Metaphase Cytogenetic Techniques in Multiple Myeloma

Metaphase chromosome studies in multiple myeloma (MM) are performed as part of the diagnostic workup, as surveillance to monitor the therapeutic response, and at relapse to help direct therapy. Unfortunately, the abnormal clones in many patients have a low proliferative activity and therefore, in many cases, the analyzable metaphase cells are derived from normal hematopoiesis. This limitation has been overcome in part by the use of fluorescence in situ hybridization (FISH) of interphase nuclei, which is an important adjunct to metaphase analysis. However, the metaphase karyotype remains the primary cytogenetic tool used at our institute for diagnostic and prognostic purposes. To maximize the possibility of detecting abnormal cells in conventional metaphase studies, we routinely employ at least three different cell harvest techniques on each marrow specimen. These include a direct harvest, a 24 h culture, and either a synchronized or unsynchronized 48 h culture. Recently, fine needle aspirates of solitary plasmacytomas guided by magnetic-resonance imaging have also been shown to provide diagnostic metaphase karyotypes. Regardless of the origin or quality of the specimen, some uninformative cytogenetic results may simply be due to insufficient number and type of cultures being initiated and subsequently examined.