Journal List > Lab Med Online > v.5(3) > 1057270

Kim, Choi, Lee, Shin, Cheong, and Kim: Evaluation of the Effectiveness of the Heavy-Light Chain Quantitative Test

Abstract

Background

The heavy-light chain (HLC) quantitative test can identify and quantify the heavy and light chains of each immunoglobulin class. The purpose of this study was to evaluate the effectiveness of the HLC quantitative test.

Methods

To evaluate the effectiveness of the HLC quantitative test, a systemic review of the literature, using Ovid-MEDLINE, EMBASE, Cochrane library, and eight domestic databases including KoreaMed, was performed until October 10, 2013. We included five cohort studies and one diagnostic evaluation study in the final evaluation. Two reviewers independently assessed the quality of the included studies and extracted data from the studies. The quality of the studies was assessed according to the Scottish Intercollegiate Guidelines Network (SIGN) tool.

Results

A correlation between the HLC quantitative test and previous assays was evaluated in one study, which enrolled patients with increased monoclonal IgA. The correlation coefficient was reported as 0.94 in this study. The clinical significance of the quantitative HLC test to predict a prognosis was also reported in five cohort studies. The survival rate in patients with higher HLC ratio was significantly lower and the increased IgA κ/λ ratio or IgM κ/λ ratio was significantly correlated with higher survival rate in patients with monoclonal gammaglobulinemia.

Conclusions

The HLC quantitative test is an effective test that can quantitatively measure the identified immunoglobulin type and predict the prognosis of patients with monoclonal gammopathy.

Figures and Tables

Fig. 1

Publications selected for the evaluation of the heavy-light chain quantitative test, according to the literature search strategy.

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Table 1

Ovid-MEDLINE, Ovid-EMBASE search strategy

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No. Search terms Ovid-MEDLINE Searched no. Ovid-EMBASE Searched no.
Patient 1 Monoclonal gammopathy.mp 3,633 4,602
2 Monoclonal immunoglobulin*.mp 1,772 6,615
3 Myeloma.mp 46,229 62,477
Patient total 4 OR/1-3 49,162 66,973
Index test 5 Heavy chain.mp AND quantification.mp 218 314
6 Light chain.mp AND quantification.mp 143 247
7 Hevylite.mp 3 41
8 HLC.mp 357 491
Index test total 9 OR/5-8 689 1,000
Total 10 4 AND 9 54 138
Table 2

Levels of evidence

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1++ High quality meta-analyses, systematic reviews of RCTs, or RCTs with a very low risk of bias
1+ Well-conducted meta-analyses, systematic reviews, or RCTs with a low risk of bias
1- Meta-analyses, systematic reviews, or RCTs with a high risk of bias
2++ High quality systematic reviews of case control or cohort studies
High quality case control or cohort studies with a very low risk of confounding or bias and a high probability that the relationship is causal
2+ Well-conducted case control or cohort studies with a low risk of confounding or bias and a moderate probability that the relationship is causal
2- Case control or cohort studies with a high risk of confounding or bias and a significant risk that the relationship is not causal
3 Non-analytic studies, e.g., case report, case series
4 Expert opinion
Table 3

Grades of recommendations

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A At least one meta-analysis, systematic review, or RCT rated as 1++ directly applicable to the target population or a body of evidence consisting principally of studies rated as 1+, directly applicable to the target population, demonstrating an overall consistency in the results
B A body of evidence, including studies rated as 2++, directly applicable to the target population and demonstrating an overall consistency in the results or extrapolated evidence from studies rated as 1++ or 1+
C A body of evidence, including studies rated as 2+, directly applicable to the target population and demonstrating an overall consistency in the results or extrapolated evidence from studies rated as 2++
D Evidence level 3 or 4 or extrapolated evidence from studies rated as 2+
Table 4

Literature selected for the evaluation of the heavy-light chain quantitative test

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Research type Author (Publication yr) Subjects Index test Comparator Level of evidence
Diagnostic evaluation study Wolff (2013) 68 patients with monoclonal IgA Heavy-light chain quantitative test (IgAκ·λ) SPE, IFE, FLC ratio 2+
Cohort study Bradwell (2013) 339 patients with multiple myeloma Heavy-light chain quantitative test (IgGκ·λ, IgAκ·λ) - 2+
Cohort study Ludwig (2013) 156 patients with multiple myeloma Heavy-light chain quantitative test (IgGκ·λ, IgAκ·λ) - 2+
Cohort study Katzmann (2013) 999 patients with monoclonal gammopathy of undetermined significance Heavy-light chain quantitative test (IgGκ·λ, IgAκ·λ, IgMκ·λ) - 2+
Cohort study Koulieris (2012) 103 patients with multiple myeloma Heavy-light chain quantitative test (IgGκ·λ, IgAκ·λ) - 2+
Cohort study Tovar (2012) 37 patients with multiple myeloma who underwent autologous hematopoietic stem cell transplantation Heavy-light chain quantitative test (IgGκ·λ, IgAκ·λ, IgMκ·λ) - 2+

Abbreviations: SPE, serum protein electrophoresis; IFE, immunofixation electrophoresis; FLC, free light chain.

