Paper about immune deficiency in CLL

[AdrianUK]

This is a good read. And if you have a doctor or friend who says early cll isn’t associated with immune problems, could be a useful paper to show them.

academic.oup.com/bmb/articl...

[Cllcanada Top Poster CURE Hero]

Good general paper, perhaps a bit aging, in the era of small molecule inhibitors...

Take home is get your vaccines updated, Shingrix and Prevnar13 are important.. discuss these with your CLL specialist.

Angela Hamblin is working on the 100,000 Genome project at Oxford...😃

~chris

[Benlewis in reply to Cllcanada]

Hi Chris this paper is saying that vaccinations are ineffective for CLL patients. I hope I’m missing something or that thinking has changed?

[Cllcanada Top Poster CURE Hero in reply to Benlewis]

Yes that's true to any extent... we certainly do not get full benefit from most vaccines, however we go get some benefit.., so better to be vaccinated than not...

A new study of Imbruvica (ibrutinib) suggests it may aid in antibody production ... so patients on this treatment may get better benefit than perhaps someone on watch and wait requiring treatment...

Its a sliding scale... and everyone is different...

Prevnar13 and an annual flu shots are a must.. Shingrix is a bit early to tell yet...

~chris

[Sushibruno in reply to Cllcanada]

Hi Chris what is prevnar 13?

[Cllcanada Top Poster CURE Hero in reply to Sushibruno]

Its the children's pneumonia vaccine... it works better than the adult vaccine on CLL patients... its CDC recommended for immunocompromised patients... ask your GP

~chris

[Sushibruno in reply to Cllcanada]

Thank you, Chris

[SeymourB in reply to Cllcanada]

Chris -

My titre reports show that the pneumovax23 has 12 of the 13 serotypes that prevnar13 has. Pneumovax23 lacks only serotype 6A. I've had both vaccines twice in the last 5 years. But Prevnar13 is conjugated with diphtheria protein. I wonder if that is what makes the difference between the two.

en.wikipedia.org/wiki/Pneum...

en.wikipedia.org/wiki/Pneum...

Of the 23 serotypes, I mounted a barely adequate response to 12 of 23 (>0.3mcg/mL) serotypes. Only 4 were above 1mcg/mL. I have chronic sinus, ear, and eye infections, and unusual gut symptoms. On this basis, my immunologist is pursuing approval of SCIG (subcutaneous immunoglobulin G) therapy with my insurance company. Stay tuned for the outcome of the negotions in a month or so.

My titre report for diphtheria went from 1 IU/ml in 2012, to 1.78 in 2017, to 0.5 in 2018, where >0.01 IU/mL is protective. My last Prevnar13 was in 2013. So It really dropped off in the last year.

I am on watch and wait, with no significant lymph node problems, Trisomy 12, mutated heavy chains.

Still working everyday from home when I don't have an active fever.

So I have to say, yes, early stage is clearly immunosuppressed in my case.

=seymour=

[Cllcanada Top Poster CURE Hero in reply to SeymourB]

Hi seymour

There is overlap of serotypes... if 1-12 is just adequate then, perhaps another Prevnar 13 ...

Prevnar13 is suppose to be a one shot deal, and it might be in children, but in CLL we could need to be done again.

Here in the Canadian Govs take on this.. in more detail than I can handle... 😂

canada.ca/en/public-health/...

[opal11uk in reply to Cllcanada]

My husbands Haematologist is a Mr Hamblin at Colchester General Hospital, wonder if they are related?

[Cllcanada Top Poster CURE Hero in reply to opal11uk]

Terry had two sons Richard and David...

[Jm954 Administrator]

A lot has moved on in the 10 years since this paper.

[Newdawn Administrator]

What does interest me in this article (which I admit I haven’t had time to fully read yet) as I’m still deep in bereavement issues and sorting, is the recognition of immunosupression right from the start.

When my labs were relatively low, I suffered a couple of very serious infections which had me hospitalised. I defeloped sepsis with both. The response I received from medics as they wheeled me in to a 4 bedded Ward next to Typhoid Mary was the fact that I was still somehow immune intact as I wasn’t neutrophenic. This from the article validates the points I made to them about this;

‘The immunodeficiency chiefly manifests as hypogammaglobulinaemia but involves all elements of the immune system. It is caused by the interpolation of tumour cells among immunological cells and mediated by bi-directional cell contact and secretion of cytokines, which both sustain and invigorate the tumour and suppress immunity. CLL treatment generally makes the immunodeficiency worse.’

