Should I be worried?

[Vindicatrix]

Hi All, my Haemo Lady, just called me with my Bone Marrow Biopsy results, She, said they were heavily infiltrated with CLL.

A recent body scan also showed a large lump in my stomach, she is not sure if it is related to my CLL, or perhaps an aggressive lymphoma. She has ordered a needle biopsy of this lump, and hopes I will have a date within two weeks.

My concern is that I had a full body scan in June, and September, and this recent one in December and although most of my nodes were growing, there seemed to be no specific concern about this present lump.

Once she has the result of this biopsy, and more recent bloods, she will tell me the treatment I need. It seemed originally, that I was going to be put on 'Veneloclax' and 'Obintuzumab', but that has been put on hold until the result of the needle biopsy. She tells me depending on this, it may be some other type of Chemo that's needed.

Due to language problems, I was unable to understand the exact name of the drug, but it may have been 'Acalabrutinib' which she said is one of the treatments that is permanent.

My recent bloods of 4th December show: Haemoglobin, 107. overall WBC, 110. Platelets, 162. WBC 3.64. and Lymphocytes,104. I have to be honest, I don't really know what they all mean. But she seemed to indicate that, those that readings meant treatment was needed now.

Any views or experiences related to this post will be very much appreciated.

All the best to all, and have a very 'Merry Xmas' and Hogmany'😀 Ron

[AussieNeil Partner Administrator]

Hi Ron,

With your haemoglobin at 107, you are approaching the trigger level of 100 for starting treatment. That's a proxy measurement showing (your confirmed) heavy bone marrow infiltration, though encouragingly, your platelet count of 162 and I think you meant your neutrophil count of 3.64 are excellent in such circumstances.

This pinned post covers the treatment triggers: healthunlocked.com/cllsuppo... From that post, you'll find that the nodal dimensions for starting treatment are 100mm (about 4 inches) in the longest dimension. I'm not sure why your specialist is performing a needle biopsy to check for aggressive lymphoma (better known as Richter's Transformation (RT)); presumably that's where her experienced assessment of you may be apparent. Usually patient symptoms, plus possibly a high LDH result, can indicate possible RT. In such cases, a PET scan is used to check for any highly active nodes and if found, a biopsy is performed if an active node is easily accessible, which is then checked for RT pathology. (A needle biopsy can miss transformed lymphocytes.) If you had RT, I'd think you'd probably be feeling much worse. It's reasonably common to develop massive nodes as treatment time approaches.

Neil

[Living_and_Learning in reply to AussieNeil]

Neil, your replies are always so thorough and calming. Thank you.

[Vindicatrix in reply to AussieNeil]

'AussieNeil', as usual your extensive knowledge, and presentation of it, allows me (And many of us I suspect) to (Calm Down) and take in what's happening to us, without too much panic and angst. It reassures me somewhat, and I would like to thank you for that.

I accept what you say about the possible early intervention of the needle biopsy. Whilst I have faith in my Haematologist, and the MDT which made the decisions, I am aware that she and her department are under immense pressure, (She herself pointed this out to me)

She is a recently employed 'Locum', working in a department which should have four haematologists, and has only her, at the moment.

I am also a little concerned with her knowledge and understanding of the English language, as I have difficulty with some of the words and phrases she uses, sometimes when they are crucial to my treatment, and understanding of it.

I appreciate that this is always a sensitive area when dealing with new Medics from abroad. Many people are as a result, refraining, from asking for clarification, and it is easier to say nothing, than be accused of some type of racism, or causing offence. (I really don't know what the answer is) in the present climate.

Having said that, I do feel that she is genuinely trying to do her very best for me. She encourages me to keep in regular touch, as sometimes, she needs and wants reminded of information pertaining to my tests and appointments.

In view of this, you, and the other very knowledgeable contributors to this Website, make things much easier for us, in the various situations we find ourselves in.

Personally, I do find it hard to keep up with the never ending flow of specialised information which is extremely important to us, but this forums input is helps us enormously.

Thanks again, AussieNeil, and have a good and Merry Aussie Xmas, and Hogmany. Ron

[Skyshark]

I had one lymph node in my jaw go from not noticeable to gobstopper size in 2 days. The "frankenfurter" conglomeration of lymph nodes found in my abdomen by CT scan was 14cm x 1cm (picture a sausage!). There was concern about Richter's Syndrome. They did a biopsy on the "frankenfurter" and sent the specimen off for a 2nd opinion. It came back as CLL.

Bone marrow was 75% infiltration and blood was still OK except for lymphs. I've seen people report 100% infiltration but I can't remember if that affected their other bloods.

Then they did a PET scan. Low SUV. They should have done the PET scan to find target before biopsy, the node with highest SUV.

