End of the Road - 8 weeks from Diagnosis to No Hope

[Alcof]

Well it has been a very short ride. Hopes were dashed today when our doctor said he didn't think my Dad would survive ATG treatment and there was nothing he could do for us. I asked how long he thought we had - that people with AA usually take a year to die without treatment, didn't they? He said it would be a lot sooner than that given his age and deterioration. It could be any time.

So now we have to decide how to die.
Or mortgage the farm to pay for some Eltrombopag. Can't get it any other way in New Zealand except to buy it ourselves. $8,000 USD a month. And who knows if that will work.

Has anyone else had experience with being turned down treatment with ATG? What path did you choose to take?

Sorry if this has been a dark post. It has been a bit of a dark day for us.

Appreciate any thoughts.

[Marlene]

Sorry to hear this. My first reaction is to get a second opinion. And IMO, if he's still on cyclo, I would consider stopping it. Doesn't appear it's helping. I would be looking into supporting him via nutrition and maybe some alternative approaches. Palliative care is needed in that his transfusions need to be managed well. Get his red cell up to decent level and determine a threshold for transfusions. It usually around 8 for HGB. For platelets, it can be as low as 5K as long as there is no prolonged bleeding. But most usually use 10K.

He may benefit from growth factors like procrit or neupogen. They can run a blood test to check his own EPO levels and if it's below 500, procrit may help boost the production of red blood cells. But it can take up to 14 weeks before you can actually see an increase in transfusion intervals.

What are his D, B12, folate, iron, copper, B6 and zinc levels? The D, B12 and folate need to be at an optimal level. Low-normal or high levels of B12/folate need to be explored. If he's taking supplements now, he would have to stop them 4 or 5 days before testing to a more accurate read.

I would also venture to guess that the antibiotics disrupted his digestive system's bacteria and he probably needs to restore it back to a good balance with probiotics.

Many time with this disease, it gets really dark before it gets better.

[Hopeful]

Originally Posted by Alcof

Well it has been a very short ride. Hopes were dashed today when our doctor said he didn't think my Dad would survive ATG treatment and there was nothing he could do for us. I asked how long he thought we had - that people with AA usually take a year to die without treatment, didn't they? He said it would be a lot sooner than that given his age and deterioration. It could be any time.

So now we have to decide how to die.
Or mortgage the farm to pay for some Eltrombopag. Can't get it any other way in New Zealand except to buy it ourselves. $8,000 USD a month. And who knows if that will work.

Has anyone else had experience with being turned down treatment with ATG? What path did you choose to take?

Sorry if this has been a dark post. It has been a bit of a dark day for us.

Appreciate any thoughts.

Alcof,

I am sorry to hear this news, but I would not give up hope! If I were in your situation, I would seek out another opinion. However, I would not stop the cyclosporine if his kidneys are handling it okay. It takes 2-3 months for cyclosporine to build up in a person's system. What is his current dosage and what is his weight in kilograms? I just want to confirm that he is on a standard dosage (5mg/kg/day).

Has he stopped the prednisone? Prednisone is not a treatment for AA and has terrible side effects including increasing the risk of infection.

The infections that he picked up are likely responsible for his increased transfusion requirements. Fevers will burn through platelets and RBCs at a rapid rate.

It takes ATG/Cyclosporine 3-9 months to work (typically). Cyclosporine alone is a weaker immune suppressant. So it seems logical to me to think that it may take longer than 8 weeks to see results, especially if he picked up some infections during that time. Are you seeing any signs of stabilization of his condition?

[Hopeful]

It is my understanding that the excitement around Eltrombopag is when it is used *in combination* with ATG. I haven't read or heard anything about its effectiveness when used alone. This is likely because the immune attack must still be stopped.

A good predictor of response to immune suppression from NIH is the level of ARC or ALC. Having ARC levels above 25,000 or ALC levels above 1,000 increases the probability of a response (60-80% vs 40% with low ARC/ANC).

I remember reading a paper about using a lower dose of ATG over a longer length of time for older patients. I posted it in this forum before but will have to dig it up.

Here is a great presentation out of Europe on treating older patients with AA that I found. It discusses using Cyclosporine alone, ATG success with older patients, and low dose ATG:

https://www.ebmt.org/Contents/Resour...helliFinal.pdf

Good luck!

