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314 results on '"Cilloni D"'

1. Strategies for minimal residual disease detection: current perspectives

Author

Andreani G and Cilloni D

Subjects
Minimal residual disease, Acute leukemia, multiparameter flow cytomethy, real-time quantitave polymerase chain reaction, next generation sequencing, digital PCR, Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Giacomo Andreani, Daniela Cilloni Department of Clinical and Biological Sciences, University of Turin, Turin, Italy Abstract: Currently, the post-remission treatment in acute leukemia is based on the genetic profile of leukemic cells at diagnosis (ie, FLT3 ITD positivity) and on the level of measurable residual disease (MRD) after induction and consolidation chemotherapy. Two methods are currently preferred for MRD evaluation in many centers: multiparameter flow cytometry and real-time quantitative PCR. Additional methods such as next-generation sequencing and digital PCR are under investigation, in an attempt to increase the sensitivity and thus allowing the detection of small clones. Many studies suggest that MRD positivity after chemotherapy is associated with negative prognosis, and the reappearance of MRD during follow-up allows impending relapse to be identified and consequently enables early intervention. Finally, MRD positivity before hematopoietic stem cell transplantation is predictive of the outcome. Although the significance of MRD in acute leukemia has been widely explored, the assessment of molecular MRD is not yet a routine practice. In this review, we describe the significance of MRD in different settings and the main markers and methods used for MRD detection. Keywords: minimal residual disease, acute leukemia, multiparameter flow cytometry, real-time quantitative polymerase chain reaction, next-generation sequencing, digital PCR

Published
2019

2. First-hit SETBP1 mutations cause a myeloproliferative disorder with bone marrow fibrosis

Author

Crespiatico, I, Zaghi, M, Mastini, C, D'Aliberti, D, Mauri, M, Mercado, C, Fontana, D, Spinelli, S, Crippa, V, Inzoli, E, Manghisi, B, Civettini, I, Ramazzotti, D, Sangiorgio, V, Gengotti, M, Brambilla, V, Aroldi, A, Banfi, F, Barone, C, Orsenigo, R, Riera, L, Riminucci, M, Corsi, A, Breccia, M, Morotti, A, Cilloni, D, Roccaro, A, Sacco, A, Stagno, F, Serafini, M, Mottadelli, F, Cazzaniga, G, Pagni, F, Chiarle, R, Azzoni, E, Sessa, A, Gambacorti Passerini, C, Elli, E, Mologni, L, Piazza, R, Crespiatico I., Zaghi M., Mastini C., D'Aliberti D., Mauri M., Mercado C. M., Fontana D., Spinelli S., Crippa V., Inzoli E., Manghisi B., Civettini I., Ramazzotti D., Sangiorgio V., Gengotti M., Brambilla V., Aroldi A., Banfi F., Barone C., Orsenigo R., Riera L., Riminucci M., Corsi A., Breccia M., Morotti A., Cilloni D., Roccaro A., Sacco A., Stagno F., Serafini M., Mottadelli F., Cazzaniga G., Pagni F., Chiarle R., Azzoni E., Sessa A., Gambacorti Passerini C., Elli E. M., Mologni L., Piazza R., Crespiatico, I, Zaghi, M, Mastini, C, D'Aliberti, D, Mauri, M, Mercado, C, Fontana, D, Spinelli, S, Crippa, V, Inzoli, E, Manghisi, B, Civettini, I, Ramazzotti, D, Sangiorgio, V, Gengotti, M, Brambilla, V, Aroldi, A, Banfi, F, Barone, C, Orsenigo, R, Riera, L, Riminucci, M, Corsi, A, Breccia, M, Morotti, A, Cilloni, D, Roccaro, A, Sacco, A, Stagno, F, Serafini, M, Mottadelli, F, Cazzaniga, G, Pagni, F, Chiarle, R, Azzoni, E, Sessa, A, Gambacorti Passerini, C, Elli, E, Mologni, L, Piazza, R, Crespiatico I., Zaghi M., Mastini C., D'Aliberti D., Mauri M., Mercado C. M., Fontana D., Spinelli S., Crippa V., Inzoli E., Manghisi B., Civettini I., Ramazzotti D., Sangiorgio V., Gengotti M., Brambilla V., Aroldi A., Banfi F., Barone C., Orsenigo R., Riera L., Riminucci M., Corsi A., Breccia M., Morotti A., Cilloni D., Roccaro A., Sacco A., Stagno F., Serafini M., Mottadelli F., Cazzaniga G., Pagni F., Chiarle R., Azzoni E., Sessa A., Gambacorti Passerini C., Elli E. M., Mologni L., and Piazza R.

Abstract

SETBP1 mutations are found in various clonal myeloid disorders. However, it is unclear whether they can initiate leukemia, because SETBP1 mutations typically appear as later events during oncogenesis. To answer this question, we generated a mouse model expressing mutated SETBP1 in hematopoietic tissue: this model showed profound alterations in the differentiation program of hematopoietic progenitors and developed a myeloid neoplasm with megakaryocytic dysplasia, splenomegaly, and bone marrow fibrosis, prompting us to investigate SETBP1 mutations in a cohort of 36 triple-negative primary myelofibrosis (TN-PMF) cases. We identified 2 distinct subgroups, one carrying SETBP1 mutations and the other completely devoid of somatic variants. Clinically, a striking difference in disease aggressiveness was noted, with patients with SETBP1 mutation showing a much worse clinical course. In contrast to myelodysplastic/myeloproliferative neoplasms, in which SETBP1 mutations are mostly found as a late clonal event, single-cell clonal hierarchy reconstruction in 3 patients with TN-PMF from our cohort revealed SETBP1 to be a very early event, suggesting that the phenotype of the different SETBP1+ disorders may be shaped by the opposite hierarchy of the same clonal SETBP1 variants.

Published
2024

3. SARS-CoV-2 infection in patients with chronic lymphocytic leukemia: The Italian Hematology Alliance on COVID-19 cohort

Author

Merli, M, Ferrarini, I, Merli, F, Busca, A, Mina, R, Falini, B, Bruna, R, Cairoli, R, Marchetti, M, Romano, A, Cavo, M, Arcaini, L, Trentin, L, Cattaneo, C, Derenzini, E, Fracchiolla, N, Marchesi, F, Scattolin, A, Billio, A, Bocchia, M, Massaia, M, Gambacorti-Passerini, C, Mauro, F, Gentile, M, Mohamed, S, Della Porta, M, Coviello, E, Cilloni, D, Visani, G, Federici, A, Tisi, M, Cudillo, L, Galimberti, S, Gherlinzoni, F, Pagano, L, Guidetti, A, Bertu, L, Corradini, P, Passamonti, F, Visco, C, Merli M., Ferrarini I., Merli F., Busca A., Mina R., Falini B., Bruna R., Cairoli R., Marchetti M., Romano A., Cavo M., Arcaini L., Trentin L., Cattaneo C., Derenzini E., Fracchiolla N. S., Marchesi F., Scattolin A., Billio A., Bocchia M., Massaia M., Gambacorti-Passerini C., Mauro F. R., Gentile M., Mohamed S., Della Porta M. G., Coviello E., Cilloni D., Visani G., Federici A. B., Tisi M. C., Cudillo L., Galimberti S., Gherlinzoni F., Pagano L., Guidetti A., Bertu L., Corradini P., Passamonti F., Visco C., Merli, M, Ferrarini, I, Merli, F, Busca, A, Mina, R, Falini, B, Bruna, R, Cairoli, R, Marchetti, M, Romano, A, Cavo, M, Arcaini, L, Trentin, L, Cattaneo, C, Derenzini, E, Fracchiolla, N, Marchesi, F, Scattolin, A, Billio, A, Bocchia, M, Massaia, M, Gambacorti-Passerini, C, Mauro, F, Gentile, M, Mohamed, S, Della Porta, M, Coviello, E, Cilloni, D, Visani, G, Federici, A, Tisi, M, Cudillo, L, Galimberti, S, Gherlinzoni, F, Pagano, L, Guidetti, A, Bertu, L, Corradini, P, Passamonti, F, Visco, C, Merli M., Ferrarini I., Merli F., Busca A., Mina R., Falini B., Bruna R., Cairoli R., Marchetti M., Romano A., Cavo M., Arcaini L., Trentin L., Cattaneo C., Derenzini E., Fracchiolla N. S., Marchesi F., Scattolin A., Billio A., Bocchia M., Massaia M., Gambacorti-Passerini C., Mauro F. R., Gentile M., Mohamed S., Della Porta M. G., Coviello E., Cilloni D., Visani G., Federici A. B., Tisi M. C., Cudillo L., Galimberti S., Gherlinzoni F., Pagano L., Guidetti A., Bertu L., Corradini P., Passamonti F., and Visco C.

Abstract

COVID-19, the disease caused by SARS-CoV-2, is still afflicting thousands of people across the globe. Few studies on COVID-19 in chronic lymphocytic leukemia (CLL) are available. Here, we analyzed data from the CLL cohort of the Italian Hematology Alliance on COVID-19 (NCT04352556), which included 256 CLL patients enrolled between 25 February 2020 and 1 February 2021. Median age was 70 years (range 38–94) with male preponderance (60.1%). Approximately half of patients (n = 127) had received at least one line of therapy for CLL, including 108 (83.7%) who were on active treatment at the time of COVID-19 or received their last therapy within 12 months. Most patients (230/256, 89.9%) were symptomatic at COVID-19 diagnosis and the majority required hospitalization (n = 176). Overall, after a median follow-up of 42 days (IQR 24–96), case fatality rate was 30.1%, and it was 37.5% and 24.4% in the first (25 February 2020–22 June 2020) and second wave (23 June 2020–1 February 2021), respectively (p = 0.03). At multivariate analysis, male sex (HR 1.82, 95% CI 1.03–3.24, p = 0.04), age over than 70 years (HR 2.23, 95% CI 1.23–4.05, p = 0.01), any treatment for CLL given in the last 12 months (HR 1.72, 95% CI 1.04–2.84, p = 0.04) and COVID-19 severity (severe: HR 5.66, 95% CI 2.62–12.33, p < 0.0001; critical: HR 15.99, 95% CI 6.93–36.90, p < 0.0001) were independently associated with poor survival. In summary, we report a dismal COVID-related outcome in a significant fraction of CLL patients, that can be nicely predicted by clinical parameters.

