Disease progression - a recent post showed this topic.
My question to the very valued, educated members - is it a sign of disease progression due to a person suffering increased infections or has 'catching' more infections caused disease progression ?
I understand the answer from the perspective of each person is unique.
But is there any research on numbers ?
If it were a proven fact that CLLers staying clear of infections had less disease progression, well lets bring on the isolation bubble !!
Good question Aussiejo and I too would be interested to hear of any relevant research beyond what I mention below with some numbers to quantify the risk. There are suspicions that certain viruses (herpes) may be behind the development of CLL in some individuals, but it is obviously not a strong link or we'd be more certain of the association. The outlook for those with CLL is also worse if you have been previously exposed to Epstein-Barr virus or Cytomegalovirus (CMV). Unfortunately, CMV is common, with about 80% of the older population testing positive for a previous infection.
See:
books.google.com.au/books?i...
There's also evidence that progression/clonal expansion/evolution in some variants of CLL is driven by yeasts:
jem.rupress.org/content/210...
Makes sense to me, because if your CLL clone is exposed to the antigen to which it is sensitive, it is going to multiply more rapidly and there will be more opportunities for DNA transcription errors to create clones that may be more aggressive.
As CLL progresses, your body's ability to mount an effective response against illnesses falls away, (antibody levels fall and perhaps also neutrophil levels), so infections tend to be more frequent and take longer to get over. Chemotherapy treatments only worsen that situation (hence W & W). That lowered immunity can set up a vicious circle in which your health deteriorates because you can't stay fit due to illness related fatigue (in addition to what you may already have from your CLL). You are more likely to get secondary infections or be more susceptible to reinfection when you've just got over the last infection...
I lived that in my first two years after my CLL diagnosis and had to quit work and work at keeping my distance from others to just get on top of the frequent infections. That long period of being under the weather hit my fitness really hard and it was a long slow recovery to get back to an acceptable level of fitness, which was still well down on what it used to be.
Way back in 2006, Chaya Venkat reviewed a paper that showed how the rate of infection of CLL patients varied with different prognostic markers:
clltopics.org/Complications...
So it seems like it is a bit of both - disease progression due to a person suffering increased infections and 'catching' more infections causing disease progression.
All the above conjecture aside, as Chaya pointed out (and was not popular for doing so), "CLL is a cancer of the immune system that is supposed to protect us from infections. It follows from this that people with CLL have less than effective immune defenses, are therefore more likely to contract infections and, once infected, are more likely to die from them. Infections are the single biggest killer of CLL patients. So, if your oncologist told you at your CLL diagnosis that you are not going to die from CLL, that when you die it is most likely going to be from something else, he was partly right. The part he may have left out is this: the “something else” that is likely to kill you is an uncontrolled infection caused by the CLL or treatment for it. "
Neil
Hi Neil,
Excellent counterpoint to my conjecture. We may both have equally valid viewpoints depending on the subset of patients observed. I am convinced that there exists an opportunity to really understand the immune function from studying patients like me who demonstrate a high degree of immune function in spite of aggressive and large tumor burden with patients like you who demonstrate globally dysfunctional immune response to all classes of pathogens even in early stages of CLL when Tumor burden is low.
My fear, confined to a knowledge point of view, is now that we have much more effective small molecular and target specific drugs that might become used much earlier in the W&W period, that the pool of patients with immune response polar extremes will not be available to study in the way that exists now. After all, if our immune functions were theoretically perfect, both you and I would not only be free of infections but CLL/SLL as well.
Good thread and thanks to Aussiejo for the question.
WWW
It is certainly an interesting question for the data analysts. Last year I couldn't remember a day without some sort of infection and my WBC doubled. This year, my rate of infections doesn't seem so bad (or am I getting used to the new reality?) but arthritis seems to be running rampant all over my body. Now where the fatigue made keeping fit a losing battle, the pain in my joints now has me almost immobile, except for the changing of positions due to discomfort. Add this new factor in and I would suppose that the rate of infections will start increasing once more and then worse arthritis, and progressions of the disease...it's a snowball rolling down a hill.
Just going from my own experience, I find that taking vit C regularly as well as a teaspoon or 2 soda bicarbonate a day really helps in keeping an internal environment that is not conducive to cold or flu bugs etc. v unscientific but working for me the last couple of years.
