Multiple Myeloma

Overview

What is multiple myeloma?
Multiple myeloma is a cancer that affects certain white blood cells called plasma cells. It accounts for about one per cent of all cancers worldwide. About four to five people in every 100,000 are diagnosed with it each year.

How does multiple myeloma develop?
The human body is made up of tiny building blocks called cells. Normal cells grow and multiply when the body needs them and die when the body does not need them.
Cancer is made up of abnormal cells that grow whether the body needs them or not. Multiple myeloma is a cancer that starts in the plasma cells, a type of white blood cell. Plasma cells make proteins that help the body fight disease. These cells are found in the soft, inner part of our bones called bone marrow. Multiple myeloma starts when the plasma cells become abnormal. It's also called myeloma or plasma cell myeloma.

Effects of multiple myeloma
Cancerous plasma cells are called myeloma cells. Myeloma cells crowd out the normal bone marrow, so there is not enough room for the bone marrow to make as many healthy cells. This can lead to several types of blood problems

·Low red blood cell count. This condition is called anaemia. We diagnose anaemia with a blood test. Anaemia can cause tiredness and other problems.
·Low white blood cell count. This condition is called neutropenia. It weakens the body's ability to fight infection.
·Low platelet count. This condition is called thrombocytopenia. It can lead to bleeding. Although this cancer starts in the blood cells, it also affects the bones. Myeloma cells can damage the bone structure. Bones can become weak and more likely to break.

Multiple myeloma and hypercalcaemia
Because they destroy bone, myeloma cells can cause calcium that's stored in the bone to be released into the bloodstream. This can lead to too much calcium in the blood, a condition called hypercalcemia. Hypercalcemia can damage the heart, nerves and kidneys. Signs of hypercalcaemia include
·constipation
·tiredness
·frequent urination
·frequent thirst
·muscle weakness

Multiple myeloma and kidney function
Multiple myeloma can also affect the kidneys. Myeloma cells make large amounts of abnormal proteins called M proteins. These M-proteins circulate in the blood and can overload the kidneys, causing them to stop working properly.


Symptoms

Multiple myeloma symptoms
The symptoms of multiple myeloma may be similar to those of other bone diseases or medical problems. Always ask your doctor for a diagnosis.
Each person's symptoms may be different. Myeloma cells and antibodies can cause symptoms such as
·Pain in the bones
·Bone fractures
·Weakness
·Tiredness
·Weight loss
·Repeated infections
·Nausea
·Vomiting
·Constipation
·Problems passing urine
·Weakness or numbness in your legs
·Back pain
·Rib pain

Multiple myeloma diagnosis
If you have any of the above symptoms, we will order a range of tests to confirm the diagnosis, including imaging scans and a biopsy.


Risk Factors

Risk factors for multiple myeloma
There's no way to know for sure if you'll get multiple myeloma. There is also no known way to prevent it. Certain factors make you more likely to develop this type of cancer.
Doctors do not know what causes multiple myeloma. The risk factors that have been identified only slightly increase your chances of getting this type of cancer. However, it's important to tell your doctor if you have symptoms of multiple myeloma and any of the following risk factors

· Age over 65: As you get older, you are more likely to develop multiple myeloma. Most people with myeloma are diagnosed after the age of 65. People under the age of 35 are rarely affected by the disease.

·Men: Men are slightly more likely than women to develop multiple myeloma.

·Family history: You are more likely to get multiple myeloma if a parent or sibling has the disease. Researchers study families in which more than one person has multiple myeloma. However, such families are extremely rare.

·Working with chemicals: Exposure to petroleum products may increase your risk of developing multiple myeloma. If you use industrial chemicals at work, make sure you follow the guidelines for working safely with them.

·Exposure to high levels of radiation: People who have been exposed to high levels of radiation, such as atomic bomb survivors, may have an increased risk of multiple myeloma. However, although researchers have suggested that exposure to radiation may be a risk factor, it only accounts for a very small number of cases.

