low dose naltrexone

[Lbrown]

Hi,

I did a search and could not find naltrexone discussed on this site. Has it been discussed before? I thought I remembered reading about it.

A nurse suggested I could try low dose naltrexone for my red cell aplasia, and I was wondering if anyone had any experience with it.

Thanks,
Deb

[Marlene]

Hi Deb,

I have not heard of anyone trying LDN for blood disorders. I've read about this a while back and keep it on the back burner in the off chance we need to consider it in the future. I have mostly read about the success in MS. It doesn't cure it but can greatly reduce symptoms and progression which is a big deal for those dealing with active MS. Here's a link of MS users you may find interesting. They talk about their experience with LDN.

http://neurotalk.psychcentral.com/thread50240.html


I assume you've checked out the LDN site. http://www.lowdosenaltrexone.org/

The story behind LDN is pretty interesting and worth exploring. Please let us know if you pursue this. It appear to be very low risk.

Good luck in your search.
Marlene

[Lbrown]

Thanks Marlene.

I am on an experimental treatment. Although I am feeling pretty good and not immune suppressed, and I've had a huge improvement in certain areas, it doesn't seem to be helping my HGB (I have low WBC and pure red cell aplasia - which to me basically adds up to aplastic anemia).

I've looked into valproic acid but the hematologist won't consider it. My other doctor was going to look into it.

A nurse advocating the experimental treatment I'm on for most other things, thinks LDN might be worth a try.

I am getting near the end of my rope with the continual transfusions and the up and down of fatigue. I'd like to have some options in my back pocket that are less drastic than ATG or chemo. The hematologist has already mentioned IVIG. I've already tried cyclosporine with a partial response. I will look into LDN some more, it might be ok in conjunction with or instead of what I'm currently taking.

Deb

[Hopeful]

Not to confuse things further, but do you know what your absolute reticulocyte count was at diagnosis?

I remember seeing a presentation on the AA&MDS International Foundation website that said having a normal or high absolute reticulocyte count at diagnosis was one of the most promising indicators that someone would respond to ATG. I think the chance of a response to ATG was something around 80%. The fact that you had a partial response to cyclosporine also makes it seem like your disease is immune related.

Have you considered the possibility of doing ATG without cyclosporine? They do a skin sensitivity test first to determine if you are hyper-sensitive to the ATG. Also, do you know what dose of cyclosporine you were on before? If it was more then 5 mg/kg/day, that could be the reason for your extreme reaction to it. Current research indicates that more than this just causes increased toxicity without any added benefit. However, some doctor's aren't up on the latest research and will prescribe higher doses.

Mild red cell aplasia can be seen with aplastic anemia.

Have you been tested for PNH with flow cytometry?

[Lbrown]

Hi,

My retic count at diagnosis was 48 on a scale of 25 - 100, but it should have been high due to the anemia - in a healthy person at least.

My retic count now on this treatment is 4. It's absolute count not % for both.

I took 450 mg of cyclo a day, I was at 89 kgs for awhile.

My alternatives for some reason all involve prednisone, which I will not take. My dad took it for years and years and I am not going there.

I've no idea if I was tested for PNH so I guess I haven't been. I only had the 1 BMB, in which they couldn't get any aspirate and couldn't tell the immunophenotype on the cells they did get (she "assumes" they are suppressor T cells).

I don't feel like doing ATG or chemo on an assumption. I can't even figure out if ATG would be a permanent thing. I asked, but I never get much of a definitive answer. I would also like to try less harmful treatments first. I feel much better but my blood counts have not improved.

I am a 45 yr old female.

Deb

[Hopeful]

Hi Deb,

Are you being treated at a facility that specializes in aplastic anemia and other rare bone marrow failure diseases? This is extremely important. You want to at least consult with a specialist who has seen many patients with these diseases vs. just a handful. If you have aplastic anemia, you don't want to fool around with experimental treatments. I am amazed that they didn't try and do another BMB on you, especially if there was no aspirate with the first. You really need the aspirate to help with the diagnosis.

