Time for ATG to show first signs of effectiveness

[lcl]

Curious to hear some anecdotal comments about response time to hATG for VSAA.

How long did/does it take to see the first signs that the immunosupression is working?

These are ANY results, not definitive rebounded counts but the time elapsed before even the first sign that the treatment is having some effect.

[Margaret W]

It took about 4 months for the hATG that I had to cause a tiny uptick in my counts, but the full effect didn't occur for a couple of years. I was still having weekly transfusions two years later. I think everyone's bone marrow and disease react differently to ATG.

[jef dk]

For me it took 3 months before the first signs of improvement. And. I am still on a slowly increase of my count after 11 months.

[rmcrob]

I had an ATG treatment about a month ago. Just a few days after the treatment my HGB surprisingly jumped up to over 11 from about 9. Then over the next couple weeks it drifted back down to 9ish.

Looks like it is a matter of waiting. Lots of things in life are like that, aren't they?

[lcl]

Thanks for the feedback. My son had hATG 8 weeks ago for idiopathic VSAA. He is receiving transfusions 1-2x per week and his ANC is hovering between .00 and .05. His counts and transfusion dependence have not improved at all. Its reassuring to know that some people don't see any, even slight, improvements for months. Regardless, I was expecting to see a little something by now. The waiting game continues...

[Hopeful]

Hi lcl,

Has your son been tested for the genetic causes of VSAA?

Have they started the transplant search? Do they have a plan to move to transplant after a certain number of months?

It would be good to have a back-up plan ready, should it be needed. A transplant may be the required cure.

I do hope you see some sign soon!

[Amz904]

Hey lcl,

I was diagnosed with VSAA in December 2013, and received hATG+cyclosporine the first week of Jan 2014. The first few months were really difficult, and it was even worse getting my labs everyday and not seeing any real improvement. But don't get discouraged! You just need to keep reminding yourself that it is a slow process and just need to take it one day at a time.

Here's a chart I made of my counts from Feb-July 2014. I stopped adding to it since after july I was finally transfusion free and things have gone up hill ever since


WBC (range per month)
feb: >0.1-0.1
march: 0.2-0.4
april: 0.5-0.7
may: 0.8-1.1
june: 1.2-2.1
july: 2.2-2.9


ANC (what it was at the end of each month)
feb: 0.02
march: 0.10
april: 0.27
may: 0.59
june: 1.25
july: 1.74


RBC (units per month)
feb: 14
march: 8
april: 3
may: 2
june: 2
july: 0


Platelets (units per month)
feb: 9
march: 6
april: 5
may: 4
june: 0
july: 0

So around the 12 week mark (end of march) is when I noticed a positive trend in my counts. I definitely recommend keeping track of how many units of RBCs and Platelets your son is getting every month. For me personally, it felt like I was getting the same number every month, but when I actually counted I realized I was slightly improving every month. When my doctor saw my blood counts in May he honestly wasn't too impressed and wanted to go forth with a bone marrow transplant, but when I showed him how many less transfusions I was getting a month, he changed his mind and decided to wait and see for another few months. I'm so glad he did, since I'm doing great ever since!

Also I had one of my doctors tell me in the hospital, that slow responses can actually be a good thing since in his experience those with slower responses were less likely to relapse later on vs those patients whose counts recovered very quickly after ATG. Not sure how true that really is haha, but thinking about that kept me positive during my slow recovery

Good luck to your son!

[lcl]

RE: Hope's questions...
1. Genetic Testing - All tests were ordered and completed and were negative for the major genetic causes. Diagnosis remains idiopathic VSAA.

2. He does not have any sibling matches which is why they went to immunosupression. They have entered his criteria National Marrow Donor Program. He does not have any "perfect" matches but there are several suitable options, though not ideal.

3. Regarding back up plans there are several courses of action we may consider which include 1) another round of hATG 2) a round of rATG 3) hATG supplemented with Eltrombopag/Promacta 4) Non familial BMT or 5) familial non matched BMT.

