Updated: March 2, 2008
Long Term Survival
Are CLL Patients Living Longer?
If Not a Cure, At Least Longer Life?
A new article has been published in Blood Journal on the subject of long term survival of CLL patients. The paper, based on SEER survey data, is reviewed in our article titled Are CLL Patients Living Longer? (3/2/2008)
When You Have Been Around the Track a Few Times
Salavge Therapy Produces Grim Statistics
There are not many good therapy choices for CLL patients who become resistant to fludarabine and Campath. While a number of salvage therapies are in use, the results are variable and the survival statistics are grim. We agree with the experts in the field that a wider range of approaches and more effective agents are desperately needed for these patients. Refractory CLL is our review the literature and the latest reported results of salvage treatment for refractory CLL. (10/14/2007)
The New Think on CLL Is Finally Here
The Dawn of a New Era
An important new review article has been published in the New England Journal of Medicine. The Rai/Binet staging systems have been important in triggering therapy decisions. In this article the authors, who include Dr. Kanti Rai himself, bluntly state that the staging system with its emphasis on watch & wait should be replaced by better methods using modern prognostic indicators. We cover this important article as well as several other related works in The Dawn of a New Era. (2/24/2005)
Insight, Advances and Research
Tracking Down Clues in Population Data
Dr. Tim Call is a hematologist/oncologist at Mayo Clinic, Rochester, MN and an Assistant Professor of Medicine at the Mayo Clinic College of Medicine. He has done much important work in the area of familial CLL and lymphoma, and is responsible for developing a database at Mayo Clinic on the familial incidence of B-cell malignancies including CLL, B-cell lymphomas and a few related diseases. You might recall his name as an author on the Mayo Best Practices article – Current Approach to Diagnosis and Management of CLL. We are pleased that he has written this article, Familial CLL, addressed to the patient community. We strongly encourage that our readers register in one of the recommended databases when appropriate. (7/13/2004)
Familial CLL: Not the Worst Day in Your Life
Genetic Predisposition and Anticipation
To Know or Not to Know: That Is the Question
Not the Worst Day of Your Life is a review of the research findings on the familial aspects of CLL. It is well documented that CLL strikes more than one person in some families, there is clearly a predisposition to the disease that has been passed on from one generation to the next in these families. Some day, this type of research may prove to be the key that unlocks the CLL puzzle. In addition the data show that in families where the disease strikes several generations, the children of a CLL patient are likely to be diagnosed with the disease at an younger age compared to the parent. Finally, we discuss some of the difficult issues involved in testing children for potential problems down the road that may never materialize. (2/12/2004)
Adhesion, Homing and Resistance to Therapy
Why Peripheral Blood Numbers Do Not Tell the Whole Story and Why CLL Cells are Hard to Kill.
It's a Tale of Adhesion Factors, Chemokine Trails, Receptors and Blockers
The behavior of CLL as a disease and the different characteristics exhibited by strains with different clonal genetic aberrations are all related to cellular chemistry. We examine a number of critical aspects such as resistance to therapies, bulkiness of lymph nodes, infiltration of bone marrow and the support structure for CLL cells in their preferred environments. We also look at some futuristic possibilities for therapies in this article titled Adhesion, Homing and Resistance to Therapy. (12/8/2003)
Nature of CLL
Clonal Evolution: How the Disease Grows and Evolves
In this article, Clonal Evolution, we review important new research into the mechanisms by which clonal B-CLL cells become more aggressive and harder to kill. We look at the implications for treatment strategy and offer a new approach to managing the disease. (11/7/2003)
The Case for Risk Rating: Staging Does Not Measure Closeness of Bone Marrow Failure
Rai/Binet Staging Do Not Predict Survival
Staging Does Not Predict Survival examines a newly published journal article which draws attention to the criteria used in the Rai and Binet staging systems in the light of current understanding of the causes of clinical measurements. The Rai-Binet systems are not good predictors of survival because they do not consider why anemia and thrombocytopenia occur in different CLL patients. (11/3/2002)
Night Sweats, Fever and Fatigue and Their Causes and Treatment
Disease Progression Correlates to Increasing B Symptoms
