White Blood Cells (WBCs) are Leukocytes, which is where the "Leuk" in "Leukemia" comes from. These cells are made in the bone marrow and circulate around the body doing their jobs. The root of the problem in Leukemia is in the bone marrow, where the cells are made.
There are several sub-categories of WBCs. Think of them as your body's military & law enforcement, and the different sub-categories are branches of the Military. WBCs normally make up about 1% of the "population" of cells in your blood. Most people recognize the need for a military, but you wouldn't want to see too many of them, getting into our daily lives. Most war zones are giant models of Leukemia in action.
Red Blood Cells are the long-haul truckers, carrying vital stuff back and forth around the whole body. Platelets are the construction workers, and highway maintenance crews, fixing the infrastructure. These guys are often part of the collateral damage when the WBCs get out of control. This is the case with Dave - right now, there just aren't enough truckers or maintenance crews to keep up with demand.
The different branches of the White Blood Cell (military) are:
Neutrophils (Army, Navy, & Air Force) - the first responders, the grunts. They go after bacteria and fungi. They make up 65% of the WBC military. They take large casualties at the site of conflicts, and their dead bodies are the main component of pus.
Lymphocytes (FBI & the CIA) - They infiltrate other cells in the body, looking for terrorists (intracellular pathogens and viruses) and organized crime (cancer.) They also carry out assassinations on wacko cells. They are the second-largest category, and usually make up about 25% of the WBCs. There are two sub-categories of Lymphocytes: B-cells & T-cells. In CLL (Dave's cancer,) it's the B-cells that are causing the problems. More about them later.
Basophils & Eosinophils (IRS, ATF, & EPA enforcement) - Small number of specialized cells that focus on parasites and allergens.
Monocytes & Macrophages (MPs and interrogators) - Besides ordinary defensive activities, these cells also gather information on the enemy when they take them into custody, and then this information is passed along to the Lymphocytes, who use it to tailor specific defenses.
Dave has CLL, or Chronic Lymphocytic Leukemia. "Leukemia" just means too many white blood cells. "Lymphocytic" means that it's the Lymphocytes which are getting out of control. There are so many of them, that they are interfering with the other blood cells, including the other kinds of white blood cells (like the Neutrophils.) Furthermore, they are dysfunctional Lymphocytes, so they're not even doing their own jobs very well.
Not enough Neutrophils is called Neutropenia. Without his "first responder" Neutrophils, Dave is particularly vulnerable to bacterial & fungal infections. His dysfunctional Lymphocytes leave him vulnerable to viruses. These dysfunctional Lymphocytes are hard to stop, harder to remove. (More about treatment, down the page.)
OK, so that's the general picture. But the specifics matter. If you say that someone has CLL, it's about as informative as saying that they have a feline pet. You were thinking, maybe tabby cat, but what about the guy who had a 400 lb Bengal tiger in his NY city apartment? There are many different kinds of CLL, and they differ according to the nature and degree of the Lymphocyte dysfunction. There may be chromosome abnormalities and/or immunoglobulin mutations that distinguish more aggressive and less aggressive forms of the disease. Some people can live for decades with CLL, and they only need occasional chemotherapy pills to keep it in line. Other people require the most radical treatments in order to survive for a couple of years.
Then there's the staging. CLL is a cancer (meaning uncontrolled growth of a cloned cell, in this case a B-cell lymphocyte) and all cancers are staged, by assigning a number between 0 and 4, indicating the progression of the disease. Higher numbers indicate a more dire situation.
I do know that Dave is Stage 3, but, I don't know the status of his chromosome abnormalities and immunoglobulin mutations. I'm pretty sure they ran the tests, but I can't get anyone to tell me the results. I do know that they put him on a "shock and awe" regimen of pretty high-powered chemo drugs. His oncologist went on vacation right after Dave started chemo, and the guy who's covering doesn't seem to want to share much info. So I'm waiting for the main doc to return.
Chemotherapy is the most common tactic used against the dysfunctional Lymphocytes, and that's what Dave is getting. But Chemo is like a nuclear bomb. Chemotherapy drugs cause tremendous collateral damage, taking out large numbers of all the other, different kinds of blood cells (plus some of the other cells in the body, like the lining of the GI tract.) Fludarabine, which is the primary chemotherapy drug that Dave is taking, will suppress T-cells to levels as low as AIDS for as long as 2 years. Plus, chemotherapy can create the seeds of other cancers, which will manifest at some point in the future. And just like bombing Afghanistan didn't rid the world of al-Qaida, chemotherapy doesn't completely eliminate the dysfunctional Lymphocytes. After each bout of chemo, a few of them start reassembling and growing more cells, and each time they do this, they get more resistant to the drug, until finally it doesn't work. Then you have to find a new drug. How rapidly the cancer cells get resistant to chemo depends on which version of CLL Dave has, and how aggressive it is. Some get resistant in 19 months, some take 15 years. The period during which the chemo is over, the body is recovering from the fallout, and the dysfunctional Lymphocytes are plotting a return, is called "Remission."
There are other treatments besides chemotherapy.
