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Although monoclonal proteins are a feature of plasma cell dyscrasias, they can also be detected in other B-cell malignancies such as chronic lymphocytic leukaemia (CLL) and non-Hodgkin lymphoma (NHL) [656][657]. Consistent with this, many studies have demonstrated that inclusion of sFLC analysis in a screening panel alongside serum protein electrophoresis (SPE) identifies additional patients with CLL or lymphoma (Chapter 23).

The incidence of sFLC abnormalities varies widely according to the lymphoid subtype (Table 30.1). For example, an abnormal κ/λ sFLC ratio is found in approximately 5% of patients with Hodgkin lymphoma (HL; Section 31.2) but around 50% of patients with mantle cell lymphoma (MCL; Section 31.4). sFLCs may be produced directly by the tumour (e.g. diffuse large B-cell lymphoma [DLBCL]; Section 31.3) or by B-cells in the surrounding microenvironment (e.g. HL; Section 31.2).

There is a growing body of literature on the use of sFLCs as a prognostic marker in lymphoid malignancies (Table 30.1). For example, in DLBCL the absolute κ and λ sFLC levels were more predictive of outcome than the sFLC ratio (Section 31.3.2), whereas in MCL the sFLC κ/λ ratio but not absolute levels were associated with overall survival (Section 31.4). In CLL, both a monoclonal and a polyclonal sFLC elevation are associated with inferior outcome (Section 33.3). It should be noted that polyclonal FLC elevation may be due to renal impairment or polyclonal stimulation (Chapter 7).

Disease Incidence of sFLC abnormalities Prognosis Monitoring
Abnormal κ/λ
sFLC ratio
Elevated
concentration
Abnormal κ/λ
sFLC ratio
Elevated
concentration
HL[658][659][660][661]5 - 7% ~30%
(κ and/or λ)
NHLDLBCL [662][663][664]9 - 14% 19 - 32%
(κ and/or λ)
FL[657]4 - 8% unknown unknown unknown unknown
MZL: MALT[657]16% unknown unknown unknown unknown
MCL[657][665][666][667]36 - 77% 40%
(κ and/or λ)
BL[657]12% unknown unknown unknown unknown
WM [668][669][670]77% 83%
(iFLC)
unknown
CLL [671][672][673][675][676][678]30 - 40% 32%
(κ and/or λ)

Table 30.1. Summary of the incidence of FLC abnormalities, and the role of sFLC measurements in HL, NHL and CLL. ✓: parameter shown to be of value; ✗: parameter shown not to be of value; iFLC: involved FLC; HL: Hodgkin lymphoma; NHL: non-Hodgkin lymphoma; DLBCL: diffuse large B-cell lymphoma; FL: follicular lymphoma; MZL: marginal zone lymphoma; MALT: lymphoma of mucosa-associated lymphoid tissue; MCL: mantle cell lymphoma; BL: Burkitt lymphoma; WM: Waldenström’s macroglobulinaemia; CLL: chronic lymphocytic leukaemia.

sFLCs may be a useful marker for monitoring lymphoma. Their short serum half-life and the large clinical range provide a sensitive marker for assessment of response to treatment. The sFLC component indicating response may vary between the different lymphoma subtypes. For example, in Waldenström’s macroglobulinaemia (WM), the involved FLC (iFLC) concentration was found to be a useful marker to monitor disease and may show response to treatment and progression earlier than IgM measurements (Section 32.3.2). In MCL, both the κ/λ sFLC ratio and summated κ + λ FLC concentrations (ΣFLC) may be informative for monitoring (Section 31.4). In cryoglobulinaemia, sFLCs could possibly serve as a useful tool for monitoring response, since direct measurement of cryoglobulins is technically difficult (Section 34.2).

sFLC concentrations may also have prognostic value in predicting the risk of developing NHL in immunosuppressive states (e.g. HIV infection or recipients of solid organ transplants) and in conditions associated with chronic B-cell activation (e.g. primary Sjögren’s syndrome and hepatits C virus infection). These are discussed in Chapter 35.

References