What are "Plasma Cells"?

Plasma cells are "B" lymphocytes in their final stage of development, when they are actually producing antibodies to fight "germs" like bacteria, viruses, fungi or protozoan parasites. They are an integral part of the immune system. There are basi-cally two types of immunity, called "cellular" and "humoral" immunity. Lymphocytes are white blood cell (about 30% of adult's while blood cells) that are actively involved in both types of immunity. "Cellular" immunity means that the white blood cells directly kill foreign invading germs, such as by enveloping and digesting them, while the "humoral" type means that the invaders are coated by antibodies and then gradually enveloped and digested by other white blood cells. The invading germs have markers on their cell surfaces, called "antigens" which tell the immune system that they are foreign to the body. The two common types of lymphocytes are "T" and "B" cells. "T" cells specialize in recognizing germs and activating the immune system, while "B" cells produce specific antibodies against the antigens that the "T" cells have recognized. The "B" cells go through a number of stages of development, and the final one is that they are specifically programmed to become antibody producing factories. The antibodies produced are specific to attack a particular kind of germ or foreign tissue. At this final stage of development, they are called"plasma cells".

What is a Plasmacytoma?

Plasmacytoma is basically a cancer of the plasma cells, meaning that they are multiplying out of control. The body normally keeps a tight control on it's cells division; cell division is controlled by the genetic material ("genes") inside each cell. Cells commonly divide rapidly in womb life, childhood and puberty, to grow the adult body. After this, most divide more slowly to replace cells lost through old-age or injury. Blood cells, which include red cells to carry oxygen, white cells to fight infection, and platelets for clotting, continue to divide rapidly in adults, for these cells are usually short-lived. For the immune system, a great quantity of specific antibody is only needed to fight a specific invader, since the antibody produced for each type of germ is different. Thus, only particular white blood cells will be needed in large quantity. For example, if a person has strep, there is no need to be producing massive quantities of antibody against tetanus! Interestingly, the immune system is partly regulated by a class of "T" lymphocytes, called "T-suppressor" cells, which block excessive production of unneeded antibodies. Thus, the "T" lymphocytes not only stimulate the immune system via the "T-Helper" cell, but they also calm it down through the "T-Suppressor" cells.A cancer of the the immune system starts in just one cell . There are particular cancers for "T" cells and "B" cells, including leukemiasandlymphomas . A plasmacytoma is the particular name for uncontrolled division of the plasma cells. Since it starts in just one cell, all of the plasma cells produced should appear identical, and moreover, produce the same antibody, also called "immunoglobulin" . These exact copies of the original plasma cell which first produced the effective antibody are called"clones" . When this production is well controlled, it fights disease. When it is out of control, it gains the capacity to invade and destroy normal tissue; this is cancer. For plasma cell cancer, when it is found in just one place in the body (usually bone) it is called (solitary) plasmacytoma . When it is in multiple areas, it is called "multiple myeloma".

How common is Plasmacytoma?

There are about 12,000 new cases of "plasma cell neoplasms", which includes plasmacytoma and multiple myeloma, each year in the U.S.A. About 1,000 of these cases are"solitary plasmacytoma" each year, the remainder aremultiple myeloma at diagnosis. The number of cases increases with age. 98% of patients are over 40 years old, and 60% of patients are males. The disease is more common in Black individuals than Whites. Multiple Myeloma causes about 7000 deaths per year.

Concerning plasmacytomas, there are two basic types--"solitary plasmacytoma of bone" and"extramedullary plasmacytoma" . Obviously, the plasmacytoma of bone starts in bone. In contrast, the "extramedullary" type starts in soft tissue like fat or muscle. These types have different characters. Generally, the "plasmacytoma of bone" is more likely to progress to multiple myeloma (>70% at 10 years) than "extramedullary plasmacytoma (20% at 10 years). Multiple plasmacytomas are multiple myeloma by definition.

What Causes or Increases the Risk for Plasmacytoma?

Like any cancer, the particular reason why one person gets a plasmacytoma and another does not remains unknown . However, several things have been noted to increase the risk for plasma cell neoplasms, called "risk factors"

Radiation Exposure - About 5 times the normal expected number of plasma cell cancers were seen in the Japanese atomic bomb survivors, this was not noted, however, until 20 years after the war! Routine X-rays are a minimal risk.

