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51. Higher-order connections between stereotyped subsets: implications for improved patient classification in CLL

Author

Agathangelidis, A. Chatzidimitriou, A. Gemenetzi, K. Giudicelli, V. Karypidou, M. Plevova, K. Davis, Z. Yan, X.-J. Jeromin, S. Schneider, C. Pedersen, L.B. Tschumper, R.C. Sutton, L.-A. Baliakas, P. Scarfò, L. van Gastel, E.J. Armand, M. Tausch, E. Biderman, B. Baer, C. Bagnara, D. Navarro, A. Langlois de Septenville, A. Guido, V. Mitterbauer-Hohendanner, G. Dimovski, A. Brieghel, C. Lawless, S. Meggendorfer, M. Brazdilova, K. Ritgen, M. Facco, M. Tresoldi, C. Visentin, A. Patriarca, A. Catherwood, M. Bonello, L. Sudarikov, A. Vanura, K. Roumelioti, M. Skuhrova Francova, H. Moysiadis, T. Veronese, S. Giannopoulos, K. Mansouri, L. Karan-Djurasevic, T. Sandaltzopoulos, R. Bödör, C. Fais, F. Kater, A. Panovska, I. Rossi, D. Alshemmari, S. Panagiotidis, P. Costeas, P. Espinet, B. Antic, D. Foroni, L. Montillo, M. Trentin, L. Stavroyianni, N. Gaidano, G. Francia di Celle, P. Niemann, C. Campo, E. Anagnostopoulos, A. Pott, C. Fischer, K. Hallek, M. Oscier, D. Stilgenbauer, S. Haferlach, C. Jelinek, D. Chiorazzi, N. Pospisilova, S. Lefranc, M.-P. Kossida, S. Langerak, A.W. Belessi, C. Davi, F. Rosenquist, R. Ghia, P. Stamatopoulos, K. ERIC, the European Research Initiative on CLL

Subjects
hemic and lymphatic diseases
Abstract

Chronic lymphocytic leukemia (CLL) is characterized by the existence of subsets of patients with (quasi)identical, stereotyped B-cell receptor (BcR) immunoglobulins. Patients in certain major stereotyped subsets often display remarkably consistent clinicobiological profiles, suggesting that the study of BcR immunoglobulin stereotypy in CLL has important implications for understanding disease pathophysiology and refining clinical decision-making. Nevertheless, several issues remain open, especially pertaining to the actual frequency of BcR immunoglobulin stereotypy and major subsets, as well as the existence of higher-order connections between individual subsets. To address these issues, we investigated clonotypic IGHV-IGHD-IGHJ gene rearrangements in a series of 29 856 patients with CLL, by far the largest series worldwide. We report that the stereotyped fraction of CLL peaks at 41% of the entire cohort and that all 19 previously identified major subsets retained their relative size and ranking, while 10 new ones emerged; overall, major stereotyped subsets had a cumulative frequency of 13.5%. Higher-level relationships were evident between subsets, particularly for major stereotyped subsets with unmutated IGHV genes (U-CLL), for which close relations with other subsets, termed “satellites,” were identified. Satellite subsets accounted for 3% of the entire cohort. These results confirm our previous notion that major subsets can be robustly identified and are consistent in relative size, hence representing distinct disease variants amenable to compartmentalized research with the potential of overcoming the pronounced heterogeneity of CLL. Furthermore, the existence of satellite subsets reveals a novel aspect of repertoire restriction with implications for refined molecular classification of CLL. Key Points: • In a series of 29 856 CLL patients, the incidence of BcR stereotypy peaked at 41%. • Higher-order relations exist between stereotyped subsets, particularly for those from U-CLL, for which satellite subsets were identified. © 2021 American Society of Hematology

Published
2021

53. Innovative therapeutic strategy for B-cell malignancies that combines obinutuzumab and cytokine-induced killer cells

Author

Pieta, A. D., Cappuzzello, E., Palmerini, P., Ventura, A., Visentin, A., Astori, G., Chieregato, K., Mozzo, V., Perbellini, O., Tisi, M. C., Trentin, L., Visco, C., Ruggeri, M., Sommaggio, R., and Rosato, A.

Subjects
Clinical/Translational Cancer Immunotherapy, Lymphoma, B-Cell, combined modality therapy, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Antibodies, Monoclonal, Humanized, adoptive, hematologic neoplasms, immunotherapy, Mice, Antineoplastic Agents, Immunological, Cytokine-Induced Killer Cells, Mice, Inbred NOD, Animals, Humans, Female, RC254-282, Aged
Abstract

Background Patients affected by aggressive B-cell malignancies who are resistant to primary or salvage chemoimmunotherapy have an extremely poor prognosis and limited therapeutic options. Promising therapeutic success has been achieved with the infusion of CD19 chimeric antigen receptor-T cells, but several limits still restrain the administration to a limited proportion of patients. This unmet clinical need might be fulfilled by an adoptive immunotherapy approach that combines cytokine-induced killer (CIK) cells and monoclonal antibodies (mAb) to the CD20 antigen. Indeed, CIK cells are an effector population endowed with antitumor activity, which can be further improved and antigen-specifically redirected by clinical-grade mAb triggering antibody-dependent cell-mediated cytotoxicity. Methods CIK cells were generated from peripheral blood of patients affected by different B-cell malignancies using a blinatumomab-based cell culture protocol. Effector cells were combined with the anti-CD20 mAb obinutuzumab and their therapeutic activity was assessed both in vitro and in vivo. Results CIK cells were successfully expanded in clinically relevant numbers, starting from small volumes of peripheral blood with extremely low CD3+ counts and high tumor burden. This relied on the addition of blinatumumab in culture, which leads to the simultaneous expansion of effector cells and the complete elimination of the neoplastic component. Moreover, CIK cells were highly cytotoxic in vitro against both B-cell tumor cell lines and autologous neoplastic targets, and had a significant therapeutic efficacy against a B-cell malignancy patient-derived xenograft on in vivo transfer. Conclusions The combination of an easily expandable CIK cell effector population with a mAb already in clinical use establishes a tumor antigen-specific redirection strategy that can be rapidly translated into clinical practice, providing an effective therapeutic alternative for B-cell malignancies without any need for genetic modifications. Additionally, the approach can be potentially applied to an extremely vast array of different tumors by simply substituting the targeting mAb.

Published
2021

54. Corrigendum to 'Insight into the mechanism of cytotoxicity of membrane-permeant psoralenic Kv1.3 channel inhibitors by chemical dissection of a novel member of the family' [Redox Biol. 37 (2020 Sep 6) 101705–101721](S2213231720309101)(10.1016/j.redox.2020.101705)

Author

Peruzzo, R., Mattarei, A., Azzolini, M., Becker-Flegler, K. A., Romio, M., Rigoni, G., Carrer, A., Biasutto, L., Parrasia, S., Kadow, S., Manago, A., Urbani, A., Rossa, A., Semenzato, G., Soriano, M. E., Trentin, L., Ahmad, S., Edwards, M., Gulbins, E., Paradisi, C., Zoratti, M., Leanza, L., and Szabo, I.

Published
2021

55. Effectiveness of ibrutinib as first-line therapy for chronic lymphocytic leukemia patients and indirect comparison with rituximab-bendamustine: Results of study on 486 cases outside clinical trials

Author

Morabito, F., Tripepi, G., Del Poeta, G., Mauro, F. R., Reda, G., Sportoletti, P., Laurenti, L., Coscia, M., Herishanu, Y., Bossio, S., Varettoni, M., Murru, R., Chiarenza, A., Visentin, A., Condoluci, A., Moia, R., Pietrasanta, D., Loseto, G., Consoli, U., Scortechini, I., Rossi, F. M., Zucchetto, A., Al-Janazreh, H., Vigna, E., Martino, E. A., Cassin, R., D'Arrigo, G., Galimberti, S., Rago, A., Angeletti, I., Biagi, A., Del Giudice, I., Bomben, R., Neri, A., Fronza, G., Monti, P., Menichini, P., Olivieri, J., Cutrona, G., Rossi, D., Cuneo, A., Di Raimondo, F., Gaidano, G., Polliack, A., Trentin, L., Foa, R., Ferrarini, M., Gattei, V., Gentile, M., Morabito F., Laurenti L. (ORCID:0000-0002-8327-1396), Rossi F. M., Galimberti S., Monti P. (ORCID:0000-0002-2586-1881), Rossi D., Foa R., Gentile M., Morabito, F., Tripepi, G., Del Poeta, G., Mauro, F. R., Reda, G., Sportoletti, P., Laurenti, L., Coscia, M., Herishanu, Y., Bossio, S., Varettoni, M., Murru, R., Chiarenza, A., Visentin, A., Condoluci, A., Moia, R., Pietrasanta, D., Loseto, G., Consoli, U., Scortechini, I., Rossi, F. M., Zucchetto, A., Al-Janazreh, H., Vigna, E., Martino, E. A., Cassin, R., D'Arrigo, G., Galimberti, S., Rago, A., Angeletti, I., Biagi, A., Del Giudice, I., Bomben, R., Neri, A., Fronza, G., Monti, P., Menichini, P., Olivieri, J., Cutrona, G., Rossi, D., Cuneo, A., Di Raimondo, F., Gaidano, G., Polliack, A., Trentin, L., Foa, R., Ferrarini, M., Gattei, V., Gentile, M., Morabito F., Laurenti L. (ORCID:0000-0002-8327-1396), Rossi F. M., Galimberti S., Monti P. (ORCID:0000-0002-2586-1881), Rossi D., Foa R., and Gentile M.

