48 results on '"Tanasi, I."'
Search Results
2. BH3 mimetics in relapsed and refractory adult acute lymphoblastic leukemia: a Campus ALL real-life study
- Author
-
Malfona, F., Tanasi, I., Piccini, M., Papayannidis, C., Federico, V., Mancini, V., Roncoroni, E., Todisco, E., Bianchi, S., Ciotti, G., Chiusolo, Patrizia, Gentile, M., Gianfelici, V., Giglio, F., Malagola, M., Mule, A., Saraceni, F., Vetro, C., Zallio, F., Cappelli, L. V., Pizzolo, G., Foa, Robin, Bonifacio, M., Chiaretti, S., Chiusolo P. (ORCID:0000-0002-1355-1587), Foa R., Malfona, F., Tanasi, I., Piccini, M., Papayannidis, C., Federico, V., Mancini, V., Roncoroni, E., Todisco, E., Bianchi, S., Ciotti, G., Chiusolo, Patrizia, Gentile, M., Gianfelici, V., Giglio, F., Malagola, M., Mule, A., Saraceni, F., Vetro, C., Zallio, F., Cappelli, L. V., Pizzolo, G., Foa, Robin, Bonifacio, M., Chiaretti, S., Chiusolo P. (ORCID:0000-0002-1355-1587), and Foa R.
- Abstract
N/A
- Published
- 2024
3. Daratumumab with or without chemotherapy in relapsed and refractory acute lymphoblastic leukemia. A retrospective observational Campus ALL study
- Author
-
Cerrano, M, Bonifacio, M, Olivi, M, Curti, A, Malagola, M, Dargenio, M, Scattolin, A, Papayannidis, C, Forghieri, F, Gurrieri, C, Tanasi, I, Zappasodi, P, Starza, R, Fracchiolla, N, Chiusolo, P, Giaccone, L, Del Principe, M, Giglio, F, Defina, M, Favre, C, Rizzari, C, Castella, B, Pizzolo, G, Ferrara, F, Chiaretti, S, Foa, R, Cerrano M., Bonifacio M., Olivi M., Curti A., Malagola M., Dargenio M., Scattolin A. M., Papayannidis C., Forghieri F., Gurrieri C., Tanasi I., Zappasodi P., Starza R. L., Fracchiolla N. S., Chiusolo P., Giaccone L., Del Principe M. I., Giglio F., Defina M., Favre C., Rizzari C., Castella B., Pizzolo G., Ferrara F., Chiaretti S., Foa R., Cerrano, M, Bonifacio, M, Olivi, M, Curti, A, Malagola, M, Dargenio, M, Scattolin, A, Papayannidis, C, Forghieri, F, Gurrieri, C, Tanasi, I, Zappasodi, P, Starza, R, Fracchiolla, N, Chiusolo, P, Giaccone, L, Del Principe, M, Giglio, F, Defina, M, Favre, C, Rizzari, C, Castella, B, Pizzolo, G, Ferrara, F, Chiaretti, S, Foa, R, Cerrano M., Bonifacio M., Olivi M., Curti A., Malagola M., Dargenio M., Scattolin A. M., Papayannidis C., Forghieri F., Gurrieri C., Tanasi I., Zappasodi P., Starza R. L., Fracchiolla N. S., Chiusolo P., Giaccone L., Del Principe M. I., Giglio F., Defina M., Favre C., Rizzari C., Castella B., Pizzolo G., Ferrara F., Chiaretti S., and Foa R.
- Published
- 2022
4. The clinical experience of compassionate use program for avapritinib: implications for drug positioning in the therapeutic scenario of systemic mastocytosis
- Author
-
Mannelli, F., Crupi, F., Zanotti, R., Pagano, Livio, Rapezzi, D., Tanasi, I., Criscuolo, Marianna, Bonifacio, M., Fresa, Alberto, Guglielmelli, P., Vannucchi, A. M., Pagano L. (ORCID:0000-0001-8287-928X), Criscuolo M., Fresa A., Mannelli, F., Crupi, F., Zanotti, R., Pagano, Livio, Rapezzi, D., Tanasi, I., Criscuolo, Marianna, Bonifacio, M., Fresa, Alberto, Guglielmelli, P., Vannucchi, A. M., Pagano L. (ORCID:0000-0001-8287-928X), Criscuolo M., and Fresa A.
- Abstract
In systemic mastocytosis, cytoreductive treatment is indicated for advanced systemic mastocytosis (AdvSM) variants. The treatment scenario is rapidly diversifying especially with the introduction of KIT tyrosine kinase inhibitors. Avapritinib is a second-generation potent and selective inhibitor of the mutant KIT D816V that, based on the results of pivotal clinical trials, was approved for the treatment of adults with AdvSM by the regulatory agencies US FDA and EMA. The present article reports the experience of treating SM patients with avapritinib in an Italian compassionate use program. The data from our case series confirm the drug as being active after multiple lines of treatment allowing rapid achievement of profound responses, making it also an effective bridging strategy to allogeneic transplant in eligible patients. However, the anticipated wider use of avapritinib in the near future will require careful monitoring of side effects, especially in heavily pretreated patients.
- Published
- 2023
5. Multicenter retrospective analysis of clinical outcome of adult patients with mixed-phenotype acute leukemia treated with acute myeloid leukemia–like or acute lymphoblastic leukemia–like chemotherapy and impact of allogeneic stem cell transplantation: a Campus ALL study
- Author
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Lazzarotto, D., Tanasi, I., Vitale, A., Piccini, M., Dargenio, M., Giglio, F., Forghieri, F., Fracchiolla, N., Cerrano, M., Todisco, E., Papayannidis, C., Leoncin, M., Defina, M., Guolo, F., Pasciolla, C., Delia, M., Chiusolo, Patrizia, Mule, A., Candoni, A., Bonifacio, M., Pizzolo, G., Foa, R., Chiusolo P. (ORCID:0000-0002-1355-1587), Lazzarotto, D., Tanasi, I., Vitale, A., Piccini, M., Dargenio, M., Giglio, F., Forghieri, F., Fracchiolla, N., Cerrano, M., Todisco, E., Papayannidis, C., Leoncin, M., Defina, M., Guolo, F., Pasciolla, C., Delia, M., Chiusolo, Patrizia, Mule, A., Candoni, A., Bonifacio, M., Pizzolo, G., Foa, R., and Chiusolo P. (ORCID:0000-0002-1355-1587)
- Abstract
Mixed-phenotype acute leukemia (MPAL) is a rare disease. Treatment is often similar to that of acute lymphoblastic leukemia (ALL), but the outcome in adults and the role of allogeneic stem cell transplantation (AlloSCT) are not well defined. We report on 77 adult patients diagnosed with MPAL over the last 10 years and treated with a curative intent. Median age was 49 years; 7.6% of cases had a BCR::ABL1 rearrangement. Thirty patients (39%) were treated with an acute myeloid leukemia (AML)–like induction and 47 (61%) with an ALL-like scheme. The complete remission (CR) rate was 67.6% and an ALL-like therapy was associated with a better CR rate (P = 0.048). The median OS was 41.9 months; age ≤ 60 years was associated with a better OS (67 vs 26 months, P = 0.014). An AlloSCT was performed in 50 patients (65%). The 5-year OS of transplanted patients was 54%. The OS post-AlloSCT was better in patients who were minimal residual disease (MRD)-negative prior to transplant (75.8% vs 45.2%, P = 0.06). This study shows that MPAL patients respond better to an ALL-like induction therapy; that consolidation therapy should include, whenever possible, an AlloSCT and that MRD negativity should be a primary endpoint of treatment.
- Published
- 2023
6. Assessment of the efficacy and tolerability of ruxolitinib for the treatment of myelofibrosis patients in a real-life setting: An Italian MYNERVA Project
- Author
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Coltro, G., Sant'Antonio, E., Palumbo, G. A., Mannelli, F., De , Stefano, V., Ruggeri, M., Elli, E. M., Zanotti, R., Borsani, O., Bertozzi, I., Duminuco, A., Betti, S., Carli, G., Cavalca, F., Tanasi, I., Rumi, E., Randi, M. L., Garibaldi, B., Loscocco, G. G., Guglielmelli, P., and Vannucchi, A. M.
