Watch & Worry
One of the more infamous phrases that patients learn soon after the CLL diagnosis is “Watch & Wait”. It is understandable that most of us chickens re-phrase the “W&W” to mean a more realistic “Watch & Worry”. It is a hard concept to accept and seems counter intuitive at first blush. The general understanding of cancer treatment is that it is better if the cancer is diagnosed early so that we can hit it right away with everything we got, from multiple fronts – surgery, radiation and chemotherapy. Why is this not the recommended approach for CLL as well?
Beast of a different color
Many solid cancers have a short fuse and you do have to hit them and hit them hard first chance you get, to increase your chances of a full cure. That is not the case with the majority of CLL patients. While some patients do have aggressive CLL, majority of CLL patients have at least a little bit of time to think, learn, plan. Oncologists who give patients the bum’s rush into therapy immediately after initial (often unconfirmed) diagnosis of CLL are not doing them any favors.
Another reason why solid cancers are treated as soon as they are discovered is to avoid metastasis of the cancer to other parts of the body. When the cancer is localized to a specific region, say the breast, skin, liver or lungs or whatever, it is more vulnerable to therapy targeted to that specific region. Think of a small group of terrorists conveniently gathered in a single house, ripe for a well targeted attack by the good guys. Metastasized cancer that has spread elsewhere is a lot harder to eradicate. Now we are talking of house-to-house searching, trying to take out bad guys that can blend in with the general population. Guerrilla warfare is never as easy as surgical strikes, and it always costs a lot more innocent civilian lives.
CLL does not fit into this general understanding we have of solid cancers. CLL is a blood cancer, and CLL cells circulate in the blood. Where does blood go in your body? Everywhere! In other words, right from the get-go, CLL is present in every nook and cranny of your body, every place where blood flows. CLL is 100% metastasized from the day it is diagnosed. Worrying about CLL spreading through metastasis is a bit like bolting the barn door after the horse has gone over to the next county – no, make that the next state!
Making the case for waiting for as long as possible
Watch & Wait makes sense for CLL, most of the time. It gives you a chance to get your ducks in a row:
- Did you get that all important second opinion confirming the diagnosis? Are you sure what you have is indeed CLL, not a kissing cousin like MCL, NHL, SLVL or some other bit of nasty alphabet soup? Your game plan depends on what you have. Getting a rock-solid diagnosis is the first step. Most insurance companies are only too happy to cover the cost of a second opinion. Make sure you use that option!
- May be you got lucky, you have the “smoldering CLL” variety that does not require treatment for a long time, if ever. There is nothing to be gained by rattling a quiet and peaceful hornets nest with a long stick, is there?
- Maybe you got unlucky, your CLL is an aggressive variety and you have the worst case FISH result – 17p deletion, with unmutated IgVH thrown in for bad luck. If this is your profile, single agent fludarabine is not such a good idea, and you may want to be extra nice to all those siblings your parents were generous enough to give you. One of them may be a perfect match for a mini-allo stem cell transplant down the road. No point rushing into therapy before you get a good fix on the lay of the land, no point in signing up for therapy options that are not going to do much for you, except deal with a lot of adverse effects.
- Clonal evolution sometimes happens all by itself. But more often, it is thought to happen after treatment with heavy duty chemotherapy drugs, many of which are mutagenic. Why help your CLL cells learn new tricks, become that much more dangerous and hard to kill, before you have to?
- Most therapy options leave patients with immune systems that become even more dysfunctional than they were to begin with. For that lovely remission patients hope to get there is generally a price to pay – anemia, neutropenia, increased susceptibility to infections to name a few possibilities. Some folks luck out, but others report significant loss of quality of life. Why bring on these problems sooner than you have to?
Is there risk in waiting too long?
Yes, there is such a thing as sticking your head in the sand and waiting ‘forever’. Remember, the phrase is Watch & Wait“, not just “Wait”. The “Watch” part of the equation is equally important, and it rules out sticking-head-in-sand as a sound game plan. Taking a vacation from CLL is all good and fine. But there is a limit to it. I had reason to read the riot act to a close friend recently on this subject.
I must have one of the largest anecdotal databases on CLL. I hear from literally thousands of patients from all over the world, describing their particular situation. Once in a while the letters give me a perspective that I think is important to share with the general patient community. I heard from “Greg”, a smart and detail oriented software engineer a couple of weeks ago. It is not his real name or profession – we are very careful to protect patient confidentiality – but the case history I report is true. This is what Greg had to say (published with his permission):
My experience with the “good kind of cancer” began 4 years ago (December 2004) when I noticed a lymph node under my chin while shaving one morning. I was officially diagnosed with CLL / SLL soon after. Although my FISH test said I had “normal” results, I did have elevated CD38 and ZAP70. My absolute lymphocyte count was in the normal range, bone marrow was 30 to 40% infiltrated with lymphocytes, and my initial CT scan showed only 1-2 cm lymph nodes. I was reassured there was not much to worry about and that sometimes these nodes may even melt away by themselves.
Later I noticed other small nodes in my arm pit but these and the nodes under my chin stayed pretty much stable over the next two and one half years of W&W. I had no symptoms and I remained in good physical condition.
Sometime towards the end of 2007 the white count had increased to 39 thousand. Not all that high compared to some patients I had heard about, and I drew comfort from the stable size of the lymph nodes under my chin, the ones I tracked each day while I shaved. They were my “sentinel nodes”, the canary in the mine I hoped would give me advance notice of progressive disease.
My doctor ordered a CT scan anyway. I was not too thrilled about that. Why get all that radiation exposure if things were stable? But I went along with his recommendation. CT scan of the abdomen showed it was basically a solid mass of swollen lymph nodes packed together tightly. The whole mass was 20 cm x 17 cm x 13 cm. I feel I have been betrayed / fooled by the small and deceptively stable nodes under my chin and in my armpit. I had no way of knowing what was going on deep in my abdomen where it was impossible to “feel” anything in just a physical examination. Even my belt size stayed the same!
Now with a better awareness of the aggressive nature of my brand of CLL/SLL, I am trying to decide my best therapy choices. Most likely I will go for a stem cell transplant sooner rather than later. The first step is to get a good remission ahead of the transplant. The bulky nodes are proving to be tough to eradicate.
Greg did what most of us do, believe the evidence he could see (stable size of nodes under his chin and armpit, reasonably low white blood count), and not worry too much about what he could not see – the abdominal nodes that could only be detected by CT scans. Now he faces tough choices and not a lot of time to get his ducks in a row. As most of you know, “bulky” disease (usually defined as bigger than 5 cm) is a lot harder to treat. Drugs like Campath do not work very well on large lymph nodes – in fact these patients are described as “Campath ineligible”. If fludarabine does not work, or contra-indicated for some reason (as in 17p (p53) deletion, or autoimmune disease such as AIHA), we are looking at a patient with significant similarities to the “Double Refractory” folks we discussed in the earlier article on Humax-CD20. For perfectly understandable reasons, Greg waited too long, it would seem.