A number of papers examine the immediate causes of the symptoms associated with advanced blood cancers. An alphabet soup of cytokines can be identified as the culprits. The available treatments for these symptoms are, of course, palliative in nature. Curing the cancer would be the best way of eliminating the symptoms. To get the details, read our review of B-Symptoms. (7/30/2003)
Genetic Mutations and Their Effect on Overall Survival
Important Paper Identifies Common Genetic Abnormalities
The difference between good prognosis and poor prognosis for a CLL patient resides at least in part on the particular genetic abnormality that characterizes the patient's disease. Stilgenbauer, Dohner, et al., lay out some basic correlative data on common mutations and survival expectations associated with them. Therapy choices should be made based on the risk associated with each type of abnormality. To learn more, read our review of their paper, Genetic Abnormalities in Blood Cancers. (5/22/2002)
Swollen Lymph Nodes
by Chaya Venkat
There is really not much mystery about swollen lymph nodes in CLL. Enough CLL patients have had lymph node biopsies so we know what makes them large: they get stuffed with lots and lots of clonal CLL cells, and the structure of the lymph node grows in order to make space for all these new residents. Why do some patients have large lymph nodes and relatively low WBC numbers? Think of it this way: there are three buckets. one is the bone marrow, the second is lymph nodes, and the third is peripheral blood. The CLL cells distribute themselves between these three buckets. Those with most of the CLL cells in the bone marrow and a puny 5-10% left over in the blood are at the “leukemic” end of the spectrum. Those with most of the CLL cells residing in the swollen lymph nodes are more the “lymphoma” type. In fact, there is no real distinction between CLL, a leukemia, versus SLL, a lymphoma, except in the sense that the cancer cells seem to prefer one location more than the other in the two types. Get this point folks: bulky lymph nodes represent a reservoir of a large number of CLL cells, that can multiply quite happily in the lymph nodes, providing more copies of themselves. Very often, with most therapies, the cancer cells in the blood are the most accessible, and therefore the easiest to kill. From everything I have read, CLL cells in peripheral blood pose little danger, over and beyond providing a pool of cancer cells for future proliferation. It is the accumulation of these cancer cells in the bone marrow that is the real danger, at sufficiently high levels it shuts down the absolutely vital production of other cell lines like red blood cells, that can only be made in the bone marrow. Heavy infiltration of the lymph nodes, to the tune where they are bulky means that when the CLL decides to go into a higher proliferation mode, maybe kicked off by something as innocent as a slight viral infection, the numbers can go up very quickly indeed. This is why we have the definitions of PR, NPR, CR etc. All of these various definitions of response to therapy take into account the response of the lymph nodes. They are a serious aspect of the disease, more so if they threaten other vital functions, such as squeezing shut blood flow in adjoining arteries, etc.
Inflammation, Infections and Cancer
by Chaya Venkat
I have been interested in the connection between chronic inflammation and cancer for some time. Attached below is an URL of a paper that discusses this relationship in some detail.
Most researchers seem to agree that this relationship exists, and manipulating it provides a route for the potential control or even prevention of cancer. We have published several articles on CLL Topics on the role of drugs such as Celebrex in the inhibition of Cox-2, and the inflammatory pathways associated with it. Also “nutraceuticals” such as curcumin (from the spice turmeric), catechins (from green tea) etc which are known to be anti-inflammatory and also considered to be of great interest in cancer prevention / control strategies.
Much more specifically, there has been a lot of discussion on this site on the Nf-KB pathway, which is triggered when the body goes into an inflammatory mode. It is known that when this important pathway is triggered, the cells on which this switch is “ turned on” go into a proliferative mode, as well as become protected from apoptosis (cell death). Normally, the Nf-KB pathway is not routinely turned on, but it now known that this pathway is stuck in the “on” position for large majority of cancer cells, including CLL cells, making it possible that this contributes to greater proliferation rates for the cancer cells, as well as making them harder to kill. A number of drugs, including simple ones like aspirin, are known to be blockers of the Nf-KB pathway. One of them which is similar to aspirin, a simple molecule called methyl salicylate is actually in clinical trials for B-cell cancer.