Published
2023

4. AVALON: The Italian cohort study on real-life efficacy of hypomethylating agents plus venetoclax in newly diagnosed or relapsed/refractory patients with acute myeloid leukemia

Author

Todisco, E, Papayannidis, C, Fracchiolla, N, Petracci, E, Zingaretti, C, Vetro, C, Martelli, M, Zappasodi, P, Di Renzo, N, Gallo, S, Audisio, E, Griguolo, D, Cerchione, C, Selleri, C, Mattei, D, Bernardi, M, Fumagalli, M, Rizzuto, G, Facchini, L, Basilico, C, Manfra, I, Borlenghi, E, Cairoli, R, Salutari, P, Gottardi, M, Molteni, A, Martini, V, Lunghi, M, Fianchi, L, Cilloni, D, Lanza, F, Abruzzese, E, Cascavilla, N, Rivellini, F, Ferrara, F, Maurillo, L, Nanni, J, Romano, A, Cardinali, V, Gigli, F, Roncoroni, E, Federico, V, Marconi, G, Volpi, R, Sciumè, M, Tarella, C, Rossi, G, Martinelli, G, Todisco E, Papayannidis C, Fracchiolla N, Petracci E, Zingaretti C, Vetro C, Martelli MP, Zappasodi P, Di Renzo N, Gallo S, Audisio E, Griguolo D, Cerchione C, Selleri C, Mattei D, Bernardi M, Fumagalli M, Rizzuto G, Facchini L, Basilico CM, Manfra I, Borlenghi E, Cairoli R, Salutari P, Gottardi M, Molteni A, Martini V, Lunghi M, Fianchi L, Cilloni D, Lanza F, Abruzzese E, Cascavilla N, Rivellini F, Ferrara F, Maurillo L, Nanni J, Romano A, Cardinali V, Gigli F, Roncoroni E, Federico V, Marconi G, Volpi R, Sciumè M, Tarella C, Rossi G, Martinelli G, Todisco, E, Papayannidis, C, Fracchiolla, N, Petracci, E, Zingaretti, C, Vetro, C, Martelli, M, Zappasodi, P, Di Renzo, N, Gallo, S, Audisio, E, Griguolo, D, Cerchione, C, Selleri, C, Mattei, D, Bernardi, M, Fumagalli, M, Rizzuto, G, Facchini, L, Basilico, C, Manfra, I, Borlenghi, E, Cairoli, R, Salutari, P, Gottardi, M, Molteni, A, Martini, V, Lunghi, M, Fianchi, L, Cilloni, D, Lanza, F, Abruzzese, E, Cascavilla, N, Rivellini, F, Ferrara, F, Maurillo, L, Nanni, J, Romano, A, Cardinali, V, Gigli, F, Roncoroni, E, Federico, V, Marconi, G, Volpi, R, Sciumè, M, Tarella, C, Rossi, G, Martinelli, G, Todisco E, Papayannidis C, Fracchiolla N, Petracci E, Zingaretti C, Vetro C, Martelli MP, Zappasodi P, Di Renzo N, Gallo S, Audisio E, Griguolo D, Cerchione C, Selleri C, Mattei D, Bernardi M, Fumagalli M, Rizzuto G, Facchini L, Basilico CM, Manfra I, Borlenghi E, Cairoli R, Salutari P, Gottardi M, Molteni A, Martini V, Lunghi M, Fianchi L, Cilloni D, Lanza F, Abruzzese E, Cascavilla N, Rivellini F, Ferrara F, Maurillo L, Nanni J, Romano A, Cardinali V, Gigli F, Roncoroni E, Federico V, Marconi G, Volpi R, Sciumè M, Tarella C, Rossi G, and Martinelli G

Abstract

Background: Venetoclax in combination with hypomethylating agents (HMA) is revolutionizing the therapy of acute myeloid leukemia (AML). However, evidence on large sets of patients is lacking, especially in relapsed or refractory leukemia. Methods: AVALON is a multicentric cohort study that was conducted in Italy on patients with AML who received venetoclax-based therapies from 2015 to 2020. The study was approved by the ethics committee of the participating institution and was conducted in accordance with the Declaration of Helsinki. The effectiveness and toxicity of venetoclax + HMA in 190 (43 newly diagnosed, 68 refractory, and 79 relapsed) patients with AML are reported here. Results: In the newly diagnosed AML, the overall response rate and survival confirmed the brilliant results demonstrated in VIALE-A. In the relapsed or refractory AML, the combination demonstrated a surprisingly complete remission rate (44.1% in refractory and 39.7% in relapsed evaluable patients) and conferred to treated patients a good expectation of survival. Toxicities were overall manageable, and most incidents occurred in the first 60 days of therapy. Infections were confirmed as the most common nonhematologic adverse event. Conclusions: Real-life data show that the combination of venetoclax and HMA offers an expectation of remission and long-term survival to elderly, newly diagnosed patients, and to relapsed or chemoresistant AML, increasing the chance of cure through a different mechanism of action. The venetoclax + HMA combination is expected to constitute the base for triplet combinations and integration of target therapies. Our data contribute to ameliorate the understanding of venetoclax + HMA effectiveness and toxicities in real life.

Published
2023

5. Deferasirox in the management of iron overload in patients with myelofibrosis treated with ruxolitinib: The multicentre retrospective RUX-IOL study

Author

Elli, E, Di Veroli, A, Bartoletti, D, Iurlo, A, Carmosino, I, Benevolo, G, Abruzzese, E, Bonifacio, M, Bergamaschi, M, Polverelli, N, Caramella, M, Cilloni, D, Tiribelli, M, Pugliese, N, Caocci, G, Crisa, E, Porrini, R, Markovic, U, Renso, R, Auteri, G, Cattaneo, D, Trawinska, M, Scaffidi, L, Biale, L, Bucelli, C, Breccia, M, Gambacorti Passerini, C, Palumbo, G, Latagliata, R, Palandri, F, Elli E. M., Di Veroli A., Bartoletti D., Iurlo A., Carmosino I., Benevolo G., Abruzzese E., Bonifacio M., Bergamaschi M., Polverelli N., Caramella M., Cilloni D., Tiribelli M., Pugliese N., Caocci G., Crisa E., Porrini R., Markovic U., Renso R., Auteri G., Cattaneo D., Trawinska M. M., Scaffidi L., Biale L., Bucelli C., Breccia M., Gambacorti Passerini C., Palumbo G. A., Latagliata R., Palandri F., Elli, E, Di Veroli, A, Bartoletti, D, Iurlo, A, Carmosino, I, Benevolo, G, Abruzzese, E, Bonifacio, M, Bergamaschi, M, Polverelli, N, Caramella, M, Cilloni, D, Tiribelli, M, Pugliese, N, Caocci, G, Crisa, E, Porrini, R, Markovic, U, Renso, R, Auteri, G, Cattaneo, D, Trawinska, M, Scaffidi, L, Biale, L, Bucelli, C, Breccia, M, Gambacorti Passerini, C, Palumbo, G, Latagliata, R, Palandri, F, Elli E. M., Di Veroli A., Bartoletti D., Iurlo A., Carmosino I., Benevolo G., Abruzzese E., Bonifacio M., Bergamaschi M., Polverelli N., Caramella M., Cilloni D., Tiribelli M., Pugliese N., Caocci G., Crisa E., Porrini R., Markovic U., Renso R., Auteri G., Cattaneo D., Trawinska M. M., Scaffidi L., Biale L., Bucelli C., Breccia M., Gambacorti Passerini C., Palumbo G. A., Latagliata R., and Palandri F.

Abstract

Deferasirox (DFX) is used for the management of iron overload (IOL) in many haematological malignancies including myelofibrosis (MF). The ‘RUX-IOL’ study retrospectively collected 69 MF patients treated with ruxolitinib (RUX) and DFX for IOL to assess: safety, efficacy in term of iron chelation response (ICR) and erythroid response (ER), and impact on overall survival of the combination therapy. The RUX–DFX therapy was administered for a median time of 12.4 months (interquartile range 3.1–71.2). During treatment, 36 (52.2%) and 34 (49.3%) patients required RUX and DFX dose reductions, while eight (11.6%) and nine (13.1%) patients discontinued due to RUX- or DFX-related adverse events; no unexpected toxicity was reported. ICR and ER were achieved by 33 (47.8%) and 32 patients (46.4%) respectively. Thirteen (18.9%) patients became transfusion-independent. Median time to ICR and ER was 6.2 and 2 months respectively. Patients achieving an ER were more likely to obtain an ICR also (p = 0.04). In multivariable analysis, the absence of leukocytosis at baseline (p = 0.02) and achievement of an ICR at any time (p = 0.02) predicted improved survival. In many MF patients, the RUX–DFX combination provided ICR and ER responses that correlated with improved outcome in the absence of unexpected toxicities. This strategy deserves further clinical investigation.