Most of us are squeamish about getting CT scans. Who wants to get a dose of radiation for no good reason? There are now tentative links between CLL and radiation exposure, which makes this decision to scan or not scan all the more tricky – but more about that in another article I have on the drawing board. For now, the take home message is that while you don’t want to over-indulge in unnecessary CT scans, it might be a good idea to consider getting a scan and bite the bullet once in a couple of years.
This is particularly true for people who tend to have most of their disease in bulky lymph nodes, folks whose disease is more like SLL than CLL. Do you have 12 Trisomy or 11q or 17p deletions? Bulky disease is more of an issue for patients with these FISH abnormalities. Placing your bets on relatively low and stable blood counts may not be sufficient insurance for you, if you are in this group. You may need more frequent CT scans to keep an eye on things, do justice to the “Watch” part of W&W. I will be the first to admit this is a tough call to make, no black or white slam-dunk choices. I have come to appreciate how many of the decisions we have to make in CLL arena fall into grey areas.
Got stem cells?
Hematopoietic stem cells (HSC) are a precious resource. These cells live in specialized niches within your bone marrow. When called upon they can produce all the various cell lines in your blood, important cell lines such as red blood cells, platelets, neutrophils etc. Each and everyday blood stem cells give birth to and replace the zillions of blood cells lost to wear and tear. Think of your bone marrow as a factory, and the stem cells as vital machinery that churns out the necessary red blood cells, platelets, neutrophils etc. simplifying things just a little, three things can get in the way of proper functioning of the factory, bringing the production of life giving red blood cells, platelets and neutrophils to a grinding halt.
First, if the factory floor gets cluttered to the rafters with garbage so that there is little room for the machinery to work properly, you can imagine this would get in the way of producing the needed cell lines. When your bone marrow gets increasingly infiltrated with useless CLL cells, this is exactly what happens. As the disease burden in the bone marrow increases, this congestion is reflected in increasing anemia (reduced red blood cell production), easy bruising (reduced platelet production, increased risk of infections (reduced production of neutrophils). The only way to fix this problem is to do a hefty job of spring cleaning, free up space in the factory floor – namely, initiate therapy to reduce the number of CLL cells infiltrating the bone marrow.
A second reason why stem cells stop producing the needed cell lines in sufficient quantities is if for some reason they do not get the right signals. Our bone marrow invented the concept of “just in time manufacturing” long before we discovered it as an efficient way of controlling manufacture of widgets on factory floors in the real world. The signals to stem cells to get off their behind and produce more cells come in the form of growth factor cytokines. And yes, cancer can interfere with the proper levels of these production signals.
Fortunately, we now have man-made versions of these production signals. Most of you are familiar with drugs such as Procrit (man-made epoietin, the signal calling for production of more red blood cells), Neupogen (man-made GCSF demanding goosed up neutrophil production), Leukine (GM-CSF calling for more macrophages and neutrophils). Provided the stem cells are in good shape and the factory floor is not too crammed with junk, giving patients these emergency orders to increase production has the desired effect. There are dangers associated with using man-made growth factors indiscriminately, as we identified in the dark side of epo. More is not necessarily better. Several CLL “opinion leaders” who swore by double and triple shots of epo as a therapy strategy were very upset with me when I started writing about the risk of excessive growth factor use. I think time has proven I was right on issuing this warning at a time few people were aware of the risks.
But the third reason why production may come to a grinding halt is the most dangerous one of them all, because we do not have an easy fix for solving the problem. What if the precious stem cells gradually die off? After all, it is no use sending emergency order for increased production, and /or making sure the factory floor is pristine clean, if the stem cell machinery is busted once and for all. If the stem cells are dead or dying, we have no way of fixing it. Patients with stem cell aplasia (fancy words for dead and dying stem cells) become transfusion dependent. They will need regular infusions of red blood cells, platelets etc just to stay alive. The only long term viable option is to bring in brand new machinery, a new batch of stem cells from the outside – namely, a stem cell transplant with stem cells donated by a willing donor.
What kills stem cells?
Just like other cells in our body, stem cells too die if they are burned by radiation, poisoned by chemotherapy drugs etc. That is why getting the drug dosages right is so important and it is such an integral part of every clinical trial. Drugs (and radiation) have to be carefully titrated; just enough to kill cancer cells but not so much that irreversible damage is done to other parts of the body – most importantly not so much that the precious stem cells in our bone marrow are damaged.
But how about CLL cells? Do CLL cells kill stem cells? Does increasing level of bone marrow infiltration by CLL cells do more than just clutter up the works? Are we looking at more than just sidelining the stem cells for a while, easily fixed by giving the bone marrow a good spring cleanout? Do CLL cells damage the machinery to the point where it cannot be fixed? The abstract below sheds some light on this important issue. It seems there is reason to worry that increasing hordes of CLL cells in the bone marrow can cause irreversible damage to stem cells, one more reason why waiting too long can be a self-defeating strategy.
Science. 2008 Dec 19;322(5909):1861-5.
Leukemic cells create bone marrow niches that disrupt the behavior of normal hematopoietic progenitor cells.
Colmone A, Amorim M, Pontier AL, Wang S, Jablonski E, Sipkins DA.
Department of Medicine, Section of Hematology/Oncology, University of Chicago, 5841 South Maryland Avenue MC 2115, Chicago, IL 60637, USA.
The host tissue microenvironment influences malignant cell proliferation and metastasis, but little is known about how tumor-induced changes in the microenvironment affect benign cellular ecosystems. Applying dynamic in vivo imaging to a mouse model, we show that leukemic cell growth disrupts normal hematopoietic progenitor cell (HPC) bone marrow niches and creates abnormal microenvironments that sequester transplanted human CD34+ (HPC-enriched) cells. CD34+ cells in leukemic mice declined in number over time and failed to mobilize into the peripheral circulation in response to cytokine stimulation. Neutralization of stem cell factor (SCF) secreted by leukemic cells inhibited CD34+ cell migration into malignant niches, normalized CD34+ cell numbers, and restored CD34+ cell mobilization in leukemic mice. These data suggest that the tumor microenvironment causes HPC (blood stem cells) dysfunction by usurping normal HPC niches and that therapeutic inhibition of HPC interaction with tumor niches may help maintain normal progenitor cell function in the setting of malignancy.