Abstract

n/a

Published
2021

56. Comparison of ibrutinib and idelalisib plus rituximab in real-life relapsed/resistant chronic lymphocytic leukemia cases

Author

Morabito, Francesco, Tripepi, G., Del Poeta, G., Mauro, F. R., Reda, G., Sportoletti, P., Laurenti, Luca, Coscia, M., Herishanu, Y., Bossio, S., Varettoni, M., Murru, R., Chiarenza, A., Visentin, A., Condoluci, A., Moia, R., Pietrasanta, D., Loseto, G., Consoli, U., Scortechini, I., Rossi, Federica Maria, Zucchetto, A., Al-Janazreh, H., Vigna, E., Martino, E. A., Mendicino, F., Cassin, R., D'Arrigo, G., Galimberti, Sofia, Rago, A., Angeletti, I., Biagi, A., Del Giudice, I., Bomben, R., Neri, A., Fronza, G., Monti, Paolo, Menichini, P., Cutrona, G., Jaksic, O., Rossi, Dario, Di Raimondo, F., Cuneo, A., Gaidano, G., Polliack, A., Trentin, L., Foa, Robin, Ferrarini, M., Gattei, V., Gentile, Marino, Morabito F., Laurenti L. (ORCID:0000-0002-8327-1396), Rossi F. M., Galimberti S., Monti P. (ORCID:0000-0002-2586-1881), Rossi D., Foa R., Gentile M., Morabito, Francesco, Tripepi, G., Del Poeta, G., Mauro, F. R., Reda, G., Sportoletti, P., Laurenti, Luca, Coscia, M., Herishanu, Y., Bossio, S., Varettoni, M., Murru, R., Chiarenza, A., Visentin, A., Condoluci, A., Moia, R., Pietrasanta, D., Loseto, G., Consoli, U., Scortechini, I., Rossi, Federica Maria, Zucchetto, A., Al-Janazreh, H., Vigna, E., Martino, E. A., Mendicino, F., Cassin, R., D'Arrigo, G., Galimberti, Sofia, Rago, A., Angeletti, I., Biagi, A., Del Giudice, I., Bomben, R., Neri, A., Fronza, G., Monti, Paolo, Menichini, P., Cutrona, G., Jaksic, O., Rossi, Dario, Di Raimondo, F., Cuneo, A., Gaidano, G., Polliack, A., Trentin, L., Foa, Robin, Ferrarini, M., Gattei, V., Gentile, Marino, Morabito F., Laurenti L. (ORCID:0000-0002-8327-1396), Rossi F. M., Galimberti S., Monti P. (ORCID:0000-0002-2586-1881), Rossi D., Foa R., and Gentile M.

Abstract

Objectives: To compare the capacity of ibrutinib (IB) and idelalisib-rituximab (IDELA-R) of prolonging overall survival (OS) as in CLL patients, previously treated with chemotherapy only. Methods: A real-life cohort of 675 cases has been identified and investigated in the database of the groups participating in the study. Results: At an unadjusted univariate analysis, a significant death risk reduction was observed favoring IB (IDELA-R vs IB HR = 0.5, 95% CI = 0.36-0.71) although with some limitations due to the non-randomized and retrospective nature of the study and to the lower number of patients in the IDELA-R group (112 cases) related to the current prescribing practice. To overcome the potential problem of confounding by indication, we adjusted the association between the type of therapy and mortality for all variables significantly associated with OS at Cox univariate analysis. Furthermore, those variables, differently distributed between the two study groups, were introduced into the multivariate Cox model to improve the effectiveness of the analysis. By introducing all these variables into the multiple Cox regression model, we confirmed the protective effect of IB vs IDELA-R (HR = 0.67, 95% CI = 0.45-0.98, P =.04) independent of potential confounders. Conclusions: Although our analysis presents some constraints, that is, the unavailability of additional potential confounders, and the retrospective nature of the study, this observation may be of help for the daily clinical practice, particularly in the absence of randomized trials comparing the two schedules.

Published
2021

57. Prognostic impact and risk factors of infections in patients with chronic lymphocytic leukemia treated with ibrutinib

Author

Mauro, F. R., Giannarelli, D., Visentin, A., Reda, G., Sportoletti, P., Frustaci, A. M., Chiarenza, A., Ciolli, S., Vitale, C., Laurenti, L., De Paoli, L., Murru, R., Gentile, M., Rigolin, G. M., Levato, L., Giordano, A., Del Poeta, G., Stelitano, C., Ielo, C., Noto, A., Guarente, V., Molica, S., Coscia, M., Tedeschi, A., Gaidano, G., Cuneo, A., Foa, R., Martelli, M., Girmenia, C., Gentile, G., Trentin, L., Laurenti L. (ORCID:0000-0002-8327-1396), Gentile M., Molica S., Tedeschi A., Foa R., Martelli M., Gentile G., Mauro, F. R., Giannarelli, D., Visentin, A., Reda, G., Sportoletti, P., Frustaci, A. M., Chiarenza, A., Ciolli, S., Vitale, C., Laurenti, L., De Paoli, L., Murru, R., Gentile, M., Rigolin, G. M., Levato, L., Giordano, A., Del Poeta, G., Stelitano, C., Ielo, C., Noto, A., Guarente, V., Molica, S., Coscia, M., Tedeschi, A., Gaidano, G., Cuneo, A., Foa, R., Martelli, M., Girmenia, C., Gentile, G., Trentin, L., Laurenti L. (ORCID:0000-0002-8327-1396), Gentile M., Molica S., Tedeschi A., Foa R., Martelli M., and Gentile G.

Abstract

Ibrutinib represents extraordinary progress in the treatment of chronic lymphocytic leukemia (CLL). However, treatment-related adverse events limit the benefit of this agent. This obser-vational, multicenter study focused on the incidence, risk factors, and prognostic impact of infections in 494 patients with CLL treated with an ibrutinib-based treatment. Ibrutinib was given to 89 (18%) previously untreated patients (combined with rituximab, 24) and 405 (82%) relapsed/refractory patients. Pneumonia (PN), grade ≥3 non-opportunistic infections (NOI), and opportunistic infections (OI) were recorded in 32% of patients with an overall incidence rate per 100 person-year of 15.3% (PN, 10%; NOI, 3.3%; OI, 2%). Infections were the reason for the permanent discontinuation of ibrutinib in 9% of patients. Patients who experienced pneumonia or a severe infection showed a significantly inferior survival than those who were infection-free (p < 0.0001). A scoring system based on the three factors associated with a significant and independent impact on infections—PN or severe infection in the year before starting ibrutinib, chronic obstructive pulmonary disease, ≥2 prior treatments—identified patients with a two-to threefold increase in the rate of infections. In conclusion, the results of this study highlight the adverse impact of infectious events on the outcomes of CLL patients treated with ibrutinib.

Published
2021

58. Management of chronic lymphocytic leukemia in Italy during a one year of the COVID-19 pandemic and at the start of the vaccination program. A Campus CLL report

Author

Cuneo, A., Rigolin, G. M., Coscia, M., Quaresmini, G., Scarfo, L., Mauro, F. R., Motta, M., Quaglia, F. M., Trentin, L., Ferrario, Alberto Alfredo, Laurenti, Luca, Reda, G., Ferrari, A., Pietrasanta, D., Sportoletti, P., Re, F., De Paoli, L., Foglietta, M., Giordano, A., Marchetti, M., Farina, L., Del Poeta, G., Varettoni, M., Chiurazzi, F., Marasca, R., Malerba, L., Ibatici, A., Tisi, Maria Chiara, Stefoni, V., Leone, M., Barate, C., Olivieri, J., Murru, R., Gentile, Marino, Sanna, A., Gozzetti, A., Gattei, V., Gottardi, D., Derenzini, E., Levato, L., Orsucci, L., Penna, G., Chiarenza, A., Foa, Robin, Ferrario A., Laurenti L. (ORCID:0000-0002-8327-1396), Tisi M. C., Gentile M., Foa R., Cuneo, A., Rigolin, G. M., Coscia, M., Quaresmini, G., Scarfo, L., Mauro, F. R., Motta, M., Quaglia, F. M., Trentin, L., Ferrario, Alberto Alfredo, Laurenti, Luca, Reda, G., Ferrari, A., Pietrasanta, D., Sportoletti, P., Re, F., De Paoli, L., Foglietta, M., Giordano, A., Marchetti, M., Farina, L., Del Poeta, G., Varettoni, M., Chiurazzi, F., Marasca, R., Malerba, L., Ibatici, A., Tisi, Maria Chiara, Stefoni, V., Leone, M., Barate, C., Olivieri, J., Murru, R., Gentile, Marino, Sanna, A., Gozzetti, A., Gattei, V., Gottardi, D., Derenzini, E., Levato, L., Orsucci, L., Penna, G., Chiarenza, A., Foa, Robin, Ferrario A., Laurenti L. (ORCID:0000-0002-8327-1396), Tisi M. C., Gentile M., and Foa R.