Heredity - Close relatives of patients with plasma cell cancer have a higher risk of getting it than the general population. Men and Women get the disease in equal numbers.

Carcinogens are chemicals that increase the risk of cancers. They are suspected of causing a gene disturbance in multiple myeloma, leading to an uncontrolled growth of plasma cells. (Cigarette smoking and alcohol intake do not appear to increase the risk.)

Can Plasma Cell Cancer be Prevented?

At this time, besides being prudent about not exposing one's self to unnecessary radiation or carcinogens, there is no known way of preventing plasma cell cancers.

What are the Symptoms of Plasmacytoma?

This of course depends upon it's location, and whether it is in bone or the soft tissues. For "solitary plasmacytoma of bone" the most common symptom is pain in the local area, or a"pathologic fracture" from weakening of that area of bone. There can be compression of nerve roots in the spine from a growing tumor. Alternatively, there are often no symptoms ; the disease is detected on a routine X-ray for a physical exam or by a chiropractor. For "extramedullary plasmacytoma" the most common symptom is a fleshy swelling which continues to enlarge over several months. The and symptoms of multiple myeloma are several areas of bone pain and anemia (with paleness and weakness).

How is Plasmacytoma Diagnosed and Evaluated?

When a patient presents with symptoms suspicious for a plasma cell cancer, such as new bone pain, an X-ray may show "lytic" (clear) areas in the bone, which is where the hard outer shell ("cortex") of bone is being destroyed by tumor. The only way to absolutely diagnose any cancer is to get a "biopsy", that is a sample of it. This sample can be obtained using a needle to punch through the skin and into the involved bone. In plasmacytoma or multiple myeloma, it will show lots of "plasma" cells when examined under a microscope. Also a bone marrow biopsy will show excessive plasma cells, called"plasmacytosis", if the disease is widespread. It is important to note that other conditions than plasma cell cancers can cause plasmacytosis. These include drug reactions, rheumatoid arthritis and cirrhosis of the liver. However, in combination with bone lesions, it strongly suggests a plasma cell cancer.

A patients who has lytic (destructive) bone lesions without another evident cancer to explain them will have laboratory studies performed on their blood and urine looking for evidence of abnormal immunoglobulin production. Recall that these immunoglobulins are the antibodies that the plasma cells produce. The most common type is Immunoglobulin G, abbreviated "IgG", followed by immunoglobulins "A", "D" and "E". The doctor orders a blood test called an "immunoglobulin electrophoresis" to look and see if a particular immunoglobulin is being disproportionately produced. If it is, a "monoclonal spike" will be seen on the immunoglobulin electrophoresis, this simply means that something is being produced by a specific type of plasma cell, and may or may not indicate cancer. In fact, elderly people can develop a "monoclonal gammopathy of unknown significance" (MGUS for short) which is entirely without symptoms but occasionally progresses to multiple myeloma. When a plasma cell cancer is present, we expect to see characteristic bone lesions in addition to the "monoclonal spike". Quite simply, if just one lesion is seen, this is a solitary plasmacytoma, while if multiple areas of bone destruction are seen, this is multiple myeloma. In patients with a plasma cell cancer, 55% produce excessive IgG, 20% produce too much IgA, and only 1% produce too much IgD or IgE. The more advanced the disease the higher the production rates of these immunoglobulins. If the immunoglobulin level is less than 2.0 grams per 100 milliliters of blood, and the X-ray is normal, its probably MGUS. If, on the other hand, the IgG or IgA level is greater than 7.0 grams per 100 milliliters of blood, and the X-ray is abnormal, this is almost certainly a plasma cell cancer, even without doing a biopsy of the bone. The level of the immunoglobulin produced is related to the"myeloma cell mass", that is the number of cancerous plasma cells, and so tells how advanced the disease is. The abnormal immunoglobulin produced is also called the "M" protein, and monitoring it's level during treatment can show the progress of the therapy.