PMID: 19095944
OK, I admit this abstract is not the easiest to read and understand. Some of these researchers need to get remedial writing courses, lean how to contstruct sentences in English that native speakers can understand. Fortunately, a more user-friendly version of the same information is written up in the article below. Think of this as Darwinian fight to the death at the cellular level. CLL cells in the bone marrow and stem cells compete for the same resources, the same niches in which to grow and thrive. Kicking out the stem cells and making it hard for them to come back home is a classic survival strategy adopted by cancer cells. It is as if drug dealers and mobsters move into a nice neighborhood. If allowed to get out of hand the bad guys get the upper hand and law abiding families start moving out. In no time at all once lovely homes and streets become home to dope peddlers and thugs and the old neighborhood that we cherished starts dying. Yes, there is such a thing as waiting too long. “CLL holidays” that last too long can be expensive affairs, as I told my friend.
http://www.medicalnewstoday.com/articles/133633.php
Stem Cells And Leukemia Battle For Marrow Microenvironment
Medical News Today
20 Dec 2008 – 1:00 PST
Learning how leukemia takes over privileged “niches” within the bone marrow is helping researchers develop treatment strategies that could protect healthy blood-forming stem cells and improve the outcomes of bone marrow transplantation for leukemia and other types of cancer.
In a paper in the journal Science, available early online Dec. 19, 2008, researchers from the University of Chicago Medical Center show that by blocking one of the chemical signals that leukemic cells release, they could help prevent the cells that mature to become red and white blood cells from being shut down by the cancerous invader.
“We found an approach, in our mouse model, that could help protect the cells that give rise to healthy blood cells, and improve their accessibility for use in autologous transplantation,” said study author Dorothy Sipkins, MD, PhD, assistant professor of medicine at the University of Chicago Medical Center. “The next step is to confirm this in human studies.”
Sipkins and colleagues study the molecular characteristics of tissue microenvironments, or “niches,” within the bone marrow where normal, healthy bone marrow stem cells divide and mature. From these niches, the stem cells produce all the different types of blood cells involved in transporting oxygen from the lungs to the rest of the body, fighting off infections and controlling blood clotting.
In patients with leukemia, however, these stem cells lose their powers. Part of the problem is that they are being crowded out by the rapid multiplication and spread of diseased cells as they take over the bone marrow, but this isn’t always the explanation.
Sipkins and colleagues have shown that the process is far more complicated, and focused, than simply overcrowding. Using sophisticated microscopy tools, they developed systems to monitor the movements of leukemia cells and hematopoietic progenitor cells (HPCs)–a group of cells that includes stem cells as well as more differentiated, though still primitive, progenitor cells that give rise to the various kinds of blood cells–as they struggled for these coveted niche sites.
One of the first actions of cancer cells, they found, is to settle into these niches, taking over the specialized supportive environments that HPCs need to perform their crucial role.
Within days of taking over a niche, leukemia cells began releasing a chemical signal, called stem cell factor (SCF), which attracts normal stem cells back to sites near their now-captive niche. Within one month, the leukemic cells could induce HPCs to leave even tumor-free niches and migrate to malignant sites.
But when the HPCs arrive, other signals released by leukemic cells interfere with the production of healthy new blood cells. As their microenvironments were taken over, the number of HPCs declined. HPCs also stopped responding to drugs designed to coax them out of the bone marrow and into the blood stream, where they could be harvested and used for transplantation.
Sipkins’ team was able to blunt this effect by blocking the release of stem cell factor by tumor cells. When the researchers inhibited stem cell factor, the number of HPCs went back up, as did their ability to migrate out of the bone marrow.
“Our data suggest that therapeutic targeting of SCF may increase the hematopoietic reserve and improve outcomes for bone marrow transplantation and autologous stem cell harvest in the setting of hematopoietic malignancy,” the authors conclude.
“This is not a cure for leukemia,” Sipkins said, “but it’s one more tool. We like to hit cancer from all sides. This approach could potentially boost the immune system’s response to the cancer by protecting the HPCs that are the source of mature immune cells. It could also maintain the patient’s ability to tolerate treatment and to remain active.”
“If human stem cells respond in the same way as mouse cells do, it could buy us time to apply other therapies,” Sipkins added. “By preserving the activity of HPCs and potentially boosting the immune system, the body’s own weapon again leukemia, we support the patient and take away one of the disease’s weapons.”
It could also make transplantation an option for more patients, enabling physicians to collect stem cells from the peripheral blood, which could be banked for bone marrow “rescue,” a technique that restores the patient’s marrow after it was damaged by high-dose chemotherapy targeted at the leukemia.”
Editorial
Anyone looking for easy answers or short sound bites that give us the perfect game plan is in for disappointment. CLL is a confusing and complicated disease. So are most cancers, but for cancers with very short fuses patients don’t have a chance to get confused before time runs out and things can get complicated awfully quickly. There is not enough time to dither, patients are up to their ahem knees in alligators before there is a chance to understand, get the lay of the land and actually hope to influence the outcome with a good game plan. Most that patients can do is find a good doctor and punt, hoping they made the right choice.
CLL is a “good” cancer because most patients do have time to come to grips with it. But that is also what makes it so scary and frustrating. As with all things that go bump in the night, you have the option of pulling the bed sheets over your head and pretend you never heard that “thump” and try to go back to sleep Or, you can get out of bed, get the flash light from the night stand and go out to investigate. What you do depends on your personality, your way of doing things. There are no absolute right answers, the “right” answer is the one that is right for you and your family. My job? Make sure the batteries are working in the flashlight, in case you want to go out and investigate. The choice is yours, as it should be.
I will not pretend to you that any of these are easy slam-dunk choices. The devil is indeed in the details, and there are no guarantees. My husband PC was fully aware of the risks of his aggressive “Bucket C” type CLL; he was perhaps one of the most informed CLL patients in the world. He and I made the best choices we could, given the cards we were dealt.
The half-empty glass view is that he did not survive the cord blood transplant. The half-full glass perspective is that knowing about his risk of infections and skin cancer kept him healthy and out of hospitals. Being proactive about keeping his galloping CLL under control with the least damaging drugs we could find meant he had terrific quality of life for the seven years between his diagnosis and death.
Was it worth it? Would I recommend the same strategy to him again if I had a choice? You bet! I miss my husband more than words can say. But I do not have the added agony of woulda, coulda, shoulda eating away at my gut. I wish he never had CLL, I wish he had a more indolent variety of it. But given that he did have CLL and it was a Bucket C variety, we played the hand we were dealt to the best of our ability. And no one can ask more of themselves than that. Cold comfort, but as they say, it beats a kick in the backside.
33 comments on "To Wait, or Not to Wait"
CLL is a very complex disease and while it is a malignant disease it’s complex interactions with the various parts of the immune system and the microenvironment within the marrow and lymph nodes make it a tad different from many solid tumors.
As I have previously communicated to you in a private message, I have reason to believe that certain cohorts of CLL patients may be better served by early (and perhaps , ongoing) therapy directed against their CLL.
Most likely this will not be best accomplished by what we traditionally consider to be chemotherapy (which is, by definition, toxic and not necessarily as discriminating as we would wish), but rather by means that act more directly on the abnormal cells and upon their ability to interact with their microenvironment.
