underdiagnosed so we really don't know true numbers of who has what. How many people are tired and never see someone who recognizes the possible causes. Health care for all. Thanks for listening.

[Birgitta-A]

Hi Caregiver,
Very positive that you try to learn as much as possible about your husband's disease and do so much of the paperwork and phone calls at the same time as you make your meals super-healthful.

You know the first 4 years after my dx MDS Interm-1 I only received supportive therapy since I was afraid of the adverse effects of chemo. My EPO was high so I never reveived Aranesp or similar drugs.

Then I needed txs every week and accepted Thalidomide that has very positive effect during almost 3 years and now I am taking Revlimid with good result.

Hope your husband's disease will continue to low grade!
Kind regards
Birgitta-A

[Mseth]

Hi Caregiver,

Your husband's MDS seems similar to my mother's MDS, with the red cells affected, monthly transfusion, while whites & platelets are normal. I agree with you on the amount of paperwork, appointments, tracking blood counts etc etc, its quite a handful and added to that is the fear of the unknown and progression of the disease.
MDS is a rare and rarely diagnosed problem in India, hence no centers of excellence and limited experience in hospitals here.
Has revlimid been recommended as a treatment option?

[Caregive]

Mseth, thank you. No, revlimid has't been mentioned. What is it supposed to do? I'll have to ask at our next appt. Next event is getting a port put in. Lady at the hospital on the phone was so very nice. Such things do help the situation. Peripheral appointments, for other things, coming up too but April should be a quiet month so we can go visit out of town. And get the garden going. We went to a place of excellence and got a second opinion. Same as first opinion with some slight changes. On we all go.

[Mseth]

Hi Caregiver,

Revlimid is an oral immunomodulatory drug, approved for MDS with del 5q chromosome abnormality. In non del 5q MDS, the response is betwen 20%-25%Some forum members with non del5q are responding to this drug and are transfusion independent.
Since the response rate is low, its a personal choice between trying it or staying with supportive care, i.e. transfusions.
All the Best!!

[Mseth]

After a consistent drop in Ferritin initially, thers negligible decrease in the last month from 2086 to 2045. Does this happen during chelation? Increasing the Asunra(exjade) dose may help but will also increase creatinine.
Wheatgrass juice did not help earlier, can IP6 help in chelation?

[Birgitta-A]

Hi Mseth,
You know the ferritin value can continue to be high because your mother has had an infection lately. One ferritin value does not really tell us much about the chelating effect of Exjade.

IP6 is supposed to have a chelating effect like wheatgrass juice but only some patients response to that drug.
Kind regards
Birgitta-A

[Caregive]

Birgitta, what is IP6?

[Birgitta-A]

Hi Caregiver,
IP6 is Inositol. The drug is supposed to be an iron chelater but can also chelate magnesium, cupper, zinc and other metals. As Marlene writes the balance between these metals is very important.
kind regards
Birgitta-A

[Marlene]

From everything I've read on IP6, it's not going to be very effective when iron is very high. You would need to take very large doses and I'm just not a fan of that. All antioxidants have some level of chelation properties but they are not very efficient in extreme cases that occur with transfusions. I don't think you would see any movement in iron levels.

[Mseth]

Hi Birgitta-A,

Yes maybe some hidden infection leading to high ferritin. She also had unexpected lower than usual counts during this blood test, could this also be due to an infection?

[Birgitta-A]

Hi Mseth,
Yes, infections can decrease all counts - that is why I always live like I have low WBC even when they really are OK. Three times the neutrophils have been so low that I got fever (38.5) and had to go to the hospital for antibiotic intravenously.
Kind regards
Birgitta-A