Abstracts Clinical Lymphoma, Myeloma & Leukemia September 2023 S386 MPN-183 Interferon Treatment Suppresses In Vitro NETosis in Neutrophils Derived from Patients With Myeloproliferative Neoplasms Bahaa Atamna MD1, Idan Goldberg MD1,2,3, Erez Halperin MD1, Adi Shacham-Abulafia MD1,2, Avi Leader MD1,2, Galia Spectre MD, PhD1,2, Pia Raanani MD1,2, Galit Granot PhD4, Shirly Partouche PhD4, Ofir Wolach MD1,2 1Institute of Hematology, Davidoff Cancer Center, Beilinson Hospital, Rabin Medical Center, Petah Tikva, Israel. 2Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. 3Department of Internal Medicine F – Recanati, Beilinson Hospital, Rabin Medical Center, Petah Tikva, Israel. 4Felsenstein Medical Research Center, Beilinson Hospital, Rabin Medical Centerl, Petah Tikva, Israel Introduction: During recent years, there has been an increased use of interferon as first or second line of treatment for myeloproliferative neoplasms (MPN) mainly polycythemia vera (PV) and essential thrombocytosis (ET). Interferon treatment reduces erythrocytosis, thrombocytosis, spleen size and the rate of thrombotic and hemorrhagic complications. The mechanism by which interferon acts in MPN is not fully understood. Multiple factors affect the high tendency for thrombotic events in MPN patients. Several studies have demonstrated increased neutrophil extracellular traps (NETs) formation among patients with MPN. NETs formation (NETosis) might contribute to the thrombotic tendency in MPN. Thus, understanding the influence of cytoreductive therapy on NETosis might be of clinical interest. We aim to evaluate the influence of interferon on NETosis of neutrophils derived from patients with MPN. Methods: We enrolled untreated patients with MPN at a tertiary medical center. Neutrophils were harvested from all blood samples and were divided into plates that were incubated with interferon and plates that were not exposed to interferon. NETosis was assessed by measurement of neutrophil elastase activity in all samples. Our results are being validated by cell death ELISA kit (Rosche) and by immunofluorescence staining. Results: 13 patients (8 men and 5 women) with MPN were included in our cohort. MPN was PV in 7 patients, ET in 5 patients and unclassified in 1 patient. Among all 13 samples, the level of neutrophil elastase activity was significantly lower in samples that were incubated with interferon in comparison to samples that were not incubated with interferon (19.8mU/mL (±17.3) vs 16.2 mU/mL (±16.53), respectively (P=.0005)). Among samples derived from controls, the level of NET-bound neutrophil elastase activity did not significantly differ between neutrophils that were incubated with interferon in comparison to samples that were not incubated with interferon. Conclusion: Our preliminary data suggest that treatment of blood samples from patients with MPN with interferon reduces NETosis in vitro. Our results generate the hypothesis that the reduction in NETosis by interferon treatment contributes to its therapeutic effect in MPN. This hypothesis should be further investigated. Keywords: NETosis, myeloproliferative neoplasms, interferon, polycythemia vera, essential thrombocytosis MPN-193 Incidence of Blast Phase in Myelofibrosis According to Anemia Severity Barbara Mora MD1, Margherita Maffioli MD1, Elisa Rumi MD2,3, Paola Guglielmelli MD4, Marianna Caramella MD5, Andrew Kuykendall MD6, Francesca Palandri MD7, Alessandra Iurlo MD8, Valerio De Stefano MD9, Jean-Jacques Kiladjian MD10, Elena M Elli MD11, Nicola Polverelli MD12, Jason Gotlib MD13, Francesco Albano MD14, Richard T Silver MD15, Giulia Benevolo MD16, David M Ross MD17, Timothy Devos MD18, Oscar Borsani MD2,3, Tiziano Barbui MD19, Matteo G Della Porta MD20, Lorenza Bertú PhD21, Rami Komrokji MD6, Alessandro M Vannucchi MD4, Francesco Passamonti MD8 1Hematology, Department of Oncology, ASST Sette Laghi, Ospedale di Circolo, Varese, Italy. 2Department of Molecular Medicine, University of Pavia, Pavia, Italy. 3Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. 4Center of Research and Innovation of Myeloproliferative Neoplasms, University of Florence, Florence, Italy. 5Hematology, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy. 6Malignant Hematology Department, Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, USA. 7Institute of Hematology “Seràgnoli”, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy. 8UOC Hematology, Foundation IRCCS Ca’Granda Ospedale Maggiore Policlinico, Milan, Italy. 9Hematology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy. 10Hôpital Saint-Louis, Université Paris Cité, Paris, France. 11Division of Hematology and Bone Marrow Unit, IRCCS San Gerardo dei Tintori, Monza, Italy. 12Unit of Blood Diseases and Stem Cell Transplantation, ASST Spedali Civili di Brescia, Brescia, Italy. 13Division of Hematology, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, USA. 14Hematology - Dept. of Emergency and Organ Transplantation, University of Bari, Bari, Italy. 15Richard T. Silver Myeloproliferative Neoplasms Center, New York-Presbyterian Weill Cornell Medical Center, New York, USA. 16Hematology Unit, AOU Città della Salute e della Scienza di Torino, Turin, Italy. 17Haematology Directorate, SA Pathology, Royal Adelaide Hospital, Adelaide, Australia. 18Department of Hematology, KU Leuven University Hospitals Leuven, Leuven, Belgium. 19FROM Research Foundation, ASST Papa Giovanni XXIII, Bergamo, Italy. 20Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy. 21Department of Medicine and Surgery, University of Insubria, Varese, Italy Context: Myelofibrosis (MF) is frequently characterized by anemia and in 10-20% of cases it can evolve into blast phase (BP). Anemia in MF is associated with reduced survival and, in primary MF (PMF), also with risk of BP. Interest in studying anemiaimproving molecules is growing in MF, though the impact of such treatments on BP occurrence is unknown. Objective: To report the incidence of BP according to anemia severity in large real-world cohorts of PMF and secondary MF patients, treated with or without JAK inhibitors (JAKi), mainly ruxolitinib (RUX). Patients: A total of 2,025 MF patients from the database of the University of Insubria
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