Treatment options - what should I be asking?

Hi all, I've been reading here since January since my first ITP incident but this is the first time I've posted.
I have had ITP for several years but it's never really been a problem apart from lots of ugly bruises. In Jan I started bleeding and discovered my count was 1 (in hindsight, there were lots of things I could have noticed before then, but I didn't know any better).
iVIG brought my count up but it won't stay there. I had big doses of steroids which gave me steroid psychosis, and as soon as I came off the steroids my count went back to 5 and I was admitted for IVIG again.
I was then given Rituxmab, 4 doses of 100mg, and kept on a very low dose of steroids. The Rituximab finished three weeks ago and we were in the 'wait and see' period as I understand it can take a while to work once the course has finished. Unfortunately I started having more symptoms and a blood test showed my platelets back down to 8. I've managed to avoid more IVIG but I'm back on a big dose of prednisone and trying not to kill anyone. I'm also on iron tablets as I'm anaemic now.

I have an appointment with the haematologist next week and he has initially suggested either immunosuppressants (azathioprine) or TPOs (romiplostim or Eltrombopag) and he seems to favour the TPOs. I'd be grateful if anyone had suggestions of what I need to consider between he two treatments. I am in the U.K., so I don't have to consider cost, and I would be self-injecting rather than going to the Dr weekly. I know that I am not very good at taking tablets and I worry that the dietary restrictions of Eltrombopag would be too difficult for me.

I am not hugely opposed to surgery although I have had plenty before. Would it be better to push for a splenectomy now? I understand they work better in younger patients and I am currently 33.

I've had a bone marrow biopsy and although there were 'some features of myelodysplasia' my haematologist is confident that as I responded to IVIG this is not the case. Are there any other tests I should be asking about?

I had cancer, chemotherapy and radiotherapy in 2010. I had fewer options for treatment with that....all these decisions are a bit overwhelming!

Kate
Before you even consider a splenectomy I suggest you request an indium scan. They are available in the UK but not at all centres. This will show if your platelet destruction is confined to the spleen.

I would also ask what grade of MDS you have as TPO's can have an effect on it.

Would it be fair to say Kate that you have a strong steroid response and a strong IVIG response? That is, steroids brought your counts above 100 in a few days? That IVIG brought your counts into the hundreds and then fell off after 4 weeks? From reading your post I think I know the answers. Just want to verify the data.

Thanks Hal....the IVIG brought my count up over 100 but it has not remained there, even with a continuing dose of steroids.
Hospital 1st admission - IVIG and IV prednisone, count up to 300. Home with 70mg steroids, steroid psychosis, count back to 5 within 2-3 weeks.
Hospital 2nd admission - IVIG but no IV prednisone, count up to over 50, home with 40mg steroids then on to Rituximab.
I think this counts as a response to IVIG, just not one that will stick around.

Ok, I'm reading that you have a good or strong response to IVIG and a weak response to steroids. Does that sound right? This is because you got up to 300 with it and they only gave you IVIG on second hospital visit because they knew steroids didn't help on first visit. Or, did you refuse steroids?

If I've got your responses right, this is my non-doctor opinion. LOL, you may have the same ITP type (3) as I believe I do. But, there are two confounding issues. First, did you contract a second ITP type recently to cause your ITP to get worse, or did the one type just get worse. No one knows. Second, the IVIG response of 2 weeks is a little short and that suggest the possibility of a second ITP type (3 & 4) as well. If they didn't give you a lot of IVIG then that would explain the lesser response (good instead of strong).

If I were you I'd try either Promacta or NPlate. Let me speak in terms of Promacta doses as I'm not familiar with NPlate doses. If you have pure type 3 ITP then you will be very sensitive and will need just a 25 mg, or possible less, dose. If you have types 3 and 4 then you'll likely need 50 or possible 75 mg dose. The response tells you how big of a problem may lie ahead.

For type 3 only, you may find PDSA forum users ' zomzombie ' and ' heyseuss ' interesting reads. For zomzomie a splenectomy worked for 1 week. From these folks you will find Azathioprine and Cyclosporine will fail in raising counts. Danazol worked well in both cases. I have not found anyone with type 3 get remission through Rituxan. Blah, too late to tell you.

For type 3 & 4 both, then I can't contribute because the situation is too complex for my simplistic methods. Danazol, or Fostamatinib, or both might work.

Hope this helps...

Hal:
Can you post a link that explains Type 1, Type 2 and Type 3 etc ITP? I've never seen ITP divided into 'types' like diabetes is.