I also hear rumors that a new small molecule drug of unspecified nature is likely to be in clinical trials soon at M. D. Anderson, and this molecule is supposed to be an extremely effective blocker of the Nf-KB pathway. If successful, this orally administered drug is expected to provide a non-toxic and simple method for maintaining patients in long term remission. I understand it is a derivative or variant of an already well known anti-inflammatory drug.
IDEC-152 is another very interesting monoclonal antibody. As we have discussed before, this monoclonal targets CD23 marker on CLL cells. CD23 is the activation marker for cells, high levels of this marker means the Nf-KB pathway is activated on these cells and they are in a proliferative mode. It is an elegant concept, killing specifically the very cancer cells that are multiplying rapidly and trying to protect themselves from death. Even more interesting is the combination of this monoclonal antibody with Rituxan. Combination of the two monoclonals gets the cancer cells in the cross-hairs, as it were, and has the potential for much higher levels of efficacy, without increasing the toxicity. This kind of a combination would be of particular interest to those of us who do not exhibit either marker (CD20 or CD23) to very high levels, and the combination of the two may get us to the critical levels required for efficient CLL cell kill. In fact, I have written about murine (mouse) studies where the survival of animals with lymphoma was much higher when both monoclonals were co-administered, a classic case of synergy where 2 plus 2 is more than four. I am aware there is an ongoing clinical trial (phase-1) using IDEC-152 by itself for CLL patients. I would very much like to see this trial get beyond the phase-1 stage, and especially see combinations of the two monoclonals used together in CLL.
The following is a link to a technical paper that discusses this topic in some detail: Chronic Inflammation and Cancer.
Blood, Marrow and Nodes
Blood Counts are a Dim Reflection of Disease Progression
by Chaya Venkat
Here are some fundamentals of what this disease is all about.:
The source of the disease is the bone marrow and in the lymphatic system. That is where all the action is. That is where the new generations of blood cells are created. Not in the peripheral blood. Think of the former as the factory, the later as the highways leading to and from the factory. Clearing up the traffic on the highways does not solve the problem if the factory is not functioning right, not making the right widgets.
Since we cannot easily measure the populations of the various cell types in the bone marrow or lymph nodes (imagine having a lymph node biopsy or a bone marrow biopsy done as frequently as a simple blood test), doctors and patients depend upon the ever popular CBC (Complete Blood Counts). Normally, when the bone marrow, lymph nodes and peripheral blood are in equilibrium, the counts in the peripheral blood reflect, very roughly, what is happening in the bone marrow and lymph nodes. The CBC therefore has some limited diagnostic value. Some patients have very advanced disease, as measured by swollen nodes, spleen, infiltrated marrow and other complications, but relatively low WBC, and vice versa.
CLL patients do not die because there are too many white blood cells (WBC) in their peripheral blood, CLL cells or otherwise. Yes, the blood's viscosity increases slightly, and the pumping action of the heart becomes more difficult, when the WBC reach very, very high numbers. I am talking about ranges in excess of 200K. This is very rare phenomenon. Several of the consortium experts don't believe this is ever a real problem, other more immediate problems (see below) will get you first.
One of the things that kills CLL patients is the bone marrow getting so packed with cancer cells that it stops producing the good infection fighting cells of the immune system, and simple infections that are easily shaken off by normal people become life threatening in the case of CLL patients. Viral, bacterial and fungal infections are what kill majority of CLL patients.
Also, the gradual decay of immune surveillance means that secondary cancers can take hold. MALT, the topic of discussion in recent articles, is one of them. It may be triggered by H. Pylori, a bug that lives in the stomach and gut. It becomes active and takes advantage of the situation to proliferate, when there is no immune system able to fight it.
Also at issue is the effect of diseased spleen and liver, which not only stop doing their normal functions but may start chewing up perfectly good red blood cells and platelets as they get progressively more diseased. This is the onset of autoimmune hemolytic anemia (AIHA) and thrombocytopenia, both of which are alarmingly common in CLL patients. The former causes anemia, progressive fatigue and inability for the body to carry out its vital oxygen transport, the later can result in strokes, uncontrolled bleeding etc.