When a patient has excessive immunoglobulin production from an abnormal clone (subgroup) of plasma cells, it may also show up in the urine. Specifically, the "M-protein" is composed of both heavy and light "chains" of protein, and the "light" chains can be excreted by the kidney into the urine. There are only two types of light chains, "kappa"or"lambda", and a patient will have only one type in the urine. The amount of these light chains in the urine can tell us how advanced the disease is. Less than 4 grams of light chains in the total urine produced over 24 hours means limited disease, while greater than 12 grams is a marker for advanced disease.

When patients have excessive light chains in the urine, of either the kappa or lambda type, this is called"Bence-Jones Proteinuria". The classic Bence-Jones test was a simple assay of the protein in the urine. High Bence-Jones protein is very suspicious for a plasma cell cancer.

Yet another marker of extent of plasma cell disease is a blood test called "serum beta-2 microglobulin" which indicates excessive production of immunoglobulins by an abnormal group ("clone") of plasma cells. This test also tells the effectiveness of therapy, if the beta-2 microglobulin level changes.

Other tests are standardly obtained to help distinguish between solitary plasmacytoma and multiple myeloma, and give the extent of disease (called the"stage" ) for all plasma cells cancers. These tests include:

1) Complete Blood Count ("CBC") --anemia is common with multiple myeloma (but not with solitary plasmacytoma). Anemia becomes significant when the blood hemoglobin level falls to below 10 grams per 100 mL. of blood. At this level, the patient starts appearing pale and feels fatigued. The CBC gives the number of platelets in blood, normally about 200,000 per mL. If they platelets all below 50,000 ("thrombocytopenia") clotting ability will be reduced, below 20,000 the risk for spontaneous internal bleeding is very high. Also, bacterial infections are increased in patients with myeloma (this is the major cause of death from the disease) and a CBC will suggest whether or not an infection is present. Finally, the blood counts give an indication of the patient's ability to tolerate chemotherapy, which normally depresses blood counts.

2) Serum Chemistries ("SMA panel") tells the makeup of the fluid that carries the blood cells, that is the liquid portion of the blood. Besides telling about liver and kidney function, this test will give the "serum calcium" level. Serum calcium is raised in myeloma, but not in solitary plasmacytoma. This is thought to be due the myeloma cells producing a factor (osteoclast activating factor) which then reabsorbs the bone, weakening it while raising the blood calcium level. Very high serum calcium leads to drowsiness, then coma and death. Kidney function is very important in life expectancy for multiple myeloma patients-- "as go the kidneys, so goes the patient". The kidneys can fail in plasma cell cancers by getting clogged up with light chains (the Bence-Jones proteins). Signs of kidney failure include "blood urea nitrogen"(BUN) of over 60 mg. per 100 mL. of blood and serum "creatinine" of greater than 2.0 mg per 100 mL. Both of these are measured in a standard chemistry panel.

3) Radiologic studies includeX-ray of the effected bone, as well as a "skeletal survey" which is a set of X-rays of the whole body to look for more bone tumors. A "bone-scan" , where some contrast dye is injected into an arm vein; special films are taken to look for bone lesions. In multiple myeloma there is often a "diffuse" thinning of bone, so the scan may just show whole-skeletal bone loss in this disease (called "diffuse osteopenia") and may not be helpful. A "CTscan" and/or Magnetic Resonance Image (MRI ) is important to get for a soli- tary plasmacytoma, as it may showextension of the tumor beyond the bone into the local soft tissues. To improve the accuracy of CT scan, it can be done with "contrast", injected into an arm vein, which highlights blood vessels. Insist on "omnipaque" contrast or equivalent; although it is more expensive, it is more comfortable and less likely to cause allergic reactions or kidney problems. For MRI, a different type of contrast dye, called "gadolinium" may be used to high- light blood vessels. MRI is 3 times as expensive as CT Scan (~$1000) but is more accurate for defining the extent of a tumor into neighboring muscle and fat. CT scan is particularly good for determining extent along a bone. MRI scans are routinely gotten of the spine if the patient has symptoms of spinal cord or nerve root compression, this has replaced the older (and less comfortable) "myelogram" test where contrast was actually injected around the spinal cord. Other radiographic tests, such as barium enemas, liver-spleen scans, and Intra-Venous Pyelograms ("IVP") of the urinary tract are only gotten based upon specific symptoms, and if their results may change the planned therapy-- to save discomfort and cost.

