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  #1  
Old Mon Sep 5, 2011, 07:42 AM
pvinod pvinod is offline
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ATG on Dec 2010 but not response yet Please guide all

Hi All,

My 4 years daughter suffering from AA since April 2010. H-ATG treatment on middle of Dec 2010. But still her count is too low. nutrophil is only 2 and Lymphocytes is 93.

Please guide all what should do we have to now? Do we have to try 2nd time H-ATG?

For BMT, my daughter and wife have 6/5 match. Doctor suggesting that. but we are afraid.

When she is diagnosed she fall in non-severe AA, but right she has VSAA.

On first ATG, doctor start Csa from 10th day of ATG with 0.3 ml as her weight is 11kg, after 2 month increase dose 0.6 ml, but due to gum sensitivity decrease dose at 0.5 ml. so late start of Csa , increasing, decreasing dose affect on response? due to this she has not response yet?

Please guide me all. We are from India country, Gujarat state, Ahmedabad city.
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Kavya; my daughter age 4.5; diagnosed AA 2010; treated with ATG in December 2010; currently on cyclosporine; 6 month over for ATg but still transfusion dependent;
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  #2  
Old Mon Sep 5, 2011, 04:07 PM
Karenish Karenish is offline
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Same here, I had ATG Rabbit.... just awaiting results from a recent bone marrow biopsy to see if anything has had an affect in the marrow. some people do respond after the initial 6 months, one person I know did not respond until month ten and then was transfusion independent within three months. Unfortunately this disease is totally unique for each and everyone of us. Your child is a bit like me, I am producing nutrafils and white cells, enough to keep me infection free, but not enough platelets or haemoglobin.
I think dependent on the bone marrow results, if there is no activity they may well offer a second dose of the rabbit, perhaps your daughter should be checked for the same and have a second dose of the horse? try to stay positive, there are lots more treatment options out there. xx
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  #3  
Old Thu Sep 15, 2011, 07:29 AM
pvinod pvinod is offline
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Hi Karenish,

Thanks. just wanted to ask some things which match with my daughter or not.

have you fall in Severe AA or Very severe? when my daughter diagnosed with AA she falls in non severe AA, but we are late and when we took the ATG she had very severe AA. nutrophil is only 2.

I am happy that you have sufficient nutrophil and wbc. so After ATG that was increase or before ATG you have sufficient nutrophil?

Have you start CSA same day with ATG or later after that?
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Kavya; my daughter age 4.5; diagnosed AA 2010; treated with ATG in December 2010; currently on cyclosporine; 6 month over for ATg but still transfusion dependent;
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  #4  
Old Thu Sep 15, 2011, 05:03 PM
Karenish Karenish is offline
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Well, my whites and neuts have climbed slowly since rabbit atg and cyclosporin. i have a diagnosis of very severe aa, (they reckoned 3 more days and I would not be here) neuts were 0.08, plates <10. whites non existent and an hb of about 5!!!
All my other counts have not really fallen below 8.5 hb, plates 10, neuts 1.8 and whites 1.2 since the ATG mainly because they kept giving me transfusions.... however, this is the first time ever...this week, that i have gone 3 weeks without red blood cell transfusion!!! so, you just never know - I have always believed that I would beat this disease and that I trust my body 100% to mend itself to its own agenda and that nobody could force it.
I am truly hoping that your little one is the same, have they discussed another dose of the atg?

Last edited by Karenish : Thu Sep 15, 2011 at 05:04 PM. Reason: missed out a word
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  #5  
Old Fri Sep 16, 2011, 05:11 AM
pvinod pvinod is offline
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Thanks Karenish,

Our routine doctor force for BMT, so we want to take other opinion.

yes as you said my daughter and you have same situation, difference is H-ATG and R-ATG.

but still we have doubt for CSA, we start CSA from 10th day and CSA level till 2 month is 64. so feel due to that still we have not response.

have you start from same day ATG and with correct dose?
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Kavya; my daughter age 4.5; diagnosed AA 2010; treated with ATG in December 2010; currently on cyclosporine; 6 month over for ATg but still transfusion dependent;
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  #6  
Old Fri Sep 16, 2011, 05:47 PM
Hopeful Hopeful is offline
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Hi pvinod,

Is your daughter on Sandimmune Cylosporine or modified Cyclosporine (like Neoral)? The bioavailability of these drugs are different. So the dosings are different. In the US, it is more common to use the modified version. I think it has been found to be more effective, but don't remember the specifics right now.

