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  #1  
Old Tue Feb 25, 2014, 02:06 PM
AAteen AAteen is offline
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Time for transplant?

I have not posted here for long but visited this forum from time to time. My prayers are with you all who suffer or have loved ones suffering from this disease.

My teenage niece was diagnosed moderate AA in early 2009 and treated ATG in mid-2010 with limited response (pre ATG: Hgb 7 – 8, ANC: 0.8 – 1, Plt 15k to 20k). Initial response of RBC and ANC to the ATG was quite good, but declined soon. Platelet rose very slowly, reached 48k highest at about 6 months after ATG, but then declined to 20k - 30k, then 14k - 20k. Seems ATG had initial effect but cannot sustain. My niece was RBC transfusion free for one year until early 2012. In early 2013, she got serious infection and required platelet transfusion for the 1st time (total 4 times in 2 months). She then resumed cyclosporine alone in March 2013, and then platelet and Hgb rose to just above transfusion threshold until early this year when she required RBC transfusion again. Currently still on cyclosporine (150 mg twice per day)

The recent BMB in Jan 2014 revealed chromosome abnormality of trisomy 8. There was no cytogenetic abnormality before ATG and this is the first cytogenetic study after ATG. We wondered whether the cytogenetic abnormality is caused by the ATG treatment or the cyclosporine. Doctor worry that it will progress to MDS and AML and recommend BMT, even no sibling match. Best unrelated donor available is only 7/8 match with mismatch at HLA- B allele. We in Hong Kong only conduct HLA typing for HLA-A, B, C and DRB1. Doctors seem not concerned about the mismatch. But as there is no 8/8 match identified, we are very hesitant. I know there are clinical trials of Promacta on AA and MDS patients in US, but Hong Kong has not introduced this drug. Our doctor not favour 2nd ATG because of unsatisfactory response to 1st ATG.

We are terrified by the 15% to 20% death rate (quoted by our doctor) for MUD transplant in the first year and the GVHD which could be very serious and complicated. My niece and her mother are too scared to think of the tough road ahead. We are lost and it is difficult to find any AA patients who have gone through BMT or their carers to talk to, as there are very few AA cases in Hong Kong.

Thanks for reading my story, and thanks in advance for any information, advice or sharing, in particular considerations on whether and when to go for BMT, and what we should pay attention to in preparing for transplant.
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AAteen, niece dx moderate AA early 2009;ATG in mid 2010 with partial response;currently on cyclosporine; cytogenetic abnormality of trisomy 8 found in early 2014
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  #2  
Old Tue Feb 25, 2014, 02:44 PM
Relentless Against SAA Relentless Against SAA is offline
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AAteen,
I am so sorry that you and your family are going thru this. It isn't easy, I know first hand. We have many of the same questions and concerns that you have.

Question: How long was your niece on Cyclosporine and how quickly did they taper the med?
Does your country say when they might allow clinical trials of Promacta? As you have probably read, NIH reports very promising results with few side effects from the med. NIH had such positive results in SAA, GSK is applying for the med to be fast tracked so it will be available for patients outside of clinical trail. NIH is also offering a Promacta trial for moderate AA.

I am curious about the B mismatch. Did your doctors give you information what is to be expected with this mismatch..? Will they handle the transplant any different than a 10/10 match. Do they plan on using stem cells or bone marrow donor cells? I have heard different opinions on this topic from staff at transplant centers here in the US and am wondering what your docs recommend.

Please know that I am thinking about you and your family. Please keep us posted.
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  #3  
Old Thu Feb 27, 2014, 08:29 AM
AAteen AAteen is offline
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Thank you Relentless. My niece started to taper cyclosporine about 8 months post ATG and the taper completed in about 4 months’ time. About 4 months after taper completion, her platelets dropped to about 20k-25k and then 15k -20 k range. Platelet transfusion still not required but re-started RBC transfusion. She resumed cyclosporine since March 2013 and became transfusion independent for 8 months and needed RBC transfusion again in Jan 2014.

