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Multiple Myeloma – Symptoms, Diagnosis, Prognosis And Treatment

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Multiple Myeloma – Symptoms, Diagnosis, Prognosis And Treatment

Multiple myeloma represents a malignant proliferation of plasma white cells ( a special type of mature, antibody-secreting B white cells), which are derived from a single clone.

The body responds to tumor products by symptoms given by organ dysfunction:

  1. Bone pain or fracture
  2. Renal failure
  3. Susceptibility to infection
  4. Anemia 
  5. Hypercalcemia
  6. Abnormalities of blood coagulation
  7. Neurologic symptoms

As in many other forms of neoplasia, the main cause of multiple myeloma is not known.

Multiple Myeloma

The incidence of multiple myeloma increases with age. The median age of diagnosis is 68 years and men are affected more often than women. It was observed that multiple myeloma occurred, with increased frequency, in people who were exposed to the radiation of nuclear warheads in World War II, after a 20-year latency.

The malignant plasma cells all belong to a single clone, and the excessive antibodies they produce are identical monoclonal antibodies. These accumulate in the bloodstream and can be detected by serum protein electrophoresis (normally serum antibodies are of many forms and show a varied distribution of size in the electrophoresis test). In plasma cell myeloma, there is a large amount of one type of antibody wich form a characteristic spike.

Gel Electrophoresis

Gel Electrophoresis

Excessive production of light-chain antibody fragments by malignant plasma cells results in their accumulation in blood and urine. When are found in urine, these light-chain fragments are called Bence Jones proteins. Bence Jones  proteins accumulate in the kidneys and cause kidney damage, therefore this is an important aspect to the pathogenesis of multiple myeloma.

Malignant plasma cells tend to accumulate in bone where they enhance osteoclastic activity and produce bone lesions. Pathologic fractures, especially compression fractures of the vertebral collumn are common.

Bone destruction releases calcium into the bloodstream, the result of this process is hypercalcemia.

Multiple Myeloma Signs And Symptoms

Most of the clinical manifestations of multiple myeloma are caused by bone and renal damage.

  • Bone pain is the most common symptom of multiple myeloma affecting nearly 70% of patients.The pain usually involves the back and  ribs and unlike of metastatic carcinoma, which is often worse at night,the pain of myeloma is precipitated by movement.  Persistent pain which appear in a patient with multiple myeloma usually signifies a pathological fracture ( fractures with no known trauma). Radiological studies of the ribs, spine, skull and pelvis showed a characteristic appearance of the bone, called “honeycomb appearance”, due to the aspect of lucid areas given by the demineralised bone.
Multiple Myeloma X-Ray
  • Renal failure is a complication experienced by approximately 50% of patients with plasma cell myeloma. Renal function may decline over time culminating in chronic renal failure especially in case of dehydration. Renal failure is due to a combination of factors: hyperproteinemia, Bence Jones proteinuria, hypercalcemia, hyperuricemia, recurrent infections and use of non-steroidal agents for pain control.
Renal Failure
  • Chronic complications of hypercalcinemia may dominate the clinical picture. Such manifestations may include neurologic symptoms : lethargy, weakness, depression and confusion.
Clinical Picture
  • Susceptibility for chronic infections is the next most common problem in patients with multiple myeloma.The most common infections are pneumonia and pyelonephritis. This is due to diffuse hypogammaglobulinemia if the M component is excluded. The hypogammaglobulinemia is related to both decreased production and increased destruction of normal antibodies.
E Coli
  • Anemia occurs in 80% of multiple myeloma patients. It is usually normocytic and normochromic and related to the replacement of normal marrow by expanding tumor cells. Tumor cells also play a part in inhibiting hematopoiesis.
Multiple Myeloma Patient

Multiple Myeloma Diagnosis

Basically, the diagnosis of multiple myeloma is suspected on:
  1. Monoclonal antibody peak,detected on serum protein electrophoresis
  2. Presence of Bence Jones proteinuria
  3. Hypercalcemia
  4. Evidence of bone lesions
The diagnosis is confirmed by bone marrow biopsy
Normally the cell component of bone marrow comprises about 5%. For the diagnosis of a multiple myeloma, the cell component of bone marrow should comprise a minimum of 10%-15%.
The onset of multiple myeloma is generally slow and insidious. Affected individuals remain asymptomatic until the disease is fairly advanced. The asymptomatic stage often lasts for many years after malignant transformation of the blood cells. During this time the only complaint of the patient may be frequent infections. Early diagnosis is usually possible due to findings of protein in the urine or high serum calcium levels on routine examination. Bone pain is usually the first symptom of multiple myeloma.
Myeloma Cells

Multiple Myeloma Prognosis And Treatment

Antineoplasic agents may be used to induce and maintain a remission in plasma cell proliferation. The best chemotherapy regimen has not yet been determined.

High dose chemotherapy followed by allogeneic bone marrow transplantation is becoming the most common course of treatment. However the mortality rate associated with transplantation is high (app. 50%). autologous stem cell transplantation is considered to be optimal therapy for most patients. Pharmacological management of renal dysfunction is also necessary. Chronic bone pain may require narcotic and non-narcotic pain relievers. Localised application of radiation to bone lesions may reduce bone pain in some cases.