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  #1  
Old Thu May 2, 2013, 03:20 PM
KMac KMac is offline
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Treatment for Low WBC in Aplastic Anemia

Hi all,

I am still fighting my nemesis, low white blood counts, 14+ months post-ATG. Fortunately, my red blood and platelets are holding in quite well, they are almost normal (Hgb 13.2, Plt 135). Unfortunately, my ANC has been trending down since the start of the year, taking a sharp turn for the worse at my CBC yesterday, where it was 560 (it has generally been between 700 and 1000). Yet I feel well (other than some fatigue), and I am not getting sick, even in a flu season for the record books, even surrounded by sick family members and sick people at clinic visits.

Further, my 12 month post-ATG BMB showed great improvement (20 to 30-fold more cellularity than pre-ATG), with a normal distribution of healthy white blood cells in the marrow.

So my crucial dilemma is, what should I do for treatment? I would love to hear from anyone else fighting AA (or another bone marrow failure disorder), who has had a good treatment response in terms of red blood and platelets, but has had to fight chronic neutropenia like I have. Specifically, I have questions in the following areas:

1) ATG - My doctor is considering a second round of ATG, or perhaps another immunosuppressant. I am open to this, but I am wondering if there is any data on outcome for this in my specific case, especially as ATG hits the white blood cells so hard. Has anyone started a course of ATG with their red blood and platelets at very good levels, specifically to deal with their chronic neutropenia?

2) Prophylactic antivirals, antibiotics, antifungals - I've been on 1600 mg/day of the antiviral acyclovir since before I started ATG last year. The plan is to keep me on this at least as long as I'm on cyclosporine, primarily to prevent shingles and related viral issues. Further, if my ANC does not rise, my doctor would like to restart me on a prophylactic antibiotic and antifungal ASAP. If I am not getting sick, I'm not comfortable with this. I fear adverse reactions to being on strong antibiotics and antifungals indefinitely as a prophylactic measure. Had anyone else had experience with taking (or NOT taking) these over a long term while chronically neutropenic?

3) Cyclosporine - My doctor had planned to start tapering me off cyclosporine at 12 months post-ATG, but due to my low ANC he would like to wait another full year to start the taper. I tolerate the cyclo fairly well, but it does give me high blood pressure and elevated creatinine (baseline 0.8, currently about 1.3), and my understanding from the latest NIH studies is that long term full-dose cyclo after ATG response had become controversial. Further, I wonder if there is any chance that the Cyclosporine (or for that matter the acyclovir, or my anti-blood pressure med amlodipine) could be contributing to my low ANC?

4) Neupogen - I was on regular neupogen for the first 8 months post-ATG - 1 to 3 times a week. My ANC responded well and quickly, but of course fell just as quickly. My order at the clinic is for neupogen anytime my ANC is below 750. But I have been refusing it lately. My doctor is OK with that, but wants to give it to me again if my ANC falls below 500. My concern is that my online research suggests neupogen is not indicated for SAA patients as a long term treatment. Has anyone else with SAA been kept on neupogen for several months or more to deal with chronic neutropenia?

...In short, at this point I wonder if any of the medications I am on contribute to my low white blood count. As such, a big part of me wants to begin tapering these meds, as opposed to starting on more of them. If I am going to start taking more powerful pharmaceuticals, I want them to be of the sort that have a fighting chance of fixing the root cause of my problem (such as ATG), not just temporary protective measures, such as neupogen or antibiotics, which have risks and dubious long-term value, especially when given to people who are not getting sick.

Thank you to everyone who read this very long post! I know I need a second hematologist's opinion, but figured I would start here.
__________________
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.
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  #2  
Old Thu May 2, 2013, 06:52 PM
NLJabbari NLJabbari is offline
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Hi Kevin,

Unfortunately, I don't really have answers to your questions, but I do have a couple of comments, a suggestion, and a question.

Have you tried getting in touch with AAMDS. They might be able to give you contact #'s for AA specialists throughout the country who might be able to answer your question via phone call or email.

