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3 results on '"Lorella De Paoli"'

1. Clinical significance of chromatin-spliceosome acute myeloid leukemia: a report from the Northern Italy Leukemia Group (NILG) randomized trial 02/06

Author

Chiara Caprioli, Federico Lussana, Silvia Salmoiraghi, Roberta Cavagna, Ksenija Buklijas, Lara Elidi, Pamela Zanghi', Anna Michelato, Federica Delaini, Elena Oldani, Tamara Intermesoli, Anna Grassi, Giacomo Gianfaldoni, Francesco Mannelli, Dario Ferrero, Ernesta Audisio, Elisabetta Terruzzi, Lorella De Paoli, Chiara Cattaneo, Erika Borlenghi, Irene Cavattoni, Monica Tajana, Anna Maria Scattolin, Daniele Mattei, Paolo Corradini, Leonardo Campiotti, Fabio Ciceri, Massimo Bernardi, Elisabetta Todisco, Agostino Cortelezzi, Brunangelo Falini, Chiara Pavoni, Renato Bassan, Orietta Spinelli, and Alessandro Rambaldi

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Secondary acute myeloid leukemia (sAML) after myelodysplastic or myeloproliferative disorders is a high-risk category currently identified by clinical history or specific morphological and cytogenetic abnormalities. However, in the absence of these features, uncertainties remain to identify the secondary nature of some cases otherwise defined as de novo AML. To test whether a chromatin-spliceosome (CS) mutational signature might better inform the definition of the de novo AML group, we analyzed a prospective cohort of 413 newly diagnosed AML patients enrolled into a randomized clinical trial (NILG AML 02/06) and provided with accurate cytogenetic and molecular characterization. Among clinically defined de novo AML, 17.6% carried CS mutations (CS-AML) and showed clinical characteristics closer to sAML (older age, lower white blood cell counts and higher rate of multilineage dysplasia). Outcomes in this group were adverse, more similar to those of sAML as compared to de novo AML (overall survival, 30% in CS-AML and 17% in sAML vs 61% in de novo AML, P

Published
2020
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2. High Throughput Molecular Characterization of Normal Karyotype Acute Myeloid Leukemia in the Context of the Prospective Trial 02/06 of the Northern Italy Leukemia Group (NILG)

Author

Renato Bassan, Chiara Pavoni, Pamela Zanghì, Elisabetta Todisco, Nicola Stefano Fracchiolla, Anna Michelato, Leonardo Campiotti, Federico Lussana, Roberta Cavagna, Annamaria Scattolin, Giacomo Gianfaldoni, Chiara Caprioli, Erika Borlenghi, Fabio Ciceri, Ernesta Audisio, Alessandro Rambaldi, Lorella De Paoli, Tamara Intermesoli, Elisabetta Terruzzi, Orietta Spinelli, Ksenija Buklijas, Lara Elidi, Silvia Salmoiraghi, Paola Stefanoni, Paolo Corradini, Daniele Mattei, Irene Cavattoni, Monica Tajana, Elena Oldani, Salmoiraghi, S, Cavagna, R, Zanghì, P, Pavoni, C, Michelato, A, Buklijas, K, Elidi, L, Intermesoli, T, Lussana, F, Oldani, E, Caprioli, C, Stefanoni, P, Gianfaldoni, G, Audisio, E, Terruzzi, E, De Paoli, L, Borlenghi, E, Cavattoni, I, Mattei, D, Scattolin, A, Tajana, M, Ciceri, F, Todisco, E, Campiotti, L, Corradini, P, Fracchiolla, N, Bassan, R, Rambaldi, A, Spinelli, O, Salmoiraghi, S., Cavagna, R., Zanghi, P., Pavoni, C., Michelato, A., Buklijas, K., Elidi, L., Intermesoli, T., Lussana, F., Oldani, E., Caprioli, C., Stefanoni, P., Gianfaldoni, G., Audisio, E., Terruzzi, E., Paoli, L. D., Borlenghi, E., Cavattoni, I., Mattei, D., Scattolin, A., Tajana, M., Ciceri, F., Todisco, E., Campiotti, L., Corradini, P., Fracchiolla, N., Bassan, R., Rambaldi, A., and Spinelli, O.

Subjects
Oncology, Acute Myeloid Leukemia, Cancer Research, medicine.medical_specialty, NPM1, Context (language use), Gene mutation, Molecular marker, lcsh:RC254-282, Article, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, hemic and lymphatic diseases, Medicine, Prospective cohort study, molecular marker, business.industry, Induction chemotherapy, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Transplantation, Leukemia, 030220 oncology & carcinogenesis, NGS, embryonic structures, business, 030215 immunology, Cohort study
Abstract

