Experience with ATG and Cyclosporin

[Data]

My doc called me today and said it "looks like" I have aplastic anemia. I have an appointment with her on Monday to "discuss options" as she put it. From what I have read ATG and Cyclosporine is a typical treatment. I am curious as to how this is gen - orally, IV, at home, as an inpatient, how long, side affects, etc? I am just trying to learn a little before I talk to her and would greatly appreciate any comments or suggestions?

Thanks and good luck to all of you in your journeys.

Data

[sbk007]

I forgot to ask if you ever had a second opinion?
Is that her way of saying you do have AA?? "Looks like" and "you have" mean different things but perhaps not in docspeak. Most of the Docs I meet have a habit of talking a lot without saying much or displaying any emotion, poker faces. It is a great idea to empower yourself so you can understand what she's saying and respond intelligently and ask questions. I don't know much about AA but if you search for ATG you'll find a lot of stuff. I hope you're feeling well. Take Care, Steve

[Data]

Originally Posted by sbk007

I forgot to ask if you ever had a second opinion?
Is that her way of saying you do have AA?? "Looks like" and "you have" mean different things but perhaps not in docspeak. Most of the Docs I meet have a habit of talking a lot without saying much or displaying any emotion, poker faces. It is a great idea to empower yourself so you can understand what she's saying and respond intelligently and ask questions. I don't know much about AA but if you search for ATG you'll find a lot of stuff. I hope you're feeling well. Take Care, Steve

Steve,
I agree on the "DocSpeak". Sometimes I think they talk like lawyers to limit their liability. I have not gotten a second opinion but am considering it before starting treatment.

Data

[sbk007]

Data, I'm surprised your hematologist didn't suggest you see someone that treats a lot of AA cases. Most local heme's don't see many cases whereas the experts see clusters. I think you have nothing to lose by getting a second opinion and hope you'll ask your hematologist what she thinks about that. From personal experience and what I see on here its typical to get a second or even 3rd opinion by an expert in the field.
Take Care

[Data]

Originally Posted by sbk007

Data, I'm surprised your hematologist didn't suggest you see someone that treats a lot of AA cases. Most local heme's don't see many cases whereas the experts see clusters. I think you have nothing to lose by getting a second opinion and hope you'll ask your hematologist what she thinks about that. From personal experience and what I see on here its typical to get a second or even 3rd opinion by an expert in the field.
Take Care

007,
Thanks for the comment. I am concerned about my hematologist also. I discovered she is not board certified in hematology. She is only board certified in oncology. Also, one of the criteria for AA is "Anemia with corrected reticulocyte count < 1 %" and in all the blood tests she has ordered, reticulocyte hasn't been one of them. I am seriously considering getting a 2nd opinion, especially before I start something as drastic as ATG/CsA.

Thanks again and good luck to you!!!

Data

[KMac]

Hi Data,

I am sorry to hear of your possible diagnosis, but glad you found this forum. I want to preface all I say below with the disclaimer that I'm just a patient, so though I believe I am on the right track, I'm not technically qualified to be fully confident on this.

I strongly agree with Steve that you'd be well-advised to 1) empower yourself to ask the doctor educated questions about your condition and possible treatments, and 2) get a second opinion.

I think it is crucial when talking with the doctor to flesh out her level of expertise & previous experience in treating aplastic anemia. To be honest, I've heard several unsettling stories of aplastic anemia patients being treated with a brutal combination of arrogance and incompetence by doctors who know very little about this disease. Aplastic anemia is a very rare & mysterious condition that can run several possible courses, and as such there is no substitute for extensive previous experience in treating it. A given hematologist may be quite good at treating leukemia for example, may be a perfectly competent doctor, yet still not be qualified to treat an aplastic anemia patient due to lack of experience with this particular condition. And I am afraid under those circumstances ego often gets it the way, and the said doctor doesn't humble themselves in the face of what they don't know, doesn't refer you to or even consult with the proper expert on crucial treatment questions.