[Sally C]

Hi Hopeful,
I have to respectfully disagree with your statement about Eltrombopag. My husband has been transfusion free for 3 years now after taking Eltrombopag started in the spring of 2011. He came off of Eltrombopag once his platelets went over 100,000 - which he still maintains to this day - and has taken no more Eltrombopag. He never took ATG. He had over 125 platelet/blood transfusions before taking Eltrombopag.
He did have Campath in Spring of 2009 but it did not help his counts and nearly killed him with an infection a month after.
NIH has had wonderful success with Eltrombopag although I can't say what treatments the other patients had.
If anyone is interested in reading a more detailed account of my husband's journey, please look up my past posts on Promacta (Eltrombopag).
God Bless all,
Sally

[Hopeful]

Hi Sally,

I am going to respectfully counter-argue

Campath is a heavy-duty immune suppressant. Although your husband's marrow may not have been able to recover on its own after the treatment, I can still make the argument that it may have stopped the immune attack. If your husband didn't have the Campath, it is unclear whether he would have had the same result with eltrombopag alone. I am theorizing that his marrow needed the eltrombopag to kick start it into making blood cells again. Of course, I have no proof of this theory and am just basing it on what I am heard/read. If I am wrong, it wouldn't be the first time!

I remember some NIH presentations that talked about positive results from using eltrombopag for refractory AA that didn't respond to IST. They didn't talk about using it as a first line of treatment though.

[Hopeful]

Hi Sally,

I see that there are clinical trials out there right now that use eltrombopag alone for first line treatment of AA. I didn't realize this, as I had only heard the very positive preliminary results of eltrombopag used on refractory SAA patients. Hopefully, good news will come from these studies!

I am going to eat my humble pie now

[Alcof]

Hopeful, thank you so much for your continuing advice regarding AA. Its such a relief having an extra research head in this fight. Because we are back fighting today after yesterdays news. We are not giving up.

Sally C, thank you so much for your story! Ray of hope that Eltrombopag alone can work. I just need to get me some now...I will go find your story and read it all.

Hopeful, can you post links to the studies around Eltrombopag as first line treatment? I haven't found those myself yet. I too had only heard of Eltrombopag used for refractory AA or for moderate AA after ATG treatments. This is very promising.

In fact today I did a crazy, mad thing and wrote to Glaxosmithkline in NZ to see if they might be charitable and send some my way. Why not? Nothing to lose. Make them say no. If you don't ask, you don't get!

We considered a second opinion. But it is quite clear that the Doctor who has treated the most AA patients in this country, administers nearly all the ATG in this country is our Haematologist. Anyone else would probably just refer back to him. And he is very good. His concerns are around the fact that my Dad has diverticulitis in his gut (potential infection) and his kidneys flared up when he had pneumonia 6 weeks ago. That and the fact that my father can no longer walk and is not strong at the moment. 8 weeks ago he was fit as a fiddle, no underlying conditions. He is neutropenic now and that just makes him the ticking time bomb.

Hopeful, great advice about the fact that we're burning through blood products and that relating back to infections etc. That gave us a lift that it wasn't the disease necessarily getting worse. And today is day 9 since his last red transfusion. Only had platelets yesterday. This is the biggest gap we have seen. Too soon to call it an improvement. But I think what you say about cyclosporine taking a while to build up in the system makes sense. So we are going to try for at least another 4 weeks to trully make sure that avenue is exhausted. He is on 400mg per day for body weight around 95kg. (he is a tall man - good weight for his BMI).

Marlene, thanks so much for your very real advice on the palliative care side and managing the transfusions. Also the vitamin side is not something we had looked into fully. We are going next week to see a holistic healer of sorts to cover off all our chances. My Mum and Dad have been health freaks for years and will definitely look into levels. We are taking astaxanthin as a stab in a hopeful direction. We are going to contact hospice now also - just so that side is ready.

Thanks Marrowforum team. It really does feel like a team effort when I post on here. It gives me the confidence to say the things to the doctors, nurses etc that have to be said. (including expressing my frustration that they put him on prednisone in the first place. Glad we have kicked that one to the curb).

[Mseth]

Hi Alcof,

In India, Glaxo markets eltrombopag under the brand name Revolade. I do not know the cost, but I am sure it is reasonably subsidised in India. You can try and see if there is a way to get it. You could search the internet for more information.

All the best!!

[Marlene]

Alcof,

Just make sure if you engage hospice that it's not the same as palliative care. Not all hospices do palliative care. There are distinctions and sometimes they get lost during these times.

And, if you choose to add in supplements, there are forms that are better to use than some of the ones doctors usually prescribe/use. You can always check back here when you find out his nutritional status. You may want to ask the doctor for copies of the blood test. They should have checked his B12, folate and iron early on and so it may be helpful to get those results now. And just know, the blood serum test for B12 and folate are not definitive.

My husband's journey was a long and difficult one. He had one foot in the grave more than once and when he was discharged from the hospital, he was getting red cells twice a week and platelets 2-3 times a week. And he was neutropenic.

