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1. Incidence of blast phase in myelofibrosis according to anemia severity

Author

Barbara Mora, Margherita Maffioli, Elisa Rumi, Paola Guglielmelli, Marianna Caramella, Andrew Kuykendall, Francesca Palandri, Alessandra Iurlo, Valerio De Stefano, Jean‐Jacques Kiladjian, Elena M. Elli, Nicola Polverelli, Jason Gotlib, Francesco Albano, Richard T. Silver, Giulia Benevolo, David M. Ross, Timothy Devos, Oscar Borsani, Tiziano Barbui, Matteo G. Della Porta, Lorenza Bertù, Rami Komrokji, Alessandro M. Vannucchi, and Francesco Passamonti

Subjects
acute myeloid leukemia, essential thrombocythemia, myelofibrosis, polycythemia vera, ruxolitinib, Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Abstract Myelofibrosis (MF) is a clonal malignancy 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‐ also with an increased probability of BP. Conventional treatments for anemia have limited effectiveness in MF. Within a dataset of 1752 MF subjects largely unexposed to ruxolitinib (RUX), BP incidence was 2.5% patients per year (p‐y). This rate reached respectively 4.3% and 4.5% p‐y in case of patients with common terminology criteria for adverse events (CTCAE) grade 3/4 and grade 2 anemia, respectively, that represented together 32% of the cohort. Among 273 MF cases treated with RUX, BP incidence was 2.89% p‐y and it reached 4.86% p‐y in subjects who started RUX with CTCAE grade 2 anemia (one third of total). Within patients with red blood cell transfusion‐dependency at 6 months of RUX (21% of the exposed), BP rate was 4.2% p‐y. Our study highlights a relevant incidence of BP in anemic MF patients, with a similar rate whether treated with or without RUX. These findings will help treating physicians to make decisions on the safety profile of innovative anemia treatments.

Published
2023
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2. Assessment of the efficacy and tolerability of ruxolitinib for the treatment of myelofibrosis patients in a real‐life setting: An Italian MYNERVA Project

Author

Giacomo Coltro, Emanuela Sant'Antonio, Giuseppe A. Palumbo, Francesco Mannelli, Valerio De Stefano, Marco Ruggeri, Elena M. Elli, Roberta Zanotti, Oscar Borsani, Irene Bertozzi, Andrea Duminuco, Silvia Betti, Giuseppe Carli, Fabrizio Cavalca, Ilaria Tanasi, Elisa Rumi, Maria L. Randi, Bruno Garibaldi, Giuseppe G. Loscocco, Paola Guglielmelli, and Alessandro M. Vannucchi

Subjects
efficacy, myelofibrosis, ruxolitinib, safety, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Incorporating real‐world data in the drug development process allows the improvement of health outcomes by providing better representation of actual patterns of drug safety and efficacy. Aims and Methods Here, we present the results of a retroprospective, observational real‐life study of 154 patients with myelofibrosis treated with ruxolitinib in a real‐life setting in seven Italian centers of the MYNERVA project. Results Median drug exposure was 29 (range, 3–98) months. Discontinuation rate was 27% after a median time of 13 (range, 3–61). While hematological toxicities were in line with previous findings, infections occurred frequently, representing a not negligible cause of discontinuation and death. Anemia, symptoms, and spleen responses were obtained at any time in 23%, 91%, and 68% of patients, respectively; most patients achieved their responses by week 24. Larger splenomegaly and delayed treatment initiation correlated with lower spleen response at 24 weeks. Spleen response was associated with a superior overall survival, regardless of DIPSS. Of interest, both achievement and loss of spleen response had prognostic implications. Discussion and Conclusion Overall, our findings provide insights on the efficacy and safety of ruxolitinib in a real‐world, multicenter cohort of Italian MF patients.

Published
2023
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4. Clinical impact of mutated JAK2 allele burden reduction in polycythemia vera and essential thrombocythemia

Author

Guglielmelli, Paola, primary, Mora, Barbara, additional, Gesullo, Francesca, additional, Mannelli, Francesco, additional, Loscocco, Giuseppe Gaetano, additional, Signori, Leonardo, additional, Pessina, Chiara, additional, Colugnat, Ilaria, additional, Aquila, Raffaela, additional, Balliu, Manjola, additional, Maccari, Chiara, additional, Romagnoli, Simone, additional, Paoli, Chiara, additional, Nacca, Elena, additional, Fagiolo, Lorenzo, additional, Maffioli, Margherita, additional, Barbui, Tiziano, additional, Passamonti, Francesco, additional, and Vannucchi, Alessandro M., additional

Published
2024
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5. Earth's Isostatic and Dynamic Topography—A Critical Perspective

Author

Alessandro M. Forte and David B. Rowley

Subjects
Geophysics. Cosmic physics, QC801-809, Geology, QE1-996.5
Abstract

Abstract Earth's topography arises from the linear superposition of isostatic and dynamic contributions. The isostatic contribution reflects the distribution of thickness and density of the crust overlying a static, non‐convecting mantle. We argue that isostatic topography should be limited to the crust, thereby delimiting all sources for dynamic topography below the Moho. Dynamic topography is the component of the topography produced by normal stresses acting on the Moho that deflect the isostatic topography away from crustal isostatic equilibrium largely as a consequence of mantle flow dynamics. These normal stresses arise from pressure variations and vertical gradients of the radial flow in the convecting mantle. The best estimate of dynamic topography is from the residual topography, which is the difference between observed topography and crustal isostatic topography. Dynamic and residual topography are the same. It is clear that thermal anomalies horizontally advected by plate motions would not exist if the mantle were not convecting, therefore their contribution to topography is inherently dynamic in origin. The global integral of dynamic topography that encompasses all non‐crustal buoyancy sources is demonstrated to be equal to zero. It follows that mantle convection cannot change the mean radius or mean elevation of the Earth. Since changes in ocean basin volume driven by changes in mean depth of the oceans are inherently part of dynamic topography, thereby requiring that continental elevations must also change, such that the global integral of these perturbations must also be equal to zero. This constraint has important implications for global long‐term sea level and the stratigraphic record, among other features of the Earth system impacted by changes in Earth's dynamic topography.

