diease

Multiple Myeloma


OVERVIEW OF Multiple Myeloma :

Multiple myeloma is the type of cancer which develops in the plasma cells.


STRUCTURE of Multiple Myeloma :

Normal plasma cells are found in the bone marrow and it is the important part of the immune system. Lymphocytes are one of the main types of white blood cells in the immune system that include T cells and B cells. They are present in many areas of the body such as lymph nodes, bone marrow, intestines and the bloodstream.

When B cells respomds to an infection, they get mature and changes into the plasma cells.

Plasma cells make antibodies that help the body to attack and kill the germs.

Plasma cells are found mainly in the bone marrow. The bone marrow is the soft tissues inside the bones. In addition to plasma cells, normal bone marrow is also home for other blood cells such as red cells, white blood cells and platelets.

When these plasma which make their origin from the B lymphocytes grows out of control becomes cancerous which is called as the multiplemyeloma. The abnormal proteins includes immunoglobulin, monoclonal protein,, M spike or paraprotein.

There are, however, other plasma cell disorders that also have abnormal plasma cells but do not meet the criteria to be called active multiple myeloma. These other plasma cell disorders include:

  • Monoclonal gammopathy of uncertain significance (MGUS)
  • Smoldering multiple myeloma (SMM)
  • Solitary plasmacytoma
  • Light chain amyloidosis.


EPIDEMIOLOGY :

The incidence of Multiple Myeloma  is 0.7/1,00,000 population 


CAUSES :

Food habits- food rich in fat and oil

Age

Familial history/ genetics

Inflammatory bowel disease- ulcerative colitis and crohns disease

Chronic exposure to radiation

Smoking

Alcohol consumption

Ingestion of higher amount of NSAIDs

Ebstein barr virus


PATHOPHYSIOLOGY :

Multiple myeloma cells shows malignancy with the plasma cells. This result in the activation of the osteoclast which result in the resorption of the bone and suppress the activity of the bone forming cells that is the osteoblast. Multiple Myeloma cells initiates the cytokines production which in turn increases the osteoclastic activity.

The osteoclastogenic activating factors include RANKL, MIP-1α, TNF-α, Interleukin 3 (IL-3), and IL-6, Ephrin B 2, Annexin.

Adhesive interaction of the myeloma cells and stromal cells results in the activation of the  RANKL which in turn increases the osteoclastic activity of  the cells.


COMMON CLINICAL SIGNS AND SYMPTOMS :

  • Bone pain
  • Weakness and fatigue
  • Weight loss and loss of appetite
  • Upset stomach
  • Constipation
  • Confusion
  • Frequent infections
  • Severe thirst
  • Weakness or numbness in your arms and legs


DIAGNOSTIC :

Blood test:

The routine blood test is done to look  for the anaemia, lymphocytosis and other cell count.

Blood chemistry tests:

Creatinine: high amount of creatinine indicates that the kidney is not functioning properly.

Albumin: low amount of this protein in blood indicates multiple myeloma

Calcium: since the patient with multiple myeloma tends to have increase in the bone resorption the blood calcium levels are increased in them.

Lactic dehydrogenase: it is the metabolic product and the rise in LDH indicates that the disease has worst prognosis.

Urine test:

The urine test is indicated to check for the multiple myeloma proteins. These test are also known as protein electrophoresis and urine immunofixation.

Quantitative immunoglobulins:

This test measures the blood levels of the different antibodies. The antibodies include IgA, IgD,IgG,IgM.

 

Electrophoresis:

The antibody produced by the multiple myeloma is monoclonal. Serum protein Electrophoresis is used to measure the monoclonal antibody test. Immunofixation or immunoelectrophoresis is used to determine the exact type of abnormal antibody. This abnormal protein includes monoclonal immunoglobulin, monoclonal protein, M spike or paraprotein.

The  antibodies consists of 2 Heavy chain and 2 Light Chain. Sometimes the light chain proteins are excreated in the urine which are termed as Bence Jones proteins. This test is known as urine protein electrophoresis. The urine is collected for 24 hours of time period and not the routine urine is collected.

Serum free light chains:

This test detects the light chain in the blood. The light chains are known as kappa and lambda. And they are present in 1:1 ratio normally.

Beta 2 microglobulin: It is useful for patients prognosis. High level indicates the worst prognosis.

