Does Better Understanding of CLL Lead to Longer Life?
Back in 2001 when I heard about CLL for the first time, Dr. John Gribben was at the forefront of CLL research at Dana Farber. Couple of years later he moved back home to the UK and he is now at the prestigeous Barts. Dr. Gribben is one of the experts whose publications I track as a matter of course. His most recent article in Blood does a great job of pulling together all the modern understanding of CLL and guidelines for frontline treatment of patients. Abstract of Dr. Gribben’s article is below.
Blood. 2009 Oct 22.
How I treat CLL upfront.
Gribben JG.
Institute of Cancer, Queen Mary University of London, Barts and The London School of Medicine and Dentistry, London, United Kingdom.
Chronic lymphocytic leukemia (CLL) remains incurable, with patients having a clinical course of disease progression to requirement for treatment followed by an unremitting course of relapse of disease. Over the past decade there have been major advances in understanding of the pathophysiology of CLL and in the treatment of this disease. This has led to greatly increased response rates and durations of response, but until recently little evidence that this had led to improvement in survival. Advances in the use of prognostic factors that identify patients at high risk of progression have led us to the question that if there still a role for a “watch and wait” approach in asymptomatic high risk patients or if they should be treated earlier in their disease course. Questions remain including; what is the optimal first line treatment and its timing and is there any role of maintenance therapy or stem cell transplantation in this disease? CLL is a disease of the elderly and not all of these patients are eligible for aggressive upfront chemo-immunotherapy regimens, so what is the optimal treatment approach for more frail elderly patients? It is highly likely that our treatment approaches will continue to evolve as the results of ongoing clinical trials are released and that further improvements in the outcome of this disease will result from identification of therapies that target the underlying pathophysiology of CLL.
PMID: 19850738
As Dr. Gribben point out, over the last decade we have made huge strides in better understanding of the pathology of CLL. Better drug cocktails yield higher response statistics and longer remission periods. But until very recently there has been no concrete proof that patients were living any longer because of all this new fangled stuff. Even more important, there is a lot of confusion about when to start therapy and what to use as frontline treatment. This “Best Practices” paper pulls together all the important stuff we have learnt over the last decade and how it fits into your modern treatment game plan.
Who Is Most at Risk of Getting CLL?
Dr. Gribben gives up-to-date CLL statistics that you might find interesting. Here are some highlights from his article. Remember, these are statistics based on general population. They may not reflect your specific situation.
- Roughly 15,500 people will be diagnosed with CLL in the USA in 2009. Of these, more than half (just over 9,000) will be men. No question, there does seem to be a slight male bias in this disease.
- Median age at diagnosis is 72 and death due to CLL is at age 79. Almost 70% of patients are older than 65 years and patients younger than 45 is just 2%. If you are a very young CLL patient, consider yourself specially “blessed” – not that you asked for it or anything.
- CLL is small potatoes when it comes to incidence in the general public. Just a tad over 4 people out of 100,000 get CLL each year. When statistics are examined from 1975 through 2006, there does not seem to be any increase in this rate.
- The single biggest risk factor of getting CLL is a family history of CLL or other lymphoid cancers. CLL is a familial cancer. Remember that the next time you are reading about long term research. Your kids and grandkids may benefit from our dedication today.
Accurate Diagnoses CLL
Half the battle is making sure the initial diagnosis of CLL is correct, since there are many “kissing cousins” that sort of look like CLL and might fool the local ‘strip-mall oncologist’ that sees just one or two cases of CLL each year.
For starters, CLL is always a cancer of B-lymphocytes. What used to be called T-cell CLL has now been classified as T-prolymphocytic leukemia and a totally different beast. I need apologize no longer for not talking about this T-cell cancer. It is not in my sand box. So there.
When the disease is present mostly in the blood (as demonstrated by elevated absolute lymphocyte counts in a CBC blood test) it is called CLL. If the disease is preferentially present in enlarged lymph nodes it is called SLL. But when rubber meets the road there is no real difference between the CLL and SLL and they are treated the same way. Dr. Gribben recommends a proper biopsy of an accessible lymph node and review of the biopsy specimen by an expert pathologist for confirmation of SLL. He does not recommend the easier fine needle aspiration of lymph node for SLL diagnosis. Fine needle aspiration is a bit of a hit-or-miss affair. The needle may / or may not hit the exact location where some SLL cells are hanging out, your results may vary accordingly. Classic CLL requires no lymph node biopsy since the disease is clearly present in the blood and can be detected by means of blood tests.
He also thinks a bone marrow biopsy (BMB) is not needed at the time of diagnosis except in special circumstances. He uses a BMB when it is time for treatment, in order to get a good sense of the lay of the land. It may also be necessary to do a BMB sooner if the patient has cytopenias (low red blood cells and low platelets), to figure out if the root of the problem is autoimmune disease (AIHA or ITP) or compromised bone marrow function.
Mug-Shot of CLL cells
Alongside is a picture of what CLL cells look like when they are viewed under a microscope. CLL cells are small, round B-cells (stained dark purple in this slide). Often, there are “smudge cells”; think of them as cells that have gotten squished flat. It seems CLL cells are a bit more fragile than normal B-cells and they are more likely to get bent out of shape in the process of making a microscope slide of the sample. You can see some of these smudge cells in the picture.
Accurate CLL diagnosis requires certain features. First, ALC has to be more than 5.0K, as seen in a CBC. If the ALC count is less than 5.0K it is called monoclonal B-lymphocytosis (MBL). We discussed MBL in detail in an earlier article. If you have not done so already, please read our recent articles on CBC, ALC, red blood cells and platelets to become familiar with the acronyms.
Phenotype: Devil is in the Details
The next step is to conduct a flow cytometry test. All cells have a number of special structures on their surfaces. These are given names “cluster designations” or “CD” numbers. Different cell types have different set of CD types present on their surface. Flow cytometry looks not only to see what CDs are present, but also how densely they are packed on the cell. For example, “bright” expression of a particular CD type (say, CD19) means there are many thousands of copies of CD19 present on each cell. A “dim” expression of CD20 for example means there are far smaller number of CD20 groups present per CLL cell. Some labs use “+” for dim, “++” for intermediate and “+++” for bright expression of various CD clusters.
