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The International Myeloma Foundation is proud to have sponsored and coordinated the development of the International Staging System (ISS) for Multiple Myeloma in 2005. The ISS was developed through a collaborative research initiative conducted by 17 myeloma institutions around the world.  Based on that research, the factors found to best stratify patients’ prognosis into a three-stage classification were two blood proteins: serum beta 2 microglubulin and serum albumin.

In August, 2015 the International Myeloma Working Group (IMWG) published its Revised International Staging System (R-ISS), which combines the ISS with chromosomal abnormalities detected by interphase fluorescent in situ hybridization (FISH) and serum lactate dehydrogenase (LDH). Clinical data from 4,445 patients with newly diagnosed myeloma in 11 international clinical trials were pooled and analyzed to create this updated simple yet powerful prognostic staging system.   



Serum ß2 microglobulin < 3.5 mg/l
Serum albumin ? 3.5 g/dl
Standard-risk chromosomal abnormalities (CA)
Normal LDH

Not R-ISS stage I or III

Serum ß2 microglobulin ? 5.5 mg/L and either
High-risk CA by FISH
High LDH

Related Links:

Understanding Your Test Results

Revised International Staging System for Multiple Myeloma

©2015 International Myeloma Foundation



Genetic Testing is performed on a patient's bone marrow biopsy specimen at the time of diagnosis to help predict the behavior of the myeloma and its response to various treatment strategies.   A patient's biopsy specimen may be sent to a large academic center for genetic testing if the local oncologist is not associated with a laboratory that is equipped to perform the tests.

  • Conventional Metaphase Cytogenetics  (karyotyping) is a test in which the bone marrow biopsy specimen is placed into a special dish and allowed to grow in the laboratory.  Cells are later taken from the growing sample and stained. The laboratory specialist uses a microscope to examine the size, shape, and number of chromosomes in the cell sample.  The stained sample is photographed to provide a karyotype, which shows the arrangement of the chromosomes.  Certain abnormalities can be identified through the number or arrangement of the chromosomes.   This test is particularly valuable for identifying higher-than-average-risk myeloma in patients with fewer than two copies of each chromosome (hypodiploidy) and in those with deletion of chromosome 13 during cell division.
  • Fluorescence In Situ Hybridization (FISH) provides researchers with a way to visualize and map the genetic material in an individual's cells, including specific genes or portions of genes. This is important for understanding a variety of chromosomal abnormalities and other genetic mutations. Unlike most other techniques used to study chromosomes, FISH does not have to be performed on cells that are actively dividing.  It is useful for defining high-risk myeloma in patients with certain chromosomal translocations (which occur when chromosomes inappropriately exchange sequences of genetic material during cell division) and/or in those who have a deletion of the short arm of chromosome 17.
Role of FISH in Myeloma Risk Stratification
XIIth International Myeloma Workshop in Washington, DC
Rafael Fonseca, M.D.
Mayo Clinic
Scottsdale, Arizona
Genetic Changes in Myeloma: Prognostic Implications
XIIth International Myeloma Workshop in Washington, DC
Herve Avet-Loiseau, M.D.
Institute de Biologie
Nantes, France

International Myeloma Working Group (IMWG) Molecular Classification of Multiple Myeloma: Spotlight Review
Published in Leukemia (2009), 1–12