Don't get hung up on your daughter's low trough level if she is on the right dosage of the drug. Most children (and some adults like me) are not able to achieve the targeted trough levels because the drug is metabolized too quickly. That's why some people push for looking at the 2 hour cyclosporine levels vs. the trough. The trough is more effective for telling if you are receiving too much of the drug.

For comparison, my trough levels when I was on a normal dose of modified cyclosporine (5mg/kg/day) were between 50 and 75. Increasing the cyclosporine dosage brought more toxicity, but no faster improvement in my counts. It took large amounts of the drug to bring up my trough levels a small amount.

Here is a good paper about this and other Cyclosporine issues. The Cyclosporine in this paper is the modified form, not Sandimmune:
http://onlinelibrary.wiley.com/doi/1...7.06903.x/full

I still encourage you to talk to a doctor on the BMT team now. After doing so, your questions about whether or not to move to BMT will become a lot clearer because you will understand the odds for your particular situation. Your daughter is young. Young kids with a perfect sibling match have excellent survival with BMT. I don't know the statistics for parent donors or for patients with many transfusions. However a BMT doctor will lay all this out for you, and then you will know if you should save this as a last resort or go now.

Wishing you and your daughter the best!
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52 yo female, dx 9/08, AA/hypo-MDS, subclinical PNH, ATG/CsA 12/08, partial response. Tried slow cyclosporine taper over 4+ years. Platelets fell, so back on cyclosporine. Trisomy 6 clone in 5% of cells.
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  #7  
Old Mon Sep 19, 2011, 05:37 AM
pvinod pvinod is offline
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Hi Hopeful,

Thanks. I do not have much knowledge about CSA company and other form, but we are using the cyclosporine neoral novartis as our doctor prescribed.

we are using the syrup so dose in ml , so I cannot know how much mg per day. But right now she is on 0.5 ml twice a day.

Thanks Again.
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Kavya; my daughter age 4.5; diagnosed AA 2010; treated with ATG in December 2010; currently on cyclosporine; 6 month over for ATg but still transfusion dependent;
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  #8  
Old Wed Sep 21, 2011, 01:14 AM
Hopeful Hopeful is offline
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Hi pvinod,

Neoral by Novartis is modified cyclosporine. So, that is good. I found this on the web that gives the dosage as 100 mg/ml.

https://members.kaiserpermanente.org...oln&index=true

I wasn't sure from your posting whether your daughter is taking .5 ml once or twice a day. If your daughter is 11 kg, then taking a total of .5 ml a day would be close to the "typical" dosage of 5 mg/kg/day. If she is taking a total of 1 ml/day, then she is taking close to 10 mg/kg/day, which is pretty high.

Here's the math: 100mg=1ml, so .5 ml=50mg
5mg/kg/day=x/11kg/day x=55mg/day (this is the typical dosage)


Was your daughter initially taking a total of .3 ml/day or .3ml twice a day?
.3 ml twice a day would be close to a typical dosage of 5 mg/kg/day.

If you were to repeat ATG soon, I am guessing that your daughter would just continue on cyclosporine all the way through. I think the only reason why some places stagger it is because they don't want to bombard a patient with a bunch of new potent drugs at the same time (ATG, prednisone, and cyclosporine) in case they react badly to one of them.

Again, I am not a doctor. This is just my understanding of the dosages. Please correct me if you think I have it wrong!
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52 yo female, dx 9/08, AA/hypo-MDS, subclinical PNH, ATG/CsA 12/08, partial response. Tried slow cyclosporine taper over 4+ years. Platelets fell, so back on cyclosporine. Trisomy 6 clone in 5% of cells.
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  #9  
Old Wed Sep 21, 2011, 06:10 AM
pvinod pvinod is offline
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Hi Hopeful,

Thanks a lot. You made a lot of search for me my daughter.

Right now she is taking a 0.5 ml twice a day and after ATG 0.3 ml twice a day.

As per math dose is high, we will discuss with our doctor. That is right that she has very hair grow on face/body and gum swelling.

sorry, but could not get your Repeat ATG line.

Thanks Again.
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Kavya; my daughter age 4.5; diagnosed AA 2010; treated with ATG in December 2010; currently on cyclosporine; 6 month over for ATg but still transfusion dependent;
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  #10  
Old Wed Sep 21, 2011, 06:45 AM
pvinod pvinod is offline
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Hi Hopeful,

I also got very good information about CSA from your given link.

