ASH 2019: A Clinical Trial of Cannabis As Targ... - CLL Support

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ASH 2019: A Clinical Trial of Cannabis As Targeted Therapy for Indolent Leukemic Lymphoma

avzuclav profile image

"Conclusion

:

This study demonstrates that it is safe to administrate a single dose of Sativex to elderly patients with indolent B-cell lymphoma with regards to adverse events. We show that the cannabis compound quickly reduces lymphoma cell numbers in peripheral blood. There was no evidence of activation of caspase 3; this suggests that the reduction of lymphoma cells in blood might be due to redistribution from blood rather than apoptosis. We have also detected an apparent circadian rhythm of the peripheral numbers of malignant lymphocytes.

Our findings suggest that the drug might promote homing of lymphoma cells from blood into secondary lymphoid organs where they receive pro-survival signals. Therefore, this cannabinoid compound should be used with caution in patients with indolent leukemic lymphomas. Further studies are needed to dissect the signaling pathways affected by cannabinoids in B-cell lymphoma."

source:

ashpublications.org/blood/a...

41 Replies

Wow. That is soo interesting. Hope everyone will read this carefully.

I figure even if any of these supplemental drugs work they are killing off the easy pickings. Will leave room for the meaner clones to take up residence.

So does this translate to no cannabis use ? Thanks !

cllady01 profile image
cllady01Volunteer in reply to Shrink

Yes, Shrink. Looks like a no-go for CLL. It says the med. causes the CLL cells in the blood to seek out another place to hide where they can continue to live and grow.

jijic profile image
jijic in reply to Shrink

Whoops, too late for me!

Thanks for sharing this. I’ve been using cannibus to help me sleep, I guess to play it safe I should try something else. Yeesh.

AussieNeil profile image
AussieNeilAdministrator

This paper concludes that cannabinoids most likely encourage lymphocytes to move to the nodes and spleen where CLL cells will survive longer and propagate. We've known for a long time that CLL cells are at their most vulnerable in the blood, so if we want to reduce our tumour burden, we actually want something that has the opposite effect. That's in part how Ibrutinib works and why about two thirds of those taking Ibrutinib see their lymphocyte counts increase initially!

The trial patients are nearly all early stage CLL patients. Phrases that jump out are "The larger median nadir on treatment day was not due to increased cell-death as measured by activated caspase 3", (hence the conclusion that "Our findings suggest that the drug might promote homing of lymphoma cells from blood into secondary lymphoid organs where they receive pro-survival signals". which is exactly what you don't want, and hence "Therefore, this cannabinoid compound should be used with caution in patients with indolent leukemic lymphomas".

Also "Changes in clonal B cells were the same as in lymphocytes", and "The cannabis compound reduced lymphocyte levels both in CB1-positive and CB1-negative lymphoma" are consistent with what was presented in the paper Cannabinoid Receptors Are Overexpressed in CLL but of Limited Potential for Therapeutic Exploitation, from PLOS1, June 2016: journals.plos.org/plosone/a...

From the Discussion section: "While we did find that cannabinoids reduced viability of CLL primary cells considerably independent of CNR mRNA expression, we found healthy cells to be affected to the same degree. Thus—and in contrast to other malignancies—our data suggest cannabinoids to be of poor therapeutic potential for treatment of CLL..."

I've wondered if there are any natural substances that encourage the movement of B-lymphocytes between lymphoid organs and peripheral blood, as Ibrutinb and other BTK inhibitors can do, so it is interesting to find one that does the opposite. This also highlights why any assessment of any treatment needs to look at more than just changes in the lymphocyte count and should determine what's happening to the tumour burden and the subsequent impact on other blood counts from possible increased bone marrow infiltration. Makes me wonder about how many people who claim to have found an alternative treatment that lowers their lymhocyte count, are actually making their CLL worse!

Neil

Benlewis profile image
Benlewis in reply to AussieNeil

Neil if Lymphocytes survive longer in the nodes and spleen and are more vulnerable in the blood, then wouldn’t that mean that SLL (where lymphocytes tend to be in the nodes) is potentially a more serious condition than CLL (where lymphocytes tend to be found more in the blood)?