- Subjects
safety ,Cancer Research ,Oncology ,ruxolitinib ,efficacy ,Radiology, Nuclear Medicine and imaging ,myelofibrosis - Published
- 2023
7. P535: UPDATES FROM ITALIAN MULTICENTER REAL-LIFE EXPERIENCE ON CPX-351 THERAPY IN YOUNG PATIENTS (<60 YEARS OLD).
- Author
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Garibaldi, B., primary, Franciosa, M., additional, Pilo, F., additional, Menotti, D., additional, Cardinali, V., additional, Brunetti, L., additional, Martino, E. A., additional, Vigna, E., additional, Tanasi, I., additional, Duminuco, A., additional, Maugeri, C., additional, Parisi, M. S., additional, Fiumara, P. F., additional, Mauro, E., additional, Gentile, M., additional, Martelli, M. P., additional, Capelli, D., additional, Romani, C., additional, Galimberti, S., additional, Palumbo, G. A., additional, Di Raimondo, F., additional, and Vetro, C., additional
- Published
- 2022
- Full Text
- View/download PDF
8. P357: MULTICENTER RETROSPECTIVE ANALYSIS OF CLINICAL OUTCOME OF ADULT PATIENS WITH MIXED-PHENOTYPE ACUTE LEUKEMIA (MPAL) DIAGNOSED AND TREATED IN THE LAST TEN YEARS. A CAMPUS-ALL STUDY.
- Author
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Lazzarotto, D., primary, Tanasi, I., additional, Vitale, A., additional, Piccini, M., additional, Dargenio, M., additional, Giglio, F., additional, Forghieri, F., additional, Fracchiolla, N., additional, Cerrano, M., additional, Todisco, E., additional, Papayannidis, C., additional, Leoncin, M., additional, Defina, M., additional, Guolo, F., additional, Pasciolla, C., additional, Delia, M., additional, Chiusolo, P., additional, Mulè, A., additional, Candoni, A., additional, Bonifacio, M., additional, Pizzolo, G., additional, and Foà, R., additional
- Published
- 2022
- Full Text
- View/download PDF
9. Daratumumab with or without chemotherapy in relapsed and refractory acute lymphoblastic leukemia. A retrospective observational Campus ALL study
- Author
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Cerrano, M., Bonifacio, M., Olivi, M., Curti, A., Malagola, M., Dargenio, M., Scattolin, A. M., Papayannidis, C., Forghieri, F., Gurrieri, C., Tanasi, I., Zappasodi, P., Starza, R. L., Fracchiolla, N. S., Chiusolo, Patrizia, Giaccone, L., Del Principe, M. I., Giglio, F., Defina, M., Favre, C., Rizzari, C., Castella, B., Pizzolo, G., Ferrara, F., Chiaretti, S., Foa, R., Chiusolo P. (ORCID:0000-0002-1355-1587), Cerrano, M., Bonifacio, M., Olivi, M., Curti, A., Malagola, M., Dargenio, M., Scattolin, A. M., Papayannidis, C., Forghieri, F., Gurrieri, C., Tanasi, I., Zappasodi, P., Starza, R. L., Fracchiolla, N. S., Chiusolo, Patrizia, Giaccone, L., Del Principe, M. I., Giglio, F., Defina, M., Favre, C., Rizzari, C., Castella, B., Pizzolo, G., Ferrara, F., Chiaretti, S., Foa, R., and Chiusolo P. (ORCID:0000-0002-1355-1587)
- Abstract
n/a
- Published
- 2022
10. Corrigendum: 'Venetoclax in combination with hypomethylating agents in previously untreated patients with acute myeloid leukemia ineligible for intensive treatment: a real-life multicenter experience' (Leukemia Research (2022) 114, (106803), (S0145212622000297), (10.1016/j.leukres.2022.106803))
- Author
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De Bellis, E., Imbergamo, S., Candoni, A., Lico, A., Tanasi, I., Mauro, E., Mosna, F., Leoncin, M., Stulle, M., Griguolo, D., Pravato, S., Trentin, L., Lazzarotto, D., Di Bona, E., Sancetta, R., Lucchini, E., Poiani, M., Palmieri, C., and Zaja, F.
- Published
- 2022
11. Corrigendum to 'Venetoclax in combination with hypomethylating agents in previously untreated patients with acute myeloid leukemia ineligible for intensive treatment: a real-life multicenter experience' [Leukemia Res. 114 (March 2022) 106803](S0145212622000297)(10.1016/j.leukres.2022.106803)
- Author
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De Bellis, E., Imbergamo, S., Candoni, A., Lico, A., Tanasi, I., Mauro, E., Mosna, F., Leoncin, M., Stulle, M., Griguolo, D., Pravato, S., Trentin, L., Lazzarotto, D., Di Bona, E., Sancetta, R., Lucchini, E., Poiani, M., Palmieri, C., and Zaja, F.
- Published
- 2022
12. The Role of Notch and Wnt Signaling in MSC Communication in Normal and Leukemic Bone Marrow Niche
- Author
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Takam Kamga, P. (Paul), Bazzoni, R. (Riccardo), Dal Collo, G. (Giada), Cassaro, A. (Adriana), Tanasi, I. (Ilaria), Russignan, A. (Anna), Tecchio, C. (Cristina), Krampera, M. (Mauro), Takam Kamga, P. (Paul), Bazzoni, R. (Riccardo), Dal Collo, G. (Giada), Cassaro, A. (Adriana), Tanasi, I. (Ilaria), Russignan, A. (Anna), Tecchio, C. (Cristina), and Krampera, M. (Mauro)
- Abstract
Notch and Wnt signaling are highly conserved intercellular communication pathways involved in developmental processes, such as hematopoiesis. Even though data from literature support a role for these two pathways in both physiological hematopoiesis and leukemia, there are still many controversies concerning the nature of their contribution. Early studies, strengthened by findings from T-cell acute lymphoblastic leukemia (T-ALL), have focused their investigation on the mutations in genes encoding for components of the pathways, with limited results except for B-cell chronic lymphocytic leukemia (CLL); in because in other leukemia the two pathways could be hyper-expressed without genetic abnormalities. As normal and malignant hematopoiesis require close and complex interact
- Published
- 2021
- Full Text
- View/download PDF
13. Small Molecule Inhibitors of Microenvironmental Wnt/beta-Catenin Signaling Enhance the Chemosensitivity of Acute Myeloid Leukemia
- Author
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Kamga, PT, Collo, G, Cassaro, A, Bazzoni, R, Delfino, P, Adamo, A, Bonato, A, Carbone, C, Tanasi, I, Bonifacio, M, Krampera, M, Kamga, PT, Collo, G, Cassaro, A, Bazzoni, R, Delfino, P, Adamo, A, Bonato, A, Carbone, C, Tanasi, I, Bonifacio, M, and Krampera, M
- Published
- 2020
14. PCN188 Identification of Patients with Chronic Myeloid Leukemia (CML), Multiple Myeloma (MM) and Myelodysplastic Syndromes (MDS) Using Real-World DATA: Findings from the Prihta - Ematologia project
- Author
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Degli Esposti, L., primary, Perrone, V., additional, Becchetti, A.G., additional, Bovo, C., additional, Giobelli, L., additional, Greco, C., additional, Poggiani, C., additional, Sangiorgi, D., additional, Tanasi, I., additional, Andretta, M., additional, and Krampera, M., additional
- Published
- 2020
- Full Text
- View/download PDF
15. PB1930 CORRELATION BETWEEN LEVELS OF EARLY MOLECULAR RESPONSE AND BCR-ABL TRANSCRIPT TYPE IN STABLE DMR ATTAINMENT IN CML PATIENTS TREATED WITH IMATINIB
- Author
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Tiribelli, M., primary, Bonifacio, M., additional, Binotto, G., additional, Griguolo, D., additional, Scaffidi, L., additional, Frison, L., additional, Miggiano, M.C., additional, Calistri, E., additional, Stulle, M., additional, De Biasi, E., additional, Sartori, R., additional, Stella, R., additional, Tanasi, I., additional, Ruggeri, M., additional, Damiani, D., additional, Semenzato, G., additional, Krampera, M., additional, and Fanin, R., additional
- Published
- 2019
- Full Text
- View/download PDF
16. PS1461 FAMILIAL OCCURRENCE OF SYSTEMIC AND CUTANEOUS MASTOCYTOSIS IN AN ADULT MULTICENTER SERIES: A REPORT OF 22 CLUSTERED CASES
- Author
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Tanasi, I., primary, Bonifacio, M., additional, Pizzolato, M., additional, Grifoni, F.I., additional, Sciumè, M., additional, Elena, C., additional, Benvenuti, P., additional, Mannelli, F., additional, Parente, R., additional, Schena, D., additional, Scaffidi, L., additional, Bonadonna, P., additional, Papayannidis, C., additional, Rondoni, M., additional, Criscuolo, M., additional, Vannucchi, A.M., additional, Triggiani, M., additional, Martinelli, G., additional, Krampera, M., additional, and Zanotti, R., additional
- Published
- 2019
- Full Text
- View/download PDF
17. Daratumumab with or without chemotherapy in relapsed and refractory acute lymphoblastic leukemia. A retrospective observational Campus ALL study
- Author
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Marco Cerrano, Massimiliano Bonifacio, Matteo Olivi, Antonio Curti, Michele Malagola, Michelina Dargenio, Anna Maria Scattolin, Cristina Papayannidis, Fabio Forghieri, Carmela Gurrieri, Ilaria Tanasi, Patrizia Zappasodi, Roberta La Starza, Nicola Stefano Fracchiolla, Patrizia Chiusolo, Luisa Giaccone, Maria Ilaria Del Principe, Fabio Giglio, Marzia Defina, Claudio Favre, Carmelo Rizzari, Barbara Castella, Giovanni Pizzolo, Felicetto Ferrara, Sabina Chiaretti, Robin Foà, Cerrano, M, Bonifacio, M, Olivi, M, Curti, A, Malagola, M, Dargenio, M, Scattolin, A, Papayannidis, C, Forghieri, F, Gurrieri, C, Tanasi, I, Zappasodi, P, Starza, R, Fracchiolla, N, Chiusolo, P, Giaccone, L, Del Principe, M, Giglio, F, Defina, M, Favre, C, Rizzari, C, Castella, B, Pizzolo, G, Ferrara, F, Chiaretti, S, and Foa, R
- Subjects
Humans ,Antibodies, Monoclonal ,Hematology ,MED/38 - PEDIATRIA GENERALE E SPECIALISTICA ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,Human ,Retrospective Studies - Published