How is the Extensiveness of a Plasma Cell Cancer Gauged?

Like all cancers, the extent is given by the"stage" . It is important to determine the stage accurately, the above tests are part of the"staging evaluation" . The "Reed" system is most commonly used:

Staging of Plasma Cell Cancers:

"Stage I" means the blood count is normal, the calcium is normal, and the X-ray shows at most just one bone lesion. The M-protein is low, as are the light chains in urine. This is the stage for all solitary plasmacytomas.

"Stage II" means between stages "I" and "III". It is multiple myeloma.

"Stage III" includes several possibilities. The patient may haveanemia (hemoglobin value of less than 8.5),hypercalcemia (high serum calcium of >12.0), more than 3 lytic bone lesions, and/or high levels of M-protein production (> 7 grams IgG per 100 mL. blood) or high amounts of light chains in the urine.

**A subgroup of "A" or "B" can be added to each stage:
"A" means good kidney function (BUN < 60 and Creatinine < 2.0)
"B" means failing kidney function (BUN > 60 and Creatinine >2.0)

What is the conventional survival for plasmacytoma and multiple myeloma?

This depends upon the whether the plasmacytoma is "of bone" or "extramedullary",
and for multiple myeloma the stage of the disease:

Note how important good kidney function is to longer survival!

What is the Conventional Treatment for Solitary Plasmacytoma?

Once multiple myeloma has been ruled out, radiation therapy is the conventional treatment for solitary plasmacytoma (whether it's of bone or the extramedullary type). Bone pain is relieved in plasma cell cancers with relatively low doses of radiation, 20 - 30 Gray (units of radiation) are palliative. While these low doses can be appropriate for pain relieve from multiple myeloma bone lesions, they are inappropriately low for solitary plasmacytoma. Plasma cells used to be thought to be exquisitely sensitive to radiation, but recent research has shown that they require at least 50 Gray (and possibly up to 70 Gray) to kill them.

The technique of radiation is important for controlling the disease. There is often an extension of the plasmacytoma into the local soft tissues (muscles, fat). This is a reason to do adequate pre-treatment radiology studies to account for this. Obviously, it is critical to include the entire area of disease in the radiation field to cure s plasmacytoma. The disease may have invaded into the marrow of the bone, and spread in the marrow cavity. Thus, theentire bone is properly treated for solitary plasmacytoma.

Radiation Therapy to the for plasma cell cancers has been used for cure of solitary plasmacytoma, for palliation (symptom relief) of multiple myeloma, and as part of the procedure for bone marrow transplant (to be discussed). Radiation kills cancer cells by damaging their genetic material ("DNA"), they die when they try to divide. Thus, damaged cancer cells die even after the treatment is complete. Radiation will also kill normal cells, which limits the amount that can be given. However, it usually takes more radiation to kill normal cells than cancer cells, and normal cells can often repair the radiation damage, while cancer cells can not. Nevertheless, it is important to be as exacting as possible in the administration and dose of radiation, so as to minimize the injury to adjacent normal cells. Some organs particularly sensitive to radiation damage include the liver, lung, heart, stomach, kidney, bowel, and spinal cord. When giving treatment to these areas, the doses to each organ must be carefully limited to avoid unnecessary injury.

