What does astrology have to do with Multiple Myeloma? More than you might think.
Cancer is the fourth sign of the zodiac spanning June 22 to July 22. The crab is the mascot of the Cancer zodiac sign. The letters C-R-A-B also stand for four clinical manifestations of Multiple Myeloma, a cancer of the blood resulting from the proliferation of malignant plasma cells. The presence of CRAB criteria are important diagnostic indicators of Multiple Myeloma. In 2003, the International Myeloma Working Group (IMWG) defined the CRAB criteria in the British Journal of Hematology(1).
C stands for Calcium. Patients with Multiple Myeloma can have elevated levels of calcium (hypercalcemia) due to the breakdown of bone. Hypercalcemia resulting from Multiple Myeloma must be differentiated from other causes such as overactivity of the parathyroid glands, medications and excessive use of calcium and Vitamin D supplements.
R stands for Renal. Many patients with Multiple Myeloma have some degree of renal insufficiency at diagnosis. If untreated, patients with Multiple Myeloma can progress to a condition called myeloma kidney and may lose their kidney function completely. Patients with acute kidney injury (AKI) resulting from Multiple Myeloma need to be differentiated from those with AKI from other causes to make sure the correct treatment is initiated.
A stands for Anemia. In Multiple Myeloma, cancerous plasma cells invade the bone marrow and can disrupt normal hematopoiesis or blood formation. This results in decreased red blood cell production and the condition called anemia. Anemic patients often complain of fatigue which is one of the common signs of Multiple Myeloma.
B stands for Bone. Many patients with Multiple Myeloma have bone lesions. These lesions are caused by the destruction of bone in areas where cancerous plasma cells have made a niche in the bone marrow. In these areas malignant plasma cells cause the activation of osteoclasts that in turn, cause bone resorption and the release of calcium from the bone into the serum. The bone in these areas may be weakened and fractures are often an unwanted sequela.
Following routine laboratory evaluations (Freelite® serum free light chain assays, serum protein electrophoresis, immunofixation electrophoresis), it is important for clinicians to be able to differentiate CRAB conditions resulting from Multiple Myeloma from other causes. Individual CRAB criteria can be associated with many pathologies and the faster the root cause of symptoms are diagnosed, the faster the patient will receive appropriate treatment.
- Br. J Haematol 2003 Jun; 12: 749
4 Clinical Uses of the Ideal Biomarker
There are a variety of biomarkers detected by lab tests, but not all of them are equal in their clinical utility. Using the clinical applications as outlined by the Biological Definitions Working Group *, an ideal biomarker can be used for all four of the following clinical uses or applications:
Identify a disease or abnormal condition
Stage a disease or classify the extent of disease
Indicate disease prognosis
Monitor clinical response to an intervention
For Multiple Myeloma and related disorders, the ideal biomarkers for identification, staging, prognosis, and monitoring are free light chains, the short protein chains on the antibody. There are two types of light chains: lambda (λ) chain, kappa (κ) chain. As ideal as free light chains are as biomarkers, they’re only as clinically useful as the test that is sensitive enough to detect them.
Freelite® is a simple, quantitative blood test that is able to detect very high levels of free light chain concentrations, as well as very low concentrations into the normal range, allowing physicians the ability to quantitatively monitor disease response and relapse. Freelite and serum protein electrophoresis (a lab test that detects intact immunoglobulins) provide 100% diagnostic sensitivity for Multiple Myeloma when combined.
The serum free light chain test (i.e., Freelite) is recommended by the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines®) and the International Myeloma Working Group (IMWG) for use in the initial diagnostic workup of Multiple Myeloma and related disorders.
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(*In order to provide clarity on what a biomarker is, an expert working group (Biological Definitions Working Group) was convened by the National Institutes of Health in 2001 and charged with defining the term biomarker and outlining, using consistent terminology, the potential clinical applications of biomarkers. The BDWG defines a biomarker as: “a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.”)
10 Warning Signs of Immune Deficiency
Opportunistic pathogens (bacteria and viruses) that can cause infection are ubiquitous in our normal environment.
Normally, cells and protein mediators in immunocompetent individuals are able to kill pathogens before they cause serious illness. However, those people with a disease of the immune system such as Primary Immunodeficiency Disease (PID) can become seriously ill, sometimes with permanent damage to their organs, if they are not properly diagnosed and treated.
According to the World Health Organization there are more than 185 different manifestations of PID.
Though symptoms of Primary Immunodeficiency Disease can vary, frequent infection – particularly of sinuses, ears, and lungs – is common at an early age. The Jeffrey Modell Foundation (JMF) has developed a list of 10 warning signs of immune deficiency:
JMF recommends that children and adults who are affected by two or more of these warning signs of immune deficiency should be evaluated for the possibility of an underlying Primary Immunodeficiency.
Testing for Primary Immunodeficiency
More than half of Primary Immunodeficiency Diseases are disorders resulting in antibody (immunoglobulin) deficiencies. Levels of immunoglobulin (IgA, IgG, IgD, IgE, IgM) and immunoglobulin subclasses (IgA1, IgA2, IgG1, IgG2, IgG3, IgG4) are easily measured by a simple blood test. Additional tests such as Vaccine Response to protein antigens (Tetanus Toxoid and/or Diphtheria Toxoid), protein conjugate antigens (Hib) and polysaccharide antigens (PCP) may be needed.
An additional group of proteins involved in the innate immune system are known collectively as Complement, which includes whole proteins and protein fragments C1 through C9. Once activated, the Complement system sets off a cascade of events resulting in destruction of a target cell. Individual Complement proteins can be measured as well as the overall functioning of the Complement system by a test called CH50.
To learn more about diagnostic tests available for Primary Immunodeficiency, contact Binding Site (firstname.lastname@example.org).
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