AussieNeil profile image
AussieNeilAdministrator in reply to Benlewis

Indeed an "SLL" diagnosis has an associated poorer prognostic outcome than a "CLL" diagnosis. Part of that can attributed to the typical later stage of an SLL diagnosis, but not all.

Interestingly, it was only determined several years ago that CLL cells in the blood are in their dormant phase. It was thought by extrapolation that this was also the case when they were in the lymphoid organs. (It's much easier to obtain CLL cells for research from a blood draw than by doing a node biopsy). It has been known for longer that CLL cells set up a protective microenvironment in nodes and bone marrow, which is why they are harder to kill there.

Neil

Benlewis profile image
Benlewis in reply to AussieNeil

Very interesting. Thanks!

I didn’t know that.

It is so true about being diagnosed later if the CLL/SLL presentation is in lymph nodes mostly and,like mine are abdominal and pelvic cavity,

it takes time to diagnose as there is a lot of room to grow.

Does this mean that my CLL/SLL started in the lymph nodes before it showed in my blood? I never thought to ask about it.

Good luck with your treatment Neil.

Dana

BluMts profile image
BluMts in reply to studebaker

I had a similar situation to you. Yes, you are correct. And very correct about being diagnosed late as a result. Though have to say that if years and years ago I had seen the specialist who finally understood what was going on, think he would have diagnosed correctly back then.

AussieNeil profile image
AussieNeilAdministrator in reply to studebaker

Thanks :) .

Yes, SLL generally starts in a node and CLL in the bone marrow. SLL is potentially curable by radiation treatment if it is limited to just one node or a few nodes close together.

Around 15 or more years ago, I noticed a lump pop up on my thigh, which my GP dismissed as harmless, but was subsequently identified by my haematologist as a swollen lymph node. A few years later a blood test showed neutropenia, which was ignored by another doctor. It was just below the lower reference range at 1.6, which indicated that my bone marrow was becoming significantly infiltrared. 2.5 years later, my neutropenia worsened, dropping to 0.4 by the time I was diagnosed with CLL/SLL via peripheral blood flow cytometry.

MyRoc profile image
MyRoc in reply to AussieNeil

Neil, thank you so much for yet another eye opening analysis! I have recently started mixing a little cannabis oil into linseed oil as a ‘body rub’ which has been great for dry skin. Do you think I should stop even though it’s an external application? I noticed new nodes running along the creases at the top of my leg last night after doing a 4 day fasting mimicking diet (and stopping Budwig for that time) 🙏🏻

AussieNeil profile image
AussieNeilAdministrator in reply to MyRoc

I don't know how absorbent the oil is when topically applied, but it should be a safer means of use than orally. It would be interesting to see if the new nodes shrink after a break from external application.

Neil

I’ve been taking high strength CBD oil for about a year before my CLL diagnosis because it has an amazingly positive effect on my arthritic knees and I’ve continued to do so. I now know I’ve had very low levels of CLL for about 6 years so I’m not connecting the CBD oil with a trigger but it’s upsetting to think it may be making it worse! I know what my knees feel like when I stop taking it. It’s frustrating enough to be told I’m ill but there is no medicine to help and now something I considered to be not much more than a food supplement is actively bad for me. My wbc count has stayed static since my diagnosis in February and I put that down to all the healthy changes I’ve made to my lifestyle whereas in reality the CBD oil for my knees might have been skewing the results and actually making it worse 🥺

Hi Pumpkin, I'd continue doing exactly what you've been doing. Quality of life should be the primary concern of us all in my opinion. My disease has been nodal since day one prior to using canabis product and continues in the same vane. Canabis improves my quality and it's obvious to me and my doc the ibrutinib is getting to my lymphocytes in the nodes undeterred.

BluMts profile image
BluMts in reply to PumpkinTyger

Hi Pumpkin, I feel your distress. We've all been there as so much info is coming out on everything. I think people were more peaceful when less information on drug side effects was available. Ignorance is bliss at the time but not so blissful in retrospect.

Can you speak with anyone friendly who is scientific? Maybe someone like that would put this in perspective.

Personally I understand Livinglifewell's thought pattern and honestly wish I was more like him. But I cannot second his advice to you. I don't trust we begin to know about Canabis. Yes I know this is CBD oil and the difference.

