ALERT: avoid this post if you are the kind of person who does not want to know about statistics and odds of disease progression. This is deliberately an unlocked post so do not share your own results in the comments section unless you are happy for them to be shown in google search results. Feel free to Direct Message me if you want to discuss this post more privately.
Although it seems it’s not in routine use yet, and doesn’t necessarily influence treatment decisions I share a link below to a prognostic index for CLL. You can take the test and identify which risk group it places you in.
A large study of thousands of patients from before the use of more modern specific therapies was used to create this index. It came up with a clear way of categorizing patients into very high, high, intermediate, and low risk groups. This has been confirmed to be useful twice since in different studies.
There is an online calculator that can be used to identify which risk group you fall into. This risk group influences the length of time to when you need treatment and survival rates.
Be wary of the survival rates since they may well be too pessimistic in the modern era. All the signs suggest that these results may well be much better in the era of FCR, Ibritunib, Venetoclax, other agents, and stem cell transplants where needed. And, whilst FCR doesn’t seem to work for high risk patients, other treatments do often work very well, so this survival gap may well narrow or even disappear in the future. It is vital to remember when assessing data on survival that by definition it is old data on the day it is published, especially in a period of time when new better treatments are being released all the time and we are getting better at knowing when and how to treat our disease in all its manifestations.
The risk stratification should still help predict who is most likely to need treatment soonest. But don’t be overly alarmed if you are high risk or overly reassured if you are low risk. Some high risk patients will still not need treatment for years and some low risk patients may need treatment quickly.
There are five critical variables, the data suggests nothing else matters much in predicting prognosis:
•Age (with over 65 being slightly worse)
•Clinical stage (with advancing stage making the prognosis slightly worse)
•serum B2 microglobulin (with levels over 3.5 having a significantly worse prognosis)
•Mutatation status with unmutated status having a significantly worse prognosis
•TP53 mutation or /17p deletion with either or both having a very significantly worse prognosis.
One of the variables I don’t know the result for me personally, and am not sure if I’ve been tested for or not (serum B2 micro-globulin). Is that a test others have had routinely?
I ran the test twice once assuming low levels of my missing result, and once high. Because of my other markers this single item would push me personally either into the high or intermediate risk group (it might not be so important for you). This did make me want to check with my team if that test has been done on me already.
There are links to the original papers. On the MD Calc page, perhaps the most interesting of which is the Danish population study which was done after the advent of FCR and shows reasonably good survival rates even for the very highest risk patients.
The real problem with these types of statistics is they are only valid in groups of people....it is like saying if you walk slow, don't look both ways carefully you will be run over by a truck in 4 years....that certainly could happen...and even be likely....except maybe the car that was suppose to run you over has an over cautious driver who stops and lets you cross the street...so I dunno....do you start the clock again at that point....missed KaBlaaam all together ....and now have to worry about sharks....There are so many ways to meet our maker...CLL is just one of bazillions. I just can't worry about any of them because it is way above my pay grade....
Totally agree with the caveats. But for some reason I find it strangely comforting to know in which risk cohort I am. It doesn’t eliminate the uncertainty for sure. But it just feels like it’s a bit of a handle on it. I have a strong sense that I will need treatment in the not too distant future despite my risk grading, however. This is just because of the number of problems I’ve had this last year, and the sense of deterioration in my fatigue levels, some growth in lymph nodes etc. I suspect that trajectory of disease is very important here. Which is why a sage experienced CLL patient suggested in a group I was in that the doctors have a much better idea about how your cll will progress when you make it to about eighteen months....so I’ve got a few months yet to hit that milestone.
I did not mean to suggest you could not cope with and handle the CLL issue in your own way. I apologize if I came across like that. For me, I don't worry much about TFT/OS issues...I tend to read all kinds of medical literature (much not even CLL related)...the reading of which freaks me out usually.
It is definitely important to learn about, and understand CLL and the possible progression...no question.
