Cesarina Giallongo, Annalisa Chiarenza, Claudio Tripodo, Andrea Gallamini, Nunziatina Laura Parrinello, Alessandra Romano, Piera La Cava, Francesco Di Raimondo, Daniele Tibullo, Stefano Pileri, Massimo Ippolito, Calogero Vetro, Giovanna Motta, Sebastiano Cosentino, Ugo Consoli, Anastasia Laura Caruso, Loredana Villari, Romano, A., Laura Parrinello, N., Vetro, C., Tibullo, D., Giallongo, C., La Cava, P., Chiarenza, A., Motta, G., Caruso, A., Villari, L., Tripodo, C., Cosentino, S., Ippolito, M., Consoli, U., Gallamini, A., Pileri, S., and Di Raimondo, F.
// Alessandra Romano 1 , Nunziatina Laura Parrinello 1 , Calogero Vetro 1 , Daniele Tibullo 1 , Cesarina Giallongo 1 , Piera La Cava 1 , Annalisa Chiarenza 1 , Giovanna Motta 1 , Anastasia L. Caruso 1 , Loredana Villari 2 , Claudio Tripodo 3 , Sebastiano Cosentino 4 , Massimo Ippolito 4 , Ugo Consoli 5 , Andrea Gallamini 6 , Stefano Pileri 7 , Francesco Di Raimondo 1 1 Division of Hematology, AOU “Policlinico - Vittorio Emanuele”, University of Catania, Catania, Italy 2 Division of Pathology, AOU “Policlinico - Vittorio Emanuele”, Catania, Italy 3 Tumor Immunology Unit, Department of Health Science, University of Palermo, Palermo, Italy 4 Nuclear Medicine Center, Azienda Ospedaliera Cannizzaro, Catania, Italy 5 Division of Hematology, ARNAS Garibaldi, Catania, Italy 6 Research, Innovation and Statistics Department. A. Lacassagne Cancer Centre, Nice, France 7 Unita di Diagnosi Emolinfopatologica, IEO, Milano, Italy Correspondence to: Alessandra Romano, email: sandrina.romano@gmail.com Francesco Di Raimondo, email: diraimon@unict.it Keywords: Arginase-1, Hodgkin lymphoma, PET-2 Received: June 30, 2016 Accepted: September 05, 2016 Published: September 14, 2016 ABSTRACT Purpose: Neutrophilia is hallmark of classic Hodgkin Lymphoma (cHL), but its precise characterization remains elusive. We aimed at investigating the immunosuppressive role of high-density neutrophils in HL. Experimental design: First, N-HL function was evaluated in vitro , showing increased arginase (Arg-1) expression and activity compared to healthy subjects. Second, we measured serum level of Arg-1 (s-Arg-1) by ELISA in two independent, training ( N = 40) and validation ( N = 78) sets. Results: s-Arg-1 was higher in patients with advanced stage ( p = 0.045), B-symptoms ( p = 0.0048) and a positive FDG-PET scan after two cycles of chemotherapy (PET-2, p = 0.012). Baseline levels of s-Arg-1 > 200 ng/mL resulted in 92% sensitivity and 56% specificity to predict a positive PET-2. Patients showing s-Arg-1 levels > 200 ng/mL had a shorter progression free survival (PFS). In multivariate analysis, PET-2 and s-Arg-1 at diagnosis were the only statistically significant prognostic variables related to PFS (respectively p = 0.0004 and p = 0.012). Moving from PET-2 status and s-Arg-1 level we constructed a prognostic score to predict long-term treatment outcome: low s-Arg-1 and negative PET-2 scan (score 0, N = 63), with a 3-Y PFS of 89.5%; either positive PET-2 or high s-Arg-1 (score 1, N = 46) with 3-Y PFS of 67.6%, and both positive markers (score 2, N = 9) with a 3-Y PFS of 37% ( p = 0.0004). Conclusions: We conclude that N-HL are immunosuppressive through increased Arg-1 expression, a novel potential biomarker for HL prognosis.