To receive therapy, a patient is first seen in "consult" by a "radiation oncologist", a cancer physician who specializes in administering radiation. S(he) reviews the patient's medical record, complaints, and radiology films. After explaining the possible benefits and side-effects of radiation, the patient is scheduled for a "simulation" . This means the area to be treated is marked out on a replica treatment machine, and films are taken. Watercolor marks are painted on the patient to denote the treatment area, and eventually small, permanent tattoos are placed on the skin. Sometimes the patient is sent for a CT scan along with the simulation, the whole process takes less than 2 hours, and is painless. Information from the simulation and relevant scans is placed into a "treatment planning computer", which generates a"plan" . This plan tells how much radiation is going to the tumor area, and how much to adjoining normal tissues. The plan is reviewed by the radiation oncologist and also by a specially licensed Radiation Physicist prior to starting therapy. The patient then comes in for their "treatment start" . They are placed on a hard, flat table in a specially shielded room and aligned with laser lights. The actual treatments are given by "Radiation Therapists", or"R.T.T's", who are first certified for diagnostic X-rays and then get additional training to deliver therapy. For the first treatment, "verification films" are taken to ensure proper positioning; they do not tell anything about the cancer. The actual treatment only takes a couple of minutes and is given with a "Linear Accelerator" (aka "LINAC" ), or older Cobalt-60 technology, which precisely aims a beam of photons at the treatment area. The head of the machine can swivel about the patient, to give the treatment from several angles. The patient needs only to lie still. Areas that are not to be treated can be "blocked"with special lead-type blocks in the head of the treatment machine. The accuracy of modern treatment machines means that if, for example, the hip joint is being treated, only ~1% of the radiation dose will be absorbed by the nearby testicles in a male, not enough to cause sterility. Normally, patients are treated 5 days a week, Monday through Friday, taking only several minutes each day.

The usual dose of radiation for solitary plasmacytoma is~60 Gray (units of radiation) given at about 2 Gray per day over 5 to 7 weeks. Sometimes, a larger area (i.e. whole bone) is treated initially, and then a "cone down" or "boost" is used to narrow the high dose treatment to the specific tumor area as seen on X-ray. Treatment itself is painless, the patient does not become "radioactive", have holes burned in them, or lose their scalp hair except from treatment to the scalp. The side effects from irradiation are divided into two general categories, "acute" and"late" effects."Acute" effects occur during the treatment period, and commonly resolve afterward. "Late" effects may occur months to years after treatment, and may improve very slowly or never resolve. Expected early reactions include include skin redness, possible peeling, and mild fatigue. "Late" reactions depend on the area irradiated. In general we expect skin thickening, and slightly more brittle bones in the treatment area. If the whole circumference of an extremity is treated, it interferes with lymph drainage and that limb may swell ("edema"). Sparing even a thin strip of skin can allow a pathway for lymph drainage and prevent later edema problems. If the spinal cord is treated, as is necessary for vertebral body involvement, later nervous system symptoms can occur (tingling, shock-like sensations) but paralysis ("transverse myelopathy) occurs less than 1% of the time if the "cord dose" is kept below 50 Gray. In general, any area treated to a high dose (lung, liver, kidney) doesn't work properly in the future, but this is limited to the exact area treated, and need not cause any symptoms. Breaking the treatments into many"fractions" (instead of giving it all at one time) helps reduce the chance of late effects. In general, radiation alone is well tolerated, and properly administered can cure localized solitary plasmacytoma. The main problem is that the disease already has unrecognized spread, and become multiple myeloma, in many patients. However, if there are a limited (i.e. 2 or 3) separate sites of involvement, it may still be curative to give each of these high-dose radiation. Our treatments seldom kill "the last cancer cell" in the body; they merely drastically reduce the number present. It is the immune system which "mops up" the last remaining cancer cells (a paradox since our treatments often weaken the immune system!). The point is, as the number of cancer cells is progressively lowered, the chance for "cure" correspondingly increases.

What is the Conventional Treatment For Multiple Myeloma?

Given that the majority of patients with plasma cell cancers have multiple myeloma, and that currently the majority of patients with solitary plasmacytoma of bone will eventually develop it, the treatment for it is discussed. Prior to chemotherapy, multiple myeloma was a universally fatal disease with an average life expectancy of just one year.

Radiation treatment was useful for relieving pain, but not curative. Chemotherapy was the first treatment to definitely extend life in multiple myeloma, andit remains the conventional treatment. Administered by a "medical oncologist", the first agent shown effective was Melphalan, an "alkylating agent" related to mustard gas. It causes profound lowering the the blood count, including the plasma cells causing the disease. Response to the disease with Melphalan alone is about 30%, with respond ers living an average of 3.5 years. An important advance was the addition of the corti-sone-like Prednisone to Melphalan therapy. This doubles to response rate to 60%, but unfortunately doesn't extend average survival for responders, still being 3.5 years. Both of these drugs can be given by mouth, and dose is monitored based upon blood counts. It is usually given on four consecutive days every 4 to 6 weeks. Side effects of this can include nausea, anemia, infections, diarrhea, mouth sores, facial hair growth, fat moving to the face and abdomen, bone weakness and mood swings.