I don’t think we disagree at all Scott and I certainly wasn’t offended. I guess as a doctor by background (not a haematologist) I’m always going to be a bit of a sucker for data and attempts to at least pretend to understand. But you are dead right. The biggest challenge in cll is learning to live with an uncertainty we should really have already had. One of the reasons some of our friends and family find it difficult to talk about CLL is that they aren’t comfortable facing up to potential mortality and even morbidity. I know I wasn’t before my diagnosis
Oh, you are a doctor....sorry I call you a whitecoat :))))
I understand what you say about people finding it difficult to talk about...I am thankful I have both my wife and sister who know if I want to talk about it and if so, are happy to listen to me without feeling awkward. Both understand I am not worried about the CLL in a life ending way...more of how it has impacted me now way...and I am fine with laughing about it.
I’m a psychiatrist who then moved into pharmaceutical Medicine. I’m officially still the medical director for a Pharma company but am on long term sick leave. I’ve run a lot of clinical trials and understand the process of getting a drug from the test tube to the market place including dealing with pricing and reimbursement.
BIG DATA like these are what we should cherish and support ~~ even while being focused on one’s personal circumstances.
Big Data bring several advantages over the micro-perspective available from speculations based on one’s own personal data. This is because group data smooth-out the peculiarities inherent within individuals and produce a risk-analysis based on a cluster of people with similar characteristics. Big data allows for comparing oneself to peers with similar prognoses, trajectories-towards-treatment, and lifestyle factors.
Only with such macro-scale data are we able to:
1. Better analyze the impact of social factors that contribute to disease progression ~~ e.g., nutritional status, the stressors on the body of having an outlier BMI, exercise regularity, etc.
2.Make better decisions about when-to-treat ~~ since group data deemphasize the idiosyncrasies within each of us, as individuals, and focus on the ‘big-picture.’ These decisions are less likely to be influenced by ‘what has worked in the past’ for a particular physician ~~ thereby reducing the inherent (but unintended…) bias in those physicians who select only from a small subset of all the treatment options available.
3.Access stronger justifications for a wider spread of effective treatments than those based largely on local regulations that may be overly influenced by cost-factors. Decisions to withhold diagnostic or treatment options become less viable when multi-nation data demonstrate the value of early marker-identification and a full array of treatment options. For example ... We frequently read in this HU-CLL mention that in some countries the CLL-person has no access to identifying markers for the deletion of 17p (FISH) or TP53 mutation (sequencing) until immediately prior to treatment. And, in some countries access to novel agents is closed because of political/cost factors. With access to BIG DATA these practices are <less supportable> because the data from other settings point to the enduring value of early access to diagnostic indicators and a full array of treatment options.
4.Group data are critical to assessing the viability of new treatment approaches. Efficacy, effectiveness and utility assessment of new treatments in clinical trials <require> careful control of as many factors as possible so the clinical scientists can determine whether or not for a GROUP of people a medicine ‘works.’ Individual data are by their nature representative only of a single, anecdotal data point. If something ‘works’ for me then it’s largely unknown whether or not a mediating variable within me was the critical catalyst that brought about success (or failure). But, if that same medicine works for 100-people ‘like me’ then my personal idiosyncrasies are likely not an influence on whether I reach minimal residual disease.
Large data sets and the prognostications available from them are weak determiners for what may be best for an individual, but what they’re wonderful at doing is to classify folks into bands-of-risk ~~ just as this tool attempts.
The problem with this data is that we are not comparing like with like. The data sets they are referring to bear no resemblance to practice these days so are worthless when looking at survival.
I really hope and suspect that the survival rates will definitely improve. The time to treatment rates I guess will be more likely to stay the same. Also, however, since 50% of people with cll die of an infection and the treatments don’t actually improve our immunity I feel we need to become much better at managing infection risk than we currently are.
I'm not sure how useful this prognostic index is in predicting survival as it is based on data from chemoimmunotherapy since 2008. "Our data presented here provide the basis for external validation of the CLL-IPI in a population-based cohort exposed to chemoimmunotherapy."
The new targeted treatments have completely changed the landscape of CLL treatment and, I would suggest, any previously published survival data based on chemoimmunotherapy is out of date and no longer applicable.
This report from a year ago shows that even R/R high risk patients have survivals longer than those quoted in the Blood report.
I agree the time to treatment is not likely to change much, but given the data was collected from 2008, those that were treated would have had chemotherapy. Most importantly, these statistics are for groups. As individuals, we don't know whether we will be creating one of the early or late steps in the curves.
