Beta 2 Microglobin - an exquisitely sensitive marker for disease activity in many hematologic disorders.

[Mikey47]

Increased serum beta2 microglobulin levels reflect increased activity of the disease process in question and can be an exquisitely sensitive marker for this purpose in many hematologic disorders.

The reference range of beta2 microglobulin in urine samples is 0-0.3 µg/mL. In serum or plasma samples, the reference range is 0-3 µg/mL according to the link below. On the excel spreadsheet that was supplied by the CLLSA back in 2010, the range is 1 - 2. Age is probably one of the factors that might explain the variation in range. In any case it seems that the lower the better.

emedicine.medscape.com/arti...

I have seen my B2M lowered from 7.9 (!!!! yikes!!) to 3.3 (as of 27 March) since taking Imbruvica

According to Michael Keating, 'The beta-2-microglobulin level has been confirmed as a major prognostic factor'.

In my experience, the B2M is not routinely given. Prior to the study I have always had to ask for it. If anyone else has further info on the significance of B2M as a prognostic factor I'd welcome it.

[AussieNeil Partner Administrator]

Hi Mikey,

Thanks for sharing how dramatically your B2M results have fallen - to almost within normal range after you commenced treatment! That must be very encouraging. Given the gradual improvements seen with Imbruvica, it may well continue to drop further.

Was it because B2M was included in the spreadsheet that you asked about having your level tested?

My haematologist has checked my levels a few times since diagnosis (which have been within the normal range), but interestingly not at diagnosis. I don't know if this test is done in Australia for all CLL patients, but don't recall the phlebotomist having to check what was required to perform the test - unlike a flow cytometry test!

I don't have my notes with me on the prognostic significance of B2M, but thanks for alerting our community about this test. Those concerned about how rapidly their CLL is progressing now have another test which they can ask their specialist whether it is worthwhile doing.

Neil

[Mikey47 in reply to AussieNeil]

Hi Neil,

When I was diagnosed in 2010 one of the first things I did was sign up to the CLLSA. I was sent a very comprehensive pack including a 33 page document on the diagnosis, staging and treatment of CLL including info on every aspect of the Complete Blood Count and chemistry, Immunoglobulins, etc. and among this LDH and B2M.

I read, at the time, Michael Keating's President's Corner at CLL Global where he talked about the importance of B2M as a prognostic factor. It was at Queen Alexandra hospital at Portsmouth after my move from London where I first asked for my B2M level to be checked when I asked for a CT scan as there were obvious things that they were missing at QA. It was then (according to their lab) 9.7!!!. I asked for a referral to Bournemouth for possible trial and second opinion.

I was fortunate to get on to the Ibrutinib arm of the RESONATE2 study and during the screening process my B2M level was checked at 7.9. Now I'm hoping to see it soon in the 1 - 2.0 range thanks to Ibrutinib/Imbruvica

The spreadsheet supplied by CLLSA is also very comprehensive and may be still available. I have all my results over the last 4 years on it.

[ThreeWs]

Hi Mikey,

I too noticed a direct relationship to the progression of my CLL and the increase in B2M. B2M is another test that is not universally used by all Heme/Oncs. Where I was monitored prior to going to OSU my Heme/Onc used B2M and it got up to 5.6 at a time when my marrow was 91% infiltrated, ALC was around 326k and my nodes were growing everywhere.

I am glad to hear of your response to Ibrutinib.

WWW - a fellow happy Ibru Lab-Rat

[Mikey47 in reply to ThreeWs]

Thanks Threews, It's good to be back in the gym again also after 3 years (sciatica!!)

from a very happy fellow Ibru lab rat

Mikey

[Mikey47 in reply to Mikey47]

WOW!! I just read (Wikipedia) that a B2M level >4 = a median overall survival of 12 months!! I wonder if I didn't get a narrow escape when I got onto this Ibrutinib study with a B2m of 7.9!!!

[Cllcanada Top Poster CURE Hero in reply to Mikey47]

Here is an excellent paper on B2M ... probably better than Wikipedia onlinelibrary.wiley.com/sto...

