PLoS One. 2015 Feb 10;10(2)

γ-Herpesvirus Load as Surrogate Marker of Early Death in HIV-1 Lymphoma Patients Submitted to High Dose Chemotherapy and Autologous Peripheral Blood Stem Cell Transplantation.

Pratesi C1, Zanussi S1, Tedeschi R1, Bortolin MT1, Talamini R2, Rupolo M3, Scaini C1, Basaglia G1, Di Maso M2, Mazzucato M4, Zanet E3, Tirelli U5, Michieli M3, Carbone A6, De Paoli P7.

Author information1Microbiology, Immunology and Virology Unit, CRO National Cancer Institute, IRCCS, Aviano, Pordenone, Italy.2Epidemiology and Biostatistics Unit, CRO National Cancer Institute, IRCCS, Aviano, Pordenone, Italy.3Cellular Therapy and High-Dose Chemotherapy Unit, CRO National Cancer Institute, IRCCS, Aviano, Pordenone, Italy.4Stem Cell Collection and Processing Unit, CRO National Cancer Institute, IRCCS, Aviano, Pordenone, Italy.5Division of Medical Oncology A, CRO National Cancer Institute, IRCCS, Aviano, Pordenone, Italy.6Department of Pathology, CRO National Cancer Institute, IRCCS, Aviano, Pordenone, Italy.7Scientific Directorate; CRO National Cancer Institute, IRCCS, Aviano, Pordenone, Italy.

Abstract

Autologous stem cell transplantation (ASCT) is a feasible procedure for human immunodeficiency virus-1 (HIV-1) lymphoma patients, whose underlying disease and intrinsic HIV-1- and ASCT-associated immunodeficiency might increase the risk for γ-herpesvirus load persistence and/or reactivation. We evaluated this hypothesis by investigating the levels of Epstein-Barr virus (EBV)- and Kaposi sarcoma-associated herpesvirus (KSHV)-DNA levels in the peripheral blood of 22 HIV-1-associated lymphoma patients during ASCT, highlighting their relationship with γ-herpesvirus lymphoma status, immunological parameters, and clinical events. EBV-DNA was detected in the pre-treatment plasma and peripheral blood mononuclear cells (PBMCs) of 12 (median 12135 copies/mL) and 18 patients (median 417 copies/106 PBMCs), respectively; the values in the two compartments were correlated (r = 0.77, p = 0.0001). Only EBV-positive lymphomas showed detectable levels of plasma EBV-DNA. After debulking chemotherapy, plasma EBV-DNA was associated with lymphoma chemosensitivity (p = 0.03) and a significant higher mortality risk by multivariate Cox analysis adjusted for EBV-lymphoma status (HR, 10.46, 95% CI, 1.11-98.32, p = 0.04). After infusion, EBV-DNA was detectable in five EBV-positive lymphoma patients who died within six months. KSHV-DNA load was positive in only one patient, who died from primary effusion lymphoma. Fluctuations in levels of KSHV-DNA reflected the patient's therapy and evolution of his underlying lymphoma. Other γ-herpesvirus-associated malignancies, such as multicentric Castleman disease and Kaposi sarcoma, or end-organ complications after salvage treatment were not found. Overall, these findings suggest a prognostic and predictive value of EBV-DNA and KSHV-DNA, the monitoring of which could be a simple, complementary tool for the management of γ-herpesvirus-positive lymphomas in HIV-1 patients submitted to ASCT.

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