Yeh. This is always the case. Doctors deal in probabilities all the time. We are told things like “most people with cll are over 70” but that’s no comfort to those of us who are way younger.
Not very comforting to those of us who are over 70, Ha Ha. The difference affects your out look and I tend to go along with Scotty. Time to treatment understanding is important to me because I have many things to get done for my family's sake. Putting that aside, being over 70 means that I have had a good life knowing full well everybody passes and we will all cross that path. I feel sorry for those under 70 as they will stress over CLL and it will impact their lives. You rarely see posters here who are over 70. Maybe because they are not as comfortable with computers as I am or they have other problems bigger than CLL? May God Bless all of you and shoulder some of your worry.
Soo true! I'm 52 and was diagnosed 1 1/2 years ago. WBC was elevated each lab results 3 yrs prior. I'm very uninformed about my diagnosis. Treatment plan is watch & wait. Have troubling symptoms but told that I'm good. Looking for second opinion. Any suggestions? I live in the Philadelphia area.
While you have included plenty of disclaimers, I doubt they will be absorbed by many readers. As you noted a large study "from before the use of more modern specific therapies was used to create this index." It doesn't even include FCR or BR, so that means that very few of us will actually have treatments on which these survival statistics were determined! We know that survival times have improved - even before FCR. I also believe that well informed members of this community will have much improved survival times, just from being an informed patient.
Realistically, all we need to do is survive long enough to be able to access the better treatments/cures? currently being developed.
Absolutely. Having had a horrible pneumonia which my docs said could easily have killed me which was what prompted my diagnosis, I do think we need to be doing more as a community to think about ways to reduce infection risk and how to manage infection when it comes. So for example my GP and I have decided between us that we will have a rather low threshold for antibiotics for me...but we weren’t told to do that specifically by my Consultant.
The CLL specialist who diagnosed me and thought my chances of a long w & w were good, even possibly in the 'treatment will not be required' sector, was specific in saying that antibiotics should be used sooner rather than later in the case of infections.
Hi Adrian, Have you been offered ivig? I have immunaglobulin infusions every 4 weeks and I have been well apart from urine infections. I take a small antibiotic daily to stop these. With the promise of new drugs I was full of hope for the future. That was before I found out that the Nhs will most likely refuse to give me Ibrutinib. I was in remission for 5yrs and 2 yrs later I am heading for more treatment. Im 60 and the new rules will exclude me. Anne
Hey Anne. Are you in contact with the journalist, Mike, and the patient groups about this? We need more people to speak up about it. Also contact your MP. I’m apparently not at the stage yet where immunoglobulin infusions are justified. My count is below normal (5) but my understanding is it has to get lower than that.
Hi, I have signed an online petition. I havent been told that I wont get Ibrutinib but consultant has said how well Id done on Fcr. I dont know who the journalist is. I was daunted about writing to my MP but I know Im being stupid. Anne
Did you have any warning you’d be one of those who transform? Were you 17p deleted for example? Having done some digging do you get the feeling transformation is more common in people who have chemo?
Slightly cheeky thought. Right now might be quite a good time to get a annuity when it comes to retirement time if you have CLL. If the pension funds treat us a bit like we are smokers and give us a reduced life expectancy they may give us an increased annual income based on our capital...which if treatments are as good as we think they are will work out very well for us!
No warning... I'm FISH normal... mutated... no symptom indications, B2M was fine LDH high normal... just had finished treatment with FR and felt great... clinical CR.
Then transformed.... BANG💥💥💥
Treatment does increase risk, but so does, age and length of watch and wait... 40 % transform prior to any treatments...
13q mutated fairly low rate of transform, but trisomy 12 with a NOTCH1 mutation, are higher risk, as are 17p and TP53, c-MYC, VH4-39, complex kareotype etc.
The rates of Richter's in novel agents is about the same as chemo, but still pretty early...
If RT is in the cards...you play the hand... huge unmet need and quite poor understanding, but things have improved a bit...at least we aren't excluded from every clinical trial, just some...
Based on information available in 2008. Don't think this tells us anything more than the Rai or Binet systems. Some patients follow predictable patterns and some don't and charts and graphs, especially those based on data more than two years old don't tell us any more than the old ones did.
Find a specialist who knows what's available for you today. Someone forgot to tell CLL cells how they are supposed to behave, which makes these predictions worthless for each individual!