CLL cells have their own particular profile of CDs. Think of it as a fingerprint of this particular variety of cancer cells. The fingerprint is different if we are talking of some other B-cell cancer. Flow cytometry looks for this unique fingerprint and it is very useful in confirming CLL – as well as ruling out some of the “kissing cousin” cancers. It is particularly important to rule of more dangerous varieties of B-cell cancers such as mantle cell lymphoma. The table below gives the fingerprint profiles of the various B-cell cancers. Depending upon the sophistication of your testing lab all or only some of these CDs may be studied and reported.
Staging
There are two classic staging systems, Rai and Binet. The Rai staging system is used most often in the USA and the Binet system is used in Europe. Both systems have become a tad of date as we have learned more about CLL, but both staging systems still retain value and it is therefore important for us to learn about them.
The Rai system looks at increasing accumulation of CLL cells. It therefore focuses on ALC, presence of more and larger swollen lymph nodes over time, swollen spleen and liver, all of them choke full of CLL cells. Anemia and thrombocytopenia (reduced red blood cells and platelets, respectively) is attributed to bone marrow getting progressively packed with CLL cells and therefore preventing the bone marrow from producing new red blood cells and platelets as the old cells get worn out and die.
At the time of diagnosis about 25% of patients are Rai Stage 0. We have discussed the relevance of Rai Staging in much greater detail in an earlier article. In a less fortunate 20% of patients the disease is advanced and accompanied with anemia and thrombocytopenia. B-symptoms (weight loss, fevers, night sweats, extreme fatigue) are present at time of diagnosis in 20% of cases and may require treatment right away.
The Binet system considers three potential sites of lymph nodes (cervical, axillary, inguinal – see picture below for locations) as well as spleen and liver. Patients are staged according to the number of these five possible sites where disease is present. Anemia (hemoglobin less than 10) and thrombocytopenia (platelets less than 100K) are the other two factors taken into account in Binet staging.
CLL staging is done using either one or combination of Rai and Binet staging systems along with CBC and physical examination. CT scans and BMB are not necessary or recommended for staging purposes. But Dr. Gribben cites an exception to the general rule about early use of CT scans:
“Although care has to be taken not to over-use CT scans in early stage patients, in patients identified at higher risk of progression, CT scans provide a more accurate assessment of intra-abdominal disease than clinical examination and upstaging a patient by CT scan criteria alone has prognostic significance. I therefore find it useful to perform CT scans to determine baseline adenopathy in patients who present with poor prognostic features, particularly del 11q, since this is often associated with an increased frequency of intra-abdominal lymphadenopathy.”
Prognosis
The biggest advances in our understanding of CLL has come in the area of modern prognostic indicators. Dr. Gribben reviews the importance of FISH, IgVH gene mutation status, ZAP70, CD38 expression in determining the risk status of patients. Below is his list of poor prognostic indicators in CLL. We have discussed some of these in an earlier article “What type of CLL do you have”? in patient-friendly language. I recommend you review it if you are not sure of your particular risk “Bucket”.
As Dr. Gribben points out, “a current challenge is to understand how we should use this new information in clinical practice”. Here are some interesting quotes from the paper:
“However useful the biomarkers may be in predicting how cohorts of patients will behave, they are less precise in predicting outcome in Individuals.
“It is often the patient who demands the results of the prognostic tests. Certainly, if I were to be diagnosed with CLL I would want to have as much prognostic information as possible for planning purposes.
“My own experience is that patients usually request these tests hoping that they will have good prognostic markers and the finding of poor risk factors can often lead to increased anxiety, while not changing management, and this requires considerable time in the clinic explaining the potential significance of the findings.
Editorial Comments
OK Doc. We get it. If you got CLL, you would want to know all the prognostic information for “planning purposes”. But a generic Joe Patient walks in, unprepared and uninformed, he may not be able to deal with the bad news and it takes up too much of professional time walking him through all this complicated stuff, not to mention holding his hands as it were.
But how about the patients’ “planning purposes”? We too have lives, families, finances and stuff that can benefit from having a rough idea of what is coming at us round the curve in the road. But I accept we live in the real world, we understand limited time is available to each patient during expert consultations.
So, how about this Doc, how about truly informed and involved patients? Patients who learn about all this difficult stuff on their own time, patients who come to you for the facts, just the facts, and all the hand holding and emotional and educational support is done elsewhere? Would that not be a good solution for all parties concerned? How do you feel about patient-friendly educational websites that present credible information such as this excellent article of yours, reviews that are CME (continuing medical education) suitable to layperson patient audience?
Patient follow-up
Dr. Gribben follows patients every three months for physical examination, history and blood counts. If the track record shows an indolent disease, it may be OK to see the patient less frequently. He pays special attention to any changes in symptoms (such as development of B-symptoms, increasing adenopathy at one site, elevated LDH – lactate dehydrogenase) since this may suggest transformation to more aggressive Richter’s disease. He does not use routine CT scans, only in specific circumstances as we discussed earlier.
Frontline therapy: When, What Why
One of the most interesting and useful aspects of this paper are the excellent flowcharts Dr. Gribben has included for therapy decision making. Here is his approach to frontline therapy:
- This chart is very easy to follow. The present day standard of care is to initiate treatment only when the patient is symptomatic, until then the safest course seems to be good old Watch & Wait. There are always special circumstances and we discussed some of these in an earlier article “To wait or not to wait”.
- Dr. Gribben has a full section on treatment of elderly patients who are not in the pink of health even without CLL. For them, chlorambucil may be the best bet. Recent comparisons between fludarabine versus chlorambucil as single agent therapies in such patients have shown little advantage for fludarabine. Chlorambucil is easier to tolerate, cheaper, easier to dispense and has fewer adverse effects.
