5 months after ATG - are we seeing a response?
 

It has been 5 months after ATG, and we have yet to see a clear response.

Prior to ATG on 9/18/2014, his WBC 3.4, HGB 7.8, PLT low teens (transfusion weekly).

After ATG, he has yet to have a blood transfusion, but had weekly transfusion of 1 unit PLT till 11/25/2014.

Today blood test results: His WBC 2.4, HGB 8.1, PLT 17 (again, last PLT transfusion was 11/25/2014 and his PLT jumped up to 37 at one point but mostly in 20s).

He is on Cyclosprine 250mg twice a day. (500 mg per day)

Are we seeing a response yet? We are very anxious.

Hi hxmxsx,

I would take the transfusion independence as a positive sign that there was an immune attack going on that is responding to the ATG/CyA. The drop in platelets could have been a mild virus or lab variation. It takes a while for the marrow to rebuild itself. Stay positive!

Thank you Hopeful! We are keeping positive attitude.

It has been 200 days since my husband underwent h-ATG treatment. His blood work shows little response: Plt: 18, Hgb: 7.7, WBC: 2.4 and ANC 0.9. He is on cyclosporine 525 mg/day (about 6mg/kg/day). The doctor is concerned about his kidney level. Creatinine: 1.62. He is also on Eltromobag 50mg for 2 weeks now. The doctor will reduce his Cyclosporine by 25 mg starting today and will increase his Eltromobag to 100mg.

The doctor is very straightforward with him. If, by the time he is not responding to Eltromobag 150mg which is about 4 weeks from now, he will have to go through r-ATG.

By the way, his platelet transfusion (1 unit) was on 11/23/2014 and his last RBC transfusion (2 units) was 10/28/2014.

Any comments are welcome as we are not optimistic. Thanks.

Hello,

I am sorry to hear that your husband hasn't had much improvement in his counts. My wife, Claire, is also reaching her 6 month mark post her 2nd ATG. (She received her 1st horse ATG in Nov 2011 and went into remission with counts near normal. But she relapsed in Oct 2014 and received 2nd horse ATG). She is on 200mg Cyclo + 200mg Promacta (started after ATG at 25mg and increased to 200mg)

However, her counts are not so encouraging either. Platelet once hit 24K but has gradually moved downward. Latest count is 13K. ANC is around 800~900. HGB is constantly dropping but very slowly. Her last transfusion was in early Feb.

We know that some people take more than 6 months before they start to see solid response, but we too are getting tired waiting. We have started looking at BMT option now. Claire has 9/10 match donor.

What is your husband's absolute reticulocyte count? Claire just measured hers and it is now at 45 which is within normal range. I don't understand why these baby red cells are not maturing. Also, Claire's bone marrow biopsy in Feb showed that her bone marrow has shown significant improvement. She was below 10% when diagnosed but now it is at 40%. Yet, her counts are still not moving....I really wonder why.

David

I am sorry that your husband didn't have a further response yet. Here is a recent article about the treatment of refractory AA. I hope things turn for him.

http://asheducationbook.hematologyli...2013/1/87.full

An update as of 6/19/2015
 

My last update was on 4/10/2015 and since then my husband's situation has greatly improved. It was all because of Eltrombopag 100mg. In the mean time, the doctor has reduced his Cyclosporine down to 100 mg daily and to 100 mg every other day starting next week. His blood count: Plt: 38, Hgb: 11.1, WBC: 4.1 and ANC 1.95. His doctor is very pleased with his response to Eltrombopag and is thinking about reducing it in the near future. We are not so sure about it since his platelet is still on the low side. Any comments?

Congratulations on your husband's response to Eltrombopag!

I don't have personal experience with this drug but have read that in clinical trials they like to consider discontinuing it at 12 weeks if there is no response because of the risk of clonal evolution (specifically monosomy 7).

Is it possible to separate the Cyclosporine taper from the Eltrombopag taper in case the Cyclosporine is having any effect?

Hi Hxmxsx,
My husband was the first MDS patient in The National Institutes of Health's clinical trial for Eltrombopag. He started in March, 2011 and stopped in July, 2012. It is a bit different from your husband's as Don was on no other MDS medications. They did a slow increase until he reached 150mg./day and once his platelets were over 100,000 they did a slow taper due to increased risk of clots with platelets over 100,000. Before that he had absolutely no response to Campath or Cyclosporine. The cyclo also caused potential kidney problems. The all-time low for his platelets was 4,000 and he received over 125 blood/platelet transfusions before taking Promacta. He still maintains his 100,000 range of platelets to this day and it also increased his reds and whites. He remains transfusion independent and has been for over 3 years and is on no MDS medications at all. It truly performed a miracle.
I have not heard of what Hopeful mentioned about a 12 week limit on Eltrombopag. NIH never spoke of a time limit other than the 100,000 platelet count although Don does not have an issue with monosomy 7. His chromosomal problems are trisomy 8 and deletion 20. They started the clinical trial for MDS because of the great success they had with their AA patients.
I hope this helps and I wish you the best. Please feel free to ask me any questions either on Marrowforums or my personal e-mail
address - shcalvert3@aol.com.
God Bless,
Sally

I should correct my above post and say that 12 weeks was the point when an initial response was evaluated and that after 16 weeks the Eltrombopag was stopped if no response.