The Danish study replicated this basic risk stratification system. Actually I don’t think we should ignore all this. It is unlikely to be irrelevant in the modern era especially in time to treatment. And it neatly has identified the five items that are pointers to likely speed of progression.
It may get used in clinical trials first, but it will be a while before it is used much in the clinic... just too new and things take time to change...
It's a work in progress... There have been a number of prognostic initiatives, the Germans have their GO-GO system and MD Anderson has their own...
It's likely to be an evolutionary adoption... of the IPI. After all, Rai and now the modified Rai, and Binet have co-existed for 20 years...
Would be interesting to see the German and MD Anderson systems. Do you have links to that and the data behind them? What I like about this one is it actually is based on a large data set. And it allows some weighting to be given to the different factors. What doesn’t seem to me to be included but I suspect may be very important (tho difficult to measure) is the rate of change or trajectory of the illness. So for example for me I was very alarmed when I was first diagnosed and told I “probably” had CLL for years. Because I knew I’d had some screening bloods done for an insurance health assessment just a few months before. And I knew they’d come back normal. So I thought I’ve gone in a couple of months
from a normal white count to a lymphocyte count of at the time not far off 20. I thought that doesn’t sound too “chronic” to me! Then I discovered the health assessment hadn’t included an FBC and I hadn’t had one for a few years. That was much more reassuring. Then I heard about the idea of MBL and really slow growing cancer cells that can be hidden for years but still affect immunity...and remembered I’d had shingles twice YEARS ago. That made me think I’d probably been living with this for a very long time. Trajectory is surely everything.
How About this stat, 100% of everyone alive will eventually die. Find Jesus Christ and then live the Hell of of every day and love the heck out of People.
CLL is heterogeneous, diverse and fluid. Care is needed when extrapolating from the general to the specific, and vice versa.
Nonetheless Adrian, point well made with the indicator. My wife had Ca Breast 5 years ago, her risk indicator was crucial in choosing treatment options. Eg. Choose not to have chemo... against hosp advice. NICE dragging feet... we paid for the Oncotype test... which is now standard. So far so good! ...
Where does this leave us living with CLL? 50% die from infection. Is this something that needs unpicking? Is there data on which infections do the most harm, most prevalent? Is there any commonality? Are there too many of us not taking proper precautions? Could this area of care be better? Are there guidelines? I know friends with CLL who have a much more optimistic attitude to infection than I do... but I have seen sepsis - they haven't!
An important point for me is while deep remission may be gained my immunity will remain impaired. My neuts maybe plentiful but the T lymphoocytes not up to 100% performance... as my Haematologisr reminded me last week. What does that mean? Are there specific infections I am more susceptible to? Viral. Bacterial. Fungal. Will my Lyme Disease re-elected?
It's not something I can contemplate undertaking Just now having just done 4 weeks into FCR cycle 1 and having been severely neutropenic while wife and daughter suffering full on viral respiratory infections. I felt under siege.
What I want to to is get on my mountain bike and go riding off piste through the wilderness again. But do i have the courage? Already had Lyme Disease!
I am grateful for the diverse debate and sharing. There is only so much my family can take of my wild unfettered machinations, many of whom simply don't understand the implications of CLL, impaired immunity and arduous months on chemotherapy.
Thanks Jig. As I understand it pneumonia is the most common killer of cll patients. There’s a lot of data on how keeping up to date with the dentist can reduce the risk of pneumonia so on the basis of bacteria in the mouth can become bacteria in the lungs, there seems to be a consensus that treating throat infections with antibiotics is worth considering.
Certainly any temperature should be quickly checked out by a doctor in my view (and that’s something my Haem team definitely underlined). Fungal infections can also be an issue. I’ve already had a toenail infection and a lots of issues with persistent thrush. Some people seem to get cellulitis and osteomyelitis more easily. So again awareness of anything odd including specific areas of bony pain.
Vaccinations are critical and as early as possible. There are pinned posts on these.
Then we all have to decide how far we want to go with reducing our risks of catching infections from others. Some take this too far. Sadly there seems to be little clear cut advice on this. There are books which talk about precautions for neutropenia insourcing specific diets. But much of that is probably too much for us when we don’t have neutropenia.
