Cyclosporin Taper?

[JodyW]

My question is about tapering. Trevor began ATG/Cycl treatment in March and was on 700 mg Cyclo. 350 2x day. On May 1 he was dropped to 350 mg 1x per day. I was able to speak with a Dr. who saw him at the clinic and discussed why he was not on the 350 given 1/2 every 12 hours. He agreed it should be that way and changed his dose to 175 2 x day. He also said Trevor's level's were good at 267. and he wanted them between 100-300. (not sure what that level is but he said it says the cyclosporin is at the right amount). But then he said he was going to start to taper him 50 mg a month beginning next month.

So questions-
When does one start to taper?
What does a normal taper look like?
What do you look for to make sure its not to much?
How low do they go with a taper?
I read on another tread that it can cause a replapse, what should one be looing for to determine how its going?
Trevor's last cbc was WBC 2.3, Plt. 90 , Hg 8.9. At what levels does one look to do a taper?


Thanks,

[Ryan Jay]

Cyclosporine taper is a really hot topic.

Actually, I get a little frustrated with how much contradictory stuff you find out there.

Traditionally, cyclosporine was cut off cold turkey at about 6 months after a response.

Then, when so many AA patients started relapsing, some doctors pushed for a long slow taper to reduce the risk of relapse. I have seen some doctors advocate a 25 mg drop every 3 months.

Some data from Europe supported this approach.

BUT,

According to new research done at the NIH, they have seen no difference in the relapse rate between a long slow tape and an abrupt stop.

Now, some doctors have discussed a very strange phenomenon of taking the Cyclosporine dose all the way down to 25 mg...to the point where it's no longer detectable in the blood. The patient holds his counts fine; then they take that last little dose off, and then the counts start to fall. So there are many cases out there of patients who take 25 mg daily just to keep the little demons in check.

Of course, you also have to factor in the liver and the kidneys. You know how that goes.

Anyway, your son's doctor is the expert, but don't be afraid to bring research and ask questions. My hemo was very receptive to my suggesting a long taper.

Hope this helps.

[Ryan Jay]

700 mg daily sounds a little high to me, so it was probably good to take him down a bit. I´m 6,4 260 pounds and 325 daily is enough for me. But everyone is a little different.

Some doctors still believe in giving patients a mega-dose of cyclosporine at the beginning; others disagree.

At one of the conferences, a "famous" doctor told us that he brings the Cyclosporine down slowly (25 mg per 2/3 months) meanwhile he keeps montoring the patient's CBCs. If he sees a clinically significant drop in the counts, he'll bring the Cyclosporine dose back up to about 50 mgs above the nadir.

So, let's say you got down to 75 mgs daily, and your counts started to dip, he'd pop you back up to 125.

[Lisa V]

Originally Posted by Ryan Jay

Now, some doctors have discussed a very strange phenomenon of taking the Cyclosporine dose all the way down to 25 mg...to the point where it's no longer detectable in the blood. The patient holds his counts fine; then they take that last little dose off, and then the counts start to fall. So there are many cases out there of patients who take 25 mg daily just to keep the little demons in check.

Ryan, is there a study or something in writing that cites this phenomenon? I'd be really interested in finding out more about this, as it tends to support my gut feelings about the way certain medications can work.

Also, wasn't there just a recent study that found evidence that a sizable percentage of patients (30%?) will relapse with a quick taper but that this can often by averted by a long, slow taper? I forget what forum thread this was on, but it seemed like it came out only about a year ago. And now they're saying it makes no difference? I don't know what to believe anymore, but as someone whose husband relapsed after a fast taper, I'd go with the slower the better. Maintaining that last 25mg sounds like a good plan to me too.

[Ryan Jay]

Hi,

Both Dr. Scheinberg and Dr. Antin mentioned it in their presentations at the AAMDS regional conference in Boston. I think Scheinberg was recorded talking about at the Arizona conference as well.