Our doctor said whether it is stem cell or bone marrow transplant depends on which collection method the donor will choose. Doctor did not mention about the expected outcome of B mismatch, but they seem not too concerned. Also has not mentioned any difference in handling the transplant compared to 8/8 match (we do not type for DQB1 and hence the best possible match is 8/8). Thanks for reminding. I will raise the questions in our next appointment.
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AAteen, niece dx moderate AA early 2009;ATG in mid 2010 with partial response;currently on cyclosporine; cytogenetic abnormality of trisomy 8 found in early 2014
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  #4  
Old Thu Feb 27, 2014, 05:17 PM
Relentless Against SAA Relentless Against SAA is offline
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AAteen,
Thanks for answering.
We get different opinions from different members of our transplant team. The doc has said that he would like to use peripheral blood for stem cells because Aplastic Anemia patients have issues with rejection. We hear complete opposite opinions from 2 of the nurse transplant coordinators who work with him (I have never pointed this out to any of them). The coordinators say that in Aplastic Anemia patients you prefer marrow over peripheral blood as a source of stem cells. There is less GVHD with marrow donation. In Leukemia Some GVHD is good to keep the Leukemia in check but with AA you want to avoid all GVHD. The two coordinators say that there should be communication with the donor as to why marrow is really beneficial to the patient. Both coordinators say that many donors understand they are saving a life and are willing to donate marrow, not all, but many.

I recently read an article published 4-19-12 by Neal Young in which he states that rejection is now less problematic, probably because patients are moving faster to transplant and avoiding heavy transfusion burdens, less immunogenic blood products and more efficacious conditioning regimens. Later in the article he states " In SAA GVHD is unequivocally to be avoided and its occurrence decreases survival and long term quality of life. Thus bone marrow is preferred source of stem cells in SAA. The article is titled " How I treat acquired Aplastic Anemia". It is packed with wonderful information. I plan on showing our transplant doc this article and give him a chance to explain his position. I am sure he will love that but I have to understand his reasoning.

Our doc didn't mention any concerns about a B mismatch either. Yet, I am terrified about not having a 10/10 match out there somewhere just in case we need it. Please let me know what your doc has to say at next appt.

Last edited by Relentless Against SAA : Thu Feb 27, 2014 at 06:50 PM.
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  #5  
Old Fri Feb 28, 2014, 12:39 AM
Hopeful Hopeful is offline
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Hi AATeen,

Since your niece does not have a sibling match and responded to the initial ATG (as well as a restart of cyclosporine), I think that you should discuss with her doctor trying a second round of ATG. It may be that the cyclosporine alone is not strong enough to combat the immune attack. Trisomy 8 is a sign that an immune attack is going on.

A second round of ATG is the accepted protocol in the US for someone without a good match that had a response to ATG the first time. People do respond to the second round of ATG, including some people on this forum. Don't delay!