Kate:
I agree with Mrs. B. I would definitely go for the Indium if possible. It will not guarantee splenectomy success, but can predict failure. Also, I would ask more questions about the myelodysplasia before you consider the TPO's. I know a woman who had a situation similar to yours. She had some abnormalities on her bone marrow biopsy, but was diagnosed with ITP, treated for ITP, and responded to the treatments. Her doctor kept an eye on her and repeated the biopsy about a year later. She then ended up with a diagnosis of MDS which was the reason for the low platelets. I am not implying that you will. All I'm saying is that a response to treatments wouldn't necessarily rule that out as a cause of low counts. The only problem at this point would be treating with the TPO's which could possibly exacerbate the problem. Maybe a second opinion would be good at this point? Better to be safe than sorry.

Right. I was using numbers 1 through 4 for brevity in explanation. Purely for convenience and not by any standard.

Type . Antibody
1 . . . . .GPIIb/IIIa (anti-GP) (aka CD41/CD61) (most prevalent ITP type)
2 . . . . .GPIb/IX (anti-GP) (aka CD42b/CD42a)
3 . . . . .Antibodies to Thrombopoietin (anti-TPO)
4 . . . . .Antibodies to Thrombopoietin Receptors (anti-cMpl)

Link describing the four known ITP types (Dec 2016)
www.bloodjournal.org/content/128/22/2548?sso-checked=true

I think, Hal, you need to be very careful about drawing conclusions about which treatments will work best dependent on your typing of ITP. No doctor has as yet come to such conclusions and I really think you should not be implying to new patients that this is a good working theory.

With regard to the question of splenectomy, apparently only 2% of patients in the UK have the surgery today, and those tend to be people with other issues also, so you might want to put that to the back just now and look at other options. Another immunosuppressant treatment of choice in the UK is mycophenolate. Many try that before the TPO drugs but there is some anecdotal evidence that using the TPO drugs early on in the treatment course brings a faster remission than when left to later. I'm like you and prefer the injection to the tablet TPO and have done well on it. Where are you in the UK?

Hi Kate, if you check out my posts you will see that I had a time in 2015 when I was pancytopenic , had quite empty bone marrow and the future looked bleak. I did not have MDS symptoms but it was looking like aplastic anemia was round the corner. Going back to eltrombopag on a 75mg dose changed all that: red cells and white cells quickly normalised and platelets gradually crept up to my present 112. we have now started to gradually reduce the dose , hoping all stays good. I have not yet had a repeat bone marrow biopsy but it would be interesting to see what has happened there.

Thank you Sandi. The MDS thing is certainly lurking at the back of my mind! (Well, ok, at the front quite a lot of the time).
The bone marrow biopsy was performed by the original (locum) haematologist who has since left. My new (permanent) haemo gave me the impression that it is all a bit based on 'interpretation' and so because I responded to the IVIG he is happy with the opinion that I don't have MDS. But you're saying this may not be the case?
The alternative would be another bone marrow biopsy which he is reluctant to do so soon - and so am I to be honest, it was the most traumatic thing I've ever had done (and I've had a lot!)

Thanks anon. (Is there a way to tag people on here? Am I replying properly? lol).
The Dr has not said anything about my type of ITP so I don't know that would be a helpful place to start the discussion with him.
It's not that I am desperate for a splenectomy (!) I suppose in my mind, I see it as being a potential 'fix' rather than having to be a lifelong treatment. All my previous treatments...this is bringing back a lot of emotional 'stuff' and I suppose really I just want to be done with it all.
I'm on the Isle of Wight, right down South We only have one hospital here and I've only just seen a haematologist who is not a locum. The joys of rural living

Kate33 wrote: Thanks anon. (Is there a way to tag people on here? Am I replying properly? lol).
The Dr has not said anything about my type of ITP so I don't know that would be a helpful place to start the discussion with him.
It's not that I am desperate for a splenectomy (!) I suppose in my mind, I see it as being a potential 'fix' rather than having to be a lifelong treatment. All my previous treatments...this is bringing back a lot of emotional 'stuff' and I suppose really I just want to be done with it all.
I'm on the Isle of Wight, right down South We only have one hospital here and I've only just seen a haematologist who is not a locum. The joys of rural living

Kate, the Isle of Wight looks pretty! You've certainly come to the right place for asking questions about your condition. Definitely a lot of knowledgable people here.

I'm sorry to hear that your diagnosis is bringing a lot for you to deal with emotionally. I've had ITP all of my life and have mostly accepted that that is the way it will be, but my oldest son looks like he may have an autoimmune condition that is one of these "deal with it all of your life" things, and I'm having a lot of emotional upheaval as well! Life likes to keep us on our toes. From my experiences, knowledge and education are your best weapons in dealing with the decisions that you will have to make as you investigate treatment options. There is a lot of empowerment in really feeling like you understand where you are and what options you can take to move you forward.