They chuckled when they called it the "homeopathic dose." I think it would be worth doing an investigation as to why this occurs.

The NIH is a little strange about how they define "relapse." Actually, they have a very tight definition of "needing more treatment." Maybe that had something to do with it.

I think it was a European study that showed that a long slow taper reduced relapse to 6%.

[triumphe64]

I know with my PRCA, when I eliminated the prednisone, my counts dropped. So now I take 2 1/2 Mg every other day. It works. My doctor says she has many patients who take a homeopathic dose of some medication for one disease or another. She can't explain it, but she goes with what works.

[KimO]

My daughter relapsed 14 months after finishing a taper that began at 7 months post treatment and lasted about 9 months. For the last 10 months she has been on a 300 mg per day dose of cyclo (200 mg in the eve and 100 mg in the morning to work around side effects) and her counts have been low normal since about three months after resuming the dose. When we consulted at Seattle Cancer Care about a bone marrow transplant they indicated that her chances were good of getting off of cyclosporine completely "within the next five years" but did not want to go on record with a suggested taper schedule.

At her hemo appt last week we all agreed to try dropping 25 mg every three months with monthly CBCs in order to be able to monitor if counts begin to drop. The first four decreases will come out of the higher dose. If it ends up she needs a therapeutic dose long-term it will be easier to determine the lowest amount that works if the taper is very slow. If she is able to taper completely the proposed schedule will take three years.

[rschem]

I was DX saa aug. 2008 treated with horse ATG.350 cyclosporn a day now on 250/day.My DR will not tapper me off cyclosporn.I seem to be tolerating it well.No more tremors or shakes and no mouth sores.Creatine levels were up to 160 but are down to @ 130. I am 64,maybe my age has to do with the descion to keep me on the clclosporn.I seem to be doing well.I do't get neerly as tired although I sleep 10-11 hrs a night and 1-1.5 hrs pm.My platlets and hg are @ 130.

[JodyW]

KimO,

It looks like are children are about the same age. Can you tell me what thought process the doctors used for beginning the taper? Were her numbers good so they said, lets try it? Was it just because it was 7 months? Did she go back on cyclo as soon as her numbers started to drop or was there some specific level that concerned them. I dont think Trevor's numbers are that high to be considering it. They say it is very toxic and they want him off as soon as possilbe, but these docs are not AA specialists so they may not have the same thought process as a AA specialist.

Thanks,

[KimO]

Yes Jody, Shauna is also 23. She was 19 when she was diagnosed. The first taper the docs were going by the protocol that said start tapering at six months (and her numbers were in the low normal range at that point) but I think we were waiting until she returned home from school in Seattle to start so that's why it was 7 instead of 6. I had read the data on better success with a very slow taper so that's why I advocated for but Shauna was really tired of being on cyclosporine so she was all for getting off of it as soon as possible. The compromise was a 9-month taper. Her numbers initially rose as we tapered so we wondered whether it was because her kidneys and liver were happier. However, over the second half of those nine months the platelets seem to drift down. I keep charts on everything so I even ran a trend graph to confirm but the docs were sure that as long as she was still in the normal range we were fine. Her platelets drifted from around 200 to the 150-160 range by the end of the taper and then seemed to hold there while she was off the cyclo for those 14 months -- some months a little higher and one was lower. Then the last test before she headed back to Seattle for he senior year of college the platelets dropped significantly and her ratio of lymphocytes flip-flopped so that the lymphs were about double her neuts. I couldn't convince them it was the start of a relapse so we had to wait another week to establish a trend. Then when they dropped further they started her back on the 300 mg of cyclosporine. At first they continued to drop but not as fast, followed by a couple of weeks of holding steady, then they very slowly started to head in the right direction. It was like watching a bungee jump in slow motion. Now she's been on cyclosporine for the 9 months and the numbers are normal again so we will be trying the extra slow taper to see what happens. The doctor we talked to at Seattle Cancer Care was very experienced in AA and immunosuppression in particular but she said that there is no magic schedule -- it's more of an art than a science to adapt the schedule to the patient based on how it goes. My gut feeling is that Shauna is probably one of those that will need to be on cyclosporine for a long time if not the rest of her life. What we're trying to do now is find out what the lowest magic number is that keeps her immune system in check. I'm happy to answer any other questions and if you want to exchange emails I think we can send those to each other the address through the message system on this board so that we don't have to post them on the internet. I'm praying for full recovery for Trevor so he can go on and have a great life!