- But if the patient is younger and in better physical shape, the choice of therapy depends on whether or not he has the dreaded p53 deletion (FISH test). Alemtuzumab (Campath) is one of the few drugs that is known to work well with p53 deleted patients. Dr. Gribben does not mention a couple of others, Revlimid, flavopiridol etc, that are also thought to work in these patients. But that is perhaps because these drugs are not quite there in terms of full fledged clinical trials certifying their usefulness in p53 deleted patients.
- In keeping with recent emerging expert consensus, Dr. Gribben recommends eventual mini-allo transplants for patients in this high risk group.
- In the absence of p53 deletion or mutation, Dr. Gribben recommends FCR, the triple combo showcased at M. D. Anderson. FCR is potent chemoimmunotherapy and it gives excellent response rates and deep responses to many patients. While 6 cycles of FCR is no walk in the park, the remissions are longer lasting than most other therapy regimens. Life after FCR remission ends can be problematic, as we discussed in an earlier article.
While this flowchart may look simplistic, notice there is “or clinical trial” at two different points in the chart. This covers all the other drugs and their various combinations, both recent and a few years older. Dr. Gribben gives a good review of the results obtained in many of the clinical trials that have been pivotal in defining the advantages and disadvantages of these other options.
As I said, this is an excellent and expert overview of the CLL scene. Long as this review has been, I have done it scant justice since there is a lot more detail than I have addressed. Thank you Doc, for your thoughtful and well considered comments. Muchas gracias, on behalf of several thousand of our determined members. Our guys are going to be that much better informed the next time they see their local oncologists. Heck, they might even give a printout of your article to their local healthcare provider at their next meeting, bring this valuable “Best Practices” guidance to his/her attention. I am all for access to important information, it does not matter much to me whether it is trickle down through traditinal channels or bottom up on patient advocacy / education forums such as this one.
59 comments on "“How I Treat CLL Upfront”"
MY HUSBAND DIED LAST JUNE FROM CLL, OR RATHER COMPLICATIONS ASSOCIATED WITH THE TREATMENT OF CLL. HE WAS GIVEN CAMPATH AND HAD TUMOR LYSIS SYNDROME, WHICH HE COULD NOT COMBAT.
HE WAS DIAGNOSED IN 2005 AND ONLY LASTED 4 YEARS. HE HAD THE 17P AND 11Q DELETIONS AND THE UNMUTATED GENE. WE WENT TO SO MANY DOCTORS AND EVEN MD ANDERSON HAD NOTHING TO OFFER US. I REALLY THINK THAT FOR THE MOST PART OUR LOVED ONES ARE GINNUEA PIGS. NOTHING WE TRIED HELPED AT ALL AFTER HIS FIRST TREATMENT(FCR)WHICH HE BECAME RELAPSED TO.
I WOULD RECOMMEND WAITING AS LONG AS POSSIBLE FOR YOUR FIRST TREATMENT. THAT TREATMENT SHOULD HELP SOMEWHAT. MAY GIVE YOU A COUPLE OF YEARS. AFTER THAT, FORGET IT. JUST ENJOY YOUR LIFE AND THE TIME YOU HAVE LEFT. FURTHER TREATMENT WILL MOST LIKLEY JUST CAUSE MORE HARM THAN GOOD.
I AM SORRY TO SAY THIS. BUT WHEN I THINK OF WHAT MY HUSBAND WENT TRHOUGH, TO NO AVAIL, THIS IS MY RECOMMENDATION FOR ALL OF YOU WHO ARE IN THE SAME BUCKET.
LYNN TORTORELLO
Quotation: “The single biggest risk factor of getting CLL is a family history of CLL or other lymphoid cancers. CLL is a familial cancer.”
Isn’t this statement in an absolute oppposition to majority views in science?
Maxi
Maxi:
No, I do not believe it is in opposition at all. I do not know a single expert that does not agree CLL is a familial cancer, and the impact of family history on risk of CLL is a direct quote from Dr. Gribben’s paper.
I try hard to make sure my editorial comments are identified as such. The familial nature of CLL and its impact on risk of incidence is the opinion of experts, not just my take on things.
As Always – Excellent work from our first, best advocate. Thank you Chaya. I have copied this for my family.
Matthew
Thank you Chaya for a good article. By taking Dr. Gribben’s information & including the additional charts & verbiage that you provided as given all of us a Very good “Best Practices” knowledge to take to our Doctors to review where we stand. This is especially good for new CLL patients.
Be well!
thanks for finding all this info for us. “watch and wait” seems to be the kaiser standard of treatment, and while i am asymptomatic in my 3rd year of diagnosis, having all the bad markers is a mental strain. the question for me is, once my desease goes south, do i really want to treat with such a bad prognosis?…bob armstrong
Very informative as usual, many thanks Chaya.
Dave
I was diagnosed in 2001. The diagnosis (summarised) was Lymphoproliferative disorder, pathologist says “circulating monoclonal kappa CD19, CD20 positive lymphocytes coexpressing CD5 but not CD23 or CD10, immunophenotype not tyical for CLL.” Pathologist didn’t feel comfortable labelling it as CLL.
How can I find out what this means and its implications? My Dr. said it’s close enough to CLL to be dealt with in the same fashion. I’d like to know it this is true, etc.
Thanks
EAC
I was diagnosed in 1996 at the age of 55 years. My CBC
last month showed a white count of @200K. I have not had any treatment. I am a female and enjoy excellent health except for CLL. I am very active and if I began any treatment my biggest fear is that it will make me ill and unable to be active. There is no cure for CLL today! I believe for a person my age the “watch and wait” theory has worked well.
Chaya,
Under the important features for “poor prognosis” is listed “Ki67 and p27” which I do not recognize and “Thymidine Kinase” Which I am familiar with but have never had it done as part of testing. I believe it is mainly done in Europe. What gives and can these features help in defining mechanisms of disease that would suggest better targeted therapies, particularly in the newer clinical trial areas?
WWW
Fangfarrier
Fantastic article Chaya. A must read for the newly diagnosed and an update for the rest of us.
