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April 2001 Volume 4, Issue 4:
Chromosome 13 and New Ways To Stage Myeloma
By Brian G.M. Durie, MD*
04.01.01
When the diagnosis of myeloma is first established, the central question is: What is the prognosis in my case? What can I expect?

Traditional Staging
Over the years, different tests have been introduced to determine the stage and prognosis of the myeloma. Early disease is Stage I or II, limited to one part of the body and/or with minimal spread elsewhere. More advanced or progressive disease is Stage III, frequently with several areas of bone involvement and/or anemia plus higher levels of myeloma protein in the blood and/or urine. Kidney function is also an important factor. Patients with Stage IIIA with normal kidney function (serum creatinine <2mg%) do better than patients with Stage IIIB disease with a serum creatinine >2mg%.

New Factors
Increasingly, new factors have been evaluated and introduced. Serum ß2 microglobulin (Sß2M) is the most generally useful additional blood test. It is particularly helpful for patients with IgG myeloma in whom higher levels correlate with more advanced disease and poorer outcome with treatment. With the advent of high dose chemotherapy (e.g. high dose melphalan) with peripheral stem cell transplant, numerous studies confirmed the benefit of Sß2M measurement as a prognostic factor in this setting. Un-fortunately, different research groups have used different “cut-off” values to assess prognosis (e.g. 2.5, 4.5 or 6.5) depending upon the disease setting and test methodology. Some laboratories have switched to normal ranges of <0.25, which make it particularly confusing! However, the concept of “lower is better” remains the same.

Chromosome 13
Chromosome 13 incorporates a gene called the retroblastoma gene (Rb), which produces Rb protein capable of inhibiting myeloma cell growth. It is an “anti-oncogene” – if it is missing or mutated (abnormal) myeloma grows more and can be more resistant to treatment. Absence of or a defective Chromosome 13 has been correlated with poorer prognosis. In a recent analysis of transplanted patients by a French group (IFM), Chromosome 13ABN assessed, using a fluorescent (FISH) technique testing fresh bone marrow cells, proved to be a critical determinant of poorer outcome. Chromosome 13 testing by FISH is therefore a useful new test. Does every new patient now need to have this test? Strangely, probably not! Although abnormal Chromosome 13 is highly predictive, similar prediction can be achieved using a combination of other factors including lg type, age and sex, along with traditional Stage and Sß2M. Obviously, if FISH analysis is available, that information is directly useful. In the future, it may be that therapy will be specifically targeted to Chromosome 13 abnormalities because of its biologic role in myeloma cell growth. In the meantime, other readily available factors can be used to assess outcome and help direct treatment selection.

* Blood 2001, Vol 97: 1566-1571


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