Published
2022

6. A prognostic model for patients with lymphoma and COVID-19: a multicentre cohort study

Author

Visco, C, Marcheselli, L, Mina, R, Sassone, M, Guidetti, A, Penna, D, Cattaneo, C, Bonuomo, V, Busca, A, Ferreri, A, Bruna, R, Petrucci, L, Cairoli, R, Salvini, M, Bertu, L, Ladetto, M, Pilerci, S, Pinto, A, Ramadan, S, Marchesi, F, Cavo, M, Arcaini, L, Coviello, E, Romano, A, Musto, P, Massaia, M, Fracchiolla, N, Marchetti, M, Scattolin, A, Tisi, M, Cuneo, A, Porta, M, Trentin, L, Turrini, M, Gherlinzoni, F, Tafuri, A, Galimberti, S, Bocchia, M, Cardinali, V, Cilloni, D, Corso, A, Armiento, D, Rigacci, L, La Barbera, E, Gambacorti Passerini, C, Visani, G, Vallisa, D, Venditti, A, Selleri, C, Conconi, A, Tosi, P, Lanza, F, Candoni, A, Krampera, M, Corradini, P, Passamonti, F, Merli, F, Visco C., Marcheselli L., Mina R., Sassone M., Guidetti A., Penna D., Cattaneo C., Bonuomo V., Busca A., Ferreri A. J. M., Bruna R., Petrucci L., Cairoli R., Salvini M., Bertu L., Ladetto M., Pilerci S., Pinto A., Ramadan S., Marchesi F., Cavo M., Arcaini L., Coviello E., Romano A., Musto P., Massaia M., Fracchiolla N., Marchetti M., Scattolin A., Tisi M. C., Cuneo A., Porta M. D., Trentin L., Turrini M., Gherlinzoni F., Tafuri A., Galimberti S., Bocchia M., Cardinali V., Cilloni D., Corso A., Armiento D., Rigacci L., La Barbera E. O., Gambacorti Passerini C., Visani G., Vallisa D., Venditti A., Selleri C., Conconi A., Tosi P., Lanza F., Candoni A., Krampera M., Corradini P., Passamonti F., Merli F., Visco, C, Marcheselli, L, Mina, R, Sassone, M, Guidetti, A, Penna, D, Cattaneo, C, Bonuomo, V, Busca, A, Ferreri, A, Bruna, R, Petrucci, L, Cairoli, R, Salvini, M, Bertu, L, Ladetto, M, Pilerci, S, Pinto, A, Ramadan, S, Marchesi, F, Cavo, M, Arcaini, L, Coviello, E, Romano, A, Musto, P, Massaia, M, Fracchiolla, N, Marchetti, M, Scattolin, A, Tisi, M, Cuneo, A, Porta, M, Trentin, L, Turrini, M, Gherlinzoni, F, Tafuri, A, Galimberti, S, Bocchia, M, Cardinali, V, Cilloni, D, Corso, A, Armiento, D, Rigacci, L, La Barbera, E, Gambacorti Passerini, C, Visani, G, Vallisa, D, Venditti, A, Selleri, C, Conconi, A, Tosi, P, Lanza, F, Candoni, A, Krampera, M, Corradini, P, Passamonti, F, Merli, F, Visco C., Marcheselli L., Mina R., Sassone M., Guidetti A., Penna D., Cattaneo C., Bonuomo V., Busca A., Ferreri A. J. M., Bruna R., Petrucci L., Cairoli R., Salvini M., Bertu L., Ladetto M., Pilerci S., Pinto A., Ramadan S., Marchesi F., Cavo M., Arcaini L., Coviello E., Romano A., Musto P., Massaia M., Fracchiolla N., Marchetti M., Scattolin A., Tisi M. C., Cuneo A., Porta M. D., Trentin L., Turrini M., Gherlinzoni F., Tafuri A., Galimberti S., Bocchia M., Cardinali V., Cilloni D., Corso A., Armiento D., Rigacci L., La Barbera E. O., Gambacorti Passerini C., Visani G., Vallisa D., Venditti A., Selleri C., Conconi A., Tosi P., Lanza F., Candoni A., Krampera M., Corradini P., Passamonti F., and Merli F.

Abstract

Lymphoma represents a heterogeneous hematological malignancy (HM), which is characterized by severe immunosuppression. Patients diagnosed of coronavirus disease 2019 (COVID-19) during the course of HM have been described to have poor outcome, with only few reports specifically addressing lymphoma patients. Here, we investigated the clinical behavior and clinical parameters of a large multicenter cohort of adult patients with different lymphoma subtypes, with the aim of identifying predictors of death. The study included 856 patients, of whom 619 were enrolled prospectively in a 1-year frame and were followed-up for a median of 66 days (range 1-395). Patients were managed as outpatient (not-admitted cohort, n 5 388) or required hospitalization (n 5 468), and median age was 63 years (range 19-94). Overall, the 30- and 100-days mortality was 13% (95% confidence interval (CI), 11% to 15%) and 23% (95% CI, 20% to 27%), respectively. Antilymphoma treatment, including anti-CD20 containing regimens, did not impact survival. Patients with Hodgkin’s lymphoma had the more favorable survival, but this was partly related to significantly younger age. The time interval between lymphoma diagnosis and COVID-19 was inversely related to mortality. Multivariable analysis recognized 4 easy-to-use factors (age, gender, lymphocyte, and platelet count) that were associated with risk of death, both in the admitted and in the not-admitted cohort (HR 3.79 and 8.85 for the intermediate- and high-risk group, respectively). Overall, our study shows that patients should not be deprived of the best available treatment of their underlying disease and indicates which patients are at higher risk of death. This study was registered with ClinicalTrials.gov, NCT04352556.

Published
2022

7. Clonal hematopoiesis by DNMT3A mutations as a common finding in idiopathic splanchnic vein thrombosis

Author

Carrà, G, Giugliano, E, Camerlo, S, Rosati, G, Branca, E, Maffeo, B, Russo, I, Piazza, R, Cilloni, D, Morotti, A, Carrà, Giovanna, Giugliano, Emilia, Camerlo, Sofia, Rosati, Giorgio, Branca, Enrica, Maffeo, Beatrice, Russo, Isabella, Piazza, Rocco, Cilloni, Daniela, Morotti, Alessandro, Carrà, G, Giugliano, E, Camerlo, S, Rosati, G, Branca, E, Maffeo, B, Russo, I, Piazza, R, Cilloni, D, Morotti, A, Carrà, Giovanna, Giugliano, Emilia, Camerlo, Sofia, Rosati, Giorgio, Branca, Enrica, Maffeo, Beatrice, Russo, Isabella, Piazza, Rocco, Cilloni, Daniela, and Morotti, Alessandro

Published
2023

8. LABNET AML: AN EFFICIENT NETWORK THAT CONNECTS HEMATOLOGY CENTERS AND LABORATORIES FOR A HIGH-LEVEL DIAGNOSTIC/PROGNOSTIC WORKUP OF AML

Author

Voso, M, Cucci, R, Messina, M, Santoro, A, Divona, M, Albano, F, Ottaviani, E, Bertorelle, R, Guerrasio, A, Gottardi, E, Izzo, B, Tarantini, G, Scardocci, A, Siragusa, S, Forghieri, F, Cairoli, R, Cambo, B, Vallisa, D, Venditti, A, Ferrara, F, Mannina, D, Cilloni, D, La, S, Piciocchi, A, Falini, B, Pane, F, Saglio, G, Vignetti, M, Amadori, S, Voso MT, Cucci R, Messina M, Santoro A, Divona M, Albano F, Ottaviani E, Bertorelle R, Guerrasio A, Gottardi E, Izzo B, Tarantini G, Scardocci A, Siragusa S, Forghieri F, Cairoli R, Cambo B, Vallisa D, Venditti A, Ferrara F, Mannina D, Cilloni D, La SalaE, Piciocchi A, Falini B, Pane F, Saglio G, Vignetti M, Amadori S, Voso, M, Cucci, R, Messina, M, Santoro, A, Divona, M, Albano, F, Ottaviani, E, Bertorelle, R, Guerrasio, A, Gottardi, E, Izzo, B, Tarantini, G, Scardocci, A, Siragusa, S, Forghieri, F, Cairoli, R, Cambo, B, Vallisa, D, Venditti, A, Ferrara, F, Mannina, D, Cilloni, D, La, S, Piciocchi, A, Falini, B, Pane, F, Saglio, G, Vignetti, M, Amadori, S, Voso MT, Cucci R, Messina M, Santoro A, Divona M, Albano F, Ottaviani E, Bertorelle R, Guerrasio A, Gottardi E, Izzo B, Tarantini G, Scardocci A, Siragusa S, Forghieri F, Cairoli R, Cambo B, Vallisa D, Venditti A, Ferrara F, Mannina D, Cilloni D, La SalaE, Piciocchi A, Falini B, Pane F, Saglio G, Vignetti M, and Amadori S

Published
2021

9. The giant hect e3 ubiquitin ligase herc1 is aberrantly expressed in myeloid related disorders and it is a novel bcr-abl1 binding partner

Author

Ali, M, Panuzzo, C, Calabrese, C, Maglione, A, Piazza, R, Cilloni, D, Saglio, G, Pergolizzi, B, Bracco, E, Ali M. S., Panuzzo C., Calabrese C., Maglione A., Piazza R., Cilloni D., Saglio G., Pergolizzi B., Bracco E., Ali, M, Panuzzo, C, Calabrese, C, Maglione, A, Piazza, R, Cilloni, D, Saglio, G, Pergolizzi, B, Bracco, E, Ali M. S., Panuzzo C., Calabrese C., Maglione A., Piazza R., Cilloni D., Saglio G., Pergolizzi B., and Bracco E.