Your articles are always eagerly anticipated.
Many thanks
Hugh
“It is often the patient who demands the results of the prognostic tests. Certainly, if I were to be diagnosed with CLL I would want to have as much prognostic information as possible for planning purposes.
“My own experience is that patients usually request these tests hoping that they will have good prognostic markers and the finding of poor risk factors can often lead to increased anxiety, while not changing management, and this requires considerable time in the clinic explaining the potential significance of the findings.”
Chaya thank you for keeping us informed and taking the time to break things down in terms we can understand.
I absolutely disagree with good doctor’s above broad statement! Yes there are patients who really don’t want to hear the particulars of their disease however there ARE those of us who feel empowered and less of a victim when we are fully and factually informed. As for my husband and I we become anxious when we feel we are not being leveled with. I agree wholeheartedly with Chaya. Eileen
Chaya,
thanks much. It is always informative. More information only has helped me at least understand what I am being told and stimulates better questions. FCR (2x) seemed to work well but then some lymph nodes began to increase and I also has anemia and low WBC so they have changed regime to R plus prednisone with great response but I may not be able to use FCR or maybe can later but the information above will help me understand my options. I encourage everyone to become as informed as possible and part of that is to learn to manage our anxiety that is quite a job and very challenging to help our spouse.
Again thank you.
Jerry
I find these comments very interesting as even this small sample shows the wide variety of ways that CLL can affect us. I was diagnosed in July 2000 at age 52. I was initially W&W and that lasted only a relatively short time. By December 2002 I was in treatment with RFC which I had through May 2003, the full protocol. That was followed up with Campath from December 2003 into February 2004 (I received injections only once per week — not the standard three times– and only for a total of seven weeks) and have been in “complete remission” since midFebruary 2004. I am tremendously healthy and active. Other than my semiannual check-ups with Dr. Coutre, CLL has no impact on my life at this time.
Hello,
The doctor here referred me to the local CLL Supportorg for info., also ro the Macmillan society (a charity), I do wish they had been much more currant and factual, like you are! You really are excellent; you credit people with brains and do not seem to think that age is an automatic disqualifier to unddrstanding and independent thought. Good for you and even better for your readers.
Any site which purports to give information needs to be regularly updated, like yours.
Must say, go easy on, or don’t let separate organisations for had-holding proliferate; they may forget that people are independent /entitled to be so, even if they have this or other cancers!
Thank you again, for your clear, “clean” information.
Mette
Chaya,
Again, thank you for all the valuable information.
Rita
My father had Hodgkins Disease and I have CLL/SLL so for me the familial prognosis has validity. I am 67 was diagnosed 5 years ago.
I am now 27 months into remission after FCR ( my second visit to chemo)and trying very hard to justify my membership in the SKI club.????? spending the kids inheritence!
The point I want to make is that the longer the remission goes on the more you think about “where to go from here” at the appropriate time. It is not an easy condition to think about especially as it took 6 months from the end of treatment for my counts to get above the critical level. Having said that today the counts are remarkable and I feel fine.
I read you regularly and have taken many aspects of my treatment into my own hands….HOW!!! after my hematologist told me that I could get all the prognostic tests done I wanted but it would not change the way he would treat me, I changed Doctors got on to a plane and flew to the Mayo (I live in Canada) and had all the test done and then with my new Dr and the Mayo reports was able to make sensible decisions on treatment. For me to leave my life in he hands of anyone regardless of who they are without being fully informed of all aspects of the disease and treatment options is unthinkable.
Yes I understand that at the present time (I don’t believe in miracles) the ultimate prognosis is terminal, but the days weeks years ahead of me until that time I want to maximise and enjoy life to the fullest during that period what ever it may be.
It is also interesting that I have found music which has given my overworked brain box a different passion to placate the constant and unrelenting thought processes about where I am and where I am going.
Check out “Haemo Blues” a song for all of us on http://www.Haemo Blues.com
Derek Halifax Canada
WillB425
Being in the W/W catagory for the past eleven years…and absorbing as much of the information as possible…I like the observation made by LYNN TORTORELLO above…She writes….
“I WOULD RECOMMEND WAITING AS LONG AS POSSIBLE FOR YOUR FIRST TREATMENT. THAT TREATMENT SHOULD HELP SOMEWHAT. MAY GIVE YOU A COUPLE OF YEARS. AFTER THAT, FORGET IT. JUST ENJOY YOUR LIFE AND THE TIME YOU HAVE LEFT. FURTHER TREATMENT WILL MOST LIKLEY JUST CAUSE MORE HARM THAN GOOD.”
Friends who have undergone the Chemo treatments have expressed the same sentiments. (…just something to evaluate and consider…and with new advance may not be good advice six months from now??).
Chaya…you are greatest…thx.
To LYNN TORTORELLO:
I’m very sorry to learn of your husband’s passing. This must be a terribly hard time for you while you face so many changes in your world. You may email me offline mamalee50@gmail.com.
To Chaya:
Thank you for another clear abstract including the graphics and charts, and of course your input. We value your input to these articles, as much as the material itself. Because of your dedication and diligence we are informed about CLL in our lives or that of loved ones.
Linda
I would just like to make a few comments;
Dr. Gribben wrote this article for doctors, not for patients. Given that his audience is principally hematologists/oncologists who read the journal Blood, there is absolutely nothing offensive about his statements regarding the utility of various prognostic tests in assessing the likely outcomes of individual patients.
There most certainly is reason to expect individual patients to experience adverse outcomes with therapy, but the flow chart that he utilizes makes it clear that treatment should not be considered until patients become symptomatic. The chart suggests very different courses at that juncture depending upon the patient’s status as regards overall health and the persence or absence of 17p deletion/p53 allelic mutation.
Dr.Shanafelt and his colleagues at the Mayo Clinic wrote a similar and equally informative article in 2006 which appeared in the Annals of Internal Medicine.