If methods can be devised to suppress the growth of nasty clones without disrupting other important bodily functions, the mission will be accomplished, even if the cancer has not technically been cured. The ideal scenario, of course, would be to suppress the malignant clones while allowing repair of the innate immune system which might in turn destroy the residual abnormal cells.
Alternatives, of course, involve early HSCT or variations thereof (eg, NK cell therapy).
Allowing malignant cells to grow unchecked also permits them more opportunity to make an ever increasing number of errors in replication (clonal evolution). Some therapies (eg, purine analogs) may also increase the propensity for this change.
Other therapies which lead to ADCC or CDCC or which “unblock” apoptosis or interfere with various cell-to-cell signaling may accomplish these goals with less toxicity, and conceivably could be used (if necessary) on a chronic basis…converting CLL to a truly chronic illness.
The goal should be either to achieve a dependable, looong-term remission or a cure. A few years of remission with little likelihood of achieving a second or third remission doesn’t cut it, especially if other risks (AIHA or Richter’s transformation) are brought into play,
Certainly those patients who can be identified to have non-aggressive disease (a cut above MBL so to speak) or who are of particularly advanced age or who have severe comorbidities would best be served by watch and wait protocols.
In many instances no therapy is actually the best option with malignant (and non-malignant) conditions when other circumstances indicate little likelihood of success and great chance of harm. Most “end of life” therapies are terribly frustrating and (sadly) fruitless.
I hope that researchers continue to explore early treatment in select groups of patients with CLL who are younger and who have bad prognostics as that is the best hope for such patients to reach old age. I had hoped to “watch and wait” for many years, but was not granted that wish. Now I intend to be much more proactive.
Keeping patients in Watch & Wait for long periods without needing aggressive therapy is the name of the game. Every day we gain thusly is a day we can spend enjoying life rather than dealing with chemo side-effects. Since we do not yet have full bore CURE available (with the exception of mini-allo transplants), the next best things are:
* Low toxicity therapies that give nice long remissions without paying a huge price in terms of adverse effects. Remember the concept of “FCR Lite” that we advocated way back in 2002? In the next week or so I will be reporting the latest data from the large (unfortunately single arm) study done at U of Pittsburg regarding this approach. Impressive results, to say the least.
* Low impact therapy options that can keep previously untreated patients continue to be in that special virginal state. If we can put off first therapy for a while longer by taking a low impact drug with minimal adverse effects, what is not to like? Hence our interest in EGCG, the green tea component.
We sponsored the clinical trial using EGCG at Mayo with your hard earned cash. I am delighted to report I have just read the full length pre-publication paper reporting the results of the Phase -1 of this trial. As soon as I have permission to review this article for you I will do so. For now, you have to take my words for it that the results will knock your socks off!!
You want to do your bit for science and the patient community, as well as do yourself some good by enrolling in the Phase-2 of the EGCG study? Write to me and I will help you register for this important trial. You will have access to the pharmaceutical grade of EGCG (rather than the lawn clippings most of us can buy from internet peddlers or health food stores), and you will be carefully monitored while you are taking it. This is about as close to a free lunch as you are going to get, in my opinion.
I thought this might be a good place to insert a plug for my wife’s blog. Although I haven’t updated it recently, along with Harvey’s Journal, I think it provides a great deal of insight into the mini-allo transplant process. My wife was Patient One for a reduced intensity (mini-allo) transplant at The Mayo Clinic. Our blog is a blow-by-blow, day-by-day journal of the process. It isn’t easy! But it CAN be done and it CAN be a cure!
I am writing this from The Mayo Clinic in Rochester, MN. My wife is fast approaching her three year transplant anniversary. She is completely CLL free, her blood counts are perfect, and she is doing reasonably well. She has had some difficulty with GvHD. We are slowly working through these issues. She has been taking ECP treatments. ECP (extra corporal photopheresis) involves removing the blood, centrifuging it into components, tagging it with a maker, irradiating it with UV light, and returning it to the body. Researchers do not have a clear idea of why it works but for some people it helps to alleviate problems associated with GvHD. Treatments require 2 days per month (1 treatment per day, about 3 hours in length) for up to 18 months.
In any case, for more details about an actual mini-allo transplant here is the link:
My next piece of advice to those diagnosed with CLL is to seek treatment from a major medical center!!! i cannot stress this enough. You local doctor will likely kill you!!! There is absolutely no question in my mind that my wife would not be alive today if she had remained with our local (quack) er…doctor. If you are a Bucket B or C individual RUN, don’t walk to The Hutch, Mayo, M.D. Anderson, Dana Farber, University of MN, etc. to find a real expert that deals with ONLY CLL! A general oncologist doesn’t have the knowledge to treat the more aggressive forms of this disease!
My last piece of advice is to read this site religiously. It is the best site out there for CLL info!
Bruce:
Terrific news about your wife’s transplant outcome. It affirms my own understanding of mini-allo transplants.
I must say, however, your comments about local oncologists are a little extreme. I can understand your frustration. PC went through several local practitioners until we found one we could work with. But pragmatism requires that we work with the situation we have, change it for better when we can, and not burn bridges we may need later on. Not everyone can afford to go to expert centers. Not every insurance company will cover out-of-state medical expenses. And most definitely not all local practitioners are quacks that will kill you, in my opinion.
As I said, I understand your frustration but let us not throw the baby out with the bathwater. Many of the Humax-CD20 infusions that PC got were at a hard working and very busy local oncology practice. The office went through hell and highwater in terms of paperwork because this was (still is) an experimental drug. PC got excellent and compassionate care at this practice and I cannot be grateful enough to the doctors and excellent nurses there that took care of my husband.
A small bit of housekeeping: “Updates” has already become a high traffic site, less than one week after we went online. The spam bots have already found us. In an effort to block messages that sell viagra, sex toys, stock tips, free money from Nigeria etc, our website software flags and blocks as spam any comment that carries live links in it. It is then a huge hassle for me to strip off the live link and re-publish the comment. I would greatly appreciate it if our members do not include live links in their comments – it would save me a lot of hassle.
Chaya,
I am intrigued re. the Phase 2 trial for Green Tea. I have been taking 1000mg per day since 2006 and my counts and presentation have remained stable. I may be hindered if I have to travel a distance for a trial as I am preserving my work accruals because I may be able to retire in 17 mos. Will the phase 2 trial require travel to a Center far from home?
Chris Randolph
Adks. NY
Chris:
I am pretty sure participating in the EGCG or for that matter any clinical trial will mean traveling to the trial center several times. That is because you are truly an experimental subject when you are in one of these things, and they need to monitor you, collect blood, get data, poke and prod you etc. The EGCG trial is conducted at the Mayo Clinic, Rochester, balmy Minnesota.
There’s an old song: “You take the high road and I’ll take the low road and I’ll be in Scotland afore ye.” For a great multitude of CLLers, those without the best and those without the worst disease, there is still no clear consensus on when and how to treat. It is possible that for all of our careful guesswork, many of us will end up in the same place at about the same time.
