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MULTIPLE MYELOMA
Definition:
Multiple Myeloma is a malignancy
characterized by a proliferation of plasma cells. Plasma cells
are mature B lymphocytes produced in the bone marrow which
function to produce immunoglobulins(antibodies) necessary to
fight infection. The increase in B cells therefore increases the
amount of circulating immunoglobulins(Ig). This increase has the
potential to affect many organ systems which will be discussed in
further detail below.
Below is a three dimensional picture of an
immunoglobulin. You can see the high level of complexity
involved. The "H" stands for heavy chains and the
"L" represents light chains.
There are two types of light chains:(AKA Bence-Jones proteins)
1. kappa chains
2. lambda chains
Full immunoglobulins can deposit within the cells of the kidney
and cause renal failure. A good way to measure this is
quantifying the amount of Bence Jones proteins in the urine.
Clinical Manifestations:
1.
Median age is around 60 years of age
2. Bone pain secondary to pathologic fractures-plasma cell tumors
commonly infiltrate the bone and cause bone degradation and
fractures (see x-ray below)
3. Fatigue from anemia(decreased red blood cells) secondary to
replacement of normal bone marrow tissue by plasma cells
4. Recurrent infections from the deficiency of normal
immunoglobulins
Laboratory and Radiographic
Analysis
1.
Anemia from decreased RBC production
2. High serum calcium from bone degradation (see x-ray below)
Plasmacytomas induce osteoclastic activating factor (OAF) which
stimulates osteoclasts to break down bone tissue. Osteoclasts
normally do this to break down old bone tissue and then
osteoblasts come in and make new tissue.
x-ray of the forearm
-you can see the lucent areas where plasma cell tumors are simply eating away the bone. With minimal pressure a fracture can occur.
3. Elevated serum renal chemistries(BUN,
creatinine, etc) to indicate renal impairment from the deposition
of immunoglobulins in the kidney
4. "M" spike or monoclonal spike-When a patient is
evaluated for MM, urine and serum proteins are evaluated by a
process known as electrophoresis. If MM is present, a specific
immunoglobin(i.e. Ig A, IgG, IgM etc) is substantially elevated.
Normal electrophoretic pattern of albumin,
alpha, beta, and gammaglobulins (immunoglobulins are types of
gamma globulins)
Abnormal gamma globulin spike diagnostic of
MM
5. Peripheral blood smear will reveal Rouleaux Formations where RBCs stack on top of each other like a roll of coins.(below). This occurs because Immunoglobulins act "sticky" and cause red blood cells to stick together.
6. Bone marrow aspiration reveals increased number of immature plasma cells >10% and the presence of Mott cells(below). A Mott cell is a plasma cell with numerous vacuoles (smaller circles in the cell) which contain immunoglobulins.
7. Elevated beta-2 microglobulin and Lactate Dehydrogenase(LDH) are not specific for MM but are used for prognostic factors
1. Supportive Treatment:
--pain control for bone fractures
--treatment of underlying infections
--prevent renal failure with adequate hydration, control of
elevated calcium, avoidance of nephrotoxic drugs and IV contrast
2. Chemotherapy:
Untreated MM
--low risk disease- melphalan and prednisone(MP) are commonly
administered first with a 40% response rate
--higher risk disease- vincristine, adriamycin,
dexamethasone(VAD) are commonly used as first line agents
You may encounter the use of the use of lomustine (CCNU) and
carmustine (BCNU) for first course therapy as well.
Resistent MM
--if resistent to previously mentioned chemotherapy then VAD +
cyclophosphamide, etoposide, and GM-CSF is given
--if still resistent then myeloblastive treatment and stem cell
transplant is the next treatment of choice
3. Radiotherapy:
--Local radiotherapy (30-40Gy) is effective
in helping with bone pain and spinal cord compression
4. Interferon:
--Alpha interferon can prolong remission,
but has not shown a significant increase in survival rate.
5. Supportive Therapies:
--a. Chronic Anemia- Erythropoietin (Epogen,
Procrit) stimulates production of RBCs
--b. Chronic Infection-If chronic infections are occuring
secondary to chemotherapy induced neutropenia (decreased WBCs),
then G-CSF(Neupogen) can be given. Chronic bacterial infections
secondary to decreased normal gammaglobulins can be treated with
replacement gammaglobulin.
--c. Recurrent fractures- can be treated with bisphosphanates
(Aredia, Fosamax, etc) which may delay or prevent pathologic
fractures
Bibliography:
Images:
1. IgG1-from the Dept of Chemistry at the University of Kansas
www.chem.ukans.edu/chem
2. x-ray-from the Univ of Washington-
www.rad.washington.edu/UnknownCases/Unk46/Unknown46.answers.html
3. normal electrophoresis from the Univ of Washington-
-www.rad.washington.edu/UnknownCases/Unk46/Unknown46.answers.html
4. abnormal
electrophoresis-www2.cyber.vt.edu/sdru/problems/intro/answer6.htm
5. Rouleaux Formation from Webpath-on my link page
6 & 7-Univ of Virginia-www.med.virginia.edu
Other Source:
1."Cancer Management: A Multidisciplinary Approach",
Pazdur et al., second edition 1998, PRR publishers of New York