Feel for you . It is a real worry to lose your mobility. As for infections and increased blood count that does seem to happen-when I had gangrenous gall bladder my count went through the roof but after removal it went down again. Now my GP factors in unknown or un diagnosed infection every time my count goes up. However the Clear trial does not seem to indicate the use of antibiotics slows the increase. Keep trying to get relief from arthritic pain an take care
For DocM, arthritis is a cruel disease and I don't know if the side effects of medication make it worth taking for some with the condition. Have you tried turmeric? It is probably too mild an anti-inflammatory to do much for bad arthritis and it is not without its risks, but it just might also help your CLL.
For Chrisfer, yes the preventive role of vit C is controversial and I've also heard, I think from the blood counts expert (Susan Leclair), that it can increase the growth of CLL. But if it works for you...
Speckly, when I was on IV antibiotics early this year, my ALC dropped to its lowest level in 4 years. It has since rebounded to their pre treatment level. Of particular interest to Aussiejo, there's a CLEAR (CLL Empirical Antibiotic Regimen) phase 2 trial to check if antibiotics can slow progression open in the UK:
updates.clltopics.org/3431-...
cancerresearchuk.org/about-...
Enrolment finishes today! Better hurry if you are interested!
Neil
Tried Neil but was not eligible. That's why I know the results of phase 1 . I really believe it would help especially for watch and wait. Thanks for the info though you are so knowledgeable and a real asset to the site
Speckly, I drew a blank when trying find any results from the CLEAR trial. Why are they continuing with phase 2 if the results from phase 1 weren't encouraging, do you know? There was also some valid criticism of why antivirals weren't included as well as antibiotics in the CLEAR trial, which is a strange omission given the hints that several viruses could influence progression.
Am seeing my consultant on Monday so will ask. He told me it did work but only for a very small percentage of participants. He had said if it worked I would get the benefit of the treatment without the trial but last time I saw him he said no to that. Will try and get access to the scientific papers as I am not really up to the technical details and let u know.
Thanks for asking
Thanks for following this up. I hope that they can determine why it works for some patients. It sure would be an attractive alternative to more expensive treatment with greater side effects, even if it just defers the time until they become necessary.
Hi DocM,
A curious side note that might tie into our CLL. In the early 1990s I began to suffer the pain of OA (osteoarthritis) so bad I lived on Aspirin and other OTC pain killers. I began Tai-Chi after a particular bad session of pinching the sciatic nerve in my back after a long canoe trip. After about one year of twice daily Tai-Chi practice (It took me that long just to learn the moves well) I never had a repeat of the almost annual nerve pinching and my OA became progressively better. I stopped any pain meds about 3 years after doing Tai-Chi twice a day every day.
At NIH when studied for my CLL I had two doctors come up to me after my CT-scan asking if I was Wayne Wells. They were amazed I was not using a cane or in a wheelchair do to the "severity" of OA they observed. They were further astonished when I told them I had no pain. I continued to experience transient arthralgia in thigh tendons near groin on right side that is quite painful at times but may be triggered by occasional attempts to get back to drinking alcohol
I am working on it. Can't say OA pain can be cured by Tai-Chi practice but I can say I am afraid to stop given the condition I was in in the 1990s. The associated inflammation with OA may contribute to our CLL.
WWW
Interesting comments.
I have Crohn's disease to add to CLL & i tell both Consultants about the fatigue, more worrying though this year has been the aches & pains especially when i move.
I struggle to get out of bed & walk to the toilet where i drop myself on the loo then find it hard to lift myself up, this continues through the day, i seem to seize up.
I get really bad pains in my joints especially legs where i find laying down is the only answer but then get restless legs.
If i get down on the floor i cannot lift myself up, so have to crawl up the furniture 
An interesting thread, is it the infection or the effect of the inflammatory response our bodies mount when countering infection that is a culprit?
Understanding of the day to day effects of chronic inflammation or inflammatory responses caused by infection, injury and irritation on CLL development might help us. There is much research in this area which is fueling the development of the new pathway inhibitor drugs now coming available to treat CLL.
However this does not aid us live with CLL and inflammation on a day to day basis outside of treatment. Some guidance or a definitive study of strategies that may reduce the impact of inflammation would be very helpful in understanding if this also impacts on CLL progression. (i am sure if there are reliable and current papers out there on this Chris, will know where they are)
There is definitely a chicken and egg scenario in this area. CLL seems to feed on pro-inflammitory signals which also prevent CLL cell death and in turn CLL cells secrete further inflammatory signals which feed the background inflammatory condition .
There is no doubt in my own mind that when I experience the inflammatory effect of an infection or the exaggerated response to an insult, I seem to experience a knock on effect in other areas which aggravates other chronic inflammatory issues, could this have been fueling CLl development?