CLL has its own natural history that is influenced by what it does when left unchecked — crowding out stem cells, or creating the setting for AIHA or ITP, or evolving into clones that are more difficult to kill. That natural history is also influenced by the treatments we throw at it, and these treatments may have a beneficial effect on that history by forestalling, say, immune dysfunction that creates AIHA. Of course, just the opposite can happen — treatment can lead to AIHA, or to marrow problems that prevent proper functioning of stem cells, or to the natural selection of chemo-resistant clones.
In 2006, I saw two respected experts, Januario Castro and John Byrd. Castro said I had some “pretty good sized (4 cm) lymph nodes” and that I needed treatment with FR and should consider a Campath chaser; Byrd got out his tape measure and said that since the lymph node mass on my neck was less than 10 cm, it was nothing to worry about. He said that I did not need treatment at all and that I had not needed treatment in the past when I had used single-agent Rituxan to manage what the available tests (CD38, FISH) indicated at first might be a somewhat indolent, or at least Bucket “B,” disease.
I am not sure who is right and who is wrong. In this debate among experts — take Terry Hamblin’s go-slow approach vs. Michael Keating’s more aggressive outlook — both sides make valid points.
On the one hand, it can be argued that there may be less risk in allowing CLL to take its natural course to a great extent (to the point where several NCI guidelines are setting off alarm bells.) There are no studies to prove that my decision to use single-agent Rituxan has been or will be helpful in prolonging my life. As Dr. Hamblin forever points out, what may seem logical on the face of things can turn out to be wrong when all the properly-sorted data is in. Assuming we ever have that data, which we often don’t, which just leads to more educated guessing.
On the other hand, it can be argued that regimens such as FCR are showing an ability to extend remissions more than in the past. Assuming you are lucky enough not to be among those who come down with Richter’s Transformation, melanoma, and other effects of suppressed T cells or mutagenic therapy. And assuming that depth of remission really equals longer overall survival in CLL, which is not a logical slam dunk, and which is an important but oft-overlooked question; it really is the million-dollar question as far as I’m concerned.
Call it intuition, but I still find myself more in the conservative axis of thought, the if-it-ain’t-just-about-entirely-broke-don’t-risk-making-it-worse-by-trying-to-fix-it school.
In the absence of very clear reasons to pursue treatment — examples would include crashing marrow, hidden lymph node masses that present a real danger, hemolysis — I am yet to be convinced that the desire to do what APPEARS to be prudent always outweighs the wisdom of waiting.
(In the meantime, I am all for the careful monitoring of everything, and Chaya you are to be commended for wrenching many a neck back from the sands of complacency. I had a CT scan today, in fact.)
In the end, we patients take big chances either way, and we are all walking to Scotland at paces over which we have less control than we’d like, and pretty much in the dark.
No one has the answers here, and when the only available therapies were toxic (alkylating agents and then purine analogs) the concept of taking the path of least resistence (don’t treat what isn’t broken) clearly made the most sense.
Many medical therapies have the potential to do more harm than good, or, at best, have limitations on the upside (such as toxicity, limited duration of response, etc) and significant downside.
When this is the case, avoiding therapy, especially when not particularly symptomatic makes sense.
I am, overall, a “therapeutic nihilist” when it comes to treating problems that most likely cannot be “fixed” as the pain most often exceeds the gain.
My concern, in this instance, is that left to their own devices, the malignant lymphocytes in some types of CLL (this is, after all, a heterogeneous disease) may only become more and more mischievous, until a “point of no return’ (ie, little likelihood of therapeutic benefit) is reached.
In such patients, if less toxic therapy can suppress the involved cell’s growth, a state of equilibrium may be achievable.
This is the case in certain chronic inflammatory conditions which are variations of disorders of immune (usually involving lymphocytes) dysfunction. When this state can be achieved, the patient’s disease progresses much more slowly (or not at all) and many horrendous complications can be avoided. When the equilibrium is lost (eg, if therapy is discontinued or fails to work any longer) there is often rapid progression to trouble and usually great difficulty achieving another state of remission. The goal, therefore, is to get the Genie back into the bottle and keep him there.
Please, any info on the EGCG trial would be appreciated.
Thanks for all you do for all of us.
My everyday task of checking the TOPICS only to find nothing was richly rewarded with UPDATES.God bless you and your work.
I will update the EGCG results from the Phase -1 trial as soon as I have permission from the authors – which will be as soon as the article is formally published. As you can understand, they do not want “Updates” to scoop their formal presentation.
Responding to some of the comments from 11qRick:
Yes, while we are waiting for a CURE to be invented, the next best thing is to find a way of taking down the CLL tumor burden in the blood, lymph nodes, bone marrow etc periodically, so that it does not get too big for its britches. Letting it get out of control may make it harder to control later on, may cause secondary problems such as autoimmune disease, secondary cancers and if we get really unlucky, damage to the precious stem cells.
But how do we achieve this periodic scaling back of the CLL level without causing more damage? Standard chemotherapy drugs available to us to date are all toxic to some level – some more than others. Kicking the beast back into its cage is good, but only if in the process we have not made it a more dangerous beast.
What are the least dangerous options that are worth considering, not to cure the darn disease but to get us breathing room?
1. For a subset of patients with the right prognostic indicators EGCG seems to be a good option.
2. Monoclonal antibodies are not completely without risks – witness the documented risk of opportunistic infections with Campath, Humax-CD20 and even Rituxan. There is also the risk of “using up” these bullets (people do develop Rituxan resistance, documented to do so, and it is only a matter of time before research confirms the same is true for the other monoclonals as well). But many patients have voted with their feet, single agent Rituxan maintenance remains very popular. Humax-CD20 may take over this role when it becomes commercially available.
3. Immune modulators such as Revlimid (lenalidomide) are all the rage, either by themselves or in combination with other drugs. For PC, it worked very well. It got him a good response in shrinking his swollen lymph nodes when Humax + fludarabine were unable to do so. The side effects (tumor flare, potential tumor lysis etc) are not trivial. Some patients cannot tolerate it. But if it works for you, this is an important drug to have in your tool kit.
4. Steroids have become popular, again. Drugs such as prednisone, dexamethasone seem to go in cycles, each new generation of patients (and their doctors) finding value in these gluco-corticosteroids. A number of excellent review articles have just been published on this subject and I will be reviewing them in the next few weeks.
5. Increasing the oomph of existing drugs or reducing their toxicity is not a sexy home run, but it is very important to keep these bunts coming. I refer to combinations such as “FCR Lite”, Rituxan + GMCSF, Rituxan + short duration Campath, and who knows Rituxan + beta glucan down the road if the research we are funding at the Holden Cancer Center pays dividends.