Published
2022
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6. Long‐term overall survival and toxicities of ABVD vs BEACOPP in advanced Hodgkin lymphoma: A pooled analysis of four randomized trials

Author

Marc P. E. André, Patrice Carde, Simonetta Viviani, Monica Bellei, Catherine Fortpied, Martin Hutchings, Alessandro M. Gianni, Pauline Brice, Olivier Casasnovas, Paolo G. Gobbi, Pier Luigi Zinzani, Jehan Dupuis, Emilio Iannitto, Alessandro Rambaldi, Josette Brière, Laurianne Clément‐Filliatre, Marian Heczko, Pinuccia Valagussa, Jonathan Douxfils, Julien Depaus, Massimo Federico, and Nicolas Mounier

Subjects
ABVD, BEACOPP, Hodgkin lymphoma, overall survival, progression‐free survival, secondary cancers, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Purpose We explored the potential overall survival (OS) benefit of bleomycin, etoposide, doxorubicin (Adriamycin), cyclophosphamide, vincristine (Oncovin), procarbazine, and prednisone (BEACOPP) over doxorubicin (Adriamycin), bleomycin, vinblastine, and dacarbazine (ABVD) in a pooled analysis of four randomized trials. Patients and methods Primary objective was to evaluate the OS impact of BEACOPP using individual patient data. Secondary objectives were progression‐free survival (PFS), secondary cancers, and use of autologous stem cell transplantation (ASCT). Results About 1227 patients were included. The 7‐year OS was 84.3% (95% CI 80.8‐87.2) for ABVD vs 87.7% (95% CI 84.5‐90.2) for BEACOPP. Two follow‐up periods were identified based on survival curves and hazard ratio (HR) over time. For the first 18 months, there was no difference. For the second period of ≥18 months, ABVD patients had a higher death risk (HRABVD vs BEACOPP = 1.59; 95% CI 1.09‐2.33). A Cox model stratified by trial and evaluating the effect of treatment and International Prognostic Index (IPI) score as fixed effects showed that both were statistically significant (treatment, P = .0185; IPI score, P = .0107). The 7‐year PFS was 71.1% (95% CI 67.1‐74.6) for ABVD vs 81.1% (95% CI 77.5‐84.2) for BEACOPP (P

Published
2020
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8. The Sensitivity of Joint Inversions of Seismic and Geodynamic Data to Mantle Viscosity

Author

Chang Lu, Alessandro M. Forte, Nathan A. Simmons, Stephen P. Grand, Marie N. Kajan, Hongyu Lai, and Edward J. Garnero

Subjects
Mantle Density Anomaly, Mantle Viscosity, Mantle Flow, Seismic Tomography, LLSVP, Joint Inversion, Geophysics. Cosmic physics, QC801-809, Geology, QE1-996.5
Abstract

Abstract Seismic tomography has revealed the existence of large‐scale velocity heterogeneities in the mantle. The interpretation of seismic velocity anomalies in terms of temperature and chemical composition is nonunique. We use geodynamic observations including gravity, plate motions, dynamic topography, and excess ellipticity of the core‐mantle boundary combined with seismic observations to investigate the thermo‐chemical structure of the mantle through joint inversions. An outstanding issue, however, is the physical connection between mantle density anomalies and the surface geodynamic observations, which requires knowledge of the mantle viscosity structure. Here we perform joint inversions assuming different viscosity profiles and examine the dependence of the results on the viscosity. We first assume that mantle heterogeneity is due to thermal variations, which places a constraint on the relation between seismic velocity and density, and we subsequently relax the constraint to allow for potential nonthermal effects. In all of our joint inversions, a nonthermal origin of density anomalies is required to explain the geodynamic data, though the amount varies with the assumed viscosity structure. A common observation is a high‐density chemical signal in the center of the large low‐shear‐velocity provinces at the base of the mantle resulting in a near neutral or slightly dense overall buoyancy there. Using the derived density models and their corresponding viscosity profiles, we also calculate instantaneous mantle flow fields. The predicted flow fields derived from joint inversions are generally similar but are quite different from flow fields using density models derived from a posteriori scaling of pure seismic tomography models.