There are several side effect of CSA, till date I am not aware about it.

Our doctor regularly make every 15 days SGPT and creatine test. but they came normal till now. Despite SGPT and creatine, lots of other side effect of CSA which we should have to monitor regularly. Doctor cannot take care of all, but we are living with her so its our job to notice each and every changes on her. she is little so she also cannot tell us if she has feeling different.

Thanks again.
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Kavya; my daughter age 4.5; diagnosed AA 2010; treated with ATG in December 2010; currently on cyclosporine; 6 month over for ATg but still transfusion dependent;
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  #11  
Old Thu Sep 22, 2011, 01:32 AM
Hopeful Hopeful is offline
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Hi pvinod,

It sounds like your daughter's doctor has been following good protocol. He started her on 5 mg/kg/day and when she did not respond, he tried increasing her cyclosporine dosage. The same was done for me when the doctors felt my response was stalled. As I said before, the increased dosage did not raise my counts, but that may not be the case for everyone. So, that is why this approach is tried. It is so difficult for you because your daughter can't tell you how she is feeling. Do you notice behavior changes on the higher dosage? The higher dosage made me overwhelmingly tired.

The creatinine can creep up, and if the trend is getting higher, you should discuss lowering her cyclosporine to prevent irreversible kidney damage.

Quote:
If you were to repeat ATG soon, I am guessing that your daughter would just continue on cyclosporine all the way through. I think the only reason why some places stagger it is because they don't want to bombard a patient with a bunch of new potent drugs at the same time (ATG, prednisone, and cyclosporine) in case they react badly to one of them.
In this comment, I was just saying that your doctor probably delayed the cyclosporine because he didn't want to over-burden your daughter's system. Some people have bad reactions to cyclosporine and most people have severe reactions to ATG. So, he was probably trying to be conservative and separate the two powerful drugs. Thinking about this some more, I don't think delaying cyclosporine a week or two after ATG would make a huge difference in response because it takes a month or more for the cyclosporine to build up in your system to therapeutic levels.

I hope you are investigating the BMT option in parallel. Talking to a transplant doctor does not mean that you are committing to the procedure. You are lucky that you are a 5/6 match for her!
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52 yo female, dx 9/08, AA/hypo-MDS, subclinical PNH, ATG/CsA 12/08, partial response. Tried slow cyclosporine taper over 4+ years. Platelets fell, so back on cyclosporine. Trisomy 6 clone in 5% of cells.
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  #12  
Old Thu Sep 22, 2011, 05:19 AM
pvinod pvinod is offline
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Thanks Hopeful.

yes, doctor seems good, but we (me and my wife) are in hurry. Doctor still say to wait for December end, and if need plan BMT in January. But we are now worried and want quick result. She is now near to 5 years age, but still not going school due to diseases.

Anyway Thanks again.
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Kavya; my daughter age 4.5; diagnosed AA 2010; treated with ATG in December 2010; currently on cyclosporine; 6 month over for ATg but still transfusion dependent;
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  #13  
Old Thu Sep 22, 2011, 06:21 PM
Hopeful Hopeful is offline
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What is your daughter's current HGB, platelets, and ANC? The number of interest is the one before a transfusion, not after. Has the distance between her transfusions increased at all? Has she shown any improvement in any of her counts?
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52 yo female, dx 9/08, AA/hypo-MDS, subclinical PNH, ATG/CsA 12/08, partial response. Tried slow cyclosporine taper over 4+ years. Platelets fell, so back on cyclosporine. Trisomy 6 clone in 5% of cells.
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  #14  
Old Fri Sep 23, 2011, 02:35 AM
pvinod pvinod is offline
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Currently when HB reach at 6 we transfuse blood , again after around 30 days it reach 6.

platelets reach around 3000 at every week, so we transfuse 2 PRC every week.

Nutrophil count is 9 and lymphocytes is 87.

WBC is 4000.
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Kavya; my daughter age 4.5; diagnosed AA 2010; treated with ATG in December 2010; currently on cyclosporine; 6 month over for ATg but still transfusion dependent;
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  #15  
Old Fri Sep 23, 2011, 07:09 AM
pvinod pvinod is offline
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Additionally, which question we should have to ask doctor? Can again born marrow biopsy give us direction? If doctor suggest BMT than we should have to force for second round of ATG?

For BMT I have one big question that if BMT was unsuccessful than what can happen? a died risks there?

