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Annals of Oncology Advance Access published online on May 22, 2009
Annals of Oncology, doi:10.1093/annonc/mdp006
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© The Author 2009. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

Cell-free circulating DNA in Hodgkin's and non-Hodgkin's lymphomas

S. Hohaus*, M. Giachelia, G. Massini, G. Mansueto, B. Vannata, V. Bozzoli, M. Criscuolo, F. D'Alò, M. Martini, L. M. Larocca, M. T. Voso and G. Leone

Istituto di Ematologia e di Anatomia Patologica, Università Cattolica S. Cuore, Rome, Italy

* Correspondence to: Dr S. Hohaus, Istituto di Ematologia, Universita’ Cattolica S. Cuore, L.go A. Gemelli 1, 00168 Rome, Italy. Tel: +39-06-30154180; Fax: +39-06-35503777; E-mail: stefan.hohaus{at}rm.unicatt.it

Background: Levels of cell-free circulating DNA have been correlated to clinical characteristics and prognosis in patients with cancers of epithelial origin, while there are no data on patients with B-lymphoproliferative diseases.

Patients and methods: Cell-free DNA levels in the plasma samples of 142 patients with lymphomas [45 with Hodgkin's lymphoma (HL), 63 with diffuse large B-cell non-Hodgkin's lymphoma (DLBCL), 24 with follicular, and 10 with mantle cell non-Hodgkin's lymphoma (NHL)] at diagnosis and of 41 healthy individuals were determined using a quantitative PCR for the β-globin gene.

Results: Levels of circulating DNA in patients with HL, DLBCL, and mantle cell NHL were significantly higher than in controls (P < 0.01 for all). Increased levels of plasma DNA were associated with advanced stage disease, presence of B-symptoms, elevated lactate dehydrogenase levels, and age >60 years (P = 0.009; <0.0001; <0.0001; 0.04, respectively). In HL, histological signs of necrosis and grade 2 type of nodular sclerosis were associated with increased plasma DNA. Elevated plasma DNA levels were associated with an inferior failure-free survival in patients with HL (P = 0.01) and DLBCL (P = 0.03).

Conclusion: Quantification of circulating DNA by real-time PCR at diagnosis can identify patients with elevated levels that are associated with disease characteristics indicating aggressive disease and poor prognosis.

circulating DNA, Hodgkin's lymphoma, non-Hodgkin's lymphoma, prognosis, quantitative PCR

Received for publication August 21, 2008. Revision received December 21, 2008. Accepted for publication December 23, 2008.


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