High deletion of 13q ??

[Cfarrar]

Does anyone know the prognosis for being 13q deleted by 85%? I have no other factors other than I am mutated. Just got two conflicting opinions and I would love some clarity. Thanks for your input!

[AussieNeil Partner Administrator]

What were the conflicting opinions? 13q del and mutated IGHV puts you into the best possible category and you may never need treatment.

Neil

[Cfarrar in reply to AussieNeil]

I guess the higher the % of deletion the worst the prognosis. Unfortunately that would include me since I have 85% deletion.

[AussieNeil Partner Administrator in reply to Cfarrar]

Have you found any studies relevant to non-chemo treatments which you would receive? The newer targeted therapies are game changers. Also, always remember that. CLL is an extremely heterogeneous illness and markers are only indicative of group outcomes, not that of an individual.

Neil

[Cfarrar in reply to AussieNeil]

Sorry but what do you mean by heterogeneous illness?

[AussieNeil Partner Administrator in reply to Cfarrar]

Outcomes with CLL are particularly diverse, from a few people needing treatment soon after diagnosis, to people never needing treatment. If you look at the scatter plots of markers vs time to treatment for example, (scatter plots are a tool for identifying possible correlations), you'll find there are points (representing patients) all over the place, not a tight, predicable grouping. That's why markers are only indicative of the more likely outcome for a group with those markers; they are not definitive.

[Cfarrar in reply to AussieNeil]

Thanks so much for explaining. You are super smart 🙂

[Luap001 in reply to AussieNeil]

I learned particularly from the Rosenquist presentation of 31 March that was posted on this site that not all IGHV mutations are favorable. It is in fact a spectrum. Some versions of the mutation are extremely favorable but there are others at the other extreme that are akin prognostically to a TP53 mutation. If I were mutated and due for testing ahead of treatment, I would ask for the detail regards the IGHV mutation. According to Rosenquist, only about 40% of the astronomical number of possible IGHV mutations have been characterized well enough to be placed into one of five categories according to prognostic significance. If your particular mutation has been studied, you would then have a more complete picture as it were and you never know where these things can lead. Perhaps, beyond prognostics, they may learn if there is any predictive value in terms of response to various treatments.

[AussieNeil Partner Administrator in reply to Luap001]

Further to my earlier reply above regarding the heterogeneous nature of CLL and your summary of the Rosenquist presentation, do keep in mind the relative frequency of these different mutations. Also, I've observed quite different conclusions when researchers have duplicated similar studies in CLL patients. That's to be expected when you consider the often small cohorts studied, along with the different genetics, treatment history, age and so on.

Neil

[Cfarrar in reply to AussieNeil]

I’m really not that smart 😕could you explain this to me in simpler terms?

[AussieNeil Partner Administrator in reply to Cfarrar]

Basically, CLL is a relatively rare cancer, so it is challenging for researchers to get access to a study group which is large enough for meaningful conclusions to be drawn from the study, particularly when you start looking for rare situations within CLL. You just don't get enough people with those specific rare markers for any meaningful conclusions. If you are studying just those with mutated IGHV, you've already eliminated half your potential candidates! You also get lots of what are called 'confounding factors', such as age, how long since diagnosis, the influence of other chronic health conditions, previous treatments, (which do leave their shadow in the development of harder to treat sub-clones, or variants of the original CLL clone), drugs (prescribed and recreational - the latter which may not be disclosed), fitness, diet and so-on. CLL progression has so many potential drivers, all competing for influence, some cancelling out and some working together, so it can be very hard to work out what specifically is the predominant influencing factors.

Finally, don't keep putting yourself down. I'm sure you have skills I don't have!

Neil

[Cfarrar in reply to AussieNeil]

Well I can make a mean lasagna 😊 thank you so much for explaining this to me it’s very kind of you. Are you in the medical field you seem extremely knowledgeable.

[AussieNeil Partner Administrator in reply to Cfarrar]

There you go! I've been reading up on medical research while you've been perfecting your cooking! When I was diagnosed with stage 4 CLL/SLL over 12 years ago, there wasn't much in the way of treatment options, so I decided to learn what I could about how to live well with CLL and pass that knowledge on to others who were prepared to become involved patients. My mother was a nurse and encouraged me to read her medical text books, but I figured I wasn't smart enough to become a doctor .