The fact that I had hypogammaglobulinaemia (basically means reduced immunoglobulins/antibodies) didn’t register with them as a relevant factor for further acquired risk. At one point a nurse pointedly told me I wasn’t neutrophenic and I summoned her over and told her to sit down and explain exactly what she understood by that statement. She hadn’t a clue!

Newdawn

[AdrianUK in reply to Newdawn]

Yes. I had a pneumonia which went sceptic and triggered my diagnosis when I wasn’t even low on antibodies and even had two bouts of shingles several years before I got diagnosed. I’m one of those who would then go on to get reduced antibodies tho.

[Cllcanada Top Poster CURE Hero in reply to AdrianUK]

Zoster virus is kept in check by CD4+ T cells primarily... they often run an HIV test if there are no other indications for immunodeficiency... but CLL can impact those as well, as can treatment.

Certainly we are at high risk for zoster reactivations... so, the new vaccine is very important.

Dr. Hamblin used to quip, that after FCR, many patients had CD4 levels that equaled an AIDs/HIV patient and counts often remained low for a year or more...

~chris

[SeymourB in reply to Newdawn]

@Newdawn -

This whole thing about neutropenia (low neuts) vs. hypogammaglobulinemia (low Ig's) is one of the big things that scare me about hospitals and current medical education.

Low neuts are clearly a bigger problem than low Ig's. But low Ig's also mean higher susceptibility to viruses - for which there are few drugs - as well as lack of response to common microbes that evade neutrophils, like the common staphylococcus aureus.

I hope you are getting some good help with your grieving process.

=seymour=

[Newdawn Administrator in reply to SeymourB]

You’re absolutely right Seymour but it’s not widely accepted as an issue by medics in hospital and certainly not understood by nurses. It’s such an unquantifiable risk in many ways and at the time I had an infection, the origins of which they just couldn’t locate and never did.

I did however end up with a severe secondary infection at the site of the cannulas in my hands and needed even more powerful IV antibiotics to tackle that! Your mention of the microbes that evade neutrophils like staph therefore resonates with me.

Thank you for your kind enquiries about my feelings of grief which I’m working through but obviously not looking forward to the funeral next week.

Kind regards,

Newdawn

[SeymourB in reply to Newdawn]

@Newdawn -

All I can recommend for grief is to do some kind of symbolic art, craft, music, or poetry. I don't recover from death quickly myself.

Try not to hug too many at the funeral. Wear a mask if you must - tell people it's to protect them from you, if you must. Perhaps this is another reason why veils and gloves became popular. Take a decongestant beforehand. I can't help but think that funerals have led to many "coincidental" deaths that we find poetic from a distance. Up close, it's about clogged sinuses, hands, lips, and lowered immune systems of all involved.

=seymour=

[Newdawn Administrator in reply to SeymourB]

Thanks Seymour and amazingly, I foolishly hadn’t given that close exposure too much thought.

As I’m not widely disclosed, a mask would create some alarm and it’s not the right venue to ‘come out’ about my CLL as it were. However, I will take all the necessary hygiene precautions. The closest people to me who know, are being amazing in their support and practical help. It’s probably made me realise I need to let people know now.

Appreciatively,

Newdawn

[opal11uk]

Wow, thats quite a read and such long words lol, now I have to read it again to get the full understanding. Just out of interest, my husband was diagnosed this year and after he had Shingles last year so I am guessing it could return. This really is a watch and wait situation but at least now I am more aware of what to look for and how to react. Since his diagnosis he has purposely lost over a stone in weight and feeling better for it, he is happy in himself and busy with his garden and I am praying that this will continue for a long time to come. We all live in hope.......

[SeymourB in reply to opal11uk]

@opal11uk -

On getting shingles twice:

webmd.com/skin-problems-and...

Even if you don't get shingles twice, the "gift" keeps on giving in the form of neuralgia that follows the nerve that was affected. For me, it comes out at times of stress. Mine broke out in the upper trigeminal nerve from forehead back across to the back of the skull. It also went into my eye on that side. During times of stress, I feel like I have a grit of sand in my eye, and I can feel the path of the nerve across my scalp, along with a massive headache.