Best of luck!
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55 yo female, dx 9/08, AA/hypo-MDS, subclinical PNH, ATG/CsA 12/08, partial response. small trisomy 6 clone, low-dose cyclosporine dependent
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  #6  
Old Fri Feb 28, 2014, 12:43 AM
Hopeful Hopeful is offline
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Quote:
Originally Posted by Relentless Against SAA View Post
AAteen,
Thanks for answering.
We get different opinions from different members of our transplant team. The doc has said that he would like to use peripheral blood for stem cells because Aplastic Anemia patients have issues with rejection. We hear complete opposite opinions from 2 of the nurse transplant coordinators who work with him (I have never pointed this out to any of them). The coordinators say that in Aplastic Anemia patients you prefer marrow over peripheral blood as a source of stem cells. There is less GVHD with marrow donation. In Leukemia Some GVHD is good to keep the Leukemia in check but with AA you want to avoid all GVHD. The two coordinators say that there should be communication with the donor as to why marrow is really beneficial to the patient. Both coordinators say that many donors understand they are saving a life and are willing to donate marrow, not all, but many.
I have also read from a variety of sources that marrow is preferred to peripheral blood for AA. I know some centers don't want the extra hassle and will only do peripheral blood. However, I recall seeing graphs where problem-free survival was ~10% better with marrow transplants than peripheral blood for AA patients.
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55 yo female, dx 9/08, AA/hypo-MDS, subclinical PNH, ATG/CsA 12/08, partial response. small trisomy 6 clone, low-dose cyclosporine dependent
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  #7  
Old Fri Feb 28, 2014, 08:16 AM
Relentless Against SAA Relentless Against SAA is offline
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Hopeful,
Thank you for your response.
We are hoping to start Promacta and plan on having excellent results! Our docs 100% agree with you that transplant should not be the second step of treatment. I do continue to research info on all avenues of treatment for Aplastic Anemia including transplant. I want to be completely prepared if someday the doc walks in and says "You need to go to transplant now"
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  #8  
Old Tue Mar 4, 2014, 10:31 AM
AAteen AAteen is offline
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Relentless, thank you for sharing your experience. I previously learnt from our doctor that the choice of marrow or peripheral blood as a source of stem cell is entirely up to the donor, and they will not attempt to explain or communicate in such a way to influence donor’s decision. Thanks also for sharing Dr Neal Young’s article, which is very informative. Will bring up some issues to discuss with our doctor at our next appointment. Are you going to start Promacta? Any tentative date?

Hopeful. thank you for your advice. We have mentioned 2nd ATG before to our doctor but he did not recommend. He said that as my niece’s response to 1st ATG was not satisfactory, it is unlikely that she will get good response to 2nd ATG. He also said that if 2nd ATG did not work and proceed to BMT then, my niece’s health conditions will then have deterioriated and will affect BMT outcome. Doctor’s concern now is mainly Trisomy 8 as it may signal emerging MDS. My niece resists BMT very much as it sounds too scary to her. Since she does not feel too bad now, except that she needs RBC transfusion every few months, she is not willing to bear the risks of BMT. In fact in 1st ATG, my niece responded quite well initially in RBC and ANC but bounced back and could only maintain slightly above transfusion threshold. Will bring up the option of 2nd ATG again in our next medical appointment

I wonder if trisomy 8 is uncommon in AA patients and the probability of AA with trisomy 8 evolving to MDS/AML? Any insight or information sharing is very appreciated.
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AAteen, niece dx moderate AA early 2009;ATG in mid 2010 with partial response;currently on cyclosporine; cytogenetic abnormality of trisomy 8 found in early 2014
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  #9  
Old Tue Mar 4, 2014, 08:27 PM
Relentless Against SAA Relentless Against SAA is offline
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AAteen,
Thanks for your reply.
I am sorry that your bone marrow team is unwilling to communicate with the donor. It does make sense that the donor would want to donate peripheral stem cells if they do not understand the need for marrow stem cells.

We do not have a start date for the Promacta. The docs want to wait and watch for a little while. I promise to let you know if they do start Promacta.

Question:
Was your niece on steroids right after the ATG to prevent serium sickness? Is this when her counts were at their best? Steroids seem to stimulate the bone marrow. Sometimes counts come down as they taper the steroids. Just wondering.
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  #10  
Old Sat Mar 8, 2014, 01:23 AM
dfantle dfantle is offline
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Leung, I'm so sorry to hear your niece has relapsed.

Heading to transplant can be scary, especially without a full match. However if your transplant Dr's have a lot of experience with both stem cell and bone marrow methods, hopefully they will be able to answer your questions to help with your concerns.

As you mention, the advantage of the transplant for your niece is it should take care of the Trisomy 8 & AA.

Regarding the steroids, from what I've heard transplant docs prefer patients don't use them if they may need a transplant, unless absolutely necessary. This is because they lower immune function which can be problematic for potential fungal infections & this could delay transplant.