I understand your problem. Without a strong knee it's difficult to keep fit. I do a boringly easy knee exercise that's turned both my knees stronger and stopped the pain and inflamation., plus stopped the knee cap seeming to pop out of its moorings😉. on slightly down hill walks. If interested message me for instructions. Probably I would try to build up the knees before cutting down slowly on the CBD oil and trying to find some topical anti-inflamitory to rub on... and hope that in a few years time that's not exposed as dangerous. 😂😁

PumpkinTyger profile image
PumpkinTyger in reply to BluMts

Thanks for the tips but I already do a lot to strengthen my knees. I have very hyper mobile joints and the arthritis is related to old injuries. They swell up for no reason sometimes and CBD balm rubbed into the joint helps, as well taking it internally. So I’ve just been using that today.

This is very interesting. I specifically asked at NIH when I joined the Natural History Study last month if it's OK to take medical marijuana with SLL. I also asked the prescribing doctor as well as my team at Moffitt. I was given the OK from all of them. I just sent my team at Moffitt a copy of the link and will be interested in their response. I don't find that it helps at all with pain but it does help me to sleep.

avzuclav,

Out of desperation we all want some relief, and I have considered CBD as a possible aid for nausea, sleep, cramps, and joint paint.

There are some that I know who use CBD's and claim positive results. One of them is a trial participant with a very similar risk profile to mine and progression state. We also entered the trial at the same time. When we were were scheduled for bone marrow biopsy, the individual did not meet the required decrease in node measurement and had to have additional drug interaction prescribed. After reading this post, I cannot help but wonder if the CBD influenced this individual's node involvement. Should note though that after a short period of the prescribed treatment, the person did meet the criteria for BNB and showed clear of CLL.

I chose not to take any supplements during my clinical trial, so as not to cause any inaccurate measures. Glad I have been dragging my feet on trying CBD, because most of my aggravations have diminished in my 12th month of treatment.

Thank You for the post,

JM

BluMts profile image
BluMts in reply to Smakwater

Smakwater and czbm, I was given CBD oil as a loving gift. Strong and good quality. I had some bad joint times after starting IB. Much less now, probably just me now. Anyway it was given with much love and I'd been thinking, in desperation, about getting some. Have to admit I take a lot of supplements but I could not bring myself to take it. I know CBD has not got the hallucigen that Canabis offers. But its clear there are other potent chemicals in Canabis and I've seen people destroyed by it. I've felt for years that it's had a surprisingly easy ride by scientists and psychiatrists. For the reason that I feel Canibis has not been sufficiently explored, I have held back on taking CBD. This new report ads to my caution.

Smakwater profile image
Smakwater in reply to BluMts

Those who I know, have said that the CBD definitely helps with some adverse conditions.

The person I referred to in the trial also was eventually determined to be clear of CLL in the marrow. I do not know for sure if the CBD was an influence or not.

The jury is still out on much of this. At this point I am in a good position to wait.

If you need some relief maybe discuss it with your doctor, They may have a way to monitor it.

JM

AussieNeil profile image
AussieNeilAdministrator in reply to Smakwater

Thanks for sharing that interesting observation about the person in your clinical trial using CBD oil who struggled to get their nodes down. While the differences are most likely explainable by the heterogeneous nature of CLL, you do wonder, given this research implies that CBD counteracts an important Ibrutinib mechanism that results in nodes shrinking by forcing CLL cells into the blood where they are more vulnerable.

This interchange of CLL cells between the nodes and peripheral blood was only discovered relatively recently. That Ibrutinib changed these dynamics was unexpected. In the first few years of experience with Ibrutinib, we even had community reports from members, where their inexperinced with Ibrutinib oncologist had taken them off Ibrutinib, concerned that it was worsening their CLL.

If nothing else, this shows the importance of monitoring the full extent of CLL involvement during any treatment, not just easily measured parameters.

Neil

Smakwater profile image
Smakwater in reply to AussieNeil

Somewhere I heard someone say "I'd rather be Lucky than Good".

I wonder?

