TARC is a specific and sensitive serum marker for classical Hodgkin’s lymphoma in children

Introduction Pediatric classical Hodgkin’s lymphoma (cHL) is characterized by Hodgkin Reed-Sternberg (HRS) cells located in an inflammatory microenvironment. HRS cells and microenvironment communicate through active crosstalk. This results in secretion of blood biomarkers, which may serve as surrogate markers for lymphoma viability [1], [2]. One promising biomarker in adult patients with cHL is “Thymus and Activation-Regulated Chemokine” (TARC) [3], [4]. So far, TARC levels in pediatric cHL patients have not been reported. The objectives of this study were to investigate TARC as a diagnostic marker in pediatric cHL patients and to define normal TARC values in non-cHL children.

Methods In thismulti-center prospective study, plasma and serum samples were collected of newly diagnosed cHL patients before start of treatment (n=43). To define normal values of TARC in children, samples were collected from non-cHL randomly selected patients from different outpatient clinics (n=80). TARC levels were measured by enzyme-linked immunosorbent assay (R&D systems, Human CCL 17/TARC Quantikine ELISA Kit). TARC levels of the cHL patients were compared to the non-cHL group to obtain ROC curves and calculate the AUC, to assess sensitivity and specificity and accuracy of TARC as a diagnostic marker. In addition, we assessed the association between TARC levels and disease characteristics.

Results The non-cHL patients had a median plasma TARC value of 71 pg/mL (range 18-762), compared to 13984 pg/mL (range 197-73174) in cHL patients (p<0.001). Serum TARC levels were 317 pg/mL (range 27-1300) in non-cHL patients versus 31110 pg/mL (range 826-176451) in cHL patients (p<0.001). For plasma, with a cut-off level of 942 pg/ml, TARC level provides a sensitivity of 98% (95% CI 88%-100%), specificity of 100% (95% CI 95%-100%). The area under the curve (AUC) was 0.999 (95% CI 0.998-1). For serum, with a cut-off level of 1300pg/ml, sensitivity was 97% (95% CI 85-100%), specificity 99% (95% CI 93%-100%), AUC 0.998 (95% CI 0.994-1). TARC levels were associated with treatment level according to the EuroNet-PHL-C2 protocol, bulky disease, the presence of B-symptoms and with ESR. TARC levels were not associated with Ann Arbor staging and CRP levels.

Conclusion TARC was found to be a specific and sensitive diagnostic marker for pediatric cHL. Moreover, this non-invasive marker could be of great value as screening test in the diagnostic work-up for pediatric patients with enlarges lymph nodes.

Conflict of Interest:

No conflict of interest.

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