Multiple Myeloma – Stages, Risk factors and Medications.

Introduction

Multiple myeloma is a cancer that occurs in a type of white blood cell called plasma cell. Plasma cells help to fight infections by making antibodies that recognize and attack germs. Multiple myeloma causes cancer cells to accumulate in the bone marrow, where they crowd out healthy blood cells. Rather than producing helpful antibodies, the cancer cells produce abnormal proteins that can cause kidney problems. This type of cancer is also known as Kahler Disease, Myelomatosis, plasma cell myeloma, and plasma cell dyscrasia begins in the plasma cells of blood.

 

Stages of Multiple Myeloma

The stages of multiple myeloma are based on the levels of M protein, the number of bone lesions, the number of red blood cells, and calcium levels. These levels can also be subdivided into A and B based on the function of the kidney.

Stage I: Early disease with symptoms and some bone damage.

Stage II: More advanced symptoms and damage.

Stage III: Still more myeloma cells are found throughout the body.

A new staging system, called the International Staging System (ISS), is becoming more widely accepted. It is based on the results of two blood tests (for beta 2-microglobulin and albumin) and seems to be a more reliable way to stage the disease.

History and evolution

Although multiple myeloma has probably been present for centuries, the first welldocumented case was published less than 160 years ago. The famous patient, Thomas Alexander McBean excreted large amounts of a peculiar protein that was studied by Henry Bence Jones. Jones was a well-recognized physician as well as chemist. Less than a half-century ago, Bence Jones protein was found to consist of monoclonal light chains.

Otto Kahler described a patient with autopsy-proven multiple myeloma; this patient survived eight years after the onset of symptoms despite the absence of effective therapy. The discovery of Roentgen’s rays facilitated the diagnosis of multiple myeloma. Serum electrophoresis followed by immunofixation allowed physicians to readily make the diagnosis. Melphalan was introduced for therapy half a century ago but little progress was made until autologous stem cell transplantation became available almost 20 years ago. This was followed by the introduction of the “novel” agent’s thalidomide, bortezomib and lenalidomide in the last decade.

Epidemiology of multiple myeloma

Multiple myeloma affects thousands of people worldwide and is the second most common cancer of the blood only to non-Hodgkin’s lymphoma. Multiple myeloma accounts for around 1% of all cancers worldwide and for about 2% of cancer-related deaths. The most common age of onset is between 65 and 70 years. However, recent estimates suggest that the age of onset is actually decreasing. Currently, nearly 45,000 people are affected with this cancer in the United States and around 14,600 new cases of the disease are diagnosed annually.

Male gender increases the risk for multiple myeloma, which is slightly more prevalent in men than women. African Americans appear to be at the highest risk for the disease, while Asians are at the lowest risk. One study demonstrated that the incidence of myeloma in African Americans is 9.5 per 100,000 people while among Caucasian Americans, the rate is 4.1 per 100,000 individuals. In the African American population, myeloma is among the top ten cancers to cause death.

Risk factors

• People with monoclonal gammopathy of undetermined significance (MGUS) seem to be at higher risk for developing multiple myeloma, but MGUS patients are generally watched very closely for abnormalities.
• Those with family members with multiple myeloma are also at a slightly higher risk of developing the disease as well.
• A small number of cases of patients with high radiation exposure have also lead to multiple myeloma.
• Finally, some industries including agricultural, petroleum, leather, and cosmetology seem to report a higher number of cases.

Causes of multiple myeloma

• Oncogenes and tumor suppressor genes mutation
• Excessive production of interleukin-6 (IL-6) hormone by dendritic cells, develops plasma cell tumors which causes the development of multiple myeloma

Signs and symptoms

The earliest stages have no noticeable symptoms, so a diagnosis is often made under routine blood testing. The following list offers signs and symptoms of multiple myeloma:

• Bone pain (often lower back, spine, and ribs)
• Broken bones or osteoporosis (pelvis, spine, ribs, and skull)
• Weakness/exhaustion/fatigue
• Loss of appetite
• Confusion
• Parched
• Fevers/Infections, especially pneumonia
• Weight loss
• Nausea/vomiting
• Constipation
• Abnormal frequency of urination

Hyperviscosity syndrome (thickening of blood): Signs include shortness of breath, confusion, or chest pain.

Cryoglobulinemia: Signs include pain and numbness in extremities in cold we’;ather.

Amyloidosis: Signs include low blood pressure, numbness in extremities, and kidney, heart, or liver failure.

