I’ve been following this forum for a while, since my mom(she is 60 y.o.) was diagnosed with CLL 4 years ago. Her initial WBC was around 20.000. She has been on W&W schedule for all the time. Never got any treatment. On last visit to our hematologist, he told us that the time is come for treatment! Although, she has no any symptoms (fever, fatigue, night sweats etc.) or signs (Hb and PLT levels are normal, no significantly enlarged lymph nodes, however she has several LAP’s), just because WBC doubled in the past 6 months (from 100k to 200k), treatment scheduled for next week ( CR - Cyclophosphamide + Rituximab for 3 weeks).
Despite the fact that, I’m also doctor, I’m quite worried with the particular treatment protocol. I would like to hear from you guys. When I see many people in this forum living with CLL for many years, it kinda gives me a strength and endurance.
My mom is positive for 13q mutation. She has no other kind of mutations. Last USG scan revealed some hypo-echoic areas in the spleen. Our hematologist told us not to worry but he ordered MR scan, just in case.
After giving some info about my mom, I would like to ask couple of questions to you guys;
1) My mom has been using Ganoderma (Reishi mushroom) products, which is I’m oppose to, but she hopes help from that. I worry it could be the reason of the rapid increase of the WBC’s. Do you guys have any opinion on the effects of Reishi products?
2) As a doctor, I know that nodules in the spleen might be associated with CLL or any other malignancies (lymphoma). Has anyone have splenic nodules ? Any experiences ?
3) Can I get advises and experiences from patients who started their treatment with CR protocol ?
I respect and love all of you guys. I wish all the best for you guys. Thanks for all the answers in advance.
Edit: *CORRECTION*
Today, I talked to doctor. He told me he meant Chlorambucil, not Cyclophosphamide. He wants to start Chlorambucil + Rituximab.
Sorry for mistake. I confused
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Did the option of also including fludarabine also come up? FCR can be effectively almost curative for many patients. Ie it can give really long remissions that for some mean they never have to be treated again. There may however be a specific reason not to use F in your mums case of course and I can only talk generalities not specifics.
Presumably the assumption is that if she has doubled lymphocyte count in the last six months she will again. Some might want to just check that trajectory before treatment but obviously we don’t know how Long she’s been on that pathway. When was she at 50,000 for example?
In Turkey are you able to get ibrutinib or venetoclax perhaps after an initial go with chemo?
Here in the UK unless you have a 17p deletion or a TP53 mutation (can you get tests for that?) or a clear medical reason not to go for FCR that is what you’d usually be offered first. Then if needed Second line treatment wirh either ibrutinib monotherapy long term or time limited rituximab plus venetoclax.
Did you see a CLL specialist? It might be worth looking at expertscspe to see who the top CLL doctors are in Turkey for a second opinion.
Adrian thanks for answer. Our hematologist is among the best Hematologists in Turkey. That’s why we trust him so much. He has been following my mom for a past couple of years. He is actually not a fan of drug therapy. However, on the last visit he told us that WBC is increasing and we should stop it. I know that FCR has been routine procedure for the first line treatment of CLL. Actually, I saw the results of one of the recent randomized controlled trial which compared FCR versus Ibrutinib+Rituximab. IR seems to have better outcomes in terms of progession free survival and adverse effects. Unfortunately, Turkish Healthcare does not pay for Ibrutinib unless you try first line protocols. You can get it by yourself but it is too expensive to afford for years. That’s why he chose to start with FCR, but without F, because the fact that F really depletes T-cells and makes immune system very weak, he does not want to give it. He does not want to weaken my moms immune system among the COVID-19.
Last year this time, her WBC was 70.000, then it started to increase gradually. It became 80k, then 90k, then 110, then 140, then 160, then 180 and finally 200k this month. From 70k to 110k it took around 6 months. From 110k to 200k it took another 6 months. She was diagnosed in late 2016. First 3 years increase of WBC was slow ( 20k to 70k in 3 years).
We have done all kind of genetic tests (p53, 17p, trisomy, 13q, other kind of translocations and mutations related with CLL etc.) she only has 13q, as far as we know. Hematologist ordered another p53 test, in the case of new mutation.