I too struggled with making the decision to move forward with my transplant but was running out of time to keep the donor who was my best match. This is because in the US, if the donor agrees to participate in the transplant, this is only guaranteed for 6 months. After this, their name returns to the full registry for others to be potentially matched to. I don't know of this is an international rule, however. This was particularly challenging because just before my transplant my numbers started improving. But as there was no guarantee they would continue to improve & I feared losing my donor, I decided to have the transplant.

One year later I am so happy I had the transplant. My SAA is gone and my transplant was successful. I pray all will go well for your niece as well.

Best wishes to you and your family
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Dena
Age 54; DX Heavy Chain (AH) Amyloidosis 6/10; AutoSCT 3/11; Amyloidosis remission 6/11; DX SAA 7/11; Horse ATG 3/12; Mini MUD SCT 1/13; Recovered from SAA 5/13 & feeling great
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  #11  
Old Sat Mar 8, 2014, 10:44 PM
Heather8773 Heather8773 is offline
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Dena thx for sharing your story
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Heather, wife of Ronald 36; dx PNH 2012; Dx VSAA 2013; eculizumab(Solaris) hATG 2/20/13 cyclosporine 400 mg daily. 37 units RBC and 15 units of platelets. Post BMT -pentam,vorconizole,valtrex, valcyte, actigall, Pepcid , prograf, magnesium.
10/10 MUD 10/10/13
Now no PNH or AA. Mixed Chimerisim
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  #12  
Old Mon Mar 10, 2014, 07:43 AM
AAteen AAteen is offline
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Thanks Dena for your sharing and concern for my niece. Glad to know that your SAA is gone. It is indeed encouraging to hear success stories. May I know if your transplant is 10/10 match? Do you have GVHD?

My niece is not on steroid currently, but has been on cyclosporine alone for a year. Not good results. Just maintain platelets around 15k – 20k and re-started RBC transfusion early this year.

In Hong Kong, we do not have “guarantee” period, and potential donors can back out any time. So we just hold the faith that those who have registered in the donor registry will “keep their promise” to donate. We have been considering the transplant option, but my niece seems has decided not to pursue this option, at least at this stage. She is not willing to bear the risks of transplant, which are too scary to her. We cannot “push” her to the transplant option as this is her decision after all. She even refused to do second ATG now, probably because the improvements gained from the 1st time experience is limited and short lived. So she just keeps cyclosporine for the time being, and “wait and watch”.
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AAteen, niece dx moderate AA early 2009;ATG in mid 2010 with partial response;currently on cyclosporine; cytogenetic abnormality of trisomy 8 found in early 2014
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  #13  
Old Fri Mar 14, 2014, 01:16 AM
Hopeful Hopeful is offline
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Hi AATeen,

I was recently listening to a presentation from NIH on the AAMDSIF website.

It was mentioned that a trisomy 8 mutation can be seen with AA and that this mutation is not associated with any negative impact on overall survival. In the Q&A at the end of the presentation, it was also mentioned that a trisomy 8 mutation can be transient. So I wouldn't panic with this finding.

You can view the presentation at:
https://live.blueskybroadcast.com/bs...=1418&CAT=7169
under the "Aplastic Anemia: Current Thinking…" tab


What is your niece's cyclosporine dosage and what is her weight in kg?
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55 yo female, dx 9/08, AA/hypo-MDS, subclinical PNH, ATG/CsA 12/08, partial response. small trisomy 6 clone, low-dose cyclosporine dependent
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  #14  
Old Fri Mar 14, 2014, 12:38 PM
KMac KMac is offline
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Yes, I found this article on the subject. On the bottom of page 3132, Graph D appears to show 100% survival at 10 years for AA patients with the trisomy 8 mutation:

http://bloodjournal.hematologylibrar.../3129.full.pdf

Also, it mentions the mutation may be transient as Hopeful heard at the AAMDS presentation. It seems perhaps the trisomy 8 mutation in AA patients has a better prognosis than a patient initially diagnosed with MDS who has trisomy 8.

