Copper deficiency induced bone marrow failure

[Chirley]

Hi Gosia, I'm pleased you are getting good care and hopefully you are having a temporary episode of serum sickness. While I was over the moon to think I was chatting with someone who knew what I was going through, I wouldn't wish it on my worse enemy.

I'm getting the most diabolical conflicting advice from my doctors. My neuro ordered Diazapam for spasticity and has never followed up. I haven't seen him since then and I have no appointments to see him. My rehab doctor changed the dose and times of the Diazapam and told me not to stop them, she even said to take extra doses when needed. This week, my haem doctor told me to start reducing the dose with the aim to be off them in a week or so, he thinks they will increase my risk of having a fall and a little spasticity/hypertonicity might be beneficial in helping me walk! Who do I believe?

I had almost daily IV Copper when I was an inpatient for three weeks and I've just finished another week of daily IV copper as an outpatient but my haem tells me my copper level isn't improving much. He said my urinary excretion must be increasing and he'll order another 24 hour excretion test later (when I've had a bit of a break from medical things). My CBC is almost normal still just low platelets (slight) and lymphs. The biochem is still abnormal. Potassium is low and decreasing each time, bicarbonate is low, eGFR is low, protein is low, liver enzymes still high. LDH is high. I can't remember the rest but there is an awful lot of red results on the results form.

I'm getting used to my new wheelchair but will still need to touch up some paintwork on the odd bit of furniture and doorways . Not to mention grazed knuckles... The cat has learned to move out of the way and my dog knows to always keep an eye on me....I think she's learned to sleep with one eye open.

I've had a LOT of Hydrocortisone in the last month or so and I'm also on Fludrocortisone daily and finally my blood pressure is responding and I've had a systolic of up to 100 once this week. Mostly it's around 90 and I function very well at that level. I just get light headed when it goes down to the mid 80s or lower.

The new treatment centre is working well. I get my own room and a bed (not a chair) and wifi is available, there is my own ensuite, the staff are lovely and there are constant offers of tea/coffee/cakes/biscuits/ sandwiches etc. The lady who makes the daycare appointments (not the medical receptionists) is coming to my house today to buy my now unnecessary treadmill.

The other treatment centre was very posh/designer label "have a nice day" kind of place. This treatment centre the staff seem more real and sincere. The emphasis is on patient care and comfort rather than on what kind of skimpy uniform the nurses can wear and whether they have a hair out of place.

It's starting to get cool here, it's down to 24/26 degrees during the day and I feel like I need a light coat. Winter is coming.

My cat just decided to hop onto my wheelchair and thinks she's found a new bed, I've got news for her

Regards

Chirley

[cathybee1]

I am so glad the transition to this new treatment center is going so well, and some of your numbers are improving. Banged up furniture can be fixed while you adjust to your new wheels.

Bruce's copper has been sitting around 59-61. He has stopped chasing finding out why, and mostly manages his situation via blood transfusions and Exjade. He is experiencing more fatigue that previously right before his transfusions. He is going approximately once a month between transfusions now.

Glad some of the medications are helping you

Hugs, Catherine

[Chirley]

Ive just finished my third daily treatment for this week and although my doctor is only supposed to attend this daycare centre on Thursdays, for some reason he popped in to see me today.

He seems to be pleased with the progress I've made .

Mondays blood tests were not as good as expected, reds, whites and platelets all low. Biochem was awful. Potassium, phosphate, calcium, protein, albumin, globulins all low and as usual raised liver enzymes.

All in all most of the blood test results came back highlighted in red. But after just two extra doses of copper and tweaking the steroids my tests are a lot better. Only low whites (slightly) and platelets (went down further for some reason), reds recovered nicely and Hb came up too. Biochem is better. Still a lot of abnormal results but generally improving.

My doctor told me today that I can hopefully start tapering the Fludrocortisone by the middle of next week. He said it has to be slow because I'm on both hydrocortisone and the Fludro at the moment and he doesn't want to cause adrenal insufficiency.