Re: Long-term use of Neupogen--quite frankly (personally) I've never heard of anyone using it for so long. Back in 2004 when my son was dx'ed w/SAA; I recall reading a medical article where it mentioned something to the effect of the use of Neupogen and incidence of relapse. I'm really not sure if "the author" was merely suggesting that there "might" be a connection or if they were just not sure at the time.
I recall being worried because my son was getting a small dose of Neupogen for approximately 5-6 weeks post ATG. In hindsight, I don't think he even needed it as his WBC/ANC rose quite rapidly and WBC was actually at 12.? when his doctor ordered us to stop! It eventually leveled off at around the 5.0-6.0 range. He however, did eventually relapse.

Re: A second round of ATG being administered even though 2 cell line numbers are doing well--That is an excellent question and one that I'm very interested in knowing too!
My son never got a second ATG course. His doctor merely increased/switch brands of CsA and his numbers bounced back. Still, I am concerned about this because like you, 2 of his Cell-lines are in normal range, but his Hgb is still low @ (8.3) ---major concern.
I was under the impression that another round of ATG was not offered bc both his WBC/ANC is within Normal range 6.1/3500 and Platelets are at 141K
Needless to say, he has been on CsA for too long and appears to be CsA dependent at this point.

I know of a few who have had 2+ courses of ATG and are doing very well with long-term remissions.

BTW, were you diagnosed VSAA? I noticed the numbers you posted below fall within that range (I think).
__________________
06/2004 my son was dx with SAA at the age of 10. No sibling BM match. He underwent ATG (H)/CsA. Relapsed 05/12 & dx'ed w/PNH. Currently in wait/see mode for Solaris as he is asymptomatic...
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Old Fri May 3, 2013, 04:44 PM
KMac KMac is offline
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Hi NLJabbari,

Thank you for the thoughtful reply! It sounds like your son and I have different yet related problems with our blood counts post-ATG. I am glad he had a multi-year remission after ATG, and that his WBC and platelets are so high. Yet I know firsthand what it feels like to have an Hgb of 8.3 and I really feel for your son there - I found it very challenging to be anemic.

I understand red blood growth factors are typically not recommended in SAA, but since it is just his red blood that is an issue, I wonder if one of those could be of help in raising his Hgb? Has your son's erythropoietin level been taken? Perhaps when that is low, a red blood growth factor would help.

I identify with your frustration about cyclosporine dependence. Since Csa hits the kidneys, I wonder whether that could retard Erythropoietin production, thereby exacerbating anemia in some patients.

One thought on a second course of ATG when only one cell line has crashed - my parents attend an AAMDS support group in New Jersey, and they posed that question there (important note, these are patients, not doctors). But the thought in their group was that a second ATG seemed odd when only the white blood is low, since ATG hits the white blood count so hard, yet if just blood or platelets were low, the patients there thought a second ATG would make sense.

I have contacted AAMDS, and found their materials to be very helpful. I think I have a good list from them of hematologists I'd like to contact with my questions. AAMDS was the first place I learned that my long-term neupogen administration was unusual.

AAMDS had a video of a talk given by an Irish hematologist, I forget his name offhand, saying that long-term neupogen is not indicated in SAA because even if it produces a response, it has no long-term benefit (and perhaps risks), but either way it just is a stopgap preventing the patient from getting the treatment they really need. Dr. Young at NIH published a paper last year, where if I understood correctly, he was even saying the same thing about long term Cylosporine use (I will try to find these links and post them here).

But then, the huge question for your son and I is - what exactly is the treatment that we need? Since 2 out of 3 blood lines are doing well for us, we seem to be in this weird sort of holding pattern.

As for my vSAA/SAA diagnosis, they never really said exactly, I think because I was right on the cusp (ANC < 200, with pancytopenia, means vSAA I believe), and either way the situation was dire and treatment was needed ASAP. My ANC did fall to 0 during ATG administration.

This is such a strange disease. Here are just a few of the many patient anomalies I know of:

1) A vSAA diagnosis gives a poor prognosis in the literature, yet I know a patient who had an ANC of 0 at diagnosis, who responded very well and very quickly to ATG, without any serious infection or complication.

2) A low reticulocyte count at diagnosis is a poor prognosis. My reticulocyte count was almost nonexistent at diagnosis, and my reticulocyte count still runs low. Yet that is the cell line in which I've had the most robust recovery, raising Hgb from under 6 to over 13.

3) My lymphocytes have never recovered. They were well into the normal range pre-ATG, and now run below 500. Of course, those include the nasty aberrant T-cells presumably causing our disease, so we aren't as worried about those being low. Yet still I find it strange, I have not found any other SAA patients who responded to treatment, yet whose lymphocyte counts stay low 1 year + post-ATG.