I had to ask my local hemotologist to do the PNH test. He didn't know anything about it, as these diseases are rare. I consult with a specialist who is an AA/MDS/PNH expert.

That presentation that I mentioned previously is called "Aplastic Anemia: Current Thinking on the Disease, Diagnosis, and Treatment" by Dr. Young. It is really good and can be found at http://live.blueskybroadcast.com/bsb...T=944&CAT=1031

In it, Dr. Young talks about a new study that indicates that patients with an Absolute Reticulocyte Count > 25k and Absolute Lymphocyte count > 1k at the time of diagnosis have a 80% response rate to ATG.

If you do go the ATG route, you are only on prednisone for a month. The doctors will try to wean you off as quickly as possible to avoid the side effects.

I really think that you should get another BMB done ASAP. Ask for the PNH test. Don't settle for not having a diagnosis. Time is of the essence! Although you may think you feel good, if you are transfusion dependent, that is not good.

[squirrellypoo]

Originally Posted by Lbrown

I can't even figure out if ATG would be a permanent thing. I asked, but I never get much of a definitive answer.

When I had it back in 1984, they told us it was a cure for life, but the current research now (coming straight from Prof Marsh's lips) is that it usually only works for 5 to 10 to 15 years. It worked for 25 years in my case, but eventually even my time was up!

I totally agree with Hopeful about finding an AA specialist and definitely getting more BMBs done. I absolutely loathe having them and find them excruciating painful, but even I recognise thhat they're the only way to really see what's going on in your marrow.

[Lbrown]

What I meant was - does ATG leave you permanently immune suppressed?

Thanks for the feedback, it gives me a lot to think about and I can see I need to make an appt with my GP of almost 20 years and see if there's somewhere else he can refer me to for another opinion. As far as I know, the nearest center that specializes in this is at Sunnybrook Hospital in Toronto. It would be a 3 - 4 hr drive but that's ok. It just depends on how long the waiting list is.

The hospital I'm at now is a teaching hospital affiliated with the local med school. My former dr there went on to specialize in BMTs, and no longer takes general patients.

Deb

[Hopeful]

ATG doesn't leave you permanently immune suppressed.

You will be immune suppressed while receiving the ATG. It will knock out all your counts so you will be neutropenic, but you will be in isolation at the hospital during this time. My ANC was above 1.0 within a week of receiving the ATG, but everyone is different.

Of course, if you do ATG with Cyclosporine, you will be immune suppressed while taking the Cyclosporine.

If you mention that you have a bone marrow failure disease that may be aplastic anemia, they should schedule you in really fast at Sunnybrook. That has been my experience...one of the benefits of the disease I guess.

Good luck and don't procrastinate! If there is an auto-immune attack going on, you want to act fast to avoid irreversible damage.

[Lbrown]

So it looks like the ATG / tacrolimus didn't work, I had ATG in July and am 4 months out. The tacrolimus doesn't have many side effects, but it also doesn't seem to be working.

I am losing my hair. I am not sure if it is the tacrolimus or the fact that I had C diff 3 times, but if it keeps up I will soon need a wig. I asked my hemtologist if I could switch back to cyclosporine but she said no. I kind of had an argument with her, but she doesn't listen anyway. I don't know how much longer I will take the tacrolimus. It costs twice as much as the cyclo, and what's the point if it doesn't work?

Anyway, I started LDN this week. My HGB was at 100 yesterday (I got 3 units last Sat). On Tues I took 1.5 mg, on Wed I took 3 mg and Thurs I took 4.5 mg. I haven't noticed any effects, but I read it can give you insomnia the first week or so. I guess I have been a bit more awake at night, that's why I started at 1.5 mg. I will continue on 4.5 mg and see what happens.

I can feel my HGB is dropping because of the tinnitus - it gets louder. With my HGB at this level I wouldn't expect to feel bad, so I don't know if the LDN is making me feel any better, and how long it would take to kick in. I also started back to work on Monday, so I have a lot going on all at once.