So. Immediately after therapy, especially if the drug used differentially takes care of CLL cells in the peripheral blood but not in the bone marrow or lymph nodes or swollen spleen, nothing much has been accomplished. This is a very small part of the total population of cancer cells, it will soon be replenished from the vast stores in the lymph nodes etc. Does it diminish the other risks of the disease? Not in my opinion. The bone marrow is still infiltrated and producing the wrong type of cells. The patient is still at risk of developing conditions that lead to sudden and serious infections, anemia, thrombocytopenia, etc.
Think of the peripheral blood CBC as a dim reflection of what is actually happening in the other more important sites of the infection. At best, it gives us some idea of what is going on, and it is used because it is done easily, and it is cheap. At worst, it totally fails to reflect the reality of swollen lymph nodes, swollen spleen, potentially infiltrated bone marrow.
There is no such thing as a free lunch. Here are some of the "costs" of an ineffective (repeat, ineffective) bout of Rituxan:
Don't get me wrong, I am a big fan of Rituxan and the other monoclonals, you can judge by the number of articles I have produced on the subject. Rituxan, Campath, IDEC152 and their combinations with immunomodulatory drugs like Interleukin-2, low dose Prednisone, GM- CSF, Interferon alpha etc are the wave of the future. I am rooting for these interesting studies to become the new standards, in our lifetimes.
But it bothers me to see the phrase "at worst, Rituxan does no harm". A small percentage of people are quite allergic to it, can have very severe responses. As "Granny" Barb can attest. A risk worth taking, since the percentage is small, if and I repeat, if one is a good candidate for this particular drug. It comes back to the good old idea, there is no such thing as a free lunch. And I for one would rather know whether or not I have the variety of CLL that is likely to respond well to Rituxan only therapy, **before** I put myself through it. Why not know what your odds are, ahead of time? I know there are no guarantees, our understanding of how these drugs work is far from perfect. But why not line up the odds a little better with prior information? As for the other questions of a more philosophical and emotional nature, I am certainly not competent to comment. Also, I am not about to tell any one what their therapy choices ought to be, it is an individuals right and responsibility to do that for himself or herself. In life, we all live with the choices we make, the roads we choose to walk.
Inherited Predisposition to CLL Is Real
by Chaya Venkat
As the mother of a talented and much beloved daughter, it is with reluctance and dread that I read this latest article in "Blood". Healthy, first degree relatives of CLL patients are likely to have an inherited predisposition to CLL, at a rate that is statistically four times higher than the normal population. Sounds scary.
Then some level of logic came to my rescue: I am personally convinced that we are a lot better off in therapy options today than we were even just a few years ago. And the rate at which new information is becoming available is increasing rapidly. Down the road, many years from now, if your son or daughter develops CLL, they will probably fix it with a quick vaccine inoculation, in the doctor's office, and that will be that.
Meanwhile, prior warned is prior armed, get your kids to stay healthy, develop life long habits of healthy living, exercise and nutrition, and not miss those routine annual check-ups. Kids think they are immortal, nothing will ever go wrong with them, until it does.
Blood, 1 October 2002, Vol. 100, No. 7, pp. 2289-2290
Inherited predisposition to CLL is detectable as subclinical monoclonal B-lymphocyte expansion
Andy C. Rawstron, Martin R. Yuille, Julie Fuller, Matthew Cullen, Ben Kennedy, Stephen J. Richards, Andrew S. Jack, Estella Matutes, Daniel Catovsky, Peter Hillmen, and Richard S. Houlston
From the Academic Unit of Haematology and Oncology, University of Leeds, HMDS, West Yorkshire; Academic Department of Haematology and Cytogenetics, Institute of Cancer Research, Surrey; Section of Cancer Genetics, Institute of Cancer Research, Surrey, United Kingdom.
Monoclonal chronic lymphocytic leukemia (CLL)-phenotype cells are detectable in 3.5% of otherwise healthy persons using flow cytometric analysis of CD5/CD20/CD79b expression on CD19-gated B cells. To determine whether detection of such CLL-phenotype cells is indicative of an inherited predisposition, we examined 59 healthy, first-degree relatives of patients from 21 families with CLL. CLL-phenotype cells were detected in 8 of 59 (13.5%) relatives, representing a highly significant increase in risk (P = .00002). CLL-phenotype cell levels were stable with time and had the characteristics of indolent CLL. Indolent and aggressive clinical forms were found in family members, suggesting that initiation and proliferation involves distinct factors. The detection of CLL-phenotype cells provides a surrogate marker of carrier status, potentially facilitating gene identification through mapping in families and direct analysis of isolated CLL-phenotype cells.