Here are the dosing notes from the maker of Eltrombopag, just as another reference point:
https://www.gsksource.com/pharma/con...G-COMBINED.PDF

I am no expert, but you may want your husband to have his cytogenetics checked if remaining on the drug for an extended period of time. Cytogenetic changes seems like one of the bigger unknowns/risks with this drug.

Hi Hopeful and Hxmxsx,
Hopeful, I'm not sure who you were posting to but I want to address what you said. If I remember correctly, the clinical trial that Don was in assessed his platelet count after 3 mos. or 12 weeks. If he didn't have a response or needed platelet transfusions during that time, he would have been removed from the trial. It didn't have anything to do with any danger - it was just the protocol NIH and Glaxo decided on. After that, as I mentioned, the only reason they would take him off Promacta if he had a response time was if his platelets went over 100,000 which they did and he stopped taking the drug.
As far as Don's cytogenetics, his initial biopsy showed only deletion 5. After he received Campath, his deletion 5 disappeared and he then came up with the trisomy 8 and del. 20. He lost the trisomy 8 for a short period of time but it came back. His deletion 20 and trisomy 8 have remained consistent since then.
I don't remember if what you have read was part of the listed concerns with Promacta when he went into the trial. He has had probably 6 to 8 biopsies since 2012 when he stopped Promacta and his cytogenetics have remained the same. The last biopsy performed was in March, 2015.
One thing I will tell you is that our oncologist - who at one point had Don on her "death list" - told us that he was alive today because he was willing to take a chance. As we know these drugs and treatments all have potential side effects. With Don it was somewhat of a no brainer as nothing else had worked and he was willing to take a risk** - which paid off in spades. But of course each person and case is different and these decisions ultimately can only be made by the individual patient, their doctors and loved ones.
Best wishes,
Sally

**I just read my post to Don. He said the bigger risk to him was not taking the drug...

Hi SallyC,

The uneasiness that I have heard concerning Eltrombopag, and why researchers are still encouraging that it only be used within a clinical trial, is because they now think that some patients may have a small monosomy 7 clone or other cytogenetic abnormality, undetected at diagnosis, that may be stimulated to expand by this drug.

Here is a very recent interesting article from the New England Journal of Medicine in which Dr. N. Young and Dr. P. Scheinberg talk about these concerns.

http://www.nejm.org/doi/pdf/10.1056/NEJMc1209254

I think that it is a very good sign that your husband's cytogenetics have remained very stable :)

Thank you for the information Hopeful.
With these diseases you sure don't know what may happen with the different treatments. As Don has said in the past - you just have to pick your poison and pray for a good outcome. We were very blessed!
The article you linked is about Aplastic Anemia patients of which Don has MDS. A few of the doctors in this link have been or still are doctors at NIH. Dr. Olnes was one of Don's doctors a few years ago. Dr. Neal Young is over Hematology at NIH and Dr. Philip Scheinberg may still be there as well.
While they have had great success at NIH with Promacta and AA, there are obviously risks involved as with any treatment. When Don signed the release form for Campath, one of the "side effects" listed was death. And the Campath darn near killed him.
These decisions regarding treatments are very personal for sure. But in Don's case he really didn't have much choice.
I wish everyone well in their decisions about treatments. While Don is doing extremely well post-Promacta, it was not a cure as we all know. But at the same time, we can only hope that he will continue to do well as they really don't know what the future holds long-term with Promacta.
Thank you so much for your concern and input!
God Bless,
Sally

SallyC and Hopeful, thank you so much for the information. The doctor at UCSF was very careful so he ordered BMB after 8 weeks on eltrombopag and again in another 6 months. He didn't increase his level to 150 mg as suggested by clinical trial guideline and is talking about taking him off Eltrompobag in the near future. That's what worries me as I would think we should at least wait until his platelet gets over 100,000. Right now he is at 38,000. Now he is seeing the doc and does WBC every month.

Thank you so much!

By the way, since he is taking off cyclosporine so early he has lots of cyclosporine left. Do you know where we should donate? Or anyone on this forum may need it? The expiration dates are Nov 2015 and Feb 2016.

more update
 

My husband's recent blood test 7/31/2015 shows a drop of platelet to 13 from 38 on 6/19/2015. His WBC and HGB didn't change (4 and 11). He increased Eltromobag to 150mg per day and started Cyclosporine 250mg twice a day. Keep our finger crossed and keep praying. He may have to do r-ATG.

Update 10/20/2015
 

As I said in my previous post, my husband's platelet dropped to 13 on 7/31/2015 and he was put on increased level of Eltrombopag and restarted cyclosporin. This has caused a significant improvement over time. We believe the previous drop of platelet was due to the premature reduction of cyclosporin (zero) while on Eltrombopag 100mg. Now after almost 2 months of combined Eltrombopag and cyclosporin, his last CBC taken on 10/9/2015 was: WBC 6.1 HGB 12.2 and Platelet 98. During this time frame, he was closely monitored by taking weekly CBC and he has actually winding down Eltrombopag to 50 mg. All in all, very good progress.

Reducing cyclosporin by the right amounts at the right time is a tricky balancing act. We hear about many patients who have reduced their dose or stopped taking cyclosporine, then had to increase it again and try to reduce it again later. My wife was one of them.

The body's reaction must be specific to each patient, because even the best doctors have to take educated guesses about the ideal dosage reduction schedule.

You're making progress. Good luck.

Great to read of your husband's progress, hxmxsx!