Cyclosporine before ATG - Newly diagnosed and New Zealand treatment options

[Alcof]

My father was diagnosed with AA in June this year after GP took bloods and discovered bruising etc. After been admitted to our local hospital he was given blood transfusions and then a bone marrow tap that gave the diagnosis. He was then prescribed doses of prednisone and cyclosporine and sent home after 3 days to await an appointment with the main city hospital. After having a conversation with city doctor he was sent home again. He then contracted pneumonia and was hospitalised. Then contracted hospital bugs and was treated with extreme antibiotics. In conjunction with this has been receiving platelets and full blood transfusions and continuing with prednisone and cyclosporine. He is now home, bed ridden after beating all the infections. He has extreme muscle weakness and finds it hard to walk, sit up etc. Now we are in holding pattern for a new appoint in a month with city doc, waiting for bloods to go down and back and forwards to get transfusions.

Questions:
1)Has anyone else been prescribed cyclosporine before ATG? I have scoured dozens of forums and no one has mentioned it that I have found.

2)City doctor is all about Rabbit-ATG. We live in New Zealand which doesn't seem to have a lot of experience with AA. I have read Dr Youngs recent publications that states Horse-ATG is considered first line treatment. My father is 72 - it seems to me that we should be trying to get onto Horse as we don't have as much time to muck about! Advice?

3)I also wanted to find out if there was an easier way of working transfusions into our lives. Since being sent home we have only experienced the emergency room route as our results came back low on a Friday and we were told to wait until Monday unless we got the mouth ulcers or blood coming out anywhere etc...Thus the emergency room trip on Saturday at 5am. How have others managed their blood count maintenance and transfusions?

4) Best posts for understanding blood count language? Everyone here so good at putting down what their counts are and I don't know where to start. We have never focused on this detail yet and it seems we must.

Appreciate any help you can provide. We are resilient and determined but we know this will be a long road. Can't believe that 8 weeks ago my Dad was out working the farm....

[curlygirl]

I'm sorry you're Dad has been through all of this.

To answer your main question, my son started his cyclosporine at the same time as the ATG. Not before but he did start them together. So I think starting the cyclosporine before may not hurt, but you'll want other people to chime in.

For the type of ATG, for some reason Horse ATG was pulled from the European and Latin American market in 2007 or 2008. I don't know why, I've searched on the internet but can't find a reason. So it is actually not available there. So in Europe they use Rabbit ATG exclusively. I don't know if it is available in Australia or New Zealand.

I'm not sure about managing the transfusions. They would wait below 10k to transfuse platelets at my son's hospital so that meant if he had 22k on Friday I'm sure he would have been at his 6k by Sunday. Then he'd still have 6k on Monday and they'd transfuse him them. If my son was sick with a fever his doctors would transfuse at a hemoglobin of 7.5 because he would burn through his blood with a fever. Otherwise they transfused below 7. Sometimes you can't help the ER visits.

ATG makes you feel very sick and tired. It took about 8 weeks for my son to start feeling normalish again.

I hope your father feels better soon.

[curlygirl]

This link is from an article from the UK, but here is a history of the rabbit vs. horse preparations. It says ATGAM is administered for 8-14 days, but I thought NIH recommends 4 or 5 days only (my son had 4):

http://www.medicinesresources.nhs.uk...Dec%202012.pdf


"The standard ATG preparation used for the treatment of AA in the UK had been horse ATG (Lymphoglobuline®, Genzyme), however this was withdrawn from the market in 2007 and replaced by rabbit ATG (Thymoglobuline®, Genzyme). Rabbit ATG had previously been used mostly for a second course of immunosuppressive therapy (IST) in patients who had relapsed or were refractory to a first course of horse ATG (2, 3). Thymoglobuline® is licensed in the UK for immunosuppression in solid organ transplantation; it is not licensed for the treatment of AA (4).

Atgam® (another horse ATG preparation) is approved in the US for the management of allograft rejection in renal transplant patients and for the treatment of moderate to severe AA in patients who are unsuitable for bone marrow transplantation (5). For AA the recommended dose regimen is 10-20 mg/kg daily for 8 to 14 days; additional alternate-day therapy up to a total of 21 doses can be administered. Because thrombocytopenia can be
associated with its administration, patients may need prophylactic platelet transfusions to maintain platelets at clinically acceptable levels.

Atgam® is not licensed in the UK but is available on a named patient basis (6)."

[Alcof]

Originally Posted by curlygirl

This link is from an article from the UK, but here is a history of the rabbit vs. horse preparations. It says ATGAM is administered for 8-14 days, but I thought NIH recommends 4 or 5 days only (my son had 4):

http://www.medicinesresources.nhs.uk...Dec%202012.pdf


"The standard ATG preparation used for the treatment of AA in the UK had been horse ATG (Lymphoglobuline®, Genzyme), however this was withdrawn from the market in 2007 and replaced by rabbit ATG (Thymoglobuline®, Genzyme). Rabbit ATG had previously been used mostly for a second course of immunosuppressive therapy (IST) in patients who had relapsed or were refractory to a first course of horse ATG (2, 3). Thymoglobuline® is licensed in the UK for immunosuppression in solid organ transplantation; it is not licensed for the treatment of AA (4).