I believe Dr. Neil Young from NIH, the pioneer of ATG/CsA treatment, would agree with the jist of what I just said above, although he puts it in more polite non-accusatory terms. To paraphrase what he says at the end of the video below "there are very few excuses today for aplastic anemia patients not to be seen at a center with deep expertise & experience treating this condition".

https://www.youtube.com/watch?v=02rvFOFYOVw

All that said, in some cases even the best experts can disagree on treatment paths in aplastic anemia. There was an article on the AAMDS website a while back (I highly recommend AAMDS, they are a wonderful resource) about a family whose child has SAA. They took the child to see some top experts, and were left with contradictory treatment suggestions. In that case, I personally wouldn't blame the doctors at all. Rather, unfortunately the science isn't always established enough for even the best SAA doctors to have a unity of opinion. And in this situation, disagreement is a good healthy thing I believe, the discourse helps advance the cutting edge of the science (along those lines if you can get somewhere with multiple SAA experts, I think that is best). I think very highly of my treatment center (Colorado Blood Cancer Institute), and several times during my treatment the doctors would discuss/debate what to do at a particular juncture (and I am happy to report I've went from near death to having my life & health restored).

All that said, what is the patient to choose when you know the best doctors sometimes disagree? Whose advice do you go with? I agonized over this, thinking "who am I to cast the deciding vote here, I know nothing about hematology?". But all of us as patients are the definitive experts on our symptoms, the sum total of our past experience, our hopes for the future, and the risk/benefit trade-offs we are willing to accept. It may not be scientific, but when the science isn't completely there, we are left with intuition, with the small quiet voice in our heads (or sometimes the screaming terrified voice in our heads) pointing towards the best personal path. I think this is even sometimes the case with the doctors themselves. Again, Dr. Young said something to this effect, that he feels the most promising advances in treating aplastic anemia come from hematologists operating within the established framework of knowledge, but using intuition to build upon this framework.

[KMac]

So I've said a lot of broad philosophical stuff about seeking aplastic anemia treatment, now I'll get to the specifics, starting with areas where to my understanding the best experts may disagree, and then list the questions I'd ask your doctor were I in your shoes. Here are the areas where I think there may be disagreement (hence for you and your intuition to help decide):

1) Sometimes, instead of ATG/CsA, it is recommended the patient go immediately into transplant. Generally, if you are under 40 and have a sibling donor, I believe transplant is the preferred option, but boundaries between which way to go are not solid rock walls in any way. I for example was over 40 at diagnosis, yet my siblings were tested, and had one of them matched I would have went the transplant route.

2) There is a promising new treatment for aplastic anemia which again NIH has discovered called eltrombopag. The FDA has approved it as a salvage treatment (i.e. if the first treatment does not work and transplant is not an option). However, NIH is currently conducting trials including eltrombopag along with ATG/CsA. They cannot provide specifics as the trial is not complete, but in presentations they state that they are very excited about the results to date, and eltrombopag may revolutionize aplastic anemia treatment. Unlike ATG/CsA which just supresses your immune system (but often that is enough in itself), eltrombopag also actually stimulates the marrow to grow and produce healthy blood cells. So perhaps you would have the opportunity to decide if you'd like to take part in this trial.

3) Here's a controversial one - Johns Hopkins offers a treatment called High Dose Cyclophosmamide. To my understanding, it's a massive chemotheraphy dose to wipe out nearly all your bone marrow, leaving just the most basic pluripotent stem-cells (i.e. those from which all other blood cells can develop). The idea is to 'reboot' your hematologic system, with whatever defect which caused the aplastic anemia being destroyed in the process. Anecdotally there are cases of excellent sustained recovery, but NIH is strongly convinced this isn't a good treatment path based on their analysis, due to high toxicity, fatality, and sometimes poor recovery. This is a prime example of where the best experts, who I trust are well-meaning and qualified, still profoundly disagree (I personally cast my vote with the NIH treatment path).

4) Prophylactic treatments, when to use them, and which ones? Specifically antivirals, antibiotics, antifungals, and a drug called neupogen which can temporarily boost your white blood count to prevent infection. It is very common for hematologists to use some or all of the above, for some time period, to protect the patient from life-threatening complications due to low white blood count, while they are waiting for the true treatment to work.

5) When do you "pull the trigger"? By this I mean whatever the treatment, at what point do you apply it, and at what point do you stop applying it or taper it? How low does the hemoglobin and platelets get before you transfuse? How low does the ANC (neutrophils, a type of white blood) get before you give neupogen? How long do you keep giving it? Do you give prophylactic antivirals, antibiotics, & antifungals (and if so which ones), or do you only apply these in case of infection? What is a proper cyclosporine trough level for a given patient? I've heard vigorous debate on some of these questions. As my doctor said to me, everything can come at a cost, as these treatments often have side effects.

[KMac]

...and now for the sort of questions to consider asking your doctor for you case:

1) How many previous aplastic anemia patients has she treated? What were the treatments? Does she have experience in transplants, or making the decision when to bring a patient into transplant. Does she work directly with any Centers of Excellence (e.g. NIH, The Cleveland Clinic, Fred Hutchinson) when treating aplastic anemia patients?