It takes time to recover from the infections and toxicity of the antibiotics. Both take a toll on the bone marrow. Lots of baby steps.

[Sally C]

Dear Alcof,
I am so sorry for your Father's situation. But with this disease you never know when it could turn around. Don's situation was so dire at one point that he was on his oncologist's "death list".
I think contacting Glaxo was a great idea - I just wish you were in the US so you could possibly go to The National Institutes of Health (NIH). They truly saved Don's life and are on the cutting edge. The NIH had such great success with their AA patients taking Eltrombopag that they decided to try it on their MDS patients. Don was their first MDS guinea pig and he is now their star patient - the biggest response and the only one who has maintained his counts after stopping the drug.
I wish you and your Father the very best. Keep the faith - it could all turn around. It's such a strange disease and so unpredictable! I'm so glad you have found Marrowforums. The people who post here have personal experience for you to draw on - and they are very caring and so supportive. We're all in this together.
Hopeful, I was getting ready to eat my own humble pie as NIH had never mentioned a connection with immune suppression and Promacta so I really couldn't disagree with you. Thank you for investigating it further. As you know - knowledge is so key with these marrow diseases and treatments.
Warmest wishes to all - and God Bless,
Sally

[Marlene]

Wonder if Danazol would be an option. It's a synthetic androgen similar to testosterone and has been used in SAA. If you search on it on this forum you'll find a few people who participated in a clinical trial. I can't remember if it was for AA or MDS though.

http://www.ncbi.nlm.nih.gov/pubmed/21279356

[triumphe64]

Originally Posted by Marlene

Wonder if Danazol would be an option. It's a synthetic androgen similar to testosterone and has been used in SAA. If you search on it on this forum you'll find a few people who participated in a clinical trial. I can't remember if it was for AA or MDS though.

http://www.ncbi.nlm.nih.gov/pubmed/21279356

Danazol has definitely helped me. PRCA only affects red cells, but Danazol is now the only med I take.

"Greg H" on these boards has written many very good postings about it. There is also a poster with AA and a TERC mutation who has had success. I'm sorry, but I've forgotten her name. If you search the member list for Greg H you can see all his posts. He writes for a living, so they are among the best on this site.

[Chirley]

Alcof, you could also ask your fathers doctor to write a letter to Glaxo asking for compassionate use of the drug. It holds a little more power if the doctor does it. Surely, it's the least the doctor can do. As you say, if you don't ask you will never know.

[Hopeful]

Hi Alcof,

Currently, I see that Eltrombopag is only used in NIH clinical trials without IST and as a first line treatment for cases of moderate AA. Unfortunately, there are no results yet as to its effectiveness without IST. Ethically this makes sense to me because ATG/CyA is the gold standard for AA and has a 60-80% success rate. Moderate AA typically gets a watch-and-wait approach in the US. So, it seems like a less risky approach to try this experimental drug without IST on patients who aren't in crisis mode yet.

I still believe that if there is an immune component to a person's AA, that has to be addressed as well. However, there are probably some people who's AA was caused by something else like a toxin or virus that has since left their body but that has left their marrow too fragile to recover. So perhaps, Eltrombopag alone will help these people. It will be interesting to see the results from this trial! Who knows..perhaps Eltrombopag alone can alter the course of a person's immune response. It works for ITP, another auto immune disease.

If you do get a hold of Eltrombopag, you should write/call NIH on their suggested dosage/duration.

On a side note...
That link that I included previously shows that Danazol has a 47% success rate as a first line of treatment for AA.

[Alcof]

With thanks to marrow forum advice, I brought the possibility of Danazol as a treatment up with my Dad's doctor. And this evening he has just had his first dose. I did read in the research that there wasn't much success (if any) for Very Severe Aplastic Anemia but it is something. And something is better than nothing! So now Dad is continuing with Cyclosporine and Danazol.

We still haven't given up the idea of privately sourcing some Eltrombopag. I am writing to the Doctor to ask what suggestions he has and whether he will back up my letter to Glaxosmithkline. My brother is going to try and find it in various locations when he travels for his work at a hopefully cheaper rate. He is going to Europe and Middle East so fingers crossed he comes across a source.

Dad is in hospital at the moment fighting what was an unknown infection. My mother was the one who found it. She was helping him shower yesterday and found a black lump at the base of his spine. No wonder he was uncomfortable sitting! No one else had found it - and now it is being drained and HOPEFULLY that one will be taken care of and we can get infection free again. Each infection we find and beat is another day he is with us. And I had thought infection meant colds and flus. Oh what a steep learning curve this has been!

[Cheryl C]

Great news that you've taken a step forward (Danazol) with your dad's treatment! Sorry to hear of the infection - unfortunately all too common with marrow disease.