For those of us with children (or siblings), the abstract below is like a kick in the stomach.
These researchers examined first degree relatives of CLL patients, people who are in apparent good health. Flow cytometry done on 33 relatives showed that 6 out of the 33, a whopping 18% of the relatives examined, showed the tell-tale CD5/CD19/CD20/CD23 positivity, the classic pattern for monoclonal B-cell phenotype. This 18% is to be compared with 0.7% or so one would expect in a normal population.
Just to be clear, this does not mean the 6 relatives above have CLL. Some or even all of them may be ultimate smolderers that continue indefinitely below the threshold defined for CLL diagnosis, never even aware that they had a sub-detection level of B-CLL monoclonal phenotype. If a tree falls in the forest, and there is no one to see it, does it matter?
All the same, I am happy that there is continuous and encouraging spate of new drugs and new therapy protocols being investigated. For those of you who chose to participate in clinical trials, thank you, there is a new generation out there whose lives may some day be saved because of your generosity.
Cytometry 2003 Mar;52B(1):1-12
B-cell monoclonal lymphocytosis and B-cell abnormalities in the setting of familial B-cell chronic lymphocytic leukemia.
Marti GE, Carter P, Abbasi F, Washington GC, Jain N, Zenger VE, Ishibe N, Goldin L, Fontaine L, Weissman N, Sgambati M, Fauget G, Bertin P, Vogt RF Jr, Slade B, Noguchi PD, Stetler-Stevenson MA, Caporaso N.
Flow and Image Cytometry Section, Laboratory Stem Cell Biology, Division of Cell and Gene Therapies, Center for Biologics Research and Evaluation, Food and Drug Administration, Bethesda, MD
BACKGROUND: Among all hematologic malignancies, B-cell chronic lymphocytic leukemia (BCLL) has the highest familial clustering (three- to sevenfold increase), strongly suggesting a genetic component to its etiology. Familial BCLL can be used as a model to study the early pathogenesis of this disease.
METHODS: We examined nine kindreds from the National Cancer Institute's Familial BCLL Registry, consisting of 19 affected members with BCLL and 33 clinically unaffected first-degree relatives. Flow cytometric immunophenotyping to detect a B-cell monoclonal lymphocytosis (BCML) was performed. Monoclonality was confirmed by polymerase chain reaction analysis of whole blood DNA. Cell cycle analysis for aneuploidy was conducted.
RESULTS: In all affected individuals, we observed the classic BCLL CD5/CD19/CD20/CD23 immunophenotypic patterns. Six of the 33 unaffected individuals (18%) had evidence of BCML. Additional individuals (13/33, 39%) showed some other abnormality, whereas 14 individuals (42%) were normal. Based on an estimated prevalence of 0.7% for BCML in the general population, the finding of six subjects (18%) with clonal abnormalities in this relatively modest sample was significantly greater than expected (i.e., 18% vs. 0.7%, P < 5.7 x 10(-9)).
CONCLUSIONS: Individual components of BCML and other B-cell abnormalities were observed in almost half of the apparently unaffected individuals. Our findings suggested that BCML may be an early detectable abnormality in BCLL. The spectrum of some of these observed abnormalities suggested the involvement of different B-cell subpopulations or different pathways in clonal evolution. Population-based, longitudinal studies will be required to determine the incidence of BCML and other B-cell abnormalities and their relation to disease progression in BCLL and other closely related B-cell lymphoproliferative disorders. Cytometry Part B (Clin. Cytometry) 52B:1-12, 2003. Published 2003 Wiley-Liss, Inc.
Probability of a Cure for CLL
by Chaya Venkat
Some patients are under the impression that CLL cells do not die. CLL cells do die, they are not immortal. The problem is that they live longer than they should, and just as in human populations, when life spans increase, even without any change in the birth rate, there is an overall population explosion. Billions upon billions of new cells are created daily. If the CLL cells are truly immortal and did not die at all, they would accumulate so fast we would all be giant lymph nodes and nothing else, in a matter of days and months.