Articles such as these are very useful to help us to learn more about best practices and, at times, to educate our treating physicians, but as they are written by physicians for physicians, there is no reason to feel animus over any specific positions taken or advice offered by the authors…they are not telling us (as patients) what we should or should not do.
Good luck to all,
Rick
Rick,
That is an excellent point. We as CLL patienhts tend to take some of this information personally and fail to realize that articles such as these are written for the professional.
Another reason why sites such as these are of such value.
I was just diagnosed in September after a routine physical exam and blood work that showed an elevated Lymph count of 28K. I know pretty low for most of you. I am only 50. After researching what a elevated count could mean, I actually went to my doctor and said “Do I have CLL”? He thought i probably had an infection and was over-reacting as did my wife. Redid the blood work and referred me to the Hemo/Onocology center. Walking into a “Cancer” clinic for the first time had me just totally freaked out. More blood tests, One CT Scan, and a Flow Cytometry later I was confirmed. Deletion 13q and CD-38 negative or I guess low. Now I am told to watch and wait? That seems really like a reactionary approach. Isn’t there something I can be doing pro-actively?? I don’t expect treatment at all. I hate drugs anyway. But now I get to wait to see if this develops further over time. I am newbie here for sure.
I love this site though. It’s given me so much more information about my illness than my doctor ever has explained. God bless you all.
Chaya,
I’ve had CLL since 2002 so have reading your postings since that time. It’s made me feel informed and able to speak with my doc and ask intelligent questions. I feel that’s he’s following good protocol too. He keeps some of your information in my file. My FISH test was the first one he had run. Keep up the great work.
Kodirea
Chaya,
I am new to the disease. I was diagnosed about a year and a half ago and I am one of the “blessed” patients who is under 45. I was diagnosed at the age of 38. I now have turned 40 and am trying to absorb the latest information to really understand what it is I have.My health is very good and my counts have not moved yet. Your insight and up to date information is helping me quench my thirst to understand this disease. Thank you and I look forward to more.
How did I get CLL? No one in my family has had this disease…on either side or back at least two generations. I believe I got it after I was operated for a GIST in August 2005..The operation was called a Whipple. I lost half my pancreas, gall bladder plus the tumor area.. Did they take out too many lymph nodes. I got type 2 diabetes also. I am in the “watch and wait” stage, with only several nodes in my neck slightly swollen…..I just joined this site and thank you for the information and frank discussion. I am now 70…….
Thank you for this excellent post, Chaya. Dr. Gribben was my oncologist when he was at Dana Farber Cancer Institute and I can personally attest to his excellence, and beyond that he is a very humble and warm human being. To meet him you would never know he was an internationally respected specialist. He cares for each of his patients as if your health was THE most important thing. I was diagnosed at the age of 48 and at 50, I went into treatment with a WBC of 115 in Dec of 2003. Having been through it all, I would not rush into any treatment, but when you can’t function due to your illness, I think it is time to face treatment. By May of 2004, after 6 treatments with FCR I was in complete remission (PCR Negative) and celebrated my 5th year of remission in May of 2009. The last thing Dr. Gribben said to me was “Think cure.” Just a personal note in esteem and gratitude for Dr. Gribben and his work on our behalf.
chaya
Thanks for the excellent article and your continuing efforts on our behalf.I was diagnosed in 2004 and blood figures have become depressingly bad .Fortunately no physical symptoms and all the prognostic test results are good.I am in good physical shape through regular gym work and have no other health problems.Heres the rub- I am 74 and my Doc has 70 as a notional cut off for FCR treatment ,which is my prefered option.So the the longer my physical health remains good, the less likely I am to be seen as a candidate for FCR.Any thoughts ?
ROBERTO
Chaya,
I looked for the full text of the article but it was epub ahead of print. You’ve got the full text? When will it be published? You know me, I like to read the original.
suz
Roberto:
I believe there are no hard and fast rules about age restrictions in order to qualify for FCR treatment. In any case, how old you are is not as important as how healthy you are. I am willing to bet you will be able to sweet-talk your doctor into FCR, if that is what you want and IF that is what is right for you.
Rick:
My respect for Dr. Gribben is obvious, I hope. And I do know BLOOD is a professional journal. Nevertheless, there is an all too common assumption that patients are not quite competent enough to be fully informed and participate in their own healthcare – and I object strongly to that slam dunk assumption. Some patients cannot handle it. Others can. One shoe does not fit all. In the final analysis it is all about informed consent – whether it be clinical trials or potentially life saving (or life threatening) therapy options.
Patients who ask for prognostic information have a right to it. Plain and simple. An absurd but not totally out of line analogy is a bank manager who refuses to hand over money in the customer’s account when presented with a valid check – because he does not think the customer is wise enough to spend his money prudently. He may well be right about the customer’s profligacy, but that does not give him the right to refuse the man his money!
No disrespect intended to your fellow brethren in white, but we are adult patients, we have a cancer and need medical care, but that does not mean we have signed away our rights as consumers or adult human beings. How people respond to crises is very personal and individual, a lot depends on their personalities as well as their support systems. Dr. Gribben would be the first to admit he does not have professional training as a psychologist – how can he tell whether or not a given patient is a good candidate for full prognostic information disclosure, all in the course of a fifteen minute consultation? By asking our doctors to become our surrogate guardians and father confessors we are asking too much of them – and too little of ourselves.
Lindacarole:
Not all CLL is familial. A very substantial percentage of CLL patients are the very first ones in their family to have been diagnosed with it. There are some hints that CLL may be triggered by exposure to certain pesticides (Agent Orange may be implicated, for example), especially in individuals pre-disposed to cancer. It goes back to the concept of “seed and soil”.
Waynewells:
Dr. Gribben has given a long list of all the potential prognostic indicators. Some are more “popular” than others. Most centers do the IgVH, FISH, CD38 and Zap70 and call it a day. Others have their pet indicators (B2M is very popular at M. D. Anderson). The pattern of use of these prognostic indicators is also determined by geography.