Its still only the 10 week mark and he has had a very slight lift in ANC from .02 to .10 - .12. His platelet and hemoglobin transfusions are still weekly at a minimum and sometimes platelets 2x per week.

Each course of action has serious trade-offs and BMT can lead to host/graft issues and once you go that route you can't go back to immunosupression. On the flip side, the longer we try immunosupression and he remains neutropenic the more prone to fungal, bacterial and viral infections he becomes.

No great choices at this point but he has good doctors so we will be able to make a fairly well informed decision in the coming months if the first round of immunosupression doesn't kick in.

Hopefully we see a spike in counts over the next 3-4 weeks or its back to the drawing board.

RE: AMZ's post: Thanks. That does give some anecdotal evidence that for some people this takes closer to 6 months to really kick in. We are finally seeing some very small lifts in ANC but nothing dramatic yet. The hospital actually has a web portal with all of his test results charted and graphed. I was tracking it in excel but we got signed up for the website which is a great tool. I haven't been tracking the infusion units, just the counts, but I believe all of his infusion orders are tracked on the website as well, I will check. Good idea to not only track the counts but what they are pumping in. I can say without getting into the numbers that its been fairly consistent, some weeks are better than others but its been pretty steady. Glad to hear that the treatment worked for you with no relapse. That is our concern right now. All the other treatments carry alot of additional risks that can lead to new complications down the road.

[mharrell]

My son had ATG for AA almost ten years ago, right after he turned 18. It took a good six months to kick in.

Edited to add: He hasn't relapsed. However, following the ATG, he was on cyclosporin for a long, long time - two years, if I recall - with a very, very slow taper.

[lcl]

Well, its been 14 weeks and the results of the most recent biopsy show a cellularity of ~20%. While better than the 10% that was tested in January the doctor noted that the marrow is more or less unchanged. No clonal issues at this point which is good. We have no sibling matches and no perfect unrelated matches so the 2 choices are haplo BMT or hATG with PROMACTA and cyclo. We are going to parallel path and start a 2nd round of ATG in 2 weeks and this time add the PROMACTA (Eltrombopag). The BMT team will start working up a protocol now and we will give the next round of IS another 3 months to see if it takes. Tough call given VSAA with ANC sub .10, weekly transfusions and high end on the neutropenic spectrum but supportive care thus far has been working well with only a few hospitalizations. Will provide an update 6 weeks into the new IS with PROMACTA added, hopefully it spurs the marrow to start growing back.

[Matthew42]

Originally Posted by Margaret W

It took about 4 months for the hATG that I had to cause a tiny uptick in my counts, but the full effect didn't occur for a couple of years. I was still having weekly transfusions two years later. I think everyone's bone marrow and disease react differently to ATG.

Interesting. I read this about someone else on here.

My mother has had transfusions for over a year since ATG. Her neutrophils went up to 1200 for about 3-4 months and then dropped down to to 600. They seem to be trending upwards again. Who know?

Her platelets are consistently very low.

My mother has not gotten weekly blood transfusion since ATG. She sometimes goes every 14-21 days, or every 7 -11. There is still no pattern to her blood line.

She did have a real response in the neutrophil line, so ATG was doing something.

We are thinking about doing Campath, but we are going to wait a few more months. We were told that ATG could take a very long time to work because of her age. It could take closer to two years to get a real response in the platelet and blood line, even though the neutrophils came up to 1200 nine months after ATG. So, my mother has shown to be a very, very slow responder, but a responder indeed, at least in the neutrophil line. Dr. Young confirmed this with my mother's current hematologist.

With aplastic anemia, you never know. It's a very mysterious disease. Dr. Young said that he is still mystified with it.

[Matthew42]

I was doing research, and I found out that if a person goes without a blood transfusion (not platelet line) for around 3 weeks or more right after having received ATG, it is proof of a response to immunosuppressant therapy. I am saying this as my mother indeed went over three weeks without blood after she got ATG.

Now, it's been over a year since ATG, and she is still getting weekly platelet transfusions. Her blood line is highly unpredictable: a few months ago, she went three weeks without blood, and then needed blood weekly for a month; after that, shewent almost 2 weeks for a month, and now she is needing it every week I have no clue what is going on.