Published
2020
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9. Role of TGF‐β1/miR‐382‐5p/SOD2 axis in the induction of oxidative stress in CD34+ cells from primary myelofibrosis

Author

Chiara Rossi, Roberta Zini, Sebastiano Rontauroli, Samantha Ruberti, Zelia Prudente, Greta Barbieri, Elisa Bianchi, Simona Salati, Elena Genovese, Niccolò Bartalucci, Paola Guglielmelli, Enrico Tagliafico, Vittorio Rosti, Giovanni Barosi, Alessandro M. Vannucchi, Rossella Manfredini, and the AGIMM (AIRC‐Gruppo Italiano Malattie Mieloproliferative) investigators

Subjects
miR‐382‐5p, oxidative stress, primary myelofibrosis, reactive oxygen species, superoxide dismutase, TGF‐β1 signaling, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Primary myelofibrosis (PMF) is a myeloproliferative neoplasm characterized by an excessive production of pro‐inflammatory cytokines resulting in chronic inflammation and genomic instability. Besides the driver mutations in JAK2, MPL, and CALR genes, the deregulation of miRNA expression may also contribute to the pathogenesis of PMF. To this end, we recently reported the upregulation of miR‐382‐5p in PMF CD34+ cells. In order to unveil the mechanistic details of the role of miR‐382‐5p in pathogenesis of PMF, we performed gene expression profiling of CD34+ cells overexpressing miR‐382‐5p. Among the downregulated genes, we identified superoxide dismutase 2 (SOD2), which is a predicted target of miR‐382‐5p. Subsequently, we confirmed miR‐382‐5p/SOD2 interaction by luciferase assay and we showed that miR‐382‐5p overexpression in CD34+ cells causes the decrease in SOD2 activity leading to reactive oxygen species (ROS) accumulation and oxidative DNA damage. In addition, our data indicate that inhibition of miR‐382‐5p in PMF CD34+ cells restores SOD2 function, induces ROS disposal, and reduces DNA oxidation. Since the pro‐inflammatory cytokine transforming growth factor‐β1 (TGF‐β1) is a key player in PMF pathogenesis, we further investigated the effect of TGF‐β1 on ROS and miR‐382‐5p levels. Our data showed that TGF‐β1 treatment enhances miR‐382‐5p expression and reduces SOD2 activity leading to ROS accumulation. Finally, inhibition of TGF‐β1 signaling in PMF CD34+ cells by galunisertib significantly reduced miR‐382‐5p expression and ROS accumulation and restored SOD2 activity. As a whole, this study reports that TGF‐β1/miR‐382‐5p/SOD2 axis deregulation in PMF cells is linked to ROS overproduction that may contribute to enhanced oxidative stress and inflammation. Our results suggest that galunisertib may represent an effective drug reducing abnormal oxidative stress induced by TGF‐β1 in PMF patients. Database linking GEO: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE103464.

Published
2018
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10. The prognostic contribution of CBL, NRAS, KRAS, RUNX1, and TP53 mutations to mutation‐enhanced international prognostic score systems (MIPSS70/plus/plus v2.0) for primary myelofibrosis

Author

Loscocco, Giuseppe G., primary, Rotunno, Giada, additional, Mannelli, Francesco, additional, Coltro, Giacomo, additional, Gesullo, Francesca, additional, Pancani, Fabiana, additional, Signori, Leonardo, additional, Maccari, Chiara, additional, Esposito, Maria, additional, Paoli, Chiara, additional, Vannucchi, Alessandro M., additional, and Guglielmelli, Paola, additional

Published
2023
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11. A globally applicable “triple A” risk model for essential thrombocythemia based on Age, Absolute neutrophil count, and Absolute lymphocyte count

Author

Tefferi, Ayalew, primary, Loscocco, Giuseppe G., additional, Farrukh, Faiqa, additional, Szuber, Natasha, additional, Mannelli, Francesco, additional, Pardanani, Animesh, additional, Hanson, Curtis A., additional, Ketterling, Rhett P., additional, De Stefano, Valerio, additional, Carobbio, Alessandra, additional, Barbui, Tiziano, additional, Guglielmelli, Paola, additional, Gangat, Naseema, additional, and Vannucchi, Alessandro M., additional

Published
2023
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14. Incidence of blast phase in myelofibrosis according to anemia severity

Author

Mora, Barbara, primary, Maffioli, Margherita, additional, Rumi, Elisa, additional, Guglielmelli, Paola, additional, Caramella, Marianna, additional, Kuykendall, Andrew, additional, Palandri, Francesca, additional, Iurlo, Alessandra, additional, De Stefano, Valerio, additional, Kiladjian, Jean‐Jacques, additional, Elli, Elena M., additional, Polverelli, Nicola, additional, Gotlib, Jason, additional, Albano, Francesco, additional, Silver, Richard T., additional, Benevolo, Giulia, additional, Ross, David M., additional, Devos, Timothy, additional, Borsani, Oscar, additional, Barbui, Tiziano, additional, Porta, Matteo G. Della, additional, Bertù, Lorenza, additional, Komrokji, Rami, additional, Vannucchi, Alessandro M., additional, and Passamonti, Francesco, additional

Published
2023
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16. The international consensus classification of myeloid neoplasms and acute Leukemias: myeloproliferative neoplasms

Author

Thiele, Jurgen, Kvasnicka, Hans Michael, Orazi, Attilio, Gianelli, Umberto, Gangat, Naseema, Vannucchi, Alessandro M., Barbui, Tiziano, Arber, Daniel A., Tefferi, Ayalew, Thiele, Jurgen, Kvasnicka, Hans Michael, Orazi, Attilio, Gianelli, Umberto, Gangat, Naseema, Vannucchi, Alessandro M., Barbui, Tiziano, Arber, Daniel A., and Tefferi, Ayalew

Abstract

A group of international experts, including hematopathologists, oncologists, and geneticists were recently summoned (September 2021, Chicago, IL, USA) to update the 2016/17 World Health Organization classification system for hematopoietic tumors. After careful deliberation, the group introduced the new International Consensus Classification (ICC) for Myeloid Neoplasms and Acute Leukemias. This current in-depth review focuses on the ICC-2022 category of JAK2 mutation-prevalent myeloproliferative neoplasms (MPNs): essential thrombocythemia, polycythemia vera, primary myelofibrosis, and MPN, unclassifiable. The ICC MPN subcommittee chose to preserve the primary role of bone marrow morphology in disease classification and diagnostics, while also acknowledging the complementary role of genetic markers for establishing clonality, facilitating MPN subtype designation, and disease prognostication.