I had chicken pox twice as a child, so I expect I might be at higher risk to get shingles again.

I'm glad your husband enjoys his garden - it's so good for body and soul. But do caution him about wearing gloves.

=seymour=

[opal11uk in reply to SeymourB]

That sounds very painful. My husband had shingles which only manifested itself on/in his head, big painful sores which lasted quite a while, thankfully he was treated with anti virals and eventually it disappeared. The irony was that I had been vaccinated earlier in the year but he wasn't as he was not the same age but I do wonder if his shingles was a precursor to diagnosis if CLL. Yesterday was his birthday and an appointment with the Haematlogist for the results of the last blood test, which was a FISH test, and the doctor explained about the T cells, mutations etc., which of course went over our heads but he re-iterated that this was unlikely to cause any problems as it was dormant (not the right word I know) and that he didn't want to see hubby for 12 months, then after some chat decided to have him back in in 6 months so to me that meant he was keeping a watchful eye on my husband. As well as the shingles last year, he had Hepatitis when he was in his 30's and was born jaundiced and I am wondering if this is also significant, I guess we will never know.

[SeymourB in reply to opal11uk]

Opal11uk -

I did get the antiviral valacyclovir within 48 hours. I took the older and cheaper acyclovir for several years as well. I can't say that acyclovir had any effect at all. It was like throwing popcorn at a bull dog.

Now, I value my shingles as a way to keep my stress lower. If my eye clouds up, it's time to disconnect from the computer. It's interesting to see what other situations bring it on - tax time in the U.S., and deaths of relatives or friends. Any emotional situation, really.

I think dormant is indeed the proper term for what your husband exerienced. I don't think the virus is well understood yet.

It is all SO complicated - even for immunologists. They must have to read an encyclopdia a year to keep up with research. But they do try to extract general rules, and those rules are changing bit by bit, year by year. This is all to our benefit in the long run, but I think the average older GP is woefully clueless, and feels like a 1960s mechanic working on a 2018 car. There's still fuel, electricity, and exhaust, but so many more wires and pipes.

=seymour=

[opal11uk in reply to SeymourB]

Thank you Seymour for your reply. Stress, yes indeed, I had a series of ITA's last year plus we were moving so think you have that bang on, now we are settled and he is busy in his garden, loving every day of it and I am keeping well after change of medication so his stress levels are now zero, best keep it that way !!!!!

[SMS-not-cll]

Wow! So much of this information is still new to me, but your posting this article could not have come at a better time as I am determined to have as much knowledge as possible for my upcoming hematologist, immunologist, rheumetoligist, and internist appointments in the next two months.

Many thanks, Adrian.

Wishing good days and good health to all.

SMS

[newyork8]

I don't think it is clear that removing cll cells from the patient restores immunity. There must be more to it...perhaps not understood. In other words does immunity improve as the CLL burden declines or is eliminated? Not in my case as meadured by IGA, IGG etc.

[AdrianUK in reply to newyork8]

Also is there a difference in how they are Eliminated? Ie would long term immunity improve if we are treated with more specific drugs. One thing which fascinated me was that the risks of serious infection on ibritinib seems to be higher at the beginning...could it be that the body’s defenses begin to improve over time?

[Cllcanada Top Poster CURE Hero in reply to AdrianUK]

All CLL treatments wipe out the entire B cell population... the CLL holy grail would be a targeted treatment which only kills malignant B cells, leaving the good B cells untouched.. but this has always eluded researchers...

There is a chance that ROR1 might be that target, but too early to say yet... perhaps the next five years will yield something.

But CLL in and of itself does a number on immunoglobulins, so who knows.

There was a suggestion recently that Imbruvica (ibrutinib) may restore antibody production from vaccines but early days still...

~chris

[Cllcanada Top Poster CURE Hero]

Here is Dr. Terry Hamblin... this was recorded for the CLLPAG 2009 conference in Canada, which he was unable to attend, due to illness.

Terry was a great supporter of CLL patients... this information is for a historical rear view... much has changed.

youtu.be/PEywGT7odFw(Not working as expected?)