Abstract

HERC E3 subfamily members are parts of the E3 ubiquitin ligases and key players for a wide range of cellular functions. Though the involvement of the Ubiquitin Proteasome System in blood disorders has been broadly studied, so far the role of large HERCs in this context remains unexplored. In the present study we examined the expression of the large HECT E3 Ubiquitin Ligase, HERC1, in blood disorders. Our findings revealed that HERC1 gene expression was severely downregulated both in acute and in chronic myelogenous leukemia at diagnosis, while it is restored after complete remission achievement. Instead, in Philadelphia the negative myeloproliferative neoplasm HERC1 level was peculiarly controlled, being very low in Primary Myelofibrosis and significantly upregulated in those Essential Thrombocytemia specimens harboring the mutation in the calreticulin gene. Remarkably, in CML cells HERC1 mRNA level was associated with the BCR-ABL1 kinase activity and the HERC1 protein physically interacted with BCR-ABL1. Furthermore, we found that HERC1 was directly tyrosine phosphorylated by the ABL kinase. Overall and for the first time, we provide original evidence on the potential tumor-suppressing or-promoting properties, depending on the context, of HERC1 in myeloid related blood disorders.

Published
2021

10. P1010: RUXOLITINIB IN MYELODEPLETIVE MYELOFIBROSIS: RESPONSE, TOXICITY, AND OUTCOME

Author

Palandri, F., primary, Bartoletti, D., additional, Breccia, M., additional, Auteri, G., additional, Elli, E. M., additional, Trawinska, M. M., additional, Polverelli, N., additional, Tiribelli, M., additional, Benevolo, G., additional, Iurlo, A., additional, Tieghi, A., additional, Heidel, F. H., additional, Caocci, G., additional, Beggiato, E., additional, Binotto, G., additional, Cavazzini, F., additional, Miglino, M., additional, Bosi, C., additional, Crugnola, M., additional, Bocchia, M., additional, Martino, B., additional, Pugliese, N., additional, Romagnoli, A. D., additional, Mazzoni, C., additional, Scaffidi, L., additional, Isidori, A., additional, Cattaneo, D., additional, Krampera, M., additional, Pane, F., additional, Cilloni, D., additional, Semenzato, G., additional, Lemoli, R. M., additional, Cuneo, A., additional, Abruzzese, E., additional, Vianelli, N., additional, Cavo, M., additional, Bonifacio, M., additional, and Palumbo, G. A., additional

Published
2022
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12. P1011: PREDICTORS OF COVID-19 DISEASE AND SURVIVAL TO COVID-19 IN MPN PATIENTS TREATED WITH RUXOLITINIB

Author

Palandri, F., primary, Bartoletti, D., additional, Elli, E. M., additional, Auteri, G., additional, Bonifacio, M., additional, Benevolo, G., additional, Heidel, F., additional, Trawinska, M. M., additional, Rossi, E., additional, Bosi, C., additional, Tieghi, A., additional, Tiribelli, M., additional, Iurlo, A., additional, Polverelli, N., additional, Caocci, G., additional, Binotto, G., additional, Cavazzini, F., additional, Beggiato, E., additional, Cilloni, D., additional, Tatarelli, C., additional, Mendicino, F., additional, Miglino, M., additional, Bocchia, M., additional, Crugnola, M., additional, Mazzoni, C., additional, Romagnoli, A. D., additional, Rindone, G., additional, Ceglie, S., additional, D’Addio, A., additional, Santoni, E., additional, Cattaneo, D., additional, Lemoli, R. M., additional, Krampera, M., additional, Cuneo, A., additional, Semenzato, G., additional, Latagliata, R., additional, Abruzzese, E., additional, Vianelli, N., additional, Cavo, M., additional, Andriani, A., additional, De Stefano, V., additional, Palumbo, G., additional, and Breccia, M., additional

Published
2022
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14. Myeloablative conditioning with thiotepa-busulfan-fludarabine does not improve the outcome of patients transplanted with active leukemia: final results of the GITMO prospective trial GANDALF-01

Author

Bonifazi, F., Pavoni, C., Peccatori, J., Giglio, F., Arpinati, M., Busca, A., Bernasconi, P., Grassi, A., Iori, A. P., Patriarca, F., Brunello, L., Di Grazia, C., Carella, A. M., Cilloni, D., Picardi, A., Proia, A., Santarone, S., Sorasio, R., Carluccio, P., Chiusolo, Patrizia, Cupri, A., Luppi, M., Nozzoli, C., Baronciani, D., Casini, M., Grillo, G., Musso, M., Onida, F., Palazzo, G., Parma, M., Tringali, S., Vacca, A., Vallisa, D., Sacchi, N., Oldani, E., Masciulli, A., Gheorghiu, A., Girmenia, C., Martino, M., Bruno, B., Rambaldi, A., Ciceri, F., Chiusolo P. (ORCID:0000-0002-1355-1587), Bonifazi, F., Pavoni, C., Peccatori, J., Giglio, F., Arpinati, M., Busca, A., Bernasconi, P., Grassi, A., Iori, A. P., Patriarca, F., Brunello, L., Di Grazia, C., Carella, A. M., Cilloni, D., Picardi, A., Proia, A., Santarone, S., Sorasio, R., Carluccio, P., Chiusolo, Patrizia, Cupri, A., Luppi, M., Nozzoli, C., Baronciani, D., Casini, M., Grillo, G., Musso, M., Onida, F., Palazzo, G., Parma, M., Tringali, S., Vacca, A., Vallisa, D., Sacchi, N., Oldani, E., Masciulli, A., Gheorghiu, A., Girmenia, C., Martino, M., Bruno, B., Rambaldi, A., Ciceri, F., and Chiusolo P. (ORCID:0000-0002-1355-1587)

Abstract

The outcome of refractory/relapsed (R/R) acute leukemias is still dismal and their treatment represents an unmet clinical need. However, allogeneic transplantation (allo-HSCT) remains the only potentially curative approach in this setting. A prospective study (GANDALF-01, NCT01814488; EUDRACT:2012-004008-37) on transplantation with alternative donors had been run by GITMO using a homogeneous myeloablative conditioning regimen with busulfan, thiotepa and fludarabine while GVHD prophylaxis was stratified by donor type. The study enrolled 101 patients; 90 found an alternative donor and 87 ultimately underwent allo-HSCT. Two-year overall survival of the entire and of the transplant population (primary endpoint) were 19% and 22%, without significant differences according to disease, donor type and disease history (relapsed vs refractory patients). Two-year progression-free survival was 19% and 17% respectively. The cumulative incidences of relapse and non-relapse mortality were 49% and 33% at two years. Acute grade II-IV and chronic GVHD occurred in 23 and 10 patients. Dose intensification with a myeloablative two-alkylating regimen as sole strategy for transplanting R/R acute leukemia does seem neither to improve the outcome nor to control disease relapse. A pre-planned relapse prevention should be included in the transplant strategy in this patient population.

Published
2022

15. OUTCOMES OF RELAPSED OR REFRACTORY AND NEWLY DIAGNOSED ACUTE MYELOID LEUKEMIA AFTER HYPOMETHYLATING AGENT AND VENETOCLAX. THE ITALIAN REAL-LIFE EXPERIENCE BEFORE PUBLIC HEALTH REIMBURSEMENT (AVALON STUDY)

Author

Todisco, E, Papayannidis, C, Fracchiolla, N, Cerchione, C, Marconi, G, Petracci, E, Zingaretti, C, Vetro, C, Martelli, M, Zappasodi, P, Di Renzo, N, Cignetti, A, Lussana, F, Mattei, D, Ciceri, F, Facchini, L, Selleri, C, Fumagalli, M, Audisio, E, Griguolo, D, Basilico, C, Manfra, I, Borlenghi, E, Cairoli, R, Salutari, P, Gottardi, M, Molteni, A, Martini, V, Lunghi, M, Fianchi, L, Cilloni, D, Lanza, F, Abruzzese, E, Cascavilla, N, Rivellini, F, Ferrara, F, Maurillo, L, Nanni, J, Romano, A, Cardinali, V, Gigli, F, Vincenzo, F, Volpi, R, Sciume, M, Tarella, C, Rossi, G, Martinelli, G, Todisco, E, Papayannidis, C, Fracchiolla, N, Cerchione, C, Marconi, G, Petracci, E, Zingaretti, C, Vetro, C, Martelli, M, Zappasodi, P, Di Renzo, N, Cignetti, A, Lussana, F, Mattei, D, Ciceri, F, Facchini, L, Selleri, C, Fumagalli, M, Audisio, E, Griguolo, D, Basilico, C, Manfra, I, Borlenghi, E, Cairoli, R, Salutari, P, Gottardi, M, Molteni, A, Martini, V, Lunghi, M, Fianchi, L, Cilloni, D, Lanza, F, Abruzzese, E, Cascavilla, N, Rivellini, F, Ferrara, F, Maurillo, L, Nanni, J, Romano, A, Cardinali, V, Gigli, F, Vincenzo, F, Volpi, R, Sciume, M, Tarella, C, Rossi, G, and Martinelli, G

Published
2021

16. Different isoforms of the B-cell mutator activation-induced cytidine deaminase are aberrantly expressed in BCR–ABL1-positive acute lymphoblastic leukemia patients

Author

Iacobucci, I, Lonetti, A, Messa, F, Ferrari, A, Cilloni, D, Soverini, S, Paoloni, F, Arruga, F, Ottaviani, E, Chiaretti, S, Messina, M, Vignetti, M, Papayannidis, C, Vitale, A, Pane, F, Piccaluga, P P, Paolini, S, Berton, G, Baruzzi, A, Saglio, G, Baccarani, M, Foà, R, and Martinelli, G

Published
2010
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23. Transplantation induces profound changes in the transcriptional asset of hematopoietic stem cells: Identification of specific signatures using machine learning techniques