As a person who was diagnosed with CLL/SLL with clonal issues, chasing CLL into lymph nodes where they might mutate doesn't sound like a good idea. I'd love to have an alternative to traditional pharma (and preferably a cure from any source) but I do worry about consumers hanging on to a thread of hope in supplement company marketing messages, and missing the fine print.

I wasn’t taking it to help with the CLL but for my knees, where it was very effective. So the marketing wasn’t misleading or giving me false hope. What they do need to do, in the light of this new research, is to have a contra indications list and include those with a diagnosis of CLL as contra indicated for this product. I don’t suppose there is a way to measure whether the nodal load has gone up in relation to blood levels? I don’t have raised nodes yet so can’t tell for myself.

I have a friend that gives his dog CBD oil for joint pain and I totally understand why that can help and I think 40% of the US population has used some sort of Marijuana derived product. Maybe someone can ask their doc and post? I don’t go back to OH until Feb but I don’t mind asking Dr. Byrd who for sure has thought about this.

I could email my doc with this but I can guess that her response will be don't take it! What else could she say? I'm really disappointed but I guess knee ache versus survival isn't really a contest

AussieNeil profile image
AussieNeilAdministrator in reply to thompsonellen

Your pet on pot, or even CBD: Not a good thing, a vet toxicologist explains by John P. Buchweitz, Toxicology and Nutrition Section Chief, Michigan State University, with my emphasis.

THC is known to be toxic to dogs. According to the Merck Veterinary Manual, common signs of marijuana toxicosis that owners may notice include inactivity; incoordination; dilated pupils; increased sensitivity to motion, sound or touch; hypersalivation; and urinary incontinence. A veterinary exam can reveal depression of the central nervous system and an abnormally slow heart rate. Less common signs include restlessness, aggression, slow breathing, low blood pressure, an abnormally fast heart rate, and rapid, involuntary eye movements. In rare cases, animals can have seizures or become comatose.

:

As for hemp and CBD oils – as a toxicologist, I am skeptical at best.

It is difficult to watch our pets suffer through anxiety or pain from ailments such as cancer. However, although these products have been touted for their therapeutic potential, none of them have gone through the rigor of an FDA approval. Anecdotal findings and limited case studies in humans do not constitute the wealth of information that is needed to establish these products as “safe” for our pets.

For people, there is an inclination to deem products that originate from plants as being “natural,” and thus rather arbitrarily “safe.” This, too, can be harmful. Simply put, “natural” does not always equal “safe.”

theconversation.com/your-pe...

BluMts profile image
BluMts in reply to AussieNeil

Thanks for your post. It was very very interesting to read what the toxicologist and nutrition expert had to say. If he can see these problems I don't know why many experts on human health and behaviour can't. Cannabis has become fashionable and presumably safe. I know someone who has lived on different continents and in 3 different countries where Marijuana has traditionally been grown by some small holders. So access to the plant is easy. Sure it seems to make people happy and social and funny etc, etc. But it's clear that it's got distructive effects with long term frequent use, on brains, nervous systems and who knows what else. Maybe, well nourished middle class social users won't see this and it's the poor overworked mal-nourished who will. I haven't a clue, only casual observations. So I'm cautious.

AussieNeil profile image
AussieNeilAdministrator in reply to BluMts

With regard to safety:

Canabinoids and Ibrutinib are not a good mix

healthunlocked.com/cllsuppo...

There's significant variation in dose accuracy in online sales

healthunlocked.com/cllsuppo...

With respect to CLL, bearing in mind that we've now learned that it may act to increase the CLL tumour burden other than in our blood, there does appear to be reasonably good evidence that canabinoids can help with treatment induced nausea, when the other usual remedies don't work and again with treatment related pain relief. Some find it useful for other purposes, but as we learn more about it, it certainly isn't living up to the hype as a safe, effective cure for CLL!

