Severe neutropenia

[chriswg]

Hi all

I was just browsing the site and though I'd post our story as the community here seem so nice and supportive. I hope you don't mind English people - it seems to be mainly Ozzies and Americans

My wife has been in and out of hospital a lot during 2012 - about 50 days so far. It started with mouth ulcers which were so sort she stopped eating, this led to constipation which led to hemorrhoids which became infected. She has suffered from neutropenia for the last 10 years but usually a trip to the doctors and some antibiotics clears things up. She had never had to go to hospital before. Her sister has the same problem although we though she had it worse since she had been to hospital a few times for IV antibiotics and G-CSF injections. They both developed it in their early 20's. My wife is now 34 her sister is about 46.

This time, after having had temperatures for a few days despite having antibiotics we took her to the hospital for blood tests. Her neutrophils were 0.00. Oh dear. After a couple of weeks of strong antibiotics the infection cleared up and she was discharged - for a day. The next day temp was over 39 so we got her straight back for another 10 days. This pattern has continued for the last few months although she has managed a couple of 3 week stints at home. We think the hemorrhoid keeps getting infected but they can't operate because of her neutropenia - a proper vicious circle.

We are fortunate to have been referred to Prof Judith Marsh at Kings College Hospital as she is one of the UK's leading experts in this area. We have had every blood test imaginable done along with ongoing genetic tests on her bone marrow. So far she has come up negative to every test they have run. I'm not sure if that is good news or not! She was also seen my Prof Mufti who is head of the department and one of the world experts in investigating the genetic causes of the myelodysplastic syndromes.

The bone marrow investigation showed hardly any white blood stem cells being produced, but the red cells (18.1) and platelets seem to be okay. She has had 7 or 8 blood transfusions while in hospital as she has had bouts of anemia. The red cell count could be due to a transfusion, or maybe the red cell factory has reopened for business. The white cells haven't got above 0.04 throughout the process and this could be due to machine errors as at that low an amount its impossible to be accurate.

Over the last 10 years her neutrophils have usually been around the 1.0 to 1.5 mark. When she was pregnant this went up to around the 4.0 mark both times. Apparently this is fairly normal but it proves her bone marrow can work given the right stimulus right?

So that's where we are at the moment. She's been out of hospital for nearly 3 weeks although she currently has what might be an infected ulcer in her mouth so we might be back in soon. We have more genetic test results due in a couple of weeks time. The G-CSF injections haven't done anything, we've been told that steroids might be an option depending on the results of these tests. If not then they might have to look into a bone marrow transplant but I don't like the look of the survival stats. I'm assuming that would be a last resort only.

Any thoughts or ideas would be gratefully received.

[Sally C]

Hi Chriswg,
Am in Bethesda for husband's bmb at NIH so don't have but a second.
But when Don's neutrophils hit 0.0 he got an infection and was in the hospital for two weeks with 24/7 iv's of antibiotics and then sent home with two more weeks of twice a day iv's of antibiotics. He had diverticulitis and our oncologist treated it as if he had sepsis. He came through it just fine. Perhaps they need to keep your wife on antibiotics for a much longer time.
I hope this helps.
God Bless,
Sally

[chriswg]

Thanks Sally, we thought the same thing, especially after the first and second discharges resulted in her going back after a day the first time and a week the second time. Last time she was in for 10 days and her infection markers came down to 33 (10 is considered normal background markers). She hasn't had a temperature for 3 weeks so hopefully that infection was killed off.

The initial infection was Ecoli which had spread and poisoned her blood. It explains why I came home from work and found her in bed not making much sense. She asked if the kids were up yet even though it was 3pm on a school day and couldn't remember what month it was or how old she was. She just kept trying to convince me she was fine!

[cathybee1]

Unfortunately there's many causes of neutropenia. Bruce had 10 years of neutropenia...and that followed almost 2 years of antibiotics for a bone infection. We were relying on the Westergren Sed rate testing to monitor the infection -- Bruce's was way over 100 for quite a while. It was late in the game before he started growth factors -- they finally knocked back the bone infection for him but didn't do more than temporarily increase his counts. Subsequently, some hematologists told us that extended antibiotic therapy could permanently suppress the white blood cell line. Others have said it could have been the start of MDS manifesting itself. Point is, it is often very difficult to find a cause for these problems, and the doctors must resort to treating the symptoms. The good news is there are many more treatments now than there were 10 years ago and it sounds like your wife is getting excellent care.

