BETA - What are beta 2 macroglobulin, LDH and albumin? Why are the tested at diagnosis? How often should they be tested?

Should microglobulin and LDH tests be repeated or is once enough? Another common question we get is what's going on with mybeta2 microglobulin and the LDH. Let's start with the LDH. The LDH is a non-specific marker. It can be elevated for other reasons, but it turns out it also tells you indirectly about aggressive behaviour by myeloma. So we normally will do it at baseline and actually I repeat it with some frequency depending on where patients are if we want to have that extra measurement of where the myeloma activity might be. In reality for the beta2 microglobulin you only have to do it once at diagnosis. I sometimes see people do it as part of monitoring to see the response and it's really not that good of a marker so I would say it's not necessary as a monitoring marker. It's being incorporated into the original staging system, what's called the International Staging System, the ISS, and then also the revised International Staging System which by the way includes now genetic factors as well as the LDH. So these are numbers. Beta2 microglobulin is a membrane protein that's expressed on plasma cells. LDH is an enzyme that's present in any tissue in the body and it has a function to convert something called lactic acid to pyruvic acid. When there is tissue destruction the LDH can go up and albumin is another protein that's created by the liver. Those three numbers are the basis for the International Staging System suggested by the International Myeloma Working Group and looking at those three numbers can put patients into stage one, stage two and stage three. We know that high levels of beta2 microglobulin or low albumin and high LDH represent high risk myeloma and the reverse, low numbers represent stage one. LDH is increased in multiple myeloma fairly infrequently and when you see high LDH in myeloma it usually indicates an aggressive myeloma and this is one indication in our center if you see a patient with high LDH to do a PET CT scan because those patients sometimes do present with what's called extremodolary plasma cytoma or extremodolary disease and those patients can also have plasma cell leukemia. So high LDH pushes us to do PET scan and flow cytometry in the peripheral blood. Beta2 microglobulin is a protein that's secreted by the plasma cells but it's very non-specific meaning patients that have kidney problems will have very high levels of beta2 microglobulin. So it's a reflection on both the myeloma tumor load as well as the kidney function. Albumin is a little bit confusing because albumin is another protein but it's the most common protein in the body. Albumin is manufactured by the liver and in myeloma you can have low albumin which is a bad marker or poor prognostic marker and that can be related to inhibition of the manufacturing of the albumin in the liver. There is a cytokine or a substance secreted by the myeloma cells called interleukin 6 and we know that interleukin 6 can inhibit albumin production in the liver and we also know that albumin can be secreted in the kidney. So whether it's a production issue or ability to maintain the albumin in the serum can be an issue for patients and albumin has always been used in monitoring patients. LDH is also used in monitoring patients so if the LDH is high and it comes down as treatment that's a good marker. Beta2 microglobulin is less reliable in monitoring response to treatment as I said it's a marker of the kidney function and the tumor load but we usually don't use it alone as a marker for tumor load.