Haematologica 2003 - Supplements

P7.4
ROLE OF SERUM FREE LIGHT CHAIN
MEASUREMENTS IN DISEASE DIAGNOSIS AND
MONITORING
AR Bradwell, GP Mead, MT Drayson, at the time of
presentation, RA Kyle, JA Katzmann,
Measurement of urine free light chain concentrations is important
for assessing monoclonal plasma cell diseases. However, the
kidneys can metabolise 10-30gm of free light chains per day, so
that urine concentrations may not accurately reflect tumour
synthesis. Therefore, from a theoretical viewpoint, serum
measurements would be preferable, just as blood glucose
measurements are better than urine measurements for managing
patients with diabetes mellitus. Unfortunately, serum
measurements have been hampered by the lack of high affinity
antisera that are specific for free light chains. Recent
publications indicate that satisfactory serum immunoassays have
now been developed and are useful in a variety of clinical
situations. 1,2
In a study of patients with light chain multiple myeloma,
immunoassays for serum free light chains were compared with
traditional urine tests. 3 Of 224 patients tested at entry to clinical
trials, all were correctly identified from serum samples. During
monitoring of 82 patients, changes in serum and urine free light
chains correlated, but urine free light chains became negative in
26 patients compared with normalisation of serum free light
chains in only 9 of the patients. Thus, serum assays could replace
Bence Jones protein urine tests for patients with light chain
multiple myeloma.
In patients with nonsecretory multiple, increased concentrations
of either kappa or lambda free light chains (and abnormal
kappa/lambda ratios) were detected in the sera of 19 out of 28
patients. 4 A further four patients had suppression of one or both
light chains while the remaining five sera had normal or raised
free light chain concentrations with substantially normal
kappa/lambda ratios. Six of the patients with an elevated single
free light chain, who were studied during follow-up, had changes
in disease activity that mirrored changes in free light chain
concentrations.
Serum free light chain concentrations have also been assessed in
497 patients with intact immunoglobulin multiple myeloma at the
time of clinical presentation. These comprised 314 patients with
IgG, 142 with IgA, 36 with IgD and 5 patients with IgE multiple
myeloma. The results showed that overall 88% had elevated free
light chains with the following breakdown: IgG 84%, IgA 92%,
IgD 94% and IgE 100%. Some patients had normal or reduced
concentrations of free light chains but abnormal κ/λ ratios
indicating monoclonality in association with bone marrow
suppression. In total, 95% of patients had abnormal free light
chain concentrations or abnormal κ/λ ratios. This percentage is
higher than previously reported, reflecting the increased
sensitivity of the free light chain immunoassays. A comparison
was also made between the effect of treatment on the serum
concentrations of intact monoclonal immunoglobulins and free
light chains. Because the serum half-life of free light chains is
only 2-6 hours, compared with 21-25 days for IgG, short-term
responses to therapy could be identified. This might be useful for
identifying the most suitable treatment regimens in patients who
are refractory to conventional chemotherapy.
Other studies have shown that serum free light chains are
elevated in nearly all patients with AL amyloidosis, 2,5 light chain
deposition disease 2 and Waldenstrom’s macroglobulinaemia.
In conclusion, serum free light chain measurements may obviate
the need for urine tests in most patients with monoclonal plasma
cell diseases. The serum assays may also find use in the early
assessment of responses to treatment because of their short halflife
compared with intact monoclonal immunoglobulins.
Bradwell AR, Carr-Smith HD, Mead GP, Tang LX, Showell PJ,
Drayson MT, Drew R. Highly sensitive automated immunoassay
for immunoglobulin free light chains in serum and urine. Clin
Chem 2001; 47: 637-80.
Katzmann JA, Clark RJ, Abraham RS, Bryant S, Lymp JF,
Bradwell AR, Kyle RA. Serum reference intervals and
diagnostic ranges for free κ and free λ immunoglobulin light
chains: Relative sensitivity for detection of monoclonal light
chains. Clin Chem 2002; 48: 1437-44.
Bradwell AR, Carr-Smith HD, Mead GP, Harvey TC, Drayson
MT. Serum test for assessment of patients with Bence Jones
myeloma. Lancet 2003; 361: 489-491.
Drayson MD, Tang LX, Drew R, Mead GP, Carr-Smith HD,
Bradwell AR. Serum free light-chain measurements for
identifying and monitoring patients with nonsecretory multiple
myeloma. Blood 2001; 97: 2900-02.
Abraham RS, Katzmann JA, Clark RJ, Bradwell AR, Kyle RA,
Gertz MA. Quantitative analysis of serum free light chains. A
new marker for the diagnostic evaluation of primary amyloidosis.
Am J Clin Pathol 2003; 119: 274-278.
Figure. Serum free light chain concentrations in normal
individuals and patients with diseases associated with raised
monoclonal and polyclonal light chain concentrations. Typical
sensitivity limits for serum protein electrophoresis (SPE) and
immunofixation electrophoresis (IFE) are shown. (LCMM =
light chain multiple myeloma: NSMM = nonsecretory multiple
myeloma: IIMM = intact immunoglobulin multiple myeloma:
High pIgG = polyclonal hypergammaglobulinaemia).
P7.5
INVESTIGATION OF RESIDUAL DISEASE BY
QUANTITATIVE PCR IN MULTIPLE MYELOMA
Paolo Corradini 1 , Matteo Carrabba 1 , Marco Ladetto 2 ,
Vittorio Montefusco 1 , Gösta Gahrton 3
1
Hematology – Bone Marrow Transplantation Unit, Istituto
Nazionale dei Tumori, Dipartimento Scienze Mediche - University
of Milano, Italy; 2 Dept. Hematology, University of Torino; 3 on
behalf of the Myeloma Subcommittee of the European Group for
Blood and Marrow Transplantation (EBMT)
In a previous study, we have shown that molecular remission can
be attained after allogeneic transplantation of hematopoietic stem
cells (allo-HSCT). Our study was based on a nested PCR
S46