title: Safety and efficacy of ruxolitinib in splanchnic vein thrombosis associated with myeloproliferative neoplasms.
abstract: Splanchnic vein thrombosis (SVT) is one of the vascular complications of myeloproliferative neoplasms (MPN). We designed a phase 2 clinical trial to evaluate safety and efficacy of ruxolitinib in reducing splenomegaly and improving disease-related symptoms in patients with MPN-associated SVT. Patients diagnosed with myelofibrosis (12 cases), polycythemia vera (5 cases) and essential thrombocythemia (4 cases) received ruxolitinib for 24 weeks in the core study period. Spleen volume was assessed by magnetic resonance imaging (MRI) and splanchnic vein circulation by echo-Doppler analysis. Nineteen patients carried JAK2V617F, one had MPLW515L, and one CALRL367fs*46 mutation. Eighteen patients had spleno-portal-mesenteric thrombosis, two had Budd-Chiari syndrome, and one had both sites involved; 16 patients had esophageal varices. Ruxolitinib was well tolerated with hematological toxicities consistent with those of patients without SVT and no hemorrhagic adverse events were recorded. After 24 weeks of treatment, spleen volume reduction ≥35% by MRI was achieved by 6/21 (29%) patients, and a ≥50% spleen length reduction by palpation at any time up to week 24 was obtained by 13/21 (62%) patients. At week 72, 8 of the 13 (62%) patients maintained the spleen response by palpation. No significant effect of treatment on esophageal varices or in splanchnic circulation was observed. MPN-related symptoms, evaluated by MPN-symptom assessment form (SAF) TSS questionnaire, improved significantly during the first 4 weeks and remained stable up to week 24. In conclusion, this trial shows that ruxolitinib is safe in patients with MPN-associated SVT, and effective in reducing spleen size and disease-related symptoms.
authors.affiliation: CRIMM-Centro Ricerca e Innovazione per le Malattie Mieloproliferative, Azienda Ospedaliera-Universitaria Careggi, Florence, Italy.|DenoThe Excellence Center, Florence, Italy.|Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Lisa
authors.initials: L
authors.lastname: Pieri
authors.affiliation: CRIMM-Centro Ricerca e Innovazione per le Malattie Mieloproliferative, Azienda Ospedaliera-Universitaria Careggi, Florence, Italy.|DenoThe Excellence Center, Florence, Italy.|Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Paoli
authors.affiliation: Internal Medicine and Hepatology, Azienda Ospedaliera-Universitaria Careggi, Florence, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Arena
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Marra
authors.affiliation: Department of Cardiology, Azienda Ospedaliera-Universitaria Careggi, Florence, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Mori
authors.affiliation: Department of Cardiology, Azienda Ospedaliera-Universitaria Careggi, Florence, Italy.
authors.forename: Mery
authors.initials: M
authors.lastname: Zucchini
authors.affiliation: Department of Experimental and Clinical Biomedical Sciences, University of Florence - Azienda Ospedaliera-Universitaria Careggi, Florence, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Colagrande
authors.affiliation: Department of Experimental and Clinical Biomedical Sciences, University of Florence - Azienda Ospedaliera-Universitaria Careggi, Florence, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Castellani
authors.affiliation: Department of Hematology, Hospital Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: Arianna
authors.initials: A
authors.lastname: Masciulli
authors.affiliation: IRCCS Policlinico San Matteo Foundation, Center for the Study of Myelofibrosis, Biotechnology Research Area, Pavia, Italy.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Rosti
authors.affiliation: Institute of Hematology, Catholic University, Rome, Italy.