Published
2023

20. Safety and efficacy of fedratinib, a selective oral inhibitor of Janus kinase‐2 ( <scp>JAK2</scp> ), in patients with myelofibrosis and low pretreatment platelet counts

Author

Claire N. Harrison, Nicolaas Schaap, Alessandro M. Vannucchi, Jean‐Jacques Kiladjian, Francesco Passamonti, Sonja Zweegman, Moshe Talpaz, Srdan Verstovsek, Shelonitda Rose, Jun Zhang, Oumar Sy, Ruben A. Mesa, Hematology, and CCA - Cancer Treatment and quality of life

Subjects
Sulfonamides, Pyrrolidines, Platelet Count, Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2], myelofibrosis, Janus Kinase 1, Hematology, Janus Kinase 2, Thrombocytopenia, JAK, fedratinib, platelets, thrombocytopaenia, Double-Blind Method, Primary Myelofibrosis, Nitriles, Humans, Protein Kinase Inhibitors
Abstract

Contains fulltext : 282573.pdf (Publisher’s version ) (Open Access) Fedratinib, an oral Janus kinase-2 (JAK2) inhibitor, is approved for patients with myelofibrosis (MF) and platelet counts ≥50 × 10(9) /l, based on outcomes from the phase 3, placebo-controlled JAKARTA trial in JAK-inhibitor-naïve MF, and the phase 2, single-arm JAKARTA2 trial in patients previously treated with ruxolitinib. We evaluated the efficacy and safety of fedratinib 400 mg/day in patients with baseline platelet counts 50 to

Published
2022
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23. Portosystemic shunt is an effective treatment for complications of portal hypertension in hepatic myeloid metaplasia and improves nutritional status

Author

Silvia Aspite, Filippo Schepis, Davide Roccarina, Stefano Gitto, Michele Citone, Chiara Di Bonaventura, Marcello Bianchini, Umberto Arena, Alessandro M. Vannucchi, Paola Guglielmelli, Francesca Campani, Fabrizio Fanelli, Fabio Marra, and Francesco Vizzutti

Subjects
Hepatology, Nutritional Status, Portosystemic shunt, Esophageal and Gastric Varices, Hepatic myeloid metaplasia, Treatment Outcome, Nutritional status, Primary Myelofibrosis, Portal hypertension, TIPS, Hypertension, Portal, Humans, Neoplasm Recurrence, Local, Portasystemic Shunt, Transjugular Intrahepatic, Gastrointestinal Hemorrhage
Abstract

In patients affected by myelofibrosis with hepatic myeloid metaplasia (HMM), portal hypertension (PHT) complications may develop. In this case series, we analysed the efficacy and safety of transjugular portosystemic shunt (TIPS) in the treatment of PHT-related complications and its effects on the nutritional status. Six patients were evaluated and the average follow-up period after TIPS was 33 (IQR 5) months. None of the patients developed hepatic failure, nor any recurrence of variceal bleeding was recorded. No additional paracentesis or endoscopic prophylactic treatment for PHT-related complications were required. In all subjects, the average dose of diuretics was almost halved three months after TIPS. Three patients died during the follow-up, but none for liver-related causes. All patients showed an improvement in the global nutritional status. In conclusion, TIPS represent an effective and safe treatment option for patients affected by complications of PHT secondary to HMM and drives to an improvement of the nutritional status.

Published
2022
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24. Assessment of the efficacy and tolerability of ruxolitinib for the treatment of myelofibrosis patients in a real‐life setting: An Italian MYNERVA Project

Author

Coltro, Giacomo, primary, Sant'Antonio, Emanuela, additional, Palumbo, Giuseppe A., additional, Mannelli, Francesco, additional, De Stefano, Valerio, additional, Ruggeri, Marco, additional, Elli, Elena M., additional, Zanotti, Roberta, additional, Borsani, Oscar, additional, Bertozzi, Irene, additional, Duminuco, Andrea, additional, Betti, Silvia, additional, Carli, Giuseppe, additional, Cavalca, Fabrizio, additional, Tanasi, Ilaria, additional, Rumi, Elisa, additional, Randi, Maria L., additional, Garibaldi, Bruno, additional, Loscocco, Giuseppe G., additional, Guglielmelli, Paola, additional, and Vannucchi, Alessandro M., additional

Published
2023
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25. Protective ileostomy creation after anterior resection of the rectum: Shared decision‐making or still subjective?