6. One intriguing approach that is under-used in my opinion is radio-immunotherapy with drugs such as Bexxar and Zevalin. You can look up our full length articles on the subject of Bexxar on the CLL Topics website. If you are early stage patient with DEMONSTRATEDLY clean bone marrow (this is very important, Bexxar therapy mandates less than 20% bone marrow involvement), radio-immunotherapy with these drugs may be a good way of getting long remissions. The large scale studies from U of Michigan demonstrate excellent and multi-year remissions with Bexxar, in a population of NHL patients. This is worth exploring, in my opinion.
7. What about good old bendamustine (also sold under the more sexy name of “Treanda”)? It may have value as yet another powerful chemotherapy drug with toxicity to match. It might have a role to play in folks who are fludarabine refractory and running out of options. Is it the next best thing since sliced bread? Hardly, in my opinion, notwithstanding the marketing hype surrounding this drug.
Bottom line, I do not think any of us can afford to ignore developments, either in the research arena or in our own bodies. Ignorance is not bliss. David, I am glad that riot act I read you had the desired effect. Do let me know when you get the CT scan results.
Chaya…
A suggestion…not sure how easy it will be to implement, but I thought I’d at least mention it.
Other groups (not other CLL groups…yours is the only one worth monitoring!) that I belong to that have comments, alert the registered members with an email that points to the group and the topic that has been ammended or added to. One can then go there and read the new stuff, and not miss any additional comments in previous updates. Some even provide a link that makes it easier.
It appears to be automatic when ever a comment or update is amended.
I just checked back on the previous CLL updates this morning, and found a couple more comments that have been added since the last time I was there.
I can see where this is going to get cumbersome on this end when one has a large number of updates and comments to sort through…and then occasionally check back to previous updates to see if there are any new comments.
Is there some way that Radha can implement a notification procedure to our mail boxes when a new update and/or comment is created? Hopefully automatically….
Harley (11qHarley! I just realized where 11qRick got his moniker from…guess I’m just slow…and me with the same deletions )
Chaya,
You may have pointed this out but perhaps the best reason of all to W&W is becasue of these new developments. I am stage 0 with an intermediate prognosis at 45 years old. My money (and hope) is that within the time I will need treament that there will be better treatments if not a cure available to me. I guess my hope is in the future.
Hi Harley,
This is Radha. Unfortunately, WordPress (the software on which this site is based) does not allow email notification of new posts for subscribers. I realize that this feature might make it easier for some to get the latest articles hot off the presses, but it is not in our site plan for the time being. I will keep my eye out for possible avenues to implement this in the future, but it will be a while in coming, if it ever does!
Thanks Radha…
>>the software … does not allow email notification<<
That’s what I thought, but I had to ask.
I guess that’s one of the habits that the membership here picks up quickly…ask EVERYONE about EVERYTHING!
Harley
Dear Chaya,
I am sorry to change the subject, but after reading the above article about EGCG, Would you consider doing a blog on PEITC? What do you think about a combnation of EGCG and PEITC? Sounds pretty powerful to me if they are compatible. They could be synergistic!!! Just wanted to know your thoughts!! Many Thanks!!
With Kindest Regards!!
Raymond Parker
For those of you who may be unfamiliar with this compound, PEITC (chemical name: Phenethyl Isothiocyanate) is found in a variety of cruciferous vegetables (cabbage, broccoli etc). As Raymond points out, this natually occurring compound may have the ability to kill a variety of cancer cells.
I have been keeping an eye on PEITC for quite some time. However, I have yet to come across any professional journal publications exploring its use in well conducted human cancer clinical trials, let alone specific to CLL. A while back the NCI sounded interested in conducting some trials but I do not know what came of those plans.
Ray, you seem to be interested in this compound. If you come across articles that may be of interest to us do let me know. I will be happy to review the information. But I try not to get too excited until there is credible (mainstream) information – a personal bias that I freely admit. Several pairs of eyes keeping watch for interesting stuff is a lot better than just me watching. We are stronger when we work together.
In the meanwhile, eat your vegetables! Maintaining a good and varied diet is something that you should be doing anyway. Dietary guidance should be in the “Owner’s Manual” for all cancer patients.
Dear Chaya, not sure what is the easiest way to contact you my husband, who is W&W but suddenly seems to be progressing unfavorably, and I, are interested in the EGCG trial. I have been following this site since his diagnosis last Dec and reading every publication from “Blood” to blogs and yours has been the most helpful. I started using your “charts” the first day I found them and Drs are very impressed by “MY” organizational skills, lol. Can you please contact me so I can get some much needed inf? We live in Northern Idaho but are over in the Seattle, WA area looking into the medical scene here. Have seriously been considering trying to get into MD Anderson etc. Fred Hutchinson is right here but they seem very transplant minded and we aren’t quite ready for that route. Keep up the good work…this update site was much needed and appreciated, thank you for your hard work and determination even after your loss. April.
April:
I just sent you a personal email with contact information. I will be happy to help you and your husband in any way I can.
Chaya
First I just want to add my thanks to you and to the power you spread with your efforts. I found your site soon after I was diagnosed in November 2005 and have been reading it faithfully since then. The information and common sense you put out to the society of people with CLL helps us all to better understand what we have and what to do with this disease. I have read with great interest this information and the comments on W&W. This is the tactic that I have been following for the last three years. The interesting thing is that my WBC was originally found to be +/-42,000 and over the last three years it has slowly gone up to 65,000 with various fluctuations in between-sometimes as much as 7,000 to 8,000 both up and down between blood tests. I have discussed with my doctor that this represents a relatively small percentage increase overall. The other thing is that I have absolutely no other symptoms. No enlarged lymph nodes, no tiredness, no nothing. If I hadn’t had a routine physical I still wouldn’t know that I have this. My platelet count is beginning to get a little lower (110-115) and with that high a WBC my % Neuts are pretty high. I understand that you are not a physician but I’m sure you have been made aware of many stories and have heard of many different situations. I was just wondering if there are other people in the community of who have counts this high and are still Watching and Waiting? My general philosophy is that I would like to not get involved with chemo until my body really needs it but at the same time I don’t want to wait too long and miss the boat.
Again, thank you for all you do, I hope you know how much comfort your work gives to people who could use all the comfort they can get.
bob
Bob:
You are right about my anecdotal database of CLL patient profiles – it must be one of the largest in the world!
Yes, I have heard from patients still in W&W, no symptoms worth noting, and WBC getting close to 200K or even higher. (By the way, I think you meant to say % Lymphs and not % Neuts in your comment above).
It sounds like you have an relatively benign form of this disease. The slow decline in platelts is something to keep an eye on, but clearly you are doing the right thing in not treating this indolent form of CLL. I hope you stay in W&W for many more years!
