CLL is only about lymphocytes? Perhaps not... monocyte/macrophage may play a role

[Cllcanada]

From this study...

'CLL patients have leukemic cells expressing high levels of immune-suppressing factors, low levels of adhesion and co-stimulatory molecules, lower numbers of natural killer cells, and deregulated T cells with an impairment of immunological synapse formation. The alterations described in our study further contribute to characterizing the complexity of factors potentially involved in the acquired immune deficiency of CLL patients.

In conclusion, we detected altered composition and deregulation of genes involved in phagocytosis and inflammation in blood monocytes obtained from CLL patients, suggesting that CLL-mediated “education” of immune elements may also include the establishment of a skewed phenotype in the monocyte/macrophage population.'

haematologica.org/content/9...

[AussieNeil Partner Administrator]

According to the paper, we don't even fully know what monocytes do in healthy people!

"The full spectrum of monocyte functions, and in particular the specific functions of different monocyte subsets, is not completely known but comprises anti-inflammatory properties, tissue repair and angiogenesis."

Good to see researchers chipping away at these knowledge boundaries - who knows what may come out of it? Perhaps a greater understanding of the protective microenvironment CLL cells weave around them which could lead to improved prognosis and treatment.

Thanks,

Neil

[Valour in reply to AussieNeil]

I am trying to understand trisomy 12 and 17p. Is it fair to say that the 17p impedes the bodies ability to fight anti-inflammatory properties because it is broken which doesn't permit the body to repair well or do I have this all wrong? Also, the Trismony 12 is where I have 3 instead of 2 so it produces something in 3's and I would like to know how it works as well? Any knowledge in lay terms would be most appreciated. Yes we read about it on line but not understanding it.

[AussieNeil Partner Administrator in reply to Valour]

17p (deletion) and trisomy 12 are DNA (chromosome) changes in the CLL cells. The deletion or addition of chromosomes impacts what genes are active in the CLL cells and hence how our CLL progresses and very importantly, how it responds to different treatments.

Neil

[Valour in reply to AussieNeil]

Do you happen to know how these chromosomes impact the genes of the active CLL cells? I know the treatment response time seems to be less then those without the 17 p from what I've read.

[Cllcanada Top Poster CURE Hero in reply to Valour]

Trisomy 12 is an oddball in CLL, the added chromosome causes problems.

For other markers, 13q, 11q, 17p have gene damage...

[Valour in reply to Cllcanada]

So is it fair to say that these markers require different pathway treatment which is either still to come or is in early stage of trials. Do you happen to know any treatment drug that is used for 17p patients. To date my WBC test results are good at 5000 but as I read here I'm aware that WBC isn't the golden goose standard I need to be concerned with the percentage of lymphocytes in my remaining WBC. Thanks again for your knowledge

[Cllcanada Top Poster CURE Hero in reply to Valour]

17p require special treatment and has for the past 10 years or so... currently the treatments are ibrutinib, idelalisib or venetoclax, or a clinical trial with combination therapies, perhaps the best option...

Don't track your WBC or lymphocyte percent.. the better number is the absolute lymphocyte count called ALC or LYMPH#

~chris

[Valour in reply to Cllcanada]

I started this journey on 4/4/2018 in a clinical trial of Acalabrutinib, Obinutuzumab, and next month will begin Venetoclax. So looks like I'm good with the treatment plan. ALC or LYMP is how it is listed in the overall blood results test correct? What are good and bad numbers if using percentages and do you know what treatments are available to today to address this problem given the number is poor?

[Justasheet1 in reply to Valour]

Val,

Can you share some info on your trial please?

I’ve never heard of it.

Thanks,

Jeff

[Valour in reply to Justasheet1]

I started my free Trial on 4/4/2018 at The James Cancer Center Ohio State University. It consists of Acalabrutinib, Obinutuzumab, and Venetoclax as I understand it the Acalabrutinib (2 pills daily) is a second generation of ibrutinib and if I understand it they search and destroy bad cells of a specific pathway which is different from the Obinutuzumab (infusion done in the clinic and will consist of 5 5/2/2018 -5/30/2018 then not again until 6/27/2018 when 4 more will happen ending 9/19/2018 as my calendar only goes that far so there could be more scheduled after that) and it too gathers and destroys bad cells and very quickly too, Venetoclax (a pill and since I'm not on it yet I don't know how many or how often but that starts 5/30/2018 and continues through 9/17/2018 or beyond as again that is the end of my calendar) is again has a targeted pathway for cells that were not in the other two's path. I'm not sure if my understanding is correct but at this stage I am very limited. It may help you to know that when I was told I had CLL I was also told without treatment I would be dead within the year so clearly I'm not a watch and wait due to the advanced fatigue, the aggressive nature of 17p and trisomy 12 and swollen lymph nodes. I am 74 yrs young in a couple weeks which is useful information. I am trying to learning about BK inhibitors, T cells, lymphocytes, monocytes, neutrophil and other unfamiliar words that are becoming very important to know something about. I hope I have answer your questions and may your journey be shortened due to a total healing.

[Justasheet1 in reply to Valour]

Thanks for your detailed reply. I just couldn’t find that trial listed. Thanks, Jeff

[Valour in reply to Cllcanada]

Do you know what the difference is between idelalisib and Obinutuzumab or if they are second generations, benefits of one to the other, different pathways any information would be appreciated

[Cllcanada Top Poster CURE Hero in reply to Valour]

Idelalisib, works upstream from Imbruvica (ibrutinib) on the BCR receptor pathway at PI3K...

Gazyva (obinutuzumab) is a CD20 monoclonal antibody... the next generation of Rituxan...

Two very different treatments.