Neil

Thanks for the insight. I’ll let my friend know. I prefer a glass of wine or beer myself. :)

AussieNeil profile image
AussieNeilAdministrator in reply to PumpkinTyger

There might be a few possible ways to determine if there has been a shift of CLL to the lypmphoid organs:

- measuring the diameter of surface nodes in the neck, armpits or groin

- perhaps an increase in Lactate Dehydrogenase (LD/LDH) in a blood test indicating greater tumour activitity

- perhaps a drop in other blood counts, such as haemoglobin, platelets or perhaps neutrophils. That might not happen until the bone marrow has a fairly high rate of infitration

Unfortunately, the paper didn't disclose how much the ALC changed in the test subjects. Given all the hype we've over the years about cannabis curing CLL, offhand I can recall just one person claiming a significant drop in his lymphocyte count ascribed to it. Most don't see much of a change it seems.

Hi Neil, thanks for the suggestions. I’m relatively new to this, only diagnosed in February, and didn’t know that CBD oil was being touted as a cure. I was already using it successfully for my joint aches and pains but upped the dose for no scientific reason just that I have been diagnosed with a chronic cancer and thought it might help and wasn’t dangerous!

For now I’ve stopped taking it internally but using the balm directly on my knee. I’ll speak to my oncologist to see if there is a way to measure other markers to see how active the CLL is other than in my blood.

I now know that my count had been slowly rising since 2013 but since diagnosis has remained static. I have made major lifestyle changes and spent a lot of money on supplements, herbs and so on but the main thing I put the static growth down to is intermittent fasting, I’m still overweight but have lost 4kg in 6 months which will have reduced my inflammatory markers. And is not only free but actively saves me money, so I feel it’s ok to spend on other stuff. Which I'm taking for my symptoms not as a cure.

So it’s really disappointing to think that the positive static growth may have been caused by CBD oil chasing the CLL into my body where it is causing harm.

Thanks for your input.

AussieNeil profile image
AussieNeilAdministrator in reply to PumpkinTyger

Thank you for sharing your experiences. I consider that your observation about the possible benefit of reducing inflammation by losing weight to be very astute. Our most knowledgeable contibutor Chris/Cllcanada experienced a remission after a significant reduction in his weight and considered that weight loss and improved fitness to be the probable cause. I suspect that many members who ascribe a particular diet for an improvement in their health with CLL would have achieved the same result from just the associated weight reduction, possibly assisted by improved fitness.

Neil

I talked to my specialist about this study and he is now recommending to his patients to NOT use CBD products at all.!

His thinking is that they may or may not work for pain, but they are likely not good for CLL.

This study overlaps my experience really well! I had 2 knee replacements last year an used CBD to help control pain, which it did well. It should be noted that I had no symptoms last year until after I started using the CBD! Within a month of rehabilitation of knee #2 I had growing painful nodes throughout my body! Since I have pretty good markers, this was unexpected.

Now I am convinced that my rapid decline is because of the CBD!

Glad they are doing trials on CBD!

Imbruvica for almost 2 years-heavy marijuana use before during and now-facing per blood work only 5% of the out of range readings is left-My first 6 weeks with Imbruvica typically rough on the body when cleansing begins horrible pain non stop for several days used CBD-anything that might provide relief to both shin bones-everyone involved with my treatment understood my cannabis usage and didn't caution me at any point-my recovery has been wonderful--I did switch to before bed at night taking my imbruvica-seem to have some more energy in daytime.

Marijuana often creates fatigue regardless of your health and condition

I do most of my smoking and eating of marijuana late afternoon and evening.

I believe that my fatigue is with me forever--who knows Maybe I won't be taking Imbruvica for the remainder of my life--will likely be ingesting marijuana unless something radical happens

AussieNeil profile image
AussieNeilAdministrator in reply to wilhoitaz

Did you read this post, which explained why using marijuana while taking Ibrutinib can set you up for more severe side effects? The interaction of marijuana with many drugs (about 450) is not well appreciated by many doctors.

healthunlocked.com/cllsuppo...

Great that your blood work is nearly normal.

Neil

wilhoitaz profile image
wilhoitaz in reply to AussieNeil

This study came after my journey-My oncologist is aware of my marijuana use-I am not critical of study-not necessarily recommending use to anyone--wasn't aware of it-- I have smoked most of my life and will continue unless my health givers or I note any issues --Again my recovery has been wonderful--I thank God daily

Unfortunately research is new on marijuana was considered toxic until recently-I expect conclusions all over the place next few years

It is at this point helpful to me for many little CLL related quirks

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