Bone marrow tests

Myeloma usually grows inside the bone marrow. Bone marrow tests (aspirate and biopsy) are performed routinely to diagnose multiple myeloma and are also used for monitoring during the course of treatment. A bone marrow biopsy provides: 

• information about the amount of disease
• its aggressiveness
• molecular/genetic abnormalities that help predict the disease course

Bone marrow biopsies are necessary because they provide the only direct access to tumor cells for examination. Such biopsies do not always present an accurate sample of what is occurring elsewhere in the marrow; myeloma is patchy and is not distributed evenly throughout the bone marrow. 

Other tissue biopsies are performed less frequently to determine if myeloma is present outside the bone marrow. A biopsy may also be performed in early-stage disease on a solitary plasmacytoma (myeoma composed of plasma cells).

Bone Marrow Aspiration and Core Biopsy

Bone marrow aspiration and bone marrow core biopsy are methods to collect both the liquid and solid parts of the bone marrow. In aspiration, a syringe draws out the liquid part of the marrow. In a core biopsy, a special hollow needle captures a sample of the spongy bone in the marrow along with its contents. 

Bone marrow aspiration and core biopsy may be uncomfortable or painful, but must be performed. These essential tests provide samples for the only direct means of examining the myeloma cells under a microscope. All other tests (of the blood and urine) rely on indirect markers of what myeloma cells are doing. 

A pathologist examines the actual cells. The pathologist writes a report on how many of the cells in the sample are abnormal plasma cells and what they look like. Words like mature, immature, and atypical may appear in your report.

Next, the samples collected through aspiration and core biopsy undergo the following assessments:

Immunophenotyping

In immunophenotyping, flow cytometry identifies protein markers on the surface of myeloma cells. Immunophenotyping is used to determine:

• stringent complete response (sCR)
• minimal residual disease (MRD), which indicates a near total eradication of myeloma cells

The IMF's Black Swan Research Initiative funded and developed Next Generation Flow (NGF) cytometry testing. NGF tests detect MRD. MRD is the presence of residual tumor cells after treatment has been completed and complete remission (CR) has been attained.

Cytogenetics, Also Known as Karyotyping

Standard cytogenetics (karyotyping) is the assessment of the chromosomes in a cell's nucleus during cell division. Cytogenetics is also called karyotyping because a karyotype is the number and appearance of chromosomes in a cell's nucleus.

This test is routinely performed on the bone marrow of newly diagnosed myeloma patients. It is sometimes repeated after treatment, especially after high-dose therapy with stem cell rescue (autologous stem cell transplant). Cytogenetics tests, along with FISH (discussed next), determine if there is loss of chromosome 13 during myeloma cell division. Cytogenetics can detect the loss of chromosome 13 with more precision than FISH tests. Loss of chromosome 13 usually indicates other genetic abnormalities are present in the myeloma cells.

Fluorescence In-Situ Hybridization (FISH)

FISH provides a way to map the genetic material, including genes and portions of genes, found in the myeloma cells. These tests improve understanding of a variety of genetic mutations that may show a patient’s risk status.

FISH demonstrates:

• the movement of genetic material from one chromosome to another (translocations) and/or
• the absence of genetic material on chromosomes (deletions)

Certain deletions and translocations are known to be signs of myeloma that is more aggressive (high-risk multiple myeloma). These high-risk mutations include the following:

• Translocation (4;14), which is movement of gene segments from chromosome 4 to 14
• Deletion 17p, which is the loss of the short arm (top part) of chromosome 17, where a major tumor suppressor gene (the p53 gene) is located
• Translocation (14;16), which is movement of gene segments from chromosomes 14 to 16
• 1q+, which is the addition of an extra-long arm (bottom part) of chromosome 1

Gene Expression Profiling (GEP)

GEP is performed on RNA extracted from myeloma cells. The genes present in the RNA are then probed on a special computer chip to provide a detailed picture of disease biology. GEP can:

• identify the dominant clone at any particular time in a patient’s disease course
• classify myeloma into different molecular subgroups
• identify the gene expression profile of patients with high-risk myeloma

GEP does not provide information about:

• non-dominant disease clones
• “driver” genetic mutations that allow the myeloma to grow and develop in new areas of the body

Various institutions have developed different GEP high-risk expression profiles that have not yet been standardized. GEP is not widely available.

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