Lymphs were over 100 when I started on V+O. Lymphs + nodes >10cm, I was high risk TLS, inpatient for first dose of Obin. De-bulking on Obin brought the bloods to normal on first IV, with platelets dipping below 100 but it only worked on squishy lymph nodes, there was still a core of the hard gobstopper node in my jaw. Due to lymph node size by CT scan in week 3, I was still high risk TLS for Ven ramp up week 4, two more stays as inpatient for 20mg and 50mg Ven. Lymph nodes in jaw had all gone by end of week 2 of cycle 2 on 100mg/day Ven, I think the "frankenfurter" must have gone about then as well. CT scan at cycle 5 showed all nodes normal and spleen under 13cm. Unconfirmed complete remission, now on blood test, appointment and prescription every 2 cycles.

I hope yours goes as well or better than mine. (First 100mg of Obin took 8 hours, I was cooking at 38°C.)

Bloods cycle 8

[Vindicatrix in reply to Skyshark]

That's great news about possible remission Skyshark, you must be feeling relieved and a little relaxed approaching Xmas. Have a good one.

Regards Ron

[SofiaDeo]

IDK how much/what percentage "heavily infiltrated" means. My rapid onset CLL had my bone marrow almost pure white (according to doc) yet cell parameters hadn't fallen below normal. I started looking at treatments, selected one (it was a clinical trial), and by the time I got things lined up & started, my red cell lines started dropping. This was mmm 3-4 months.

As AussieNeil poined out, it's not unusual for some people to get lymph nodes growing. A needle biopsy is not recommended if someone is lookin to rule out a RT, you should have a slice biopsy of the questionable node. However, people with RT generally have a number of grossly abnormal labs as well as various symptoms, which you aren't reporting. And your labs show you are getting near "red blood cells low enough to recommend treatment" but unless you are having other symptoms, you aren't quite at "you should treat NOW, immediately". I think it's preferable to start slightly before one "should", because there is no way of knowing if any cell lines may dip a bit more because of the the drugs before returning to normal.

Some specialists like BTK treatment for heavily nodal CLL, but if you would prefer V&O I am not aware that there is documentation saying one versus another should be used. The most recent treatment algorithms don't show a preference.

nature.com/articles/s41408-...

So as you can see, either a BTK with or without obinituzumab, is recommended equally with V&O. And everyone would like people to start with a trial, so we can actually gather data to make determinations *if* one turns out to be better than another. Even though you are using already approved drugs, it's only by trial participation can data be correctly gathered to find out if one actually is better than another.

But it's up to you. If you don't want a trial, and you prefer one treatment over another, don't let any doc try to tell you one is definately better than another.

[Skyshark in reply to SofiaDeo]

CLL14 Ven-Obi hazard ratio for lymph node(s) >= 5cm is 1.918

Elevate TN Acalabrutinib doesn't give a direct hazard ratio for bulky disease but gives the hazard ratio against the Chl-O CIT arm. Overall 0.2, Lymphs >= 5cm 0.14 and lymphs < 5cm 0.23.

Acalabrutinib hazard ratio for lymph node(s) >= 5cm ??? 0.2/0.14 = 1.4 ??? or ??? 0.23/0.14 = 1.64 ???

If it's 1.64 the hazard ratio VenO / Acala = 1.167, there isn't very much difference. Bulky disease carries a higher risk.

But by multivariate analysis both find the critical size is 5cm and not iwCLL 10cm.

nature.com/articles/s41467-...

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

[SofiaDeo in reply to Skyshark]

These links compare chlorambucil containing regimens, which I am not sure would not be 100% relevant here. I am not sure of what you are trying to point out with the hazard ratios, because while they may be observations done during the study, there is nothing in the discussion indicating anyone was trying to make conclusions regarding those data points. You can't take the V&O subset conclusions from a study of a (V&O regimen vs. the chlorambucil group), and compare that data to the BTK group of a different study, (BTK vs. BTK/chlorambucil patients).

One would need to actually compare V&O versus BTK regimes to try to say "one is better than another" and even then, with our cancer being rare, it will take lots of patient numbers to get to that point. At some point, when we get enough data points from various studies, I am sure someone will run a meta analysis, trying to match patients and see how they compare, but neither of these do that.

Hence the recommendation nowadays for everyone to try to be admitted to a study; we really really need this data! The numbers were large enough to be statistically significant, so the discussion talks about how the non-chlorambucil group fared better. But the exact percentages aren't set in stone for patients overall, since the numbers are so low. The numbers may change when studies are done involving 500 patients in each arm, and may change again when there are 1000 or 10,000 patients worth of data. And again, this was comparing 1 set of drugs to a chlorambucil containing regimen. You can't pull the non chlorambucil data's conclusions from each study and compare them to each other.

None of the patient characteristics in either study referred to nodal disease extent, nor was there any reference in the discussion. So the SLL subset hasn't been discussed, and we can't draw conclusions. Simply collecting certain data points is not enough to reach a definitive conclusion from what they observed, it's a starting point.. It can offer topic for discussion, and point the way for further studies, and suggest certain possible outcomes, which is great. But it's not a conclusion. None of those numbers can be quoted as a certainty across the board, that wasn't what the study was designed to do, And the discussion in each study contains no mention of how nodes or node size affected outcomes. There was more talk about the effects of del17 p and TP53.