- 2022
18. Underlying systemic mastocytosis in patients with unexplained osteoporosis: score proposal.
- Author
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Tanasi I, Crosera L, Taus F, Orsolini G, Adami G, Olivieri F, Bernardelli A, Bonadonna P, Nalin F, Sella S, Giannini S, Liu Y, Mannelli F, Vanderwert F, Bonifacio M, Krampera M, Rossini M, Lyons JJ, and Zanotti R
- Subjects
- Humans, Female, Male, Middle Aged, Aged, Adult, Tryptases blood, Bone Marrow pathology, Mastocytosis, Systemic complications, Mastocytosis, Systemic blood, Mastocytosis, Systemic diagnosis, Osteoporosis
- Abstract
Background: A score to predict the association between unexplained osteoporosis and an underlying systemic Mastocytosis (SM) is lacking., Objective: This study aimed at identifying criteria able to predict the diagnosis of SM without skin involvement and provide an indication for bone marrow (BM) assessment., Methods: We included 139 adult patients with unexplained osteoporosis and suspected SM. After BM evaluation, 63 patients (45.3 %) were diagnosed with SM, while the remaining 76 patients (54.7 %) negative for clonal mast cell (MC) disorders, constituted our control group. Univariate and multivariate analysis identified three independent predictive factors: age (<54 years: +1 point, >64 years: -1 point), serum basal tryptase (sBT) levels >19 ng/mL (+2 points) and vertebral fractures (+2 points)., Results: These variables were used to build the OSTEO-score, able to predict the diagnosis of SM before BM assessment with a sensitivity of 73.5 % and a specificity of 67.1 %. Patients with a score < 3 had a lower probability of having SM compared to patients with a score ≥ 3 (28.5 % and 71.4 %, respectively, p < 0.0001). When sBT levels were corrected for the presence of hereditary alpha-tryptasemia (HαT) using the BST calculater (https://bst-calculater.niaid.nih.gov/) recently published [1,2], the sensitivity of ΗαT-adjusted OSTEO-score increased to 87.8 %, and the specificity reached 76.1 %. Also, the positive predictive value of a score ≥ 3 increased to 85.2 %., Conclusions: Further studies are needed to validate these results and characterize the role of tryptase genotyping in patients with unexplained osteoporosis in reducing the risk of misdiagnosing patients with SM. Our proposed scoring model allows the identification of patients with the highest probability of having SM, avoiding unnecessary BM studies., Competing Interests: Declaration of competing interest All the authors have approved this manuscript and declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
19. Mast Cell Disorders and Hymenoptera Venom-Triggered Anaphylaxis: Evaluation and Management.
- Author
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Boggs NA, Tanasi I, Hartmann K, Zanotti R, and Gonzalez-de-Olano D
- Abstract
Patients with Hymenoptera venom allergy (HVA), especially those with severe anaphylaxis, frequently have concomitant clonal mast cell disease (MCD) in the form of systemic mastocytosis or monoclonal mast cell activation syndrome. Detection of clonal MCD is important because it will have significant consequences for managing HVA. Therefore, we recommend patients with HVA be systematically screened for clonal MCD. The pretest probability of clonal MCD can be assessed in a stepwise fashion starting with examination of the skin for typical monomorphic maculopapular cutaneous mastocytosis lesions; measurement of the baseline serum tryptase (BST) and tryptase genotyping for patients with BST greater than 11 ng/mL; followed by the Red Española de Mastocitosis score, which is calculated using anaphylaxis clinical features, BST, and the patient's sex. A bone marrow biopsy should be performed in patients with monomorphic maculopapular cutaneous mastocytosis, a Red Española de Mastocitosis score of 2 or greater, or an elevated BST based on tryptase genotype. Patients with HVA and a clonal MCD should be treated with immunotherapy directed against the Hymenoptera venom for which they are sensitized. For this high-risk subgroup of patients with HVA, it is recommended to continue immunotherapy for more than 5 years or indefinitely and to carry at least three epinephrine autoinjectors. Future studies should determine whether KIT D816V-selective tyrosine kinase inhibitors are effective at preventing or reducing the severity of Hymenoptera-venom triggered anaphylaxis in patients with clonal MCD., (Published by Elsevier Inc.)
- Published
- 2024
- Full Text
- View/download PDF
20. Long-term remissions with Gilteritinib in early relapse after allogeneic stem cell transplantation of FLT3/NPM1 mutated acute myeloid leukemia.
- Author
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Tamellini E, Sorio M, Andreini A, Tecchio C, Nadali G, Bernardelli A, Ferrarini I, Crosera L, Vatteroni A, Simio C, Benedetti F, Krampera M, and Tanasi I
- Abstract
Early post-allogeneic hematopoietic stem cell transplantation (allo-HSCT) relapse in patients with acute myeloid leukemia (AML) has an almost invariably dismal prognosis. Recent studies have demonstrated that FLT3 inhibition enhances the graft-versus-leukemia effect in vitro and in vivo. Thus, FLT-3 inhibitors may be viable treatment options in this setting. Here, we report three patients with FLT3 and NPM1 mutated AML who relapsed early after allo-HSCT and were treated with gilteritinib (associated with donor lymphocyte Infusion in two patients) to achieve long-term remission without a second transplantation., Competing Interests: The authors declare no conflict of interest. Disclosure forms provided by the authors are available on the website., (Copyright Ⓒ2024 Asia-Pacific Blood and Marrow Transplantation Group (APBMT).)
- Published
- 2024
- Full Text
- View/download PDF
21. Comparison between indolent systemic mastocytosis and clonal mast cell disease not meeting WHO diagnostic criteria: A nationwide multicenter retrospective analysis.
- Author
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Sciumè M, Serpenti F, Zanotti R, Bonadonna P, Tanasi I, Crosera L, Elena C, Mannelli F, Crupi F, Papayannidis C, Sartor C, Soverini S, Rondoni M, Eller-Vainicher C, Pravettoni V, Rivolta F, Alberti Violetti S, Croci GA, Migliorini AC, Bolli N, Giannarelli D, and Grifoni FI
- Subjects
- Humans, Retrospective Studies, Male, Female, Middle Aged, Aged, World Health Organization, Adult, Mastocytosis, Systemic diagnosis, Mastocytosis, Systemic pathology
- Published
- 2024
- Full Text
- View/download PDF
22. BH3 mimetics in relapsed and refractory adult acute lymphoblastic leukemia: a Campus ALL real-life study.
- Author
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Malfona F, Tanasi I, Piccini M, Papayannidis C, Federico V, Mancini V, Roncoroni E, Todisco E, Bianchi S, Ciotti G, Chiusolo P, Gentile M, Gianfelici V, Giglio F, Malagola M, Mulé A, Saraceni F, Vetro C, Zallio F, Cappelli LV, Pizzolo G, Foà R, Bonifacio M, and Chiaretti S
- Subjects
- Adult, Humans, Acute Disease, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy
- Published
- 2024
- Full Text
- View/download PDF
23. The clinical experience of compassionate use program for avapritinib: implications for drug positioning in the therapeutic scenario of systemic mastocytosis.