We love people from all over the world here. You're right, a lot of Americans and Aussies post. Maybe it's just we outtalk everyone else.

[chriswg]

We got a few more negative results this week along with a positive result for Lupus Anticoagulant. Dr Google suggests this means she is actually more susceptible to thromboses, but it isn't related to the main Lupus. Not a nice thing to see on a letter though.

Neutrophils still at 0.00, WBC is 0.15 (IIRC). She's also still struggling to put on any weight despite eating a lot. I think she's down to about 92 lbs at the moment.

The only positive news is that she is still at home and infection free. That's nearly 4 weeks since she was last discharged.

[Sara J]

Hi Chriswg,
Welcome from another Brit! My husband has AA, first diagnosed when he was a teenager. Fortunately, his neutrophils only dropped to 0.8 but I wanted to let you know that he did respond to steroid treatment. I hope it helps your wife. In the meantime, I would also recommend looking at the partners and carers section of the forum as partners need support too!
All the best,
Sara

[chriswg]

Thanks Sara, I'll check it out.

Do you know if there are risks involved with the steroids? The Professor started saying there could be side-effects that outweigh the benefits but got disturbed and didn't finish explaining. I don't know why they aren't using this time to try a cocktail of steroids and max dose G-CSF. It's frustrating sitting around waiting and hoping she doesn't pick up another infection.

[Sara J]

We were told that steroids are for a short time only. They suppress the immune system, hopefully giving time for the bone marrow to start working again. There is a risk of raised blood pressure and it can increase appetite - a good thing for your wife, maybe. For more information, have you seen the aa&mds website? Highly recommended.
Sara

[chriswg]

Today is the start of the steroid trial. If she doesn't respond to them then they are out of ideas. They aren't giving her G-CSF injections with the steroids though which I thought strange but I trust they know best. Prof Mufti has taken over the case and he is a world leader in blood disorders, plus Prof Marsh is still on the case too as she is the UK's leading expert on bone-marrow disorders. They are both scratching their heads with this one though! If they can't figure it out who is there to escalate it to?

A stem cell transplant seems like the only probably cure, but it's a dangerous procedure considering she doesn't seem that unwell at the moment. She'd been home nearly 6 weeks with no infections. Yesterdays blood test was still showing neutrophils at 0.02 which is as good as 0 apparently. They originally emailed 0.2 and we got excited, then they emailed back to say they'd made a mistake and it was indeed 0.02

[Sara J]

Hi Chriswg,
I noticed that you mentioned Lupus earlier on. Might it be worth asking to see a rheumatologist? I'd recommend a search for Lupus on this forum. Also, don't be afraid to ask your consultant to explain what is happening. I usually take a notebook with questions I'd like to ask. Often, you can't take in everything they say and having a notebook helps me. I also keep a folder for all Rich's blood results and letters.
In the meantime, I hope the steroids start to work soon.
All the best,
Sara

[chriswg]

5 days in and the steroids don't seem to be doing anything. Total WBC is up from 0.23 to 0.36 but neutrophils are only accounting for 0.02 of that. I asked if they could give her G-CSF in tandem with the steroids but they were reluctant too since in the past she hasn't responded to them at all.

So, another week of steroids and another check up on Monday in London. This feels like the last chance saloon for her and it's starting to get very upsetting. They haven't talked next steps yet but I don't know if we would want to take the 60% survival odds of a bone marrow transplant. Even if we did it might not work in the long term if there is an underlying problem outside of the bone marrow that they haven't discovered.

I'm searching and searching every day but I can't find a single story or article of anyone with the exact same symptoms as her. Almost all the cases are anomalies at birth but she was fine for the first 20 years of her life. Then 12 years of being slightly neutropenic, now total neutropenia and no response to any traditional medications. I knew she was special when I married her but I didn't realize how special

[Chirley]

Hi, it must be very frightening at this point.