Author

Cilloni, D., Petiti, J., Campia, V., Podesta, M., Squillario, M., Montserrat, N., Bertaina, A., Sabatini, F., Carturan, S., Berger, M., Saglio, F., Bandini, G., Bonifazi, F., Fagioli, F., Moretta, L., Saglio, G., Verri, A., Barla, A., Locatelli, Franco, Frassoni, F., Locatelli F. (ORCID:0000-0002-7976-3654), Cilloni, D., Petiti, J., Campia, V., Podesta, M., Squillario, M., Montserrat, N., Bertaina, A., Sabatini, F., Carturan, S., Berger, M., Saglio, F., Bandini, G., Bonifazi, F., Fagioli, F., Moretta, L., Saglio, G., Verri, A., Barla, A., Locatelli, Franco, Frassoni, F., and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

During the phase of proliferation needed for hematopoietic reconstitution following transplantation, hematopoietic stem/progenitor cells (HSPC) must express genes involved in stem cell self-renewal. We investigated the expression of genes relevant for self-renewal and expansion of HSPC (operationally defined as CD34+ cells) in steady state and after transplantation. Specifically, we evaluated the expression of ninety-one genes that were analyzed by real-time PCR in CD34+ cells isolated from (i) 12 samples from umbilical cord blood (UCB); (ii) 15 samples from bone marrow healthy donors; (iii) 13 samples from bone marrow after umbilical cord blood hematopoietic cells. The results show that transplanted CD34+ cells from adult cells acquire an asset very different from transplanted CD34+ cells from cord blood. Multivariate machine learning analysis (MMLA) showed that four specific gene signatures can be obtained by comparing the four types of CD34+ cells. In several, but not all cases, transplanted HSPC from UCB overexpress reprogramming genes. However, these remarkable changes do not alter the commitment to hematopoietic lineage. Overall, these results reveal undisclosed aspects of transplantation biology.

Published
2020

30. Two conserved glycine residues in mammalian and Dictyostelium Rictor are required for mTORC2 activity and integrity

Author

Pergolizzi, B., Panuzzo, C., Ali, M. S., Lo Iacono, M., Levra Levron, C., Ponzone, L., Prelli, M., Cilloni, D., Calautti, E., Bozzaro, S., and Bracco, E.

Subjects
Protein–protein interaction, Mammalian target of rapamycin, AKT, AKT, Dictyostelium, Mammalian target of rapamycin, mTOR, PKB, Protein–protein interaction, Rictor, mTOR, Dictyostelium, PKB, Rictor
Published
2019

37. PS981 LONG TERM AML SURVIVORS HAVE INCREASED MORTALITY AND HIGH PREVALENCE OF CLONAL HEMATOPOIESIS

Author

Ilani, N. Chapal, primary, Niemeyer, E., additional, Cohen, N. Mendelson, additional, Moskovitz, Y., additional, Oron, B., additional, Mitchell, A., additional, Minden, M.D., additional, Tanay, A., additional, Balicer, R., additional, Biezuner, T., additional, Cilloni, D., additional, Metzeler, K., additional, Ofran, Y., additional, Kaushansky, N., additional, and Slush, L., additional

Published
2019
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38. A phase II, multicentre trial of decitabine in higher-risk chronic myelomonocytic leukemia

Author

Santini, V., Allione, B., Zini Tanzi, Gina, Gioia, D., Lunghi, M., Poloni, A., Cilloni, D., Sanna, A., Masiera, E., Ceccarelli, M., Abdel-Wahab, O., Terenzi, Andrea, Angelucci, E., Finelli, C., Onida, F., Pelizzari, A., Ferrero, D., Saglio, G., Figueroa, M., Levis, A., Zini, G. (ORCID:0000-0002-8208-066X), Santini, V., Allione, B., Zini Tanzi, Gina, Gioia, D., Lunghi, M., Poloni, A., Cilloni, D., Sanna, A., Masiera, E., Ceccarelli, M., Abdel-Wahab, O., Terenzi, Andrea, Angelucci, E., Finelli, C., Onida, F., Pelizzari, A., Ferrero, D., Saglio, G., Figueroa, M., Levis, A., and Zini, G. (ORCID:0000-0002-8208-066X)

Abstract

Chronic myelomonocytic leukemia (CMML) is a complex clonal hematological disorder classified among myelodysplastic (MDS)/myeloproliferative neoplasms. Prognosis is poor and there is a lack of effective treatments. The hypomethylating agent decitabine has shown activity against MDS and elderly acute myeloid leukemia, but there is little data focusing specifically on its efficacy in CMML. In this prospective, phase 2 Italian study, CMML patients received intravenous decitabine 20 mg/m2per day on Days 1-5 of a 28-day treatment cycle. Response was evaluated after four and six cycles; patients responding at the end of six cycles could continue treatment with decitabine. Forty-three patients were enrolled; >50% were high-risk according to four CMML-specific scoring systems. In the intent-to-treat population (n=42), the overall response rate after six cycles was 47.6%, with seven complete responses (16.6%), eight marrow responses (19%), one partial response (2.4%) and four hematological improvements (9.5%). After a median follow-up of 51.5 months (range: 44.4-57.2), median overall survival was 17 months, with responders having a significantly longer survival than non-responders (P=0.02). Grade 3/4 anemia, neutropenia and thrombocytopenia occurred in 28.6%, 50% and 38% of patients, respectively. Decitabine appears to be an effective and well-tolerated treatment for patients with high-risk CMML.

Published
2018

40. Temsirolimus, an mTOR inhibitor, in combination with lower-dose clofarabine as salvage therapy for older patients with acute myeloid leukaemia: results of a phase II GIMEMA study (AML-1107)

Author

Amadori, S, Stasi, R, Martelli, Am, Venditti, A, Meloni, G, Pane, F, Martinelli, G, Lunghi, M, Pagano, L, Cilloni, D, Rossetti, E, DI RAIMONDO, Francesco, Fozza, C, Annino, L, Chiarini, F, Ricci, F, Ammatuna, E, La Sala, E, Fazi, P, Vignetti, M., Amadori, S, Stasi, R, Martelli, Am, Venditti, A, Meloni, G, Pane, Fabrizio, Martinelli, G, Lunghi, M, Pagano, L, Cilloni, D, Rossetti, E, Di Raimondo, F, Fozza, C, Annino, L, Chiarini, F, Ricci, F, Ammatuna, E, La Sala, E, Fazi, P, Vignetti, M., Amadori S., Stasi R., Martelli A.M., Venditti A., Meloni G., Pane F., Martinelli G., Lunghi M., Pagano L., Cilloni D., Rossetti E., Di Raimondo F., Fozza C., Annino L., Chiarini F., Ricci F., Ammatuna E., La Sala E., Fazi P., and Vignetti M.

Subjects
age factors, tor serine-threonine kinases, adenine nucleotides, disease-free survival, antineoplastic combined chemotherapy protocols, acute, acute myeloid leukaemia, administration /&/ dosage/adverse effects, administration /&/ dosage/adverse effects/analogs /&/ derivatives, adverse effects/therapeutic use, aged, antagonists /&/ inhibitors, arabinonucleosides, clofarabine, drug therapy, elderly patients, female, humans, leukemia, male, mammalian target of rapamycin, methods, middle aged, myeloid, salvage therapy, sirolimus, temsirolimus, temsirolimu, ACUTE MYELOID LEUKEMIA, AKT/MAMMALIAN TARGET OF RAPAMYCIN (MTOR), Clofarabine, ELDERLY PATIENTS, Adenine Nucleotides, administration /&/ dosage/adverse effects, Age Factors, Aged, Antineoplastic Combined Chemotherapy Protocols, adverse effects/therapeutic use, Arabinonucleosides, administration /&/ dosage/adverse effects, Disease-Free Survival, Female, Humans, Leukemia, Myeloid, Acute, drug therapy, Male, Middle Aged, Salvage Therapy, methods, Sirolimus, administration /&/ dosage/adverse effects/analogs /&/ derivatives, TOR Serine-Threonine Kinases, Leukemia, Myeloid, Acute, Settore MED/15 - Malattie del Sangue
Abstract

The mammalian target of rapamycin (mTOR) signalling pathway has emerged as an important therapeutic target for acute myeloid leukaemia (AML). This study assessed the combination of temsirolimus, an mTOR inhibitor, and lower-dose clofarabine as salvage therapy in older patients with AML. Induction consisted of clofarabine 20 mg/m2 on days 15 and temsirolimus 25 mg (flat dose) on days 1, 8 and 15. Patients achieving complete remission with (CR) or without (CRi) full haematological recovery could receive monthly temsirolimus maintenance. In 53 evaluable patients, the overall remission rate (ORR) was 21% (8% CR, 13% CRi). Median disease-free survival was 3.5 months, and median overall survival was 4 months (9.1 months for responders). The most common non-haematological severe adverse events included infection (48%), febrile neutropenia (34%) and transaminitis (11%). The 30-d all-cause induction mortality was 13%. Laboratory data from 25 patients demonstrated that a >50%in vivo inhibition of S6 ribosomal protein phosphorylation was highly correlated with response rate (75% with inhibition versus 0% without inhibition; P = 0.0001), suggesting that targeting the mTOR pathway is clinically relevant. The acceptable safety profile and the predictive value of target inhibition encourage further investigation of this novel regimen.

