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Multiple Myeloma                                                                                                                                                  

Basic lab:  

  1. CBC, serum calcium & creatinine, serum protein electrophoresis or immunoglobulin electrohphoresis,
    UA, 24-hr urine protein & immunoglobulin electrophoresis, 24-hr urine Bence-Jones protein collection.  
  2. Bone marrow biopsy & aspiration if IgG>2.5 g/dL or IgA>1.5 g/dL or IgM>3 g/dL.  
  3. Skeletal x-ray survey for lytic lesions.

MM is uncommon in persons younger than 40 years; the incidence increases rapidly after age 50, equally in men and women.  
MM is characterized by


Diagnostic Criteria for Various Gammopathies

Multiple Myeloma (MM)

The diagnosis of MM requires at least one of the following major criteria:
- plasmacytoma;
- bone marrow with at least 30% plasma cells; and
- M protein on serum electrophoresis showing levels of IgG >3.5 g/dl, IgA >2.0 g/dl, or
- urine light-chain (Bence-Jones protein) excretion > 1 g/24 hr
One or more of the following minor criteria are also required:
- bone marrow plasmacytosis greater than 10%
- M protein in serum or urine but less than the levels listed above under major criteria;
- lytic bone lesions; and decreased residual immunoglobulins.

Differentiation of MGUS from Multiple Myeloma and Macroglobulinemia

Differentiation of the patient with benign monoclonal gammopathy from one in whom multiple myeloma, macroglobulinemia, or a related disorder eventually develops is very difficult when the M-protein is first recognized. The size of the M-protein is of some help--levels greater than 3 grams per deciliter usually indicate overt multiple myeloma or macroglobulinemia, but some exceptions, such as smoldering multiple myeloma (SMM), exist. Levels of immunoglobulin classes not associated with the M-protein (normal polyclonal or background immunoglobulins) are almost always reduced in multiple myeloma or Waldenstrom's macroglobulinemia, but a reduction may also occur in benign monoclonal gammopathy. The association of a monoclonal light chain (Bence Jones proteinuria) with a serum monoclonal gammopathy suggests multiple myeloma or macroglobulinemia, but in many patients with small amounts of monoclonal light chain in the urine, the M-protein in the serum remains stable for many years. The presence of more than 10% plasma cells in the bone marrow suggests multiple myeloma, but some patients with more plasma cells have remained stable for long periods. The presence of osteolytic lesions strongly suggests multiple myeloma, but metastatic carcinoma may produce lytic lesions as well as plasmacytosis and may be associated with an unrelated monoclonal gammopathy.


Treatment of Multiple Myeloma

Indications for therapy include the development of significant anemia, hypercalcemia, or renal insufficiency; the occurrence of lytic bone lesions; and the finding of extramedullary plasmacytomas.

Almost all patients with multiple myeloma will eventually relapse.

Treatment for Refractory Multiple Myeloma:

VBAP (vincristine, carmustine [BCNU], doxorubicin [Adriamycin]) on day 1 and prednisone daily for 5 days every 3 to 4 weeks benefits 30% of patients. It is well tolerated. If the patient's leukocyte and platelet levels are satisfactory, cyclophosphamide, 600 mg/m2 /day intravenously for 4 days (days 1-4), plus prednisone, 50 mg twice a day for the same 4-day period, followed by granulocyte colony-stimulating factor, has been helpful in patients with refractory advanced disease.

Thalidomide given orally at a dose of 200 mg/d for 2 weeks, then increased by 200 mg/d every 2 weeks, up to a maximal dose of 800 mg/d. Four (25%) achieved a partial response to therapy, with a greater than 50% reduction in the serum or urine M protein level. Responses lasted 2, 4+, 8, and 10+ months. Major adverse effects included constipation, sedation, rash, and peripheral neuropathy. CONCLUSION: Thalidomide is an active agent in the treatment of patients with advanced myeloma. (Mayo Clin Proc 2000 Sep;75(9):897-901)

Multiple myeloma has a progressive course, and the median survival is approximately 3 years.

Smoldering Myeloma

MGUS (Monoclonal Gammopathy of Undetermined Significance)

Biclonal Gammopathies

Solitary Plasmacytoma

Waldenstrom's Macroglobulinemia


Idiopathic Bence Jones Proteinuria  


Multiple Myeloma 1999 Update  
      - presented 12-3-1999 prior to the 41st American Society of Hematology Annual Meeting in New Orleans, Louisiana.

Multiple Myeloma Update March 2000 - Medscape

Postgraduate Med 8/1999;106:135 - Malcolm Brigden
SAM 1999
Dambro: Griffith's 5-Minute Clinical Consult, 1999 ed.
Goldman: Cecil Textbook of Medicine, 21st Ed., 2000

Multiple Myeloma: How Far Have We Come?    
Kenneth C. Anderson - Mayo Clinic Proceedings January 2003 Volume 78 Number 1

Current Therapy for Multiple Myeloma
S. Vincent Rajkumar - Mayo Clinic Proceedings August 2002 Volume 77 Number 8