I wonder whether clues to better treatment lie within these strange anomalies so many of us SAA patients exhibit.

I will keep you posted via this thread on what I learn (or start a new thread), and would be happy to talk with you and your son via email or phone sometime if you'd like (my email is kevin_mcnamar@yahoo.com). We have an aplastic anemia support group here in the Denver, Colorado area, if you are ever in the area. I will be thinking about you and your son, and hoping we both find solutions to make us 3 out of 3 instead of just 2 out of 3!

Best regards,
__________________
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.
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Old Fri May 3, 2013, 05:27 PM
KMac KMac is offline
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...something I wanted to add about the cyclosporine though. While stopping neupogen is more clear-cut, it sure wouldn't be an easy decision to stop or even taper the cyclosporine. I know of multiple SAA patients that are dependent upon it for several years, but the cyclosporine keeps them in remission.

My doctor thinks perhaps another round of ATG for me would enable me to get off the cyclosporine. He feels I have some residual auto-immune process that one more ATG could subdue, allowing me to hopefully enjoy a stable long term remission without cyclosporine.
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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.
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Old Sat May 4, 2013, 06:52 AM
NLJabbari NLJabbari is offline
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Hi KMac,

Yes, I guess 2 out of 3 ain't bad I should be glad that my son actually functions quite well at 8.3 He's only 19 y-o and has a whole lot more energy than I do...or at least it seems like it.

Some time ago, I read something about a program (based on Algorithms) where you plug in all the data that pertains to your AA case and it offers advice/feedback??? I'm not sure where to find this program, but I think a member on this site mentioned it. It sure would be nice if this actually existed and helped out with sorting things out. Perhaps it could answer or bring light to some of these confusing questions. I'll see if I can find that post and I'll share it if I actually come across it. You never know, it might help.

Re: Initial response post ATG. My son responded at around the 5-6 month mark. During this time, he was taking a couple of antibiotics (Oral Nystatin and Bactrim) as part of his post ATG meds. Two weeks prior to this response, I had noticed on the med literature that Bactrim/Septra "Could Cause AA!?" I told his doctor that I was uncomfortable knowing this and I wanted him off this med immediately. So, my son was taken off Bactrim/Septra and now gets a monthly dose of Pentamidine instead. Well, the reason I'm mentioning this is because after he was taken off the Bactrim, his counts began to rise! I'm really not sure if it was a coincidence or if indeed Bactrim was not a good option for him. The first line to respond were his platelets. They took off and he actually reached the 300's, the RBC were next and he reached 13.-, then the WBC. WBC stayed in the 3-4 range for quite a while (years), but than went into the 5-7 range and pretty much has stayed there.

Re: RBC Growth Factors--Not an option as his Retic and erytho, both have recently been tested and are in (Upper Range). It was discovered during his relapse BMB that he has a 20% PNH clone, but it hasn't changed as of yet and his LDH (LACTATE DEHYDROGENASE) is in the 300 range. Lots of baby red cells, but they're not making it into the bloodstream. His doctor said that they didn't find HGB in his urine either, so that's a good thing. Now we're just waiting...hoping this clone doesn't get any bigger...or worst. He should be getting another BMB this summer.

I often wonder if ALL Cyclosporine is created equal...hmmm??? My son was initially on Gengraf (Generic for Neoral). He did well on that and then was switched to Sandimmune. (Kaiser HMO) Now, his new doctor has put him back on Gengraf and thus far we're seeing positive changes. For one, he hasn't needed a blood-transfusion since switching. That's a biggie, since less transfusion is a good thing. Yes, seems like he's plateaued at 8.3 and we're okay with that for the time being.

Thus far he's tolerated CsA pretty well. No high blood-pressure and kidney function is fine. Very grateful for that...

I asked about your diagnosis vSAA vs SAA because, like you said vSAA might equal "initial" poor prognosis, but I recall reading that responders actually do better long-term and overall. I think it has something to do with the fact that if all 3 cell lines are affected at a common rate, all 3 cell lines should respond at a similar rate too and perhaps avoid this "Weird sort of holding pattern" Sort of makes sense...