·History of plasma cell disorders: Certain plasma cell disorders, such as solitary plasmacytoma and MGUS (monoclonal gammopathy of undetermined significance), can develop into multiple myeloma. A plasmacytoma is an accumulation of abnormal plasma cells in one place rather than throughout the bone marrow, soft tissue or bone. People with MGUS have the same abnormal proteins, called M-proteins, as people with myeloma, except that there is no cancer.

·Being overweight or obese: Being overweight or obese may increase your risk of developing multiple myeloma.


Diagnosis

Diagnosing multiple myeloma
Sometimes we find myeloma during a routine check-up, even if you don't have any symptoms. If you have symptoms of multiple myeloma, your doctor will ask you about
- Your medical history
- Your family history of cancer
- Your other risk factors
We may also carry out certain tests to check whether you have multiple myeloma. You may need more than one of these tests:

·X-rays
An X-ray is a diagnostic test that uses invisible beams of electromagnetic energy to produce images of internal tissues, bones and organs on film.
X-rays use invisible beams of electromagnetic energy to produce images of internal tissues, bones and organs on film. Standard X-rays are taken for many reasons, including the diagnosis of tumours or bone injuries.
Radiation during pregnancy can cause birth defects. Always tell your radiologist or doctor if you think you may be pregnant.
X-rays help the doctor to see if any of your bones are broken or affected, which is a sign of multiple myeloma.

·Blood tests
Your assessment may include specific blood tests, including (but not limited to) cell counts, measurements of various blood chemistries and markers of inflammation. We can measure many things in your blood such as salts, blood cell counts and protein markers specific to the heart (one is called BNP). Other tests may include blood chemistries, assessment of liver and kidney function, and genetic studies). In some cases, genetic testing may be recommended. We may also ask you to take part in our ongoing studies by allowing us to take and store some of your blood for future analysis.
Blood tests help your doctor check your immunoglobulin (antibody) levels. These are proteins made by your plasma cells. Multiple myeloma causes M-protein (immunoglobulin) levels to rise. Your doctor will also take a small blood sample for a complete blood count (CBC) and a comprehensive metabolic panel. This allows your doctor to check for anaemia, hypercalcaemia, kidney damage and other problems that can be caused by multiple myeloma.

·Urine tests
Urinalysis is a laboratory test of urine for different cells and chemicals, such as red blood cells, white blood cells, infections or excess protein. Urinalysis breaks down the components of urine to check for the presence of drugs, blood, protein and other substances. Blood in the urine (haematuria) can be the result of a benign (non-cancerous) condition, but it can also indicate an infection or other problem. High levels of protein in the urine (proteinuria) may indicate a kidney or cardiovascular problem.
Urine tests can help your doctor check for M-protein and other protein levels. You may need to collect urine for 24 hours for these tests. These tests can also show how well your kidneys are working. Myeloma can damage your kidneys.

·Bone marrow aspiration biopsy
Bone marrow aspiration and biopsy involves removing bone marrow, blood and a small piece of bone by inserting a needle into the hipbone or sternum. This type of biopsy is taken from either the sternum (breastbone) or the iliac crest hipbone (the area of bone on either side of the pelvis at the lower back). The skin is cleaned and a local anaesthetic is given to numb the area. A long, stiff needle is inserted into the bone marrow and cells are removed for examination; this is sometimes uncomfortable. A pathologist will examine the bone marrow, blood and bone under a microscope to look for signs of cancer. The aspiration may be followed by a core biopsy (taking a small 'chip' of bone from the marrow).
These tests look for cancer cells in the bone marrow, usually in the hip bone. They are often carried out at the same time. The area over the hip will first be numbed with a local anaesthetic. For the bone marrow aspiration, the doctor will insert a thin, hollow needle attached to a syringe into your hip bone to remove (aspirate) a sample of blood and cells from the bone marrow. This is usually followed by a bone marrow biopsy. For the biopsy, the doctor uses a larger needle to remove a small piece of bone and bone marrow from your hip bone. A pathologist will then examine the cell samples for cancer. A pathologist is a doctor who specialises in looking at cells under a microscope to check for problems, including cancer. A biopsy is the only way for your doctor to know for sure if you have cancer.