Several of the comments above has asked about the EGCG clinical trial at Mayo Clinic. I’m in the study, so here’s some information for those interested. You can read about it at the “Clinical Trials” web site (clinicaltrials, then add “.gov”)–it’s Study #NCT00262743. (I hope this citation avoids the “link” problem Chaya noted in her response to Bruce.) The description there will answer most questions. In short, participants have to be Stage 0, 1 or 2, and cannot have had treatment for their CLL. It requires extensive initial lab work, bone marrow biospsy, ct scans, etc. to get into the study. If accepted, there are monthly visits to Mayo for 6 months (for blood work and exam), and then you can remain on a maintenance dosage of the drug for a year for free (with 3-month visits to Mayo). Participants don’t pay for the drug or for blood work related to the study; they do pay for everything else (and it gets pricey–so check insurance coverage). The oncologists are fantastic there (I see Clive Zent, and have also seen Tait Shanafelt (study principal investigator). I have no regrets about participating, and will continue with my doctor at Mayo forever (of course, it helps that I live in Minneapolis–90 miles from the Clinic). For more information, the study coordinator is Michelle Roos, phone #507-538-7036.
Jim
Thanks for posting the information about the EGCG trial, and thanks too for that clever way of getting around the live links issue. Smart man!
One additional comment from my buddy Tait is that the Phase -II EGCG trial is offered at Mayo Clinic in Rochester MN as well as Scottsdale AZ. It appears the Mayo Clinic in Florida is not going to open their part of the trial any time soon. There is also a chance that Duke will open a center as well.
I second Jim’s comments about the Mayo Clinic(Rochester MN version, not all Mayo’s are created equal in my opinion)doctors. Clive Zent, Neil Kay, Tait Shanafelt and Tim Call are my absolute favorite CLL experts – it also helps they are my favorite human beings as well. And as my students at Princeton used to complain, I am a very tough taskmaster. I don’t grade on a curve and I do not believe in grade inflation, not when it comes to judging CLL experts. Each of these guys has done huge amounts of pro-bono work for our patients, at my request, often over weekends and holidays. I won’t breach patient confidentiality but I am not gilding the lily when I tell you their quick and effective intervention made all the difference in several cases of badly mis-diagnosed and incorrectly treated patients.
Chaya,
The literature and a recent poster at ASH again speaks to the limited role of CT scans in CLL. That said, CLL is a lymphocytic cancer, and much of the activity, especially in the “stable” phase may be occurring in the nodes, not the blood or even the marrow.
Relapses may show up in nodes first, and that will effect treatment decisions. Whether it effects outcomes is more in doubt.
As you have pointed out, studies results don’t answer questions that were not designed or powered to assess. Unless your circumstances are lock stepped with those in the study cohort, please exercise caution in extrapolating the results to your situation. This caveat applies not just to the fine studies of the role of CT in CLL, but to all the treatment studies as well.
Be well
Brian
Chaya,
This concept of when to initiate treatment or stay with watch and wait is complicated. We can’t let our tumor load get too high, yet treatment too often can have its own poor side effects.
Wondering about solid numbers though.
I read an article a while ago where Byrd at Ohio watches & waits until around 300. In my visits with MDAnderson, they wanted to start my first treatment of FCR around 150.
Wondering about your own thoughts Chaya. I guess the best answer would be it depends on your specific CLL.
In my case I am 13q and unmutated.
At this point my plan is to treat with a combo of Rituximab and high dose prednisone.
Would like to stay away from fludarabine since I have unmutated CLL.
I plan on my frist treatment when I’m close to a lymphocyte count of 150.
Do you have any lymphocyte count numbers that you like for treatment?
Thanks,
Leo
First of all, I cannot recommened – period – since I am not a medical doctor.
But if you were to ask me my layperson perspective on a given number of ALC or WBC when treatment should be initiated, I believe there is no such number. SLL folks can have masive tumor load with hardly any of it showing up in blood counts. CLL folks can have very high WBC but if there is no nodal involvement the actual number of CLL cells in the body can be quite small. Each of us is unique, hence the need for competent evaluations at regular intervals.
Morning Leo (and Chaya)…
I’m a good example of the inability of the WBC or ALC to predict treatment.
My WBC count was 66,000 in 2005. At that time, my doctor said that she had seen it as high as 150,000 in other patients and not needing treatment. My nodes were visible, but the scans and palpating didn’t produce any reason to treat yet.
The following year mine climbed to 92,000 (ALC was 83,000), but then started dropping, and by September of 2007 when I started treatment, it was back down to 70,000.
We started the treatment because internal nodes were getting much too large. One was reported as pressing on my bladder. Not to mention that I was having a hard time shaving the chipmunk cheeks without slicing them! I never did have much of a swollen spleen.
So, I went both ways…we were first waiting for the WBC to get out of hand, which it never really did (for a CLL patient anyway), then switched to monitoring the nodes as they started enlarging.
After my first treatment, the WBC count dropped to less than 7,000 and after the Campath (which ended a year ago next month) has remained about 3,000-5,000.
Harley
Hi Chaya and all,
I find the wait & watch to be a curse and a blessing. Bob Parker may take note that I am currently with a tumor ALC at 211,000 WBC at 242,000 and could probably be classed as “bulky disease by the numerous large nodes primarily about my neck but extending to clusters in the clavicle area, axial, groin, above right elbow, two small lumps in the left cheek and unknown internal involvement. I am 13q del., IgVH mutated, CD38-, ZAP-70 58% pos but probably not accurate as it was done in a commercial lab. I was diagnosed on Sept. 2006 with an ALC of 23,200. Two and one half years later at 65 I frequently go out X-country skiing in mountainous terrain and have no “B” symptoms, in fact I don’t get sick with flu or colds even when my wife and friends get sick. Nodes are becoming uncomfortable at times and my spleen occasionally “talks” to me.
I had an onc who was willing to treat with R+FFP which has some unknown risk regarding Hepatitis A,parvovirus and anaphalactoid reaction. My leaning is toward the least toxic protocol avoiding Fludarabine. My dilemma is how to assess my profile? Does my high Beta-2M (hovering around 4000),my relatively rapid tumor growth and lymphadenopathy trump the “good” markers stated above? I have had a consultation with Byrd who confirmed the CD38- and the 13q but could not get a clone for the IgVH ???? I have been HemeScanned and nothing other than the 13q single allele deletion showed up.
If I were reasonably assured that I were not chemo resistant I would probably take the FR bullet. Tugging on the other side is the rapid environment of new therapeutic developments that pulls me toward trying to buy time by foregoing the “big guns”. There is a crying need for in vivo testing to have patients receive the best result from what options currently exist.
REGARDING Green Tea (EGCG) I have experimented on myself with CanTea Max (hard candy lozenges) and Teavigo capsules by taking an escalating dose from 213mg up to 1,043mg daily over a period of eight months. I started each escalation right after a two month blood draw and charted my blood work using your great charts. After averaging out the upward curve I could not discern a bit of difference.