Author

Balla, Andrea, primary, Saraceno, Federica, additional, Rullo, Marika, additional, Morales‐Conde, Salvador, additional, Targarona Soler, Eduardo M., additional, Di Saverio, Salomone, additional, Guerrieri, Mario, additional, Lepiane, Pasquale, additional, Di Lorenzo, Nicola, additional, Adamina, Michel, additional, Alarcón, Isaias, additional, Arezzo, Alberto, additional, Bollo Rodriguez, Jesus, additional, Boni, Luigi, additional, Biondo, Sebastiano, additional, Carrano, Francesco Maria, additional, Chand, Manish, additional, Jenkins, John T., additional, Davies, Justin, additional, Delgado Rivilla, Salvadora, additional, Delrio, Paolo, additional, Elmore, Ugo, additional, Espin‐Basany, Eloy, additional, Fichera, Alessandro, additional, Flor Lorente, Blas, additional, Francis, Nader, additional, Gómez Ruiz, Marcos, additional, Hahnloser, Dieter, additional, Licardie, Eugenio, additional, Martinez, Carmen, additional, Ortenzi, Monica, additional, Panis, Yves, additional, Pastor Idoate, Carlos, additional, Paganini, Alessandro M., additional, Pera, Miguel, additional, Perinotti, Roberto, additional, Popowich, Daniel A., additional, Rockall, Timothy, additional, Rosati, Riccardo, additional, Sartori, Alberto, additional, Scoglio, Daniele, additional, Shalaby, Mostafa, additional, Simó Fernández, Vicente, additional, Smart, Neil J., additional, Spinelli, Antonino, additional, Sylla, Patricia, additional, Tanis, Pieter J., additional, Valdes‐Hernandez, Javier, additional, Wexner, Steven D., additional, and Sileri, Pierpaolo, additional

Published
2022
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26. Diagnostic and therapeutic challenges in mast cell sarcoma

Author

Mannelli, Francesco, primary, Gesullo, Francesca, additional, Mannarelli, Carmela, additional, Vanderwert, Fiorenza, additional, Lazzi, Stefano, additional, Mungai, Francesco, additional, Berti, Valentina, additional, Santi, Raffaella, additional, Guglielmelli, Paola, additional, and Vannucchi, Alessandro M., additional

Published
2022
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29. Clinical and molecular predictors of fibrotic progression in essential thrombocythemia: A multicenter study involving 1607 patients

Author

Ayalew Tefferi, Elena Rossi, Naseema Gangat, Silvia Betti, Alessandro M. Vannucchi, Carmela Mannarelli, Chiara Paoli, Francesco Ramundo, Chiara Maccari, Giuseppe Gaetano Loscocco, Animesh Pardanani, Yamna Jadoon, Sara Ceglie, Paola Guglielmelli, Francesca Gesullo, and Valerio De Stefano

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Risk category, Young Adult, Internal medicine, medicine, Humans, Aged, Retrospective Studies, Aged, 80 and over, business.industry, Essential thrombocythemia, Retrospective cohort study, Hematology, Variant allele, Janus Kinase 2, Middle Aged, Prognosis, medicine.disease, Fibrosis, Multicenter study, Mutation, Cohort, Disease Progression, Female, business, Receptors, Thrombopoietin, Thrombocythemia, Essential
Abstract

The current retrospective study involving a total of 1607 patients was designed to identify clinical and molecular variables that were predictive of inferior myelofibrosis-free survival (MFS) in WHO-defined essential thrombocythemia (ET), utilizing three independent patient cohorts: University of Florence, Italy (n = 718); Mayo Clinic, USA (n = 479) and Policlinico Gemelli, Catholic University, Rome, Italy (n = 410). The Florence patient cohort was first examined to identify independent risk factors for MFS, which included age > 60 years (HR 2.5, 95% CI 1.3-4.9), male sex (2.1, 1.2-3.9), palpable splenomegaly (2.1, 1.2-3.9), CALR 1/1-like or MPL mutation (3.4, 1.9-6.1) and JAK2V617F variant allele frequency > 35% (4.2, 1.6-10.8). Subsequently, an operational molecular risk category was developed and validated in the other two cohorts from Mayo Clinic and Rome: "high molecular risk" category included patients with JAK2V617F VAF >35%, CALR type 1/1-like or MPL mutations; all other driver mutation profiles were assigned to "low molecular risk" category. The former, compared to the latter molecular risk category, displayed significantly higher risk of fibrotic transformation: Florence cohort with respective fibrotic transformation risk rates of 8% vs. 1.2% at 10 years and 33% vs. 8% at 20 years (p

Published
2021
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31. Lenalidomide: A double‐edged sword for concomitant multiple myeloma and post‐essential thrombocythemia myelofibrosis

Author

Alessandro M. Vannucchi, Giada Rotunno, Ilaria Romano, Francesco Mannelli, Federica Vergoni, Paola Guglielmelli, Elisabetta Antonioli, and Giuseppe Gaetano Loscocco

Subjects
Male, Oncology, medicine.medical_specialty, Osteolysis, Monoclonal Gammopathy of Undetermined Significance, Dexamethasone, Bone Marrow, Risk Factors, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Hydroxyurea, Myelofibrosis, Lenalidomide, Multiple myeloma, Aged, Sequence Deletion, Aspirin, Post-Essential Thrombocythemia Myelofibrosis, business.industry, Remission Induction, Hematology, medicine.disease, Primary Myelofibrosis, Concomitant, Stomatitis, Aphthous, Calreticulin, Multiple Myeloma, business, Thrombocythemia, Essential, medicine.drug
Published
2021
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32. SF3B1 mutations in primary and secondary myelofibrosis: Clinical, molecular and prognostic correlates

Author

Loscocco, Giuseppe G., primary, Guglielmelli, Paola, additional, Mannelli, Francesco, additional, Mora, Barbara, additional, Mannarelli, Carmela, additional, Rotunno, Giada, additional, Pancani, Fabiana, additional, Maccari, Chiara, additional, Bartalucci, Niccolò, additional, Romagnoli, Simone, additional, Coltro, Giacomo, additional, Passamonti, Francesco, additional, and Vannucchi, Alessandro M., additional

