The Living Saga of Garvin Smith - Are you Dying to Read It? Part 6

Okay, it’s official. The biopsy revealed that I possess a strain of incurable follicular lymphoma. While it is incurable, conventional medicine is able to beat it into remission with a 70% success rate, with a median life span of ten years before reoccurrence, but with a wide (one to twenty year) variance. My oncologist said that he has never seen a case that hasn’t been beat into remission. Now this can be viewed two ways: one; that the medical profession is being cautious with its statistics, or, two; for each new case that my oncologist sees cured it brings us closer to seeing the 30% that doesn’t get cured (statistically speaking, of course). After discussion with my oncologist, we decided upon an altered chemotherapy approach, as the R-CHOP method Rituximab, Cyclophosphamide (Cytoxan), Hydoxydaunorubicin (doxorubicin), Oncovin (vincristine), and Prednisolone was just too scary. However, after researching our alternate plan, it’s not much better: Rituximab, Fludarabine, Cytoxan, and Prednisone. (sounds almost evil, doesn’t it?)
I started the Prednisone yesterday. This is a member of the glucocorticoid class of hormones. This means they are steroids but, unlike the anabolic steroids that we hear about regarding sports medicine, these are "catabolic" steroids. Instead of building the body up, they are designed to break down stored resources. Glucocorticoids hormones are produced naturally by the adrenal glands.
The uses of glucocorticoids (like Prednisone) include cancer chemotherapy (especially in the treatment of lymphoma) Prednisone is activated by the patient's liver into Prednisolone. Prednisone is effective in destroying the lymphocyte cells that are a major problem with lymphomas. Your body creates some 17,000 lymphocytes a day, and they are programmed to die at a certain time so that the indicated reference number of lymphocytes in a normal person is 1,000 to 1,100. When I first sought treatment, about two months ago, my lymphocyte number was 5,300. Yesterday that number was 23,000! It is time. . . for the “juice” (chemotherapy)!
Chemotherapy is the general term for any treatment involving the use of chemical agents to stop cancer cells from growing. Chemotherapy can eliminate cancer cells at sites great distances from the original cancer. As a result, chemotherapy is considered a systemic treatment. Chemotherapy works by destroying cancer cells; unfortunately, it cannot tell the difference between a cancer cell and some healthy cells. So chemotherapy eliminates not only the fast-growing cancer cells but also other fast-growing cells in your body, including, hair and blood cells. Some cancer cells grow slowly while others grow rapidly. As a result, different types of chemotherapy drugs target the growth patterns of specific types of cancer cells. Each drug has a different way of working and is effective at a specific time in the life cycle of the cell it targets.
An undesirable consequence of chemotherapy affecting your body—not related to your cancer—is referred to as a complication of treatment, or a side effect. Some common side effects of chemotherapy are:
• Low white blood cell count
• Low red blood cell count
• Low platelet count
• Nausea
• Vomiting
• Hair loss
• Fatigue
Some side effects may be temporary and uncomfortable. Some can cause dose reductions and treatment delays or even be life-threatening.
I start taking Rituximab, Fludarabine, and Cytoxan on Monday. Rituximab is a newer drug (approved 1997) that destroys both normal and malignant B cells that have CD20 on their surfaces, and is therefore used to treat diseases which are characterized by having too many B cells, overactive B cells or dysfunctional B cells, like Lymphoma. B cells are lymphocytes that play a large role in the humoral immune response (as opposed to the cell-mediated immune response, which is governed by T cells). The principal functions of B cells are to make antibodies against antigens, perform the role of antigen-presenting cells (APCs) and eventually develop into memory B cells after activation by antigen interaction. B cells are an essential component of the adaptive immune system. Follicular B cells (FO B cells) are a type of B cell that reside in primary and secondary lymphoid follicles (containing germinal centers) of secondary and tertiary lymphoid organs, including spleen and lymph nodes. As shown above, in my case it’s the B cells that are out of control. Rituximab (Rituxan) is a new type of drug known as a monoclonal antibody, meaning it's 'trained' to do a very specific job within the body—something like a 'magic bullet'. Rituximab's narrow job is to seek out B-cell lymphocytes by finding a certain protein on the surface of the cell, and kill them.
Fludarabine is highly effective in the treatment of chronic lymphocytic leukemia, and is classified as an antimetabolite. Antimetabolites are very similar to normal substances within the cell. When the cells incorporate these substances into the cellular metabolism, they are unable to divide. Antimetabolites are cell-cycle specific. They attack cells at very specific phases in the cycle. Cancer is characterized by cell division, which is no longer controlled as it is in normal tissue. "Normal" cells stop dividing when they come into contact with like cells, a mechanism known as contact inhibition. Cancerous cells lose this ability. Cancer cells no longer have the normal checks and balances in place that control and limit cell division. The process of cell division, whether normal or cancerous cells, is through the cell cycle. The cell cycle goes from the resting phase, through active growing phases, and then to mitosis (division).
The ability of chemotherapy to kill cancer cells depends on its ability to halt cell division. Usually, the drugs work by damaging the RNA or DNA that tells the cell how to copy itself in division. If the cells are unable to divide, they die. The faster the cells are dividing, the more likely it is that chemotherapy will kill the cells, causing the tumor to shrink. They also induce cell suicide (self-death or apoptosis).
Chemotherapy drugs that affect cells only when they are dividing are called cell-cycle specific. Chemotherapy drugs that affect cells when they are at rest are called cell-cycle non-specific. The scheduling of chemotherapy is set based on the type of cells, rate at which they divide, and the time at which a given drug is likely to be effective. This is why chemotherapy is typically given in cycles.