Thoughts I have had about EGCG available to patients are: Can we be sure we are getting the active catechins we are told by the advertising? In the case of the CanTea Max 71mg EGCG per lozenge I had a discussion with Chris Dwyer (CLLCANADA) and he raised the issue of whether the catechins can withstand the heat from making it into a hard candy. I called Origin BioMed and talked with Liam who was very interested to try and help me answer the questions – has the establishment of the EGCG been tested from post-production lozenges and at what heat are the lozenges made. He called me back to say the lozenges were made at 300 degrees (he presumed F) and said they were made according to a process dictated by a Mitsui Norin scientist in Japan and that Origin BioMed was just the manufacturer, which really did not satisfy my question. Any comments Chaya?
We the ones dancing with the CLL Bear owe you much. Love ya!!
WWW
Evening, Wayne…
I had the same questions about how much EGCG we were actually getting in the green tea concentrations (after seeing what they were using in the Mayo Clinic trial, 400 mg and up, I wanted to get as close as I could to that amount).
So, a little research took me to Consumer Labs who tested 23 (I believe…may have been more) different brands (such as GNC, Teavigo, etc) green tea products for label claim, consistancy and unwanted nasty stuff like lead, etc.
Of those they studied, they only recommended a few brands…three, I believe.
I have settled on one of those. Life Extension’s Mega Green Tea Extract. It was highly rated by Consumer Labs. Met the label claim, and contained no nasties. The label claims 326.5 mg of EGCG in the 725 mg capsule.
I’ve been taking two a day (one at breakfast and one at supper) for a total of about 650 mg of EGCG, plus three cups of regular green tea.
I received an email reply from Dr. Shanafelt at Mayo Clinic when I asked him about this, saying that all I really had to watch for was the remote possibility of liver damage. At these relatively low doses (the trial patients got up to 2,000 mg daily with no adverse effects) He was not concerned.
I started taking this before I started my PCR treatment 18 months ago. Only one capsule daily then, however…I started the two a day about a year ago.
It’s probably too early for me to tell yet, but it’s been almost a year since my Campath chaser was finished, and my liver enzymes have remained fine, and my ALC is yet to reach 1,000.
My doctor thought the ALC should have recovered more by now, but is still hesitant to say that the EGCG may be having an affect.
So, I guess I am saying that I think I’ve found an accurate dosage of EGCG in those capsules, and that it appears to be working. I do not intend to stop taking them unless my doctor tells me to…and so far, she thinks that it isn’t hurting, just is not sure if it is helping.
Harley
Hi Harley,
Thanks for the tip about Consumer Labs. I think this is a good tool, however I was only able to find a handful of Green Tea supplement reviews (way less than your stated “23 or more”)??? which did not include Teavigo or Origin BioMed’s green tea lozenges. I am certain that because of CLLTOPICS and ACOR postings that Teavigo and Origin BioMed’s EGCG products are widely preferred in the CLL community. If I missed something please clue me in for it was not for lack of trying.
In general the website appears to provide useful information and defines what constitutes a quality product and possible hazards in many supplements. I only hope the subscriber fee keeps Consumer Labs free from “payola” and that they expand their product sample.
May your dance with the CLL Bear be forever slow!
Afternoon, Wayne…
I just went to Consumer Lab for a quick check (which I didn’t do BEFORE I wrote the above note … the “23” was just a guess) and did a quick search (I have not subscribed to it…I received the original information from another person who did email me a partial list).
Consumer Lab did indeed state that they tested 23 products, with 18 brand names. But you have to subscribe (which I didn’t since I found sufficient information elsewhere and I’m not interested in any other products at the moment) to see all the results.
Life Extension’s Mega Green Tea extract (I get it from Amazon.com) was one of those approved, and had the highest, confirmed EGCG content.
The consumer Lab search only shows a “sample” of three results without subscribing.
I don’t want to go into too much detail here…it’s a bit off topic in this update, and I’m beginning to sound like a salesman!
Maybe Chaya would want to revisit the green tea discussion?
Harley
All
Being a second generation CLL’er I lived with the W&W for 24 years with my mother. Literally weeks before she passed, I was diagnosed. With my children’s health now at a much higher risk I am going to do what ever I can to assist in the study and treatment of this disease. I am fortunate enough to live near the Phoenix Mayo clinic and have just been accepted into the ECGC “green tea” study. I will share with Chaya anything that I am able to as I move through this trial and any other lessons learned as I refuse to just W&W.
Jim
Jim, please accept my personal thanks as well as thanks of the CLL community.
I consider each volunteer in clinical trials a true pioneer and a hero. Without well conducted clinical trials and their research findings, we will never have better therapy choices. Many folks take green tea extracts on their own (I hope with the knowledge and consent of their local oncologists). But all of the information published by these patients on internet forums does not really help develop medically accepted therapy options. Anecdotal information is, at best, iffy. We really have no way of knowing whether or not EGCG works, how well it works, what type of patients are best served by it, until and unless we have credible results published in reputable journals.
The latest article from Mayo addresses many of these questions. I am waiting eagerly for its publication. While I have read the pre-publication copy, I am not at liberty to discuss it until it is published.
I am extremely reluctant to “recommend” any particular over the counter brand of EGCG or suggest dosages. But for what it is worth, PC too used the “Life Extension” mega green tea extract.
Hi Wayne,
After being diagnosed with CLL at 45 (unmutated, CD 38+, ZAP70+), I rarely missed a workout. I was probably in better shape after a year of W&W than I had been in the last 5-10 years. Then one day, while on the cross-trainer, I realized that it wouldn’t matter how strong my muscles were or how fit my cardiovascular system was if there wasn’t enough red blood cells in my vessels to deliver oxygen to the cells. During my two and one-half years of W&W my hematocrit had gradually dropped 12 points from 49 to 37. It reflected the fact that my bone marrow was getting pretty full of b-cells, leaving little room for red blood cells and platelets to be produced at the normal rate. I can only guess how low my hematocrit might have gone before I would have been symptomatic. I might have made it another 6 or 8 months, but probably would have significantly increased my risk of treatment complications due to the fact that I had used up all of my reserves. At the time, my b2M was 7, bone marrow was 95% CLL, and I had bulky abdominal disease. After a year and one-half of treatments, my disease is finally low enough to consider transplant.
If you are still having difficulty deciding whether you want to start treatment or not, you may want to look at the trend of your hematocrit or possibly getting a bone marrow biopsy to see how much reserve you have left.
I also wanted FR to work but my response was only so-so. However, I don’t regret trying it. The response alerted me to the fact that I wasn’t going to have much time or many chances to get my disease under control. If I had waited to start treatment until I had symptoms, I doubt that I would have been able to tolerate all the agents I needed to get my nodes below 5cm. At this point my chances with transplant are more than just a shot in the dark.
I also wish there was more science and less art in the management of CLL. Good luck with your quest to slay the dragon.
Steven
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