This is the third of four installments in a series covering investigative tools used for diagnosing multiple myeloma.

The diagnostic work-up for detecting multiple myeloma traditionally includes: (1) confirmation of excessive growth in certain plasma cells ^[1]; (2) evaluation of organ damag ^[2]e; and (3) determination of prognostic variables, which will be discussed here. The fourth article will cover specialized studies for selected patients ^[3].

After the initial diagnostic work-up has been completed, more detailed cellular and molecular studies are required. These prognostic studies evaluate variables that can determine disease behavior, define therapeutic strategies, compare results of clinical trials, and predict overall long-term outcome for myeloma patients.

A number of predictive factors have been identified in different patient populations and following a range of therapies. These factors are related to tumor burden (the number of cancer cells or size of the tumor), tumor biology, and host and microenvironmental influences, such as the density of microvessels in bone marrow.

Both patient-related and treatment-related factors may also influence outcome. Patient-related factors include patient age, serum albumin, and performance status, which measures how well a patient can perform ordinary tasks. Treatment-related factors include tandem transplant, use of novel agents, and achieving complete remission.

A new International Staging System has been proposed to predict patient outcome. The previous staging system was intended for use after standard-dose chemotherapy, but with the introduction of high-dose therapy and novel agents, the previous system is less predictive. The new system takes into account these novel treatments in both younger and older patients.

The new system is encouraging because it only uses two simple laboratory measurements: serum ß2-microglobin and serum albumin. However, it overlooks factors related to tumor biology, which may ultimately limit its usefulness. These include molecular markers and cytogenetics, which is the study of chromosomal abnormalities.

Multiple myeloma is associated with significant chromosomal abnormalities that evolve with progression of the illness. Though nearly all patients have genomic rearrangement, at diagnosis it is detectable in only one-third of patients. Detection improves to one-half on repeated analysis.

Specific chromosomal changes that are found in many patients have been identified and correlated with overall outcome. Conventional cytogenetic analysis uses molecular probes to target particular gene changes in the chromosomes of dividing cells, which is difficult. As a result, conventional analysis has been losing ground to a technique called fluorescent in situ hybridization (FISH). FISH is able to detect specific genetic changes in interphase (non-dividing) cells.

It is important to note that overall outcome for myeloma patients may vary based on other genetic and microenvironmental factors.

For more information about diagnostic criteria for multiple myeloma, see the full article in the American Society of Hematology’s 2008 Education Program Book, Hematology ^[4].