32.5. Use of sFLC and HLC analysis in IgM MGUS and asymptomatic WM

Chapter 32

Emerging evidence suggests that FLC and HLC analysis may allow improved discrimination between WM and two related conditions: IgM MGUS and asymptomatic WM [668].

Leleu et al. [668] compared involved sFLC concentrations in WM (n=98) and IgM MGUS (n=68). An abnormal κ/λ sFLC ratio was present in 76.5% and 23.5% of WM and IgM MGUS patients, respectively (p<0.001). Involved FLC concentrations were significantly higher in WM (median = 36 mg/L; range 16 - 140 mg/L) than in IgM MGUS (median 20 mg/L; range 16 - 33 mg/L): p<0.0003. Leleu and colleagues concluded that a sFLC cut-off of 60 mg/L separated WM from IgM MGUS with >95% specificity. Similar findings were also reported by Murillo-Florez et al. [724].

In a separate report, Andrade-Campos et al. [950] compared IgM HLC results from 19 WM patients and 32 asymptomatic WM with those of 39 IgM MGUS patients. The median involved/uninvolved HLC ratio was significantly higher in WM (117.5), than asymptomatic WM (62.1) or IgM MGUS (16.1; p=0.0002) patients. Furthermore, the proportion of patients with HLC pair suppression was significantly higher in WM (83.3%) and asymptomatic WM (64.3%) than IgM MGUS (46.2%, both p=0.0002). Further work is now required to study the combined use of FLC and HLC analysis to better discriminate WM and IgM MGUS.

An initial study of the prognostic value of sFLCs in asymptomatic WM by Kastritis et al. [997] concluded that an abnormal sFLC ratio was not associated with a higher risk of progression, but that bone marrow infiltration and a low haemoglobin were major risk factors for progression to symptomatic disease.


  1. Why are sFLCs useful for monitoring WM patients with cryoglobulinaemia?
  2. Is sFLC and HLC analysis included in international WM guidelines?


  1. Because sFLCs do not cryoprecipitate (Section 32.3).
  2. Yes, guidelines state that whilst they are not essential for the routine management of WM patients, further prospective evaluation is encouraged (Sections 32.3.2,32.4.1 and 32.4.2)[703].