Multiple Myeloma Diagnostic Criteria Calculator

How does the multiple myeloma diagnostic criteria calculator work?

This health tool helps the diagnosis of multiple myeloma based on patient parameters extracted from blood and biopsy tests.

The major diagnostic criteria presented in the multiple myeloma calculator is discussed below:

■ Plasmacytoma on tissue biopsy – the presence of a malignant plasma cell tumor growing within the tissue.

■ Bone marrow plasmacytosis of > 30% – the increased number of plasma cells in the bone marrow.

■ M Protein: IgG > 3.5 g/L; IgA > 2.0 g/L – the presence of antibodies. The heaviest produced antibodies in myeloma are IgG and IgA followed by IgD.

■ Urinary kappa or lambda chain excretion of > 1g / 24 hours in absence of amyloidosis – the presence of light chains (polypeptides synthesized by plasma cells which form part of immunoglobulins) in urine without any other excretion of abnormal proteins.

The minor diagnostic criteria which completes the diagnosis method is:

■ Marrow plasmacytosis of 10-30% – presence of plasma cells in bone marrow of little less than 30% (which is the value for major criteria).

■ Lytic bone lesions – myeloma is one of the types of malignancy which cause lytic lesions which are depleted areas found in otherwise dense bone. These are present in the bone metastasis of lung and breast cancer.

■ Evidence of a monoclonal protein but lessor amounts than above – presence of M protein which is produced by plasma cells.

■ Hypoglobulinemia of normal proteins: IgM < 500 mg/L, IgA < 1 g/L or IgG < 6g/L – the presence of abnormally low globulin content in the blood.

The original study looked at the clinical features of 71 patients with multiple myeloma. These have been correlated with the myeloma cell mass (which was determined from the measurements of monoclonal immunoglobulin synthesis and metabolism).

The positive diagnosis criteria are the following:

■ 1 Major Criteria and 1 Minor Criteria;

■ 0 Major Criteria and 3 Minor Criteria.

After performing bivariate correlation and multivariate regression analyses, the following have been designated as accurate predictors of the myeloma cell mass:

■ The extent of bone lesions;

■ Hemoglobin level;

■ Serum calcium level;

■ M-component levels in serum and urine.

The study also contributed with a clinical staging system for the initial assessment of diagnosed patients. This is intended to be used in clinical trials of therapy for MM.

Multiple myeloma symptoms and stages

MM is a condition characterized by the accumulation of plasma cells in the bone marrow. These produce a monoclonal protein which in turn causes organ and tissue impairment. The main cause is the incorrect genetic sequence during the terminal differentiation of B lymphocytes into plasma cells.

Symptoms of bone marrow cancer include the following:

■ Hypercalcemia;

■ Spinal cord/ Nerve compression;

■ Renal impairment;

■ Dehydration;

■ Anemia (normochromic, normocytic);

■ Bleeding/ Bruising;

■ Bone pain (e.g. backache);

■ Pathological fractures;

■ Recurrent bacterial infections.

Multiple myeloma diagnosis initially involves a series of blood and urine tests. These focus on discovering the amount of different proteins in serum and urine as well as the immunoglobulin levels (to show immune suppression). Creatinine levels also offer information on renal function.

Subsequently, bone marrow aspirate and trephine biopsy with the phenotyping of plasma cells, take place.

To ease diagnosis, several criteria based methods have been studied. Beside the one in the multiple myeloma diagnostic calculator above, there is the International Myeloma Working Group diagnostic criteria:

■ Monoclonal plasma cells in marrow ≥ 10%.

■ Monoclonal protein in serum or urine (unless non-secretory; if so, need ≥ 30% monoclonal plasma cells in bone marrow).

■ Evidence of myeloma-related organ or tissue impairment:

- Hypercalcaemia (> 10.5 mg/dL (2.6 mmol/L) or upper limit of normal).

- Renal insufficiency (serum creatinine > 2 mg/dL (176.8 μmol/L).

- Anaemia: haemoglobin < 100 g/L or 20 g below normal range.

- Lytic bone lesions, osteoporosis, or pathological fractures.

There is also a new International Staging System (ISS) which provides reliable staging which can be used in diagnosis, clinical trials and multiple myeloma life expectancy prognosis. This takes account of serum beta2-microglobulin (Sbeta2M), serum albumin, platelet count, serum creatinine, and patient age.

The table below shows the stages, their characteristics and median survival:

References

1) Durie BG, Salmon SE. (1975) A clinical staging system for multiple myeloma. Correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival. Cancer; 36(3):842-54.

2) Greipp PR, San Miguel J, Durie BG, Crowley JJ, Barlogie B, Bladé J, Boccadoro M, Child JA, Avet-Loiseau H, Kyle RA, Lahuerta JJ, Ludwig H, Morgan G, Powles R, Shimizu K, Shustik C, Sonneveld P, Tosi P, Turesson I, Westin J. (2005) International staging system for multiple myeloma. J Clin Oncol; 23(15):3412-20.

3) Roodman GD. (2010) Myeloma Bone Disease. Humana Press.

4) Rajkumar SV, Kumar S. (2016) Multiple Myeloma: Diagnosis and Treatment. Mayo Clin Proc; 91(1):101-19.

5) Choi JH, Yoon JH, Yang SK. (2007) Clinical Value of New Staging Systems for Multiple Myeloma. Cancer Res Treat; 39(4): 171–174.