Published
2022
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34. Quantitative and qualitative alterations of circulating myeloid cells and plasmacytoid DC in SARS‐CoV‐2 infection

Author

Alessio Mazzoni, Alessandro Bartoloni, Filippo Pieralli, Chiara Orazzini, Anna Vanni, Adriano Peris, Francesco Liotta, Lorenzo Cosmi, Manuela Capone, Benedetta Peruzzi, Laura Maggi, Loredana Poggesi, Alessandro M. Vannucchi, Alessandro Morettini, Sara Bencini, Lorenzo Salvati, Francesco Annunziato, Roberto Caporale, and Carlo Nozzoli

Subjects
Adult, Male, 0301 basic medicine, Myeloid, Immunology, Inflammation, Disease, Asymptomatic, Flow cytometry, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Immunology and Allergy, Myeloid Cells, Aged, medicine.diagnostic_test, business.industry, Monocyte, COVID-19, Dendritic Cells, Original Articles, Dendritic cell, Flow Cytometry, Intensive Care Units, 030104 developmental biology, medicine.anatomical_structure, Infectious disease (medical specialty), Female, Erratum, medicine.symptom, business, 030215 immunology
Abstract

SARS-CoV-2 is responsible for a new infectious disease (COVID-19) in which individuals can either remain asymptomatic or progress from mild to severe clinical conditions including acute respiratory distress syndrome and multiple organ failure. The immune mechanisms that potentially orchestrate the pathology in SARS-CoV-2 infection are complex and only partially understood. There is still paucity of data on the features of myeloid cells involved in this viral infection. For this reason, we investigated the different activation status profiles and the subset distribution of myeloid cells and their correlation with disease progression in 40 COVID-19 patients at different stages of disease. COVID-19 patients showed a decrease in the absolute number of plasmacytoid and myeloid dendritic cells, different subset distribution of monocytes and different activation patterns of both monocytes and neutrophils, coupled to a significant reduction of HLA-DR monocyte levels. We found that some of these alterations are typical of all COVID-19 patients, while some others vary at different stages of the disease and correlate with biochemical parameters of inflammation. Collectively, these data suggest that not only the lymphoid, but also the myeloid compartment, is severely affected by SARS-CoV-2 infection.

Published
2020
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35. Safety and efficacy of fedratinib, a selective oral inhibitor of Janus kinase‐2 ( JAK2 ), in patients with myelofibrosis and low pretreatment platelet counts

Author

Harrison, Claire N., primary, Schaap, Nicolaas, additional, Vannucchi, Alessandro M., additional, Kiladjian, Jean‐Jacques, additional, Passamonti, Francesco, additional, Zweegman, Sonja, additional, Talpaz, Moshe, additional, Verstovsek, Srdan, additional, Rose, Shelonitda, additional, Zhang, Jun, additional, Sy, Oumar, additional, and Mesa, Ruben A., additional

Published
2022
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36. Integration of multiparameter flow cytometry score improves prognostic stratification provided by standard models in primary myelofibrosis

Author

Mannelli, Francesco, primary, Bencini, Sara, additional, Coltro, Giacomo, additional, Loscocco, Giuseppe G., additional, Peruzzi, Benedetta, additional, Rotunno, Giada, additional, Maccari, Chiara, additional, Gesullo, Francesca, additional, Borella, Miriam, additional, Paoli, Chiara, additional, Caporale, Roberto, additional, Mannarelli, Carmela, additional, Annunziato, Francesco, additional, Guglielmelli, Paola, additional, and Vannucchi, Alessandro M., additional

Published
2022
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37. Deciphering the individual contribution of absolute neutrophil and monocyte counts to thrombosis risk in polycythemia vera and essential thrombocythemia

Author

Tiziano Barbui, Ayalew Tefferi, Curtis A. Hanson, Animesh Pardanani, Faiqa Farrukh, Paola Guglielmelli, Naseema Gangat, Valerio De Stefano, Giuseppe Gaetano Loscocco, and Alessandro M. Vannucchi

Subjects
Adult, Male, medicine.medical_specialty, Neutrophils, Gastroenterology, Monocytes, Leukocyte Count, Young Adult, Polycythemia vera, Risk Factors, Internal medicine, Humans, Medicine, Polycythemia Vera, Aged, Aged, 80 and over, business.industry, Essential thrombocythemia, Monocyte, Thrombosis, Hematology, Middle Aged, medicine.disease, medicine.anatomical_structure, Female, business, Thrombotic complication, Thrombocythemia, Essential
Published
2021
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38. Portosystemic shunt is an effective treatment for complications of portal hypertension in hepatic myeloid metaplasia and improves nutritional status

Author

Aspite, Silvia, primary, Schepis, Filippo, additional, Roccarina, Davide, additional, Gitto, Stefano, additional, Citone, Michele, additional, Di Bonaventura, Chiara, additional, Bianchini, Marcello, additional, Arena, Umberto, additional, Vannucchi, Alessandro M., additional, Guglielmelli, Paola, additional, Campani, Francesca, additional, Fanelli, Fabrizio, additional, Marra, Fabio, additional, and Vizzutti, Francesco, additional

Published
2022
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39. Impaired response to first <scp>SARS‐CoV</scp> ‐2 dose vaccination in myeloproliferative neoplasm patients receiving ruxolitinib