By way of a Next-Generation Sequencing NGS high throughput approach, we defined the mutational profile in a cohort of 221 normal karyotype acute myeloid leukemia (NK-AML) enrolled into a prospective randomized clinical trial, designed to evaluate an intensified chemotherapy program for remission induction. NPM1, DNMT3A, and FLT3-ITD were the most frequently mutated genes while DNMT3A, FLT3, IDH1, PTPN11, and RAD21 mutations were more common in the NPM1 mutated patients (p &lt, 0.05). IDH1 R132H mutation was strictly associated with NPM1 mutation and mutually exclusive with RUNX1 and ASXL1. In the whole cohort of NK-AML, no matter the induction chemotherapy used, by multivariate analysis, the achievement of complete remission was negatively affected by the SRSF2 mutation. Alterations of FLT3 (FLT3-ITD) and U2AF1 were associated with a worse overall and disease-free survival (p &lt, 0.05). FLT3-ITD positive patients who proceeded to alloHSCT had a survival probability similar to FLT3-ITD negative patients and the transplant outcome was no different when comparing high and low-AR-FLT3-ITD subgroups in terms of both OS and DFS. In conclusion, a comprehensive molecular profile for NK-AML allows for the identification of genetic lesions associated to different clinical outcomes and the selection of the most appropriate and effective treatment strategies, including stem cell transplantation and targeted therapies.

Published
2020

3. Randomized trial comparing standard vs sequential high-dose chemotherapy for inducing early CR in adult AML

Author

Arianna Masciulli, Irene Cavattoni, Anna Maria Scattolin, Pamela Zanghì, Dario Ferrero, Lorella De Paoli, Chiara Cattaneo, Paolo Corradini, Elisabetta Terruzzi, Erika Borlenghi, Orietta Spinelli, Elisabetta Todisco, Brunangelo Falini, Agostino Cortelezzi, Chiara Pavoni, Sergio Cortelazzo, Giacomo Gianfaldoni, Alessandro Rambaldi, Filippo Marmont, Tamara Intermesoli, Daniele Mattei, Cristina Boschini, Elena Oldani, Renato Bassan, Fabio Ciceri, Massimo Bernardi, Ernesta Audisio, Enrico Pogliani, Leonardo Campiotti, Alberto Bosi, Bassan, Renato, Intermesoli, Tamara, Masciulli, Arianna, Pavoni, Chiara, Boschini, Cristina, Gianfaldoni, Giacomo, Marmont, Filippo, Cavattoni, Irene, Mattei, Daniele, Terruzzi, Elisabetta, De Paoli, Lorella, Cattaneo, Chiara, Borlenghi, Erika, Ciceri, Fabio, Bernardi, Massimo, Scattolin, Anna M, Todisco, Elisabetta, Campiotti, Leonardo, Corradini, Paolo, Cortelezzi, Agostino, Ferrero, Dario, Zanghì, Pamela, Oldani, Elena, Spinelli, Orietta, Audisio, Ernesta, Cortelazzo, Sergio, Bosi, Alberto, Falini, Brunangelo, Pogliani, Enrico M, and Rambaldi, Alessandro

Subjects
Adult, Male, medicine.medical_specialty, Randomization, Adolescent, Clinical Trials and Observations, medicine.medical_treatment, Gastroenterology, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Idarubicin, Humans, Aged, Etoposide, Chemotherapy, business.industry, Hazard ratio, Remission Induction, Cytarabine, Hematopoietic Stem Cell Transplantation, Hematology, Odds ratio, Induction Chemotherapy, Middle Aged, Chemotherapy regimen, Survival Analysis, Confidence interval, Leukemia, Myeloid, Acute, Female, business, medicine.drug
Abstract

Here we evaluated whether sequential high-dose chemotherapy (sHD) increased the early complete remission (CR) rate in acute myelogenous leukemia (AML) compared with standard-intensity idarubicin-cytarabine-etoposide (ICE) chemotherapy. This study enrolled 574 patients (age, 16-73 years; median, 52 years) who were randomly assigned to ICE (n = 286 evaluable) or sHD (2 weekly 3-day blocks with cytarabine 2 g/m2 twice a day for 2 days plus idarubicin; n = 286 evaluable). Responsive patients were risk-stratified for a second randomization. Standard-risk patients received autograft or repetitive blood stem cell-supported high-dose courses. High-risk patients (and standard-risk patients not mobilizing stem cells) underwent allotransplantation. CR rates after 2 induction courses were comparable between ICE (80.8%) and sHD (83.6%; P = .38). sHD yielded a higher single-induction CR rate (69.2% vs 81.5%; P = .0007) with lower resistance risk (P < .0001), comparable mortality (P = .39), and improved 5-year overall survival (39% vs 49%; P = .045) and relapse-free survival (36% vs 48%; P = .028), despite greater hematotoxicity delaying or reducing consolidation blocks. sHD improved the early CR rate in high-risk AML (odds ratio, 0.48; 95% confidence interval [CI], 0.31-0.74; P = .0008) and in patients aged 60 years and less with de novo AML (odds ratio, 0.46; 95% CI, 0.27-0.78; P = .003), and also improved overall/relapse-free survival in the latter group (hazard ratio, 0.70; 95% CI, 0.52-0.94; P = .01), in standard-risk AML, and postallograft (hazard ratio, 0.61; 95% CI, 0.39-0.96; P = .03). sHD was feasible, effectively achieved rapid CR, and improved outcomes in AML subsets. This study is registered at www.clinicaltrials.gov as #NCT00495287.

Published
2019

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