2) A broad discussion of treatment options. I'd ask her 'off the cuff' type questions on the '5 points of potential disagreement' above such as "how do you feel about eltrombopag, would you recommend trying to get into a clinical trail with ATG/CsA/Eltrombopag?". "What is your view on complementary prophylactic drug treatement?". "What will be the test procedure for monitoring my Cyclosporine trough?" The point here isn't so much what her opinions are, but that she has opinions. If she looks dumbfounded, if she hasn't heard of eltrombopag or doesn't know what a cyclosporine trough is, that is a huge sign she is absolutely not qualified to treat aplastic anemia, and if she is a good doctor and decent person, her next step will be to refer you to someone who is qualified.

3) I agree with Steve that "looks like" aplastic anemia as she said is in no way good enough. Aplastic anemia is a "diagnosis of exclusion". In other words it is properly diagnosed when the blood counts are broadly speaking all low (pancytopenia), the marrow is hypcellular, and there are no cytogenetic or other abnormalities. Regarding your marrow, there are some specific questions to ask there:

a) What percentage is my marrow cellularity? (i.e. how hypocellular is it for my age)
b) Has the possibility of MDS reasonably been ruled out with cytogenetic testing of my marrow?
c) Has the possibility of PNH reasonably ruled been out via FISH testing of my marrow?
d) Is the blast count in my marrow within normal range.

.....also, be sure to ask for the full results of your bone marrow biopsy, which should contain all of the above. But first I'd ask her the specific questions above to be sure she's on the ball.

4) At what point would you recommend we "pull the trigger" and start treatment? Considering you are not now in the hospital (I assume), you are doing much better than many of us at diagnosis. Perhaps you only have a mild or moderate case of aplastic anemia. That would be good. But as a very helpful person from AAMDS once told me, there is a frustration for mild to moderate aplastic anemia, in that there really aren't proven treatments for that. I believe in such a case, often it is just "watch and wait", and perhaps the condition will stay stable, perhaps it'll resolve itself, perhaps it will worsen.

5) By the point above I mean specifically the blood counts - ANC, Hgb, Plt. What are those at for you now? I assume above transfusion levels?

6) Do my absolute lymphocyte count and reticulocyte count confer a good prognosis for ATG treatment? Again, if she doesn't know significance of this question, she has no business treating aplastic anemia and needs to refer you elsewhere. Specifically, NIH has found a strong correlation between a high lymphocyte count, a high reticulocyte count, and a good response to ATG. This is because your lymphocytes are the class of white blood cells which contain the rogue cells presumed to be causing the immune-mediated attack which is the root of aplastic anemia. If there are a lot of them (or at least a normal amount, you can check this on your CBC), then the ATG has a target to zero in on and kill. And your reticulocytes are the baby blood cells. If you have a normal amount of them, even if you are profoundly anemic, it suggests your marrow is still functional enough to respond to the anemia. Try not to get down if either of these are low though. I had a retic count of 0 at diagnosis, yet I still responded well. The initial point here is to make sure the doctor is right to treat your condition.

7) What are your procedures for handling the risk of analphylactic shock and oother risks associated with ATG treatment? You had asked about how ATG/CsA is administered. The ATG will be probably a week or so in the hospital, with the first four days getting the infusion (once each day). The infusion is set to run 4 hours a day, but if your body objects to that (my body did), they can slow that down considerably, so long as each of the 4 infusions are administered with a given 24-hour period. In short, ATG can be challenging, or you could sale through it. Part of the mystery of this thing.

8) What are the steps you take to prevent serum sickness post-ATG? Administration of a steroid, probably prednisone on a very high dose for a week or two, and then slowly tapered, should definitely be big part of her answer here. In case you hadn't heard about the serum sickness, it a very common but unfortunately often very unpleasant delayed reaction (allergic?) to the ATG. I got it, and it wasn't fun, but it passed.

9) How often will you be checking on me post-treatment? Under what conditions should I get myself to your office or an emergency room in between our appointments? Typically I believe she'd have you come in about 3 times a week at first to monitor your counts. But also, especially if you have a very low ANC (~500 or less), she should tell you to contact them immediately at any sign of infection, or with a fever > 100.5 F.