Singer99:
Lack of CD23 expression in phenotype is troubling. CD23 and Cyclin D1 are important in distinguishing between CLL and mantle cell lymphoma. It may be a good idea to get the flow cytometry repeated, preferably at one of the CLL expert centers, to make sure what you have is indeed CLL. A rock solid diagnosis is very important since it determines all your other decisions down the road.
Suz:
Send me a personal email and I will help you locate the full text of the article.
Its all about quality of the time God has given us! I’ve had one round at its come back but I’m still going working, exercising and enjoying my life! Good luck to all fighting the battle! Jim
Chaya:
You are right on the mark, as always. Those of us who are currently ‘watch and wait’ will keep this advice near to hand, because we know it might be needed at any moment . Thanks so much for your continuing vigilance on our behalf.
Cathy
Becky
Chaya,
Thank you so much for this website and information. Reading the information and comments of others helps me feel like I’m “doing something”. I’m 56, diagnosed a few months ago, stage 0. The “watch & wait” seems crazy. I’m looking for clinical trial to participate in so I’m at least doing something. My health is good. My only symptoms are some swollen lymph nodes and more fatigue than usual.
I count you and this website as a gift from God. Thanks again.
Joe K.
Chaya,
Let me just say thank you for your work and time. I was diagnosed with cll in april of 2008. I am a former Marine Viet Nam vet, was over in 1967 an 1968, It is said, i have this from agent orange . I am 60 years old, an watch an waiting! This type of cancer is not in my family . I wonder about my sons an my Grandkids ?
Again thank you for your work.
Thank you for all of your excellent information. I was diagnosed at 48, 4yrs ago, and my mother had cll diagnosed at about 50, I asked my dr. if I could have it because of my mom, and he said “no way”, it’s not like that. I go to a university med center for my follow up, and no one seems at all interested in the fact that my mom had it. She had it for 11 years, until it turned to NHL for the last five years of her life. So, I always wonder, will mine turn to something else. Anyway, your site is the most informative, and I really thank you for it, I wish my mom would have had something like this for her.
Chaya:
I’ve been reading your site for quite a while now and have never properly thanked you for your hard work and advocacy. You are definitely a blessing.
I am one of the “blessed”, diagnosed in 2003 at age 33, three months after a rather severe late-in-life bout with mono. I am convinced that my CLL was trigged by the EBV that causes mono. We know many cancers are triggered by viruses; is there any research going on in this direction?
I am now worried that I may have passed on a predeliction for CLL to my children; my oncologist said “don’t worry about it… go ahead and have kids!” Hopefully by the time they have to worry about it, there will be a cure.
As for me, I’m “low-risk” and as yet asymptomatic, though my counts are generally above 140k. I look out for “low-risk” clinical trials (such as the unsuccessful MyVax) until I need something like FCR, and currently take over-the-counter EGCG for what it’s worth.
Good luck and God bless to everyone, and keep up the good work Chaya.
Todd
Chaya,
I am very grateful for this site. I find it to be as informative as it can be and in plain language for most of us to understand. Like many others who have stated they do like to be informed on their own disease and how it does progress or what the next step would be, I feel it is important to be as knowledgeable as you can to make the right decisions for your own health. We are all on a journey and it is wise to know which road to take while along the way.
Many blessings to you and yours for all the unselfish work you do to keep us all informed. I usually send this to my family as I get them so they will be as educated as well.
Thank you.
Anita
Great article Chaya.
Thank you.
Monique
Quotation: “The single biggest risk factor of getting CLL is a family history of CLL or other lymphoid cancers. CLL is a familial cancer.”
I’ve been researching for 5 years about risk factors and causes of cancer. A genetic risk factor is only one factor out of four. In general the oncologists explain cancer as a “genetic” desease. It’s an easy and quick answer. And it leaves no option for other approaches/research as radiation impact, hight stress level, chemically treated nutrition etc. I’ve been diagnosed with CLL at the age of 43. For generations, not a single member of my family (mother/father side) died or has been diagnosed of cancer. They all lived a very healthy vegetarian life style as I did – and still doing. But i worked more than 20 years in an air traffic control center – exposed to radar radiation and electricity smog. How would you now explain my risk factor? The answer is not that easy, and maybe will be very frightening. So far, no Doctor has been able to answer this question on a scientific basis. As long the research concentrates on a single impact factor, the longer it takes to find the clue for a proper approach in healing CLL and cancer in general.
Last but not least – Chaya, many thanks for your work you’ve done so far. Also these numerous comments of CLL-Patients and relatives mean a lot to me.
Take care
Isabella/Switzerland
nevergiveuphope:
Regarding the familial nature of CLL, here is the direct quote from Dr. Gribben’s expert paper:
Among the strongest risk factors for the development of CLL is a family history of this or other lymphoid malignancies. A number of familial clusters of CLL have been reported, and there is genetic anticipation, the process whereby the median age at onset in a child of a multi generation family with malignancy is younger than that of the parent generations.
My husband too was the first in his family with CLL. (But his father died of colon cancer in his early fifties – and there are tentative findings that CLL patients have higher chances of having family members with other cancers, including solid cancers). He had no exposure to radiation or harmful chemicals.
Environmental factors as well as stress, radiation, prior exposure to pesticides, history of long standing and unresolved inflammatory disease, prior history of multiple bouts of pneumonia, viral disease (mononucleosis?) – some or all of these could have an impact on the incidence of CLL. But none of these have yet been proven to increase the risk of CLL. It is important to remember that.
Familial connection, on the other hand, has been proven. Every researcher who has looked at the origins of CLL has agreed there are familial clusters that are far and above random happenstance.
Chaya,
Thanks for the information and reassurance given by your site. I’m not religious but would call what you do a ministry. I was diagnosed in 1998 at age 50 and had no symptoms until 2007. After a first F&C intervention lasting 6 months I’m back in the community and just returned from a 4 week tour of Japan & Korea. It seemed everybody else had infections but me!
I only write this to say to those at the watch and wait stage that there seems to be no automatic progression and it might be best to take it as it comes. I used to follow the blood test numbers at the 6 monthly test intervals and now I just ask my specialist if its better worse or level. Maybe I’m fortunate in having the same doctor throughout and being supervised in Bournemouth, UK.