Author

Francesco Annunziato, Paola Guglielmelli, Michele Spinicci, Alessio Mazzoni, Gian Maria Rossolini, Alessandro Bartoloni, Sofia Pilerci, Lorenzo Zammarchi, Laura Maggi, Miriam Borella, Alessandro M. Vannucchi, Arianna Rocca, and Seble Tekle Kiros

Subjects
2019-20 coronavirus outbreak, Ruxolitinib, COVID-19 Vaccines, Myeloproliferative Disorders, Coronavirus disease 2019 (COVID-19), SARS-CoV-2, business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), COVID-19, Hematology, medicine.disease, Virology, Vaccination, Pyrimidines, Nitriles, Correspondence, medicine, Humans, Pyrazoles, business, Myeloproliferative neoplasm, medicine.drug
Published
2021
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40. Deciphering the individual contribution of absolute neutrophil and monocyte counts to thrombosis risk in polycythemia vera and essential thrombocythemia

Author

Farrukh, Faiqa, primary, Guglielmelli, Paola, additional, Loscocco, Giuseppe G., additional, Pardanani, Animesh, additional, Hanson, Curtis A., additional, De Stefano, Valerio, additional, Barbui, Tiziano, additional, Gangat, Naseema, additional, Vannucchi, Alessandro M., additional, and Tefferi, Ayalew, additional

Published
2021
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43. Peripheral biomarkers' panel for severe COVID‐19 patients

Author

D'Alessandro, M., Bergantini, L., Cameli, P., Curatola, G., Remediani, L., Sestini, P., Bargagli, E., Siena COVID Unit, Bennett, D., Bianchi, F., Perillo, F., Lanzarone, N., Montagnani, F., Perrone, A., Franchi, F., Scolletta, S., Mazzei, M. A., Volterrani, L., Valente, S., Zanelli, G., Migliorini, L., Rossetti, B., Fabbiani, M., Vagaggini, C., Capecchi, P. L., Cusi, M. G., Frediani, B., Cubattoli, L., Mastrocinque, E., Cameli, M., Nardi, M., Bova, G., Mezzasalma, F., Guerrini, S., Santoro, A., Antonelli, G., Giacomin, E., Gentilini, R., Sansoni, A., Corbisiero, R., Mencarelli, M., Pippi, F., Marri, D., Lanari, A., Masini, M., Stella, G., Paglicci, L., Cassol, C., Valenti, R., Caffarelli, C., Gonnelli, S., Lapi, A., Gallo, S., Donati, G., Ceccarelli, E., Mattaliano, C., Sellerio, I., Conticini, E., Cantarini, L., and Marinetti, A.

Subjects
Male, Oncology, medicine.medical_specialty, COVID19, Lymphocyte, T cell, Cell, macromolecular substances, KL-6, Lymphocytes, biomarker, prognosis, Severity of Illness Index, 03 medical and health sciences, 0302 clinical medicine, Virology, Internal medicine, Severity of illness, medicine, Humans, Lymphocyte Count, 030212 general & internal medicine, Letter to the Editor, Aged, Retrospective Studies, Innate immune system, business.industry, Mucin-1, COVID-19, KL‐6, Retrospective cohort study, Middle Aged, Lymphocyte Subsets, Killer Cells, Natural, Infectious Diseases, medicine.anatomical_structure, Biomarker (medicine), Female, 030211 gastroenterology & hepatology, business, Biomarkers, CD8
Abstract

It is widely reported in the literature that CD4, CD8 and total T cell count are significantly reduced in critically ill patients with COVID‐19. Few weeks ago, we suggested natural killer (NK) cell count as a marker of severity in 34 hospitalized COVID‐19 patients. On this topic, our research group firstly described a novel potential COVID19 severity marker, Krebs von den Lungen‐6. This study aimed to investigate how a combination of COVID19 severity markers could be helpful in the clinical management of these patients. The combination of these validated, reproducible and non‐expensive bioindicators showed a good accuracy in discriminating between severe and non‐severe patients, suggesting a promising value of this approach in the early prediction of a more aggressive disease phenotype. Despite its monocentric design, our study confirms the reliable dysregulation of innate immune responses, particularly involving NK cells, and suggests that surveillance of a peripheral biomarkers’ panel, including lymphocyte cell counts and KL‐6, may be useful in the clinical management of severe COVID‐19 patients. This article is protected by copyright. All rights reserved.

Published
2020
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44. Myelodysplasia as assessed by multiparameter flow cytometry refines prognostic stratification provided by genotypic risk in systemic mastocytosis

Author

Francesco Annunziato, Luigi Scaffidi, Annalisa Pacilli, Roberta Zanotti, Federica Irene Grifoni, Lisa Pieri, Fiorina Giona, Paola Guglielmelli, Alessandro M. Vannucchi, Francesca Gesullo, Giada Rotunno, Sara Bencini, Michelina Santopietro, and Francesco Mannelli

Subjects
Oncology, High-risk mutations, medicine.medical_specialty, Multivariate analysis, Genotype, Myelodysplasia, systemic mastocytosis, Immunophenotyping, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Mastocytosis, Systemic, Internal medicine, medicine, Humans, Systemic mastocytosis, Survival analysis, business.industry, Myelodysplastic syndromes, Hematology, Flow Cytometry, Prognosis, medicine.disease, Survival Analysis, Proto-Oncogene Proteins c-kit, Dysplasia, Myelodysplastic Syndromes, 030220 oncology & carcinogenesis, Mutation, Cohort, business, 030215 immunology, Cohort study
Abstract

