Hello All Again! Some good news

Hello to everyone and a Happy Healthy New Year!

After being out of touch (but never out of mind) for a few months with the rest of the forum we're back.

The reason we were out of touch is that we have been preoccupied by a new baby!

Since this November, our daughter Sophia now has a new baby brother!  (Who is a trait carrier, and while we don't know if he's HLA compatible to Sophia, it's really secondary to the enormous  joy of having him).

Sophia turned 3 in Sptember is still using prednisone daily due to her hemolytic anemia (we get down to what they call "one cross" on both coombs' tests but never got any better unfortunately) but at least we're been back to transfusing every 21 days (from 14) and she's adjusted well to her chelation regiment. (Tip: We own an xbox which is out of bounds -obviously- and we have a couple of platform games which are bright and fun. The deal is, once she gets her "mosquito bite" in her tummy, we get to play with the xbox -i.e. my wife and I play while she watches. It never fails. It's about an hour's investment and she actually looks forward to it. -of course the emla cream helps).

So we are happy in the midst of being stressed. What else is new? 

Anyway, we've been getting up to speed with the rest of the forum and have seen that quite a few people have been through some difficult times. Know that our prayers are with you.

We are really in the same boat.

It is nice to hear from you again InGreece!
Congratulations on your new baby!   

I am glad to know that your daughter is doing well and that her transfusion intervals are long. 
What dose of prednisone is she on currently?  Have you considered other options rather than keeping her on
long term prednisone?  My son went through rituximab treatment this summer which seems to have treated his hemolytic
anemia, at least for the time being.  He has been off of prednisone since November.  Long term prednisone use may not be good for the bones and the eyes so you may wish to speak with your hematologist or rheumatologist about other options. 

Have you also gotten genotype testing done for her?  This will prevent future exposure to antigens that cause her immune system to act and and produce autoantibodies.  I urge you to do that as soon as possible. 

I am glad that the chelation is going well - you have found a very creative way for her to get her poke that is wonderful.  Thank you for the update, and congratulations again on your baby

Best wishes,

Sharmin

Congratulations on the new arrival.

Hello InGreece

Welcome back.  Congratulations for your baby.  A baby brings so much joy in a family.  Wish all members of the family a happy new year and good health.


Take care
Jade

Thanks to everyone for their wishes!

Sharmin,

It's great to hear you've had success getting through hemolytic anemia. It's a terrible situation to find yourself in. (I can still remember the nightmare of having our daughter transfused every 2-3 days for a month until the prednisone caught up....)
Sophia's dose is between 1-2 mg per day (it fluctuates due to her responce. 2mg is about where we are) She's 13kg. and just over 3 years old (does the dosage sound too much too you. or too little? I'd appreciate comparing notes)


I wasn't aware of the rituximab treatment so I just started googling it.
From what I can see it's a pretty heavy duty drug. Also it seems to be specific in that it attacks protein cd20 (we never managed to identify what caused the hemolytic anemia to start with- although I strongly suspect it was a mistake in blood preparation.)

What was your experience? Obviously we'd love to get off the prednisone and deal with the hemolytic anemia.
If we could, there's a good chance that with a splenectomy later in life Sophia might be transfusion free as she's thalassemic via my Lepore trait and due to high Hbf her condition would be borderline intermediate.

That would be worth maybe taking certain risks.

Anyway, thanks you for bringing it up and I really hope everthing goes well  for you.

Hello InGreece,

I'm 21 yr and I got also a hemolytic anemia. It's pyruvate kinase deficiency. Has your daughter thal?  I wanted to say never heard, but is not true. I rarely hear about the use of prednise by hemolytic anaemia. Why does your doctor prescribe this?
When I was little I also had transfusions in a very short time: <2 days but never longer than 1.5 weeks. But they never suggest to take prednisone. I had my spleen out of the age of (nearly) 3yr. First it helped a bit, but it really failed. Nevertheless I am glad my parents make this decision. What's coombs' test?

I love the xbox story It's cute. I still remember when we try the tummy-thing. I always forgot that the medicine plus bag was be stucked with the stake of my bed. 

I wish you also all the best for 2009!

Dore

Hello InGreece,

I'm 21 yr and I got also a hemolytic anemia. It's pyruvate kinase deficiency. Has your daughter thal?  I wanted to say never heard, but is not true. I rarely hear about the use of prednise by hemolytic anaemia. Why does your doctor prescribe this?
When I was little I also had transfusions in a very short time: <2 days but never longer than 1.5 weeks. But they never suggest to take prednisone. I had my spleen out of the age of (nearly) 3yr. First it helped a bit, but it really failed. Nevertheless I am glad my parents make this decision. What's coombs' test?

