Malignant myeloma cells (plasma cells) accumulate in bone marrow and cause a disruption of normal bone marrow function, resulting in anemia. There is a suppression of normal immune function and the release of monoclonal protein (M protein) into the blood and/or urine. There may be damage to surrounding bone.¹

Presenting symptoms include²:

• Bone pain
  – Up to 70% of patients have bone pain at presentation. The lumbar vertebrae are common sites of pain.
• Pathologic fractures and bone lesions
  – 93% of patients have more than one site of bony involvement, often severe.
• Spinal cord compression
  – Of special concern are back pain, weakness, numbness, or dysesthesias in the extremities. The most common cause of weakness in patients with myeloma is anemia, which may be quite severe.
• Bleeding
  – Occasionally, from thrombocytopenia.
• Hypercalcemia
  – Patients may have hypercalcemia if they present with confusion, somnolence, bone pain, constipation, nausea, and thirst. This complication may be present in as many as 30% of patients at presentation.
• Infection
  – Abnormal humoral immunity and leukopenia may lead to infection. Pneumococcal organisms are commonly involved, but shingles (ie, herpes zoster) and Haemophilus infections are also common among patients with myeloma.
• Hyperviscosity
• Neurologic symptoms
  – Carpal tunnel syndrome is a common complication of myeloma. Meningitis, especially resulting from pneumococcal or meningococcal infection, is also common in patients with myeloma. Some peripheral neuropathies have been attributed to myeloma.

The most visible aspect of multiple myeloma is its effect on bones throughout the body. In the majority of patients with myeloma, soft spots develop where the bone structure has been damaged. These can extend from the inner bone marrow to the outside surface of the bone. Soft spots appear as holes on standard bone x-ray film and are referred to as osteolytic lesions. These lesions weaken the bone, causing pain and increasing the risk of fractures.³

The Durie-Salmon system has been the most widely used myeloma staging system since 1975. With this system, the clinical stage of disease (stage I, II, or III) is based on several measurements, including levels of M protein, the number of bone lesions, hemoglobin values, and serum calcium levels. Stages are further divided according to renal function, as determined by serum creatinine levels (classified as A or B).

A new International Staging System (ISS) for myeloma was recently proposed. This system, which appears to better discriminate among staging groups, is based on easily measured serum levels of beta 2-microglobulin (ß2-M) and albumin.⁴

The following table summarizes the staging criteria of both systems.⁴

Source: Classification and staging. Multiple Myeloma Research Foundation. Available at http://www.multiplemyeloma.org/about_ myeloma/2.06.html. Accessed December 2004. Reprinted with permission.

1.	Durie BGM. International Myeloma Foundation Concise Review of the Disease and Treatment Options: Multiple Myeloma. 2003 ed. North Hollywood, Calif: International Myeloma Foundation; 2003.
2.	Grethlein S. Multiple myeloma. Emedicine. Available at http://www.emedicine.com/med/topic1521.htm#target1. Accessed December 2004.
3.	Myeloma bone disease. Multiple Myeloma Research Foundation. Available at http://www.multiplemyeloma.org/about_myeloma/2.08.html. Accessed December 2004.
4.	Classification and staging. Multiple Myeloma Research Foundation. Available at http://www.multiplemyeloma.org/about_myeloma/2.06.html. Accessed December 2004.