Incidently, I was diagnosed as needing a 3x coronary bypass graft in 2001. This was performed by a surgeon who normally operates on babies hearts and it took place at the Harley Street Clinic in London. The 8 years anniversary is this month and not a single angina pain. All this was carried out and paid for in full by the English National Health Service. Speak as you find, the system has worked for me.
I took comfort from another thread where, was it Neal, coined the term ‘energy budgeting’. How appropriate, fatigue is the most annoying permanent symptom because it limits what I can get done in a day. Apparently one does slow down with age and maybe there’s an element of that. Another factor of age is that I’m seeing more and more friends with other cancers and they all seem worse. I used to feel slightly fraudulent having only Leukemia ‘lite’, now I see from this site that there is Small LL, I shall henceforth be able to look down on them as the wimps!
Great show in Toronto BTW, you had the presence of Bono, Barry Manilow and Oprah W. combined but did the Canadians really like the joshing?
Please keep it all up.
Martyn, UK
The Canadians were warm, generous and had a terrific sense of humor. I could not have asked for a more wonderful audience.
Bono, Barry Manilow and Oprah? You are kidding, right?
Bo
I was diagonosed with CLL in Dec 08 at the age of 47 with the 13q deletion, i was suffering from fatigue, constantly getting infections, and for the most part just feeling miserable. Problem was initially my WBC was slightly high and thats what lead them to check for CLL. My bloodwork since then has been great, the latest showing RBC slightly low. My dr tested for MCL but that came up negative. I have times of fatigue, chest pressure, and pain in midsection on a daily basis. My dr is thinking chemo, but if it is my CLL acting up why shouldnt it show in my bloodwork? I see sometimes people say chemo is something that should wait. MY father and brother both had prostate cancer so I figured I got it through the family line. Can you have good bloodwork but still be getting worse physically?
Like many others that have responded similarly, I also prefer to be informed and know my prognostic markers. Knowing this information, I have both continued to educate myself about possible future treatments that may be relevant (still in W&W) and have also made other plans/decisions in my life that have left me in a much more comfotable situation pyschologically.
As an action-oriented individual, having this information is definitely a god-send and has not spiraled me into depression. I hope that Dr. Gribben reads these comments and reconsiders his point of view.
Luki
Chaya,
my husband was diagnosed Oct 08/08 at 48 years old.
He was given a lymph biopsy and after cbc blood test results, his oncologyst started him on 4 weeks of Cholorambucil on Nov 12.
He has had no other marker testing at all, and has now just been asked for the 2nd time not to return for another 6 months.
At the time of his last visit his absolute Lymphs were at 4.4 and less than a month later are up to 5.3.
Also, when we asked the Dr. if he should be getting one or both of the flu shots, his response was “your guess is as good as mine…”
I’m wondering if we should seek a 2nd opinion what are your thoughts?
Maria
Thank you Chaya for your work on behalf of all of us family members and patients.
Julie Griggs
Thanks again Chaya. We do very much appreciate your efforts. I am wondering if there are any clinical trials comparing FCR to ChR. Mal
mrblot:
I do not believe anyone has done a head-to-head double arm trial comparing FCR versus chlorambucil + Rituxan (I assume that is what you meant by ChR)
Thank you Chaya, for keeping us so informed on CLL. in terms we can understand. I was diagnosed in 2007. Due to IGG defiency I am being treated with IVIG treatments monthly. It has helped with infections cutting them down to 3-4 a year.
Barb
I am a 77 year old very active male. I still work, and volunteer in the community.
Thank you for your dedication to educating us all about this disease. I was diagnosed on September 7, 2009, by an oncologist who said, “You have CLL, but don’t worry, you won’t die from it.” He then told me there was no treatment at this time, I am to watch and wait.
I was struck by his lack of empathy, and the coldness of his delivery.I immediately lost confidence in the possibility of his treating me in the future, should I (hopefully not) ever need it.
On November 17, I’m going to Scripps to see Dr. Thomas Kipps, who I understand is a profound expert in CLL. I believe it’s always good to get a second opinion, especially regarding such an important diagnosis.
Frank
jenny
my husband was diagnosed at aged 54 and he now has p53 depletion and is on campath treatment . He had polio as a child , and there is now a recognised post-polio syndrom being found in people ( a friend has it – it has affected her immune system , and she now has inflamed joints and trouble walking as a result) As CLL affects the immune system could this past polio be a ’cause ‘ of my husbands present problems ?No one in his family has had any kind of cancer . His consultant would not commit himself as to whether it could be .Any thoughts on this?
Jenny
Thanks Chaya. A very useful article and as you say, the flow chart is excellent.
CClaver my situation was similar to yours when I was first diagnosed. I am another of the young “blessed” patients, who goes against type. Diagnosed at age 40, female, no apparent family history. As far as taking a proactive approach, I highly recommend doing what you can to stay very healthy while you watch and wait. Adjust you diet to a whole-foods diet, exercise frequently, drink plenty of green tea, adjust your supplements with the help of a good dietician. Above all cut added sugar from your diet. Chaya has written about sugar and its effect on cancer cells. I think the article is stored somewhere in the archive. All of this turns into quite a full-time job once you put your mind to it and makes for a very pro-active approach. If nothing else you will find that after a few months you will look and feel younger and healthier, which is a great thing to feel at any time but especially when you’re contending with a life-threatening disease.
Hello evansjenny, concur with your comments am a 48 year old male diagnosed 10 months ago and am in W&W. I have not found much on supplements for this disease. Eating healthy should be enough from what I gather from most nutrition experts. Any comments on this would be helpful. Thanks Chaya and all.
David
Chaya,
I wouldn’t gainsay the familiar aspect in getting CLL but with all due respect, I still think that saying CLL is a familiar cancer is a much too strong expression.
Let me show some statistically numbers taken from a manual of the cancer center Munich 2008:
3.4 of 100.000 people get CLL newly each year.