·MRI SCAN
MRIs use radio waves and magnets to create images inside your body. The energy from the radio waves creates patterns made up of different types of tissue and disease. These patterns create cross-sectional images that look like slices of the body. If you have a lot of pain in a particular area, your doctor may order an MRI of your spine or a specific area of bone, such as your hip bone. Your doctor may also use this test to find out if a damaged area of your spine or bones is at risk of further damage from myeloma.
For this test, you lie still on a table while it passes through a tube-like scanner. The scanner directs a continuous beam of radio waves at the area being scanned. A computer uses the data from the radio waves to create images of the inside of your body. You may need more than one set of images. Each may take from 2 to 15 minutes. The test may take an hour or more. Ask for earplugs if they aren't provided, as there is a loud pounding noise during the scan. If you are claustrophobic, you may be given a sedative before the test.

·CT scan 
A CT scanner takes many X-rays as you move through it on a table. A computer combines these images to create detailed pictures that your doctor can view. CT scans can show early stages of bone involvement in multiple myeloma.
·PET scan 
Your doctor may also arrange for you to have a positron emission tomography (PET) scan to help determine your stage. This test scans your whole body, so it is more helpful than a series of different X-rays. The PET scan shows which parts of your body are using glucose quickly. Glucose use is a sign of active, rapidly dividing cells, such as multiple myeloma cells. For this test, you will be injected with a small amount of radioactive glucose. You then lie still on a table that is moved into the PET scanner, which rotates around you and takes pictures.

Multiple myeloma treatment
Once we have confirmed your diagnosis, we will put together a treatment plan to suit your needs. Your specific treatment will depend on many factors, including your age, general health and the severity of your disease.


Treatments

Your multiple myeloma treatment plan
Your healthcare team will determine your specific treatment for myeloma bone disease based on
·Your age, general health and medical history
·The extent of your disease
·Your ability to tolerate certain medications, procedures or therapies
·Expectations for the course of the disease
·Your opinion or preference

Treatment options for multiple myeloma
Each type of treatment for multiple myeloma has a different goal. These are the main treatment options and their goals. You may have more than one of these treatments.

Bone strengthening drugs
We may use treatment with bisphosphonates to strengthen your bones and make it harder for myeloma cells to grow.

Chemotherapy
Chemotherapy is the use of anti-cancer drugs to shrink or kill cancer cells and reduce the spread of cancer to other parts of the body.
The aim is to keep the cancer under control for as long as possible.

Radiotherapy
Radiotherapy uses high-energy radiation to kill or shrink cancer cells, tumours and non-cancerous diseases.
The aim: To relieve symptoms and help with bone pain. Radiotherapy can also prevent or treat a fracture in the area of the bone weakened by the cancer. We can also use it to cure a single cluster of myeloma cells called a plasmacytoma.

Bone marrow transplant for cancer
A bone marrow transplant is a way of replacing the blood-forming cells that have been destroyed by cancer treatment. Before your transplant, we will give you high doses of chemotherapy and radiotherapy to kill as many of your cancer cells as possible. This will kill almost all of your bone marrow and the cancer cells in it. You will then be given healthy, new stem cells to make healthy blood cells.
This is called a bone marrow transplant or a peripheral blood stem cell transplant, depending on where we take the stem cells from. Stem cells can also be taken from
·Your own bone marrow before the transplant (autologous)
·A sibling or unrelated donor (allogeneic)
The aim: To help the bone marrow to heal and continue to make healthy blood cells.
To find out more about bone marrow transplantation, click here