authors.forename: Valerio
authors.initials: V
authors.lastname: De Stefano
authors.affiliation: Institute of Hematology, Catholic University, Rome, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Betti
authors.affiliation: Department of Hematology, Hospital Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Finazzi
authors.affiliation: Department of Hematology, Hospital Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Ferrari
authors.affiliation: Department of Hematology Oncology, IRCCS Policlinico San Matteo Foundation, Pavia, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Rumi
authors.affiliation: Department of Hematology, San Bortolo Hospital, Vicenza, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Ruggeri
authors.affiliation: Department of Hematology, San Bortolo Hospital, Vicenza, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Nichele
authors.affiliation: CRIMM-Centro Ricerca e Innovazione per le Malattie Mieloproliferative, Azienda Ospedaliera-Universitaria Careggi, Florence, Italy.|DenoThe Excellence Center, Florence, Italy.|Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Guglielmelli
authors.affiliation: CRIMM-Centro Ricerca e Innovazione per le Malattie Mieloproliferative, Azienda Ospedaliera-Universitaria Careggi, Florence, Italy.|DenoThe Excellence Center, Florence, Italy.|Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Rajmonda
authors.initials: R
authors.lastname: Fjerza
authors.affiliation: CRIMM-Centro Ricerca e Innovazione per le Malattie Mieloproliferative, Azienda Ospedaliera-Universitaria Careggi, Florence, Italy.|DenoThe Excellence Center, Florence, Italy.|Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: Mannarelli
authors.affiliation: CRIMM-Centro Ricerca e Innovazione per le Malattie Mieloproliferative, Azienda Ospedaliera-Universitaria Careggi, Florence, Italy.|DenoThe Excellence Center, Florence, Italy.|Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.|University of Siena, Siena, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Fanelli
authors.affiliation: CRIMM-Centro Ricerca e Innovazione per le Malattie Mieloproliferative, Azienda Ospedaliera-Universitaria Careggi, Florence, Italy.|DenoThe Excellence Center, Florence, Italy.|Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Merli
authors.affiliation: CRIMM-Centro Ricerca e Innovazione per le Malattie Mieloproliferative, Azienda Ospedaliera-Universitaria Careggi, Florence, Italy.|DenoThe Excellence Center, Florence, Italy.|Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.|University of Siena, Siena, Italy.
authors.forename: Giuditta
authors.initials: G
authors.lastname: Corbizi Fattori
authors.affiliation: IRCCS Policlinico San Matteo Foundation, Biotechnology Research Area, Pavia, Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Massa
authors.affiliation: Department of Cellular Biotechnology and Hematology, University "La Sapienza", Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cimino
authors.affiliation: Department of Hematology, Hospital Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Rambaldi
authors.affiliation: IRCCS Policlinico San Matteo Foundation, Center for the Study of Myelofibrosis, Biotechnology Research Area, Pavia, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Barosi
authors.affiliation: Department of Hematology Oncology, IRCCS Policlinico San Matteo Foundation, Pavia, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Cazzola
authors.affiliation: Hospital Papa Giovanni XXIII and Research Foundation, Bergamo, Italy.
authors.forename: Tiziano
authors.initials: T
authors.lastname: Barbui
authors.affiliation: CRIMM-Centro Ricerca e Innovazione per le Malattie Mieloproliferative, Azienda Ospedaliera-Universitaria Careggi, Florence, Italy.|DenoThe Excellence Center, Florence, Italy.|Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Alessandro M
authors.initials: AM
authors.lastname: Vannucchi
mesh_terms: D000328:Adult; D000368:Aged; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D053612:Janus Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009196:Myeloproliferative Disorders / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D009570:Nitriles; D010976:Platelet Count; D011720:Pyrazoles / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D011743:Pyrimidines; D013152:Splanchnic Circulation / Q000187:drug effects*; D013163:Splenomegaly / Q000517:prevention & control; D016896:Treatment Outcome; D020246:Venous Thrombosis / Q000097:blood / Q000209:etiology / Q000517:prevention & control*
chemical_list: D009570:Nitriles; D011720:Pyrazoles; D011743:Pyrimidines; C540383:ruxolitinib; D053612:Janus Kinases