Please Help - What's 'Normal'?

[Kelly]

My sister is 47 years old and was diagnosed with severe aplastic anemia in December. She had been going through tests, etc. to figure it out for months and since November had been getting blood transfusions every 2 days because her platelets and cells were so low(2 transfusions each time). She had the AGT treatment (the horse one) about 2 weeks ago and was released from the hospital super fast. The ATG went well but once home she went downhill quickly. On 1000mg cyclosporine and 80mg methyprednison, plus some other drugs - can no longer walk (even ordered a walker off of Amazon believe it or not), her #'s have not improved at all and had to go back into the hospital as they had concerns for her liver. She is now on insulin because she has 'temporary' diabetes from the steroids and she was dehydrated so on liquids, she sounds like a 90 year old woman who walked 10 miles when she sits up even, she can barely pick up her cell phone. We were under the impression that the side effects for the AGT would be flu-like but this is not what we expected.

Has anyone had anything similar? We are new to this and we are looking for help understanding. Most posts I have read do not have these extreme challenges and so I am nervous something has gone wrong and none of this is 'normal'.

[Hopeful]

Hi Kelly,

Is your sister being treated by a doctor at a facility that specializes in AA? This is very important because AA is such a rare disease. If she is not, it would be wise to consult with one immediately in your area. Alternatively, NIH is not that far away.

1000 mg/day is an extremely high dose of cyclosporine. A more typical dosage is 5 mg of cyclosporine/kg of body weight/day. So 1000 mg/day would be a typical dosage for a person that weighed 440 lbs.

A high dose of cyclosporine is 10 mg/kg of body weight/day. 1000 mg/day would be considered a high dose of cyclosporine for someone who weighed ~220 lbs.

How much does your sister weigh? Have they checked her cyclosporine trough levels to see if she is at a toxic dosage regardless of her weight? How long will she be on the high dose of steroids?

Your sister's situation doesn't sound typical to me. I would seek out a second opinion ASAP.

[Neil Cuadra]

I think that 1000mg of cyclosporine isn't an unusual dose right after ATG. But you can expect the dose to be tapered as your sister recovers. She may reach a dose like Hopeful describes and stay at that level for many months or even years. This was my wife's experience.

Determining the right cyclosporine dosage over time, particularly how much to taper and when, is both art and science for hematologists. Taper too soon and you risk your blood counts dropping, and having to set your dose way up again. Taper too late and you're at a higher than necessary risk for side effects.

[Kelly]

Thank you Hopeful & Neil. She has been off the cyclo for a few days.. She weighs about 190 lbs and gained another 20 from the steroids, etc. but you are right on the cyclo maybe being too high. She has been off the cyclo for a few days now but blood #'s haven't improved. She'll continue to stay on her steroid dosage until blood #'s improve. She sounds better now but still unable to walk, etc. Hoping that it means that they just need to adjust the cyclo dosage.

She is at Albany Med and they are working with Dana Farber - at least they were. We are finding out if that is still the case as they definitely should be. Our family is very concerned and have made the suggestion that they have the hospital transport them for full care at Dana Farber.

She has asked us to be swabbed for bone marrow match and so wondering if she should've had the transplant to begin with but will still hope that this works as there is still hope there.

So the answer I see is that it's not normal that she took that bad turn and it could be that the dosages need to be adjusted.

Other family members have suggested there could be too much iron in her so they will ask the docs today about that too.

Thank you and any other thoughts would be great. I really appreciate this forum.

[Tripleal]

Hi Kelly sorry to hear of your sisters misfortunes with her treatment 1000 m of cyclo seems quite high to me but I'm no doctor ,I had atg but with minimal response ended up with bmt 18 months ago all counts in normal range at the moment . I wish your sister all the best and will remember her in my prayers ,









65 year old diagnosed with SAA October 2014

[Kelly]

Thank you Tripleal and CONGRATULATIONS on your positive counts after the BMT. That's great! I'm so sorry you had to go through all this too. All of you. What a crazy, crazy disease and so different for everyone. We hope to hear something soon for my sister and just staying positive right now.

[Hopeful]

Hi Kelly,

Your sister is lucky to have you as her advocate. You really need an expert in AA, especially since your sister is having complications. Ideally your sister would be transferred to Dana Farber. Alternatively, you could schedule an appointment there yourself for your sister and establish a rapport with the AA expert. Then you can more easily direct the treatment decisions with her local doctor. Many will respond to phone calls and emails once you have had that initial visit.