..of course, not being a doctor, I am reticent to fully trust my understanding of these things. But between this and the great info that Hopeful posted, it certainly seems like a question to raise with your niece's hematologists.

On the other side of the argument would be your niece's youth, and the promising advancements being made in MUD transplants. There is still risk, but much less than in the past, and there is a very real possibility of a full cure. This is only anecdotal, but I have seen some wonderful results of MUD transplants for SAA at my hospital, on folks much older than your niece.

I wish your niece the best in making this difficult decision. She is fortunate to have you!
__________________
Kevin, male age 45; dx SAA 02/2012 - Hgb 5.8, platelets 14, ANC 200, 1% cellularity. Received ATG 03/2012. As of 03/2015, significant improvement - Hgb 15, platelets 158, ANC fluctuates around 1000, Lymphocytes 620. Tapering cyclosporine. BMB 20-30% cellularity.

Last edited by KMac : Fri Mar 14, 2014 at 12:55 PM.
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  #15  
Old Fri Mar 14, 2014, 02:02 PM
AAteen AAteen is offline
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Hopeful and KMac, thanks a lot for the information, which has relieved my fear a bit. I will take some time to listen to the presentation and read the article.

Hopeful, my niece weighs about 50 kg and currently on 150 mg cyclosporine twice a day (i.e. 300 mg a day in total)

I will raise the information I read to our doctor if I have chance. The culture here is quite different from US, I think. Many doctors here are not willing or cannot afford to spend so much time to discuss with patients. Often, they think that they have explained enough, and it is not necessary for patients to understand so much details from the medical perspective as this is beyond the "role" of patients. They think patients should trust doctors, who will do their best to help patients.

Thanks you all for your sharing and kind words. Will keep praying for my niece and all on this forum.
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AAteen, niece dx moderate AA early 2009;ATG in mid 2010 with partial response;currently on cyclosporine; cytogenetic abnormality of trisomy 8 found in early 2014
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Old Fri Mar 14, 2014, 08:46 PM
Hopeful Hopeful is offline
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Sounds like she is on a reasonable dosage.

Our doctors are the same as yours That's why second and third opinions are welcome.
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55 yo female, dx 9/08, AA/hypo-MDS, subclinical PNH, ATG/CsA 12/08, partial response. small trisomy 6 clone, low-dose cyclosporine dependent
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  #17  
Old Sat Mar 15, 2014, 08:38 PM
dfantle dfantle is offline
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Hi AA Teen, regarding the donor. They can back out anytime here as well, but the 6 month guarantee just means their name stays out of the donor pool for 6 months so they are not available to other potential patients during this time period.

My match was a 10/10 & same blood type. However even with this good of a match, at my age GVHD risk is much higher than your niece. I was very lucky that I only had minor oral GVHD starting around 3-4 months post (I never noticed it, but my transplant dentist saw a few very minor symptoms). I have had some new mild GVHD which appeared just at my 1year anniversary. This is all very manageable, however.

My understanding is some countries only use an 8 point scoring system, where 8/8 is considered a perfect match, though I do not know what the differences are.

Regarding deciding when may be an important factor to look at to decide to forward with Transplant or not. My doctor supported my decision to wait longer for the ATG to work before moving forward with transplant as long as I stayed healthy. However, although I wasn't getting sick I started getting some minor skin infections & when this happened my white cells did not increase to fight the infection as they are supposed to & instead dropped-which doesn't happen to most AA patients. This is when we started talking about my needing transplant.
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Dena
Age 54; DX Heavy Chain (AH) Amyloidosis 6/10; AutoSCT 3/11; Amyloidosis remission 6/11; DX SAA 7/11; Horse ATG 3/12; Mini MUD SCT 1/13; Recovered from SAA 5/13 & feeling great
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Old Sun Mar 30, 2014, 06:42 AM
AAteen AAteen is offline
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Thanks for all your replies. Hope you are all doing well. Dena, good to hear that you only have minor GVHD, which are all manageable. Heather, I have read some of your earlier posts and great to know that your husband is doing well 5 months post transplant. Hope he will continue to do well. Blessings to him. For MUD transplant, GVHD is still a great problem, even with 10/10 match. That’s why we are so reluctant to go for this option before exhausting other options. My niece is too too scared to consider transplant at this stage.