[Cfarrar in reply to AussieNeil]

Well your years of study are a blessing to so many I'm sure, so as one recipient I thank you for caring about others and taking the time to give helpful information. I'm so encouraged that you have lived with CLL for so long. Are you from Australia ( wild guess). How have you handled treatment if you don't mind me asking.

[AussieNeil Partner Administrator in reply to Cfarrar]

Select my avatar to read my bio

[Cfarrar in reply to AussieNeil]

Wow Neil, I just read all about you, what a journey you have been on! You have done such an amazing job of documenting it. Thank you for letting me read and learn from you!

[cajunjeff]

There is a study out there which suggests that deletions of 13q greater than 70% confer a worse prognosis than smaller deletions with shorter time to treatment. Even if true, it might not put one in a bad category, just the bottom end of the good category.

Another study seemed to say a high deletion of 13 q is bad for other bcell cancers than Cll, but not bad for Cll. I have linked you to both studies.

Cll markers do not always accurately predict the course of our Cll. The most important marker to many doctors is mutation status. So I would think even if you progress to treatment faster, you still should do well. 13q Cll responds well to most all therapies.

pubmed.ncbi.nlm.nih.gov/215...

pubmed.ncbi.nlm.nih.gov/284....

[Tortola2019 in reply to cajunjeff]

I've read a bunch of studies that look at various factors in patients presenting with "only" a 13q14 deletion. I believe "tumor load" looks at the % of your CLL cells that have at least one chromosome bearing the deletion. I believe "bi-allelic or mono-allelic" refer to whether your cells typically have both #13 chromosomes affected (homozygous 13q14)) or heterozygous for the deletion (where one chromosome looks normal). Finally, 13q14 deletions are quantified as small or large depending on how many genes are taken out beyond the minimal critical chromosome interval (containing microRNA-15a/16-1 gene cluster). Mine removes 3.2 million bases including an important tumor suppressor gene (RB1), while others take out a thousandth of that! The data do look like a scatter plot in each of these papers with patients requiring treatment in each category. Indeed, the statistical data offered in these publications are often at the cutoff for what is "publishable" (95% confidence). See for example molecularcytogenetics.biome... their p=0.05 leads them to conclude high tumor burden is worse than low)

Interestingly, there are many people with MBL carrying 13q14 deletions that will never progress to CLL, much less need treatment. Alternatively, there are many other more aggressive hematological cancers statistically associated with 13q14...

I believe you can't predict your CLL disease course based on these 13q14 characteristics, but the odds are relatively good if that is your sole chromosomal aberration .

[Cfarrar in reply to Tortola2019]

Thank you so much for that information

[Mldeterm in reply to cajunjeff]

Lower end of a good category to be in is exactly as it was explained to us. Great links, thanks for sharing.

[GMa27]

I am 13q mutated. Was told by many specialists that I have the best markers. I enjoyed 12 years on W&W and after 3 cycles of FCR, I am in remission. Hopefully you have a long uneventful W&W. 💕

[Cfarrar]

Thank you for this!

[Big_Dee]

Hello Cfarrar

Your results look good to me. When I was first diagnosed I was 13q deleted 53% and un-mutated. My CLL was very aggressive and I required treatment in 14 months from diagnoses. I had 4 DNA genetic tests. As stated I started at 53%, then 67%, then 87% before treatment and then 13q normal after treatment. All of this within 15 month period so it will raise and drop if/when you have treatment. Blessing.

[Mldeterm]

My husband is high percentage 13q- and mutated. He started as SLL but progressed to treatment in 3 yrs. Our specialist said high percentage would correlate to an average faster time to first treatment but that he should have a good result like lower 13qs with any treatment we chose. He went with a novel agent combo trial and is off all meds and MRD-. Good luck to you!

[Cfarrar in reply to Mldeterm]

What percentage was he? What is SLL

[Mldeterm in reply to Cfarrar]

He was in the upper 80s in percentage at treatment start in May 2019. It went up as he neared treatment. SLL is the same disease as CLL but is titled that when prominently in the lymph nodes and ALC is less than 5 (WBC x Lymph %).

[Cfarrar in reply to Mldeterm]

Thank you so much for this information!