New study shows that starting treatment early, before immune damage occurs, brings real clinical benefits

New study shows that starting treatment early, before immune damage occurs, brings real clinical benefits

Having caught your attention, I must now 'fess up' and say that the study is about HIV, not CLL. You might wonder why a post about HIV on a CLL support site. Actually, there's a lot we can learn from studying not only the way HIV affects the body (with both CLL and HIV impacting the immune system), but also how the HIV community successfully lobbied for changes in how clinical trials were performed and how new drugs were made available to small numbers of patients that would normally not be considered as a viable market by pharmaceutical companies. (I'll leave those latter interesting topics for someone else to cover or for another day.)

Bridget Haire, Lecturer in ethics at UNSW Australia, with HIV prevention a speciality, has just published an article on 'The Conversation' explaining how a new study has shown that "Treating HIV early leads to better health and less transmission":

theconversation.com/treatin...

I found the above article interesting, because it appears that with CLL, we are also perhaps getting close to having a similar paper written about the best way to treat CLL, i.e. moving away from the dreaded Watch and Wait (and Worry), to where some form of treatment is provided to help us to maintain our immune function.

The rest of this post is rather technical, but I hope that you'll at least skip read it, because it touches on some important concepts about how CLL impacts you that may help you better understand how CLL affects your immunity and hence your health. Its a summary of what I learnt from reading more about T cells and how CLL impacts them, which was prompted by my reading of the above article. It also provides some background as to why tracking our Absolute Lymphocyte Count (ALC) is what we should do rather than tracking our White Blood Cell count (WBC) and why we don't need to worry about our ALC doubling time until our ALC climbs over 30 (thousand).

The clinical relevance of HIV to CLL is because both diseases involve our T helper cells, the ones that are identified by the CD4 marker. Both CLL and HIV patients are susceptible to opportunistic infections and for much the same reason. As you would expect, we share many of the same related health problems because of the effect on our T lymphocytes of our respective illnesses. Your ALC is comprised of (in decreasing order) T helper lymphocytes (marked by CD4), T cytotoxic cells (marked by CD8) and then B lymphocytes (marked by CD19). (It's actually more complex than this with variants in the T cells and other smaller populations of T cells, some of which are still being discovered, but the CD4, CD8 and CD19 lymphocytes are predominant.) The HIV virus attacks the T helper cells, and HIV progression is tracked by monitoring CD4 levels. In CLL, the normal ratio of CD4 and CD8 (cytotoxic T cells) becomes reversed and our clonal B lymophocytes - our CLL cells, also inhibit T lymphocytes. So basically, the same test (Flow Cytometry), that is used to provide a definitive diagnosis that we have CLL, is also used to track progression of HIV. The CD4 T helper cells are extremely important to immunity, because without their assistance, B lymphocytes can't make antibodies/immunoglobulins and vaccinations don't work.

More reading:

The immunodeficiency of chronic lymphocytic leukaemia (written by Prof Terry Hamblin and his daughter)

bmb.oxfordjournals.org/cont...

"In most patients with CLL, T-cell numbers are increased. This increase mainly affects CD8+ cells, but CD4+ cells are also increased, though the CD4/CD8 ratio is reversed."

This is partly why B lymphocyte (CLL cell) doubling time can't be properly assessed until your ALC is much higher than normal - above 30 (thousand) and why we need to track our ALC NOT our WBC. Even in a healthy person, B lymphocytes only comprise about 5% of the WBC. In healthy people, the WBC is mostly neutrophils.

Chronic lymphocytic leukemia cells induce changes in gene expression of CD4 and CD8 T cells (Very technical)

jci.org/articles/view/24176

Helper T Cells and Lymphocyte Activation (again very technical)

ncbi.nlm.nih.gov/books/NBK2...

What I found fascinating in this book extract was how our CD4 T helper cells are involved in determining whether we should sneeze, vomit or have diarrhoea to expel pathogens from our body!

"If the naïve T helper cell differentiates into a TH2 cell, by contrast, it will secrete interleukins 4, 5, 10, and 13 (IL-4, IL-5, IL-10, and IL-13) and will mainly defend the animal against extracellular pathogens. A TH2 cell can stimulate B cells to make most classes of antibodies, including IgE and some subclasses of IgG antibodies that bind to mast cells, basophils, and eosinophils. These cells release local mediators that cause sneezing, coughing, or diarrhea and help expel extracellular microbes and larger parasites from epithelial surfaces of the body." (my emphasis.)

If you have reached this far, congratulations! You probably need to have a rest right now to restore your worn out brain cells, so have a seat, relax and watch the river drift slowly past while the busy bird life keeps you amused.

Neil

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  • Quite appropriate Neil..... someone told me years ago... CLL after treatment, is similar to HIV/AIDs if you look at the blood...

    Reduced CD4 +T cells... we share that after treatment... with HIV patients... not perminently...but for some time...

    If you want derms or dentists that understand our wonky immune system... just ask 'who treats HIV/AIDs patients'...

    Posted in remembrance of my dear friend and mentor Tim Thompson... you taught me well... he said... CLL ...think HIV... faster service...shorter wait times!

    facebook.com/profile.php?id...

    ~chris

  • Very interesting post Neil, great comment on finding a dentist Chris.

    Last year my consultant and I were discussing dropping Aciclover and Septrin (having been on them for two years). He added CD4 and CD8 tests to my normaly full blood tests. His comment at the time was sonething like "most of our knowledge in this area is from the HIV researchers".

    Good to see sharing of research, makes the research money go further.

    Rob

  • Fascinating, but my brain hurts! I know I will keep coming back to this post so that a little more will sink in and be retained each time.

    C

  • Niel this is fascinating stuff.  Very complex but so interesting.  I have to admit I have to read this again........but as you say I am going to take a break now and enjoy the birds outside and the beautiful sunny spring day for a bit.  As a group HIV patients needed non HIV folks to get behind the push for research and treatment.  HIV treatment has finally come a long way.  This makes me happy.  Thank you for a wonderful post.

    Kathy

  • Here is link from last week, about opportunistic infections... Once more it is discussing HIV, however immunocompromised is immunocompromised..we have a lot in common..

    healthunlocked.com/cllsuppo...

    ~chris 

  • My head hurts! Thank you Neil, I will read this in bite size pieces :-))

    Peggy

  • Fascinating information! I have often wondered if there is something that should be done early on in order to stave off opportunistic infections/second cancers down the road. My ALC is still at about the 10,000 level, so I hope they move in this direction quickly!!!

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