....this is probably very overwhelming, it was for me. I am sorry to see anyone have to go through this. But with aplastic anemia, even when the prognosis seems bad, in a way the prognosis is good on the long term. This is because modern medicine (not just any modern medicine, but those with expertise in aplastic anemia specifically) is improving greatly at keeping even those with very severe aplastic anemia alive for extended periods, and more promising treatments are being discovered. And even when all else fails and your marrow is hopelessly terminally empty or diseased, that is paradoxically when the greatest hope for a true and permanent cure really kicks in, because hematologists are getting better and better at giving you a new lease on life through transplant - be that a sibling, match-unrelated donor, partially matched donor, cord blood, or some combination thereof. Survival rates are rising and graft versus host incidence is falling.

One more thing, AAMDS suggests if you are to read one article on the current "gold standard" for treating aplastic anemia, read this one:

http://www.bloodjournal.org/content/...o-checked=true

[Data]

Kevin,
Thanks for the extended reply. I really appreciate your thoughts and advice. A couple answers: No, I am not in the hospital and not transfusion dependent. Some of my counts are: WBC=1.8; Neutrophils=0.7; RBC=2.2; Hematocrit=25.4; Hemoglobin=8.8; Platelets=27. So I guess I am in the category of non-sever or moderate. I am probably too old for a transplant and don't have any close relatives. I have the results of my first biopsy and that ruled out MDS and AML. It said I had low-normal cellularity. I had another biopsy under CT guidance a week ago but don't have the results from it yet. I am supposed to discuss those results, assuming the are back, on Monday.

I had that article on "How I treat Aplastic Anemia" downloaded and have read it several times. Good article!

Thanks again for the time it took to write your thoughts and suggestions. Above and beyond the call of duty as we used to say in the US Air Force!

Data

[sbk007]

You got a lot of good info there. Don't be afraid to print out those questions and bring it with you. Its common for patients to bring lists of questions and your doctor shouldn't object. In fact she should expect it.
Don't want to beat a dead horse but I thought the "looks like" came AFTER they took the second sample w/ the CT guided BMB.. Just a little odd that she would say this without the results of the second sample because she had trouble with the first one which is why she took another..
Good Luck on Monday!!

[NLJabbari]

Hi Data,

I just want to add my two-cents worth. Please be sure that the Dr. that sees you for a second opinion is not only "Board Certified" in Hematology, but that their "Specialty" IS Hematology. If you can find an expert in treating SAA, even better!

[Data]

Originally Posted by NLJabbari

Hi Data,

I just want to add my two-cents worth. Please be sure that the Dr. that sees you for a second opinion is not only "Board Certified" in Hematology, but that their "Specialty" IS Hematology. If you can find an expert in treating SAA, even better!

I appreciate your comments and am going to take them. I am looking for a doctor/center that has more expertise in AA. My doc said I currently have moderate AA and even she recommended I seek a second opinion. I am looking at Moffitt Cancer Center in Tampa, FL; University of Florida in Gainesville, FL; or the Mayo Clinic in Jacksonville, FL.

Thanks again for the advice!!

[KMac]

Hi Data,

I'm glad to hear the current diagnosis is that the SAA is only moderate, and that the doctor recommended you get a 2nd opinion.

And you are very welcome for the input. I've been meaning to write all that down for a while now anyway.

I wish I knew of a doctor in Florida to look into seeing. But I have heard there are doctors in Florida who specialize in treating aplastic anemia.

I while back I did find these two videos, although I don't know anything about Dr. Mamus beyond this:

http://www.youtube.com/watch?v=Z7gGY9H9P2E
http://www.youtube.com/watch?v=7_Q9S9jQ3JI

Please keep us posted on how you are doing!

[Missy D.]

I just got done reading the article on the gold standard for treating AA. My dad was diagnosed with AA in September and is being treated with cyclosporine only. I'm very confused as this doesn't seem to be the standard. His doc wants to hold off on atg for now but I'm not sure why. Has anyone else had experience with this? His numbers are WBC 1.1, RBC 3.63, hgb 11, platelets 7 and ANC .93 as of yesterday. He's been getting blood and platelet transfusions every week since June although yesterday was the first time he didn't have to get blood.

[dfantle]

Missy, perhaps your Dads doc is trying Cyclosporine first to see if it alone helps with the AA. Although I'm not sure this is commonly the first treatment, it may be the mildest treatment & depending on his age & health condition the doc might have thought trying this first was a good starting point. The Cyclosporine suppresses the immune system which is the cause of AA in many cases.

However I don't believe Cyclosporine is a curable treatment which is why other treatments are more frequently recommended if the patient is strong enough to tolerate them. Even with the other treatments, patients are sometimes on cyclosporine for extended lengths of time following treatment.

Best wishes