Indeed this is a very strange disease or disease(s) as some might say. I have a feeling deep within that better treatments and understanding of this disease are in the near future. There are those few that are even brave enough to turn away from CsA, ATG, etc...and opt for Alternative methods. Of course, they are very disciplined and follow strict guidelines. Unfortunately, my son isn't that disciplined. I spend my days badgering him, asking him to please drink his water, fruits, vegetables, no fried foods etc...sometimes I bug him!

So, a second round of ATG and what to do? I think your doctor has a very valid point and yet 2 cell lines doing really well makes you wonder if the 3rd is just lagging for a bit and perhaps even due to one of your antibiotics. I hope you find an answer and that someone will give you good advice.

Take care,
__________________
06/2004 my son was dx with SAA at the age of 10. No sibling BM match. He underwent ATG (H)/CsA. Relapsed 05/12 & dx'ed w/PNH. Currently in wait/see mode for Solaris as he is asymptomatic...
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Old Sat May 4, 2013, 11:47 PM
dfantle dfantle is offline
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Hi Kevin, if you do a search under my name you may be able to find a link to the copy of the Dr Young paper which I referenced when it was published last August, I think. If you can't find it ill try to see if I have a copy and post it again.

Also recommend you try to locate a hematologist who is very experienced with AA.


I would definitely ask about the propholaxes and the GCSF shots. Your dose of the antiviral is higher than mine was post ATG (800 mg 1x day). GCSF shots for me post ATG were only if my ANC fell below 500, so as not to impact my ability to produce these on my own (tho Dr Youngs paper mentioned they will let people go down to 300 if they remain healthy). Propholaxes antibiotics post ATG were only when my ANC fell below 500 because with me, my white cell/neutrophil production was negatively impacted with some antibiotics. Also, some Docs believe being on them too long may make them less effective when needed. I was also NOT on any antifungals post ATG as they have also been known to negatively impact white cell/neutrophil production in some AA patients.

The GCSF is also known to take energy away from platelet production . So whenever I had GCSF my platelet count would fall. It's all a very delicate balance for SAA patients which is why having a hematologist with many years of AA experience is so helpful.

Good luck!!
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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

Last edited by dfantle : Sun May 5, 2013 at 12:02 AM.
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Old Sun May 5, 2013, 12:37 PM
Hopeful Hopeful is offline
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Quote:
Originally Posted by NLJabbari View Post
I often wonder if ALL Cyclosporine is created equal...hmmm??? My son was initially on Gengraf (Generic for Neoral). He did well on that and then was switched to Sandimmune. (Kaiser HMO) Now, his new doctor has put him back on Gengraf and thus far we're seeing positive changes. For one, he hasn't needed a blood-transfusion since switching. That's a biggie, since less transfusion is a good thing. Yes, seems like he's plateaued at 8.3 and we're okay with that for the time being.
Not all Cyclosporine is created equal. Sandimmune is not bioequivalent to Gengraf. Sandimmune has inconsistent absorption in the intestine, and it is no longer commonly used as an immune suppressant for bone marrow failure diseases in the US. If he was on the same dosage of Sandimmune as Gengraf, the level was probably signficantly lower in his system when he was taking Sandimmune.
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50 yo female, dx 9/08, AA/hypo-MDS, subclinical PNH, ATG/CsA 12/08, partial response. Tried slow cyclosporine taper over 4+ years. Platelets fell, so back on cyclosporine. Trisomy 6 clone in 5% of cells.
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Old Sun May 5, 2013, 06:48 PM
dfantle dfantle is offline
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When I had my ATG I was told never to switch brands because the absorption... varies by brand. I had to convince my insurance company of this, however.
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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 May 5, 2013, 09:05 PM
NLJabbari NLJabbari is offline
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Thank You Hopeful and Dfantle. Actually, I am aware that not all Cyclosporine is Bio-equivalent in that absorption rates differ. What I'm wondering or am curious about, is if there is something else in the mechanism of the different brands of Cyclosporine. It seems that there are some brands that I hadn't heard of before, that I seem to be hearing more often e.g. Tracolimus and a couple of others. Also, the "modified" brands vs "non-modified". To the best of my knowledge "modified" merely means the pills don't have that stinky skunk-like scent. Makes me wonder what is that smell and why have it at all??? There are brands that supposedly don't swell your gums and no excessive hair-growth. What exactly is happening to the body when the swelling occurs?