My wife and daughter have 6/5 match, so what are chances of success?

Hope I will not give pain by asking such question.
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Kavya; my daughter age 4.5; diagnosed AA 2010; treated with ATG in December 2010; currently on cyclosporine; 6 month over for ATg but still transfusion dependent;
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  #16  
Old Fri Sep 23, 2011, 05:52 PM
Hopeful Hopeful is offline
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Pvinod,

I encourage you to watch a few of the AA transplant videos on the AAMDSIF website, if you haven't already. Here is a link to a recent one:

https://live.blueskybroadcast.com/bs...27&MA_ID=15722

Here is a link to other ones:
https://live.blueskybroadcast.com/bs...T=944&CAT=1031

In the first video, there is a slide where a comparison is made between a second round of IST and a MUD BMT. There is also a chart that shows that for pediatric patients, a second round of IST is suggested only if there is no transplant match.

Transplants do carry the risk of death or serious side effects from GVHD. However, IST also has a risk of not working and sometimes death. Also, at some point, your daughter might stop responding to platelet transfusions. She may get less and less of a bump in her counts and then her platelets may not increase at all after a transfusion. You need to do something before this happens! Did you discuss NPlate with your doctor?

As an aside, has the time between her RBC transfusions increased from what it was?

Again, I strongly encourage you to meet with a transplant doctor quickly to fully understand your options and risks.

Don't wait until December if she is a non-responder to the first round of ATG. Something needs to be done now to stop the disease from progressing.
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52 yo female, dx 9/08, AA/hypo-MDS, subclinical PNH, ATG/CsA 12/08, partial response. Tried slow cyclosporine taper over 4+ years. Platelets fell, so back on cyclosporine. Trisomy 6 clone in 5% of cells.

Last edited by Hopeful : Sat Sep 24, 2011 at 02:20 AM.
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  #17  
Old Mon Sep 26, 2011, 05:58 AM
pvinod pvinod is offline
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Hi Hopeful,

Thanks for video link.

Till what time she can responding to platelet and blood transfusions? Means how much year anyone can live on transfusion? is there any particular criteria? Is there any fix technically period?

Our doctor says they are used NPlate in only ITP. so we are not force much.

Duration between RBC transfusion is tricky, before approximately 21 days we should have to transfuse blood. but now almost 30 days her HB back at 6. so we are transfuse blood every 30 days. so transfusion days increase, but not much and not satisfied.

Yes, we should not have to wait more, I am mentally ready for BMT, but my other family member , specially my wife and my father are still not ready , afraid.

They said , she looks very fine after transfusion , no one can say she is ill after transfusion. At least right now she can live with transfusion. They said we should have to go for BMT at very last , means when after there is no hope, after 4 - 5 years, so if anything non accepting happen in BMT, we can feel we tried all, but at end we lost. Right now if something happen in BMT, we cannot excuse our self.

but that is true, if we will not go for BMT then at least we must have to take second round of ATG. We do not have to sit idle without any treatment.

Thanks Again.
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Kavya; my daughter age 4.5; diagnosed AA 2010; treated with ATG in December 2010; currently on cyclosporine; 6 month over for ATg but still transfusion dependent;
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Old Tue Sep 27, 2011, 03:55 PM
Hopeful Hopeful is offline
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Hi pvinod,

Have the doctor's run any tests for viruses (CMV, EBV, etc.) to see why your daughter's lymphocytes are high? Also, if your daughter hasn't had a BMB in 3 months, I would push for one just to make sure there are no increased blasts.

Unfortunately, no one can predict how long a person will be responsive to platelet transfusions. If your daughter is severely neutropenic and is requiring weekly platelet transfusions, she is in a very dangerous situation. I think you are wise to be *urgently* pressing the doctor(s) for answers or additional tests or treatments. The serious risk of infection or a spontaneous bleed are high. This is in addition to the risk of no longer being responsive to platelet transfusions.

I wouldn't judge the severity of your daughter's condition by how she looks. The unusual thing about this disease is that most people would never guess how sick you are by looking at you.
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52 yo female, dx 9/08, AA/hypo-MDS, subclinical PNH, ATG/CsA 12/08, partial response. Tried slow cyclosporine taper over 4+ years. Platelets fell, so back on cyclosporine. Trisomy 6 clone in 5% of cells.
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Old Wed Sep 28, 2011, 08:44 AM
pvinod pvinod is offline
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Thanks Hopeful.

