Question: Dear Dr,

Brief:
Moderate aplastic anemia progressed to severe aplastic anemia. Evolved with trisomy 8 found later. Currently Eltrombopag and cyclosporine

Details
 My niece (East Asian), now late teens, dx moderate AA early 2009;ATG in mid 2010 with limited response; RBC tx independent for one year then. Re-start RBC tx in early 2012. Re-start cyclosporine alone in April 2013, then tx free for 9 months. Re-start RBC tx in early 2014
 Started Eltrombopag (Promacta) since Nov 2014, initially 25 mg daily for 1 month, then raised to 50 mg daily until end March 2015, then 75 mg daily until now, currently also on cyclosporine 50 mg x 2 times each day.
 Before starting Eltrombopag , platelets range 12k to 17k, ANC about 0.8 to 1.4. No noticeable improvement after starting Promacta
 Lab reports attached

Our doctors here basically have no experience in using this new drug for treating SAA. We really need expert advice from other places with more experience in using Promacta for treating AA or other bone marrow diseases, so that we can discuss with our doctors. I understand that Promacta has yielded success in clinical trial in US for AA patients and seems it is under trial for MDS patients. Questions –

1. My niece is an east asian, is 75 mg daily the maximum dose for East Asians?
2. We have started Promacta for 7 months and stayed on 75 mg daily for 2.5 months already but results are disappointing (please see CBC reports). Does it mean that Promacta has no effect on my niece? Shall we continue its use? Why or why not?
3. If continue, shall we stay on 75 mg daily or increase to 100 mg? How long should we continue to try in your opinion?
4. I recall that I have seen from articles/reports that chromosome changes (some are more complex/serious chromosome 7 changes) were reported in some patients during clinical trial of Promacta for AA. What is the chance of chromosome changes? How does it relate to the duration of use of Promacta? We are concerned as my niece is on Promacta for 7 months already.

5. If one does respond to Promacta, at which dosage level will there start to be noticeable improvement if he/she does respond? How long should we wait before we declare Promacta has no positive effects on my niece?

6. Under the clinical trial of Promacta for AA patients, are there any observations or common characteristics regarding those patients who respond well and those who do not?

7. My niece is very very scared of BMT and refused this option. Also, the best available MUD match we can find is only 7/8 at high resolution. Promacta seems give us a light of hope and my niece is a guinea pig hear in our place. However, results are so discouraging. We feel rather helpless. What are your suggested way forward and actions to be taken if you were in our place? What other advice do you have in relation to the use of Promacta?

Would also appreciate any advice regarding her disease. We have been battling this dreadful disease for years and are so tired

Best Regards,

Dear Dr. De,

Thanks for your prompt reply.

You said “For East Asian maximum dosage of promacta is 50 mg once daily” but also said “If it does not respond to 50 mg then you can increase it to 75 mg”. So , is the maximum dose for East Asian should be 50mg or 75 mg daily?

My niece is already on a dose of 75 mg daily for nearly 3 months, but still no noticeable improvement. She has started Promacta since November 2014, so 7 months already. So your advice is to continue for another 5 months (i.e. try a total of 12 months) or another 11 months (i.e. try a total of 18 months?) ? Should she continue on the current dosage (i.e. 75 mg daily)?

Your said " chances of chromosome change is 25% “ and “I year and above use causes chromosome changes”. Are these based on the findings from previous clinical trials of Promacta?

Have you come across Severe AA patients who have tried Promacta? Do they respond or not respond? If respond, what is the dosage at which noticeable improvements started to be seen?

Can cyclosporine be taken while on Promacta? My niece is currently on cyclosporine as well.

Looking forward to your expert advice.

Best Regards