Notes

This article is available from http://www.labmedonline.org

References

1. Hwang Y, Chung WS, Hong KS. Evaluation of the screening tests for the diagnosis of plasma cell neoplasm. Lab Med Online. 2012; 2:80–86.
crossref
2. Jung S, Kim M, Lim J, Kim Y, Han K, Min CK, et al. Serum free light chains for diagnosis and follow-up of multiple myeloma. Korean J Lab Med. 2008; 28:169–173.
crossref
3. Bradwell AR, Carr-Smith HD, Mead GP, Tang LX, Showell PJ, Drayson MT, et al. Highly sensitive, automated immunoassay for immunoglobulin free light chains in serum and urine. Clin Chem. 2001; 47:673–680.
crossref
4. Durie BG, Harousseau JL, Miguel JS, Bladé J, Barlogie B, Anderson K, et al. International uniform response criteria for multiple myeloma. Leukemia. 2006; 20:1467–1473.
crossref
5. Bradwell AR, Harding SJ, Fourrier NJ, Wallis GL, Drayson MT, Carr-Smith HD, et al. Assessment of monoclonal gammopathies by nephelometric measurement of individual immunoglobulin kappa/lambda ratios. Clin Chem. 2009; 55:1646–1655.
crossref
6. Scottish Intercollegiate Guidelines Network. SIGN 50: a guideline developer's handbook. Updated on March 2004. http://www.sign.ac.uk/pdf/sign50annexc.pdf.
7. Wolff F, Debaugnies F, Rozen L, Willems D, Brohet F, Brauner J, et al. Assessment of the diagnostic performances of IgA heavy and light chain pairs in patients with IgA monoclonal gammopathy. Clin Biochem. 2013; 46:79–84.
crossref
8. Bradwell A, Harding S, Fourrier N, Mathiot C, Attal M, Moreau P, et al. Prognostic utility of intact immunoglobulin Ig'κ/Ig'λ ratios in multiple myeloma patients. Leukemia. 2013; 27:202–207.
crossref
9. Ludwig H, Milosavljevic D, Zojer N, Faint JM, Bradwell A, Hübl W, et al. Immunoglobulin heavy/light chain ratios improve paraprotein detection and monitoring, identify residual disease and correlate with survival in multiple myeloma patients. Leukemia. 2013; 27:213–219.
crossref
10. Katzmann JA, Clark R, Kyle RA, Larson DR, Therneau TM, Melton LJ 3rd, et al. Suppression of uninvolved immunoglobulins defined by heavy/light chain pair suppression is a risk factor for progression of MGUS. Leukemia. 2013; 27:208–212.
crossref
11. Koulieris E, Panayiotidis P, Harding SJ, Kafasi N, Maltezas D, Bartzis V, et al. Ratio of involved/uninvolved immunoglobulin quantification by Hevylite™assay: clinical and prognostic impact in multiple myeloma. Exp Hematol Oncol. 2012; 1:9.
crossref
12. Tovar N, Fernández de, Elena M, Cibeira MT, Aróstegui JI, Rosiñol L, et al. Prognostic impact of serum immunoglobulin heavy/light chain ratio in patients with multiple myeloma in complete remission after autologous stem cell transplantation. Biol Blood Marrow Transplant. 2012; 18:1076–1079.
crossref
13. McPherson RA, Massey HD. Henry's clinical diagnosis and management by laboratory methods. In : McPherson RA, Pincus MR, editors. Laboratory evaluation of immunoglobulin function and humoral immunity. 21th ed. Philadelphia: WB Saunders;2007. p. 835–848.
14. Haemato-oncology Task Force of the British Committee for Standards in Haematology. Guidelines for the diagnosis and management of multiple myeloma 2013. Updated on 2010. http://www.bcshguidelines.com/documents/MYELOMA_GUIDELINE_updated_29_aug_RG_jzw_(3).pdf.
15. Kraj M, Kruk B, Szczepiński A, Warzocha K. Comparison of immunoglobulin free light chain (FLC), heavy chain/light chain (HLC) assays and immunofixation (IFE) in assessment of remission in multiple myeloma. Acta Haematol Pol. 2012; 43:122–131.
crossref
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