The next major advance in myeloma survival was made by giving more intensive chemotherapy. The Memorial Sloan Kettering Hospital developed a 5 drug combination called the"M2" regimen . It uses the conventional Melphalan and Prednisone, but also adds Vincristine, Carmustine and Cyclophosphamide. Naturally, these additional drugs increase side effects, and the "M2" regimen includes drugs that are given into the veins. This regimen results in a response rate of almost 90%, with average survival of 50 months (compared to 12 months for no therapy). This treatment is given until"remission" - that is where no cancerous plasma cells can be identified. Giving the "M2" regimen for longer than this (called "maintenance therapy) doesnot seem to further improve survival. About 20% of patients are actuallycured by the "M2" regimen, compared to less than 5% cured by Melphalan and Prednisone only. For patients who don't go into remission with the above drugs, the "VAD " regimen offers some hope. It contains Vincristine, Adriamycin and Dacarbazine and can produce a remission in 40% of refractory cases, with about 16 month average survival. Some patients will live much longer, however.

What is the Latest, Effective Therapy for Plasmacytoma?

The primary treatment remains radiation therapy! About 70% of solitary plasmacytomas will evolve into multiple myeloma by 8 years, and now it is thought that aggressive treatment can help prevent dissemination. 80% of failures within the original area occur within 3 years. It is important to obtain serum immunoglobulins in patients prior to treatment for solitary plasmacytoma of bone; a decreasing level can indicate successful treatment, while a rising level suggests progression to multiple myeloma. It is also possible for patients with solitary plasmacytoma to develop lesions at other sites without progressing to frank multiple myeloma. These additional sites should get aggressive radiation therapy, to at least 50 Gray. Prophylactic (preventative) chemotherapy has no proven role. While chemotherapy candelay the time to conversion to multiple myeloma (from average 30 months to 60 months) overall survival is not increased. The current best treatment is a competent radiation oncologist giving aggressive treatment to the whole bone and at least a 3 cm. (about 1 and 1/2 inch) margin around the tumor. The patients should have subsequent monitoring of their immunoglobulins in blood and urine to ensure that conversion to multiple myeloma, (which drops to 50% afteraggressive radiation therapy) is aggressively treated. Any percentage reduction in conversion to multiple myeloma is a demonstrable benefit for radiation therapy, since these patients are often cured. However, bear in mind that the disease may have already manifested as unrecognized multiple myeloma at the time radiation was given for presumed solitary plasmacytoma, so later "conversion" does not necessarily mean that failure to give proper radiation treatment was responsible.

What is the Latest, Effective Therapy for Multiple Myeloma?

Addition of Interferon-2b to the "M2" regimen markedly increases apparent cure rates, perhaps to 30%. The interferon-2b is given 3 times per week, as injections under the skin, for 2 years. Interferons, especially when first stared, tend to cause fever, muscle aches and fatigue. The most radical, yet most successful treatment to date for Multiple Myeloma is High Dose Chemotherapy followed by Bone-Marrow Transplant from a marrow donor. Alternatively, we may use bone marrow or "peripheral stem cells" from the patient themselveswhich has been cleaned ("purged") of myeloma cells, but this runs a higher risk of relapse. Bone-marrow transplant involves puncturing the hips bones many times from the donor to remove marrow. This is done under general anesthesia, is not at all dangerous, but can leave puncture scars at the top surface of both buttocks. The marrow is specially prepared and stored, while the myeloma patient is prepared for transplant. The patient's original marrow, which contains the myeloma cells, must be totally destroyed . This process is called the "marrow-ablative" regimen. This is done with using high doses of chemotherapy just prior to the transplant. Also, whole-body radiation therapy (usually 6 sessions of 15 minutes each over 3 days) may be used to be sure all the myeloma cells are killed before the transplant. Whole body radiation is especially used for relapsed patients or those somewhat resistant to the chemotherapeutic "ablation", the ideal being that every last white cell in the body should be destroyed. Donor bone marrow is then "reinfused" (that is transplanted) into a regular vein in the patient, and findsit's own way into the bone while circulating in the bloodstream. The new marrow will hopefully "take" and start producing new blood cells, but until it does the patient is at very high risk for infection and must be hospitalized in a sterilized environment. It usually takes 2-4 weeks before the new marrow is functional. Once it is, the patient can be discharged with medications to prevent infection and rejection.