Regarding the splenectomy, I was given one as a child about a year after my diagnosis. That was the standard procedure back then. However, my ITP was not magically cured and I wasn't fixed after the fact, unfortunately, so I've been managing the condition along with my lack of a spleen ever since. Just something to keep in mind as you make decisions. There really isn't a single fix, so you just have to do your homework and work with your doctor about sensible treatment plans.

Good luck and keep asking questions along the way. It is the best way to learn

Kate:
I'm not trying to imply that you may have MDS or will ever get diagnosed with MDS. I'm only suggesting a second opinion if you decide to use the TPO's. As I said, I knew a woman who had a slightly abnormal biopsy after presenting with low platelets. She was treated with IVIG and Prednisone and responded. A year later, she had a repeat biopsy that showed MDS. Her other counts began to drop (red and white) and she began treatment for MDS. She did quite well and had a long remission. She was much older than you, in her 70's. I'd just want to be sure before treating with TPO's, that's all.

If you try to talk to your doctor about what type of ITP you have, he more than likely won't know what you are talking about. ITP isn't divided into 'types' at this point in time.

I understand why you'd want a fix for ITP, but it isn't that simple. Splenectomies often fail, either right away or weeks, months or years later. There can be another whole set of problems that can occur after the splenectomy; some people end up trading one problem for another. I know all of this is confusing, but the good thing is that you don't have to make any major decisions until you are researched and ready. You have Prednisone and IVIG to fall back on in the meantime.

Thanks everyone.
Platelets were up to 274 so I am safe for now, tapering again and will start a TPO once they drop to 30.
Dr is confident that there is no MDS (he did explain it more clearly but I can't remember exactly now). And I am getting my head around this being a lifelong condition that I have to learn to live with rather than something they can just 'fix'.
I'm going to start another thread about steroids because they are utterly unbearable.

ITP isn't necessarily life long. I struggled with it for eight years and suddenly went into remission (2004). I thought it would be forever too. It might come back someday but that's okay, I did it once, I can do it again. It isn't something that you can just fix, but it gets easier. Most people find a way to manage it without major side effects, it just takes time to find the right treatment. The TPO's are usually the ones that give people their lives back and if your doctor thinks it's safe for you, it's a good next step.

274? On steroids alone? Oh my. That would make strong both IVIG and steroid response.

Why is no one considering this 274 might be part of a Rituxan response ?

Hal9000, I think because my counts post-Rituximab climbed slowly and then dropped again. It wasnt a consistent climb. I guess we will see in two weeks when I have another blood test.

Oh, a climb and a drop. Nice. You know there are studies that suggest Dex (steroids) combined with Rituxan increases the response rate. I wonder if your hema is trying to leverage that with strong steroids now.

I'm hoping for full remission. Good luck...

I had the same thought as Hal. Counts will fall until Rituxan kicks in which can take up to 12 weeks after the first treatment. I've seen people get Rituxan and not get an immediate response, then go to other treatments and counts skyrocket, then stay up. They stay up because of Rituxan, but went up because of the other treatment. Sometimes it takes a bump to get the counts up after Rituxan and then it kicks in and they stay up. The only way to know for sure is to see what happens when you start to taper. I wouldn't give up hope yet.

I thought I would pop back and update you all...we tried a couple of weeks of tapering the prednisone, and I was secretly hoping that maybe the Rituximab would kick in. My blood test this week showed my platelets had has dropped to 23

Back on a slightly higher dose of prednisone as they have had to order the Eltrombopag for me - I am the first patient at this hospital to have it! My haemotologist has used it with other patients elsewhere though. I decided to try to Eltrombopag first as I didn't want to start dealing with injections. Fingers crossed!

Good next step, Kate! Fingers crossed that this will be the one! It has a pretty good success rate. Keep us updated!

I don't know how you do with symptoms Kate but 23 sounds good compared to the start. Hopefully the number will sustain while waiting on Eltrombopag and tapering continues. Perhaps a partial remission is in store...

So....50mg Eltrombopag sent my platelets up to 578! Whoopsie.
I'm currently on 25mg, just had a blood test and I will get the results on Monday.

Still on 10mg steroids while we wait and see what happens with the Eltrombopag, hoping to continue tapering next week.

Feeling fairly positive that the Eltrombopag works, just got to get the dose right

Not sure it applies to you but folks with strong steroid response and poor IVIG response typically need less and less Promacta/NPlate over time. Hoping for the best...