- Author
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Mannelli F, Crupi F, Zanotti R, Pagano L, Rapezzi D, Tanasi I, Criscuolo M, Bonifacio M, Fresa A, Guglielmelli P, and Vannucchi AM
- Abstract
In systemic mastocytosis, cytoreductive treatment is indicated for advanced systemic mastocytosis (AdvSM) variants. The treatment scenario is rapidly diversifying especially with the introduction of KIT tyrosine kinase inhibitors. Avapritinib is a second-generation potent and selective inhibitor of the mutant KIT D816V that, based on the results of pivotal clinical trials, was approved for the treatment of adults with AdvSM by the regulatory agencies US FDA and EMA. The present article reports the experience of treating SM patients with avapritinib in an Italian compassionate use program. The data from our case series confirm the drug as being active after multiple lines of treatment allowing rapid achievement of profound responses, making it also an effective bridging strategy to allogeneic transplant in eligible patients. However, the anticipated wider use of avapritinib in the near future will require careful monitoring of side effects, especially in heavily pretreated patients., Competing Interests: FM: Speaker bureau Blueprint, Novartis, AbbVie; FC: none; RZ: Honoraria Novartis and Blueprint, advisory board Blueprint, Cogent; LP: Speaker bureau Blueprint, Gilead, Janssen, Jazz, Novartis, Pfizer, Stemline-Menarini; DR: none; IT: none; MC: Speaker bureau Novartis; MB: none; AF: none; PG: none; AMV: Speaker bureau AOP, Blueprint, BMS, GSK, Incyte, Novartis., (© The Author(s), 2023.)
- Published
- 2023
- Full Text
- View/download PDF
24. Blinatumomab differentially modulates peripheral blood and bone marrow immune cell repertoire: A Campus ALL study.
- Author
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Ocadlikova D, Lussana F, Fracchiolla N, Bonifacio M, Santoro L, Delia M, Chiaretti S, Pasciolla C, Cignetti A, Forghieri F, Grimaldi F, Corradi G, Zannoni L, De Propris S, Borleri GM, Tanasi I, Vadakekolathu J, Rutella S, Guarini AR, Foà R, and Curti A
- Subjects
- Humans, Bone Marrow metabolism, Remission Induction, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Antineoplastic Agents pharmacology, Antineoplastic Agents therapeutic use, Antibodies, Bispecific pharmacology, Antibodies, Bispecific therapeutic use, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma metabolism
- Abstract
Blinatumomab is the first bi-specific T-cell engager approved for relapsed or refractory B-cell precursor acute lymphoblastic leukaemia (B-ALL). Despite remarkable clinical results, the effects of blinatumomab on the host immune cell repertoire are not fully elucidated. In the present study, we characterized the peripheral blood (PB) and, for the first time, the bone marrow (BM) immune cell repertoire upon blinatumomab treatment. Twenty-nine patients with B-ALL received blinatumomab according to clinical practice. Deep multiparametric flow cytometry was used to characterize lymphoid subsets during the first treatment cycle. Blinatumomab induced a transient redistribution of PB effector T-cell subsets and Treg cells with a persistent increase in cytotoxic NK cells, which was associated with a transient upregulation of immune checkpoint receptors on PB CD4 and CD8 T-cell subpopulations and of CD39 expression on suppressive Treg cells. Of note, BM immune T-cell subsets showed a broader post-treatment subversion, including the modulation of markers associated with a T-cell-exhausted phenotype. In conclusion, our study indicates that blinatumomab differentially modulates the PB and BM immune cell repertoire, which may have relevant clinical implications in the therapeutic setting., (© 2023 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)
- Published
- 2023
- Full Text
- View/download PDF
25. Real-world efficacy and safety of luspatercept and predictive factors of response in patients with lower risk myelodysplastic syndromes with ring sideroblasts.
- Author
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Lanino L, Restuccia F, Perego A, Ubezio M, Fattizzo B, Riva M, Consagra A, Musto P, Cilloni D, Oliva EN, Palmieri R, Poloni A, Califano C, Capodanno I, Itri F, Elena C, Fozza C, Pane F, Pelizzari AM, Breccia M, Di Bassiano F, Crisà E, Ferrero D, Giai V, Barraco D, Vaccarino A, Griguolo D, Minetto P, Quintini M, Paolini S, Sanpaolo G, Sessa M, Bocchia M, Di Renzo N, Diral E, Leuzzi L, Genua A, Guarini A, Molteni A, Nicolino B, Occhini U, Rivoli G, Bono R, Calvisi A, Castelli A, Di Bona E, Di Veroli A, Ferrara F, Fianchi L, Galimberti S, Grimaldi D, Marchetti M, Norata M, Frigeni M, Sancetta R, Selleri C, Tanasi I, Tosi P, Turrini M, Giordano L, Finelli C, Pasini P, Naldi I, Santini V, and Della Porta MG
- Subjects
- Humans, Activin Receptors, Type II, Immunoglobulin Fc Fragments, Myelodysplastic Syndromes drug therapy, Anemia, Sideroblastic drug therapy
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- 2023
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26. Mast cell leukemia: clinical and molecular features and survival outcomes of patients in the ECNM Registry.
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Kennedy VE, Perkins C, Reiter A, Jawhar M, Lübke J, Kluin-Nelemans HC, Shomali W, Langford C, Abuel J, Hermine O, Niedoszytko M, Gorska A, Mital A, Bonadonna P, Zanotti R, Tanasi I, Mattsson M, Hagglund H, Triggiani M, Yavuz AS, Panse J, Christen D, Heizmann M, Shoumariyeh K, Müller S, Elena C, Malcovati L, Fiorelli N, Wortmann F, Vucinic V, Brockow K, Fokoloros C, Papageorgiou SG, Breynaert C, Bullens D, Doubek M, Ilerhaus A, Angelova-Fischer I, Solomianyi O, Várkonyi J, Sabato V, Rüfer A, Schug TD, Hermans MAW, Fortina AB, Caroppo F, Bumbea H, Gulen T, Hartmann K, Elberink HO, Schwaab J, Arock M, Valent P, Sperr WR, and Gotlib J
- Subjects
- Humans, Mast Cells, Abnormal Karyotype, Leukemia, Mast-Cell diagnosis, Leukemia, Mast-Cell genetics, Mastocytosis, Systemic diagnosis, Mastocytosis, Systemic drug therapy, Mastocytosis, Systemic genetics, Mastocytosis
- Abstract
Mast cell leukemia (MCL) is a rare subtype of systemic mastocytosis defined by ≥20% mast cells (MC) on a bone marrow aspirate. We evaluated 92 patients with MCL from the European Competence Network on Mastocytosis registry. Thirty-one (34%) patients had a diagnosis of MCL with an associated hematologic neoplasm (MCL-AHN). Chronic MCL (lack of C-findings) comprised 14% of patients, and only 4.5% had "leukemic MCL" (≥10% circulating MCs). KIT D816V was found in 62/85 (73%) evaluable patients; 9 (11%) individuals exhibited alternative KIT mutations, and no KIT variants were detected in 14 (17%) subjects. Ten evaluable patients (17%) had an abnormal karyotype and the poor-risk SRSF2, ASXL1, and RUNX1 (S/A/R) mutations were identified in 16/36 (44%) patients who underwent next-generation sequencing. Midostaurin was the most common therapy administered to 65% of patients and 45% as first-line therapy. The median overall survival (OS) was 1.6 years. In multivariate analysis (S/A/R mutations excluded owing to low event rates), a diagnosis of MCL-AHN (hazard ratio [HR], 4.7; 95% confidence interval [CI], 1.7-13.0; P = .001) and abnormal karyotype (HR, 5.6; 95% CI, 1.4-13.3; P = .02) were associated with inferior OS; KIT D816V positivity (HR, 0.33; 95% CI, 0.11-0.98; P = .04) and midostaurin treatment (HR, 0.32; 95% CI, 0.08-0.72; P = .008) were associated with superior OS. These data provide the most comprehensive snapshot of the clinicopathologic, molecular, and treatment landscape of MCL to date, and should help further inform subtyping and prognostication of MCL., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
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- 2023
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27. Multicenter retrospective analysis of clinical outcome of adult patients with mixed-phenotype acute leukemia treated with acute myeloid leukemia-like or acute lymphoblastic leukemia-like chemotherapy and impact of allogeneic stem cell transplantation: a Campus ALL study.