Now, since the net accumulation of CLL cells is due to the cancer cells dying at a slower rate than they are being produced, the progression of the disease can be stopped, and reversed, if we introduce a new mechanism that increases the death rate. All it takes is for the cancer cells to die faster than they are being made.
This is what sets apart indolent disease versus rapidly growing disease, it all depends on the difference between the rate of death versus rate of birth of cancer cells.
Another point to remember: majority of people have a few cancer cells in their body, caused by some random mutation or the other, and they never even know about it. The reason is that these cancer cells are rapidly killed by the immune system, before they have a chance to gain a foothold.
In a full blown case of cancer, the cancer cells have obviously won the first battle(s), gained that all-important foothold. They can now start their subversive campaign to make the immune system cells inactive and inefficient. The snowball effect will get out of hand, unless we intervene to change the rules of the game. If we give the immune system a hand, through some form of therapy, kill off the major bulk of the cancer cells, and thereby remove the chemical signals put out by the cancer cells that ties the hands of the immune system, it is possible to get back to a situation where the immune system can start doing its job again, hold the cancer at bay, eventually eradicate it.
Think of the cancer cells as the Mob. If they are allowed to flourish and get out of hand, they begin to subvert and bribe into inaction the very system (judges, police, FBI) that are supposed to control them. Get in some law enforcement from the outside, put away the majority of the mobsters for life, the remaining dregs are no longer able to bribe the local police force into inaction, and gradually they too will get cleaned out.
Bottom-line, we have to get away from the totally wrong notion that cancer cells do not die. They do. Just not fast enough. Anything we can do to increase the rate of death and slow down the rate of birth will control the cancer's progression. A cure is not only logically possible, in the case of CLL, everything I have read says it is likely to happen, in our lifetimes. I am no starry eyed optimist, but it is my considered opinion that we will start seeing indefinite "remissions", at least in some patients, sooner than many of us think. That is the basis of my motto, "stay healthy today, live to fight another day".
Weight Loss & B-Symptoms
by Chaya Venkat
We are told to watch out for unexplained weight loss, since it is one of the "b-symptoms" that indicates the CLL may be progressing more rapidly, and treatment of some sort may be indicated in the near future. Not all cancers are alike, in fact patients with hematologic malignancies have significantly smaller problem with weight loss, compared to patients with other solid tumors. Count your blessings.
There are many reasons for cancer related weight loss (the technical term is "cachexia", pronounced ka-hex-ia). Side effects of chemotherapy or radiation such as nausea, vomiting, food not tasting good, constipation and diarrhea can all contribute to weight loss. So also depression, anxiety, and changes in normal social interactions, all of which are associated with cancer. The Eastern Cooperative Oncology Group (ECOG), which analyzed 12 different clinical trials and found that weight loss predicted a shorter survival than patients who did not experience weight loss. Not only did the weight loss predict an overall poorer prognosis, but it also indicated a trend toward lower chemotherapy response rates. When looking at the prognostic effect of various cancer symptoms, it was also found that loss of appetite predicted a poor outcome for cancer patients. The best way to treat cancer cachexia is to cure the cancer. But this may not always be possible, and a number of attempts have been made to address the more immediate problem of halting unwanted weight loss. Till recently, the efforts centered on nutritional counseling, and drugs to improve appetite. While steroids undoubtedly make some patients feel better, they do not appear to affect the process of cachexia. Serotonin has been tried, since is thought to have a role in appetite control. Melatonin has also been suggested to influence TNF-alpha production, one of the cytokines implicated in cachexia.
If you have read my previous articles on changes in metabolism as a result of cancer, you will remember that while normal cells get their energy by the very efficient Krebs cycle, cancer cells are wasteful and use a very much less efficient mechanism for converting glucose to energy. Hydrazine inhibits phosphoenolpyruvate carboxykinase, an enzyme responsible for gluconeogenesis from lactate (the Cori cycle), the mechanism used by cancer cells. It was hoped that interrupting this process would normalize some aspects of glucose metabolism in cachexic cancer patients and so improve nutritional status. However, recent studies have not demonstrated any real benefit of this compound.