I don't have any answers for you except to give you a bit of my background.

Over the years blood tests showed my WCC was always slightly low but I remained well. No investigations were done. Then in 2003 I got severe atypical pneumonia and almost died. It was commented on at the time that my WCC was low and didn't respond to the infection but once again no investigations were done.

Later that year I went to the doctor because my hair was thinning and he noticed I was pale and did a blood test. I got a phone call from the lab to tell me to go to hospital because I needed a transfusion, my WCC was also very low.

Anyhow after many months of tests including three BMBs the best they came up with was cyclical neutropenia with iron deficiency anaemia. I became transfusion dependent and my neutrophils regularly dipped into the severely low category.

After a few years of this a BMB finally showed myelodysplastic syndrome and I commenced Vidaza. A progress BMB after 4 cycles of Vidaza showed the myelodysplasia was worsening and they started speeding up the process for a transplant. At this time my neutrophils were often 0.0 and I required 3 units of blood every 2 weeks.

In the meantime I started getting neurological symptoms such as numbness, tingling and loss of balance, at first this was attributed to the chemo. However, just to be safe I had an MRI of the brain and cervical spine and I was found to have a diffuse abnormality in the spinal cord. I also had a Lumbar puncture which was mostly normal except for the presence of 14-3-3 protein which is an indicator for Mad Cow disease. It was determined pretty quickly that I didn't have Mad Cow but the protein being there was still very abnormal

After another month or so I couldn't walk and was admitted to hospital.. After lots of tests they found I had a very low copper level and a very low Vit D level. As well as whacky things like pos ANA. And pos Atypical ANCA.

Anyhow I was started on copper replacement at first by S/C injection and then intravenously. My WCC very quickly became normal with the neutrophils responding very well. The lymphocytes remain low to this day. I also stopped needing transfusions and after my copper level came up into the normal range suddenly my ferritin level which had always been low despite the transfusions, shot up to over 5000. They determined that low copper levels can make some other tests like iron and ferritin unreliable.

I continue to need regular copper infusions because I excrete the copper in my urine which is not normal. I also had a karyotype micro assay performed on my blood and I was found to have a deletion of the proximal section of 15q chromosome which is normally associated with Prader Wiili syndrome even though I do not have any of the typical features of that syndrome. My parents were tested and my mother also has this chromosome deletion.

The Childrens Section of the hospital I go to now test every new Prader Willi diagnosis for copper levels and I'm led to believe they have found two children with low copper levels. So there maybe some part of the chromosome that is deleted that deals with copper metabolism and neurological and bone marrow disorders.

My thoughts are that this maybe just the tip of the iceberg and sometimes diagnosis depends on luck rather than science.

Hope things start turning around for your wife.

Regards

Chirley

[chriswg]

Hi Chirley

Thank you so much for sharing. It sounds like your situation was a lot worse than Rachel's but it's good to know that you are recovering from it quite well. It was actually from this forum that I first read about the link between copper and WBC count and last time I was in London I suggested this to the Professor and was quite surprised that they don't do a copper test as a matter of course. HE said that she didn't present in a normal low copper way and he hadn't seen a copper case leading to such low levels but he thought it would be a good idea to run the test anyway. I can't tell you how hopeful I am that the levels are low! At least then we'll have something to try and treat her with.

We are back there on Monday so hopefully we'll have those results by then.

Chris

[Chirley]

Hi Chris, I was also told that I didn't present as a "normal" copper deficient person.

My haematologist looked back on all my previous BMBs and blood tests and said there was no indication of copper deficiency in any of them and that's why they hadn't done a copper level.

I was started on prednisone at one stage when I had an infection and my neutrophils did respond but it was not a lot and it was a very short-lived response. I was never given G CSF because my haematologist believes that it can increase the blast count. I know that there is research that seems to show that it doesn't have a negative impact on blast counts but my haematologist is still very wary.

I too hope that your wife's copper level is low and she just needs some replacement but if I'm honest it could be just clutching at straws. Better to check and see and if it's not copper deficiency, then you can move on and try to find another cause.

Good luck to both of you.