However, nodules in the spleen makes me really sick. I started to be anxious about second cancer, like lymphoma. We will see what MR scan reveals.
Interesting choice. Chlorambucil is not widely used now as it is still chemotherapy but not as strong as FCR. It has been shown to be less effective than the other drugs. However it may be that he is thinking that if he used that combo it would cause less side effects than other chemo and should at least reduce the count a bit (rituximab does that well for sure and this treatment sounds like it would also allow her to qualify for ibrutinib funding.
There are differnt philosophies of treatment. Some want to try and hit the cancer really hard and possibly even cure it. For sure FCR can do that for some. But it comes at a cost of side effects.
Ibrutinib is more about keeping the cancer at bay but not really aiming to destroy it as such. But typically it comes with less side effects though you have to put up with those side effects for longer.
As a matter of interest is venetoclax available in Turkey yet? That is an interesting option as in some ways it works more like chemo (ie it destroys the cancer and in combo with rituximab or obinituzimab can less to the same long remissions that in some people begin to look rather like a cure) but in many people has even fewer side effects than Ibrutinib and is often given in a time limited way.
In short chlorambucil is a recognised treatment sometimes still used (as is also bendamustine) as an alternative to FCR that is felt to be less effective but better tolerated.
I totally agree with your statement. He wants to stop WBC increase but he also wants to avoid side effects. This is why he chose Chl-R instead of FCR. I checked some papers which showed Chl-R was effective treatment protocol in patients with CLL who are elderly and/or unfit. As you said, FCR is better protocol, however at the cost of side effects.
I also agree that he is preparing her for the possible use of Imbruvica in the future.
In terms of Ventoclax, I can say it is available in Turkey but I read the prospectus of the drug which basically says, ventoclax is used in patients who already failed certain cycles of chemo-immunotherapies or in patients who have 17p, ZAP70 and etc. mutations. Moreover, the price of the drug seems crazy, even more expensive than Imbruvica. In our case, I think it would be the last choice, if other treatment protocols (including Imbruvica) fail.
No problem. The only thing to bear in mind wirh venetoclax is that it is usually time limited (one to two years typically with either rituximab or obinituzimab) whereas ibrutinib may be given for ten years or more and doesn’t continue to work if stopped. But it sounds like in Turkey they haven’t yet licensed it for the earlier use. Most cll drugs are initially licensed say for third line then move up the ranks. Certainly that happened here. There is currently a license but no NHS funding in the Uk for venetoclax plus obinituzimab firstline and NICR is considering it.
The take home message is that things are changing all the time and there are lots of options that will work.
If your goal is simply to buy some time with this initial treatment and reduce the count then that is fine as long as you appreciate that it will not likely give a long remission which some other drugs might.
Whatever happens in the western countries in terms of novel treatments, comes here 5-10 years later. Ventoclax is available in Turkey, but probably not licensed for earlier use, as you said. It may be a good choice for rich individuals or people with broad private insurances.
1) Some patients (around 1%) actually can have their CLL stimulated by the beta glucans in mushrooms, including reishi mushrooms. healthunlocked.com/cllsuppo... While not likely, it's possible that the reishi products are causing her rapid doubling time. I hope you can convince your mother to stop taking the reishi mushroom product and have her specialist monitor her for a while longer.
2) The lymphocyte doubling time is the least important of the reasons for starting treatment. CLL specialists look for other confirming indicators that treatment is necessary: healthunlocked.com/cllsuppo...
3) I've not heard of CR treatment, just FCR or FR with the latter given sometimes in Canada. There was even a comparison trial between FR and FCR: clinicaltrials.gov/ct2/show...
I’m trying to convince her to stop taking Reishi mushroom products. I read some papers which showed it’s effect on the lymphocytosis. Some papers suggests it increases NK cells and boost immune system. However, there are no significant clinical investigations. I’m really suspicious about it.
Yes, I know that, WBC count alone is not a indication for treatment. He also did not want to start treatment. However, when he checked the results of last 6 month. He told us, WBC does not seem to stop, it increases rapidly and will increase more&more and we should stop it.