B2M is a better predictor of time to first treatment and tumour burden than overall survival...

ncbi.nlm.nih.gov/pmc/articl...

[AussieNeil Partner Administrator in reply to Cllcanada]

Chris,

Do you have a different link to the Wiley paper? I'm getting an error:

Forbidden

You don't have permission to access /store/10.1111/j.1365-2141.2009.07699.x/asset/j.1365-2141.2009.07699.x.pdf on this server.

Seems to happen whenever you reference a Wiley Online reference...

Thanks!

[Mikey47 in reply to Cllcanada]

Thanks Chris, but I can't access the online.wiley article 'forbidden'.

Interesting that the Haematologic authors think that the role of B2M ' should be re-evaluated possibly in prospective studies involving large patient cohorts'.

I had cd38+ 1% at start of my trial/study with B2M at 7.9 (reflecting my heavy tumour burden). My B2m at last testing was 3.3 and may well now be lower so that I could be a β2-m neg CD38<30% case. ' β2-m pos CD38<30% cases exhibited a TFS which was significantly lower than that of β2-m neg CD38<30% cases'. Hopefully I am now in the latter.

[Cllcanada Top Poster CURE Hero in reply to Mikey47]

Try this link... tiny.cc/i0fzex

If it doesn't work, please contact me and I will send you the paper...

The paper is called... 'Beta2-microglobulin is a better predictor of treatment-free survival in patients with chronic lymphocytic leukaemia if adjusted according to glomerular filtration rate'

Good history... with a look at why B2M has not been more fully adopted in the clinic and some of the pitfalls of its use and the proposal of using GFR to make it better and more reliable.

[Mikey47 in reply to Cllcanada]

Still 'forbidden' but I google'd it and found the .pdf file, thanks.

[Cllcanada Top Poster CURE Hero in reply to Mikey47]

So weird, it works for me everytime on the iPad in Safari... as does the tiny url...

[Mikey47 in reply to Cllcanada]

Interesting that 'we recommend its, (GFR-B2M), determination in all CLL patients at diagnosis' as it has just been excluded (B2M unadjusted) as a useful test in the most recent guidelines published by the IWCLL.. Maybe the introduction of the new non-chemo drugs have mudied the waters?

[PaulaS Volunteer]

Photo made me smile...

[zevkalman]

Here's another sensitive marker for CLL that I just learned about today: Ki-67. As part of a new patient appointment with a CLL expert at Weill-Cornell in NYC a couple of weeks ago, I had extensive blood work done. I am getting back some of the results now and it seems like a test for Ki-67 was done. In my 3-4 months that I've been learning about my disease, I had never heard of Ki-67 but today I have been reading a lot about it and it seems interesting. I will discuss this with my doctor when I see him since it is fascinating science. But apparently, it is a metric for disease proliferation. From what I seem to understand from the research papers, this antigen (Ki-67) is an indication of an aggressive disease. One paper on CLL and Ki-67 divided people into the following subgroups: one group which proliferation rate (percentage of Ki 67 positive cells) was equal or less than 2%, represented by 14 cases (29.2%) with morphological aspect of typical CLL, one group which proliferation rate was between 3% and 9% represented by 32 cases (66.6%) with morphological aspect of polymorph CLL or prolymphocytic leukemia, and a last group with proliferation rate equal or up to 10% and corresponding to two cases (4.2%) of transformation of CLL to high grade Non Hodgkin lymphoma.

Apparently, research on Ki-67 for CLL has shown that disease progression in CLL proliferates in lymph nodes and the spleen, and NOT in the blood or bone marrow. There was even a paper on targeting Ki-67 for treatment purposes. Another paper discussed how both B2M and the Ki-67 levels were strong indicators. Check out the following paper:

sciencedirect.com/science/a...

The abstract closes with the statement that: "The results of this study suggest that the plasma cKi-67 index, along with B2M level, is a strong predictor of clinical behavior in CLL."

[gotCLL]

Sorry for the late reply. I just re-searched B2 micro, here, and discovered this thread. FYI, see gotcll.wordpress.com/2013/0... for a multivariate assessment nomogram that included B2 micro.