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Lazzarotto D, Tanasi I, Vitale A, Piccini M, Dargenio M, Giglio F, Forghieri F, Fracchiolla N, Cerrano M, Todisco E, Papayannidis C, Leoncin M, Defina M, Guolo F, Pasciolla C, Delia M, Chiusolo P, Mulè A, Candoni A, Bonifacio M, Pizzolo G, and Foà R
- Subjects
- Humans, Acute Disease, Phenotype, Retrospective Studies, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma genetics, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma diagnosis
- Abstract
Mixed-phenotype acute leukemia (MPAL) is a rare disease. Treatment is often similar to that of acute lymphoblastic leukemia (ALL), but the outcome in adults and the role of allogeneic stem cell transplantation (AlloSCT) are not well defined. We report on 77 adult patients diagnosed with MPAL over the last 10 years and treated with a curative intent. Median age was 49 years; 7.6% of cases had a BCR::ABL1 rearrangement. Thirty patients (39%) were treated with an acute myeloid leukemia (AML)-like induction and 47 (61%) with an ALL-like scheme. The complete remission (CR) rate was 67.6% and an ALL-like therapy was associated with a better CR rate (P = 0.048). The median OS was 41.9 months; age ≤ 60 years was associated with a better OS (67 vs 26 months, P = 0.014). An AlloSCT was performed in 50 patients (65%). The 5-year OS of transplanted patients was 54%. The OS post-AlloSCT was better in patients who were minimal residual disease (MRD)-negative prior to transplant (75.8% vs 45.2%, P = 0.06). This study shows that MPAL patients respond better to an ALL-like induction therapy; that consolidation therapy should include, whenever possible, an AlloSCT and that MRD negativity should be a primary endpoint of treatment., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2023
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28. Assessment of the efficacy and tolerability of ruxolitinib for the treatment of myelofibrosis patients in a real-life setting: An Italian MYNERVA Project.
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Coltro G, Sant'Antonio E, Palumbo GA, Mannelli F, De Stefano V, Ruggeri M, Elli EM, Zanotti R, Borsani O, Bertozzi I, Duminuco A, Betti S, Carli G, Cavalca F, Tanasi I, Rumi E, Randi ML, Garibaldi B, Loscocco GG, Guglielmelli P, and Vannucchi AM
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- Humans, Nitriles therapeutic use, Pyrimidines therapeutic use, Italy, Treatment Outcome, Primary Myelofibrosis complications
- 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., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
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- 2023
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29. Incidence, treatment and outcome of central nervous system relapse in adult acute lymphoblastic leukaemia patients treated front-line with paediatric-inspired regimens: A retrospective multicentre Campus ALL study.
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Dargenio M, Bonifacio M, Chiaretti S, Vitale A, Fracchiolla NS, Papayannidis C, Giglio F, Salutari P, Audisio E, Scappini B, Zappasodi P, Defina M, Forghieri F, Scattolin AM, Todisco E, Lunghi M, Guolo F, Del Principe MI, Annunziata M, Lazzarotto D, Cedrone M, Pasciolla C, Imovilli A, Tanasi I, Trappolini S, Cerrano M, La Starza R, Krampera M, Di Renzo N, Candoni A, Pizzolo G, Ferrara F, and Foà R
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- Male, Humans, Incidence, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Central Nervous System, Recurrence, Treatment Outcome, Central Nervous System Neoplasms drug therapy, Central Nervous System Neoplasms epidemiology, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma radiotherapy
- Abstract
Within the Campus ALL network we analyzed the incidence, characteristics, treatment and outcome of a central nervous system (CNS) relapse in 1035 consecutive adult acute lymphoblastic leukemia (ALL) patients treated frontline with pediatric-inspired protocols between 2009 and 2020. Seventy-one patients (6.8%) experienced a CNS recurrence, more frequently in T- (28/278; 10%) than in B-ALL (43/757; 5.7%) (p = 0.017). An early CNS relapse-< 12 months from diagnosis-was observed in 41 patients. In multivariate analysis, risk factors for early CNS relapse included T-cell phenotype (p = <0.001), hyperleucocytosis >100 × 10
9 /L (p<0.001) and male gender (p = 0.015). Treatment was heterogeneous, including chemotherapy, radiotherapy, intrathecal therapy and novel agents. A complete remission (CR) was obtained in 39 patients (55%) with no differences among strategies. After CR, 26 patients underwent an allogenic transplant, with a significant overall survival benefit compared to non-transplanted patients (p = 0.012). After a median observation of 8 months from CNS relapse, 23 patients (32%) were alive. In multivariate analysis, the time to CNS relapse was the strongest predictor of a lower 2-year post-relapse survival (p<0.001). In conclusion, in adult ALL the outcome after a CNS relapse remains very poor. Effective CNS prophylaxis remains the best approach and allogenic transplant should be pursued when possible., (© 2022 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)- Published
- 2023
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30. Update on the Role and Utility of Extracellular Vesicles in Hematological Malignancies.
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Bazzoni R, Tanasi I, Turazzi N, and Krampera M
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- Bone Marrow pathology, Cell Communication, Humans, Tumor Microenvironment, Extracellular Vesicles metabolism, Hematologic Neoplasms pathology, Hematologic Neoplasms therapy, Neoplasms pathology
- Abstract
Extracellular vesicles (EVs) are membrane-surrounded cellular particles released by virtually any cell type, containing numerous bioactive molecules, including lipids, proteins, and nucleic acids. EVs act as a very efficient intercellular communication system by releasing their content into target cells, thus affecting their fate and influencing several biological processes. EVs are released both in physiological and pathological conditions, including several types of cancers. In hematological malignancies (HM), EVs have emerged as new critical players, contributing to tumor-to-stroma, stroma-to-tumor, and tumor-to-tumor cell communication. Therefore, EVs have been shown to play a crucial role in the pathogenesis and clinical course of several HM, contributing to tumor development, progression, and drug resistance. Furthermore, tumor EVs can reprogram the bone marrow (BM) microenvironment and turn it into a sanctuary, in which cancer cells suppress both the normal hematopoiesis and the immunological antitumor activity, conferring a therapy-resistant phenotype. Due to their physicochemical characteristics and pro-tumor properties, EVs have been suggested as new diagnostic biomarkers, therapeutic targets, and pharmacological nanocarriers. This review aims to provide an update on the pathogenetic contribution and the putative therapeutic utility of EVs in hematological diseases., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2022
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31. Daratumumab with or without chemotherapy in relapsed and refractory acute lymphoblastic leukemia. A retrospective observational Campus ALL study.
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Cerrano M, Bonifacio M, Olivi M, Curti A, Malagola M, Dargenio M, Scattolin AM, Papayannidis C, Forghieri F, Gurrieri C, Tanasi I, Zappasodi P, La Starza R, Fracchiolla NS, Chiusolo P, Giaccone L, Del Principe MI, Giglio F, Defina M, Favre C, Rizzari C, Castella B, Pizzolo G, Ferrara F, Chiaretti S, and Foà R
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- Humans, Retrospective Studies, Antibodies, Monoclonal therapeutic use, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy
- Published
- 2022
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32. Corrigendum to "Venetoclax in combination with hypomethylating agents in previously untreated patients with acute myeloid leukemia ineligible for intensive treatment: a real-life multicenter experience" [Leukemia Res. 114 (March 2022) 106803].
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De Bellis E, Imbergamo S, Candoni A, Liço A, Tanasi I, Mauro E, Mosna F, Leoncin M, Stulle M, Griguolo D, Pravato S, Trentin L, Lazzarotto D, Di Bona E, Sancetta R, Lucchini E, Poiani M, Palmieri C, and Zaja F
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- 2022
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33. Venetoclax in combination with hypomethylating agents in previously untreated patients with acute myeloid leukemia ineligible for intensive treatment: a real-life multicenter experience.