I think I'm improving neurologically. It's hard to tell. It seems as if it's two steps forward and one step back but I'm convinced I'm regaining a bit more function. Plasticity is a wonderful thing. I can actually walk two or three steps if I hold onto something (on my good days). Just when I get confident things are coming along nicely something brings me back to reality. For instance, I fell and put my right hand out to catch myself and I've hurt my wrist and now I'm in a brace, it makes it difficult to use the wheelchair. Then sitting in daycare for many hours at a time increases the spasticity in my legs and I have to take muscle relaxants to ease the spasms, but the relief after the spasms subside is wonderful.

I was told today that they have definitely attributed my copper deficiency metabolism problem to the chromosome deletion so at least after 9 years of investigations and treatment we finally know the root cause of the problem. It doesn't help the condition, treatment or outcome but hopefully it will help children born with this deletion because now they know to test copper levels. Previously they just attributed the neuro degeneration in these children to the whole syndrome but they are looking at it differently now. I almost feel proud that in some little way I just might help some child from dying from progressive neuro disease.

I'm incredibly tired I've been up since 5 am and it's after nine pm and do it all tomorrow again.

Goodnight.

Chirley

[Birgitta-A]

Hi Chirley,
Very positive that your Hgb and biochem are better after extra copper and that you perhaps are improving neurologically!

Wonderful that you and your uncommon disease can help children with the same chromosome aberration! I - like you and many other members - have thought many times that if your first doctor nine years ago had controlled copper your prognosis should have been much better. I admire your courage!
Kind regards
Birgitta-A

[cathybee1]

Birgitta said everything I could say, but better! It's so great to hear from you and hear you're improving.

Hugs

[Chirley]

Hi, looks like I spoke too soon. My blood results on Friday weren't good. Despite Mondays Copper level showing it was in normal range, even before this week of copper infusions, I've developed pancytopenia again.

My ceruloplasmin level was low so I'm not able to utilize the copper at a cellular level. My doctor says my liver is getting worse and I think, he was relating the lack of copper transport protein to the liver dysfunction. All my proteins are low and getting lower despite increasing my protein intake.

He said that I may have to have further venesections even though my red cell count is low because he needs to take some of the load off my liver and hope the function improves. (red cells low but Hb just in normal range).

He admits to feeling at a loss at how to treat this, apparently there is a lot that isn't known about metals and how they are metabolized. I think I might have to make an appointment to see the metabolic medicine doctor and ask him to contact my hematologist and discuss the possible reasons and treatment options for this.

I feel okay physically I'm just having problems coping with the highs and lows and the hopes and disappointments. The emotional toll is leaving me exhausted.

One positive thing is that I can start tapering the Fludrocorttisone next Thursday with the aim to cease it entirely within the following 10 days. The tapering is wholly dependent on my BP staying at 100 or above. If it drops
below that point I have to restart the full dose. Fingers crossed.

Regards

Chirley

[Birgitta-A]

Hi Chirley,
How terrible to have a disease that is so complicated as yours! You must be very tired due to the hopes and disappointments and the fact that nobody really knows what treatment you should have.

Personally I don't like the idea of venesections when your RBC count already is low. You loose a lot of valuable proteins in venesections too.

Hope your BP will continue to stay at 100 or above!
Kind regards
Birgitta-A

[cathybee1]

Chirley, this news does seem puzzling -- you truly have had a roller coaster ride the past few months. I am praying that your BP behaves and the doctors can better coordinate your care.

[Chirley]

Hi, just a quick update.

I saw the Prof of metabolic medicine today and he admitted that there is a lot of unknowns with my disorder. He verified that even though I'm having IV copper and my blood levels can look normal, that I'm not utilizing the copper at a cellular level. He said that this was the reason I had high urinary excretion. This means that despite treatment, I may still get all the other complications of copper deficiency like aneurisms, cardiac arrythmias (already have) etc.

He also said that ferritin levels are next to useless because of the copper protein/ferritin relationship so my ferritin might be higher or lower than the blood reading. This applies to the zinc level as well.

He recommended that the hematologist arrange a liver biopsy to assess metal
levels at a cell level. Yuk!

I'm feeling well and can now walk around my house with a walker (wobbly, but do able). My only real complaint is fatigue which has worsened in the last couple of weeks but that may be weather related. Short days, overcast, rainy, cool, windy, all I want to do is snuggle in and sleep. This weather is unusual for a Brisbane winter.

