title: 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.
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 12,135 copies/mL) and 18 patients (median 417 copies/10(6) 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.
authors: Microbiology, Immunology and Virology Unit, CRO National Cancer Institute, IRCCS, Aviano, Pordenone, Italy.
authors: Chiara
authors: C
authors: Pratesi
authors: Microbiology, Immunology and Virology Unit, CRO National Cancer Institute, IRCCS, Aviano, Pordenone, Italy.
authors: Stefania
authors: S
authors: Zanussi
authors: Microbiology, Immunology and Virology Unit, CRO National Cancer Institute, IRCCS, Aviano, Pordenone, Italy.
authors: Rosamaria
authors: R
authors: Tedeschi
authors: Microbiology, Immunology and Virology Unit, CRO National Cancer Institute, IRCCS, Aviano, Pordenone, Italy.
authors: Maria Teresa
authors: MT
authors: Bortolin
authors: Epidemiology and Biostatistics Unit, CRO National Cancer Institute, IRCCS, Aviano, Pordenone, Italy.
authors: Renato
authors: R
authors: Talamini
authors: Cellular Therapy and High-Dose Chemotherapy Unit, CRO National Cancer Institute, IRCCS, Aviano, Pordenone, Italy.
authors: Maurizio
authors: M
authors: Rupolo
authors: Microbiology, Immunology and Virology Unit, CRO National Cancer Institute, IRCCS, Aviano, Pordenone, Italy.
authors: Chiara
authors: C
authors: Scaini
authors: Microbiology, Immunology and Virology Unit, CRO National Cancer Institute, IRCCS, Aviano, Pordenone, Italy.
authors: Giancarlo
authors: G
authors: Basaglia
authors: Epidemiology and Biostatistics Unit, CRO National Cancer Institute, IRCCS, Aviano, Pordenone, Italy.
authors: Matteo
authors: M
authors: Di Maso
authors: Stem Cell Collection and Processing Unit, CRO National Cancer Institute, IRCCS, Aviano, Pordenone, Italy.
authors: Mario
authors: M
authors: Mazzucato
authors: Cellular Therapy and High-Dose Chemotherapy Unit, CRO National Cancer Institute, IRCCS, Aviano, Pordenone, Italy.
authors: Ernesto
authors: E
authors: Zanet
authors: Division of Medical Oncology A, CRO National Cancer Institute, IRCCS, Aviano, Pordenone, Italy.
authors: Umberto
authors: U
authors: Tirelli
authors: Cellular Therapy and High-Dose Chemotherapy Unit, CRO National Cancer Institute, IRCCS, Aviano, Pordenone, Italy.
authors: Mariagrazia
authors: M
authors: Michieli
authors: Department of Pathology, CRO National Cancer Institute, IRCCS, Aviano, Pordenone, Italy.
authors: Antonino
authors: A
authors: Carbone
authors: Scientific Directorate; CRO National Cancer Institute, IRCCS, Aviano, Pordenone, Italy.
authors: Paolo
authors: P
authors: De Paoli
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D003643:Death; D005260:Female; D018142:Gammaherpesvirinae / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism; D006801:Humans; D016483:Lymphoma, AIDS-Related / Q000175:diagnosis* / Q000378:metabolism / Q000628:therapy* / Q000821:virology; D008297:Male; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation / Q000379:methods; D011379:Prognosis; D012189:Retrospective Studies; D014182:Transplantation, Autologous / Q000379:methods; D014412:Tumor Virus Infections / Q000378:metabolism*; D019562:Viral Load
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers