Hi All
Since I started my Gardening business in July 2021, Which is going really well I find that I get tingling and numbness in my hands while working but also when at home ie just using the phone laptop etc. Has anyone else experienced this is ? it Cll related just thought I would ask.
Still on watch and wait WBC 151K
Jules the Flyer
For the last few years l have (plus 'white finger') .... I'm not sure if it's related to CLL or age...
Me too!Chrisx
Look up Raynaud's syndrome. Fingertips turn white. I have had spells of it in the past but not recently. Magnesium deficiency has been associated with it.
Thank you.
One possibility could be diabetes. If you haven't had your levels checked it would be a good move to do so. Also, numbness as you describe can be caused by poor circulation. As we age some of us get narrowing blood vessels.
Maybe a report to your regular physician for a checkup is in order? I can't think of a reason for it to be directly related to CLL.
The picture of the owl is brilliantly magnificent in its clarity. Thank you for that!
Worth checking out Carpal Tunnel Syndrome. I had numbness and tingling in my hands before I had surgery for it. Usually caused by repetitive use of the hand/s which is likely with gardening tasks.
Newdawn
I've too experienced this after gardening work. Do you find it is worse in colder weather? I recommend you ask your GP if you might be developing Carpal Tunnel Syndrome.
Love your photo. Is this a hazard you face in your gardening work? In Australia it's swooping magpies and lap wings during nesting season.
Neil
Sorry and another suggestion could be arthritis in your hands.Your local hospital may well have a hand clinic. Exercises helped with my diagnosis and also a couple of drops of black pepper oil mixed with hand cream is a great help.
Colette
Thanks all I will call the Drs in the morning. The photo was when we went on an owl flying experience......one thing I love about Gardening is the birds that come and see what I am up to blackbirds and lots of Robins its a great joy to me
I agree with Newdawn. I have had 4 hand surgeries 1 double trigger finger release, 1 carpel tunnel, and 2 basal thumb joint angioplasty. All stemming from working in a greenhouse for 30 years and 10 years in a bakery….all repetitive work. My hands are good now!!!
Panz 🙂🙏💕☘️
Hi Flyer. No words of wisdom but fab pic!Peggy🦉
Yes, great photo.I have peripheral neuropathy in my feet.
My cancerous B cells were producing cryoglobulins. If you're working outside it could be a cold reaction (just a gentle breeze in the summer was enough to give me a reaction).
Good luck finding a medical professional with working knowledge of cryoglobulinemia though!
Happy
I moved into a new home in September. Whilst decorating I experienced the same although I was also getting these sensations at the top of my arm. The doctor sent me to A and E to rule out a stroke. The dept. Were real thorough and nothing was found. As I am still experiencing these symptoms I've been referred to Neurology for further tests...more wait and worry....I've found since diagnosis every appointment heightens my fear and anxiety.The Doctor did say he believed my hands could be carpal syndrome...I bought a wrist support from Amazon...
LTG Neoprene Support Wrist Brace Use for Carpal Tunnel Arthritis Sprains Strains (Small - Medium(Right), Purple) smile.amazon.co.uk/dp/B072B...
I have found this has helped. I used to wake up with the most terrible hand pain...this has definitely alleviated that.
I was diagnosed in June last year....watch and wait Cat A.
Hoping you find this helps
Shar
Are your fingers tingling? If so, are they all affected? If not all, which fingers are tingling?
Definitely chat to your GP about it!
Jig
I have this plus my fingers get very cold and go white, I was diagnosed with Reynauds about 8 years ago. It has definitely got worse since being diagnosed with CLL 4 years ago, however they were fine when I was on FCR!!I would definitely see your GP. X
I have really poor circulation and often wake up with what feels like a "dead hand". The same with my feet if I sit on them. It has got worse over the last few years. I'm 42....
So, previous posts suggesting Raynaud’s syndrome and/or cryoglobulins might be related to CLL strike a chord with my symptoms. Raynaud’s causes construction of tiny blood vessels in response to stress and cold. I had it when I was young, but no problems with it for decades. Poor circulation in my hands and feet with neuropathy came back with a vengeance as soon as my WBC/ALC Levels climbed into CLL territory. Correlation in my case of one is perfect….but statistically meaningless. Interestingly, previous comment says circulation issue also correlated with CLL,as it was relieved by FCR, and came back when ALC progressed later? If so, then sample size of two, perfect correlation….still meaninglessness. Finally, cryoglobulins are not checked for (I asked), but are reported to inhibit circulation with slight downward changes of blood temperature in extremities., feet and hands. There are no data to say these phenomenon are associated with CLL…I don’t think patients/doctors really care much about having Raynaud’s symptoms in the face of incurable cancer of the immune system …especially during Covid, but I’d like to know. I wish there were research about this, even in the form of epidemiology of existing patients vs control group. It seems reasonable that blood with so many WBC are slowing down circulation, or are producing enough precipitating antibodies, to slow down circulation enough that persons with predisposition to poor circulation, Raynaud’s/elderly/etc wouldn’t have enhanced symptoms.
While it would be interesting to know if the incidence of Raynaud’s syndrome is higher with CLL, the mechanisms you suggest are unlikely. In healthy people, the ratio of red blood cells is about 1,000 to 1. CLL cells are also small and non sticky, barely larger than red blood cells. A healthy B cell contribution to a health WBC is roughly around 5%. You'd need a lymphocyte count of around 1,000 compared to 1.0 to have roughly equal red blood cell and CLL cell counts.
A few members have reported cryoglobulins, but CLL cells mature at a stage before they shed much in the way of immunoglobulins. It's quite common in CLL to have low immunoglobulin counts rather than high immunoglobulins, but see sciencedirect.com/science/a...
Neil
The math you’ve related is reasonable, but I draw the opposite conclusion from those numbers. Consider our smallest arteries, which are normally occupied with blood saturated with cells (blood is about 50% RBC cells by volume). The tiny RBC barely fit through capillaries lined up back to back when the ratio is 1000RBC:1WBC. With a CLL ALC OF “100”, that ratio becomes 10:1, which is roughly 10% more cells in the blood than normal, which IMHO has been maxed out by nature for the best overall fitness. Lymphocytes are very small cells indeed, but too big to pass through capillaries at all like the even smaller RBC do (which are made uniquely small by jettisoning their nuclei). Doctors suggest CLL cells don’t block the entryway to capillaries because of integrins on the surface, but this may largely be speculative. I’m glad they don’t! In any case, our resident doctor posted in the last year that we are more likely to have strokes because of the excess WBC. Thick blood when you’re carrying more cells per cubic centimeter than nature intended…I’d say having a ALC OF 100, which is500-600 billion extra blood cells on top of the normal RBC has to screw up circulation.
Your resident doctor may be interested in the views of several very experienced CLL specialists with international reputations on this topic per this post:
healthunlocked.com/cllsuppo...
Professors Tom Kipps and Terry Hamblin (who discovered the relevance of IGHV mutation status in CLL), along with Dr Kanti Rai (of Rai staging fame), set the lymphocyte threshold of 5.0 used to differentiate CLL from MBL, Dr Michael Hallek from Cologne, Germany is the principle maintainer of the iWCLL guide for the diagnosis, management and treatment of CLL and heads up the German CLL Study Group and Dr John Byrd was the recipient of a CLL Cure Hero award a few years ago, recognising his reputation. Dr William Wierda is the Professor and Medical Director for the Department of Leukemia and Executive Medical Director for Leukemia, Lymphoma and Stem Cell Transplant at The University of Texas MD Anderson Cancer Center.
They don't see leukostatis as a concern in CLL, even with much higher lymphocyte counts than 100.
Neil
Sorry, I was referring to something our resident "CLL Society MD" had said, or I thought he'd said, but I can't find it now despite looking. (Don't really have much luck searching for specific things on HealthUnlocked. ) Regardless, the 7+ year old references in that link you've shared (again) with me all simply state that high CLL ALC is not a reason to treat CLL with the available therapies... because (IMHO) all CLL therapies literally destroy what is left of your immune system.
Dr Wierda relates that one of his patients had an ALC of 250 and "had nearly a normal hemoglobin level and nearly a normal platelet count", but no symptoms...(yet). Just because he's bone marrow is still functioning well enough to crank out platelets and RBC at near normal levels doesn't mean that the niche microenvironment in the marrow and lymph nodes and spleen isn't under a constant tremendous strain. Dr. Wierda just doesn't have anything that isn't going to nuke that patient's immune system, at least all of his CD19 expressing cells. Every good CLL MDs is keenly aware of the vast literature detailing how CLL patients have compromised immune systems, but todays treatments make your immune system even worse (immediately worse than the slow attrition of high ALC)...albeit while eliminating your CLL tumorous cells. So given the ethos of do no harm, they've got to let you carry on with dysfunctioning immune system ...unless you need treatment for an awful symptom. A little neuropathy or Ranaud's-like symptoms would be insufficient to treat CLL, even if an established link were made between poor circulation and CLL ALC (which hasn't been made, nor looked at). Likewise, autoimmune diseases affecting joint mobility would be insufficient too..even if there were a link established...However autoimmune cytopenia is serious enough to treat, and there is a known link. All I'm trying to say is that 100s of billions of extra cells in your blood/microniches/invading various organs and cavities (spinal fluid/joints/pericardium) is not good for your body, but unless the symptoms are very serious or unbearable....there is no reason to 1) research these or 2) treat less serious symptoms given that they are inconsequential relative to the harms of treatment.
A broader point I've tried to make elsewhere is represented in this paper, ( jeccr.biomedcentral.com/art... )
Here's just a few lines...
"Immune dysfunction is a fundamental characteristic of CLL that can be present even in early stages of the disease. However, these immunologic aspects have been a deprioritized side in the research of this field for many years. The clinical consequences are an increased risk of secondary malignancies [15] and infections, the latter being one of the leading causes of mortality among patients with CLL [16]" I agree with your references that we don't have anything to treat CLL that is reasonable to use at the very beginning, before years of high ALC (irrevocably?) compromises your immune system. When we do, we'll treat upon diagnosis before immune damage is done.
I agree with you with respect to immune dysfunction caused by CLL, but as CLL cells are dormant in the blood stream, it's in the nodes, spleen and bone marrow where they do their damage to our immune system. My reply was only in respect to possible circulation concerns raised by this post. (I also agree with you about search being inadequate on this site.)
As I've acknowledged previously, CLL specialists see solving immune dysfunction as the last remaining challenge in order to fully cure CLL. It's why I wrote this post: healthunlocked.com/cllsuppo...
(I've also fixed the link in your excellent reference (but which doesn't mention circulation problems), so it now works - HU needs a space character/new line before and after a link to form a correct link reference.)
Getting back to CLL and blood circulation concerns, Dr Furman, another well respected CLL specialist from Weill Cornell Medicine, New York City, differentiates between blood viscosity and leucostatis in this reply from nearly 5 years ago, where he draws a very important distinction. "When we discuss viscosity of blood, we usually refer to serum viscosity, which is mostly due to the proteins in the serum (usually immunoglobulins)" and white blood cells on blood viscosity in scuba diving (where cold water temperature can be a concern).
"Re: SCUBA at 100 ft with high WBC.....helpful hints???
From: Rick Furman <rrfurman@med.cornell.edu>
Date: Wed, 13 Jan 2016 19:05:27 PST
It is an interesting biologic distinction between viscosity and leucostasis. When we discuss viscosity of blood, we usually refer to serum viscosity, which is mostly due to the proteins in the serum (usually immunoglobulins). Increased WBCs result in leucostasis, which is more the result of the WBCs interacting with the blood vessel walls and sticking, leading to blockage of flow.
We do not see leucostasis with CLL under normal situations. The WBCs in CLL are small and "not sticky". The highest WBC I have seen in a CLL patient is 762,000. The WBCs in acute leukemias are different. They are larger and tend to be sticky, and there we do see leucostasis when the blast count rises to approximately 75-100,000.
There should be no problem with diving just based upon an elevated WBC.
Rick Furman"
So in summary, as I initially pointed out, it's immunoglobulins (in particular cryoglobulins) that are the concern with respect to blood circulation, not CLL cells. Dr Furman also notes with respect to the risk of blood clots with CLL:-
"From: Rick Furman
Date: Tue, 05 Jan 2021 05:38:58 ACDT
Cancers, in general, are associated with an increased risk of blood clots. The data for CLL specifically suggests it is not. There may even be a protection afforded by the CLL due to the CD39 expression on CLL cells acting to help prevent platelet activation. Many of the studies in the literature are complicated by poor control populations.
Rick Furman, MD"
Addendum:
Please appreciate that my passion for this issue of circulation concerns driving treatment, is because I've seen many disappointing cases where 'specialists' have initiated treatment solely out of concern that lymphocyte counts are approaching 100/100,000. This just puts the patient at increased risk of infection during and for some time after treatment - sometimes indefinitely/permanently with the older 'chemo' treatments. It can also rob them of the chance of safer, yet to be approved treatments.
Neil
Agreed that available treatments are not to be initiated without serious symptoms as elucidated by current protocols (This is because the treatments undermine immune function). Thank you for pointing out the discussion on blood viscosity, especially relevant as I'm a SCUBA diver.
I concede the data regarding blood clotting shows CLL patients are not at higher risk.
However, my concern is the idea that having blood with 10% more cells circulating around than normal can not be a healthy situation within are vasculature. Agreed that such levels of cells in virtually any other leukemias would be a critical situation, but surprisingly does not pose the same catastrophic issues in CLL because the cells are smaller and less sticky to each other and to the blood vessels interior walls (endothelial cells). However, the idea that there are not consequences of excess cells on blood flow through the smallest arteries and capillaries seems inconceivable to me considering the wondrous fluid dynamics of moving RBC through the tiniest of tubes. Agreed CLL associated hypogammaglobulinemia seems counterintuitive to having cryoglobulins, however having any level of a novel protein in serum could lead to that protein sticking to itself, and since our clones produce (on their surface) a single novel protein (immunoglobulin), it seems plausible that this protein (secreted, clipped off, or from CLL cell turnover) could be around in sufficient numbers to self aggregate under certain circumstances. (In biotech, if you try and express a novel protein in cell culture, you often find the protein forms aggregates even at low concentrations.) But this is pure speculation. I guess someone could speculate that having so many extra cells even does something good for your vasculature...but my intuition says it is not benign based on the physics of circulation.
Overall, I strongly believe that running around with an ALC of near 100 takes it's toll on multiple systems each year. Moreover, these cells remain a huge target for second site mutations (and epigenetic changes) that could transform our CLL to something worse, which unfortunately does happen at a rate of ~1% of us per year. And as we've mentioned, they undermine our blood cell making system and our immune systems.
In conclusion, eliminating or even reducing our CLL cell burden upon diagnosis will certainly be advised when (and if) a treatment comes along that targets only the tumor cells (and not all CD19 cells, etc.).
Along these lines, I'm wondering if anybody is looking at CRISPR targeting of CLL cells bearing 13q14 deletions. Since ~50% of all CLL patients have some portion of this chromosome deleted, if the new sequence over the chromosome breakpoints were targeted and a suicide sequence introduced...you could specifically eliminate the CLL mutant cells in situ. Started early (upon diagnosis) you could cure CLL patients before years of high ALC cause irreparable damage. If such a scheme worked (without side effects), then you could even target 13Q in MBL patients.
Your question about the link between cryoglobulins and CLL has been posed before, but would appear rare or I expect it wouldn't be a question: europepmc.org/article/MED/3...
You're right that CLL cells can mutate to tougher clones, but treatment also accelerates this, particularly chemo treatments. The risk can't be eliminated until you can eliminate the CLL. Finding targets that are present on CLL cells and not healthy B cells is obvious what we want, but it's also obviously hard to achieve. Targeting deletions is difficult, because normally the DNA is tightly wound to fit within the ~8 micron cell nucleus. Stretched out human DNA is about 2 metres long! But see later replies about CRISPR technology.
With respect to your concern about the number of blood cells circulating, keep in mind that the healthy count range for red blood cells is around 4.3k to 5.7k, or about 1,000 times the number of lymphocytes as I mentioned before. So why don't people with ~30% more red blood cells in circulation than 4.3k (i.e. 5.7k) have health symptoms if your concern is valid? If you add lymphocytes and red blood cells together and this person had a red blood cell count of 4.3k, someone with a lymphocyte count of 100 that you are concerned about would have a red blood and lymphocyte count of just 4.4k.
Neil
"Targeting deletions is nigh impossible, because normally the DNA is tightly wound to fit within the ~8 micron cell nucleus. Stretched out human DNA is about 2 metres long!"Look at any recent publication, and targeting specific sequences within chromatin in vivo issue is not the problem. This is accomplished with high efficiency. For example, Hana, S., Peterson, M., McLaughlin, H. et al. Highly efficient neuronal gene knockout in vivo by CRISPR-Cas9 via neonatal intracerebroventricular injection of AAV in mice. Gene Ther 28, 646–658 (2021). doi.org/10.1038/s41434-021-.... Working with blood is theoretically much easier than in then the solid tissue in this report...(albeit many CLL tumor cells are sequestered within bone marrow/LN/spleen.. .
Basic protocol:
Step 1) Use the already tested monoclonal Abs tethered to a CRISPR/CAS package with high efficiency to CD19 bearing blood cells. Once bound to the CD19 cells, this CRISPR/CAS "package" might be brought into the CD19 cells with high efficiency using the nanolipid particle technology (currently being used safely for mRNA vaccines)?
Step 2) Then the CRISPR guide RNA will bind to the unique 13Q deletion endpoints. (To get this sequence for the guide RNA, perform WGS on blood gives you this sequence for $300, I've had mine for 2 years...one of the benefits of having a huge tumor clone) Of course, any other chromosomal breakpoint could be used (eg DelTP53), but again personalized to the patient's sequence.
Step 3) CAS breaks the DNA resulting in cell death, or perhaps inserts an apoptosis inducing sequence.
Step 4) Increase treatment duration and/or concentration until uMRD.
If done at low enough concentrations to begin with TLS could be avoided. Many of these reagents have human approval already.
An another tangent, I know there are several models for CLL in animal models (mice). Indeed, removing the mouse genes corresponding to the human genes removed in 13Q14 CLL patients, leads to "CLL" in mice. I'm wondering why nobody has bothered to test when during the course of MBL/CLL progression is the point of no return for reconstituting a robust immune system. That is, the mouse CLL tumor cells, if genetically engineered with an unrelated inducible suicide gene, could be removed at different times during tumor progression to see whether the healthy B-cell recover. Perhaps a mouses life is not long enough to do these experiments. I'd like to know whether my belief in early treatment of CLL (with not yet available treatments) is supported by research in the mouse systems. Of course, strong support in a mouse system is no guarantee of translation in the clinic, but a good place to start.
Indeed I'd forgotten the first CRISPR human clinical trial was approved for sickle cell anaemia nearly a year ago, so I've modified my reply. Perhaps in 10 years time we'll see it used in CLL, but I would expect other, more common cancers with simpler mutations to fix, would get priority. Currently with CLL it's far easier to find and use targets with higher expression in cancerous cells than tackle the cancer cell DNA. Given the wide range of genetic lesions involved in CLL, this will be truly personalised medicine, with 13q14 probably the first target. Just keep in mind the challenges of also tackling sub-clones...
Neil
True about the inevitable appearance of subclones, but again early treatment would address this issue too.I disagree that other cancers typically have simpler mutations...CLL is one of the most stable tumors out there, and virtually every CLLer has a unique genetic lesion in each cell of their clone, the IGHV rearrangement...which is so readily sequenced (eg to determine somatic hypermutation status). All subclones and many Richters transformations retain this BCR signature on all their tumor cells, which would allow this unique DNA to be an even better target of the complementary CRISPR guide RNA.
Moreover, solid tumors are notoriously heterogeneous and have poor access via intravenous drugs due to incomplete angiogenesis.
Thus, IMHO, CLL is the disease to tackle first with CRISPR technology. We have stable tumors that are among the most accessible to intravenous intervention.
The first blood cancer to be treated with CRISPR technology would more likely be CML, chronic myeloid leukaemia. More than 90% of cases are due to the Philadelphia chomosome mutation: en.m.wikipedia.org/wiki/Phi... chromosome That's why it was the first cancer successfully treated with an inhibitor drug imatinib/Gleevec, developed for this purpose in the mid 1990s. That's over a decade before we were able achieve a similar result with ibrutinib for CLL.
Incidentally roughly half of CLL is of the IGHV mutated variety and while there is stereotypy, it's not unique. (Added) The more aggressive unmutated IGHV version is more in need of early treatment as the IGHV mutated variant is now considered to be due to more effective DNA repair, reflecting greater genome stability, rather than the B lymphocyte going through somatic hypermutation.
We've digressed at length somewhat from TheFlyer's question.
Neil
Definitely way off topic. But I’m not talking stereotypic, I m referring to the actual DNA sequence that is produced for each patient where IGHV hyper mutation status is determined. This sequence plugged into a machine to synthesize a CRISPR guide RNA, would be specific for CLL tumor cells and no other off target. True, 90% CML have nearly identical chromosomal fusion aberrations, but you’d have to sequence the endpoints for each patient because they’re unique. This is already routinely done for the CLL IGHV chromosomal rearrangements when seeking IFHV mutational status. Agree it should be triesd with CML too, but preferably now and not one before the other
From your description it sounds postural. I recommend consulting an Osteopath. If it is postural they will be able to treat it and alleviate the symptoms. If it's not postural then you've ruled postural out and can push your GP for medical investigations. Btw, Osteopaths can also treat the symptoms of carpal tunnel syndrome.
I had something similar a few years back I was tingling even down my spine. I quit drinking the strong brewed coffee that I was drinking several cups of everyday. And within 3 days it got much better. Then it stopped completely. Perhaps worth a try
As previously mentioned by others, check out Raynaud's syndrome, especially if your finger tips ever turn white. Raynaud's has been associated with magnesium deficiency (although I am not saying all cases have this cause) but might be worth supplementing if you haven't been, just to see. As AussieNeil said -- wonderful photo!
When the hip has a problem... I look at the feet and vice versa When it comes to the hands, I look at the shoulder. Keeping the shoulder, elbow and wrist open was key for me It worked, and I used to have pain and tingling Used a Styrofoam roller to open up and did Gyrokenisis self massage and other shoulder exercises to change my alignment. Check out the Brachial Plexus nerve. Catnap7
Stunning photo. Great way to start my Monday morning. Wish I had answers for you.🙏Sally
I have waldenstrom, a lymphoma. Among its symptoms are neuropathy, numbness in hands or feet. My hand is numb periodically when using phone or pc. I exercise my hand and it disappears. I understand blood cancer can affect the extremities due to neurological impact
Venclexta and achey legs
12th Anniversary at Untreated
Covered with red spots and blotches
Going down hill fast.
Anyone out there with a very high ALC and not needing treatment.