~chris

[Kwenda]

Thanks for this Chris..

But what is written above brings out this word heterogeneous again doesn’t it.?

There is so much going on with our CLL that we are bound to be different, and with different outcomes..

AND, to use your own well-worn phrase ‘ There is much we still do not know ‘.

Dick

[Safta]

I have no idea what monocytes are, but I just did a blood profile and the monocytes are way too low. Will ask my doctor what it means and listen to his usual "wait and watch" reaction1

[AussieNeil Partner Administrator in reply to Safta]

There was a recent paper that found a correlation between a HIGH monocyte count at CLL diagnosis and a poorer prognosis.

" A monocyte count >0.91×109 L-1 at the time of diagnosis was associated with a shortened overall survival and treatment-free survival."

From Leukemia Research 37:614–618 "Another prognostic indicator for CLL - the monocyte count", by Mazumdar R, Evans P, Culpin R, Bailey J, Allsup D [2013]

My monocyte count has only been (barely) into the normal range [0.2 to 0.8] twice in over 40 blood tests since my diagnosis. It averages 0.06.

My low count monocyte has never been mentioned by my haematologist despite impaired immunity being the major impact on my quality of life with CLL. Neutrophil levels are however closely monitored.

I'll be interested to hear what answer you get. In the mean time, I hope you find the above reassuring.

Neil

[Safta in reply to AussieNeil]

I am reassured.... sort of...

[AussieNeil Partner Administrator]

To save everyone diving for Wikipedia, etc, here are my notes on what monocytes do:

Monocytes increase during severe infections, and other conditions. They remove debris and microorganisms by phagocytosis (engulfing them). Monocytes and Neutrophils come from a common moncyte/granulocyte (i.e neutrophil) progenitor. Your spleen contains about half of your reserve of monocytes (too bad if you've had a splenectomy).

Chaya Venkat explains monocytes thus:

If neutrophils are first responders to a crisis, think of monocytes as the instant responders. In neutropenic patients the very first cell line that the bone marrow is able to get out there onto the battle front are monocytes.

Monocytes are the precursors of dendritic cells and macrophages – literally garbage monsters that can eat bacteria and other other pathogens alive. Dendritic cells are essential for alerting T-cells to the exact nature of the enemy.

Without dendritic cells telling them what to fight, T-cells are blind and unable to mount an effective attack strategy.

Full details:

en.wikipedia.org/wiki/Monocyte

[2016Longevity in reply to AussieNeil]

My husbands blood-results came back with elevated neutrophils, elevated monoctyes next to 'the usual' elevated lymphocytes... Q: is this typical for CLL? The labs be repeated in 2 weeks. Q: could positive stress cause the elevation of neutrophils and monocytes? Currently a lot going on in our life

[Valour in reply to 2016Longevity]

I was told this past Wednesday that it is common to see elevated neutrophils and that they were watching those closely. Even though my were elevated (so sorry I don't have the number) it was not enough yet to require a response with meds. Hope this helps a little.

[Cllcanada Top Poster CURE Hero]

Interesting discussion....thanks.

I think this paper is pointing out a possible way in which our CLL immune systems become deficient.

It is more a 'what if' and I wouldn't worry about my monocyte counts... rather understand the fact that our immune systems are 'broken' to some extent...

~chris

[anaturallearner]

First time I've read the phrase 'acquired immune deficiency'... I think it will help me to explain to others what living with CLL means.

Beverley

[Cllcanada Top Poster CURE Hero]

Our immune deficiency is aquired in the sense of CLL causing it, but Acquired Immune Deficiency Syndrome is AIDS...

You might want to be a little cautious with the term Bev...

~chris

[Valour]

I have been wanting to post a progress report since starting treatment on 4/4/2018. I started on Acalabruitinib on 4/4/2018 and began second drug Obinutuzumab infusion the first Wednesday in May. I know the WBC count isn't as important now that I read your post but just for those who wonder about the new drugs I started my study with 70000 WBC on 4/4/2018 and by 5/16/2018 my WBC is 5000 so I'm very happy and for the record renewed energy the two prior weekends but after yesterdays treatment I was somewhat fatigued and it is a little better today. they said I could experience some fatigue after the Obinutuzumab but last time I had it I still felt like my old self if I can really remember that but better for sure. The first week of June I will begin Venetaclax while continuing the Acalabruitinib and anxious to see how that works for me. I am very pleased to date but remember I was diagnoised in November 2017 and immediately told stage 4 and with 17p and trisomy 12 so these I know have poor outcomes but being what they are I am still pleased to date with feeling better and renewed strength. I continue at 74 (next month) to work daily at a carreer I love and other than treatment days I have not missed a day due to cancer. Staying busy helps me not dwell on it and allows me to live as prior to the diagnosis. My wife studies up on CLL and keep me as informed as I wish to be which is not allot as I can trust her judgment and again wish to think of life not the possibility of death. I know enough to choose my treatments and believe I am in the best of hands. I wish everyone a journey of renewed health and a life full of living.

I will try to post again soon to update for the people who are looking and wondering as I did. I was told that if I had a blood test today I would not be considered to have CLL. I so believe we must listen to CLLcanda as the article posted is in line with what I was told by my team at Ohio State University James Center. By the way Dr James was my father-in-laws doctor and he was diagnosed with cancer 64 years ago and Dr James did a procedure that had never been tried and he lived 50 years until it came back then another 9 with treatment no it wasn't CLL but cancer then and cancer today is a lot different as back then only two specialist in the USA Dr James in Ohio and one in California to choose from. He died at 83 yrs young and lived his life full and large as if he didn't have it so I am trying to set my path closely to his.