Chirley

[chriswg]

Quick update - no joy with the steroids (as I expected). Neutrophils have been 0.00 for the last 2 weeks and haven't got above 0.02 for the last 3 months. They are going back to the drawing board with the bone marrow samples they have to see if they missed anything.

In the mean time she is being weaned off the steroids for 2 weeks then they will start her on something else that might take 2 - 3 months to start working.

Our regular consultant seems to think that she could just live a reasonably happy long life without neutrophils so they aren't really considering a stem cell transplant at this stage. She's been out of hospital for 7 or 8 weeks now with no infections. Her infection markers last week were 6.6 which is normal. They were over 200 at one stage!

[Lbrown]

What are infection markers? I've had a very low WBC and neutrophil count (WBC 0.4 - 0.6) for extended periods with no infections, but not a count of 0.

Deb

[chriswg]

Hi Deb

They are more commonly called a CRP:

http://en.wikipedia.org/wiki/C-reactive_protein

Basically it tells you if you have an infection in your bloodstream. Rachel was around the 150 mark when she first went in and I think she peaked at well over 200 before the IV antibiotics took control.

0.5 neutrophils is a reasonably good amount, any less and your body can't trigger an immune response to infections so normal antibiotics won't work.

Chris

[Lbrown]

Hi Chris,

Thanks for the clarification.

When I had my 0 WBC count 20+ yrs ago and ended up in hospital with some sort of infection and a fever of 104 - 106, I suspect now I had ehrliciosis, which wasn't recognized in humans until 1999 (I was first ill in 1991). There are several infections that they know about that will kill off white cells, lyme, rickettsia, ehrlicia, rocky mountain spotted fever. There's probably a lot more plus viruses they don't know about.

Hope Rachal is feeling better and hope her WBC & neutrophils rebound soon!

Deb

[chriswg]

Neutrophils at 0.1 today. Not great but a massive improvement on the usual 0.00 or 0.01. The doctors weren't as excited as we were

[Lbrown]

Any improvement is good news. Hope it continues.

Deb

[chriswg]

Neutrophils are up to 0.12 today but platelets are dropping. They were down to 115 today which isn't desperately low but the last 4 weeks they have gone 169, 145, 130, 115. Hopefully they will stabilize soon!

[chriswg]

Neutrophils at the dizzy heights of 0.18 today and platelets holding at 115. It's slow progress but they have said if she gets to 0.2 then getting an infection isn't likely to be as critical a problem as at 0.1.

We still have no clue why things are improving. It could be the steroids or the other immuno-suppressant drugs but I feel this improvement would have happened anyway. I think after her 3 month infection all her bone marrow was shot to pieces and has taken this long to start repairing itself. Lets hope it keep its steady progress.

[cathybee1]

Thank you for the updates. I continue to pray for both of you.

[chriswg]

Neutrophils up to 0.24 and platelets up to 134. It's still very very low but not quite as critical as it was when under 0.2. Some scales even suggest 0.2-0.5 are only moderately neutropenic which is good. They still have no idea what is working or why but until she hits 0.5 they are going to keep her on all of the prophylactic drugs in case. I think she is on a cocktail of 8 different things, some taken with food, some without, some not within 2 hours of drinking milk, it's hard to fit them all in in a day. She is lucky that so far the only real side effects are headaches. She has also managed to claw back the weight she lost. At one stage she was under 90 lbs and really struggling to gain anything. I think she is closer to a much healthier 105 lbs now.

Thanks for everyone's support through this. It's nice to be able to write down my thoughts as a coping mechanism.

[chriswg]

2 weeks after my last post neutrophils were up to 0.36 and increasing at a very steady rate of 0.06 per week. We were really positive that everything was going in the right direction and that we'd be over the magic 0.5 mark in two weeks. Wrong. This week they had dropped to 0.25 which represents quite a drop. All the stress and worry that we'd not been having for a few weeks has come flooding back and we now have a nervy week until next weeks test. I think it's a vicious circle and that the stress is a contributing factor to the neutropenia.

Has anyone been in a similar situation to this? Are the levels likely to keep slipping, or might they come back up again?