Bone marrow aspiration:

In bone marrow aspiration, the back of the pelvic bone is numbed with local anesthetic. Then, a needle is inserted into the bone, and a syringe is used to remove a small amount of liquid bone marrow. This causes a brief sharp pain. For the biopsy, a needle is used to remove a tiny splinter of bone and marrow. Patients may feel some pressure during the biopsy. There is some soreness in the biopsy area when the numbing medicine wears off. Most patients can go home immediately after the procedure.

The bone marrow tissue is examined in the lab to see the appearance, size, and shape of the cells, how the cells are arranged and to determine if there are myeloma cells in the bone marrow and, if so, how many. The aspirate (the liquid part of the bone marrow) may also be sent for other tests, including immunohistochemistry and flow cytometry, and chromosome analyses, including karyotype and fluorescent in situ hybridization (also known as FISH).

Immunohistochemistry: a part of the biopsy is treated with special proteins which causes some colour change and it is useful for detecting the multiple myeloma.

Flow cytometry:

A sample of bone marrow is treated with special proteins that stick only to certain cells.

Cytogenetics:

This test evaluates the chromosome in normal bone marrow cells and in myeloma cells. Chromosomal abnormalities such as deletions, translocations , abberations can be detected.

Fluorescent in situ hybridization(FISH):

It uses special fluorescent dyes that only attach to specific parts of chromosomes. It can find most of the chromosomal changes.

Fine needle aspiration (FNA) biopsy:

A needle is used to aspirate small fragments of tissues. It is used for cancer in the lymph node in the lungs.

Other imaging test:

Bone Xray:

The x ray predicts any abnormal area in the bone

Computed tomography:

It reveals the slice of the bone. It uses both the combination of x ray and computer aided device.

It helps to analyse the size, shape and position of any lung tumour and also it helps in the detection of enlarged lymph nodes.

It also looks for any masses in the adrenal gland, liver, brain and other organs.

 CT guided needle Biopsy:

CT scan might be used to guide a biopsy needle into this  area to get the tissue for bone cancer.

MRI scan:

It uses the soft tissue image of the organ. It uses the both the magnet and radiowaves.

It often reveals whether the cancer cells has spread to the brain or spinal cord.

Positron emmisison tomography:(PET)

 A radioactive form of sugar in injected into the blood and the positron are emitted to reveal the cancer site.

They can detect if the cancer cell has spread anywhere.

Bone scan:

A low level radioactive material is injected into the blood and collects mainly in abnormal areas of bone and resorption areas in bone can be viewed.

Other things that accounts for Multiple Myeloma:

1. A plasma cell tumor (proven by biopsy) OR at least 10% plasma cells in the bone marrow.

2. At least one of the following:

  • High blood calcium level
  • Poor kidney function
  • Low red blood cell counts (anemia)
  • Holes in the bones from tumor found on imaging studies (CT, MRI, PET scan)
  • Increase in one type of light chain in the blood so that one type is 100 times more common than the other
  • 60% or more plasma cells in the bone marrow


TREATMENT AND PROGNOSIS :

Chemotherapy:

A chemotherapy is after the sugery or before the surgery to shrink the cancer cells. A chemotherapy is nothing but the delivery of drug intravenously

Radiation therapy:

It uses powerful x rays or emission of protons to destroy the cells. The radiation therapy also aids  in shrinkage of the cells and also relief the symptoms caused by the cancer.

Immunotherapy

it is a drug treatment that uses your immune system to fight cancer. Your body's disease-fighting immune system may not attack your cancer because the cancer cells produce proteins that blind the immune system cells from recognizing the cancer cells. This immunotherapy boos those cells and helps the body to fight against it.

Drugs used: Thalidomide, lenalidomide, and pomalidomide

Targeted therapy:

This therapy involves targeting the specific organs. It involves the emission of rays.

Steroid therapy: 

Prednisone or Dexamathasone can be given to reduce the effect of plasma cells.

Bone modifying cell:

 These drugs are used to strengthen the bone. Drugs: zoledronic acid  and pamidronate, Denosumab


PROGNOSIS :

The early 5 year survival rate is 75% and to the distant spread is 53%.


PREVENTION :

Avoid smoking

Avoid air pollution areas

Avoid the exposure to the radiation and chronic chemicals

Follow healthy diet


Medicines used in the Treatment :

cyclophosphamide,

 doxorubicin

 cisplatin

carmustine