'info on treatments

This is a new one on me, having done the last two years on wait and watch. But now the hospital have finally started considering treatment for Dougie, I find that I am no nearer being comfortable with any of the alternatives.

1. What would you do if it was your kid? I am really aware that Dougie doesn't really have any medical issues with ITP - the odd bit of tiredness but thats it. So I am really anxious not to give him treatment that may give him some.

2. Which one would you try first? Dougie listened to the doctor on Friday and on the way home said his preference would be rituximab. Is this sensible to try first, or is it one to try when other things haven't worked?

3. Could someone explain to me in layman's terms how rituximab works please? The doctor said it was something to do with destroying the antibody making cells. Does it destroy them for good or just temporarily? And if you can't make ITP antibodies, then presumably you can't make other antibodies either? That soounds like it would be a problem for other illnesses too though....

4. How does IVIG work and how long does it generally last for? It seems a bit too short term to be worth the risk to me, but then I am thinking maybe 2-3 weeks?

Thank goodness we've got the whole summer to ponder these questions.I am hoping against the odds that Dougie has a higher platelet count by then so that we don't need to go there!

Thanks, Ali

Hi Ali,

I'm an adult with ITP, but I have often thought about what I would do if my kid had ITP. I have an active 11 year old who would die if he had to restrict his activities, so I can really feel for Dougie's plight. I also have a Ph.D. in biochemistry, although I no longer work in that field and I was not an immunologist, but I can probably shed some insight on the mechanisms by which IVIG and rituximab work.

IVIG is a blood product. It's made by pooling blood donated by many people and extracting antibodies from that blood, specifically, the IGG antibodies. This is then infused into patients. It's not really that clear how it works. One possibility is that some of the antibodies bind to the red blood cells and trick the spleen into destroying them instead of the platelets, but there are probably other mechanisms going on as well.It is, as you said, short term, lasting maybe 4 - 6 weeks. It's a day long infusion and more than one may be required. The side effects are head aches, vomiting and flu-ey feeling after the infusion. Some people also get aseptic meningitis, which is a very severe headache and vomiting. I think the biggest risk is that it is a blood product made from many people. That means that if there's a virus around that can't be tested for, you're at risk, in the same way that haemopheliacs got aids from their treatments in the 80's. That being said I think it's pretty safe at the moment, and probably the safest treatment for ITP. It's just so short lived and inconvenient.

Rituximab is also an antibody, but it's only one antibody that binds to the precursor to the cells that make antibodies, called B-cells. It binds only to this precursor cell, nothing else, and causes this cell to be destroyed. That's why it can take 6 weeks after the last infusion to work; it's not affecting the mature cells, only the immature cells. However, that's clearly not the whole story for ITP patients, because some people show a response to Rituximab immediately. So there's something else going on. If it works, it lasts a lot longer, with remissions lasting about a year. Some people also seem to get longer remissions from it, which make it very attractive. The side effects are again, headache and flu-ey feelings during the transmission and something called serum sickness. The big worry with Rituximab is that it suppresses all your antibodies, and some viruses can be reactivated. Some people have died when a virus called PML, which we all carry, was reactivated, but the numbers are really small. The people who died were all taking steroids or other immunosuppressents which probably didn't help.

So I think Dougie might be right on the mark in choosing Rituximab. If my kid were diagnosed with ITP and bleeding, I'd probably start with IVIG and hope that he was one of the 80% who remit. However, Dougie is clearly not one of those, yet, so rituximab is probably quite a reasonable way to go. It sure would be nice for him to have high counts for a long time.

Hope that helps. Let me know if there's anything I can explain further.

Lily

I don't know about the UK, but even with supposed "screening" of IVIG, my son did in fact get hepatitis B from the IVIG given to him. It either passed screening with known virus in it or it wasn't screened at all.

You have a really difficult choice to make. None of the drugs have a very high success rate and all can have horrible side effects. My previous haematologist has virtually given up using rituximab as the success rate seemed to be so low so I never did get to try it. I also didn't like the idea of living for a year with no B cells if it didn't even work. The PML thing is a bit scary too.

I think I'd give IVIG a try just to see how long he gets from it. You never know he might respond really well and not need it too often. Our IVIG comes from the US as they say it is then safe from CJD.

I don't envy you your job. Having to make decisions for myself has been bad enough, never mind for my child.