Social distancing can be taken too far. But for sure I don’t see people who obviously have a cold or flu and I won’t sleep in the same bed as my wife or be within a few feet of any of my family if they are unwell.
Using a clean towel each day seems to help (passing germs on shared towels is a thing)
Hand washing done properly especially before eating. Hand gel.
Then food wise, avoiding things like blue cheese, Pate etc is probably a smart thing to do. But I don’t necessarily avoid everything on the list for neutropenic diets.
There’s a general consensus that things like saunas and steam rooms and anywhere which is damp or has lots of water droplets May harbor nasty fungus. Having said that apparently there are fungal spores in every breath we take. Which does make me wonder about those air purifiers for home.
The other big one seems to be a N99 mask 😷 I bought a Cambridge masks version from amazon which also has a valve to release air you are exhaling. I use this on public transport especially if it’s crowded and/or during the flu session.
We do have to keep living. So for example I’ve not stopped going to my large church and I don’t wear a mask there.
But remembering for all of us our immunity is somewhere between a normal persons and that of someone who is totally neutropenic and defenseless. And it’s hard to be sure where.
Prophylactic antibiotics have been talked about. I was told “you’ve had two life threatening infections. When you have the third we’ll probably put you on prophylactic antibiotics”.
Antifungals and antivirals are also used prophylacticly in some people.
But at the moment if I get a sore throat and tachycardia I just go on a course if antibiotics without worrying too much if it’s bacterial or not. Interestingly that fast heart rate also goes within a couple of days so it seems to confirm our assumption that it was bacterial in those cases.
I didn’t get a temperature for weeks when I had pneumonia but did when I was finally beginning to go sceptic. So I love my Apple watch as during that whole time it was showing me how I was having runs of tachycardia. So now if I get runs of increases heart rate I tend to see it as a sign like an increased temperature.
At some point antibody replacement seems a good idea. There’s some lack of Clarity on when exactly to start that. And indeed when it will be funded. Worth finding out the rules in your area and monitoring your antibody levels as they decline.
One of the problems we have is our sluggish immune systems don’t always respond very aggressively to illnesses. This can make them seem better than they actually are. So there maybe less fluid released into lungs in pneumonia and less excitement of the inflammatory markers and less neutrophil increase in response to infection. . Again it was only when I went sceptic that my inflamatory markets suddenly went through the roof. So the take home message is see a doctor at the drop of a hat. Having a good GP who won’t fob you off seems to me like a great strategy that will help keep us out of hospital. Select one at your practice and really get to know them and then you. That will help when things get hairy.
I'm a big of big data and this is interesting. However, I don't know how predictive old data can be, especially for high risk patients as it comes from an era before there was a decent treatment option for those with 17p deletions. Let's all defy the odds together!
Data like this is the best we have. But the great news is the new treatments are prolonging peoples healthy lives so yes the actual dates are almost certainly going to be better. But to maximize that benefit we are all going to need to be better at monitoring infection risk without being paranoid in my view. It’s infection that kills 50% of us not disease progression. And NONE of the treatments will help our immune system except in the case of reversing or preventing bone marrow infiltration thereby allowing more neutrophils to be produced. But all current treatments obliterate all healthy lymphocytes alongside the cancer cells so will make things worse immune wise. Hence the use of prophylactic treatments to prevent infection with ibrutinib in the FLAIR trial for example. We are all immune compromised to some extent from the moment we are diagnosed and in many cases before that. Which is one argument for early diagnosis by the way so we can take appropriate precautions.
I'm all for preventing infection and getting the best care, both of which I do. I just know when I was diagnosed in late 2015, my family read a lot of information online that made them think I should get my affairs in order and this was quite devastating to my then 16 year old, and continues to be. I am not in denial that things can turn around without any notice, but at this point, I'm doing great and am in better shape than most people around me-e.g. ran a 10 miler a couple of weeks ago. Statistically, I should be dead in 3 months. I just want to present both sides of the story. We should all be realistic, but remain optimistic and take action to be the outlier.
Totally agree. I’m losing weight deliberately (1.5 stone so far) but finding the exercise piece is much harder for me. I seem to be badly affected by fatigue and this has me really struggling with walking etc. Am determined to try and improve fitness levels but it seems a really slow process beset with set backs for me.
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