The most radical therapy is not chemo, but bone marrow transplant, also known as a stem cell transplant. It offers the only chance, but no guarantee, of a true cure. There are at least a few different kinds of bone marrow transplant, but they all have in these things in common: the patient receives high doses of chemotherapy and total body irradiation, with the intention of killing every single white blood cell in the body. This is known as "conditioning." Then, stem cells from a closely matched donor are injected. The plan is for the donor cells to take up residence in the bone marrow, a process that may take 3 to 5 weeks. If it works, it may be a year before the immune system reaches normal levels, but if it does, and if all of the old dysfunctional cells were killed, then the cancer is really and truly gone. Of course, the "conditioning" process takes a person to the brink of death and some people fall over the brink - about 20% succumb to complications of therapy, which include massive infections, major organ failure, and secondary cancers. About 60% achieve remission lasting 2 years - I haven't been able to find numbers on longer survivals. I could be wrong on these numbers - I'm still wading through tons of material on this topic.
There's also a newer kind of transplant, called a "Mini-Transplant," that has a lower mortality, although it's still no picnic. With the "Mini," the goal of the "conditioning" is not to eliminate the entire immune system, but just enough to prevent rejection of the donated cells, and to allow a mixed population of donor and original cells to grow. The donated (healthy) T-Lymphocytes can assassinate the original cancerous cells. If the donor is a a closely matched family member, additional Lymphocyte transfusions can be given, as necessary.
Another kind of treatment for CLL is gene therapy. The goal is to trick the killer T-cells (The CIA, in our military analogy above) into targeting the cancerous B-cells. The way they do this is by removing some of the cancerous B-cells, genetically modifying the cells so that they "turn on a flashing neon sign" that signals their status. Then the modified B-cells are returned to the body, where the killer T-cells get all excited and start eliminating them, and then theoretically keep on going to eliminate the other cancer cells, too. And a similar kind of biologic treatment is monoclonal antibodies. The antibodies are made in a lab, sometimes by combining mouse and human proteins and then injected into the patient. The antibodies migrate to the B-cells and stick to them, creating a marker that signals to the killer T-cells that these particular cells need to be taken out. The obvious concern with these therapies is, what are the chances that the killer T-cells will get overly aggressive and start killing good cells? The gene therapy and monoclonal antibody therapies are still very new, not done in that many places, and I have not yet found a good source of comparison numbers for evaluating their effectiveness.
There are some interesting new clinical trials, including Radioimmunotherapy and Trojan Horses, but I'm not going to go into those now, since I still don't know about his chromosome abnormalities and immunoglobulin mutations.
Further complicating this picture is the fact that Dave had Mononucleosis (twice) in his 20s. Mono is a manifestation of the Epstein-Barr virus (EBV) which, like herpes, sticks with you for life. It hides out in the B-cell Lymphocytes, mostly under the radar, but while it was running amok, causing Mononucleosis, it very likely caused permanent damage to the T-cell Lymphocytes. This makes him exceptionally vulnerable to immunosuppressive drugs like Fludarabine & Decadron (which he's getting.) I'm hoping the doc is aware of this (yes, they were told about his mono) and has a plan for dealing with it. I'll continue to follow up, and will post the info when I get it, if any of you are still with me here, and want to know.
Adding to my worries (not Dave's - he doesn't want to know any of this stuff) are these issues:
Dave seems to be allergic to sunscreen - we've tried a few kinds now, and have not found one that he can tolerate. Not only do the chemo drugs make him more likely to suffer sun damage, but CLL patients are 10 times more vulnerable to skin cancers than the average population, and the skin cancers they get are more aggressive. So for now, we're looking at hats and walking on the shady side of the street. If you totally avoid the sun, you will likely suffer from vitamin D deficiency and, besides its well-known function in the bones, Vitamin D reduces the reproductive rate of cancer cells. So we're trying to find a good source of D3 (cholecalciferol.)
Anemia is a lack of red blood cells. Remember the long-haul truckers I mentioned near the top of this entry? Their most important cargoes are oxygen and carbon dioxide. Dave has anemia, or not enough trucks. We can speculate about the reasons - there are plenty of suspects: the over-population of dysfunctional B-cells, and the collateral damage from the chemo are probably having negative effects on the number of red blood cells. But the monster under the bed is Autoimmune Hemolytic Anemia (AIHA.) It's when the cancerous B-cells spread inaccurate information about the Red Cells, which are then targeted for elimination by the killer T-cells or the Macrophages. About 15% of CLL patients develop AIHA. It's scary and harder to control that the other causes of anemia. We hope it's not that, but we don't know at this point. So, for now, we're trying ProCrit, a drug to encourage his bone marrow to make more red blood cells. Honestly, they're not expecting much improvement - they just hope to keep his anemia from getting any worse. If it does get any worse, he'll need blood transfusions, because you have to have red blood cells to keep breathing, thinking, living.
Richter’s transformation, an aggressive B-cell lymphoma, can occur in CLL patients, often in response to a reactivation of the Epstein Barr virus (EBV). The EBV is usually kept under control by the T-cells, but many CLL treatments, including Fludarabine, repress the T-cells. This syndrome is sometimes called "diffuse large cell lymphoma." It's not common - it occurs in about 10% of CLL patients, but the prognosis is very poor - less than one year.
Believe it or not - that's a simplified version of the things I've learned in the last few weeks. I've found the CLL Topics site to be the most helpful in my search for information. They have an extensive catalog of articles related to CLL, and it's written in everyday English. You can start there and then branch out to other sites, once you've gotten the correct terminology down, and once you know what you're looking for.