Abstract

n/a

Published
2021

59. Assessment of the 4-factor score: Retrospective analysis of 586 CLL patients receiving ibrutinib. A campus CLL study

Author

Morabito, Francesco, Tripepi, G., Del Poeta, G., Mauro, F. R., Reda, G., Sportoletti, P., Laurenti, Luca, Coscia, M., Herishanu, Y., Varettoni, M., Murru, R., Chiarenza, A., Visentin, A., Condoluci, A., Moia, R., Pietrasanta, D., Loseto, G., Consoli, U., Scortechini, I., Rossi, Federica Maria, Zucchetto, A., Vigna, E., Martino, E. A., Mendicino, F., Botta, C., Caracciolo, D., Cassin, R., D'Arrigo, G., Galimberti, Sofia, Rago, A., Angeletti, I., Biagi, A., Del Giudice, I., Bomben, R., Neri, A., Fronza, G., Cutrona, G., Rossi, Dario, Di Raimondo, F., Cuneo, A., Gaidano, G., Polliack, A., Trentin, L., Foa, Robin, Ferrarini, M., Gattei, V., Gentile, Marino, Morabito F., Laurenti L. (ORCID:0000-0002-8327-1396), Rossi F. M., Galimberti S., Rossi D., Foa R., Gentile M., Morabito, Francesco, Tripepi, G., Del Poeta, G., Mauro, F. R., Reda, G., Sportoletti, P., Laurenti, Luca, Coscia, M., Herishanu, Y., Varettoni, M., Murru, R., Chiarenza, A., Visentin, A., Condoluci, A., Moia, R., Pietrasanta, D., Loseto, G., Consoli, U., Scortechini, I., Rossi, Federica Maria, Zucchetto, A., Vigna, E., Martino, E. A., Mendicino, F., Botta, C., Caracciolo, D., Cassin, R., D'Arrigo, G., Galimberti, Sofia, Rago, A., Angeletti, I., Biagi, A., Del Giudice, I., Bomben, R., Neri, A., Fronza, G., Cutrona, G., Rossi, Dario, Di Raimondo, F., Cuneo, A., Gaidano, G., Polliack, A., Trentin, L., Foa, Robin, Ferrarini, M., Gattei, V., Gentile, Marino, Morabito F., Laurenti L. (ORCID:0000-0002-8327-1396), Rossi F. M., Galimberti S., Rossi D., Foa R., and Gentile M.

Abstract

n/a

Published
2021

60. Preexisting and treatment-emergent autoimmune cytopenias in patients with CLL treated with targeted drugs

Author

Vitale, C., Salvetti, Maria Cristina, Griggio, V., Porrazzo, M., Schiattone, L., Zamprogna, G., Visentin, A., Vassallo, F., Cassin, R., Rigolin, G. M., Murru, R., Laurenti, Luca, Rivela, P., Marchetti, M., Pennese, E., Gentile, Marino, Boccellato, E., Perutelli, F., Montalbano, M. C., De Paoli, L., Reda, G., Orsucci, L., Trentin, L., Cuneo, A., Tedeschi, Alessandra, Scarfo, L., Gaidano, G., Mauro, F. R., Foa, Robin, Boccadoro, M., Coscia, M., Salvetti C., Laurenti L. (ORCID:0000-0002-8327-1396), Gentile M., Tedeschi A., Foa R., Vitale, C., Salvetti, Maria Cristina, Griggio, V., Porrazzo, M., Schiattone, L., Zamprogna, G., Visentin, A., Vassallo, F., Cassin, R., Rigolin, G. M., Murru, R., Laurenti, Luca, Rivela, P., Marchetti, M., Pennese, E., Gentile, Marino, Boccellato, E., Perutelli, F., Montalbano, M. C., De Paoli, L., Reda, G., Orsucci, L., Trentin, L., Cuneo, A., Tedeschi, Alessandra, Scarfo, L., Gaidano, G., Mauro, F. R., Foa, Robin, Boccadoro, M., Coscia, M., Salvetti C., Laurenti L. (ORCID:0000-0002-8327-1396), Gentile M., Tedeschi A., and Foa R.

Abstract

Autoimmune cytopenias (AICs) affect 5% to 9% of patients with chronic lymphocytic leukemia (CLL). Targeted drugs—ibrutinib, idelalisib, and venetoclax—have a prominent role in the treatment of CLL, but their impact on CLL-associated AICs is largely unknown. In this study, we evaluated the characteristics and outcome of preexisting AICs and described the incidence, quality, and management of treatment-emergent AICs during therapy with targeted drugs in patients with CLL. We collected data from 572 patients treated with ibrutinib (9% in combination with an anti-CD20 monoclonal antibody), 143 treated with idelalisib-rituximab, and 100 treated with venetoclax (12% in combination with an anti-CD20 monoclonal antibody). A history of preexisting AICs was reported in 104 (13%) of 815 patients. Interestingly, 80% of patients whose AICs had not resolved when treatment with a targeted drug was started experienced an improvement or a resolution during therapy. Treatment-emergent AICs occurred in 1% of patients during ibrutinib therapy, in 0.9% during idelalisib therapy, and in 7% during venetoclax therapy, with an estimated incidence rate of 5, 6, and 69 episodes per 1000 patients per year of exposure in the 3 treatment groups, respectively. The vast majority of patients who developed treatment-emergent AICs had unfavorable biological features such as an unmutated IGHV and a del(17p) and/or TP53 mutation. Notably, despite AICs, 83% of patients were able to continue the targeted drug, in some cases in combination with additional immunosuppressive agents. Overall, treatment with ibrutinib, idelalisib, or venetoclax seems to have a beneficial impact on CLL-associated AICs, inducing an improvement or even a resolution of preexisting AICs in most cases and eliciting treatment-emergent AICs in a negligible portion of patients.

Published
2021

66. Frontline treatment with the combination obinutuzumab±chlorambucil for chronic lymphocytic leukemia outside clinical trials: results of a multinational, multicenter study by ERIC and the Israeli CLL study group

Author

Herishanu Y, Shaulov A, Fineman R, BasiC-Kinda S, Aviv A, Wasik-Szczepanek E, Jaksic O, Zdrenghea M, Greenbaum U, Mandac I, Simkovic M, Morawska M, Benjamini O, Spacek M, Nemets A, Bairey O, Trentin L, Ruchlemer R, Laurenti L, Ciocan O, Doubek M, Shvidel L, Dali N, Miras F, De Meuter A, Dimou M, Mauro F, Coscia M, Bumbea H, Szasz R, Tadmor T, Gutwein O, Gentile M, Scarfo L, Tedeschi A, Sportoletti P, Vazquez E, Marquet J, Assouline S, Papaioannou M, Braester A, Levato L, Gregor M, Rigolin G, Loscertales J, Perez A, Nijziel M, Popov V, Collado R, Slavutsky I, Itchaki G, Ringelstein S, Goldschmidt N, Perry C, Levi S, Polliack A, and Ghia P

Abstract

In recent years, considerable progress has been made in frontline therapy for elderly/physically unfit patients with CLL. The combination of obinutuzumab and chlorambucil (O-Clb) has been shown to prolong progression free survival (PFS, median PFS-31.5 months) and overall survival (OS) compared to chlorambucil alone. More recently, obinutuzumab given in combination with either ibrutinib or venetoclax improved PFS but not OS when compared to O-Clb. In this retrospective multinational, multicenter co-operative study, we evaluated the efficacy and safety of frontline treatment with O±Clb in unfit patients with CLL, in a "real-world" setting. Patients with documented del(17p13.1)/TP53mutation were excluded. A total of 437 patients (median age, 75.9years; median CIRS score, 8; median creatinine clearance, 61.1 mL/min)were included. The clinical overall response rate was 80.3% (clinical complete and partial responses in 38.7% and 41.6% of patients, respectively). Median observation time was 14.1 months and estimated median PFS was 27.6 months (95%CI, 24.2-31.0). In a multivariate analysis, high-risk disease [del(11q22.3) and/or IGHV-unmutated], lymph nodes of diameter >5cm, obinutuzumab monotherapy and reduced cumulative dose of obinutuzumab, were all independently associated with shorter PFS. The median OS has not yet been reached and estimated 2-year OS is 88%. In conclusion, in a "real-world" setting, frontline treatment with O-Clb achieves PFS comparable to that reported in clinical trials. Inferior outcomes were noted in patients with del(11q22.3) and/or unmutated IGHV and those treated with obinutuzumab-monotherapy. Thus, O-Clb can be still considered as legitimate frontline therapy for unfit CLL patients with low-risk disease. This article is protected by copyright. All rights reserved.