Copper infusions scheduled for the rest of this week and a couple of days next week. I will see the hematologist on Thursday and hope he doesn't want to do a liver biopsy

Regards

Chirley

[cathybee1]

Hi Chirley! Ugh

If a liver biopsy is one test you haven't had before, Bruce's went very smoothly. There are risks. We did a lot of talking to the surgical radiologist ahead of time.

Bruce did insist on conscious sedation.

[Birgitta-A]

Hi Chirley,
Good that you now can walk around the house with a walker! Can it be the result of IV copper?

I understand that you don't like the idea of a liver biopsy - can't they measure the iron in the liver and heart with MRI? I have had that done.
http://www.ironhealthalliance.com/di...ce-imaging.jsp

Kind regards
Birgitta-A

[cathybee1]

Chirley, hope that everything is ok. I haven't seen a post from you in a while.

Hugs, Catherine

[Chirley]

Hi, I haven't been around for a while, I haven't been feeling very well but nothing to put my finger on.

No news really. For some reason my ferritin level is increasing without transfusions and I've been having some discomfort (sometimes pain) in the upper right quadrant. Liver enzymes still up but not getting any higher, for which I'm grateful. I had a venesection yesterday, maybe I'll start feeling more comfortable. I'm also booked for a liver USS tomorrow with view to avoiding the liver biopsy if everything looks okay.

I'm still having daily IV copper for 5 days every 3rd week. My copper level is mostly in normal levels now but my ceruloplasmin remains below normal. For some reason my CBC varies between all cell lines being slightly low (with normal Hb) to only the platelets being low. The platelets never reach normal levels now even though they were the only cells that remained normal until I
had Vidaza. The low ceruloplasmin is a bit of a problem because it means I can't metabolize the copper properly. My doctor hasn't said so, but I think it's the reason my CBC is still slightly abnormal with normal copper levels. I hope reducing the ferritin will help raise the ceruloplasmin.

Neurologically, I'm deteriorating slowly. I was assessed by an OT a few weeks ago and I'm losing upper body strength now. I have completely lost the use of my wrist extensors which explains why I've been having trouble using my manual wheelchair. The OT has recommended I buy a power chair and I'm just waiting for more input into which type of chair is the most suitable. I haven't been able to leave the house for anything other than medical appointments for about 6-7 weeks now so getting a power chair to be able to go shopping would be a big step forward.

I went for a driving assessment to see if I can use hand controls and while I passed the assessment it was recommended that I don't drive because it would be too tiring and would decrease my ability to complete my ADLs. The OT recommended I use the power chair in wheelchair taxis and buses instead. It would have cost around $70,000 to buy a van capable of carrying a power chair with lift and hand controls and I thought I could catch a lot of taxis and buses for that kind of money anyway and I wouldn't have the stress of battling the traffic and finding parking spots. So, I'm not particularly disappointed about not driving.

Even though I've been told that I don't have the capacity to increase my strength (too much nerve damage) I've bought myself a Wii and use that everyday to help retain the strength I do have and to help with hand eye co ordination and balance, it's also fun.

Well, that's my saga. Basically status quo. Hope I didn't bore anyone.

Regards

Chirley

[cathybee1]

Not boring at all, Chirley. I hope you get your power chair soon and that the pain resolves. I wish someone, somewhere could figure out how to stop the neurological progression.

Bruce currently is getting transfusions once a month, and taking 1000 mg of Exjade daily. He had a kidney stone last month and has some stenosis in one of the arteries leading to the kidney, but so far between that and the Exjade his creatinine levels haven't worsened. Knocking wood. The cardiologist took him off Plavix and put him on a statin. His platelets dropped below normal after he started the Plavix, and haven't returned to normal, so we don't know if they will.

I'm so glad to hear from you. Hugs,

Catherine

[Chirley]

Hi, I've been having copper every day this week and today I had another venesection as well.

My blood tests are still a lot better than before starting the copper treatments but the platelets are still very slowly declining and the liver enzymes are very slowly increasing. The ceruloplasmin level is still below normal too.