5% to 10% of them have a familiar disposition or with other words 90% to 95% have no familiar disposition.
The risk in getting CLL for first-degree relatives if a lineal ancestor had CLL is about 2 to 7 times higher than in other population.
In other words this special group of people has a risk of about 7 to 24 of 100.000 people.
For comparison about 120 of 100.000 men will get a prostate cancer and about 280 of 100.000 women (>50 age) will get a breast cancer.
So even if there is a ancestor with CLL there is an absolute low level risk to get this kind of cancer in comparison to most common other ones.
In my opinion the statement “CLL is familiar cancer” may cause unrealistic fears considering the above statistical numbers and as long as more than 90% of new CLL patients each year have no familiar disposition and the familiar risk is only 2 to 7 times higher, in my opinion this statement represents not the pure reality.
Hans
Hans:
Once again, I repeat the direct quote from Dr. Gribben’s expert paper:
“Among the strongest risk factors for the development of CLL is a family history of this or other lymphoid malignancies. A number of familial clusters of CLL have been reported, and there is genetic anticipation, the process whereby the median age at onset in a child of a multi generation family with malignancy is younger than that of the parent generations.”
Also, as I pointed out in an earlier comment, I am not disputing the majority of CLL cases are considered “sporadic”. The label “familial” does not mean all instances of CLL are linked to a family history of CLL or blood cancers, each and every time. It does mean that there is irrefutable evidence that shows there is a genetic link, that the disease occurs in familial clusters enough times that it is NOT (repeat, not) just happenstance.
The familial nature of the disease gives us great hope of finding what makes this disease tick, what particular or set of specific genetic lesions cause this disease. I do not see the tag “familial” as a curse or something to be frightened about, instead I see it as an opportunity to truly learn the face of our enemy and thereby defeat it.
I think you and I are disagreeing on semantics. In any case, you are welcome to your perspective. I am just trying to get across the point that this description of CLL is not a whim of mine, but one that is voiced by just about every CLL expert in the field.
Chaya:
I think you are right; we may be disagreeing only in semantics.
I agree absolutely that probably the only known hard fact is the familial one, to answer the question: What is the risk profile to catch a CLL?
I agree too, that the familial aspect is a good chance to learn more about CLL.
My concern was and is that somebody who throws only a glance at this familial aspect could be misled and maybe become desperate:
“Oh my God! I got CLL, what about my poor children …..” There are many more kinds of cancer which could be tragically for families than CLL.
Grandmas/grandpas or mothers/fathers with CLL shouldn’t run scared for their descendants because of the real relative low risk.
And last but not least, the risk of a traffic death in the USA (2006) is about six times higher than the risk of a familial CLL.
What I try to say is everybody should find their individual balance in handling risks: In the one hand the natural (high) risk of life itself and the other hand the (low) risk of a familial CLL.
Sorry, if my try for an additional statement to this familial matter failed – it’s not that easy to do it in a foreign language with the necessary sensitiveness.
(Now I know my November 7th statement was a little bit too short and provocative, sorry for that.)
Maxi:
Yes, I agree that a little information can be a dangerous thing.
I cannot help the patient who “throws only a glance at this familial aspect and maybe become desperate”. This site is clearly meant for people who are more thoughtful, more willing to read the details and understand the naunces. I will not “pull my punches” as they say in the USA on account of the hasty or ill-informed patient that does not want to take the trouble to read and understand. CLL is a complex disease and needs more hard work than that!
Fear is a very dangerous thing, especially when people jump to conclusions that are not justified by facts. The only antidote to fear is detailed and factual information. Familial CLL is a scientifically justified term, and while I did not invent it or do the research to prove it, I fully agree with it.
Yes, I too have a daughter and I too worry about her, since my husband died of CLL. But it does not drive me into a panic. Panic serves nothing. Instead, knowledge of the familial nature of CLL drives me into running this website to educate patients, long hours communicating with researchers doing the cutting edge work in the field so that I understand the risks better, helping my daughter maintain a healthy lifestyle that gives her best chances of resisting disease and infections.
This website tries hard not to be sensational – or superficial. But we do not shy away from telling the truth, even if that truth is scary. So, besides semantics, now I think there is a real difference of opinion here, based on our different approaches to what patients need to know. You want to protect them from frightening things. I want them to know all about such frightening things, so that they are empowered to help themselves and their families.
Maxi, let us agree to disagree, end this two-way discussion.
Thank you so very much, Chaya, for your continued support to this community. When it comes to raw information and what it means you are the Bible of CLL, or perhaps the definitive textbook for the layman.
The treatment question is huge. Especially in light of what to do when relaspe comes calling.
I was diagnosed in 2005. My bonemarrow is packed with diffuse CLL cells. 85% plus…not good. Neutrophils at about 500 not good. Yet, here I am alive and kicking five years later.
I had oncologists who told me I HAD to have treatment or I would die, and here I am. I have had others who told me to wait…the NIH. This really is a decision that is subjective and you have to be your own best physician, or really trust someone who is a CLL expert.
And, probably what is right for one CLL’er may not be right for the next.
Thanks again for more info to help us make that hard call of when to begin treatment and with what. Personally, I think the new clinical trials of things like CAL 101 hold the key. Low toxicity, next to none, take the pill, the CLL calms down, and when it comes back, take some more pills and calm it down and do that forever. Who cares if it is not a complete remission, as long as it calms down and you can live with it, just keep taking the pills.
Best Wishes to all, and much love to you Chaya.
I’m wondering why the last comments to this section are more than two years old…It’s March 2011 and I was just diagnosed with CLL. I’m 51 years old, and a female. I’m in watch and wait and educating myself, mostly through this website for it has the best data that I have found and certainly the
most in-depth. Still reading and working out questions for my Doc. While any cancer diagnosis is humbling I feel mostly grateful to have
so much time ahead of me, at least seemingly so…more tests to run of course.
Thank you from the depths of my heart Chaya for all this work you’ve done.
It is more than helpful.
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