Published
2020

67. Treatment of chronic lymphocytic leukemia in the new drugs era: the state of art in the Italian landscape

Author

Morelli, F, Innocenti, I, Autore, F, Fresa, F, Tomasso, A, Piciocchi, A, Frustaci, Am, Trentin, L, Mauro, Fr, Schiattone, L, Visentin, A, Del Poeta, G, Reda, G, Rigolin, Gm, Ibatici, A, Ciolli, S, Vitale, C, Sportoletti, P, Murru, R, Levato, L, Gentile, M, D’Arena, G, Coscia, M, Villa, Mr, Fontana, R, Efremov, D, Tedeschi, A, Scarfò, L, Cuneo, A, Foà, R, and Laurenti, L

Published
2020

69. BTK and PLCG2 mutations in patients with Chronic Lymphocytic Leukemia relapsing on Ibrutinib: a European Research Initiative on CLL (ERIC) study based on real-world evidence

Author

Scarfò, L, Bonfiglio, S, A Sutton, L, Ljungstrom, V, Pandzic, T, Cortese, D, Gaidano, G, Trentin, L, Bonello, L, Reda, G, Panayiotidis, P, Forconi, F, Stavroyianni, N, Bödör, C, Tam, C, Iyengar, S, Österborg, A, Coscia, M, Ysebaert, L, Jaksic, O, Ringshausen, I, Mulligan, S, Tedeschi, A, Strugov, V, Davis, Z, Pavlovsky, C, Marasca, R, Capasso, A, Ranghetti, P, Stamatopoulos, K, Rosenquist, R, and Ghia, P

Published
2020

70. COVID-19 severity and mortality in patients with chronic lymphocytic leukemia: a joint study by ERIC, the European Research Initiative on CLL, and CLL Campus

Author

Scarfo, L, Chatzikonstantinou, T, Rigolin, GM, Quaresmini, G, Motta, M, Vitale, C, Garcia-Marco, JA, Hernandez-Rivas, JA, Miras, F, Baile, M, Marquet, J, Niemann, CU, Reda, G, Munir, T, Gimeno, E, Marchetti, M, Quaglia, FM, Varettoni, M, Delgado, J, Iyengar, S, Janssens, A, Marasca, R, Ferrari, A, Cuellar-Garcia, C, Itchaki, G, Spacek, M, De Paoli, L, Laurenti, L, Levin, M-D, Lista, E, Mauro, FR, Simkovic, M, Van Der Spek, E, Vandenberghe, E, Trentin, L, Wasik-Szczepanek, E, Ruchlemer, R, Bron, D, De Paolis, MR, Del Poeta, G, Farina, L, Foglietta, M, Gentile, M, Herishanu, Y, Herold, T, Jaksic, O, Kater, AP, Kersting, S, Malerba, L, Orsucci, L, Popov, VM, Sportoletti, P, Yassin, M, Pocali, B, Barna, G, Chiarenza, A, dos Santos, G, Nikitin, E, Andres, M, Dimou, M, Doubek, M, Enrico, A, Hakobyan, Y, Kalashnikova, O, Ortiz Pareja, M, Papaioannou, M, Rossi, D, Shah, N, Shrestha, A, Stanca, O, Stavroyianni, N, Strugov, V, Tam, C, Zdrenghea, M, Coscia, M, Stamatopoulos, K, Rossi, G, Rambaldi, A, Montserrat, E, Foa, R, Cuneo, A, Ghia, P, Scarfo, L, Chatzikonstantinou, T, Rigolin, GM, Quaresmini, G, Motta, M, Vitale, C, Garcia-Marco, JA, Hernandez-Rivas, JA, Miras, F, Baile, M, Marquet, J, Niemann, CU, Reda, G, Munir, T, Gimeno, E, Marchetti, M, Quaglia, FM, Varettoni, M, Delgado, J, Iyengar, S, Janssens, A, Marasca, R, Ferrari, A, Cuellar-Garcia, C, Itchaki, G, Spacek, M, De Paoli, L, Laurenti, L, Levin, M-D, Lista, E, Mauro, FR, Simkovic, M, Van Der Spek, E, Vandenberghe, E, Trentin, L, Wasik-Szczepanek, E, Ruchlemer, R, Bron, D, De Paolis, MR, Del Poeta, G, Farina, L, Foglietta, M, Gentile, M, Herishanu, Y, Herold, T, Jaksic, O, Kater, AP, Kersting, S, Malerba, L, Orsucci, L, Popov, VM, Sportoletti, P, Yassin, M, Pocali, B, Barna, G, Chiarenza, A, dos Santos, G, Nikitin, E, Andres, M, Dimou, M, Doubek, M, Enrico, A, Hakobyan, Y, Kalashnikova, O, Ortiz Pareja, M, Papaioannou, M, Rossi, D, Shah, N, Shrestha, A, Stanca, O, Stavroyianni, N, Strugov, V, Tam, C, Zdrenghea, M, Coscia, M, Stamatopoulos, K, Rossi, G, Rambaldi, A, Montserrat, E, Foa, R, Cuneo, A, and Ghia, P

Abstract

Chronic lymphocytic leukemia (CLL) is a disease of the elderly, characterized by immunodeficiency. Hence, patients with CLL might be considered more susceptible to severe complications from COVID-19. We undertook this retrospective international multicenter study to characterize the course of COVID-19 in patients with CLL and identify potential predictors of outcome. Of 190 patients with CLL and confirmed COVID-19 diagnosed between 28/03/2020 and 22/05/2020, 151 (79%) presented with severe COVID-19 (need of oxygen and/or intensive care admission). Severe COVID-19 was associated with more advanced age (≥65 years) (odds ratio 3.72 [95% CI 1.79–7.71]). Only 60 patients (39.7%) with severe COVID-19 were receiving or had recent (≤12 months) treatment for CLL at the time of COVID-19 versus 30/39 (76.9%) patients with mild disease. Hospitalization rate for severe COVID-19 was lower (p < 0.05) for patients on ibrutinib versus those on other regimens or off treatment. Of 151 patients with severe disease, 55 (36.4%) succumbed versus only 1/38 (2.6%) with mild disease; age and comorbidities did not impact on mortality. In CLL, (1) COVID-19 severity increases with age; (2) antileukemic treatment (particularly BTK inhibitors) appears to exert a protective effect; (3) age and comorbidities did not impact on mortality, alluding to a relevant role of CLL and immunodeficiency.

Published
2020

71. Efficacy of bendamustine and rituximab in unfit patients with previously untreated chronic lymphocytic leukemia. Indirect comparison with ibrutinib in a real-world setting. A GIMEMA-ERIC and US study

Author

Cuneo, A, Mato, AR, Rigolin, GM, Piciocchi, A, Gentile, M, Laurenti, L, Allan, JN, Pagel, JM, Brander, DM, Hill, BT, Winter, A, Lamanna, N, Tam, CS, Jacobs, R, Lansigan, F, Barr, PM, Shadman, M, Skarbnik, AP, Pu, JJ, Sehgal, AR, Schuster, SJ, Shah, NN, Ujjani, CS, Roeker, L, Orlandi, EM, Billio, A, Trentin, L, Spacek, M, Marchetti, M, Tedeschi, A, Ilariucci, F, Gaidano, G, Doubek, M, Farina, L, Molica, S, Di Raimondo, F, Coscia, M, Mauro, FR, de la Serna, J, Medina Perez, A, Ferrarini, I, Cimino, G, Cavallari, M, Cucci, R, Vignetti, M, Foa, R, Ghia, P, Cuneo, A, Mato, AR, Rigolin, GM, Piciocchi, A, Gentile, M, Laurenti, L, Allan, JN, Pagel, JM, Brander, DM, Hill, BT, Winter, A, Lamanna, N, Tam, CS, Jacobs, R, Lansigan, F, Barr, PM, Shadman, M, Skarbnik, AP, Pu, JJ, Sehgal, AR, Schuster, SJ, Shah, NN, Ujjani, CS, Roeker, L, Orlandi, EM, Billio, A, Trentin, L, Spacek, M, Marchetti, M, Tedeschi, A, Ilariucci, F, Gaidano, G, Doubek, M, Farina, L, Molica, S, Di Raimondo, F, Coscia, M, Mauro, FR, de la Serna, J, Medina Perez, A, Ferrarini, I, Cimino, G, Cavallari, M, Cucci, R, Vignetti, M, Foa, R, and Ghia, P

Abstract

Limited information is available on the efficacy of front-line bendamustine and rituximab (BR) in chronic lymphocytic leukemia (CLL) with reduced renal function or coexisting conditions. We therefore analyzed a cohort of real-world patients and performed a matched adjusted indirect comparison with a cohort of patients treated with ibrutinib. One hundred and fifty-seven patients with creatinine clearance (CrCl) <70 mL/min and/or CIRS score >6 were treated with BR. The median age was 72 years; 69% of patients had ≥2 comorbidities and the median CrCl was 59.8 mL/min. 17.6% of patients carried TP53 disruption. The median progression-free survival (PFS) was 45 months; TP53 disruption was associated with a shorter PFS (P = 0.05). The overall survival (OS) at 12, 24, and 36 months was 96.2%, 90.1%, and 79.5%, respectively. TP53 disruption was associated with an increased risk of death (P = 0.01). Data on 162 patients ≥65 years treated with ibrutinib were analyzed and compared with 165 patients ≥65 years treated with BR. Factors predicting for a longer PFS at multivariable analysis in the total patient population treated with BR and ibrutinib were age (HR 1.06, 95% CI 1.02-1.10, P < 0.01) and treatment with ibrutinib (HR 0.55, 95% CI 0.33-0.93, P = 0.03). In a post hoc analysis of patients in advanced stage, a significant PFS advantage was observed in patient who had received ibrutinib (P = 0.03), who showed a trend for OS advantage (P = 0.08). We arrived at the following conclusions: (a) BR is a relatively effective first-line regimen in a real-world population of unfit patients without TP53 disruption, (b) ibrutinib provided longer disease control than BR in patients with advanced disease stage.

