Cyclosporine Taper

[MK921]

Hi everyone,

I am a 25 year old female, diagnosed with aplastic anemia in May 2010. When I entered the hospital, my counts usually hovered around: ANC-500, Hematocrit-20, and Platelets-10. I was receiving red blood cells about every week and platelets twice a week. I have a blog about my journey with this illness: http://meaghansbadblood.blogspot.com...bad-blood.html

I received ATG and cyclosporine in June 2010 and have been seeing my counts very slowly but steadily improve. It has been 3 months since my last red blood cell transfusion and 2 months since my last platelet transfusion. My counts at my last visit: ANC-1500, Hematocrit-30, Platelets-40.

In January it will have been 6 months since my ATG and my doctor wants to begin to taper my cyclosporine. His plan is to taper over about 3 months (25 mgs per week) but from what I read, people are less likely to relapse if they do a 6 month to 12 month taper. I've told my doctor this but he still seems confident with a 3 month taper. Any advice? I haven't had any side effects from the cyclosporine, so if there is no harm in being on it, I'm inclined to try to convince him to let me draw it out.

Thanks!

[Hopeful]

Hi Meaghan,

Your initial presentation was very similar to mine.

My local hematologist was for stopping cyclosporine at 6 months. However, I also consulted with another specialist who saw a LOT more aplastic anemia patients. He recommended that I didn't even consider tapering at 6 months while my counts (like yours) were on a slow but stable rise. His recommendation was to stay on cyclosporine until my counts were stable for 3 months and then to taper very slowly at 25mg every 3 months. I did drop my dosage significantly at 6 months from 12mg/kg/day to a more reasonable 5 mg/kg/day with no ill effects because I *felt* the dosage was toxic for me. There are no solid guidelines on cyclosporine for bone marrow failure diseases. However, there seems to be a lot of research stating that 6 months is too early to stop and that a rapid taper is not advised.

What is your current cyclosporine dosage in mg/kg/day?

[Hawaii Bill]

As long as you are not suffering from kidney toxicity and your side effects are insignificant, I would get another opinion if your doctor insists on a fast taper. If you are capable of seeing Dr Paquette at UCLA, please try.

I am convinced that I lost part of my initial response to the ATG with too fast a taper, also begun around 6 months from the first dose of ATG.

There is good enough recent research that indicates a slow taper reduces relapse. Stand fast with your doctor. Show him the research.

Good luck!

[MK921]

Right now I'm on 175 mg twice a day. Thanks for the responses. I hate the cyclosporine, but i'd much rather be on it for a while longer now than have to start all over again.

[Neil Cuadra]

I would ask the doctor if it makes sense to decide how fast to taper cyclosporine based on test results over the next months, rather than decide on the duration in advance.

You have to remember that this is a tradeoff, and the reason you don't want to stretch the taper out indefinitely is that cyclosporine has its own risks and side effects. Patients can usually put up with minor side effects like excess hair but cyclosporine can adversely affect their kidneys and blood pressure. You don't want to taper too quickly and risk a relapse but you don't want to be on cyclosporine longer than necessary and damage your kidneys. That's why it seems to me that a doctor would want to determine when to reduce the cyclosporine dose, and by how much, based on ongoing test results rather than determining how long the taper should be ahead of time.

[Hopeful]

Here is the study in support of a slow taper:

http://onlinelibrary.wiley.com/doi/1...7.06903.x/full

I've heard that NIH, on the other hand, favors a fast taper.

[Lisa V]

Thanks for posting that link, Hopeful.

I'm with the others in pushing for a slower taper. My husband is one who relapsed after a quick taper, and we had to start all over again. His doctor at the time didn't think it would matter, but I suspect he was more familiar with cyclosporine use in organ transplant patients than with the unique dynamics of ATG/cyclo and AA patients. If you can show your doctor some hard evidence in the form of a study, you may be able to have a more productive conversation.

I like Neil's idea of playing it by ear based on test results. That in itself would probably necessitate a slower taper in order to make sure your counts have stabilized at each level before making the next reduction. Seems like a common sense approach, and if you are not currently having problems with creatinine or blood pressure from the cyclo, I don't think the added risk of prolonging it a bit is enough to outweight the risk of relapse.

[MK921]

Thanks, everyone. This is all very helpful.

My doctor had said at one point that the cyclosporine may actually be keeping my counts low. Has anyone heard that before?

[Hopeful]

Originally Posted by MK921

My doctor had said at one point that the cyclosporine may actually be keeping my counts low. Has anyone heard that before?

That is very interesting. I am 2 years post ATG and am still taking cyclosporine. Since about 7 months post-ATG, my platelets have slowly risen at a rate of about 3k every 3 months.

Last month, I cut my cyclosporine by a mere 25 mg because of kidney troubles, and low and behold, my platelets jumped 15k...in 1 month! I will have to wait until next month's labs to ensure this is not a fluke.

If you have the chance, please ask your doctor why he thinks cyclosporine may keep counts low. I have always wondered if the stress on the kidneys of cyclosporine causes a decrease in the TPO generated by the kidneys, which consequently decreases platelet production.

[Lisa V]

Originally Posted by MK921

My doctor had said at one point that the cyclosporine may actually be keeping my counts low. Has anyone heard that before?

I actually asked Ken's doctor about this at his last visit, because although his Hgb and even his Plts have finally reached normal range, his white count remains on the low side. I thought that maybe the cyclo's anti-T-lymph activity might be lowering his overall WBC, since his ANC has generally been pretty good. The doctor didn't think so, though. He said that that could be a factor, but that it should be more than offset by the cyclo's keeping the disease itself in check. He didn't have an explanation for the lowish WBC, but was encouraged to see that it could still mount an effective response when needed. Who knows?

[KaydeeRichardson]

I was on cyclosporine when I was 10, not fun stuff, always left a wierd taste in my mouth!

[akita]

@Hopeful, cititing the study in your link:
"We found a significant association between relapse risk and rapid CyA tapering: 60% compared to 7·6% in the ‘slow tapering group’ (P = 0·001)."
This is a big difference!

@MK921
I had this experience with doctors , and many other have it, that tapering of medicaments is forced or forbidden. Why that?

Tapering over a longer time period could also be favourable because of a reason which has not been mentioned in this thread: It is so with neuroleptics: The body-system gets adapted to the medicament and in case of tapering there occur reactions who would initially not having to do with your primary sickness, but instead with the adaptation and its tapering.

Therefore it is advised to reduce neuroleptics very slowly except when they have not been taken over a longer period than 14 days.

The same problem it is possibly with the immunsuppressive agents after stem cell transplantation. Cyclosporine is also such a medicament. A friend of mine had a heavy worsening of her Graft-Versus-Host-Disease after a fast taper of her immunosuppression, and also i have got a new sort of GVHD - a sclerodermiforme GVHD of the skin - last autumn after too fast tapering of Prograf.

I discussed this problem with my doctor who said to me: "Of course we try to reduce the immunosuppressive agent as fast as possible as it causes unwished side-effects. We know, that some patients will get bad side effects from the reduction, but we have to try the reduction at some time-point.. We cannot see in advance which patient would tolerate it an which not. To go sure that reduction would not cause side effects we would to let all patients stay on the immunsuppressive agents for their whole life..".

My personal opinion is: that this doctor never has tried to evaluate the different experiences with the reduction of immunosuppression in the different patients.Where is the statistics for that? It is so important regarding the consequences it has for the patient, reducing slowly (how slow) or fast oder never..

Kind regards,

Margarete