Hey, Ali -

Definitely a tough decision. It seems like it may be worth a shot to try some type of treatment, since Dougie is extremely active and either has to miss out on things or has to cause worry when he participates.

I guess Rituximab is one treatment that does seem to give people a remission more often than some of the "first line" treatments, but it seems more common to try something else first. Brady had Rituximab many years ago, so I'm sure that thoughts have changed, but at that time the doctors wouldn't have used Rituximab before trying steroids, WinRho and IVIG.

Having read so many posts on this forum, it leads me to believe that Brady's IVIG response was unusual. He would usually get months out of the treatment rather than weeks and actually had a year of decent counts after one IVIG. It was worth it to us to use IVIG so that Brady could ski, wakeboard, etc. Brady received IVIG many times before a vacation, because we could always count on a big increase from it and he would be safe. But it's still considered a temporary solution.

Of course, now Brady is hovering around 60k which is a very good count but not high enough to play American football or lacrosse (his last Rhophylac/WinRho treatment was in March, 2010). We are taking a vacation in two weeks and Brady really wanted to scuba dive, but he can't unless he gets a treatment. He has elected to not treat, so no scuba diving and no American football in the Fall. It has been 9-1/2 years for Brady and I think that the decisions are still difficult ones.

If you and Dougie decide that he will receive treatment, you can always see how it works and then decide to not treat again. I guess what I'm saying is that it's not like once you treat you have to always treat, right? So - maybe after two years it's worth taking a chance on a treatment. But I understand the trepidation - I hate treating Brady and all the treatments make me nervous and I would prefer to never treat him again, so you just have to weight the risks vs. the rewards.

Good luck - and I hope that Dougie gets to enjoy an active summer!

Beth

Thank you for all your input................Sorry, I've got more questions!

- If rituximab kills off the b-cells, does that mean for life, or do they come back over a period of time?

- The haematologist mentioned that if you have this treatment it might make you more prone to catching viruses - sort of like your first term at school or something. Is it only this sort of level of increased illness or could it be more?

- Ann, I was relieved to hear that there were some precautions in place against CJD because I have been worrying about that. But how do they know that American IVIG doesn't have that problem?

- Don't know if anyone will know this, but are there any long term effects on kids who have been treated with rituximab?

- What percentage of people respond to IVIG - the doctor said that if we wanted to go down this route then he would have to do a trial to see whether it worked and for how long. so I am guessing that it doesn't work for everyone.

- elthrombopag(sp????) was mentioned as a possibility if the study opens again at the hospital. What are the common side effects of this drug?

Got to be honest and say that if either me or my husband were to make a cold decision about this now, Dougie would be safely sat in front of the TV for the foreseeable future.........but I appreciate his frustration with the condition, and I know that he can't just put his life on hold indefinitely. We are split at the moment. Dougie wants to try rituximab, his dad sort of agrees but worries about it, and I think we should try IVIG first - like Ann said, you don't know how long it will work for till you try it.

I hate giving my kids medicine at the best of times - we probably only get through a packet of paracetemol a year between all 6 of us! I am especially wary of doing anything, particularly anything that messes with Dougie's bone marrow because my dad has a cancer of the blood (myeloma), and I think that just makes me ultra cautious. And I always like to make informed decisions! Argh - life was easier when the hospital were refusing to consider treatment!

Thanks for your help, Ali.

P.S. Beth, you are right that we could start and then stop again. Dougie desperately wants to go on the school skiing trip to Italy next spring, but after that I think it would be a matter of weighing up the benefits versus the risks.

Ann, I think the consultant Dougie sees must have had a better strike rate with rituximab - I think he mentioned treating 7 patients, of whom 6 had had a response. He also mentioned that the hospital had only done 1 splenectomy for ITP in the last 7 years.

The Ivig didn't work for me and neither does it seem the rituximab has either. I have basically tried eveything bar having my speen removed and that's a very very last option. I am currently just having my counts checked every 3 weeks and not having any treatments and last count 2 weeks ago was 14, but i have decided not to worry unless i have symptoms which i haven't. I have been eating healthy and exercising every week day for about 45mins and then an hour on weekends and am feeling great, so if i was to give u my opinion as an adult with low platelets based on how i am at the moment and where i am in my life right now, i would say no to anything, but if i was a mother to a child with low counts, my decision may be different. I know my mother worries constantly about me and i am 26, so the mother (if i was a mother) in me would probally want to try everything i could before admiting defeat.