Watchful waiting: Smoldering myeloma
Watchful waiting is when we monitor your condition closely without giving any treatment until symptoms develop or change.
The aim is to monitor or control cancers that grow very slowly and are unlikely to cause harm. This type of myeloma is called smouldering myeloma. Sometimes the treatments for multiple myeloma can do more harm than good. Your doctor may recommend watchful waiting if you don't have kidney or bone damage and have little or no anaemia.
You'll probably see your doctor every three months or so. You'll have blood and urine tests and possibly X-rays. These tests will check that the cancer is not starting to actively attack your body. If it is, you'll start active treatment.
Specialized treatments for multiple myeloma
Specialized treatments for multiple myeloma include
·Combination chemotherapy
·High-dose chemotherapy followed by a bone marrow transplant or autologous peripheral blood stem cell transplant

Chemotherapy and radiotherapy
Combination chemotherapy that targets the myeloma cells is the primary treatment for multiple myeloma. You may receive chemotherapy at the Stanford Cancer Center Infusion Center. Patients with multiple myeloma may also receive radiation therapy to help control the growth of tumours in the bones and relieve pain caused by these tumours.

Clinical trials and research
Doctors in the Hematology Programme are actively studying new investigational therapies for patients with multiple myeloma. For example, doctors at Lu Daopei Hospital participated in clinical trials for a new drug called BCMA. Doctors in the Hematology Programme often bring new therapies to their patients. 


Staging

Multiple myeloma staging
Before we can decide on treatment options, we need to know the extent, or stage, of multiple myeloma. We will look at the results of blood tests, imaging tests and bone marrow tests to determine the stage of the cancer. Once we know the stage, we can plan the most effective treatment for multiple myeloma.
There are two systems for staging multiple myeloma:

·Durie-Salmon staging system
The Durie-Salmon system is the traditional system for staging multiple myeloma. It is based on four different factors:
1. The amount of abnormal monoclonal immunoglobulin in the blood or urine. A large amount of monoclonal immunoglobulin is a sign that there are many malignant plasma cells in the blood making this abnormal protein.
2. The amount of calcium in the blood. High levels of calcium in the blood are also associated with advanced bone damage. Bones normally contain a lot of calcium, and bone destruction releases calcium into the blood.
3. The amount of bone damage seen on X-rays. If there are many areas of bone damage, this is a sign of an advanced stage of multiple myeloma.
4. The amount of haemoglobin in the blood. Haemoglobin is the part of red blood cells that carries oxygen. Low levels of haemoglobin are a sign that the myeloma cells are taking up a lot of bone marrow and there is not enough room for the normal bone marrow cells that make red blood cells.
·Stages in the Durie-Salmon system
There are three different clinical stages of multiple myeloma in the Durie-Salmon system. Stage I indicates the smallest amount of tumour. Stage III indicates the largest amount of tumour.
·Stage I: X-rays and blood tests show that only a small number of myeloma cells are present in the body. Most people with this stage have no symptoms. Your doctor may say that you have a 'low tumour burden' at this stage.
·Stage II: The myeloma cells have spread throughout the body. Your doctor may say that you have an "intermediate tumour burden" at this stage.
·Stage III: X-rays and blood tests show that there are many cancer cells in the body. Your doctor may say that you have a "high tumour burden" at this stage.

·International staging system
The International Staging System is a newer system that many doctors now use to classify multiple myeloma. This system divides myeloma into three stages based only on the blood levels of beta-2 microglobulin and albumin.
·Stage I: The beta-2 microglobulin level is less than 3.5 milligrams per litre (mg/dL) and the albumin level is 3.5 grams per deciliter (g/dL) or higher.
·Stage II: Neither stage I nor III, which means either
·The beta-2 microglobulin level is between 3.5 and 5.5 (with any albumin level), or
·The albumin is less than 3.5 and the beta-2 microglobulin is less than 3.5.
·Stage III: The beta-2 microglobulin level is greater than 5.5.
(The above content is extracted from stanfordhealthcare.org)