This makes me wonder if perhaps there are differences in how they work or not and we just don't know it? My son was initially on Gengraf and responded quite well. He was weened after a year and was off all meds for about 1.5 years when his numbers began to decline once again. Then his doctor put him on Sandimmune. I asked about this, but was never quite clear as to why Sandimmune vs Gengraf which we already knew he had done quite well with. At the time, they told me it was an Immunosuppresent and that I shouldn't worry about it, so I didn't. I just assumed that since "Kaiser" is an HMO, that was the ISD that was available.
Time went by and my son never quite was able to regain the numbers he once had (All within Normal Range). We went up and down for years (about 6 years) until he was in full relapse needing transfusions once again. As if that wasn't bad enough, he was also being transferred to "Adult Medicine" at this time, meaning "New Doctors".

Long story short, the new Dr. didn't work-out for us at all. So, we did further research and found a more experienced Dr.within our HMO who besides being a Hemo specialist also teaches at Stanford University. Within a couple of weeks and by switching CsA brands back to Gengraf; my son has not needed a transfusion and his numbers are slowly rising to where they hadn't been in years. Especially his platelets. They had not been in Normal Range since about 6 years ago! I don't want to cry Victory, but it sure does feel good! The fact that his new Dr. decided to merely switch brands vs opting for another round of ATG--makes me beg to ask, "Are all CsA's created Equal?"

Again, thanks for your input I really appreciate it and I hope I haven't confused anyone.
__________________
06/2004 my son was dx with SAA at the age of 10. No sibling BM match. He underwent ATG (H)/CsA. Relapsed 05/12 & dx'ed w/PNH. Currently in wait/see mode for Solaris as he is asymptomatic...
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Old Mon May 6, 2013, 12:12 PM
Lbrown Lbrown is offline
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Hi guys,

Since you mentioned bactrim / nystatin and counts, I thought I'd chime in with my experience.

I was first diagnosed with PRCA but now they're calling it AA. I am red cell transfusion dependent. I have tried cyclosporine, IVIG and ATG/tacrolimus and quit all that 2 years ago. I believe (from lots of evidence) that chronic infection may be the cause of these blood disorders.

I tried bactrim ds for a UTI back last Sept and ended up with a fever of almost 104 and a huge drop in HGB. I thought I had the flu but now am wondering if it was the bactrim. I quit the bactrim for awhile and things went back to the way they were.

Anyway, part of my treatment involved taking 1/2 a bactrim ds every 48 hours. I waited until I was over the "flu" I had. The first time I took it, I had a severe reaction including projectile vomiting and fever. I reacted to bactrim over 20 years ago and have always avoided it. My dr encouraged me to try a smaller dose. I waited a couple weeks until I dared try again and then tried 1/8 bactrim ds and had a small reaction but nothing intolerable. I stayed at the dose for several weeks and after each dose I had less and less symptoms. Eventually I increased it by another 1/8. I noticed I had a big drop in platelets, they went down into the 20s, when they had been in the 60's - 90's for the longest time.

Around the same time, I started taking oral nystatin in a fairly large dose, daily. My WBC had been around 1.8 all the time, now dropped to 0.8, 0.7. Neutrophils dropped to 0.3. I've been here since Jan but I feel pretty good.

If this is bacterial, then I am slowly reducing my bacterial/fungal load, and eventually things should improve. I was noticing my HGB drops were slowly becoming smaller, below average, for 8 weeks in a row. I added a 2nd antibiotic - minocycline at 50 mg every 48 hrs and dropped bactrim down to 1/8 again and started ramping up the bactrim every 2 weeks. I got up to 1/2 and suddenly had a big drop in HGB. Platelets range between 30's - 50's, they did dip down into the 20's for a few weeks. I'm currently at 1/2 a bactrim ds and staying here until my HGB drop normalizes.

Anyway, my feeling is that the combo nystatin / minocycline / bactrim is fighting something. I know about the warnings for bactrim, but I wonder if it's because it is actually helping kill microbes, which would also kill the cells they are in.

I am getting a DNA test of my blood soon to test for microbes that can't be cultured, I ordered some kits from ubiome.com. It'll be interesting to see what shows up.

Thanks for letting me ramble. I am actually feeling pretty good these days. I work full time, ride my horse and have a positive outlook. I have no problems with infections even with ridiculously low WBC / ANC, no problems with bruising or bleeding, just the fatigue from anemia every 2 weeks.

This really is a strange disease.

Deb
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