Hi, thought I would share my daughter's experience with Rituximab. She's 14 now and was diagnosed with ITP a month before her 13th birthday. We tried IVIG, she had an awful reaction and can't use anymore. Steroids worked temporarily, when they tapered them her count would fall. They also tried methotrexate for a short time, it did nothing then Vincristine, it was short lived and she lost a lot of hair. They then gave her 4 infusions of Rituxamab they were uneventful and she slept through them. She has had a count between 180 and 200k since October 2010. To her it was the easiest and worked the best. She hasn't been sick at all, in fact she has been the least sick out of my three kids.
srunge

Well, our boy did sit on a bed cushion with zero platelets for 3 months and it was definitely no fun. Not sure since Hep. B can get through US screening, if CJD could too?????

But really, what I wanted to say is I would encourage you to take LOTS of time (it will literally take days of off and on reading) to look up each treatment you've been offered. Read both the science literature and then people's personal experiences. Read what the long term side effects of rituxin in an adult are (doubtful they have long term on kids who used it). Check to see which drugs can change DNA structure (the chemos, etc.). We also had a history of blood diseases in our family so this is very important as it will very much make one susceptible to this weakness coming out into active disease. Once you've read till your eyeballs feel like they will fall out, you will at least be able to have some level of confidence when you make your decision. I have found that the more knowledge I have going into these situations the less I second guess myself as a parent. It may make your son feel better too knowing that you've researched enough to have a level of confidence in your decision. AND, you may very well decide that none of the available options are acceptable to you all and go back to the drawing board. But either way, you can know that you made a decision based on solid information (and lots of it).

best wishes

Lauren - I admire your outlook! Dougie probably shares it, and if he was only wanting to exercise I wouldn't even be thinking about treating - he's done rock climbing, mountain biking, basketball, canoeing, etc etc with counts under 20 and sometimes under 10. However, you just can't play contact sports or ski with a count of 10, and thats what he wants to do. I feel that we owe it to him to at least look at the alternatives.

Srunge - your daughter's experience is exactly what is appealing about rituximab!

Patti - excellent advice on researching which I fully intend to follow. I've allowed Dougie to get on with the majority of his daily life with a count of 1, and I am thankful that we've never had to restrict his activity that much. He's been very lucky so far. I can't imagine how totally frustrated he would have been if I'd confined him to the house for three months - I so don't envy you that experience!

Hi Ali,
Our old hemonc,the one that we really liked and was pretty much a genius, said that Rituximab lowered immunity, does not destroy it completely. It does make them more susceptible to illnesses, but not considerably more. Its not like getting a splenecotomy or having major chemo that whipes out your immune system, it just modifies it a bit. It is very effective for a high percentage of ITP patients, and for those that it is effective for, according to our hemonc, it is often curative. Rituximab is a good start! IVIg is never curative, but sometimes it does seem to help some kids go into remission. If they are offering Rituximab though, I would try that...my choice. Timothy always tolerates it much better than IVIg. Much less side effects for him.

and elthrombopag...promacta...Tim hated it and for weeks threw the pills away because they made him feel weird and he was blacking out with them...having weird seizure like blackout periods while on it. As soon as he stopped the med, he stopped the blackouts. Nplate, a similar drug, does not effect him that way.

I think it is really hard as a parent to decide which treatments to try and which to not try. I have known lots of people whom Rituxan did not for, but for us it has been wonderful!

I don't comment much anymore, but I was on here a lot in 2006-2007. After 10 months of IVIG, Winrho, pred., and just low counts we tried Rituxan in October 2006 for my son (he was 3, almost 4 at the time). The treatments themselves were relatively uneventful. He had a reaction to the 1st infusion, but I had refused benadryl for him. (I was concerned benadryl made him violent as we had horrible times with IVIG...) With the first infusion he had hives and vomitted. After that I agreed to the benadryl and tylenol and he did wonderfully. He even completely slept through one.

I did think he was more sick with colds in the 3 months following rituxan, but whether it was due to that, or due to the fact that it was winter and he was back in daycare, I really can't say.