Side-effects of getting bone marrow from another individual ("allogeneic") are more than when a person donates their own marrow for later use ("autologous") . It may become possible to effectively clean a person's own marrow (purging) but this is difficult for myelomas, since they arise from the marrow itself! However, new technology using "Monoclonal Antibodies" against the leukemic cells can increase the success of self (autologous) transplants. These Monoclonal Antibodies may also be directly injected into the patient to increase the chance of remission. Recent major research on use of monoclonal antibodies is being done at the Dana Farber Cancer Center. Still, while for breast cancer transplants are autologous, for leukemia they are usually allogeneic. Expected side-effects arise from the preparation ("ablation") for the transplant, and then after the donor marrow is administered. Most common are nausea, diarrhea and fatigue.

Also, temporary hair loss ("alopecia") and permanent loss of fertility ("sterility") are expected. If radiation is used as a part of the preparation, nausea is worse, glands temporarily swell, skin redness, mouth sores and sore throat is common. These are all temporary. After the new marrow is infused, the patient is at very high risk for any infection, so preventative ("prophylactic") antibiotics are given. Also, the patient will be anemic weak from lack of red blood cells (which live about 4 months), and have easy bruising from platelets (which last about 10 days). These problems will abate as the new marrow takes over and produces blood cells. A serious side-effect of foreign bone marrow is "graft versus host disease " or "GVH" for short. This happens if the new marrow actually rejects the body it's put into. It is more likely if the previous marrow was not completely destroyed, or if the donor marrow is not a close enough match. Ironically, some degree of GVH actually seems to help prevent relapse, so it's not all bad. In an allogeneic transplant,some amount of GVH is expected, and is shown by skin splotches and blood tests. GVH is controlled with immune-suppress-ing anti-rejection drugs like prednisone and cyclosporine. This is a double-edged sword, however, since these medications also lower the immune system's ability to fight infection. In severe cases GVH can be fatal, but today it is usually well controlled with medicationOverall, the death rate ("mortality") from transplant is down to 10%, which is a major improvement over the past 10 years. There is even talk of doing the transplants at smaller community hospitals, instead of just big Universities. A whole new generation of cancer doctors has been extensively trained in doing transplants. Newer drugs which stimulate the newly infused marrow, called "Colony Stimulating Factors" (erythropoetin and neupogen) produce red cells and white cells respectively have much improved success rates.

The results of bone-marrow transplant for Multiple Myeloma now show nearly 50% survival at 5 years, so it the best available treatment (albeit drastic) for this disease. If the patient gets the transplant after attaining first remission, results for long term survival are as high as 60%! Fortunately, transplant is becoming less drastic and more routine all the time. It can now be recommended as standard for the patient with myeloma who wishes to be aggressive. The key is to consider getting in in the chronic phase of the disease, if it is gotten during the accelerated phase the survivals have only been about 10%. The three main factors that lead to failure of a bone marrow transplant are recurrence, graft versus host disease, and uncontrollable infection. We have made significant progress on all three fronts. One rare but reported reason for failure is redeveloping a new leukemia from the foreign donor marrow. A fascinating development is that the results of autologous bone marrow transplant in the chronic phase for myeloma are approaching those for a non-related donor; this is great news since appropriate donors are hard to find (although we have National Registries now). Interestingly, a major disadvantage of the autologous "self-transplant" is the absence of the GVH effect, which as mentioned actually helps prevent relapse. Again, treatment related deaths are under 10% at major academic medical centers, and survival for responders is 80-90% at 2 years, with over 40% being cured. This shows the hope for a disease which used to always be fatal.