No, our doctor never do any virus test. Is it not common that in AA have a higher lymphocytes? if so I will ask doctor for virus test.

Born marrow biopsy is also not done since last 1 year. it is done only at diagnosis time. sorry cannot understand "no increased blasts" , what does blast mean? Please guide.

Thanks again.
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Kavya; my daughter age 4.5; diagnosed AA 2010; treated with ATG in December 2010; currently on cyclosporine; 6 month over for ATg but still transfusion dependent;
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  #20  
Old Wed Sep 28, 2011, 02:43 PM
Hopeful Hopeful is offline
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Hi pvinod,

Your daughter is definitely due for a BMB. The doctor needs to rule out leukemia, as treatment would be different. Blasts are immature blood cells. They would show up in increased numbers in the bone marrow in leukemia.

Your numbers for reporting neutrophils and lymphocytes are different from ours. I am assuming that you are listing percentages??? 87% lymphocytes is pretty high - especially while on high doses of cyclosporine. I don't know if this is typical for AA. It wasn't for me. High lymphocytes can be seen when the body is fighting a virus.

Get those tests and BMB!
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52 yo female, dx 9/08, AA/hypo-MDS, subclinical PNH, ATG/CsA 12/08, partial response. Tried slow cyclosporine taper over 4+ years. Platelets fell, so back on cyclosporine. Trisomy 6 clone in 5% of cells.
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Old Thu Sep 29, 2011, 06:15 AM
pvinod pvinod is offline
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Hi Hopeful,

"leukemia" is very horrible word. Hope that not for her. will ask doctor for BMB and virus test.

Thanks.
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Kavya; my daughter age 4.5; diagnosed AA 2010; treated with ATG in December 2010; currently on cyclosporine; 6 month over for ATg but still transfusion dependent;
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  #22  
Old Thu Oct 6, 2011, 02:35 PM
Karenish Karenish is offline
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has your doc done another bone marrow biopsy on your daughter? i had rabbit the same time as her and apparently my second biopsy shows that there is a little improvement in the marrow, not a great deal but enough for doc to say lets wait and see what it does in the next few months, then another round of rabbit. xx
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Old Fri Oct 7, 2011, 06:29 AM
pvinod pvinod is offline
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Good, happy to hear.

we ask our doctor, but they do not say anything. There are also same couple of cases under our doctor, but in their they do not done BMB again. They also not done that virus test that Hopeful suggest. In general here in our state/country doctor have not make a practice like second BMB, and if we push them they feel like we are violating him.

but we will take another opinion if required.

Anyway, thanks Karenish, so what your count now? are you now transfusion independent? Have you a match donor for BMT?

in our forum is there any patient from India country? I can see mostly all from USA.
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Kavya; my daughter age 4.5; diagnosed AA 2010; treated with ATG in December 2010; currently on cyclosporine; 6 month over for ATg but still transfusion dependent;
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  #24  
Old Fri Oct 7, 2011, 10:38 AM
Neil Cuadra Neil Cuadra is offline
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Quote:
Originally Posted by pvinod View Post
in our forum is there any patient from India country? I can see mostly all from USA.
These forum members from India have posted at Marrowforums: Alex, JyotikaK, kishore_nawani, Neel, S001, and Vaidyan.

These forum members haven't posted in the forums but their profiles show that they are from India: Bishal, deoraj, firdoshr, and ritesh177s.
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  #25  
Old Sat Oct 8, 2011, 06:32 AM
Karenish Karenish is offline
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Hi Pvinod,
no I am still needing transfusions unfortunately but I believe that these are becoming less frequent. for example platelets once every two weeks. and blood once a month. However my iron levels are very high and I took exjade for a month and have developed a blind spot on the eye so have had to stop until i see the eye specialist (i am self prescribing green tea extract and wheatgrass - natural iron chelators).
Sometimes I believe that the bone marrow can be slow and all of a sudden increases the blood production but the correct protocol is for the doctors to do a second bone marrow biopsy to see if the marrow has changed its cellular activity in any way which is why you must insist they have a look for your lovely daughter!! If there is no change at all that it can be assumed that the atg has not worked and they then normally will give another atg or go for transplant if your daughter has an exact match.
Unfortunately for me I have many things going against me, my brother was not a match, I am nearly 52 years old!!! I know you may feel you are bullying the doctors but this is your right! you are the customer! If it helps take some prints off the internet of the protocols when treating AA. Good luck and god bless xx
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