Published
2012

41. Incidence, Risk Factors and Outcome of Pre-engraftment Gram-Negative Bacteremia after Allogeneic and Autologous Hematopoietic Stem Cell Transplantation: An Italian Prospective Multicenter Survey

Author

Girmenia, C., Bertaina, A., Piciocchi, A., Perruccio, K., Algarotti, A., Busca, A., Cattaneo, C., Raiola, A. M., Guidi, S., Iori, A. P., Candoni, A., Irrera, G., Milone, G., Marcacci, G., Scime, R., Musso, M., Cudillo, L., Sica, Simona, Castagna, Luigi, Corradini, P., Marchesi, F., Pastore, D., Alessandrino, E. P., Annaloro, C., Ciceri, F., Santarone, S., Nassi, L., Farina, C., Viscoli, C., Rossolini, G. M., Bonifazi, F., Rambaldi, A., Capria, S., Mastronuzzi, A., Pagliara, D., Bernaschi, P., Amico, L., Carotti, A., Mencacci, A., Bruno, Brunella, Costa, C., Passi, A., Ravizzola, G., Angelucci, E., Marchese, Alessandra Maria, Pecile, P., Ventura, Giulio, Fanin, R., Scarparo, C., Barbaro, A., Leotta, Salvatore Nuccio, Marchese, A. E., Becchimanzi, C., Donnarumma, D., Tringali, S., Baldi, M. T., Scalone, R., Picardi, A., Arcese, W., Fontana, Cecilia Alejandra, Giammarco, S., Spanu, Teresa, Crocchiolo, R., Casari, E., Mussetti, A., Conte, Eliana, Ensoli, F., Miragliotta, G., Marone, P., Arghittu, M., Greco, R., Forcina, A., Chichero, P., Di Bartolomeo, P., Fazii, P., Kroumova, V., Decembrino, N., Zecca, M., Pisapia, Giovanni, Palazzo, G., Lanino, E., Faraci, M., Castagnola, E., Bandettini, R., Pastano, R., Sammassimo, S., Passerini, R., Stefani, P. M., Gherlinzoni, F., Rigoli, R., Prezioso, L., Cambo, B., Calderaro, A., Carella, A. M., Cascavilla, N., Labonia, M. T., Celeghini, I., Mordini, N., Piana, F., Vacca, A., Sanna, Maria Maddalena, Podda, G., Corsetti, M. T., Rocchetti, A., Cilloni, D., De Gobbi, M., Bianco, O., Fagioli, F., Carraro, F., De Intinis, G., Severino, A., Proia, Anna Silvia, Parisi, G., Vallisa, D., Confalonieri, Marco, Russo, D., Malagola, M., Galieni, P., Falcioni, S., Travaglini, V., Raimondi, Maria Rosa, Borghero, C., Pavan, Giuseppe, Prete, A., Belotti, T., Ambretti, S., Imola, M., Mianulli, A. M., Pedna, M. F., Cesaro, S., Lo Cascio, G., Ferrari, A., Piedimonte, M., Santino, I., Calandrelli, M., Olivieri, Alessandra, Orecchioni, F., Mirabile, M., Centurioni, R., Gironacci, L., Caravelli, D., Gallo, S., De Filippi, M., Cupelli, L., Dentamaro, T., Falco, S., Eugenio, O. S., Marotta, S., Risitano, A., Lula, D., Musto, P., Pietrantuono, G., Traficante, A., Cerchiara, E., Tirindelli, M. C., Dicuonzo, G., Chierichini, A., Anaclerico, B., Placanica, P., Sica S. (ORCID:0000-0003-2426-3465), Castagna L., Bruno B., Marchese A., Ventura G. (ORCID:0000-0002-0304-7264), Leotta S., Fontana C., Spanu T. (ORCID:0000-0003-1864-5184), Conte E., Pisapia G., Sanna M., Proia A., Confalonieri M. (ORCID:0000-0002-3708-379X), Raimondi R., Pavan G., Olivieri A., Girmenia, C., Bertaina, A., Piciocchi, A., Perruccio, K., Algarotti, A., Busca, A., Cattaneo, C., Raiola, A. M., Guidi, S., Iori, A. P., Candoni, A., Irrera, G., Milone, G., Marcacci, G., Scime, R., Musso, M., Cudillo, L., Sica, Simona, Castagna, Luigi, Corradini, P., Marchesi, F., Pastore, D., Alessandrino, E. P., Annaloro, C., Ciceri, F., Santarone, S., Nassi, L., Farina, C., Viscoli, C., Rossolini, G. M., Bonifazi, F., Rambaldi, A., Capria, S., Mastronuzzi, A., Pagliara, D., Bernaschi, P., Amico, L., Carotti, A., Mencacci, A., Bruno, Brunella, Costa, C., Passi, A., Ravizzola, G., Angelucci, E., Marchese, Alessandra Maria, Pecile, P., Ventura, Giulio, Fanin, R., Scarparo, C., Barbaro, A., Leotta, Salvatore Nuccio, Marchese, A. E., Becchimanzi, C., Donnarumma, D., Tringali, S., Baldi, M. T., Scalone, R., Picardi, A., Arcese, W., Fontana, Cecilia Alejandra, Giammarco, S., Spanu, Teresa, Crocchiolo, R., Casari, E., Mussetti, A., Conte, Eliana, Ensoli, F., Miragliotta, G., Marone, P., Arghittu, M., Greco, R., Forcina, A., Chichero, P., Di Bartolomeo, P., Fazii, P., Kroumova, V., Decembrino, N., Zecca, M., Pisapia, Giovanni, Palazzo, G., Lanino, E., Faraci, M., Castagnola, E., Bandettini, R., Pastano, R., Sammassimo, S., Passerini, R., Stefani, P. M., Gherlinzoni, F., Rigoli, R., Prezioso, L., Cambo, B., Calderaro, A., Carella, A. M., Cascavilla, N., Labonia, M. T., Celeghini, I., Mordini, N., Piana, F., Vacca, A., Sanna, Maria Maddalena, Podda, G., Corsetti, M. T., Rocchetti, A., Cilloni, D., De Gobbi, M., Bianco, O., Fagioli, F., Carraro, F., De Intinis, G., Severino, A., Proia, Anna Silvia, Parisi, G., Vallisa, D., Confalonieri, Marco, Russo, D., Malagola, M., Galieni, P., Falcioni, S., Travaglini, V., Raimondi, Maria Rosa, Borghero, C., Pavan, Giuseppe, Prete, A., Belotti, T., Ambretti, S., Imola, M., Mianulli, A. M., Pedna, M. F., Cesaro, S., Lo Cascio, G., Ferrari, A., Piedimonte, M., Santino, I., Calandrelli, M., Olivieri, Alessandra, Orecchioni, F., Mirabile, M., Centurioni, R., Gironacci, L., Caravelli, D., Gallo, S., De Filippi, M., Cupelli, L., Dentamaro, T., Falco, S., Eugenio, O. S., Marotta, S., Risitano, A., Lula, D., Musto, P., Pietrantuono, G., Traficante, A., Cerchiara, E., Tirindelli, M. C., Dicuonzo, G., Chierichini, A., Anaclerico, B., Placanica, P., Sica S. (ORCID:0000-0003-2426-3465), Castagna L., Bruno B., Marchese A., Ventura G. (ORCID:0000-0002-0304-7264), Leotta S., Fontana C., Spanu T. (ORCID:0000-0003-1864-5184), Conte E., Pisapia G., Sanna M., Proia A., Confalonieri M. (ORCID:0000-0002-3708-379X), Raimondi R., Pavan G., and Olivieri A.

Abstract

Background Gram-negative bacteremia (GNB) is a major cause of illness and death after hematopoietic stem cell transplantation (HSCT), and updated epidemiological investigation is advisable. Methods We prospectively evaluated the epidemiology of pre-engraftment GNB in 1118 allogeneic HSCTs (allo-HSCTs) and 1625 autologous HSCTs (auto-HSCTs) among 54 transplant centers during 2014 (SIGNB-GITMO-AMCLI study). Using logistic regression methods. we identified risk factors for GNB and evaluated the impact of GNB on the 4-month overall-survival after transplant. Results The cumulative incidence of pre-engraftment GNB was 17.3% in allo-HSCT and 9% in auto-HSCT. Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa were the most common isolates. By multivariate analysis, variables associated with GNB were a diagnosis of acute leukemia, a transplant from a HLA-mismatched donor and from cord blood, older age, and duration of severe neutropenia in allo-HSCT, and a diagnosis of lymphoma, older age, and no antibacterial prophylaxis in auto-HSCT. A pretransplant infection by a resistant pathogen was significantly associated with an increased risk of posttransplant infection by the same microorganism in allo-HSCT. Colonization by resistant gram-negative bacteria was significantly associated with an increased rate of infection by the same pathogen in both transplant procedures. GNB was independently associated with increased mortality at 4 months both in allo-HSCT (hazard ratio, 2.13; 95% confidence interval, 1.45-3.13; P <.001) and auto-HSCT (2.43; 1.22-4.84; P =.01). Conclusions Pre-engraftment GNB is an independent factor associated with increased mortality rate at 4 months after auto-HSCT and allo-HSCT. Previous infectious history and colonization monitoring represent major indicators of GNB. Clinical Trials registration NCT02088840.