I asked the haematologist about all of the abnormalities today but he didn't have any answers.

Every time I come to daycare for treatment they leave my chart on my bedside table but I've never looked at it before. Today I had to move it to use my phone so I looked at the chart. The chart is dated April this year and has my diagnosis as MDS/CNS degeneration. I was told in late 2010 that my MDS diagnosis had been changed to Cu deficiency bone marrow failure. I am also
on the Federal Governments Cancer Registry.

So, I'm asking myself, is the diagnosis on my chart wrong or is Cu def BM failure now classified as a MDS subtype. Or do I still have MDS RAEB 1 and Cu deficiency?

I asked whether I need to have the liver biopsy that the Prof said I should have. The haematologist hasn't had a letter from the Prof so he said he doesn't want to do the biopsy at the moment. I rang the Profs secretary and he said that the Prof hasn't written ANY letters to my haematologist EVER. Don't you just love the way these people don't communicate! Anyhow, I asked
the secretary to ask the Prof very nicely to write a letter to my haematologist so he can be kept in the loop.

In the meantime my haematologist is considering repeating my Lumbar puncture to see if the abnormal 14-3-3 protein is still detectable and that might provide something to gauge the rate of neurological disease progression. Another LP might provide some reassurance that the degeneration has been stopped, so I'm pushing for it to be done.

The USS I had done of my liver 3 weeks ago is pretty good it just shows iron overload, hence the extra venesection today.

You know what, I'm bored with this whole thing, isn't it wonderful. So much better than lurching from crisis to crisis.

Ho hum, yawn.

[cathybee1]

Hi, Chirley.

Glad your blood levels are holding again. I hope the ceruloplasmin and liver numbers eventually start moving in the right direction.

It's surprising that the CU deficiency isn't listed on your chart. But your situation is so unique. Just wondering if there is a treatment advantage/priority given to your care based on the diagnosis listed on your chart.

Bruce and I are on our way to a remote lake cabin for a week. He is doing well, all things considered but needs a break. He is already scheduled for a transfusion as soon as he gets back. His hgb level is holding above 9 for a couple of weeks post-transfusion, and then seems to drop fairly quickly.

[Chirley]

Hi,

I realize that this isn't an issue for those who have had Vidaza for MDS but my diagnosis of MDS is in doubt.

I've had 5 cycles of Vidaza and it's just possible that I didn't need it. Now I found an Internet site that says the Vidaza given to laboratory animals caused a range of cancers. These cancers ranged from skin to lung, breast, lymphoma and Leukaemia. I can't find that site again and don't know how reliable it is.

I emailed Celgene and asked them if I could have any follow up research on the long term carcinogenic effect of Vidaza. I didn't receive a reply so I rang Celgene Australia and spoke to a patient advocate. She said that the email had been referred to her but that she wasn't permitted to let me have that information.

Does it seem right to anyone here that this kind of information can be withheld?

I'm thinking of asking the oncology pharmacist to try to get this information for me. Does anyone have access to this follow up research? If I remember correctly the rate of haematopoetic and solid tumors was quite high but I admit that I wasn't reading the article closely and was just skimming through.

I got a call from the daycare I go to with the results of my last copper level (they are taking a week to come back now!) and it was well below normal. The level has dropped considerably since I've been having venesections and it seems a bit more than co incidence.

Another thing to ask my haematologist about.

Regards

Chirley

[Neil Cuadra]

Depending on how you define "long term" there may not be human studies far back enough to show what the long term effects are. But whatever data was used to gain approval for use of the drug out to be made available to patients.

[milliken2]

Chirley;
Do you have a good rapport with your pharmacist? If so - ask him to get into his medical computer, and print out all of the information on Vidaza. Too - have you checked out the Physician's Desk Reference? Some of what you read may be 'gobletygook' to you - but if I can help, let me know.
Also - the pharmacist may also be able to give you the package insert from the manufaturer. If not - email the manufacturer and ask for a copy of the drug indications/contra-indications and specific uses. This is true of any drug that you take.
Eons ago, when I was in nursing school - you had to hand write your drug cards, but I went the extra mile, and my pharmacist always gave me a package insert (they generally throw them away) and I attached it to my drug card and care plan. Got kudos from the instructors for making the extra effort. Good Luck To You.