It looks like your sister was on 12 mg/kg/day of Cyclosporine. I was started on that dosage right after ATG as well but built up to a toxic level fairly quickly, as measured by my trough readings. If your sister starts on cyclosporine again, be sure that they check her 12 hour trough level fairly frequently at first.

Typically cyclosporine is continued a minimum of 6 months after ATG. The steroids are typically tapered off as soon as the danger of serum sickness has passed (3-4 weeks post ATG??) It is the cyclosporine and not the steroids that helps while the marrow heals. You will learn patience with this disease. It may take 3-9 months before you start seeing a rise in your sister's blood counts.

Here is a good article to read on the standard treatment of AA:
http://www.bloodjournal.org/content/...o-checked=true

Good luck!

[Kelly]

Hey Hopeful - thank you. I can only take credit for finding this amazing forum. We have a team of advocates for my sister which is helpful but not when none of us actually know anything about this disease. We never heard of it before she was diagnosed.

Okay, we are hoping she gets transferred to Dana Farber and I know she talked to the doc y'day who was in communication with the AA expert from Dana Farber That being said, she said today that they know the dose of cyclo was too high for her. So, it was probably like you but you found out quicker than she did.. when she started getting weaker figured it was just par for the course and waited to see a doctor. We all thought that was normal - the low before the high. So, now we know it's not and if there were a next time, to go right away to hospital.

She is feeling better after being off the cyclo but knows she will have to go back on just with a different dose and will push to keep her in hospital for at least the beginning of that and ensure they check her 12 hour trough levels frequently and that her body can take it. Thank you for that information as well as the article which is super helpful!!

Really really thank you. You've been amazing. I want to fly you up here to be her advocate. You've been through it so you know the questions to ask, etc. We are all so grateful.

[Hopeful]

Hi Kelly,

I don't think any of us knew about these diseases when first diagnosed! I’m glad my experience can provide some benefit to you. I know I have been helped by the shared experiences of those past and present on this forum

I had my cyclosporine checked once a week when I first started on the high dosage. This decreased to once a month on the lower dosage. Now I never have it checked, as I know how my body metabolizes the drug and am on a low enough dosage. Checking the cyclosporine trough is done by a simple blood test 12 hours after taking the pills (when the levels are the lowest). No hospitalization is necessary. For me, a trough reading above 400 was too high. As Neil pointed out, the dosing is as much an art as a science, and different doctors will have different philosophies on the numbers to target for a trough reading, if any. Feedback from the patient is important as well.

It is very important that your sister has her magnesium tested periodically as well. Cyclosporine depletes magnesium in the body, and eventually, she will need to supplement with magnesium. Magnesium is a separate test that must be ordered and is not always on a doctor’s radar to check.

Prednisone will cause muscle atrophy among other issues. I think I was tapered all the way off of it by a month from ATG. Your sister will feel a lot better when she is off the steroids!

One other tip is to start tracking your sister’s blood results on an Excel spreadsheet. Things to track include: HGB, ANC, Platelets, WBC, RBC and MCV (all to see if/when the treatment is working). Also track AST, ALP, ALT, BUN, bilirubin, and creatinine (to monitor her liver and kidney function). I would make notes of the drugs/dosings that she is on at the time of the blood draw and whether she is fighting any illness. You will be looking for trends over time, not just for a single blood test result.

Hope all goes well!

[Kelly]

Thanks Hopeful. This is all very helpful and very good idea about the spreadsheet. I will create one tonight to send to my brother-in-law.

Tracking of everything is super important. She was turning yellow because of bilirubin which we had read online could be an effect of the cyclo however the doctors wanted to test everything else so they did an mri and then an endoscopy but found nothing. There were some complications from the endoscopy which caused pancreatitis and now low calcium so they are watching that. She can't seem to catch a break.. the complications are not related to the AA so that is a plus and she still has enough cyclo in her blood to work with the ATG so fingers crossed. She was in ICU over the weekend but doing better with the hopes to be moved in the next day or 2 and then go back to the main issue - the AA - thank God.

Will write an update... thank you for all your knowledge and support.