[marmab]

I did a trial of eltrombopag (Promacta) this past spring as a last-ditch effort, before going to transplant, to try to remedy my lack of platelet production. My marrow had no megakaryocytes and was thus making no platelets; basically all I had were the ones from transfusions twice a week. I have had two rounds of ATG/CsA, and various other drugs as well. Unfortunately, I had no response to eltrombopag. I had always dragged my feet about transplant, as I was/am extremely healthy and fit. This is an odd way to make a decision, but my doctors (and second opinion doctors) finally just wore me down -- after two years -- with their arguments in favor of transplant. I am one of the lucky ones. So far, so good -- no complications. I feel absolutely great, and am extremely fortunate and thankful that it has turned out this way.

[Marlene]

Great to hear you are doing well with the transplant. I know it was a difficult decision but looks like a good one.

[marmab]

Thanks so much, Marlene. It was indeed a difficult decision for me, but I am doing extremely well, and very happy and grateful

[Alcof]

It pays to be active in the care of the ones we love. Reading the forums and making sure EVERYTHING is explained to us is so important. We really are part of the team. As such the Doctors are really throwing the Kitchen Sink and everything else at this disease that we can think of.

Dad is tolerating the Danazol very well, continuing Cyclosporine, and now he is getting daily injections of G-CSF. In addition they are really pushing the boundaries of his transfusions. Trying not to give platelets just because we are <10. He is in hospital still and they are waiting to see if there are any bleeds and if he can stabilise at very low levels. And so far so good! He has the mouth blood blisters but they are not bleeding and are still clotting. And his energy is still quite good. Eating, sitting up and all that. Still not walking much though.

And we are STILL optimistic that we might have support from Glaxosmithkline to get some Eltrombopag. They responded to my letter and requested to speak to my Dad's doctor. The Dr filled in a heap of paper work and its gone off for consideration! Feels so good to have taken a chance and have had someone listen - even if it ends in a NO answer - I'll still feel like I tried. In the meantime we are enjoying our little spell of optimism....especially given the FDA have now green lighted Eltrombopag in the US...

[KMac]

Dear Alcaf,

Your father is very lucky to have you in his corner. Keep up the good fight! It really sounds like you are doing everything humanly possible to make sure he gets the best treatment available.

And yes, I agree that loved ones advocating for him likely spur his entire treatment team to work more vigorously on making him better.

It would be great if that Eltrombopag comes through**. This can be such a difficult and mysterious disease, but often with surprising positive outcomes, and as such it's very much worth it to try multiple treatments.

**My experience suggests that it probably will, in that your father seems to be close to the model patient for that mode of treatment, since ATG and BMT are not options for him, and his platelets are low. I was personally interested in the Eltrombopag, thinking it might finally boost all my counts into the normal range. But as you can see by my numbers below, I am very fortunate to have responded well to the ATG/CsA. NIH reviewed my case and basically felt we should leave well enough alone. My own hematologist strongly agreed, feeling that Eltrombopag could be dangerous for me since my platelets are already in the normal range. I still have some fatigue, but more or less I have my health and life back. So yes, this is a brutal disease in it's overwhelming symptoms and uncertain outcome, but there is reason to be optimistic!

[Chirley]

Alcof, I'm so pleased to hear everything is coming together and that the Doctor is filling out the forms. I'm just a bit disappointed that you had to start the ball rolling rather than the Doctor initiating this himself. Thank goodness you are a very good advocate for your Dad. But what about other patients of this Doctor who don't have advocates such as yourself? Do you ever wonder why sometimes they just don't mention these options themselves and you have to do the work? I was in that position a lot for myself and now for my mother and father...it's frustrating isn't it?

[Cheryl C]

Well here's a good news story about doctors for once. Just started with a new GP today, because we've moved and I have been fighting an URTI for the last couple of weeks (silly me). Had asked the medical centre to request my records from my previous centre a couple of weeks ago.

When I went in to see the doctor, he immediately said that he'd received my fat file and had read through it! Amazing. He knew what MDS was and that I had low immunity and was really interested in my version of my history. That was a first for me and made me feel incredibly positive.

[Chirley]

I'm impressed.

My GP recently phoned me to say that he had been banned from practicing as a doctor in Australia and he was doing me the courtesy of letting me know that he wasn't just disappearing off the face of the earth and leaving me in the lurch. That makes two GPs now. The first one had an inappropriate sexual relationship with a vulnerable mentally ill patient. I don't know what my last one is supposed to have done but I hear he has moved to Qatar. I'm disappointed because he was one of the best GPs I've ever had.

Now comes the search for another GP...geez, I hate that.

I hope I find one who is willing to read my notes....that would be a bonus!