Published
2020

72. Consolidation Radiotherapy Could Be Safely Omitted in Advanced Hodgkin Lymphoma With Large Nodal Mass in Complete Metabolic Response After ABVD: Final Analysis of the Randomized GITIL/FIL HD0607 Trial

Author

Gallamini, A, Rossi, A, Patti, C, Picardi, M, Romano, A, Cantonetti, M, Oppi, S, Viviani, S, Bolis, S, Trentin, L, Gini, G, Battistini, R, Chauvie, S, Sorasio, R, Pavoni, C, Zanotti, R, Cimminiello, M, Schiavotto, C, Viero, P, Mulé, A, Fallanca, F, Ficola, U, Tarella, C, Guerra, L, Rambaldi, A, Gallamini, Andrea, Rossi, Andrea, Patti, Caterina, Picardi, Marco, Romano, Alessandra, Cantonetti, Maria, Oppi, Sara, Viviani, Simonetta, Bolis, Silvia, Trentin, Livio, Gini, Guido, Battistini, Roberta, Chauvie, Stephane, Sorasio, Roberto, Pavoni, Chiara, Zanotti, Roberta, Cimminiello, Michele, Schiavotto, Corrado, Viero, Piera, Mulé, Antonino, Fallanca, Federico, Ficola, Umberto, Tarella, Corrado, Guerra, Luca, Rambaldi, Alessandro, Gallamini, A, Rossi, A, Patti, C, Picardi, M, Romano, A, Cantonetti, M, Oppi, S, Viviani, S, Bolis, S, Trentin, L, Gini, G, Battistini, R, Chauvie, S, Sorasio, R, Pavoni, C, Zanotti, R, Cimminiello, M, Schiavotto, C, Viero, P, Mulé, A, Fallanca, F, Ficola, U, Tarella, C, Guerra, L, Rambaldi, A, Gallamini, Andrea, Rossi, Andrea, Patti, Caterina, Picardi, Marco, Romano, Alessandra, Cantonetti, Maria, Oppi, Sara, Viviani, Simonetta, Bolis, Silvia, Trentin, Livio, Gini, Guido, Battistini, Roberta, Chauvie, Stephane, Sorasio, Roberto, Pavoni, Chiara, Zanotti, Roberta, Cimminiello, Michele, Schiavotto, Corrado, Viero, Piera, Mulé, Antonino, Fallanca, Federico, Ficola, Umberto, Tarella, Corrado, Guerra, Luca, and Rambaldi, Alessandro

Abstract

PURPOSE To investigate the role of consolidation radiotherapy (cRT) in advanced-stage Hodgkin lymphoma (HL) presenting at baseline with a large nodal mass (LNM) in complete metabolic response after doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy. PATIENTS AND METHODS Advanced-stage (IIB-IVB) HL patients, enrolled in the HD 0607 trial (Clinicaltrial.gov identifier NCT00795613), with both a negative PET after two (PET-2) and six (PET-6) ABVD cycles, who presented at baseline with an LNM, defined as a nodal mass with the largest diameter $ 5 cm, were prospectively randomly assigned to receive cRT over the LNM or no further treatment (NFT). RESULTS Among 296 randomly assigned patients, the largest diameter of LNM at baseline was 5-7 cm in 101 (34%; subgroup A) and 8-10 cm in 96 (32%; subgroup B), whereas classic bulky (diameter. 10 cm) was detected in 99 (33%; subgroup C). Two hundred eighty patients (88%) showed a postchemotherapy RM. The median dose of cRT was 30.6 Gy (range, 24-36 Gy). After a median follow-up of 5.9 years (range, 0.5-10 years), the 6-year progression-free survival rate of patients who underwent cRT or NFT was, respectively, 91% (95% CI, 84% to 99%) and 95% (95% CI, 89% to 100%; P 5.62) in subgroup A; 98% (95% CI, 93% to 100%) and 90% (95% CI, 80% to 100%; P 5.24) in subgroup B; 89% (95% CI, 81% to 98%) and 86% (95% CI, 77% to 96%; P 5.53) in subgroup C (classic bulky). CONCLUSION cRT could be safely omitted in patients with HL presenting with an LNM and a negative PET-2 and PET-6 scan, irrespective from the LNM size detected at baseline.

Published
2020

73. Validation of a survival-risk score (SRS) in relapsed/refractory CLL patients treated with idelalisib–rituximab

Author

Gentile, Marino, Martino, E. A., Visentin, A., Coscia, M., Reda, G., Sportoletti, P., Mauro, F. R., Laurenti, Luca, Varettoni, M., Murru, R., Chiarenza, A., Vigna, E., Mendicino, F., Lucia, E., Bossio, S., Recchia, A. G., Moia, R., Pietrasanta, D., Loseto, G., Consoli, U., Scortechini, I., Rossi, Federica Maria, Zucchetto, A., Al-Janazreh, H., Vitale, C., Tripepi, G., D'Arrigo, G., Angeletti, I., Bomben, R., Neri, A., Cutrona, G., Fronza, G., Di Raimondo, F., Gaidano, G., Cuneo, A., Foa, Robin, Ferrarini, M., Trentin, L., Gattei, V., Morabito, Francesco, Gentile M., Laurenti L. (ORCID:0000-0002-8327-1396), Rossi F. M., Foa R., Morabito F., Gentile, Marino, Martino, E. A., Visentin, A., Coscia, M., Reda, G., Sportoletti, P., Mauro, F. R., Laurenti, Luca, Varettoni, M., Murru, R., Chiarenza, A., Vigna, E., Mendicino, F., Lucia, E., Bossio, S., Recchia, A. G., Moia, R., Pietrasanta, D., Loseto, G., Consoli, U., Scortechini, I., Rossi, Federica Maria, Zucchetto, A., Al-Janazreh, H., Vitale, C., Tripepi, G., D'Arrigo, G., Angeletti, I., Bomben, R., Neri, A., Cutrona, G., Fronza, G., Di Raimondo, F., Gaidano, G., Cuneo, A., Foa, Robin, Ferrarini, M., Trentin, L., Gattei, V., Morabito, Francesco, Gentile M., Laurenti L. (ORCID:0000-0002-8327-1396), Rossi F. M., Foa R., and Morabito F.

Abstract

N/a

Published
2020

74. Frontline treatment with the combination obinutuzumab ± chlorambucil for chronic lymphocytic leukemia outside clinical trials: Results of a multinational, multicenter study by ERIC and the Israeli CLL study group

Author

Herishanu, Y., Shaulov, A., Fineman, R., Basic-Kinda, S., Aviv, A., Wasik-Szczepanek, E., Jaksic, O., Zdrenghea, M., Greenbaum, U., Mandac, I., Simkovic, M., Morawska, M., Benjamini, O., Spacek, M., Nemets, A., Bairey, O., Trentin, L., Ruchlemer, R., Laurenti, Luca, Stanca Ciocan, O., Doubek, M., Shvidel, L., Dali, N., Miras, F., De Meuter, A., Dimou, M., Mauro, F. R., Coscia, M., Bumbea, H., Szasz, R., Tadmor, T., Gutwein, O., Gentile, Marino, Scarfo, L., Tedeschi, Alessandra, Sportoletti, P., Gimeno Vazquez, E., Marquet, J., Assouline, S., Papaioannou, M., Braester, A., Levato, L., Gregor, M., Rigolin, G. M., Loscertales, J., Medina Perez, A., Nijziel, M. R., Popov, V. M., Collado, R., Slavutsky, I., Itchaki, G., Ringelstein, S., Goldschmidt, N., Perry, C., Levi, S., Polliack, A., Ghia, P., Laurenti L. (ORCID:0000-0002-8327-1396), Gentile M., Tedeschi A., Herishanu, Y., Shaulov, A., Fineman, R., Basic-Kinda, S., Aviv, A., Wasik-Szczepanek, E., Jaksic, O., Zdrenghea, M., Greenbaum, U., Mandac, I., Simkovic, M., Morawska, M., Benjamini, O., Spacek, M., Nemets, A., Bairey, O., Trentin, L., Ruchlemer, R., Laurenti, Luca, Stanca Ciocan, O., Doubek, M., Shvidel, L., Dali, N., Miras, F., De Meuter, A., Dimou, M., Mauro, F. R., Coscia, M., Bumbea, H., Szasz, R., Tadmor, T., Gutwein, O., Gentile, Marino, Scarfo, L., Tedeschi, Alessandra, Sportoletti, P., Gimeno Vazquez, E., Marquet, J., Assouline, S., Papaioannou, M., Braester, A., Levato, L., Gregor, M., Rigolin, G. M., Loscertales, J., Medina Perez, A., Nijziel, M. R., Popov, V. M., Collado, R., Slavutsky, I., Itchaki, G., Ringelstein, S., Goldschmidt, N., Perry, C., Levi, S., Polliack, A., Ghia, P., Laurenti L. (ORCID:0000-0002-8327-1396), Gentile M., and Tedeschi A.