Systemic mastocytosis (SM) is characterized by extreme heterogeneity of manifestations and prognosis. Several disease-related biomarkers, including clinical, hematological and molecular variables, have been correlated with prognosis. Although relevant, the mutation profile closely reflects the WHO classification that has per se prognostic value. High-risk mutations (HRM) are largely confined to advanced forms, and thus fail in providing information regarding progression and outcome in the not-advanced variants. In this work, we studied hematopoietic cells by multi-parameter flow cytometry (MFC) in order to highlight dysplastic traits that might provide insights into outcome. A score previously validated for myelodysplastic syndromes, with high reproducibility in standard diagnostics, was used. The application of an MFC score to a cohort of 71 SM cases, concurrently genotyped for configuring a HRM category, resulted in the identification of two separate patients' categories (MFC+ and MFC-) characterized by significantly different clinical and laboratory features at presentation. The extent of dysplasia by MFC tended to parallel WHO-category and genotype-related stratification. MFC+ patients had shorter survival compared to MFC- ones, for whom the incidence of progression and/or death was virtually null. Of note, MFC score remained prognostically informative in unadvanced subsets. Furthermore, the integration of MFC and HRM was an independent predictor for outcome, also overcoming WHO-categories in multivariate analysis for EFS. Our results support the use of MFC analysis in the evaluation of patients with SM, alone and in combination with HRM, for refinement of prognosis assessment.

Published
2019
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45. Author response for 'Comparing the safety and efficacy of ruxolitinib in patients with Dynamic International Prognostic Scoring System low‐, intermediate‐1‐, intermediate‐2‐, and high‐risk myelofibrosis in JUMP, a Phase 3b, expanded‐access study'

Author

null Francesco Passamonti, null Vikas Gupta, null Bruno Martino, null Lynda Foltz, null Andrey Zaritskey, null Haifa Kathrin Al‐Ali, null Renato Tavares, null Margherita Maffioli, null Pia Raanani, null Pilar Giraldo, null Martin Griesshammer, null Paola Guglielmelli, null Catherine Bouard, null Carole Paley, null Ranjan Tiwari, and null Alessandro M. Vannucchi

Published
2021
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47. Clinical and molecular predictors of fibrotic progression in essential thrombocythemia: A multicenter study involving 1607 patients

Author

Loscocco, Giuseppe G., primary, Guglielmelli, Paola, additional, Gangat, Naseema, additional, Rossi, Elena, additional, Mannarelli, Carmela, additional, Betti, Silvia, additional, Maccari, Chiara, additional, Ramundo, Francesco, additional, Jadoon, Yamna, additional, Gesullo, Francesca, additional, Ceglie, Sara, additional, Paoli, Chiara, additional, Pardanani, Animesh, additional, De Stefano, Valerio, additional, Tefferi, Ayalew, additional, and Vannucchi, Alessandro M., additional

Published
2021
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48. Impaired response to first SARS‐CoV ‐2 dose vaccination in myeloproliferative neoplasm patients receiving ruxolitinib

Author

Guglielmelli, Paola, primary, Mazzoni, Alessio, additional, Maggi, Laura, additional, Kiros, Seble Tekle, additional, Zammarchi, Lorenzo, additional, Pilerci, Sofia, additional, Rocca, Arianna, additional, Spinicci, Michele, additional, Borella, Miriam, additional, Bartoloni, Alessandro, additional, Rossolini, Gian Maria, additional, Annunziato, Francesco, additional, and Vannucchi, Alessandro M., additional

Published
2021
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49. Ventricular tachyarrhythmias and sudden cardiac death in light‐chain amyloidosis: a clash of cardio‐toxicities?

Author

Carlo Fumagalli, Alessia Argirò, Giulia Nardi, Carlo Di Mario, Federico Perfetto, Marco Allinovi, Alessandro M. Vannucchi, Mattia Zampieri, Iacopo Olivotto, Francesco Cappelli, Martina Gabriele, and Elisabetta Antonioli

Subjects
Male, medicine.medical_specialty, Chemotherapy, business.industry, Ventricular Tachyarrhythmias, Amyloidosis, medicine.medical_treatment, Hematology, Middle Aged, medicine.disease, Immunoglobulin light chain, Sudden cardiac death, Death, Sudden, Cardiac, Internal medicine, Tachycardia, Ventricular, Cardiology, Humans, Medicine, Immunoglobulin Light-chain Amyloidosis, business, Aged
Published
2021
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50. Comparing the safety and efficacy of ruxolitinib in patients with Dynamic International Prognostic Scoring System low‐, intermediate‐1‐, intermediate‐2‐, and high‐risk myelofibrosis in JUMP, a Phase 3b, expanded‐access study

Author

Passamonti, Francesco, primary, Gupta, Vikas, additional, Martino, Bruno, additional, Foltz, Lynda, additional, Zaritskey, Andrey, additional, Al‐Ali, Haifa Kathrin, additional, Tavares, Renato, additional, Maffioli, Margherita, additional, Raanani, Pia, additional, Giraldo, Pilar, additional, Griesshammer, Martin, additional, Guglielmelli, Paola, additional, Bouard, Catherine, additional, Paley, Carole, additional, Tiwari, Ranjan, additional, and Vannucchi, Alessandro M., additional

Published
2021
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