Atgam® (another horse ATG preparation) is approved in the US for the management of allograft rejection in renal transplant patients and for the treatment of moderate to severe AA in patients who are unsuitable for bone marrow transplantation (5). For AA the recommended dose regimen is 10-20 mg/kg daily for 8 to 14 days; additional alternate-day therapy up to a total of 21 doses can be administered. Because thrombocytopenia can be
associated with its administration, patients may need prophylactic platelet transfusions to maintain platelets at clinically acceptable levels.

Atgam® is not licensed in the UK but is available on a named patient basis (6)."

Thanks so much for all you advice Curlygirl. Really is very welcome as we are feeling sometimes very isolated. I really do appreciate you taking the time to reply.

Yes I am yet to find any report where Cyclosporine is used before ATG...but my feeling was that it may be an advantage to be accustomed to that before the introduction of the ATG treatment....who knows.

Very interesting about Horse-ATG being not available across Europe etc. Great to have extra information ready for when I meet with the city doc next. Aim to print a few things out and ask for a please explain. Its not always easy asking doctors questions as they can sometimes be very superior in attitude.

Thanks also for the advice on managing transfusions and timings etc. I guess its good to know that it wasn't necessarily our naivety that got us into the emergency room for the transfusion.

Thanks again for the sense of connection.

[Hopeful]

Hi Alcof,

Originally Posted by Alcof

Questions:
1)Has anyone else been prescribed cyclosporine before ATG? I have scoured dozens of forums and no one has mentioned it that I have found.

I was prescribed cyclosporine alone before ATG. My local doctor was hoping that it would put my condition in remission without having to rely on the ATG. It didn't work for me. However, for an older patient, it is a reasonable thing to try since ATG is so hard on the body. In some countries, cyclosporine alone is the only option. The success rate is not as high as ATG, but I think I remember it to be 40%.

Your dad should not be on prednisone prematurely if he has AA. This is only used for the prevention of serum sickness from ATG. It is not a treatment for AA. My inexperienced doctor also tried me on this.

You will get into the rhythm of managing transfusions over time. Make sure to have blood checked early in the week so that transfusions can be scheduled before the weekend, if necessary.

Best of luck to your dad! Hope he gets on the road to recovery quickly! You don't want to delay treatment for AA, once it is diagnosed.

[Alcof]

Originally Posted by Hopeful

Hi Alcof,



I was prescribed cyclosporine alone before ATG. My local doctor was hoping that it would put my condition in remission without having to rely on the ATG. It didn't work for me. However, for an older patient, it is a reasonable thing to try since ATG is so hard on the body. In some countries, cyclosporine alone is the only option. The success rate is not as high as ATG, but I think I remember it to be 40%.

Your dad should not be on prednisone prematurely if he has AA. This is only used for the prevention of serum sickness from ATG. It is not a treatment for AA. My inexperienced doctor also tried me on this.

You will get into the rhythm of managing transfusions over time. Make sure to have blood checked early in the week so that transfusions can be scheduled before the weekend, if necessary.

Best of luck to your dad! Hope he gets on the road to recovery quickly! You don't want to delay treatment for AA, once it is diagnosed.

Thanks for the advice!

Makes sense to hope for a recovery given his age and I guess its always hard waiting. Would have been nice to understand the doctors strategy in advance.

I've found some documents now that recommend waiting for 4-6 weeks to see if there is any recovery. Its been 8 weeks now and haven't seen anything except a general deterioration in strength and constant transfusions...but we're off to see the big city doctor tomorrow and fingers crossed we can get on with trying something new!! And perhaps having a break from the cyclosporine!

Can't wait for some change. Very hard keeping Dad's spirits up when you don't have any news, and no clear path for treatment. Amazing the difference now we have this appointment tomorrow. We all have something to look forward to.

[Hopeful]

Good luck tomorrow!

I think the prednisone could be a factor in the deterioration of his strength. I had some pretty major calf and arm muscle wasting when it was prescribed for me.

[Cheryl C]

Hi Alcof

Can't help with advice about your medications but try this website for easy explanations of the results of standard blood tests:

http://www.newportnaturalhealth.com/...g-blood-tests/

or this one, where you can type the name of the test in yourself:

http://www.labtestsonline.org.au/und...lp/tab/related

All the best!

[Alcof]

Cyclosporine as first line treatment, for anyone looking for treatment options in the Elderly...

Found in Aplastic Anemia: First-line Treatment by Immunosuppression and Sibling Marrow Transplantation by Jakob R. Passweg1 and Judith C.W. Marsh

The decision whether to use ATG in older patients can be difficult and requires careful assessment and discussion of the risks with the patient. For older patients, the response rate and survival rate are lower, compared with younger patients. The response rate for patients aged > 60, 50 to 59, and < 50 years is 37%, 49%, and 57%; 5-year survival is 50%, 57%, and 72%, respectively. For patients aged > 70 years, the 10-year survival is 33%, compared with 60% for those aged between 50 and 70 years.28,29 Although there is no upper age limit for ATG treatment, consideration for treatment should be preceded by medical assessment to exclude significant comorbidities. CSA treatment alone may be considered. The current EBMT treatment algorithm proposes to treat hospitalized patients who are severely ill by ATG + CSA, if considered to be tolerable considering the comorbidity profile, whereas to start newly diagnosed patients who are well and in an outpatient setting with CSA alone.