A combination of a relatively non-toxic drug and a food supplement have shown the most promise. Ibuprofen (and several other non-steroidal anti-inflammatory drugs, or NSAIDs), in combination with fish oil seems to work best. Promising results have been seen in weight gain, improved quality of life and physical performance status in well documented studies, where nutritional counseling, appetite stimulants, NSAIDs and fish oil have been combined.
This country is obsessed with weight loss, but surely we know that unintentional weight loss in a cancer setting can be quite dangerous. If you find yourself losing weight, becoming less energetic and generally "wasting away", you may wish to click on the URL below.
It is an excellent article in Medscape that should be more widely read. You may have to register to be able to read this article, but the Medscape registration is free of charge. Please keep a record of your registration information since we will use Medscape references often. The information is provided in a patient-friendly manner, and even if you do not have the energy to read it, make sure your care-giver reads it. Families can do a lot to help in this regard.
People, there are some areas where you can influence the outcome of your condition. Better nutrition, better information, more exercise, more water, and a generally optimistic view of life will all help greatly. They will improve the quality of your life, as well as improve your chances with any therapies that you may undertake down the road. Our motto should be "stay healthy today, live to fight another day".
What Is CLL?
by Chaya Venkat
A reader asked for my help in composing a short description of the disease for a presentation he had to give. I thought it (my response) might help our new members.
There are approximately 10,000 new cases of B-cell chronic Lymphocytic leukemia (CLL) diagnosed each year, making it the most common form of leukemia in the Western hemisphere. At this stage, CLL is considered to be an incurable disease. The good news is that the median survival of about 7 years for CLL patients is longer than that for more acute forms of leukemia. However, until very recently, the majority of the patients did not achieve complete remissions after undergoing "standard" chemotherapy regimes and all patients seemed to relapse sooner or later. Some patients become resistant to the drugs, severely limiting therapy options. Many of the chemotherapy drugs used to treat CLL have substantial toxicity associated with their use. It is often a tragic choice between the patient succumbing to the disease and being unable to tolerate the toxicity of the drugs that may help hold the disease at bay.
The birth of new cells and death of old cells that have outlived their usefulness are fundamental and strictly controlled mechanisms of all living things. Old and unwanted cells obediently commit suicide ("apoptosis") when commanded to do so by chemical signals from the body, or if they become defective in some way, they are attacked and killed by the cells of the immune system. New cells are created as needed and the balance is preserved.
When this fine-tuned balance goes awry there is an unwanted accumulation of cells and the result is cancer of one sort or another. In the case of CLL, the problem appears not to be the accelerated formation of new B-cells but rather the refusal of the old ones to die on command. The malignant cells are able to accumulate in vast numbers because they have developed an ability to circumvent the death signals from the body. They are also very good at hiding from the surveillance of the immune system, since they are, in fact, an important part of the immune system themselves. This survival advantage allows the CLL cells to accumulate gradually over time.
This gradual but relentless accumulation of defective immune system cells leads to many complications. Mild infections that are readily shaken by healthy individuals may become life threatening, since the ability of the immune system to protect the body against invading bacteria or viruses is compromised. Sometimes the damaged immune system inappropriately attacks other cells in the blood, such as red blood cells and platelets, creating severe anemia (low hemoglobin) and thrombocytopenia (low platelets). Major organs such as the liver and spleen may get badly damaged, as the disease progresses. One of the major consequences of advanced CLL is that the bone marrow gets progressively packed with these dysfunctional CLL cells and becomes unable to produce all the other cell lines required for proper functioning of the body. The majority of deaths caused by CLL are due to these reasons and infections of the weakened system by pathogens.
After many decades of status quo, things are finally beginning to change for CLL patients. Recent advances in "smart drugs" such as monoclonal antibodies and radio labeled antibodies has led to more effective therapies with fewer toxic side-effects. Our understanding of how the immune system works is increasing by leaps and bounds. Designer drugs that target the cancer cells without harming the healthy cells of the body, and immunotherapy approaches that use the body's own defense systems to fight the remaining traces of cancer are making it possible to dream of a day in the near future when CLL is no longer an incurable disease.
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