[Vindicatrix in reply to SofiaDeo]

Thanks for that Sofia, jeez, it does make heavy reading for the layman/woman, whose knowledge may be negligible.

However, it is essential, I think, that we do have expert input such as your and Aussie Neils, I don't know your backgrounds, but I suspect you both have had some professional experience.

It is gratifying indeed to have such input, and we are all better off for it.

Thanks again. Ron

[SofiaDeo in reply to Vindicatrix]

LOL I started as a paid "guinea pig" in college for clinical trials, and my work has involved clinical trials in medicine, working in a number of places throughout my career that had oncology departments participating in studies. At one point I took coursework qualifying me to design/run them, including statistics classes.

[Vindicatrix in reply to SofiaDeo]

It shows in the excellent assessments and comments in your 'Posts'.😀

[Vindicatrix in reply to SofiaDeo]

That was very interesting, SofiaDeo, and I would like to thank you for your very knowledgeable input.

Are you saying I could ask for a 'Trial' the way my Haematologist presented this treatment, to me seemed to indicate that I had no choice in the matter.

Both you and AussieNeil seemed to indicate, that a needle biopsy was being done, perhaps prematurely. It appears that a 'Peta Scan' would be the first option.

Is, there any negative effects of me having a needle biopsy at this stage.?

Thanks again, you have reassured me somewhat, and I will now settle down and enjoy the 'Festive Period' without the looming presence of the dreaded 'Treatments'😀

That was said with tongue and cheek, by the way, as I really do appreciate and am grateful for, nay 'Treatments' no matter how unpleasant, as they are better than the alternatives. 😬👍

Have a stress free Xmas, and if you are Scottish, do enjoy Hogmany. Ron

[SofiaDeo in reply to Vindicatrix]

The thing about a trial, is you have to be near a place enrolled in the trial. So if there aren't any trial centers near you/your doc doesn't participate in them, that's out. I was just pointing out the top line in the published treatment algorithm for not-yet-treated patients, is that the profession would ideally like to gather this data/put people into a trial. Depending on life circumstances, it's not feasible for all. Job, kids, where you live, other disease states, all affect this. If you are interested in this, feel free to PM me & I can show you how to search the database for things available to you.

Not sure about the needle biopsy being premature, just, it's more usual for untreated people with multiple enlarged internal nodes, to assume they are part of the CLL. I haven't heard here about others commenting their docs did this. I wouldn't say it's premature, since you reported the doc is wanting to make sure it actually is CLL and not something else. The comment was more along the lines of, we have seen some people here get a RT or other DLBCL diagnosis from a needle biopsy, and the specialist consensus seems to be if one is wanting to rule out RT/other DLBCL, the consensus seems to be "use a slice not needle". So I would not worry about it, just, if for some reason the pathologist reading it says "it's not CLL" ideally get a second opinion from a place like the Mayo Clinic, if you can. Specimens can be shipped, you don't have to travel there. I know of someone here, who was told "you have a RT" that she demanded it be sent to the Mayo, and the consensus was "DLBCL but not RT". This is in the US though, not sure about Europe, AUS or elsewhere.

Anyway, it's not that what your doc is doing is "wrong". I think it's more along the lines of, it's more usual to do a CT to check on the *size* of internal nodes, instead of a PET to look at *metabolic activity within the node*. And your doc is following the protocol when trying to rule out the possibility that a secondary tumor is in the mix (which they told you). It's not common to verify there's no secondary tumor or disease transformation before starting initial treatment, but it's not unheard of. IMO it's being cautious, making sure exactly what is there. We have no way of knowing why your doc wants to double check/verify this, but it's not "wrong" to do so.

ashpublications.org/blood/a...

[Vindicatrix in reply to SofiaDeo]

Will do, as I want to know, what it is, and what it means, and if there is anything they can do about it.😀

[spi3]

My hubby started on Obinutuzumab and acalabrutinib in March 2022 - within 2 weeks he was able to walk again without a walker! and that June he started Venetoclax-(I call them his warrior Angels) -fast forward his blood had zero CLL and his bone marrow .0008 NMRD in August 2023 - we are having an other test in Jan 2024 to see if he is UMRD. I like to think that these immunotherapies act as yout DNA and give them a rest while they fight the CLL in your body. I'm praying you too have a quick recovery.

[Vindicatrix in reply to spi3]

That was so, heart warming, and reassuring, spi 3, yet another indication of the value of this forum, thank you so much, and enjoy a 'Merry Xmas' and a riotous 'Hogmany'🤪

[spi3 in reply to Vindicatrix]

May you, too, have the Merry-est Christmas!