Her neutrophils were 1200 for 4 months, and now they're 500-600. We can't get any answers. We were just told to wait several more months. If things don't change by this fall, Dr. Young would recommend Campath. He told my mother's doctor that she did indeed respond to immunosuppressant therapy (especially in the neutrophil line). He thinks she may be a very, very slow responder to ATG, and could end up responding 1.5- 2 years later (which happens sometimes, especially in older people). We shall see. You never know.

Her platelet line is the only line where there was never any change since ATG. But her doctor told us that platelets are the most stubborn of the three lines. A person can still have extremely low platelets for many months, even if neutrophils and blood come up.

[Neil Cuadra]

Matthew,

Is your mother basically OK with these routine transfusions, and is she having little or no trouble from symptoms of low counts?

Or is her quality of life poor at the moment?

I'm asking because I'd imagine that this weighs into your decision about staying in this holding pattern for more months versus giving Campath a try.

[Matthew42]

Originally Posted by Neil Cuadra

Matthew,

Is your mother basically OK with these routine transfusions, and is she having little or no trouble from symptoms of low counts?

Or is her quality of life poor at the moment?

I'm asking because I'd imagine that this weighs into your decision about staying in this holding pattern for more months versus giving Campath a try.

Thank you for responding. This is very kind of you.

She feels fine overall - she just gets pretty tired when she drops under 7.5. She functions very well in the 8's and even high 7's. It's shocking, but her doctor said it's because her body adapted very well to low hemoglobin counts. But, she said that this doesn't happen with every person. If my mother is in the 9's, she says it doesn't feel that different than 8. Only when she was in the 10's a few times did she notice somewhat of a difference. Again, the doctor said that low hemoglobin is felt differently from person to person.

I must say that she is tired of getting platelet transfusion every week because she goes right back to where she was a few days later. We are going to suggest only getting platelets when she goes under 8. This is what Dr. Young proposes. People live with platelets under 10 for years and years with ITP, but there is always a risk of internal bleeding from blows to the body, etc. You just have to learn to live with risk. By the way, she no longer has physical symptoms of low platelets, either, as her body has gotten used to the super low counts.

My mother wants to wait several more months because Dr. Young says that things can still change because my mother has had such volatile counts the past several months, on top of the high 1200 neutrophil count for 4 months (proof of a response to ATG, although the neutrophils are now back at 500-600 ) . He's had people who respond fully or partially after 2 years . But, if her quality of life starts to go down hill, then we will not sit it out another year.

Thanks again for your concern. So very kind of you.

Take good care.

[Matthew42]

My mother had another jump in blood 10-11 days after a transfusion. This has happened several times in the past. I am hoping that it holds this time. I'd like her to go around 3 weeks without blood. In March, she went almost a month without blood (could have made it, although she would have been in the high 6's or or very low 7's).

No doctor can explain to us what is going on. Why a year later with hemoglobin all over the place? Why no stability? Neutrophils and hemoglobin levels have bizarrely strange fluctuations. Only platelets are stable (always very, very low). What does this signify? My mother's doctor consults with Dr. Young at times, but he only recommended what to do if things don't get better (Campath infusion). I forgot - he did say that she did respond to ATG, but no real stabilization has happened (although her neutrophils were 1200 were four straight months). My mother's doctor says that every aplastic anemic's course is very different. It's best to not compare to other people, as every case is very different from person to person.

I don't even know if my mother is recovering, despite wild swings in blood and good neutrophils at times. All that we can do is wait a few more months. My mother will not do Campath just for the platelet line.

I think the doctor did say that any response to ATG - no matter how minimal - makes it much more likely that the person will have a response to future immunosuppressant therapy. She said that Campath is stronger, and that is what she may end up needing (as Dr. Young suggested).

[Matthew42]

Well, my mother's blood is holding again like in March. She will be going close to 3 weeks now without blood. She's holding around 8. We really don't know what to think. Her threshold for blood transfusions will now be lowered to the lower 7's.