He did not want to give F, just because do not want to deplete T cell count among the COVID-19 pandemic.
I couldn't recall anyone mentioning Chlorambucil plus Rituximab, but a search did find this one mention from 3 months ago: healthunlocked.com/cllsuppo...
Hi there, your mom is still young and should have many more good years ahead of her.
As you are a doctor, sensible and caring I’m going simply give you the iWCLL guidelines for treatment. Please come back to us if you need to but these will give you a basis for some discussions with your mom’s doctor.
I am 13w mutated. After 12 years on W&W I started chemo FCR IV. I became anemic, nodes got bigger, WBC 225k - even tho I felt fine my BMB said my marrow was full. Got my port and only needed 3 rounds. In remission 2 years.
Definitely needs to stop the mushrooms. I don't understand about why F would not be considered. Covid should have nothing to do with that. We are immune compromised to begin with. She needs the proper protocol. Would a doctor skip F during cold/flu season ?
I would get a second opinion. There are many wonderful CLL experts in the USA that don't agree. I got 2 second opinions before I started treatment. Fortunately all 3 of my doctors agreed.
Hi! I’m very glad to hear you’re on the remission! I hope you will stay on the remission forever!
I’m trying to convince her to stop mushrooms products. In terms of use of Fludarabine, since I’m not hematologist, I’m not sure about how to choose correct CLL treatment protocol. I have checked CR protocol on internet, but only thing I could find is FCR. I asked him about Fludarabine but he told me CR will be fine and Fludarabine would make her susceptible to infections. I definitely take 2nd advise from different doctor.
A doubled ALC is the weakest reason to treat. in the absence of any other signs of symptoms. Many benign cases for the finding on the spleen. Should also have IgVH mutation testing done before getting any chemo-immunotherapy because if she is un-mutated any remission is likely to be short lived. CR is not used at all in the US and most of Western Europe. Much prefer she got a targeted therapy. Stay strong, We are all in this together. Brian
Chlorambucil is less toxic and less potent than cyclophosphamide, probably because it is used at a much lower dose and is taken orally. Still it is an alkylating agent, works by messing with the DNA, immunosuppressive, and increases the risk of deleterious mutations. Some folks do very well with it, but it is not standard of care in the USA. Combining it with obinutuzumab rather than with rituximab adds oomph if that is an option. In that case, I suspect most of the benefit seen is from the antibody, and not the chemo, so I would be tempted to leave the Leukeran out.
I have had CLL for 31+ years with 17 years of Chlorambucil (Leukeran 2 mg. once a day) off and on as counts required. I was extremely happy with that...no side effects and it brought my numbers in line quickly. At the time there was very little to offer in the treatment line. A huge plus was Leukeran wasn’t so pricey. Then I needed treatment again and they thought the Imbruvica would be a good change.
I was on Imbruvica 420 for 6 months and it was working great for me until I developed 2 types of pneumonia in both lungs at the same time and they pulled me. I have been back to Watch and Weight and holding for 14 months.
I guess what I am trying to say I would go back to Leukeran in a heart beat.
We are so very fortunate to now have so many options! The very best of luck to your Mom and to you her caregiver!
Just my two cents but my husband has gotten a great response from Gazyva which is the next generation of Rituxan my husband has done very well for over six years being treated several times with the Gazyva He always was given chlorambucil with it but depleted his neutrophils count. Right now we're supposed to start Venclexyta with it but is doing well with a Gazyva alone. I wish you well with this treatment course
I’ve been living with CLL for 22 years. I have had two treatments for it : Chlorambucil and Rituxan about 13 years ago and reduced Fludara/Rituxan 10 years ago. Both were started because of a rising WBC. CR was easy and reduced the tumor load very quickly. But I wonder now to what purpose. Counts started to rise immediately after stopping. With hindsight I think I should not have been treated on either occasion.
I have lived with a WBC count varying from 150,000 to almost 300,000 for years now. I will be starting V/O in the near future because of nodes. Good luck to your Mom
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