Diagnosis and Tests

Multiple myeloma is often discovered through routine blood tests or as a result of a broken bone. All myeloma patients will show a spike in M protein, which is produced by myeloma cells, in a blood or urine test. Also, both tests will identify poorly functioning immunoglobulin, a sign of myeloma.

A diagnosis typically requires one major (a positive biopsy; bone marrow with 30%+ plasma cells; or high MCIG levels) and one minor criterion (bone marrow with 10-30% plasma cells; minor MCIG levels; tumor holes in bones; or low antibody levels) or three minor criteria.

There are typically four tests commonly employed to diagnose multiple myeloma:

1. Blood tests: To check for high levels of proteins, low levels of white blood cells and/or platelets, high levels of calcium, and creatinine levels from the kidneys.
2. Urine tests: To check for high levels of Bence Jones proteins.

• X-rays: To check for broken or thinning bones

1. Biopsies: To check tissue and/or bone marrow for cancerous cells.

To figure out the stages of MM following tests are followed:

• Blood test
• CT scan
• MRI scan

Once myeloma is confirmed, patients are classified into three categories based on their test results. This categories helps to provide treatment options accordingly.

1. MGUS
2. Asymptomatic
3. Symptomatic

Treatment and Medication

MM are often treated with radiation therapy. If the plasma cell tumor is not in a bone, it may be removed with surgery. Chemotherapy (chemo) is only used if multiple myeloma develops.

Early myeloma

• Treatment, depends on how advanced the disease is (or what stage it is in). For those in the smoldering stage (early myeloma), doctors typically do not prescribe any treatment but rather monitor the patient very closely for changes in plasma cells.
• Even some Stage I patients postpone treatment to delay adverse side effects from treatments. These patients are often watched closely without starting chemo or other treatments for myeloma. They may be started on a bisphosphonate if they have bone disease.
• Based on how abnormal the plasma cells look under the microscope and the levels of immunoglobulins, some patients with early myeloma have a high risk of progressing to active myeloma and needing treatment. In one study, treating these patients with lenalidomide (Revlimid) and dexamethasone before they developed symptoms or problems helped them live longer.

Active (symptomatic) myeloma

• Patients whose myeloma in stage II or higher or who have light chain amyloidosis are often given drug therapy. The drugs chosen depend on the patient’s health (including their kidney function) and whether a transplant is planned.
• A combination containing bortezomib (Velcade), thalidomide or lenalidomide, and dexamethasone is used. Combinations containing bortezomib are helpful in patients with kidney problems and those whose myeloma cells contain certain high risk chromosome abnormalities.
• Other combinations may be includes vincristine, doxorubicin (Adriamycin), and dexamethasone (VAD). If the patient is not expected to have a transplant, chemotherapy with melphalan and prednisone (MP) may be used, and can be combined with thalidomide.
• Bisphosphonate treatment is often started along with chemo. If the areas of damaged bone continue to cause symptoms, radiation therapy may be used.
• Multiple myeloma also receive supportive treatments, such as transfusions to treat low blood cell counts, and sometimes intravenous immunoglobulin (IVIG) for infections.
• Stem cell transplants, multiple surgeries, can be part of the treatment. A patient can store his own stem cells, or a donorís cells can be used.
• Some patients are given additional cycles of treatment after transplant. This is called consolidation treatment and increases the chance of a complete response (where signs and symptoms of the disease go away).
• Some patients (even some who didn’t have a stem cell transplant) may be given long-term treatment with thalidomide, lenalidomide, or bortezomib. This is known as maintenance treatment, and helps delay the return of the myeloma, but it can cause serious side effects.

Prevention of multiple myeloma

• Researchers have found some evidence that certain types of foods might make more or less likely to develop multiple myeloma, and anti-cancer diets may help protect you from the disease.
• In general, an anti-cancer diet that will support your efforts to prevent multiple myeloma and cancer in general will require to focus on fruits, vegetables, whole grains, beans, nuts, and fish, and eat red meat and full-fat dairy products sparingly

Cancer Diet Tips from the experts:

The American Cancer Society offers similar guidelines. The organization recommends:

• Eating fruits and vegetables at every meal
• Choosing whole grains instead of foods containing processed or refined grains
• Limiting processed and red meats
• Practicing eating habits that allow you to maintain a healthy weight
• If you drink, limiting alcohol to two drinks daily if you’re a man and one if you’re a woman