I love the xbox story It's cute. I still remember when we try the tummy-thing. I always forgot that the medicine plus bag was be stucked with the stake of my bed. 

I wish you also all the best for 2009!

Dore

Dore,

Hello! Thanks for your post.
Yes, Sophia is thal major for all practical purposes. I say this because due to her having on one side a Lepore trait it's technically classified as intermediate. It doesn;t make any difference though. She stills gets transfused every 14-21 days.

In our case we got hemolytic anemia following a transfusion when she was 18 months old. She had been transfusing for 6 months. We have been told that they have not been able to identify the reason for which this occured but my wife and I are almost certain that a mistake happened in preparing her blood which led to this situation.

Coombs tests are two types of test that detect the patient's reaction to antibodies. In a way it's teling us that the reason for the anemia is still present. That we still have an autoimmune reaction.

Prednisone you might know as cortisone. It is the standard treatment -as far as I know- to this type of hemolytic anemia as it suppreses the immune system and this way it reduces the reaction to the blood Sophia receives.

In our case a splenectomy could actually help quite a bit. However our doctors told us that, given the anemia, they don't think that it would be an option.

All the best in 2009!

Has Sophia had genotype matching for her blood?

Happy New Year Andy,

Yes.
When Sophia was first diagnosed we did the bloodwork that established her exact type. (My wife and I also gave blood at that time).

Are you asking in order to determine type? Or whether they knew what to scan against? If the latter is your concern, I suspect you are right. They made a mistake and after the event it was impossible to know exactly what they did.

I'll probably be able to find precisely what type Sophia is classified tomorrow when we visit the Hospital.

Perhaps the following can be helpful in giving you an idea about her type:
When my wife became pregnant to our son a few months ago we visited the genetics specialists at our hospitals. While conversing with the professor who had access to Sophia's medical history he commented to the effect that Sophia's type gave almost pure Hbf and had assumed -until we told him otherwise- that Sophia had not been transfused.
I am a lepore trait carrier while my wife has one of the most common -if not most common- thal major traits in the Mediterranean region.
(Btw, I later gathered that a major factor in starting the transfusion had been her bone age and hence their decision to transfuse so as to A)avoid bone problems resulting from overworking bone marrow B) Proper growth since Hbf is not considered as good as adult Hb)

Thanks again

If blood is matched to genotype rather than only phenotype, an accurate match can be made. Phenotyping will include all the antibodies picked up from transfusions and it's impossible to tell which are from transfusions and which are native. With genotype matching for every transfusion, the guesswork is eliminated and an exact match can be used, resulting in far fewer reactions to the transfused blood. We are pushing this as it is the wave of the future and eventually will be the standard for blood matching. Do you know if Sophia has an alloantibody reaction or an autoantibody reaction causing her hemolysis?

For those who wonder what is meant here by Lepore, it is another hemoglobin trait, that much like HbE can cause transfusion dependency when combined with beta thalassemia. Lisa, our founder was as Sophia is, a Lepore/beta thal. Lisa's dad was also the same and both did require transfusions, although Lisa's dad took a 5 year break from transfusion in his late teens/early 20's. Just like HbE beta thal, it can manifest as intermedia or major.

InGreece,

It is usually suggested that the maintenance dose of prednisone be given on alternate days rather than everyday.  This makes prednisone more effective and causes fewer symptoms.  Steroids are most effective when given in pulses. For example 5mg/kg for 14 days - then wean down slowly to a low maintenance dose on alternate days.  This cycle can be repeated every 6 to 8 months or as needed. 

Rituxmab is generally well tolerated and so far our results have been encouraging. 

The plan for my son was as follows:

IVIG was administered to protect him from the suppression from Rituximab. 
He was given a course of rituximab (once a week for four weeks), the course was completed in early August.
Within 6 weeks from the completion of the course of rituximab the interval between his blood transfusions increased (every 3 - 5 weeks)
Genotype testing was done
Prednisone was stopped in November - the transfusion requirement continues to be less.
He now receives genotype matched blood
IVIG every 3 weeks will continue for a few more months (this is not necessary, it is just extra protection).