[JodyW]

KimO
Thanks for all of the information it is very helpful. Trevor's numbers are starting to drop and the dr.'s are talking about increasing his cyclosporin when just last week they said they were planning on tapering it. He is now one point away from going back to transfusions.

You referenced the lymphocytes being double the neuts.. What importance does that have? I have all of Trevors cbc tests but not sure of the importance of most of the numbers. I would like to exchange emails so I will look for that contact section you mentioned.

I pray things work out for Shauna as well and appreciate you sharing her story.

[holmg418]

I am a 65 YO and was diagnosed with Severe Aplastic Anemia in Jan 2010. I had Horse ATG and then CSA. Over the next 6 months my counts recovered to near normal. I started a slow CSA taper a few months ago and we are reducing the dosage 25MGs/day every 2-3 months. So far I have reduced my dosage from 400mgs/day to the current level of 250/day.

My doctor and I are watching for signs of a relapse. What does a relapse look like? Do you usually see a drop in platelets first? Is the drop dramatic or a slow downward trend?

How long should you go between lab reports during the taper process? I get nervous dropping my CSA dosage the 25 mgs and then not getting blood work for 2 months.

When/if you do have a relapse what action do you take to get your counts back? I read someplace that it is best to raise the CSA 100 mgs. Is that true? Can/should you then try to taper again?

[rschem]

I DX2008 have been on cyclosporne for past 2.5 years My Dr recentlyhas tapered me only from 150 x2 per day to 125 x2 per day.I was quite disappointed about a year ago when I was not tappered but I am doing very well on my dosage.If I were tappered too low or off I would likley have a relapse and may not recover.Partly because of my age 64.I am quite happy with my dosage as the side efects are very miminal now.I used to have tremmors and mouth sores but not so much now.I hope this is helpful.

[Hopeful]

Hi holmg418,

I am also tapering 25mg every 2-3 months. I get my CBC done monthly. I think this is important because you want to spot the trends. I had to ask for the extra CBC, but my doctor agreed to do it without too much of a fight

The approach that I am taking is that if I see a significant drop in platelets (15-20%), and I have not been recently sick, I will ask for a retest after 1-2 weeks. If it is still dropping, then we will treat it as a relapse and increase the cyclosporine to my "stable dosage" (4-5mg/kg/day).

If things are slowly trending down and I'm worried about it, I will ask to stay on the current dose longer (or even increase it 25 mg) until things are stable.

If things are pretty stable or rising, I will continue with the taper schedule as planned.

Ultimately, you are in charge of your taper schedule! If you are worried that it is too fast, you can slow it down - just tell your doctor that you are doing so and discuss the risks/benefits.

Best of luck! Get that extra CBC! It will give you tremendous peace of mind

[KimO]

Hopeful, your schedule sounds very similar to Shauna's. She gets CBCs monthly and sees the hematologist every 3rd draw and they review to confirm whether to go down another 25 mg. This last time her WBC had dropped so they waited 2 weeks and retested to confirm it would rebound before doing the scheduled taper. She's down from 300 mg/day to 250 after 6 months. If the schedule holds the taper will take two years.

Jody, for Shauna her ratio of lymphocytes to neutrophils was far higher when she was first diagnosed and again at relapse. Normally her ratio is along the lines of 55% neutrophils and 45% lymphocytes but when she relapsed it got as bad as 80% lymphocytes. That isn't necessarily the case for others.