Abstract

In recent years, considerable progress has been made in frontline therapy for elderly/physically unfit patients with CLL. The combination of obinutuzumab and chlorambucil (O-Clb) has been shown to prolong progression free survival (PFS, median PFS-31.5 months) and overall survival (OS) compared to chlorambucil alone. More recently, obinutuzumab given in combination with either ibrutinib or venetoclax improved PFS but not OS when compared to O-Clb. In this retrospective multinational, multicenter co-operative study, we evaluated the efficacy and safety of frontline treatment with O ± Clb in unfit patients with CLL, in a “real-world” setting. Patients with documented del (17p13.1)/TP53 mutation were excluded. A total of 437 patients (median age, 75.9 years; median CIRS score, 8; median creatinine clearance, 61.1 mL/min) were included. The clinical overall response rate was 80.3% (clinical complete and partial responses in 38.7% and 41.6% of patients, respectively). Median observation time was 14.1 months and estimated median PFS was 27.6 months (95% CI, 24.2-31.0). In a multivariate analysis, high-risk disease [del (11q22.3) and/or IGHV-unmutated], lymph nodes of diameter > 5 cm, obinutuzumab monotherapy and reduced cumulative dose of obinutuzumab, were all independently associated with shorter PFS. The median OS has not yet been reached and estimated 2-year OS is 88%. In conclusion, in a “real-world” setting, frontline treatment with O-Clb achieves PFS comparable to that reported in clinical trials. Inferior outcomes were noted in patients with del (11q22.3) and/or unmutated IGHV and those treated with obinutuzumab-monotherapy. Thus, O-Clb can be still considered as legitimate frontline therapy for unfit CLL patients with low-risk disease.

Published
2020

75. COVID-19 severity and mortality in patients with chronic lymphocytic leukemia: a joint study by ERIC, the European Research Initiative on CLL, and CLL Campus

Author

Scarfo, L., Chatzikonstantinou, T., Rigolin, G. M., Quaresmini, G., Motta, M., Vitale, C., Garcia-Marco, J. A., Hernandez-Rivas, J. A., Miras, F., Baile, M., Marquet, J., Niemann, C. U., Reda, G., Munir, T., Gimeno, E., Marchetti, M., Quaglia, F. M., Varettoni, M., Delgado, J., Iyengar, S., Janssens, A., Marasca, R., Ferrari, A., Cuellar-Garcia, C., Itchaki, G., Spacek, M., De Paoli, L., Laurenti, Luca, Levin, M. -D., Lista, E., Mauro, F. R., Simkovic, M., Van Der Spek, E., Vandenberghe, E., Trentin, L., Wasik-Szczepanek, E., Ruchlemer, R., Bron, D., De Paolis, M. R., Del Poeta, G., Farina, L., Foglietta, M., Gentile, Marino, Herishanu, Y., Herold, T., Jaksic, O., Kater, A. P., Kersting, S., Malerba, L., Orsucci, L., Popov, V. M., Sportoletti, P., Yassin, M., Pocali, B., Barna, G., Chiarenza, A., dos Santos, G., Nikitin, E., Andres, M., Dimou, M., Doubek, M., Enrico, A., Hakobyan, Y., Kalashnikova, O., Ortiz Pareja, M., Papaioannou, M., Rossi, Dario, Shah, N., Shrestha, A., Stanca, O., Stavroyianni, N., Strugov, V., Tam, C., Zdrenghea, M., Coscia, M., Stamatopoulos, K., Rossi, G., Rambaldi, A., Montserrat, E., Foa, Robin, Cuneo, A., Ghia, P., Laurenti L. (ORCID:0000-0002-8327-1396), Gentile M., Rossi D., Foa R., Scarfo, L., Chatzikonstantinou, T., Rigolin, G. M., Quaresmini, G., Motta, M., Vitale, C., Garcia-Marco, J. A., Hernandez-Rivas, J. A., Miras, F., Baile, M., Marquet, J., Niemann, C. U., Reda, G., Munir, T., Gimeno, E., Marchetti, M., Quaglia, F. M., Varettoni, M., Delgado, J., Iyengar, S., Janssens, A., Marasca, R., Ferrari, A., Cuellar-Garcia, C., Itchaki, G., Spacek, M., De Paoli, L., Laurenti, Luca, Levin, M. -D., Lista, E., Mauro, F. R., Simkovic, M., Van Der Spek, E., Vandenberghe, E., Trentin, L., Wasik-Szczepanek, E., Ruchlemer, R., Bron, D., De Paolis, M. R., Del Poeta, G., Farina, L., Foglietta, M., Gentile, Marino, Herishanu, Y., Herold, T., Jaksic, O., Kater, A. P., Kersting, S., Malerba, L., Orsucci, L., Popov, V. M., Sportoletti, P., Yassin, M., Pocali, B., Barna, G., Chiarenza, A., dos Santos, G., Nikitin, E., Andres, M., Dimou, M., Doubek, M., Enrico, A., Hakobyan, Y., Kalashnikova, O., Ortiz Pareja, M., Papaioannou, M., Rossi, Dario, Shah, N., Shrestha, A., Stanca, O., Stavroyianni, N., Strugov, V., Tam, C., Zdrenghea, M., Coscia, M., Stamatopoulos, K., Rossi, G., Rambaldi, A., Montserrat, E., Foa, Robin, Cuneo, A., Ghia, P., Laurenti L. (ORCID:0000-0002-8327-1396), Gentile M., Rossi D., and Foa R.

Abstract

Chronic lymphocytic leukemia (CLL) is a disease of the elderly, characterized by immunodeficiency. Hence, patients with CLL might be considered more susceptible to severe complications from COVID-19. We undertook this retrospective international multicenter study to characterize the course of COVID-19 in patients with CLL and identify potential predictors of outcome. Of 190 patients with CLL and confirmed COVID-19 diagnosed between 28/03/2020 and 22/05/2020, 151 (79%) presented with severe COVID-19 (need of oxygen and/or intensive care admission). Severe COVID-19 was associated with more advanced age (≥65 years) (odds ratio 3.72 [95% CI 1.79–7.71]). Only 60 patients (39.7%) with severe COVID-19 were receiving or had recent (≤12 months) treatment for CLL at the time of COVID-19 versus 30/39 (76.9%) patients with mild disease. Hospitalization rate for severe COVID-19 was lower (p < 0.05) for patients on ibrutinib versus those on other regimens or off treatment. Of 151 patients with severe disease, 55 (36.4%) succumbed versus only 1/38 (2.6%) with mild disease; age and comorbidities did not impact on mortality. In CLL, (1) COVID-19 severity increases with age; (2) antileukemic treatment (particularly BTK inhibitors) appears to exert a protective effect; (3) age and comorbidities did not impact on mortality, alluding to a relevant role of CLL and immunodeficiency.

Published
2020

76. Efficacy of bendamustine and rituximab in unfit patients with previously untreated chronic lymphocytic leukemia. Indirect comparison with ibrutinib in a real-world setting. A GIMEMA-ERIC and US study

Author

Cuneo, A., Mato, A. R., Rigolin, G. M., Piciocchi, A., Gentile, Marino, Laurenti, Luca, Allan, J. N., Pagel, J. M., Brander, D. M., Hill, B. T., Winter, A., Lamanna, N., Tam, C. S., Jacobs, R., Lansigan, F., Barr, P. M., Shadman, M., Skarbnik, A. P., Pu, J. J., Sehgal, A. R., Schuster, S. J., Shah, N. N., Ujjani, C. S., Roeker, L., Orlandi, E. M., Billio, Atto, Trentin, L., Spacek, M., Marchetti, M., Tedeschi, Alessandra, Ilariucci, F., Gaidano, G., Doubek, M., Farina, L., Molica, Serena, Di Raimondo, F., Coscia, M., Mauro, F. R., de la Serna, J., Medina Perez, A., Ferrarini, I., Cimino, Giovanni, Cavallari, M., Cucci, R., Vignetti, M., Foa, Robin, Ghia, P., Gentile M., Laurenti L. (ORCID:0000-0002-8327-1396), Billio A., Tedeschi A., Molica S., Cimino G., Foa R., Cuneo, A., Mato, A. R., Rigolin, G. M., Piciocchi, A., Gentile, Marino, Laurenti, Luca, Allan, J. N., Pagel, J. M., Brander, D. M., Hill, B. T., Winter, A., Lamanna, N., Tam, C. S., Jacobs, R., Lansigan, F., Barr, P. M., Shadman, M., Skarbnik, A. P., Pu, J. J., Sehgal, A. R., Schuster, S. J., Shah, N. N., Ujjani, C. S., Roeker, L., Orlandi, E. M., Billio, Atto, Trentin, L., Spacek, M., Marchetti, M., Tedeschi, Alessandra, Ilariucci, F., Gaidano, G., Doubek, M., Farina, L., Molica, Serena, Di Raimondo, F., Coscia, M., Mauro, F. R., de la Serna, J., Medina Perez, A., Ferrarini, I., Cimino, Giovanni, Cavallari, M., Cucci, R., Vignetti, M., Foa, Robin, Ghia, P., Gentile M., Laurenti L. (ORCID:0000-0002-8327-1396), Billio A., Tedeschi A., Molica S., Cimino G., and Foa R.