Beth

[Chirley]

Thanks for your replies. I was given the normal drug info from the package by both the doctor and pharmacist and the doctor made sure I knew all about Vidaza before I agreed to have it.

I thought that the long term effect of Vidaza may not be known because it hasnt been in use for very long but it has been around since the 80s which means there should be something available after 30 years of use. The fact that there is little or no data available suggests that no one has lived long enough to suffer secondary cancers. The other alternatives are that there is data available and I can't access it or the data is still the property of Celgene and they don't want to release it.

I'm still going to ask the pharmacist to help. It would be good to know if I need screening tests for particular cancers or even just be aware not to ignore certain symptoms.

Thanks again.

Chirley

[Birgitta-A]

Hi Chirley,
As far as I understand most drugs used to treat cancer can cause other types of cancer. You know Revlimid is not approved in Europe for MDS because a few patients in one study developed AML.

Here is an abstract about therapy-related myeloid neoplasms:
http://onlinelibrary.wiley.com/doi/1...0.01100.x/full
Kind regards
Birgitta-A

[Chirley]

Thanks Birgitta, I understood the broad concept of the article. It's unfortunate that there is no real data regarding hypomethylating agents but maybe that's a good thing

I feel a little like someone who's escaped a jail cell to find I might have tunneled into the exercise yard.

I guess it's just like everyone here, there's nothing to do but wait and see.

Its 18 months since I've had a BMB and even though the last one was a vast improvement on the previous ones, it was still abnormal and now with my counts starting to bounce around a bit and my platelets steadily declining, I would feel a little more secure if I had another BMB but my doctor doesn't seem to think it's necessary.

Regards

Chirley

[Birgitta-A]

Hi Chirley,
You know I don't think you have a bone marrow disease but low copper eventually since you were born. All symptoms can depend on that - good that your bone marrow manage to produce cells after so many years with harly any copper at all.

Platelets are often a problem - they are so sensitive. I have been worried about my platelets since dx. I try to avoid everything that eventually can decrease platelets: drugs, food and other substances. I have asked my doctor when I will stop taking Thalidomide and try Revlimid instead. He has told me that we shall wait until they are 50 - last count 72.

I have not had a BMB since before Thalidomide May 2010 - I can't say I miss it though I have so severe fibrosis that they can't aspirate (that's the part that hurts).
Kind regards
Birgitta-A

[Chirley]

I'm in daycare this week. My copper level had dropped last time so my doctor increased the dose of copper sulfate from 4mgs/day to 5mgs. I asked if I could have this run in over an extra hour because I already get tummy pains and diarrhea from the 4 mgs. The nurse agreed to do this but then the pharmacist (new) came in and insisted the infusion was run faster. Needless to say I haven't had very good nights this week.

I saw my doctor this morning and I'm booked to have my liver biopsy next Tuesday. Apparently it's done with a skin local anesthetic under ultrasound in radiology. My liver enzymes are still slowly climbing despite the venesections and the Prof thinks that I have protein transport problem associated with the Hephaestrin and COMMD1 genes which causes an intestinal absorption problem and a renal tubule wasting syndrome. He thinks that the copper that I'm receiving is building up in my liver and causing damage.

The problem is that if the copper is accumulating in the liver it will cause liver failure and I'll die but if I don't get IV copper I'll get progressive neurological damage and bone marrow failure and I'll die. I've thought about what I want to do given the possible outcomes. This decision is really very easy, I've already decided what to do if the Prof is right about the copper accumulating in the liver. I've decided that I'll stop having the copper infusions and just have supportive care. I definitely don't want to die from liver failure.

Then again, there is so little known about my disorder that no one knows what's going to happen and I'll ignore this other stuff until the findings come back.

I was just interrupted by a phone call from radiology to tell me I have to be
admitted to hospital for the biopsy......has anyone else had to be admitted, does this sound routine? I HATE hospitals.

Regards

Chirley

[cathybee1]

Ugh, between a rock and a hard place. I hope the professor is wrong for a change. Bruce was admitted to hospital for his liver biopsy.