Published
2017

43. A phase II, multicentre trial of decitabine in higher-risk chronic myelomonocytic leukemia

Author

Santini, V, primary, Allione, B, additional, Zini, G, additional, Gioia, D, additional, Lunghi, M, additional, Poloni, A, additional, Cilloni, D, additional, Sanna, A, additional, Masiera, E, additional, Ceccarelli, M, additional, Abdel-Wahab, O, additional, Terenzi, A, additional, Angelucci, E, additional, Finelli, C, additional, Onida, F, additional, Pelizzari, A, additional, Ferrero, D, additional, Saglio, G, additional, Figueroa, M, additional, and Levis, A, additional

Published
2017
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44. Cardiovascular events and intensity of treatment in polycythemia vera

Author

Marchioli, R, Finazzi, G, Specchia, G, Cacciola, R, Cavazzina, R, Cilloni, D, De Stefano, V, Elli, E, Iurlo, A, Latagliata, R, Lunghi, F, Lunghi, M, Marfisi, Rm, Musto, P, Masciulli, A, Musolino, C, Cascavilla, N, Quarta, G, Randi, M. L., Rapezzi, D, Ruggeri, M, Rumi, E, Scortechini, Ar, Santini, S, Scarano, M, Siragusa, S, Spadea, A, Tieghi, A, Angelucci, E, Visani, G, Vannucchi, Am, Specchia G, Barbui T., D'Amico, A, Ferri, B, Guido, C, Marfisi, L, Pera, C, Polidoro, A, Sacco, M, Levantesi, G, Tognoni, G, Barosi, G, Carobbio, A, Leoni, P, Mulattieri, S, Tomassetti, S, Honorati, E, Ricco, A, Albano, F, Pastore, D, Carluccio, P, Mazzone, Am, Rossi, Ar, Finazzi, Mc, Delaini, F, Falanga, A, Rambaldi, A, Guaragna, G, Giannotta, A, Usala, E, Simula, Mp, Pilo, F, Cacciola, E, Pezzella, F, Seria, E, Di Francesco, E, Gallamini, A, Bertolotti, L, Antonioli, E, Guglielmelli, P, Pieri, L, Susini, Mc, Bartalucci, N, Bosi, A, D'Angelo, A, Centorrino, R, Gerace, D, Allegra, A, Cortelezzi, A, De Philippis, C, Ferretti, E, Ciceri, F, Claudiani, S, Malato, S, Trinca, S, Pogliani, Em, Belotti, A, Lanzi, E, Elli, Em, Gaidano, G, Deambrogi, C, Rossi, D, Saglio, G, Rotolo, A, Zanone, C, Bertozzi, I, Tezza, F, Aneloni, V, Quintini, G, Saccullo, G, Caracciolo, C, Cazzola, M, Casetti, I, Elena, C, Landini, B, Barulli, S, Guiducci, B, Lucesole, M, Malerba, L, Isidori, A, Grossi, A, De Stefanis, M, Biagioni, C, Merli, F, Imovilli, A, Codeluppi, K, Rubagotti, S, Romano, N, Bonini, A, Bellesia, E, Martorelli, Mc, Villani, O, Zifarone, E, Zonno, A, Santopietro, V, Za, T, Rossi, E, Ciminello, Am, Betti, S, Alimena, G, Tafuri, A, Breccia, M, Carmosino, I, Pisani, F, Romano, A, D'Andrea, M, Nobile, M, Mantuano, Fs, Rossi, G, Tricarico, M, Rodeghiero, F, Bedin, F, Lissandrini, L, Finotto, S., Marchioli, R, Finazzi, G, Specchia, G, Cacciola, R, Cavazzina, R, Cilloni, D, De Stefano, V, Elli, E, Iurlo, A, Latagliata, R, Lunghi, F, Lunghi, M, Marfisi, RM, Musto, P, Masciulli, A, Musolino, C, Cascavilla, N, Quarta, G, Randi, ML, Rapezzi, D, Ruggeri, M, Rumi, E, Scortechini, AR, Santini, S, Scarano, M, Siragusa, S, Spadea, A, Tieghi, A, Angelucci, E, Visani, G, Vannucchi, AM, Barbui, T, and CYTO-PV Collaborative Group.

Subjects
Male, Hematocrit, RECURRENT THROMBOSIS, law.invention, Aged, Antineoplastic Agents, Cardiovascular Diseases, Combined Modality Therapy, Female, Follow-Up Studies, Humans, Hydroxyurea, Janus Kinase 2, Middle Aged, Polycythemia Vera, Thrombosis, Phlebotomy, Medicine (all), LEUKOCYTOSIS, Polycythemia vera, Randomized controlled trial, law, hemic and lymphatic diseases, ESSENTIAL THROMBOCYTHEMIA, Clinical endpoint, Polycythemia Vera, Secondary Prophylaxis, ESSENTIAL THROMBOCYTHEMIA, RECURRENT THROMBOSIS, RISK-FACTOR, HEMATOCRIT, MANAGEMENT, LEUKOCYTOSIS, PREVENTION, DIAGNOSIS, EFFICACY, WARFARIN, medicine.diagnostic_test, Hazard ratio, General Medicine, medicine.medical_specialty, randomized trial, polycythemia vera, Cardiovascular event, DIAGNOSIS, WARFARIN, RISK-FACTOR, Internal medicine, MANAGEMENT, medicine, Myelofibrosis, Adverse effect, business.industry, EFFICACY, medicine.disease, PREVENTION, Surgery, Polycythemia Vera, Cardiovascular event, hematocrit, Settore MED/15 - MALATTIE DEL SANGUE, business
Abstract

A b s t r ac t Background Current treatment recommendations for patients with polycythemia vera call for maintaining a hematocrit of less than 45%, but this therapeutic strategy has not been tested in a randomized clinical trial. Methods We randomly assigned 365 adults with JAK2-positive polycythemia vera who were being treated with phlebotomy, hydroxyurea, or both to receive either more intensive treatment (target hematocrit

Published
2013

45. Comparison of 3 Tfr2-deficient murine models suggests distinct functions for Tfr2-alpha and Tfr2-beta isoforms in different tissues

Author

ROETTO A, DI CUNTO F, PELLEGRINO RM, HIRSCH E, AZZOLINO O, BONDI A, DEFILIPPI I, CARTURAN S, MINISCALCO B, RIONDATO F, CILLONI D, SILENGO L, ALTRUDA F, SAGLIO G., CAMASCHELLA , CLARA, Roetto, A, DI CUNTO, F, Pellegrino, Rm, Hirsch, E, Azzolino, O, Bondi, A, Defilippi, I, Carturan, S, Miniscalco, B, Riondato, F, Cilloni, D, Silengo, L, Altruda, F, Camaschella, Clara, and Saglio, G.

Published
2010

46. BACK TO LIFE -LIVING, TREATING, MANAGING MYELOFIBROSIS: THE BURDEN OF ILLNESS FOR PATIENTS AND THEIR FAMILIES

Author

Marini, M. G., Cappuccio, A., Abruzzese, E., Carella, A., Lunghi, M., Loiacono, I., Palumbo, G., Bonifacio, M., Cilloni, D., Iurlo, A., Andriani, A., Benevolo, G., Minoia, C., Turri, D., Elli, E. M., Falcone, A. P., Anaclerico, B., Traficante, A., Di Renzo, N., Tiribelli, M., Calistri, E., Zambello, R., Spinosa, C., Ricco, A., FRANCESCA PALANDRI, Raucci, L., Martino, B., Annunziata, M., D Alosio, M., Liberati, A. M., Caocci, G., Maffioli, M., Breccia, M., Pugliese, N., Betti, S., Giglio, G., and Reale, L.

Subjects
quality of life, myelofibrosis
Published
2014

47. Effects of the Tyrosine Kinase Inhibitor AG957 and an Anti-Fas Receptor Antibody on CD34+ Chronic Myelogenous Leukemia Progenitor Cells

Author

Carmelo Carlo-Stella, Regazzi E, Sammarelli G, Colla S, Garau D, Gazit A, Savoldo B, Cilloni D, Tabilio A, Levitzki A, and Rizzoli V

Subjects
Adult, Male, Immunology, Antibodies, Monoclonal, Apoptosis, Cell Biology, Hematology, Middle Aged, Protein-Tyrosine Kinases, Tyrphostins, Flow Cytometry, Biochemistry, Receptors, Tumor Necrosis Factor, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, hemic and lymphatic diseases, Neoplastic Stem Cells, Tumor Cells, Cultured, Humans, Female, fas Receptor, Enzyme Inhibitors
Abstract

The hallmark of chronic myelogenous leukemia (CML) is the Philadelphia (Ph) chromosome that fuses genetic sequences of the BCR gene on chromosome 22 with c-ABL sequences translocated from chromosome 9. BCR/ABL fusion proteins have a dysregulated protein tyrosine kinase (PTK) activity exerting a key role in malignant transformation. Targeting the tyrosine kinase activity of BCR/ABL or using agents capable of triggering apoptosis might represent attractive therapeutic approaches for ex vivo purging. AG957, a member of the tyrphostin compounds, exerts a selective inhibition of p210(BCR/ABL) tyrosine phosphorylation. We report here that preincubation of CML or normal CD34(+) cells with graded concentration of AG957 (1 to 100 micromol/L) resulted in a statistically significant, dose-dependent suppression of colony growth from multipotent, erythroid, and granulocyte-macrophage progenitors as well as the more primitive long-term culture-initiating cells (LTC-IC). However, AG957 doses causing 50% inhibition (ID50) of CML and normal progenitors were significantly different for multilineage colony-forming units (CFU-Mix; 12 v 64 micromol/L; P =.008), burst-forming unit-erythroid (BFU-E; 29 v 89 micromol/L; P =.004), colony-forming unit-granulocyte-macrophage (CFU-GM; 34 v 85 micromol/L; P =.004), and LTC-IC (43 v 181 micromol/L; P =.004). In 5 of 10 patients, analysis of BCR/ABL mRNA on single progenitors by reverse transcription-polymerase chain reaction showed that AG957 at 50 micromol/L significantly reduced the mean (+/-SD) percentage of BCR/ABL-positive progenitors (92% +/- 10% v 33 +/- 5%; P =.001). Because AG957 treatment resulted in significantly higher percentages of apoptotic cells (30% v 9%) in the BCR/ABL-transfected 32DLG7 cells as compared with 32D-T2/93 cells (BCR/ABL-negative), we investigated the combined effects of AG957 with the anti-Fas receptor (Fas-R) monoclonal antibody CH11 that triggers apoptosis. As compared with AG957 alone, the sequential treatment of CML CD34(+) cells with AG957 (1 micromol/L) and CH11 (1 microgram/mL) increased CFU-Mix, BFU-E, and CFU-GM growth inhibition by 1.6-fold, 3-fold, and 4-fold, respectively. In contrast, the treatment of normal CD34(+) cells with AG957 and CH11 failed to enhance AG957-induced colony growth inhibition. We conclude that (1) AG957 inhibits in a dose-dependent manner CML CD34-derived colony formation by both primitive LTC-IC as well as committed CFU-Mix, BFU-E, and CFU-GM; (2) this growth inhibition is associated with the selection of a substantial amount of BCR/ABL-negative progenitors; and (3) the antiproliferative effect of AG957 is dramatically increased by combining this compound with the anti-Fas-R antibody CH11. These data may have significant therapeutic applications.