Abstract

Limited information is available on the efficacy of front-line bendamustine and rituximab (BR) in chronic lymphocytic leukemia (CLL) with reduced renal function or coexisting conditions. We therefore analyzed a cohort of real-world patients and performed a matched adjusted indirect comparison with a cohort of patients treated with ibrutinib. One hundred and fifty-seven patients with creatinine clearance (CrCl) <70 mL/min and/or CIRS score >6 were treated with BR. The median age was 72 years; 69% of patients had ≥2 comorbidities and the median CrCl was 59.8 mL/min. 17.6% of patients carried TP53 disruption. The median progression-free survival (PFS) was 45 months; TP53 disruption was associated with a shorter PFS (P = 0.05). The overall survival (OS) at 12, 24, and 36 months was 96.2%, 90.1%, and 79.5%, respectively. TP53 disruption was associated with an increased risk of death (P = 0.01). Data on 162 patients ≥65 years treated with ibrutinib were analyzed and compared with 165 patients ≥65 years treated with BR. Factors predicting for a longer PFS at multivariable analysis in the total patient population treated with BR and ibrutinib were age (HR 1.06, 95% CI 1.02-1.10, P < 0.01) and treatment with ibrutinib (HR 0.55, 95% CI 0.33-0.93, P = 0.03). In a post hoc analysis of patients in advanced stage, a significant PFS advantage was observed in patient who had received ibrutinib (P = 0.03), who showed a trend for OS advantage (P = 0.08). We arrived at the following conclusions: (a) BR is a relatively effective first-line regimen in a real-world population of unfit patients without TP53 disruption, (b) ibrutinib provided longer disease control than BR in patients with advanced disease stage.

Published
2020

80. Cytogenetic complexity in chronic lymphocytic leukemia: Definitions, associations, and clinical impact

Author

Baliakas, P. Jeromin, S. Iskas, M. Puiggros, A. Plevova, K. Nguyen-Khac, F. Davis, Z. Matteo Rigolin, G. Visentin, A. Xochelli, A. Delgado, J. Baran-Marszak, F. Stalika, E. Abrisqueta, P. Durechova, K. Papaioannou, G. Eclache, V. DImou, M. Iliakis, T. Collado, R. Doubek, M. Calasanz, M.J. Ruiz-Xiville, N. Moreno, C. Jarosova, M. Leeksma, A.C. Panayiotidis, P. Podgornik, H. Cymbalista, F. Anagnostopoulos, A. Trentin, L. Stavroyianni, N. Davi, F. Ghia, P. Kater, A.P. Cuneo, A. Pospisilova, S. Espinet, B. Athanasiadou, A. Oscier, D. Haferlach, C. Stamatopoulos, K. on behalf of ERIC, the European Research Initiative on CLL

Abstract

Recent evidence suggests that complex karyotype (CK) defined by the presence of ≥3 chromosomal aberrations (structural and/or numerical) identified by using chromosomebanding analysis (CBA) may be relevant for treatment decision-making in chronic lymphocytic leukemia (CLL). However, many challenges toward the routine clinical application of CBA remain. In a retrospective study of 5290 patients with available CBA data, we explored both clinicobiological associations and the clinical impact of CK in CLL. We found that patients with ≥5 abnormalities, defined as high-CK, exhibit uniformly dismal clinical outcomes, independently of clinical stage, TP53 aberrations (deletion of chromosome 17p and/or TP53 mutations [TP53abs]), and the expression of somatically hypermutated (M-CLL) or unmutated immunoglobulin heavy variable genes. Thus, they contrasted with CK cases with 3 or 4 aberrations (low-CK and intermediate-CK, respectively) who followed aggressive disease courses only in the presence of TP53abs. At the other end of the spectrum, patients with CK and +12,+19 displayed an exceptionally indolent profile. Building upon CK, TP53abs, and immunoglobulin heavy variable gene somatic hypermutation status, we propose a novel hierarchical model in which patients with high-CK exhibit the worst prognosis, whereas those with mutated CLL lacking CK or TP53abs, as well as CK with +12,+19, show the longest overall survival. Thus, CK should not be axiomatically considered unfavorable in CLL, representing a heterogeneous group with variable clinical behavior. High-CK with ≥5 chromosomal aberrations emerges as prognostically adverse, independent of other biomarkers. Prospective clinical validation is warranted before ultimately incorporating high-CK in risk stratification of CLL. © 2019 by The American Society of Hematology.

Published
2019

81. Oral Prolonged-Release Oxycodone-Naloxone: Analgesic Response, Safety Profile, and Factors Influencing the Response in Patients With Advanced Cancer

Author

Corli, O, Iorno, V, Legramandi, L, Rulli, E, Roberto, A, Azzarello, G, Schiavon, S, Cavanna, L, De Santis, S, Cartoni, C, Di Marco, P, Dauri, M, Mistretta, R, Bortolussi, R, Clerico, M, Pacchioni, M, Crispino, C, Marabese, M, Corsi, N, Natoli, S, Lipari, G, Luzi, M, Palumbo, G, and Trentin, L

Subjects
patients with cancer, Constipation, Analgesic, Irritability, Settore MED/06, 03 medical and health sciences, 0302 clinical medicine, 030202 anesthesiology, oxycodone-naloxone, Medicine, factors influencing the response, Adverse effect, Oxycodone/naloxone, business.industry, Cancer, analgesia, constipation, medicine.disease, Safety profile, Anesthesiology and Pain Medicine, Anesthesia, Settore MED/41, medicine.symptom, business, Cancer pain, 030217 neurology & neurosurgery
Abstract

Background Oxycodone-Naloxone (OXN) aims to reduce opioid-related constipation while being successfully analgesic. Methods We evaluated the analgesic response, prevalence, and severity of side effects in 176 cancer patients with moderate to severe pain and treated with OXN. Patients were followed for 28 days and evaluated every seven. Pain intensity, changes of therapy, and adverse drug reactions were recorded at each visit. The primary efficacy endpoint was the proportion of responders (≥30% reduction of pain intensity from baseline to final) and final average pain score ≤4 on a 0-10 scale. Results Average and worst pain intensity, and breakthrough pain (BTP) prevalence decreased over time and 81.3% of patients were responders. The starting daily dose of OXN was raised from 25.1±13.0 mg to 44.1±29.9 mg, and dose escalation >5%/day was observed in 19.4% of patients; 40.8-46.2% and 11.0-17.0% experienced any and severe grade of constipation during the follow-up visit, respectively. Digestive system tumor, thyroid endocrinopathies, psychological irritability, and BTP increased the risk of analgesic non-response. Conclusions OXN had strong analgesic effect in moderate to severe cancer pain patients: the safety profile is in line with the common adverse effects of opioids and severe constipation was uncommon. This article is protected by copyright. All rights reserved.

Published
2019

82. An iflavirus found in stink bugs (Hemiptera: Pentatomidae) of four different species

Author

SANTOS, E. R. dos, TRENTIN, L. B., ECKER, A., SILVA, L. A., BORGES, M., MOWERY, J. D., RIBEIRO, B. M., HARRISON, R. L., ARDISSON-ARAÚJO, D. M. P., ETHIANE R. DOS SANTOS, UFSM, LUANA B. TRENTIN, UFSM, ASSIS ECKER, UFSM, LEONARDO A. SILVA, UNB, MIGUEL BORGES, Cenargen, JOSEPH D. MOWERY, USDA AGRICULTURAL RESEARCH SERVICE, USA, BERGMANN M. RIBEIRO, UNB, ROBERT L. HARRISON, USDA AGRICULTURAL RESEARCH SERVICE, USA, and DANIEL M. P. ARDISSON-ARAÚJO, UFSM.

Subjects
Chinavia ubica, Dichelops melachantus, Iflavirus, Pentatomidae, Iflaviridae, Covert infection, Euschistus Heros, Halyomorpha halys, Stink bugs
Abstract

Made available in DSpace on 2019-07-10T00:49:09Z (GMT). No. of bitstreams: 1 1s2.0S0042682219301503main.pdf: 2368020 bytes, checksum: ebf237a6a7125b843c516024ef57dd9a (MD5) Previous issue date: 2019

Published
2019

83. DNA methylation profiles in chronic lymphocytic leukemia patients treated with chemoimmunotherapy

Author

Tsagiopoulou, M. Papakonstantinou, N. Moysiadis, T. Mansouri, L. Ljungström, V. Duran-Ferrer, M. Malousi, A. Queirós, A.C. Plevova, K. Bhoi, S. Kollia, P. Oscier, D. Anagnostopoulos, A. Trentin, L. Ritgen, M. Pospisilova, S. Stavroyianni, N. Ghia, P. Martin-Subero, J.I. Pott, C. Rosenquist, R. Stamatopoulos, K.

Subjects
hemic and lymphatic diseases
Abstract

Background: In order to gain insight into the contribution of DNA methylation to disease progression of chronic lymphocytic leukemia (CLL), using 450K Illumina arrays, we determined the DNA methylation profiles in paired pre-treatment/relapse samples from 34 CLL patients treated with chemoimmunotherapy, mostly (n = 31) with the fludarabine-cyclophosphamide-rituximab (FCR) regimen. Results: The extent of identified changes in CLL cells versus memory B cells from healthy donors was termed "epigenetic burden" (EB) whereas the number of changes between the pre-treatment versus the relapse sample was termed "relapse changes" (RC). Significant (p < 0.05) associations were identified between (i) high EB and short time-to-first-treatment (TTFT); and, (ii) few RCs and short time-to-relapse. Both the EB and the RC clustered in specific genomic regions and chromatin states, including regulatory regions containing binding sites of transcription factors implicated in B cell and CLL biology. Conclusions: Overall, we show that DNA methylation in CLL follows different dynamics in response to chemoimmunotherapy. These epigenetic alterations were linked with specific clinical and biological features. © 2019 The Author(s).

