Multiple myeloma is a malignant blood disorder, constituting about 10% of all blood cancers, in which there is abnormal multiplication of plasma cells.(1) B lymphocytes are precursors of plasma cells and their role is in providing immunity by the production of immunoglobulins. Therefore, in multiple myeloma, there is overproduction of abnormal immunoglobulins (IgA, IgG and IgM) and light chains. Multiple myeloma has elevated levels of M proteins (myeloma proteins) in serum.
How Many Stages Of Multiple Myeloma Cancer Are There?
Staging of a disease is done to evaluate the growth of cancer and to determine the prognosis of the disease. Multiple myeloma has two staging systems, namely, international staging system(2) and Durie-Salmon staging system(3). International staging system (ISS) is the more common and widely used staging for multiple myeloma.
International Staging System
- Stage I- Serum albumin >35 g/l and serum β2-microglobulin <3.5 mg/l. The survival period of stage I is 62 months.
- Stage II- It is the stage that does not fall under the criteria of stage I or stage III. The survival period of stage II is 44 months.
- Stage III- Serum β2-microglobulin >5.5 mg/l. The survival period of stage III is 29 months.
Durie-Salmon Staging System
- Stage I- It is characterized by all of the following: Normal serum calcium levels and no bony lesions along with Hb >10 g/dl and low concentration of M-protein (IgG <50 g/l, IgA <30 g/l, Bence Jones protein <4 g/24 hours).
- Stage II- When the disease cannot be classified under Stage I or Stage II.
- Stage III- This stage is characterized by any of the following: Serum calcium >3 mmol/l, Hb <8.5 g/dl and detection of high concentration of M-protein (IgG >70 g/dl, IgA >50 g/l or Bence Jones protein >12 g/24 hours).
The three stages in Durie-Salmon staging system is sub-divided into A and B in which A represents normal renal function (serum creatinine <177 umol/l) and B represents abnormal renal function (serum creatinine >177 umol/l).
Other prognostic factors that help in determining the survival of the patient include evaluating cytogenetic abnormalities by FISH test. Additionally, other factors such as advanced age, high LDH and CRP, poor performance status, low platelets, M protein (e.g. IgD having more renal failure and amyloidosis), BM plasma cells >50%, circulating plasma cells, serum FLC ratio (<0.03 or >32) and high BM plasma cell labeling index (PCLI >3%). The above factors are significant for poorer prognosis and decreased survival rate.
Multiple myeloma is mostly a disease of the elderly, with a median age of occurrence between 65-70 years. Multiple myeloma is almost always preceded by premalignant monoclonal gammopathy of undetermined significance (MGUS) stage. MGUS is seen in approximately 3% of adults over 50 years of age, which progresses to multiple myeloma in 1% cases every year. Multiple myeloma can also have an asymptomatic stage known as smoldering multiple myeloma, which has a risk of transformation of about 10% per year for the first 5 years.
The most common presenting symptoms of multiple myeloma are bone pain (in about 60% cases), fatigue (in 30% cases), weight loss (in 25% cases), paresthesias (in 5% cases), weakness, infections (pneumococcus, hemophilus, escherichia), fever, lymphadenopathy, hepatomegaly, splenomegaly, hyperviscosity and spinal compression. Cardiac involvement and skin lesions may be seen in amyloid deposition.
Diagnosis Of Multiple Myeloma
The diagnosis of multiple myeloma is based on the signs of CRAB (hypercalcemia, renal insufficiency, anemia, bony lesions) in patients who are positive for M proteins/light chains and clonal plasma cells with exclusion of other related disorders, such as MGUS, smoldering myeloma, solitary plasmacytomas, primary amyloidosis, Waldenstrom’s macroglobulinemia, POEMS (polyneuropathy, organomegaly, endocrinopathies with exclusion of DM and hypothyroidism, monoclonal protein and skin changes), and plasma cell leukemia.
To be diagnosed with multiple myeloma, serum calcium levels should be >2.875 mmol/l, serum creatinine levels >177 umol/l, Hb levels <10 g/dl or 2 g/dl below normal and lytic bone lesions with severe osteopenia should be present.
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