If all goes well the expectations from this procedure are:
after suppression of Bcells - it is hoped that once they re -emerge the problematic antibodies will not return
genotype matched blood is given to prevent exposing him to the antibody that originally caused his immune system to act up and produce the autoantibody (assuming that was the cause for the autoantibody)
hopefully this will also prevent the antibody from re-emerging

If the antibody somehow re-emerges anyway, a second course of rituximab may be given - this usually resolves the problem for good.  Genotype matched blood transfusions are continued. 

Benefits seen so far:
elimination of prednisone (at the very least a break from prednisone)
decreased transfusion requirement
lower iron levels

If things work out this is an ideal situation, but the decision to do this must be considered carefully.  Several of the prominent doctors in the US agreed that this was the best course of action for my son.  This may be the only way to "reset" the immune system and stop this cycle of transfusion and rapid hemolysis. 

The negative impact of the treatment for us was:
Multiple hospital visits during the summer for one month - rituximab treatment, ivig treatments and transfusions - but in the long run we now have far fewer hospital days then what we had before.
My son had a reaction to the first IVIG treatment he was given - we discovered that this could have been avoided by giving him benadryl and hydrocortisone before the infusion.  The reaction consisted of a terrible headache and fever for several days.   He did not have any reaction to the rituximab

Since the treatment my son is taking many supplements that have improved his health and energy. 

Please let me know if you have any other questions.  For us this has been worth it, but everyone must make the best decision for themselves with health care providers.  It is a very individual decision and you must decide what is best for your child.   I personally would not like to have my son's spleen removed for several reasons.  It leaves your child open to infections, strokes, pulmonary hypertension because the spleen usually removes irregular fragments from the plasma and in its absence these fragments can cause trouble - and in some cases the original problem returns and it can be far worse.  Again, I stress the importance of genotype testing.

Best of luck with whatever you decide,

Sharmin

If blood is matched to genotype rather than only phenotype, an accurate match can be made. Phenotyping will include all the antibodies picked up from transfusions and it's impossible to tell which are from transfusions and which are native. With genotype matching for every transfusion, the guesswork is eliminated and an exact match can be used, resulting in far fewer reactions to the transfused blood. We are pushing this as it is the wave of the future and eventually will be the standard for blood matching. Do you know if Sophia has an alloantibody reaction or an autoantibody reaction causing her hemolysis?

For those who wonder what is meant here by Lepore, it is another hemoglobin trait, that much like HbE can cause transfusion dependency when combined with beta thalassemia. Lisa, our founder was as Sophia is, a Lepore/beta thal. Lisa's dad was also the same and both did require transfusions, although Lisa's dad took a 5 year break from transfusion in his late teens/early 20's. Just like HbE beta thal, it can manifest as intermedia or major.

Andy,
We've been told it's an autoantibody reaction. You are absolutely correct regarding the genotype matching. Unfortunately currently that isn't an option but there is a huge debate over here about going to this system eventually.

Sharmin,

Thanks for all the info.
It's something we'll discuss with our doctors most definitely.

When we went down to 1mg per alternate day we started having the coombs tests showing a higher antibody reaction and demonstrably saw a drop in Sophia's hb between transfusions. GIven that we had experienced nightmarish drops when it all started I think the doctor decided not to take any risks and we went back to a daily dose.

Again, thank you.

InGreece,

The genotype testing that Andy discusses can also help alleviate autoantibodies. 

Usually autoantibodies appear in chronically transfused patients after they have been exposed to something in donor blood.  Over time the immune system begins to produce autoantibodies causing AIHA.  Several thalassemia patients have AIHA which complicates thalassemia with increased transfusion requirement.  If genotype testing is done then exposure to the particular "irritant" that eventually causes the auto immune reaction, can be avoided then the problem can be alleviated. 

Although genotype testing is not available everywhere, blood samples can be sent to other labs for the testing.  Toronto Canada does genotype testing so that is one option.  There are also several labs in the United states that do genotype testing.  Please have your blood bank take a sample and have it sent abroad.  We had our son's sample sent to Toronto.  Blood samples are often sent to other countries, in the past for various tests and trials we have had our son's blood samples sent to the US, Uk etc.  So don't let this be a limitation for you.

Your blood bank should contact one of the places where genotype testing is done and find out how to collect the sample and prepare it before sending it.  I believe that the blood is not to be spun after collection.  It is best to do this soon because the sooner your daughter begins receiving genotype matched blood the sooner her auto immune system can relax. 