Cytoxan (Cyclophosphamide) is a drug that is used primarily for treating several types of cancer. In order to work, cyclophosphamide first is converted by the liver into two chemicals, acrolein and phosphoramide. Acrolein and phosphoramide are the active compounds, and they slow the growth of cancer cells by interfering with the actions of deoxyribonucleic acid (DNA) within the cancerous cells. It is, therefore, referred to as a cytotoxic drug. Unfortunately, normal cells also are affected, and this results in serious side effects. Cytoxan also suppresses the immune system and is also referred to as immunosuppressive.
So, there you have it. I apologize to any oncologists who are wincing at my brief and incomplete and possibly somewhat incorrect (due to its incompleteness) information. We all know what that’s like: when a fledgling novice tries to explain our area of expertise.
As I researched these chemo drugs and their effect on the human body (pretty drastic I must confess) I discovered an inkling of the complexity and beauty of the human body and thought about how fun it would be to be a medical doctor (maybe I’ll go back to school!) to study this complex beauty. For example I discovered that the human body makes millions of different types of B cells each day that circulate in the blood and lymphatic system performing the role of immune surveillance. They do not produce antibodies until they become fully activated. Each B cell has a unique receptor protein (referred to as the B cell receptor (BCR)) on its surface that will bind to one particular antigen. The BCR is a membrane-bound immunoglobulin, and it is this molecule that allows the distinction of B cells from other types of lymphocyte, as well as being the main protein involved in B cell activation. Once a B cell encounters its cognate antigen and receives an additional signal from a T helper cell, it can further differentiate into one of the two types of B cells listed below (plasma B cells and memory B cells). The B cell may either become one of these cell types directly or it may undergo an intermediate differentiation step, the germinal center reaction, where the B cell will hypermutate the variable region of its immunoglobulin gene ("somatic hypermutation") and possibly undergo class switching.
B cells exist as clones. All B cells derive from a particular cell, and thus, the antibodies their differentiated progenies (see below) produce can recognize and/or bind the same components (epitope) of a given antigen. Such clonality has important consequences, as immunogenic memory relies on it. The great diversity in immune response comes about because there are up to 109 clones with specificities for recognizing different antigens. A single B cell or a clone of cells with shared specificity upon encountering its specific antigen divides to produce many B cells. Most of such B cells differentiate into plasma cells that secrete antibodies into blood that bind the same epitope that elicited proliferation in the first place. A small minority survives as memory cells that can recognize only the same epitope. However, with each cycle, the number of surviving memory cells increases. The increase is accompanied by affinity maturation which induces the survival of B cells that bind to the particular antigen with high affinity. This subsequent amplification with improved specificity of immune response is known as secondary immune response. B cells that encounter antigen for the first time are known as naive B cells.

Plasma B cells (also known as plasma cells) are large B cells that have been exposed to antigen and produce and secrete large amounts of antibodies, which assist in the destruction of microbes by binding to them and making them easier targets for phagocytes and activation of the complement system. They are sometimes referred to as antibody factories. An electron micrograph of these cells reveals large amounts of rough endoplasmic reticulum, responsible for synthesizing the antibody, in the cell's cytoplasm. These are short lived cells and undergo apoptosis when the inciting agent that induced immune response is eliminated. This occurs because of cessation of continuous exposure to various colony stimulating factors required for survival.
Memory B cells are formed from activated B cells that are specific to the antigen encountered during the primary immune response. These cells are able to live for a long time, and can respond quickly following a second exposure to the same antigen.
B-1 cells express IgM in greater quantities than IgG and their receptors show polyspecificity, meaning that they have low affinities for many different antigens, but have a preference for other immunoglobulins, self antigens and common bacterial polysaccharides. B-1 cells are present in low numbers in the lymph nodes and spleen and are instead found predominantly in the peritoneal and pleural cavities.
B-2 cells are the conventional B cells most texts refer to. These are called B-2 Bombers and are now used to bomb other countries into oblivion and are stealth as they fly to their missions! Just kidding!
Marginal-zone B cells
Follicular B Cells
A critical difference between B cells and T cells is how each lymphocyte recognizes its antigen. B cells recognize their cognate antigen in its native form. They recognize free (soluble) antigen in the blood or lymph using their BCR or membrane bound-immunoglobulin. In contrast, T cells recognize their cognate antigen in a processed form, as a peptide fragment presented by an antigen presenting cell's MHC molecule to the T cell receptor.
Anyway, as I lay musing on this complex beauty of only this one very small aspect of the human body, I commented to Debbie about it, and how I was amazed that certain cells are activated by “need”, that they have “memory”, and can “learn” what role is needed and become that role! Debbie said, “Knowing this, there is no way one can deny the existence of a God.” What a beautiful concept! How can any medical doctor deny creation by a greater intelligence? I’m confident that there are some medical doctors out there who do not believe in God. I cannot go to that medical doctor for advice. To even think, or to even imagine that there is not a greater being that we, borders on lunacy and idiocy. Just think of the one Item I discussed above. And medical doctors don’t even know all there is about B-cells as it is!
I testify that there is a God in yonder heavens and that he is aware of you and me. He created us, complete with more complex beauty than just B-cells. He is our Father and His love is infinite and incomprehensible. If we ask, He will give. I asked for the gift of faith, the gift of charity, and the gift of gratitude, with real intent to do and go through whatever He required. He has provided more than I could have ever imagined. Believe me. But I have also grown closer to Him than I could have ever imagined. I love Him more than I could have ever imagined. I testify that He lives.
More to come. . .