For the LDN, I am just hoping the extra endorphins make me feel better. I don't expect it to make any difference in my counts.

I see another hematologist here next week. Since Sunnybrook gave up on me, there's no point going back.

Deb

[Marlene]

Hi Deb,

Sorry to hear the ATG did not work. I do understand why you may want to switch or stop the tacro. Sometimes you really have to push the docs to listen to you and to be more open to different possibilities. Glad you're getting second opinion.

I am very interested in your experience with the LDN. Please continue to report back on it. I know it can take a while to get the proper dosage figured out for an individual.

Is the c-diff under control at this point? Disruption of the good gut bacteria can be very taxing on your health in general.

[Lbrown]

Hi Marlene,

AFAIK the C diff is gone, the vancomycin and rifampin seems to have done the trick.

Ok, the day after I took my first 4.5 mg dose, I wanted to go shopping after work. My husband was in shock. Can't remember the last time I WANTED to go shopping. I have continued to have more energy. I rode my horse on Sat, went out to dinner, and stayed awake until midnight. Then on Sunday I went wig shopping for an hour (darn tacro!) and grocery shopping. I made dinner, gave the dog a bath, and knit a little headband for her to keep her ears out of her food. Back to work on Mon & Tues, tired but it had been rainy and dark those 2 days. Tues evening went to the barn - didn't ride but worked with my horse in the cold and then felt good after.

I can feel my HGB is dropping, I estimate it is 88 today. I feel a bit dragged but overall less fatigued than usual. The LDN caused a bit of insomnia but nothing too bad. One night I noticed my heart was beating fast, but it wasn't pounding. I was totally wired after I rode my horse on Sat - I guess I got a double dose of endorphins.

A nurse told me to expect it to take 2-3 weeks to see any difference in my counts, I am getting tested tomorrow. According to some new info on the ldnresearchtrust site, it makes you produce more lymphocytes which can temporarily exacerbate MS (most of their info is on MS). But it then makes you produce more suppressor T cells, which modulates the pesky Th1 cells that are supposedly causing the problems.

I am trying not to get my hopes up, because surely it couldn't be so simple. I could also be feeling better this week because my HGB is higher than it's been in awhile, but me wanting to go shopping is definitely something new.

But, so far so good.

Deb

[Lbrown]

Here is the info about the lymphocytes on page 2: http://www.ldnresearchtrust.org/uplo...t-nov-2009.pdf

[Marlene]

I'm glad you have more energy. I know what you mean about jumping to conclusions early on....it's the old "wait and see" . Seeing improvement in red cells can take a while. Even when John was on procrit, it took two months before we saw an increase in intervals between transfusions. So much depends on how many stem cells you are working with.

Thanks for the link...I will check it out.

BTW...I think you are the first to try LDN for blood disorders, so thanks for exploring and sharing the experience for everyone.

Marlene

[Lbrown]

My HGB yesterday was 83 - that is a drop of 17 points in 1 week, so slightly worse than normal. With MS they did warn of a temporary exacerbation of symptoms.

- my tacrolimus level is at 6, so in the therapeutic range, it is doing *nothing* other than making my hair fall out
- I feel better than I normally do at HGB 83. I ran around at agility last night without being completely out of breath.
- my sense of humour is better and I'm not so tired.
- I did not get my lymphocyte count, but will try to get it tomorrow.
- LDN is giving me weird / bad dreams, but I usually don't dream (or remember them).

Stay tuned.

Deb

ps - my counts were: HGB 83, WBC 1.5, Neut: 0.9, Plate: 160, Creatinine: 103, Lymph: 0.44
My counts last week: HGB 100, WBC 1.9, Neut: 1.2, Plate: 181, Creatinine: 125, Lymph: 0.5

I'm interested to see if my lymphocytes went up.

[Lbrown]

Marlene - thanks for the reminder that red cells take a long time to come back. My last retic count was 1.9.

[Marlene]

Ah....1.9 retic is good. John didn't start procrit until his retic count was up to 1.5 - 2%. So he was already starting to make his own red cells when they put him on procrit and it still took quite a while for it to show up in his cbc.