I just managed to get time to listen to the presentations from NIH. Not sure if I get it correctly from Dr Townsley’s presentations. Seems that rabbit ATG (vs horse) is recommended for 2nd round ATG, and stoppage (as opposed to tapering) of cyclosporine at month 6 after ATG is recommended since there is no difference between stoppage and tapering with regard to relapse risk. I recall that there has been an article saying that slow tapering reduces risk of relapse. So, there have been changes in findings in latest studies? Any ideas?

In Dr Townsley’s presentation on “New Directions in Aplastic Anemia Treatment: What’s on the Horizon?”, the results of Promacta in NIH trials sound very encouraging. I have mentioned this drug to our doctor last time, but he seemed not too interested. He said they also use this drug, but for treating other disease and not AA. They will not try Promacta on AA patients at the moment unless there is such clinical trial here or the hospital has participated in such clinical trial organized by other relevant organizations.

Relentless, you have chance to try Promacta, though not have a date yet. If one day you take this drug, I do hope you will achieve excellent results. What are your counts now? Btw, I missed your earlier question regarding the use of steroid after my niece’s 1st ATG. Yes, she was on steroid during and after ATG treatment for about I month. She achieved best counts at different time for different lines. Hgb rose right after ATG, but just for about a week, then decllined and still needed RBC transfusion at month 4 and then hovered between 8+ to 7+ for a year, just above transfusion threshold . ANC fluctuated a lot, responded quite well initially for more than a month, then dropped to slightly better than pre-ATG level, then improved a bit for a few months and then declined back to pre-ATG levels. Platelet is the hardest line with very slow and limited response, best was only 48k at around month 6, but then declined and fluctuated and declined to teens and single digit before re-starting cyclosporine alone last year.
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AAteen, niece dx moderate AA early 2009;ATG in mid 2010 with partial response;currently on cyclosporine; cytogenetic abnormality of trisomy 8 found in early 2014
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  #19  
Old Tue Apr 1, 2014, 05:03 PM
Relentless Against SAA Relentless Against SAA is offline
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AAteen,
Please read the private message I am sending to you.
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  #20  
Old Fri Apr 4, 2014, 01:17 AM
AAteen AAteen is offline
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Quote:
Originally Posted by Relentless Against SAA View Post
AAteen,
Please read the private message I am sending to you.
Hi, Relentless, I have sent you a reply private message. Please check.
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AAteen, niece dx moderate AA early 2009;ATG in mid 2010 with partial response;currently on cyclosporine; cytogenetic abnormality of trisomy 8 found in early 2014
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  #21  
Old Fri Apr 11, 2014, 01:28 AM
Relentless Against SAA Relentless Against SAA is offline
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AAteen,
I am sending you a reply thru private message
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  #22  
Old Sat Jun 14, 2014, 07:54 PM
Relentless Against SAA Relentless Against SAA is offline
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B mismatch

I have sent you a private message. Please let me know if you do not receive it. How is your niece? My prayers are with your family
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  #23  
Old Tue Jul 1, 2014, 12:53 AM
AAteen AAteen is offline
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Quote:
Originally Posted by Relentless Against SAA View Post
I have sent you a private message. Please let me know if you do not receive it. How is your niece? My prayers are with your family
Thanks Relentless. My niece's conditions is worsening. Keep praying. I have sent you a reply through private message. Please check whether you have received it.
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AAteen, niece dx moderate AA early 2009;ATG in mid 2010 with partial response;currently on cyclosporine; cytogenetic abnormality of trisomy 8 found in early 2014
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