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De Bellis E, Imbergamo S, Candoni A, Liço A, Tanasi I, Mauro E, Mosna F, Leoncin M, Stulle M, Griguolo D, Pravato S, Trentin L, Lazzarotto D, Di Bona E, Bassan R, Lucchini E, Poiani M, Palmieri C, and Zaja F
- Subjects
- Azacitidine, Bridged Bicyclo Compounds, Heterocyclic, Decitabine, Humans, Retrospective Studies, Sulfonamides, Antineoplastic Combined Chemotherapy Protocols adverse effects, Leukemia, Myeloid, Acute
- Abstract
The addition of venetoclax to hypomethylating agents (HMA-V) improved the outcome of patients with newly diagnosed acute myeloid leukemia (AML) ineligible for intensive treatment. The aim of our study was to confirm data reported in literature, in a real-life multicenter experience. We retrospectively evaluated 56 naïve AML patients who received HMA-V at 8 different collaborating Hematology Units in the North-East of Italy, from September 2018 to October 2020. Patients received azacitidine or decitabine at standard dose, adding venetoclax starting from cycle 1-3. The median time-to-response was 2 cycles and composite complete remission rate (CCR) was 67.9%. Thirteen out of 38 responders (34.2%) relapsed, with a median response duration of 13.7 months. Transfusion independence (TI) was obtained in 27 (87.0%) and 28 (90.3%) out of 31 patients for red blood cells and platelets, respectively. Median OS was 12.3 months (95% CI, 8.1-16.5), and median PFS was 11.3 months (95% CI, 4.6-17.9). Cytogenetic risk was the only variable impacting on survival, while no differences were observed stratifying patients by age, bone marrow blasts, WHO classification or type of HMA. In conclusion, our real-life multicenter experience indicates that HMA-V treatment allows achieving good response rates in naïve AML patients, ineligible for intensive chemotherapy., (Copyright © 2022 Elsevier Ltd. All rights reserved.)
- Published
- 2022
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34. A Multidisciplinary Diagnostic Approach Reveals a Higher Prevalence of Indolent Systemic Mastocytosis: 15-Years' Experience of the GISM Network.
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Zanotti R, Bonifacio M, Isolan C, Tanasi I, Crosera L, Olivieri F, Orsolini G, Schena D, and Bonadonna P
- Abstract
Systemic mastocytosis (SM) and other adult clonal mast cell disorders (CMD) are often underestimated, and their epidemiology data are scarce. We aimed at evaluating the impact of the activity of the Interdisciplinary Group for Study of Mastocytosis (GISM) of Verona on the prevalence and incidence of CMD. We examined the data of 502 adult patients diagnosed with CMD and residing in the Veneto Region, consecutively referred to GISM between 2006 and 2020. SM was diagnosed in 431 cases, while 71 patients had cutaneous mastocytosis or other CMD. Indolent SM represented the most frequent SM variant (91.0%), mainly with the characteristics of bone marrow mastocytosis (54.8%). The prevalence of SM in the adult population of the Veneto region and of the Verona province was 10.2 and 17.2/100,000 inhabitants, respectively. The mean incidence of new SM cases in Verona was 1.09/100,000 inhabitants/year. Hymenoptera venom allergy was the main reason (50%) leading to the CMD diagnosis. Osteoporosis, often complicated by fragility fractures, was present in 35% of cases, even in young patients, especially males. Our data show a higher prevalence and incidence of SM than previously reported, confirming that reference centers with multidisciplinary approach are essential for the recognition and early diagnosis of CMD.
- Published
- 2021
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35. Systemic Mastocytosis: Multidisciplinary Approach.
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Zanotti R, Tanasi I, Crosera L, Bonifacio M, Schena D, Orsolini G, Mastropaolo F, Tebaldi M, Olivieri E, and Bonadonna P
- Abstract
Systemic mastocytosis (SM) is a heterogeneous group of diseases that affect almost exclusively adults and are defined by the proliferation and accumulation of clonal mast cells (MC) in various tissues. Disease subtypes range from indolent to rare aggressive forms. Although SM is classified as a rare disease, it is believed to be likely underdiagnosed. Major signs and symptoms mainly depend on MC activation and less frequent organ infiltration, typical of more aggressive variants. Diagnosis may be challenging, and symptoms can be aspecific and involve several organs. Therefore, it is advisable to refer patients to specialized centers, having sufficient knowledge of the disease, sensitive diagnostic procedures, offering a personalized and multidisciplinary diagnostic approach, including at least hematological, allergological, dermatological, and rheumatological evaluations. A precise and timely diagnosis is required for: a) adequate counseling of patients and their physicians; b) beginning of symptomatic treatment (anti-mediator therapy); c) prevention of severe manifestations of the disease (i.e., recurrent anaphylaxis, osteoporosis, and bone fractures); d) cytoreductive treatment of advanced SM variants. This review summarizes the disease's main manifestations and describes the ideal diagnostic approach for adult patients with suspected SM, giving physicians the main notions for correct patient diagnosis and management. This review also highlights the importance of a multidisciplinary approach in this very complex disease., Competing Interests: Competing interests: The authors declare no conflict of Interest.
- Published
- 2021
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36. The serological prevalence of SARS-CoV-2 infection in patients with chronic myeloid leukemia is similar to that in the general population.
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Bonifacio M, Tiribelli M, Miggiano MC, Abruzzese E, Binotto G, Scaffidi L, Cordioli M, Damiani D, Di Bona E, Trawinska MM, Tanasi I, Dubbini MV, Velotta V, Ceccarelli G, Pierdomenico E, Lo Schirico M, Semenzato G, Ruggeri M, Fanin R, Tacconelli E, Pizzolo G, and Krampera M
- Subjects
- Adult, Aged, Aged, 80 and over, COVID-19 Serological Testing methods, Cross-Sectional Studies, Female, Humans, Immunoglobulin G immunology, Immunoglobulin M immunology, Italy, Leukemia, Myelogenous, Chronic, BCR-ABL Positive immunology, Male, Middle Aged, Prevalence, Young Adult, COVID-19 immunology, Leukemia, Myelogenous, Chronic, BCR-ABL Positive virology, SARS-CoV-2 immunology
- Abstract
Background: Patients with hematological malignancies are at an increased risk of SARS-CoV-2 disease (COVID-19) and adverse outcome. However, a low mortality rate has been reported in patients with chronic myeloid leukemia (CML). Preclinical evidence suggests that tyrosine kinase inhibitors (TKIs) may have a protective role against severe COVID-19., Methods: We conducted a cross-sectional study of 564 consecutive patients with CML who were tested for anti-SARS-CoV-2 IgG/IgM antibodies at their first outpatient visit between May and early November 2020 in five hematologic centers representative of three Italian regions., Results: The estimated serological prevalence of SARS-CoV-2 infection in patients with CML after the first pandemic wave was similar to that in the general population (about 2%), both at national and regional levels. CML patients with positive anti-SARS-CoV-2 serology were more frequently male (p = 0.027) and active workers (p = 0.012), while there was no significant association with TKI treatment type. Only 3 out of 11 IgG-positive patients had previously received a molecular diagnosis of COVID-19, while the remainders were asymptomatic or with mild symptoms., Conclusions: Our data confirm that the course of SARS-CoV-2 infection in patients with CML is generally mild and reassure about the safety of continuing TKIs during the COVID-19 pandemic. Furthermore, we suggest that patients with CML succeed to mount an antibody response after exposure to SARS-CoV-2, similar to the general population., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
- Published
- 2021
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37. Safety of local anesthesia and prevalence of hypersensitivity reactions in adult patients with clonal mast cell diseases: A retrospective single-center study.
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Tanasi I, Olivieri E, Oberti M, Lucchini G, Furci F, Zanotti R, and Bonadonna P
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- Adult, Anesthesia, Local, Humans, Mast Cells, Prevalence, Retrospective Studies, Drug Hypersensitivity diagnosis, Drug Hypersensitivity epidemiology, Hypersensitivity, Mastocytosis diagnosis, Mastocytosis epidemiology
- Published
- 2021
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38. Efficacy of R-COMP in comparison to R-CHOP in patients with DLBCL: A systematic review and single-arm metanalysis.
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Visco C, Pregnolato F, Ferrarini I, De Marco B, Bonuomo V, Sbisà E, Fraenza C, Bernardelli A, Tanasi I, Quaglia FM, and Krampera M
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- Aged, Antibodies, Monoclonal, Murine-Derived adverse effects, Cyclophosphamide adverse effects, Doxorubicin adverse effects, Humans, Prednisone, Rituximab therapeutic use, Treatment Outcome, Vincristine adverse effects, Antineoplastic Combined Chemotherapy Protocols adverse effects, Lymphoma, Large B-Cell, Diffuse drug therapy
- Abstract
Doxorubicin represents the mainstay in the upfront treatment of diffuse large B-cell lymphoma (DLBCL) patients. However, its administration is sometimes hampered by the coexistence of former comorbidities/cardiac issues, especially in the elderly population. Liposome encapsulated drug delivery systems have been adopted to reduce the exposure of normal tissues to the drug, both in solid cancers and lymphomas. Despite claims for lower toxicity, the efficacy of non-pegylated liposome doxorubicin (NPLD) in DLBCL, as compared to standard doxorubicin, has never been established. We systematically reviewed relevant literature of NPLD in lymphoma treatment. Adjusting for age/comorbidities, our metanalysis revealed that the use of combinations including NPLD (R-COMP) were non-inferior in terms of response, overall and progression-free survival to the standard of care (R-CHOP) in overlapping series of DLBCL patients. R-COMP may represent a safe and active option for elderly patients with DLBCL, or for those with some extent of cardiac impairment at baseline., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2021
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39. Familial occurrence of systemic and cutaneous mastocytosis in an adult multicentre series.