Her neutrophils dropped a little, but her platelets, surprisingly, are a tiny bit better than they have been in a long time. Who knows?

[Matthew42]

It's been 21 months since ATG for my mother. She's had a big improvement in her neutrophil line. They are now hovering between 1100-1500. Her total white count is averaging close to 3.0. Also, her platelets are holding at 10,000 after a week after a transfusion (never happened before). So, her doctor said that my mother is making 10000 platelets on her own. And, finally, her blood is only dropping by less than a point in a 7-day period.

We were going to do Campath, but because of the big improvement in neutrophils in the past month, we're going to delay things for 3-4 months. We are baffled why things have improved. Could the ATG be kicking at 21 months? It's all very bizarre. She's been off cyclosporine and Promacta for 6 months (doctor said they were not working).

We were told that once neutrophils reach 1000-1500 and stay up, they don't consider that line an issue anymore. It was also mentioned that the other two lines should start to show some improvement if the neutrophils improve that much (close to normal).

[Marlene]

Hope the improvement continues. It's long, slow journey. I hope she is starting to feel a bit better too.

[Matthew42]

Originally Posted by Marlene

Hope the improvement continues. It's long, slow journey. I hope she is starting to feel a bit better too.

It is indeed, Marlene. And her doctor said just that. She doesn't know when the blood and platelets will come up, but the fact that her neutrophils and white blood cell count are increasing so much really increases the chances that the others two lines will come up and stabilize. Who knows?! We have our fingers crossed.

Thank you so much for your kind response.

Health and happiness to you and your husband.

[Matthew42]

My mother's neutrophils are now staying at 1500 or more. However, her blood line is still not improving. The doctor said it's just a waiting game. The other lines should start to improve, but there is not any knowing when. As I said before, her platelets are holding most of them at 11,000 after a week. But, honestly, we're just so grateful that one line has normalized for almost 2 months.

[Matthew42]

Neutrophils are still at 1500 (almost 6 weeks now), and platelets are 13,000 after 6-7 days post-transfusion (never held over 10,000 after 4 days). The doctors says that its her body making the platelets at 5 days or more.

No real improvement yet in the blood line, though.

Her doctor said that if the neutrophils go up towards 1000-1500 and stay up at those levels for several weeks, there's a good chance recovery will happen. Now, the platelets are showing improvement...

We can just wait and hope the sun will shine for her once again.

[Matthew42]

Hello everyone!

I hope you are all doing super well.

Well, my mother's neutrophils are 2000. They've been around 1000-1500 for two months. The doctor said that line is now stabilized. This is supposedly excellent. But, we're still waiting for the blood and platelets to go up. I'm not sure what the issue is, but the hematologist said that it can take a good while yet for the other two lines to stabilize. She's had a slight improvement in platelets in the past two months but not enough that she can hold at 20 after a week. Her blood held for two weeks but finally dropped down so that she will need 1 unit tomorrow. We were told that all three lines don't always come up at the same time. It can really take a lot of time. But we have the neutrophils! Just wishing so strongly that the other two lines come up soon. We've been waiting for so, so long.

[Matthew42]

My mother's neutrophils have been averaging around 2500 for the past 6 weeks We still can't figure out why the blood and platelets are not following suit. We've been told that it can take several months before the other lines start to climb up. But it's really amazing that her neutrophils are over 2000. Hopefully, the other lines will start to rise in the coming months.

[Marlene]

Glad things are progressing for her even though it's at snails pace.

[Matthew42]

Originally Posted by Marlene

Glad things are progressing for her even though it's at snails pace.

Thank you so much, Marlene. I am grateful for your kindness.

We are just so happy that her neutrophils are now in the 2000's from 300-700 range or so. They're still up high, sometimes 3000-4000 range (unreal!).

Blood is holding a bit better. Platelets are just very slightly better.

We were told that blood and platelets may not rise for several months, despite what's happened with her neutrophils. It's just not predictable. It's a tri-lineage disease, but all they don't all rise necessarily at one time - sometimes months and months apart.