Role of serum free light chains in predicting HIV-associated non-Hodgkin lymphoma and Hodgkin's lymphoma and its correlation with antiretroviral therapy

National Institute for Infectious Diseases "Lazzaro Spallanzani" IRCCS, Rome, Italy.
American Journal of Hematology (Impact Factor: 3.48). 08/2012; 87(8):749-53. DOI: 10.1002/ajh.23236
Source: PubMed

ABSTRACT A nested case-control study was performed within the Italian cohort of naïve to antiretroviral human immunodeficiency virus (HIV) patients (ICONA) cohort to evaluate the role of serum free light chains (sFLC) in predicting non-Hodgkin's lymphoma (NHL) and Hodgkin lymphoma (HL) in HIV-infected individuals. Of 6513 participants, 86 patients developed lymphoma and 46 of these (NHL, 30; HL, 16) were included in this analysis having stored prediagnostic blood. A total of 46 serum case samples matched 1:1 to lymphoma-free serum control samples were assayed for κ and λ sFLC levels and compared by using conditional logistic regression. Because the polyclonal nature of free light chains (FLCs) was the focus of our study, we introduced the k + λ sum as the measurement of choice and as the primary variable studied. κ + λ sFLC values were significantly higher in patient with lymphoma than in controls, especially when considering samples stored 0-2-year period before the lymphoma diagnosis. In the multivariable analysis, the elevation of sFLC predicted the risk of lymphoma independently of CD4 count, (odd ratio of 16.85 for k + λ sFLC >2-fold upper normal limit (UNL) vs. normal value). A significant reduction in the risk of lymphoma (odd ratio of 0.07 in model with k + λ sFLC) was found in people with low sFLC and undetectable HIV viremia lasting more than 6 months. Our analysis indicates that an elevated polyclonal sFLC is a strong and sensitive predictor of the risk of developing lymphomas, and it is an easy to measure biomarker that merits consideration for introduction in routine clinical practice in people with HIV.

Download full-text


Available from: Michele Bibas, Sep 23, 2014
  • [Show abstract] [Hide abstract]
    ABSTRACT: We investigated the association between polyclonal serum-free light chains and prognostic biomarkers routinely used in the setting of HIV infection. For this purpose serum samples of 182 HIV-infected patients from the Italian Cohort of Antiretroviral Naive Patients foundation cohort were analysed. We found that polyclonal serum free light chains above the upper normal limit are strongly correlated in HIV-infected patients with advancing age, shorter time of undetectable HIV viremia, higher viral load and with lower CD4 cell count at sample.
    AIDS (London, England) 08/2012; 26(16):2107-2110. DOI:10.1097/QAD.0b013e328358d54b · 6.56 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: AIDS-related aggressive B cell lymphoma (HIV-NHL) is the second most common HIV-associated malignancy. In contrast, Hodgkin-lymphoma (HL) is one of the most common non-AIDS-defining malignancies. Current evidence-based recommendations for the treatment of HIV-associated lymphoma (HIV-lymphoma) are not available. A panel of experts in the field of HIV-related lymphoma performed literature searches of the PubMed, Medline, and Cochrane databases. The consensus process was carried out as an e-mail and meeting-based discussion group. Six cycles of R-CHOP or R-EPOCH are standard of care for patients (pts) with diffuse large B cell lymphoma (DLBCL). Pts with Burkitt lymphoma and good performance status should receive dose-intensive regimens such as the GMALL B-ALL/NHL protocol. Standard therapy has not been defined for pts with plasmablastic and primary effusion lymphoma. Pts with lymphoma in sensitive relapse should receive high-dose chemotherapy followed by autologous stem cell transplantation. Stage- and risk adapted treatment yields high remission and survival rates in pts with HIV-HL similar to those achieved in HIV-negative HL pts. Combination antiretroviral therapy (cART) should be applied concurrently to chemotherapy provided that pharmacokinetic interactions are being considered. Pts with HIV-lymphoma should usually be treated in an identical manner to HIV-negative patients.
    Annals of Hematology 06/2014; 93(6):913-21. DOI:10.1007/s00277-014-2058-4 · 2.40 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Background: Elevated polyclonal serum free light chain (FLC) levels have been associated with increased mortality and disease activity in many conditions. Currently, polyclonal FLC quantification requires summation of individual FLCκ and FLCλ assays. Here we present a single assay for combined FLC (cFLC, Combylite™) which reduces assay time and eliminates potential imprecision errors incurred by summating FLC assays (ΣFLC). Methods: Sheep FLCκ- and FLCλ-specific antibodies were conjugated to latex microparticles to quantify FLCκ and FLCλ in a single assay. Combylite results were compared to ΣFLC (Freelite®) in 132 healthy controls and 1127 patient samples. The utility of cFLC for predicting all-cause mortality in a haematological referral population was evaluated. Results: cFLC and ΣFLC results were highly concordant (Passing-Bablok equation y=0.98x-1.59 mg/L, R2=0.96). Combylite assay imprecision was low at concentrations around the upper normal range [coefficient of variation (CV) 5.5%, 54 mg/L] and the upper limit of the measuring range (CV 5.5%, 170 mg/L). cFLC levels were significantly raised in disease states compared with healthy controls. Additionally, cFLC >65 mg/L was associated with shorter overall survival in a haematological referral population (hazard ratio=4.5, p<0.001). Conclusions: cFLC values obtained using Combylite were comparable to ΣFLC results over a wide concentration range, were elevated in diseases characterised by B cell activation and were associated with increased mortality in a haematological referral population. These observations indicate the Combylite assay has value for investigating the role of B cell activation in disparate disease groups and could be considered as a surrogate indication of B cell function.
    Clinical Chemistry and Laboratory Medicine 06/2014; 52(11). DOI:10.1515/cclm-2014-0279 · 2.96 Impact Factor
Show more