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Tanasi I, Bonifacio M, Pizzolato M, Irene Grifoni F, Sciumè M, Elena C, Benvenuti P, Mannelli F, Parente R, Schena D, Scaffidi L, Bonadonna P, Papayannidis C, Rondoni M, Criscuolo M, Vannucchi AM, Triggiani M, Martinelli G, Krampera M, and Zanotti R
- Subjects
- Adolescent, Adult, Aged, Amino Acid Substitution, Family, Female, Humans, Male, Middle Aged, Retrospective Studies, Mastocytosis, Cutaneous epidemiology, Mastocytosis, Cutaneous genetics, Mastocytosis, Systemic genetics, Mastocytosis, Systemic metabolism, Mutation, Missense, Proto-Oncogene Proteins c-kit genetics
- Published
- 2021
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40. Bone Marrow Mastocytosis: A Diagnostic Challenge.
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Zanotti R, Tanasi I, Bernardelli A, Orsolini G, and Bonadonna P
- Abstract
Bone marrow mastocytosis (BMM) represents a provisional, indolent subvariant of systemic mastocytosis (SM). Utilizing WHO criteria, BMM requires bone marrow (BM) involvement and the absence of mastocytosis skin lesions. BMM is characterized by male sex prevalence, a slight increase of serum tryptase levels, low BM mast cells (MC) burden, and an indolent clinical course. BMM shows a strong correlation with severe anaphylaxis, mainly due to an IgE-mediated allergy to bee or wasp venom and, less frequently, to unexplained (idiopathic) anaphylaxis. Furthermore, BMM is often associated with osteoporosis which could be the only presenting symptom of the disease. BMM is an undervalued disease as serum tryptase levels are not routinely measured in the presence of unexplained osteoporosis or anaphylaxis. Moreover, BMM patients are often symptom-free except for severe allergic reactions. These factors, along with typical low BM MCs infiltration, may contribute to physicians overlooking BMM diagnosis, especially in medical centers that lack appropriately sensitive diagnostic techniques. This review highlights the need for a correct diagnostic pathway to diagnose BMM in patients with suspected symptoms but lacking typical skin lesions, even in the case of normal serum tryptase levels. Early diagnosis may prevent potential life-threatening anaphylaxis or severe skeletal complications.
- Published
- 2021
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41. Proposed global prognostic score for systemic mastocytosis: a retrospective prognostic modelling study.
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Muñoz-González JI, Álvarez-Twose I, Jara-Acevedo M, Zanotti R, Perkins C, Jawhar M, Sperr WR, Shoumariyeh K, Schwaab J, Greiner G, Henriques A, Caldas C, Fernández-Giménez C, Sánchez-Muñoz L, Mayado A, Pérez-Pons A, Schmitt-Graeff A, Duyster J, Tanasi I, Olivieri F, Mora-Casterá E, Luna I, Senent L, Bañas MH, Nuñez-García A, Jurado-Chacón M, Martín-Sánchez G, Colado E, Xicoy B, Gener-Ricós G, Gotlib J, Bonadonna P, Reiter A, Valent P, García-Montero AC, and Orfao A
- Subjects
- Adult, Aged, Alkaline Phosphatase blood, Core Binding Factor Alpha 2 Subunit genetics, Female, Hemoglobins analysis, Humans, Kaplan-Meier Estimate, Male, Mastocytosis, Systemic mortality, Middle Aged, Polymorphism, Single Nucleotide, Prognosis, Progression-Free Survival, Repressor Proteins genetics, Retrospective Studies, Risk Factors, Serine-Arginine Splicing Factors genetics, Mastocytosis, Systemic diagnosis
- Abstract
Background: Several risk stratification models have been proposed in recent years for systemic mastocytosis but have not been directly compared. Here we designed and validated a risk stratification model for progression-free survival (PFS) and overall survival (OS) in systemic mastocytosis on the basis of all currently available prognostic factors, and compared its predictive capacity for patient outcome with that of other risk scores., Methods: We did a retrospective prognostic modelling study based on patients diagnosed with systemic mastocytosis between March 1, 1983, and Oct 11, 2019. In a discovery cohort of 422 patients from centres of the Spanish Network on Mastocytosis (REMA), we evaluated previously identified, independent prognostic features for prognostic effect on PFS and OS by multivariable analysis, and designed a global prognostic score for mastocytosis (GPSM) aimed at predicting PFS (GPSM-PFS) and OS (GPSM-OS) by including only those variables that showed independent prognostic value (p<0·05). The GPSM scores were validated in an independent cohort of 853 patients from centres in Europe and the USA, and compared with pre-existing risk models in the total patient series (n=1275), with use of Harrells' concordance index (C-index) as a readout of the ability of each model to risk-stratify patients according to survival outcomes., Findings: Our GPSM-PFS and GPSM-OS models were based on unique combinations of independent prognostic factors for PFS (platelet count ≤100 × 10
9 cells per L, serum β2-microglobulin ≥2·5 μg/mL, and serum baseline tryptase ≥125 μg/L) and OS (haemoglobin ≤110 g/L, serum alkaline phosphatase ≥140 IU/L, and at least one mutation in SRSF2, ASXL1, RUNX1, or DNMT3A). The models showed clear discrimination between low-risk and high-risk patients in terms of worse PFS and OS prognoses in the discovery and validation cohorts, and further discrimination of intermediate-risk patients. The GPSM-PFS score was an accurate predictor of PFS in systemic mastocytosis (C-index 0·90 [95% CI 0·87-0·93], vs values ranging from 0·85 to 0·88 for pre-existing models), particularly in non-advanced systemic mastocytosis (C-index 0·85 [0·76-0·92], within the range for pre-existing models of 0·80 to 0·93). Additionally, the GPSM-OS score was able to accurately predict OS in the entire cohort (C-index 0·92 [0·89-0·94], vs 0·67 to 0·90 for pre-existing models), and showed some capacity to predict OS in advanced systemic mastocytosis (C-index 0·72 [0·66-0·78], vs 0·64 to 0·73 for pre-existing models)., Interpretation: All evaluated risk classifications predicted survival outcomes in systemic mastocytosis. The REMA-PFS and GPSM-PFS models for PFS, and the International Prognostic Scoring System for advanced systemic mastocytosis and GPSM-OS model for OS emerged as the most accurate models, indicating that robust prognostication might be prospectively achieved on the basis of biomarkers that are accessible in diagnostic laboratories worldwide., Funding: Carlos III Health Institute, European Regional Development Fund, Spanish Association of Mastocytosis and Related Diseases, Rare Diseases Strategy of the Spanish National Health System, Junta of Castile and León, Charles and Ann Johnson Foundation, Stanford Cancer Institute Innovation Fund, Austrian Science Fund., (Copyright © 2021 Elsevier Ltd. All rights reserved.)- Published
- 2021
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42. The Role of Notch and Wnt Signaling in MSC Communication in Normal and Leukemic Bone Marrow Niche.
- Author
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Takam Kamga P, Bazzoni R, Dal Collo G, Cassaro A, Tanasi I, Russignan A, Tecchio C, and Krampera M
- Abstract
Notch and Wnt signaling are highly conserved intercellular communication pathways involved in developmental processes, such as hematopoiesis. Even though data from literature support a role for these two pathways in both physiological hematopoiesis and leukemia, there are still many controversies concerning the nature of their contribution. Early studies, strengthened by findings from T-cell acute lymphoblastic leukemia (T-ALL), have focused their investigation on the mutations in genes encoding for components of the pathways, with limited results except for B-cell chronic lymphocytic leukemia (CLL); in because in other leukemia the two pathways could be hyper-expressed without genetic abnormalities. As normal and malignant hematopoiesis require close and complex interactions between hematopoietic cells and specialized bone marrow (BM) niche cells, recent studies have focused on the role of Notch and Wnt signaling in the context of normal crosstalk between hematopoietic/leukemia cells and stromal components. Amongst the latter, mesenchymal stromal/stem cells (MSCs) play a pivotal role as multipotent non-hematopoietic cells capable of giving rise to most of the BM niche stromal cells, including fibroblasts, adipocytes, and osteocytes. Indeed, MSCs express and secrete a broad pattern of bioactive molecules, including Notch and Wnt molecules, that support all the phases of the hematopoiesis, including self-renewal, proliferation and differentiation. Herein, we provide an overview on recent advances on the contribution of MSC-derived Notch and Wnt signaling to hematopoiesis and leukemia development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Takam Kamga, Bazzoni, Dal Collo, Cassaro, Tanasi, Russignan, Tecchio and Krampera.)