Published
1999

48. MDR1 protein expression is an independent predictor of complete remission in newly diagnosed adult acute lymphoblastic leukemia

Author

Tafuri, Agostino, Gregorj, C, Petrucci, Mt, Ricciardi, Maria Rosaria, Mancini, M, Cimino, Giuseppe, Mecucci, C, Tedeschi, A, Fioritoni, G, Ferrara, F, DI RAIMONDO, F, Gallo, E, Liso, V, Fabbiano, F, Cascavilla, N, Pizzolo, G, Camera, A, Pane, F, Lanza, F, Cilloni, D, Annino, L, Vitale, A, Vegna, Ml, Vignetti, Marco, Foa, Roberto, Mandelli, Franco, ON BEHALF OF THE GIMEMA GROUP, Tafuri, A., Gregorj, C., Petrucci, M. T., Ricciardi, M. R., Mancini, M., Cimino, G., Mecucci, C., Tedeschi, A., Fioritoni, G., Ferrara, F., DI RAIMONDO, F., Gallo, E., Liso, V., Fabbiano, F., Cascavilla, N., Pizzolo, G., Camera, A., Pane, Fabrizio, Lanza, F., Cilloni, D., Annino, L., Vitale, A., Vegna, M. L., Vignetti, M., Foa, R., and Mandelli, F.

Subjects
Male, medicine.medical_treatment, physiological processes, Biochemistry, Gastroenterology, Gene expression, polycyclic compounds, Prospective Studies, Prospective cohort study, P-glycoprotein, Univariate analysis, biology, GIMEMA ALL0496 protocol, adult, Remission Induction, Hematology, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Flow Cytometry, Prognosis, Treatment Outcome, Female, multiple drug resistance (MDR1), multiple drug resistance (MDR1), protein expression, independent predictor of complete remission, adult, acute lymphoblastic leukemia,GIMEMA ALL0496 protocol, medicine.medical_specialty, Adolescent, Immunology, Bone Marrow Cells, Context (language use), acute lymphoblastic leukemia, NO, Acute lymphocytic leukemia, Internal medicine, medicine, Humans, ATP Binding Cassette Transporter, Subfamily B, Member 1, neoplasms, protein expression, Analysis of Variance, Chemotherapy, Blood Cells, business.industry, independent predictor of complete remission, Cell Biology, medicine.disease, biology.protein, Adult Acute Lymphoblastic Leukemia, Blast Crisis, business, ACUTE MYELOID-LEUKEMIA, P-GLYCOPROTEIN EXPRESSION, MULTIDRUG-RESISTANCE MDR1, Biomarkers
Abstract

Little is known about the prognostic role of multidrug resistance (MDR) in adults with newly diagnosed acute lymphoblastic leukemia (ALL). In the context of the GIMEMA ALL0496 protocol, we evaluated the impact of MDR1 (protein expression and function) on the achievement of complete remission (CR) and clinical outcome. Flow cytometric analysis of MDR1 expression (D) and function (rhodamine-123 efflux) was obtained in 203 and 158 patients, respectively. MDR1 expression was detected in 44 (21.7%) of 203 patients, and function was found in 23 (14.6%) of 158 (14.6%) patients. Expression of the multidrug resistance-associated protein 1 (MRP1) and lung-resistance protein (LRP) evaluated in 43 samples was found in 13 and 26 patients, respectively. Among the 200 patients evaluable for the clinical correlation study, 125 (79.6%) of 157 without MDR1 expression achieved CR compared with 23 (53.5%) of 43 with MDR1 expression (P =.001). At univariate analysis, MDR1 expression was significantly associated with CR when considered as a dichotomized (P =.001) or continuous (P =.01) variable. At multivariate analysis, dichotomized evaluation of MDR1 expression independently predicted CR (P =.004) with age (P =.03) and CD34 (P =.03); as a continuous variable, MDR1 expression (P =.03) was the only significant factor other than CD34 (P =.01). MDR1 function failed to predict achievement of CR or of MRP1 and LRP expression. MDR1 expression did not correlate with CR duration, nor did it predict for survival duration. These results demonstrate that MDR1 expression in de novo adult ALL is an independent predictor of CR achievement.

Published
2002

49. Quality of life and physicians' perception in myelodysplastic syndromes

Author

Oliva, En, Finelli, C, Santini, Valeria, Poloni, A, Liso, V, Cilloni, D, Impera, S, Terenzi, A, Levis, A, Cortelezzi, A, Ghio, R, Musto, P, Semenzato, G, Clissa, C, Lunghi, T, Trappolini, S, Gaidano, V, Salvi, F, Reda, G, Villani, O, Binotto, G, Cufari, P, Cavalieri, E, and Spiriti, M. A.

Subjects
MYELODYSPLASIA, QUALITY OF LIFE, humanities
Published
2012

50. High frequency of endothelial colony forming cells marks a non-active myeloproliferative neoplasm with high risk of splanchnic vein thrombosis

Author

Rosti, V, Bonetti, E, Bergamaschi, G, Campanelli, R, Guglielmelli, P, Maestri, M, Magrini, U, Massa, M, Tinelli, C, Viarengo, G, Villani, L, Primignani, M, Vannucchi, Am, Frassoni, F, Barosi, G, Agimm, Investigators, INCLUDING VANNUCCHI AM, Antonioli, E, Bartalucci, N, Biamonte, F, Bogani, C, Bosi, A, Fjerza, R, Malevolti, E, Pancrazzi, A, Pieri, L, Spolverini, A, Susini, Mc, Tozzi, L, Bortoluzzi, Stefania, Bisognin, A, Coppe, A, Marchioli, R, Azzan, C, Badalucco, S, Balduini, A, Carolei, A, Currao, M, Isgrã’, Ma, Lupo, Ml, Magni, V, Cazzola, M, Bernasconi, P, Boggi, S, Elena, C, Gallãœ, A, Malcovati, L, Pascutto, C, Passamonti, F, Pietra, D, Rumi, E, Dejana, E, Corada, M, Giannotta, M, Rambaldi, A, Ferrari, Ml, Finazzi, G, Finazzi, Mc, Magri, M, Quaresmini, G, Montalvo, Ml, Ricci, C, Salmoiraghi, S, Spinelli, O, Amaru, A, Golay, J, Cilloni, D, Arruga, F, Bracco, E, Carturan, S, Gaidano, V, Guerrasio, A, Pradotto, M, Manfredini, R, Bianchi, E, Montanari, M, Salati, S, Tagliafico, E, Tenedini, E, and Zini, R.

Subjects
Male, Pathology, myeloproliferative neoplasm, Gastroenterology, Cohort Studies, Hematologic Cancers and Related Disorders, splanchnic vein thrombosis, Hemoglobins, Polycythemia vera, Molecular Cell Biology, Odds Ratio, Splanchnic Circulation, Polycythemia Vera, Aged, 80 and over, Venous Thrombosis, Thrombocytosis, Likelihood Functions, Multidisciplinary, Hematology, Middle Aged, Venous thrombosis, Oncology, Medicine, Female, Cellular Types, Research Article, Adult, medicine.medical_specialty, Clinical Pathology, Science, Sensitivity and Specificity, Myeloproliferative Disorders, Diagnostic Medicine, Internal medicine, medicine, Humans, Myelofibrosis, Biology, Myeloproliferative neoplasm, Aged, Essential thrombocythemia, business.industry, Endothelial Cells, Cancers and Neoplasms, Odds ratio, medicine.disease, Thrombocytopenia, Cross-Sectional Studies, Splanchnic vein thrombosis, business, Biomarkers, General Pathology
Abstract

Increased mobilization of circulating endothelial progenitor cells may represent a new biological hallmark of myeloproliferative neoplasms. We measured circulating endothelial colony forming cells (ECFCs) in 106 patients with primary myelofibrosis, fibrotic stage, 49 with prefibrotic myelofibrosis, 59 with essential thrombocythemia or polycythemia vera, and 43 normal controls. Levels of ECFC frequency for patient's characteristics were estimated by using logistic regression in univariate and multivariate setting. The sensitivity, specificity, likelihood ratios, and positive predictive value of increased ECFC frequency were calculated for the significantly associated characteristics. Increased frequency of ECFCs resulted independently associated with history of splanchnic vein thrombosis (adjusted odds ratio = 6.61, 95% CI = 2.54-17.16), and a summary measure of non-active disease, i.e. hemoglobin of 13.8 g/dL or lower, white blood cells count of 7.8×10(9)/L or lower, and platelet count of 400×10(9)/L or lower (adjusted odds ratio = 4.43, 95% CI = 1.45-13.49) Thirteen patients with splanchnic vein thrombosis non associated with myeloproliferative neoplasms were recruited as controls. We excluded a causal role of splanchnic vein thrombosis in ECFCs increase, since no control had elevated ECFCs. We concluded that increased frequency of ECFCs represents the biological hallmark of a non-active myeloproliferative neoplasm with high risk of splanchnic vein thrombosis. The recognition of this disease category copes with the phenotypic mimicry of myeloproliferative neoplasms. Due to inherent performance limitations of ECFCs assay, there is an urgent need to arrive to an acceptable standardization of ECFC assessment.

Published
2010

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