I recall that when my background chronic inflammatory heart condition was treated that the CLL cells in my blood responded very positively, After annually doubling steadily for over two years, they retreated for a year from my blood entirely.
Now they are back again and so are the chronic inflammations .
This 2013 MD Anderson paper although quite technical explains some of this and the how greater understanding of this is fueling the development of new treatments ncbi.nlm.nih.gov/pmc/articl...
.
The paper you site, Nick, is one of the best on this topic, and to view a cast of the players, refer to Table 1.
Cytokines and chemokines all sending the wrong signal at the wrong time, to genes that are defective or not responding... they then pass it down the chain to other genes, who shouldn't get the signal and they in turn pass it on when they shouldn't....
The CLL immune response is like an old 'plug in' telephone switchboard, where switchboard operators plug in phone connections almost at random...
Confusion reigns ... this situation was the topic of a number of comic movies of the 1920’s... and is fairly good analogy... Getting your wires crossed looms large... 
~chris
NOTCH1 plays a role in this... I just posted a new paper on this...
Hi Aussiejo,
I seriously doubt research could separate out the consequences of increased infections as a driver of the CLL mechanisms that define CLL/SLL. Without doubt infections can artificially exacerbate the symptoms of CLL progression i.e. rapid increase in certain lymphnodes and elevation of ALC (Absolute Lymphocyte Count). I would doubt that these symptoms have much affect on the underlying drivers of CLL cell proliferation or ability to avoid apoptosis (natural programed cell death). The reason for my saying so is the well known fact, observed in my own case, where elevated ALC and transient node enlargement will plateau then recede after infections run their course. This pattern of false CLL progression is the hook for quacks or folks like me who get fooled into thinking certain supplements or dubious treatments are working when it is actually the "normal" background fluctuation of response to pathogen invasion.
In my own situation and reflected in others, it is pretty clear that chronic stimulation of the BCR ("B" cell Receptor) by antigen is not only stimulating the proliferation of the cancer clone(s) but is stimulating to remaining functional arms of the immune system complex.
When my CLL was first ramping up, months prior to my DX in 2006 I not only avoided getting any usual cold or flu that Fall but lost a perennial herpes simplex outbreak and a foot fungus both of which I had chronically suffered for about 4 decades. I had one nasty head cold in the Spring of 2008 covering a time period from the Summer of 2005 (CLL likely detectable if I had had blood work) until I began Ibrutinib in the Summer of 2011. Within a couple of months on Ibrutinib I began of pattern of getting routine colds/flu again which has continued every year since the Fall of 2011. Ironically, Ibrutinib is controlling my CLL to a CR (Complete Response) in the blood (normal ALC) and no pathologically enlarged lymphnodes by CT scan. Bone marrow unknown as I have not had a BMB (Bone Marrow Biopsy). Platelets still low.
Bottom line for me is I do not believe infections, per se, have a direct driver effect on the cancer cells but I wonder if inflammation may constitute an underlying condition that drives CLL. I mention that because I have had chronic and severe Osteoarthritis for many years. Inflammatory conditions recruit leukocytes and may provide the environment for CLL to grow.
All through my W&W I had bulky nodes and eventually got an ALC of 300k + with 91% bone marrow infiltration yet remained "healthier" by definition of fewer infections than at any time prior to having CLL or since being on a drug (Ibrutinib) that has smacked the CLL Bear back into hibernation, barely detectable! Food for thought. Hope this helps more than confuses.
WWW
I am in the same position, WWW, with CR-U, (Unconfirmed) after my recent CT scan, (waiting on a BMB). My neutrophils have always been healthy but like (most?) I am hypogammaglogulinaemic.
Similarly, I have experienced more colds since starting Ibrutinib whereas I rarely had one before.
However, this is a particularly bad season with almost everyone affected in some way. Almost impossible to avoid.
I appreciate all the sharing that goes on, on this site as misery does love company. It's good to vent. From all the posts I've read, it would appear that so little is actually known about CLL...how it works, how it can be "effectively" treated as we are all so individual (remember the 60's how we all wanted to be an "individual" ...not working for us now). I have not bee able to make up my mind which is worse or better, getting treated, or leaving it alone. The jury seems to be out on that one. But life goes on...just not life as we know it. Have a Happy New Year
Time-to-first-treatment if you are Binet Stage A? Try the new International Prognostic Score (IPS-A from ICML 2019)
Iola ghulam
Secondary BR Treatment
AbbVie Pharm--positive phase 3 for CLL!
Hot flashes in CLL 