Also, as a point of reference, John's WBC and ANC would fluctuate like yours when he was in the beginnings of recovery after he stopped neupogen. At times, it put me in panic mode. It still fluctuates but we don't follow it as closely because the ANC is in a normal range now. His platelets bounce around from 90 - 107K.

I didn't realize you could be on tacrolimus and LDN at the same time. And from what I read, the crazy dreams should stop at some point.

[Lbrown]

Well, you're not *supposed* to be on immune suppressants and LDN at the same time, but they didn't give a reason for that. My choices were to take 2 together or drop the tacro and get in trouble (yes, they measure that). I might still drop the tacro, I know I want to. It's not doing anything except make me poor and bald.

I'm also wondering if the minocycline I'm on might be blocking the tacro, something like rifampicin did. Something about tacro working via the mTOR pathway and mino being a PXR agonist which might also affect mTOR somehow. Right now I don't know if I want to change anything.

Thanks for the info about John's counts fluctuating. I wasn't too excited about my WBC/Neuts.

Deb

[Lbrown]

Found out my lymphocyte count was 0.44 on Thursday, so it also dropped a bit.

There almost seems to be no correlation between my lymphocyte count and my other counts, although my hematologist told me the lymph count is the one to look at to see if things are working.

I don't get it.

[cathybee1]

Originally Posted by Lbrown

I'm also wondering if the minocycline I'm on might be blocking the tacro, something like rifampicin did...
Thanks for the info about John's counts fluctuating. I wasn't too excited about my WBC/Neuts.

Deb

This might totally be a coincidence but 10 years ago, my husband Bruce had a persistent staph infection. He was taking minocycline and rifampin. For quite a while. His WBC plummeted and never recovered.

[Lbrown]

Sorry to hear about your husband's WBC not recovering. Mine is back to where it was pre-ATG. I do believe that infections play a much bigger role in these diseases than is currently thought, whether it is viral or bacteria that can't be cultured or identified yet.

I am taking 100 mg minocycline every 2 days, so it's a very low dose, unlike the rifampin that I took.

Deb

[Lbrown]

OMG. Ok, this may mean absolutely nothing, but hey - I am ready to celebrate *any* improvement and goodness knows I have not had much to celebrate.

Look at my WBC's & neutrophils! They haven't been this high since I had prednisone right before the ATG. And look at my creatinine - I have increased my exjade which usually increases the creatinine, as does tacrolimus. I also still have some extra energy from the LDN.

I am attacking those T cells with tacrolimus, minocycline and LDN. Real interesting experiment done with mino: http://www.jleukbio.org/content/78/1/135.full

My last transfusion was Sat, Nov 27 so the HGB is nothing to get excited about but the WBC is. Even on cyclosporine my WBC was not that high.

My counts this week: HGB 103, WBC 2.4 Neut: 1.6, Plate: 97, Creat: 97, Lymph: 0.6
My counts last week: HGB 83, WBC 1.5, Neut: 0.9, Plate: 160, Creatinine: 103, Lymph: 0.44
My counts week before: HGB 100, WBC 1.9, Neut: 1.2, Plate: 181, Creatinine: 125, Lymph: 0.5

Woot!

Deb

[Lbrown]

Modulation of T Lymphocyte Function by the Pregnane X Receptor: http://www.jimmunol.org/content/184/6/2949.abstract (minocycline is a PXR agonist. So is rifampicin but it makes your body metabolize tacrolimus too fast, which is bad if you're on tacrolimus as I found out).

[Marlene]

I think you should celebrate!!!!!!

[Lbrown]

Well, it is nice to feel a little bit better, that is for sure.

Here are the possible explanations:

- I could be finally recovering from C diff (I think it may have taken a far greater toll on me than anyone but my GP realized)
- the tacrolimus could be kicking in
- the mino could be kicking in
- the LDN could be kicking in
- it's just a fluke
- maybe the ATG really did do something
- some or all of the above

So whatever it is - yay.

Deb