Sharmin

When we went down to 1mg per alternate day we started having the coombs tests showing a higher antibody reaction and demonstrably saw a drop in Sophia's hb between transfusions. GIven that we had experienced nightmarish drops when it all started I think the doctor decided not to take any risks and we went back to a daily dose.

Maintenance for antibodies can be very individual.  To this our doctor would say that it is better to give 2mg every second day than to give 1mg every day.  The 2mg every second day will have more effect and far fewer side effects.  Again, this is something that you will need to confirm with your daughters health care provider. 

Best regards,

Sharmin

A Very Large Update (apologies)

 We had an extensive conversation with our doctors today armed with the information you gave us so in that respect it was extremely useful and for that alone we so very grateful. 

First things first,

Sophia's type has been classified as beta -Delta beta Lepore. (Her genotype of beta genes was CD39/ delta beta Lepore) .

Also, her blood was initially checked genetically so they have the starting baseline (which is important since it establishes her actual own immune reactions).

On the question of if they genotype test the blood I got an answer that I'm not sure is complete: I was told that -beyond cross check, washing and filtering- all potential donor blood for Sophia is checked against the basic known antibodies on the basis of her initial baseline.

 I know it sounds silly for not clarifying but you know how it is, you receive an answer and think you are satisfied with it only to mull it some more later on and wonder if you actually did  get an answer... medical issues are particularly suited for such incidents

I'll look into it again but I have the feeling that we don't have genotype testing. In the near future I'll bring up the possibility of genotyping the donor's blood -if necessary by sending it abroad. I can already anticipate that sending blood samples outside being a huge problem. They are a specialized comprehensive center under the state health system and the system is set up so that it isn't prone to accept tests done elsewhere. 
Still, the people (as opposed to the system) are great and very cooperative so there is hope.

I brought up Rituximab and they were quite aware of it but seemed to have serious concerns about its toxicity. When I pressed the issue I got the feeling that when everything is said and done their cost/benefit analysis is that they prefer a small prednisone dose along with transfusions. The dose comes down to 1.5 mg per kg every 14 days which is not a large dose.

Right now, I think we won't press the issue for 2 reasons.  A) We still need to see if our son is HLA compatible which could in theory change matters and B) It seems that the current regime is working. If b changes I think we'll rethink and the important thing is that (thank you Sharmin!)  we now have an option.

 A final thing that emerged from the conversation we had and might be interesting: while discussing the pros and cons of rituximab I brought up the fact that a possible success with dealing with hemolysis might open the way for trying a splenectomy if we had the hemolytic anemia under control (at a later date) so as to reduce the transfusion needs and rely on Sophia's Hbf which -now suppressed- is naturally very high.
Surprisingly (to me at least) this was something that they are quite against.
They argued that the quality of Hbf is extremely low (Hbf -fetal hemoglobin, that Sophia's type has very high) is quite inefficient and that, in their department's experience (they regularly manage 450 thal children) relying on it leads to several problems including cardiological ones. Obviously, if a child has sufficiently high Hbf and no stress on her bones they might monitor and start transfusions later (we had to start because bone indications showed that we should) but I got the feeling that in the past, children with high Fetal hemoglobin relied on the Hbf  too much to their detriment.

The head of the department is Dr. Karagiorga-Lagana, an extremely able, soft-spoken and accomplished physician who has done extensive work on the matter of cardiological problems in beta thalassemia so I'd like to bring this to the forum irrespective of Sophia because it went counter to my expectations:
They seemed to be saying that it might be preferable to start transfusing (If you have access to comprehensive care, regular chelation, iron monitoring etc.,) rather than rely on a minimally "serviceable" HbF count of e.g. 8.

One final thing that came in this conversation and which I found very encouraging (and which, if you think it's useful I'll repost in the 'Searching for a cure' category).
When discussing gene therapy, towards which they are understandably cautious, I was told that while indeed we need a breakthrough on how long the therapies are effective. -Andy mentioned, I believe, 6 months efficacy in another post - there are positive signs in working under a different logic:
-So far the idea has been inserting a healthy gene.
It seems that several teams are returning and looking again at the possibility of not 'exchanging' but rather 'repairing' the existing sequence.
In the past this was not pursued as rigorously for a variety of reasons but now this avenue is opening up again and it would seem to offer greater hope as success here would have fewer complications. The underlying gene is closer to the patient.

On that positive note. thanks to everyone! As always we are so grateful for the existence of this forum. It offers real hope for us all. (and it even has me -under the insistence of my wife lol- using emoticons!)