Patients with myeloma, who don't have kidney failure, should drink lots of water!

This helps flush the "light chains" out and prevent them clogging the kidneys. This in itself may greatly help survival by reducing lethal kidney complications. Also, quickly giving antibiotics for infections is important, since infections are the leading cause of death in multiple myeloma. Remember, cancer generally kills by anemia, debility and infection. Keeping one's self in as good shape as possible, with proper exercise and nutrition, helps combat all of these. A positive attitude actually helps immune function!

Palliation (Symptom Relief):

When multiple myeloma stage III, and therapy has failed to stem spread of disease through the body, the objective is no longer cure but palliation (meaning relief of pain and other symptoms). The patient would be made as comfortable as possible, and narcotic medicines like morphine (which Osler called "G-d's own medicine) should never be withheld for fear of causing "addiction". Using "Fentanyl Patches" applied to the skin helps give a continuous amount of narcotic, eliminating the problems of forgotten doses, "loss" of narcotics, and smoothing out the dosing for less disturbing "highs and lows". Importantly, relatively low dose Radiation Treatment (to about 25 Gray in 1 - 2 weeks) can help bone pain in 90% of patients. Sometimes radiation therapy is used as an emergency measure when the cancer spreads to the spinal column and threatens to cause paralysis by pressing upon the spinal cord. Any patient with myeloma who experiences new weakness of the extremities, numbness, or loss of bowel or bladder function must be brought into the Emergency Room immediately to see whether the tumor is compressing the spinal cord causing these symptoms. Up to 60% of new back pain in a cancer patient is caused by spread of cancer there. The patient is given a painless Magnetic Resonance Imaging (MRI) scan to check for "epidural spinal cord compression". If this is caught early, and treatment is given, permanent paralysis may be prevented. It is sadly uncommon to reverse "set in" paralysis, so quick recognition is essential.

Other options for patients in severe pain for multiple areas of spread to bone include "hemi-body" radiation, and"strontium-89" . Hemi-Body radiation uses a low dose (6 to 8 Gray) in a single treatment to the upper or lower body to treat multiple areas of bony involvement; some anti-nauseants are usually necessary and it lowers blood counts. It is over 90% effective for pain relief lasting an average of 6 months. Strontium-89 is an injected radioisotope that goes through the bloodstream to all bony areas, and is especially attracted to cancerous areas. It also lowers blood counts but is very effective at palliating pain. It can only be done once. If no relief is gotten from medications or radiation, neurosurgical techniques to cut sensory nerves can usually afford relief, to this small population of patients. Even accupuncture has recently been recognized as effectively the FDA for cancer pain relief. Committing suicide because of unrelieved pain should NEVER be necessary with pain science today, if the doctor is not compassionate about pain, find someone who is!

Conclusion:

The patient with a newly diagnosed plasma cell cancer should not rely on any one therapy, but instead should use a combination approach to maximize the chance for success Specifically, besides the conventional medical therapies mentioned above, consider the use of a non-toxic, not over-expensive alternative therapy that you believe in, a program of spiritual renewal, "mind over cancer', nutritional therapy and exercise. Keep the most positive attitude possible-- research has shown this to be an important factor in survival. CancerAnswers has a transcript available on reasonable alternative treatments which you can order through our web-site. Using a true"multi-modality" approach will give the confidence that you have done everything possible for a happy outcome, and certainly improve the current quality of life.

Overall, there is more hope than ever before for patients with solitary plasmacytoma and multiple myeloma. New indicators that portend conversion of solitary disease to multiple myeloma are being investigated, and patients at high risk for conversion may benefit from early chemotherapy with or without bone-marrow transplant. If cure is the objective, consider getting treatments at a University Academic Center and joining ongoing research trials which offer the latest therapies. The National Cancer Institute has a list of open research trials on it's website, they change periodically. Understand that particular trials are only offered at particular institutions and patients must meet the "entrance criteria" to enroll. Also, by joining a trial the patient may be giving up their choice for the most effective therapy. Average survival and cure rates are higher than ever today for solitary plasmacytoma and multiple myeloma, offering new promise for prolonged survival with this disease.