- Published
- 2021
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43. Extracellular Vesicle-Dependent Communication Between Mesenchymal Stromal Cells and Immune Effector Cells.
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Bazzoni R, Takam Kamga P, Tanasi I, and Krampera M
- Abstract
Mesenchymal stem/stromal cells (MSCs) are multipotent cells residing in the stromal tissues of the body and capable of promoting tissue repair and attenuating inflammatory processes through their immunomodulatory properties. Preclinical and clinical observations revealed that not only direct intercellular communication mediates MSC properties; in fact, a pivotal role is also played by the release of soluble and bioactive factors, such as cytokines, growth factor and extracellular vesicles (EVs). EVs are membrane-coated vesicles containing a large variety of bioactive molecules, including lipids, proteins, and nucleic acids, such as RNA. EVs release their contents into target cells, thus influencing cell fate through the control of intracellular processes. In addition, MSC-derived EVs can mediate modulatory effects toward different effector cells belonging to both innate and adaptive immunity. In this review, we will discuss the literature data concerning MSC-derived EVs, including the current standardized methods for their isolation and characterization, the mechanisms supporting their immunoregulatory properties, and their potential clinical application as alternative to MSC-based therapy for inflammatory reactions, such as graft-versus-host disease (GvHD)., (Copyright © 2020 Bazzoni, Takam Kamga, Tanasi and Krampera.)
- Published
- 2020
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44. Oncogenic Mutations of MYD88 and CD79B in Diffuse Large B-Cell Lymphoma and Implications for Clinical Practice.
- Author
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Visco C, Tanasi I, Quaglia FM, Ferrarini I, Fraenza C, and Krampera M
- Abstract
Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin's lymphoma in adults. Despite the recognition of transcriptional subtypes with distinct functional characteristics, patient outcomes have not been substantially altered since the advent of chemoimmunotherapy (CIT) twenty years ago. Recently, a few pivotal studies added to the disease heterogeneity by describing several activating mutations, which have been associated with disease presentation, B-cell function and behavior, and final outcome. DLBCL arises from antigen exposed B-cells, with the B-cell receptor (BCR) playing a central role. BCR-activity related mutations, such as CD79B and MYD88, are responsible for chronic activation of the BCR in a substantial subset of patients. These mutations, often coexisting in the same patient, have been found in a substantial subset of patients with immune-privileged (IP) sites DLBCLs, and are drivers of lymphoma development conferring tissue-specific homing properties. Both mutations have been associated with disease behavior, including tumor response either to CIT or to BCR-targeted therapy. The recognition of CD79B and MYD88 mutations will contribute to the heterogeneity of the disease, both in recognizing the BCR as a potential therapeutic target and in providing genetic tools for personalized treatment.
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- 2020
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45. High-throughput analysis and functional interpretation of extracellular vesicle content in hematological malignancies.
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Tanasi I, Adamo A, Kamga PT, Bazzoni R, and Krampera M
- Abstract
Extracellular vesicles (EVs) are membrane-coated particles secreted by virtually all cell types in response to different stimuli, both in physiological and pathological conditions . Their content generally reflects their biological functions and includes a variety of molecules, such as nucleic acids, proteins and cellular components. The role of EVs as signaling vehicles has been widely demonstrated. In particular, they are actively involved in the pathogenesis of several hematological malignancies (HM), mainly interacting with a number of target cells and inducing functional and epigenetic changes. In this regard, by releasing their cargo, EVs play a pivotal role in the bilateral cross-talk between tumor microenvironment and cancer cells, thus facilitating mechanisms of immune escape and supporting tumor growth and progression. Recent advances in high-throughput technologies have allowed the deep characterization and functional interpretation of EV content. In this review, the current knowledge on the high-throughput technology-based characterization of EV cargo in HM is summarized., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Author(s).)
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- 2020
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46. Small Molecule Inhibitors of Microenvironmental Wnt/β-Catenin Signaling Enhance the Chemosensitivity of Acute Myeloid Leukemia.
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Takam Kamga P, Dal Collo G, Cassaro A, Bazzoni R, Delfino P, Adamo A, Bonato A, Carbone C, Tanasi I, Bonifacio M, and Krampera M
- Abstract
Wnt/β-catenin signaling has been reported in Acute Myeloid leukemia, but little is known about its significance as a prognostic biomarker and drug target. In this study, we first evaluated the correlation between expression levels of Wnt molecules and clinical outcome. Then, we studied-in vitro and in vivo-the anti-leukemic value of combinatorial treatment between Wnt inhibitors and classic anti-leukemia drugs. Higher levels of β-catenin, Ser675-phospho-β-catenin and GSK-3α (total and Ser 9) were found in AML cells from intermediate or poor risk patients; nevertheless, patients presenting high activity of Wnt/β-catenin displayed shorter progression-free survival (PFS) according to univariate analysis. In vitro, many pharmacological inhibitors of Wnt signalling, i.e., LRP6 (Niclosamide), GSK-3 (LiCl, AR-A014418), and TCF/LEF (PNU-74654) but not Porcupine (IWP-2), significantly reduced proliferation and improved the drug sensitivity of AML cells cultured alone or in the presence of bone marrow stromal cells. In vivo, PNU-74654, Niclosamide and LiCl administration significantly reduced the bone marrow leukemic burden acting synergistically with Ara-C, thus improving mouse survival. Overall, our study demonstrates the antileukemic role of Wnt/β-catenin inhibition that may represent a potential new therapeutics strategy in AML.
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- 2020
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47. Notch Signaling Molecules as Prognostic Biomarkers for Acute Myeloid Leukemia.
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Takam Kamga P, Dal Collo G, Resci F, Bazzoni R, Mercuri A, Quaglia FM, Tanasi I, Delfino P, Visco C, Bonifacio M, and Krampera M
- Abstract
The role of Notch signaling in acute myeloid leukemia (AML) is still under investigation. We have previously shown that high levels of Notch receptors and ligands could interfere with drug response. In this study, the protein expression of 79 AML blast samples collected from newly diagnosed patients was examined through flow cytometry. Gamma-secretase inhibitors were used in AML mouse xenograft models to evaluate the contribution of Notch pharmacological inhibition to mouse survival. We used univariate analysis for testing the correlation and/or association between protein expression and well-known prognostics markers. All the four receptors (Notch1-4) and some ligands (Jagged2, DLL-3) were highly expressed in less mature subtypes (M0-M1). Notch3, Notch4, and Jagged2 were overexpressed in an adverse cytogenetic risk group compared to good cytogenetic risk patients. Chi-square analysis revealed a positive association between the complete remission rate after induction therapy and weak expression of Notch2 and Notch3. We also found an association between low levels of Notch4 and Jagged2 and three-year remission following allogeneic stem cell transplantation (HSCT). Accordingly, Kaplan-Meier analysis showed improved OS for patients lacking significant expression of Notch4, Jagged2, and DLL3. In vivo experiments in an AML mouse model highlighted both improved survival and a significant reduction of leukemia cell burden in the bone marrow of mice treated with the combination of Notch pan-inhibitors (GSIs) plus chemotherapy (Ara-C). Our results suggest that Notch can be useful as a prognostic marker and therapeutic target in AML.
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- 2019
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48. Efficacy of tyrosine kinase inhibitors in Ph-like acute lymphoblastic leukemia harboring ABL-class rearrangements.
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Tanasi I, Ba I, Sirvent N, Braun T, Cuccuini W, Ballerini P, Duployez N, Tanguy-Schmidt A, Tamburini J, Maury S, Doré E, Himberlin C, Duclos C, Chevallier P, Rousselot P, Bonifacio M, Cavé H, Baruchel A, Dombret H, Soulier J, Landman-Parker J, Boissel N, and Clappier E
- Subjects
- Adolescent, Adult, Aged, Child, Child, Preschool, Female, Gene Rearrangement, Humans, Male, Middle Aged, Oncogene Proteins, Fusion genetics, Proto-Oncogene Proteins c-abl genetics, Young Adult, Antineoplastic Agents therapeutic use, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma genetics, Protein Kinase Inhibitors therapeutic use
- Published
- 2019
- Full Text
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