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Chapter 1

HLC assays had only recently been developed when the 6th edition of this book was published. Few HLC studies had been completed and discussion was confined to a separate chapter at the back of the book. In the current edition, HLC data and FLC data are integrated within the same chapters. For example, if your interest is in risk stratification of MGUS, Chapter 13 contains data from both FLC and HLC prognostic studies.

With regard to the potential utility of HLC analysis in the management of MM, there have been several important publications. Bradwell et al. [36] reported that abnormal HLC ratios at presentation were predictive of shorter progression-free survival, predominantly due to the influence (on the ratios) of HLC pair suppression (Section 20.4). A staging system using β2-microglobulin and extreme HLC ratios was prognostically more accurate than the current International Staging System. Ludwig et al. [37] similarly found that highly abnormal HLC ratios at presentation were associated with shorter survival and that β2-microglobulin and HLC ratios were independent prognostic markers. When monitoring disease, Ludwig et al. noted that HLC assays could give a quantitative assessment of monoclonal protein when other tests were uninformative and, in some patients, they gave a more sensitive measure of residual disease and an earlier indication of relapse (Section 18.4). Katzmann et al. [38] focused on the problems of monitoring MM patients with β-migrating IgA monoclonal proteins. They concluded that HLC assays were a suitable substitute for the alternative of electrophoresis assays and total IgA quantitation (Section 11.5), a utility similarly highlighted in a clinical case study by Donato et al. (Section 18.4.1) [39].

For an investigation of MGUS prognosis, Katzmann and colleagues [40] were able to measure HLC concentrations in archived sera from 999 MGUS patients. HLC pair suppression was found to be an independent risk factor for progression and the authors observed that as suppression was apparent several years before malignant transformation, this had implications for the understanding of myeloma biology (Chapter 13).