I can say though that we are now almost 5 years since he had Rituxan and his counts have been normal. He gets an annual cbc, and that is it. He is extremely healthy. Other than his routine physical, I don't think we've seen his pediatrician more than once or twice in the last 2 years. We have virtually no contact with his hematologist at this point.

I wish you luck in your decision. It is not easy. I'm glad we made the decision we did at the time (in hindsight), but at the time I had a lot of reservations. It is very difficult to put medications into your child's body without know what exactly the outcome will be. If you do try rituxan, I hope you he has a long, long remission, that allows him to *almost* forget about ITP.

I am fairly pro-Rituxan. I have seen many people here have great results from it here over the years. It probably has one of the greatest remission rates of all of the treatments.

As far as immunity, Donna (Lucidawn) is right. It only targets B Cells and T Cells, which are only one part of the immune system. Yes, they are important but most people do fine. They are not destroyed for life, they eventually regenerate. It would be riskier using it if a person were asplenic or using other immunosuppressants. I have not seen many cases of serious illnesses after using Rituxan, a few, but those could have occurred without the drug or may have been coincidence. I was one that had serum sickness from it and that is also a risk, but most people recover from that in a few days. It is a horrible thing to go through though.

Now, after saying all of that, I still consider Rituxan one of the heavy duty meds. I think I would prefer to try something less toxic first, such as steroids, before moving to Rituxan. It's one thing to use it for adults, and another to use it on children and young adults. It's only been around since the mid-nineties, so long term side effects are not yet known.

Thanks for the info - really helpful. Dougie has tried two fortnight courses of steroids right at the beginning of ITP but didn't have a great response (up to about 40K). However it wasn't a very high dose, only 1mg per kg, and he wasn't on it for long. I wonder if he would have a better response with a higher and longer dose. However, the consultant has now said that he should be treated with IVIG rather than steroids if he has bleeding problems in the light of this poor response, so I don't know.........

I change my mind constantly on this. I asked my medical researcher niece to do some research for me on rituximab which has put me off it a bit. Our current thinking (which is almost bound to change) is that we want to try IVIG to see if it can work for "special" occasions - like the skiing trip next February. If that works, we think we might just carry on doing nothing the rest of the time. If it doesn't work, I think we would need to think again, because I do think that Dougie needs at least the occasional period where he can get on with life.

And I am keeping everything crossed that Dougie's count goes up all by itself before we see the consultant again so that we don't have to make any decisions at all!

Ali

1mg/kg is the normal high dose of prednisolone for ITP so I don't suppose they'd think it's worth trying a larger dose.

If you do go the IVIG route don't forget that you need to test it out before the skiing trip. It doesn't always work; it didn't for me.

Ali,

I am an adult with and am just returning after a 4 1/2 year remission of ITP. Rituxan put me in remission.

A small study was done on how long the b cells took to regenerate.

A rapid B-cell depletion occurred after each therapy, and lasted up to 7 months and 10 months, respectively.

The people who were tested remained in remission after the new b cells showed up. Here is the complete study:

www.biomedcentral.com/content/pdf/ar1731.pdf The researchers found the first set of b cells that regenerated were a little weird, but it didn't last and the patients had no known side effects from it.

I was no sicker than usual during my remission. Except that I had athletes feet and had to have a toenail removed. My hema said the Rituxan would make that worse. Not a big deal. The Rituxan got rid of my eczema for a very long time also. It was a great treatment for me and I am looking to do it again soon.

That's why I never did rituximab. Because if it hadn't worked, and the success rate is less than 50%, I'd have still had no b cells for a year and had to take steroids which was the only thing at that time which worked for me, and so I'd have been doubly immunosuppressed. I didn't like that idea as I've had cancer once and being immunosuppressed might have allowed it to recur or a new one start if I'm susceptible.

Good point Ann. And one of those things that doctors do not think of. I have had irregular paps for years, I get checked every six months. They go back and forth to normal usually. The first year after I had Rituxan they took a turn for the worse, although so far no treatment necessary. I agree that it is likely due to the Rituxan. I was not asked any questions about risk factors like this prior to Rituxan treatment.

Not as scary but also showing the immune tradeoff - I never have any gum problmes and after Rituxan for a year or two my dentist started to get concerned about my gums. There are immune factors involved in gum disease too. Luckily my gums seem to be back to normal.
Erica