Published
2019

84. Cytogenetic complexity in chronic lymphocytic leukemia: definitions, associations, and clinical impact

Author

Baliakas, P, Jeromin, S, Iskas, M, Puiggros, A, Plevova, K, Nguyen-Khac, F, Davis, Z, Rigolin, GM, Visentin, A, Xochelli, A, Delgado, J, Baran-Marszak, F, Stalika, E, Abrisqueta, P, Durechova, K, Papaioannou, G, Eclache, V, Dimou, M, Iliakis, T, Collado, R, Doubek, M, Calasanz, MJ, Ruiz-Xiville, N, Moreno, C, Jarosova, M, Leeksma, AC, Panayiotidis, P, Podgornik, H, Cymbalista, F, Anagnostopoulos, A, Trentin, L, Stavroyianni, N, Davi, F, Ghia, P, Kater, AP, Cuneo, A, Pospisilova, S, Espinet, B, Athanasiadou, A, Oscier, D, Haferlach, C, Stamatopoulos, K, and ERIC European Res Initiative CLL

Abstract

Recent evidence suggests that complex karyotype (CK) defined by the presence of >= 3 chromosomal aberrations (structural and/or numerical) identified by using chromosome-banding analysis (CBA) may be relevant for treatment decision-making in chronic lymphocytic leukemia (CLL). However, many challenges toward the routine clinical application of CBA remain. In a retrospective study of 5290 patients with available CBA data, we explored both clinicobiological associations and the clinical impact of CK in CLL. We found that patients with >= 5 abnormalities, defined as high-CK, exhibit uniformly dismal clinical outcomes, independently of clinical stage, TP53 aberrations (deletion of chromosome 17p and/or TP53 mutations [TP53abs]), and the expression of somatically hypermutated (M-CLL) or unmutated immunoglobulin heavy variable genes. Thus, they contrasted with CK cases with 3 or 4 aberrations (low-CK and intermediate-CK, respectively) who followed aggressive disease courses only in the presence of TP53abs. At the other end of the spectrum, patients with CK and 112,119 displayed an exceptionally indolent profile. Building upon CK, TP53abs, and immunoglobulin heavy variable gene somatic hyper-mutation status, we propose a novel hierarchical model in which patients with high-CK exhibit the worst prognosis, whereas those with mutated CLL lacking CK or TP53abs, as well as CK with 112,119, show the longest overall survival. Thus, CK should not be axiomatically considered unfavorable in CLL, representing a heterogeneous group with variable clinical behavior. High-CK with >= 5 chromosomal aberrations emerges as prognostically adverse, independent of other biomarkers. Prospective clinical validation is warranted before ultimately incorporating high-CK in risk stratification of CLL.

Published
2019

88. TP53 disruption as a risk factor in the era of targeted therapies: A multicenter retrospective study of 525 chronic lymphocytic leukemia cases

Author

Morabito, Francesco, Del Poeta, G., Mauro, F. R., Reda, G., Sportoletti, P., Laurenti, Luca, Coscia, M., Herishanu, Y., Bossio, S., Varettoni, M., Murru, R., Chiarenza, A., Visentin, A., Condoluci, A., Moia, R., Pietrasanta, D., Loseto, G., Consoli, U., Scortechini, I., Recchia, A. G., Rossi, Federica Maria, Zucchetto, A., Al-Janazreh, H., Martino, E. A., Vigna, E., Tripepi, G., D'Arrigo, G., Galimberti, Sofia, Rago, A., Angeletti, I., Biagi, A., Del Giudice, I., Bomben, R., Neri, A., Fronza, G., Cutrona, G., Jaksic, O., Olivieri, J., Rossi, Dario, Di Raimondo, F., Cuneo, A., Gaidano, G., Polliack, A., Trentin, L., Foa, Robin, Ferrarini, M., Gattei, V., Gentile, Marino, Morabito F., Laurenti L. (ORCID:0000-0002-8327-1396), Rossi F. M., Galimberti S., Rossi D., Foa R., Gentile M., Morabito, Francesco, Del Poeta, G., Mauro, F. R., Reda, G., Sportoletti, P., Laurenti, Luca, Coscia, M., Herishanu, Y., Bossio, S., Varettoni, M., Murru, R., Chiarenza, A., Visentin, A., Condoluci, A., Moia, R., Pietrasanta, D., Loseto, G., Consoli, U., Scortechini, I., Recchia, A. G., Rossi, Federica Maria, Zucchetto, A., Al-Janazreh, H., Martino, E. A., Vigna, E., Tripepi, G., D'Arrigo, G., Galimberti, Sofia, Rago, A., Angeletti, I., Biagi, A., Del Giudice, I., Bomben, R., Neri, A., Fronza, G., Cutrona, G., Jaksic, O., Olivieri, J., Rossi, Dario, Di Raimondo, F., Cuneo, A., Gaidano, G., Polliack, A., Trentin, L., Foa, Robin, Ferrarini, M., Gattei, V., Gentile, Marino, Morabito F., Laurenti L. (ORCID:0000-0002-8327-1396), Rossi F. M., Galimberti S., Rossi D., Foa R., and Gentile M.

Abstract

n/a

Published
2019

89. Rituximab-responsive CIDP

Author

Briani, C., Zara, G., Zambello, R., Trentin, L., Rana, M., and Zaja, F.

Published
2004

90. SEQUENTIAL USE OF THROMBOPOIETIN RECEPTOR AGONISTS IN ADULT PRIMARY IMMUNE THROMBOCYTOPENIA PATIENTS: A RETROSPECTIVE COLLABORATIVE SURVEY FROM ITALIAN HEMATOLOGY CENTERS

Author

Carpenedo, M, Cantoni, S, Mazzucconi, MG, De Stefano, V, Carrai, V, Ruggeri, M, Specchia, G, Vianelli, N, Pane, F, Consoli, U, Zaja, F, Artoni, A, Trentin, L, Ferrara, F, Barcellini, W, Caramazza, D, Rossi, E, Baldacci, E, Ciminello, A, Carbone, C, Cairoli, R, Carpenedo, M, Cantoni, S, Mazzucconi, M, De Stefano, V, Carrai, V, Ruggeri, M, Specchia, G, Vianelli, N, Pane, F, Consoli, U, Zaja, F, Artoni, A, Trentin, L, Ferrara, F, Barcellini, W, Caramazza, D, Rossi, E, Baldacci, E, Ciminello, A, Carbone, C, and Cairoli, R

Subjects
Hematology
Published
2017

91. No improvement in long-term survival over time for chronic lymphocytic leukemia patients in stereotyped subsets #1 and #2 treated with chemo(Immuno)therapy

Author

Baliakas, P. Mattsson, M. Hadzidimitriou, A. Minga, E. Agathangelidis, A. Sutton, L.-A. Scarfo, L. Davis, Z. Yan, X.-J. Plevova, K. Sandberg, Y. Vojdeman, F.J. Tzenou, T. Chu, C.C. Veronese, S. Mansouri, L. Smedby, K.E. Giudicelli, V. Nguyen-Khac, F. Panagiotidis, P. Juliusson, G. Anagnostopoulos, A. Lefranc, M.-P. Trentin, L. Catherwood, M. Montillo, M. Niemann, C.U. Langerak, A.W. Pospisilova, S. Stavroyianni, N. Chiorazzi, N. Oscier, D. Jelinek, D.F. Shanafelt, T. Darzentas, N. Belessi, C. Davi, F. Ghia, P. Rosenquist, R. Stamatopoulos, K.

Published
2018

93. Efficacy of bendamustine and rituximab as first salvage treatment in chronic lymphocytic leukemia and indirect comparison with ibrutinib: a GIMEMA, ERIC and UK CLL FORUM study

Author

Cuneo, A, Follows, G, Rigolin, GM, Piciocchi, A, Tedeschi, A, Trentin, L, Perez, AM, Coscia, M, Laurenti, L, Musuraca, G, Farina, L, Delgado, AR, Orlandi, EM, Galieni, P, Mauro, FR, Visco, C, Amendola, A, Billio, A, Marasca, R, Chiarenza, A, Meneghini, V, Ilariucci, F, Marchetti, M, Molica, S, Re, F, Gaidano, G, Gonzalez, M, Forconi, F, Ciolli, S, Cortelezzi, A, Montillo, M, Smolej, L, Schuh, A, Eyre, TA, Kennedy, B, Bowles, KM, Vignetti, M, de la Seam, J, Moreno, C, Foa, R, Ghia, P, GIMEMA, European Res Initiative CLL ERIC, and UK CLL Forum

Abstract

We performed an observational study on the efficacy of ben-damustine and rituximab (BR) as first salvage regimen in chronic lymphocytic leukemia (CLL). In an intention-to-treat analysis including 237 patients, the median progression-free survival (PFS) was 25 months. The presence of del(17p), unmutated IGHV and advanced stage were associated with a shorter PFS at multivariate analysis. The median time-to-next treatment was 31.3 months. Front-line treatment with a chemoimmunotherapy regimen was the only predictive factor for a shorter time to next treatment at multivariate analysis. The median overall survival (OS) was 74.5 months. Advanced disease stage (i.e. Rai stage III-IV or Binet stage C) and resistant disease were the only parameters significantly associated with a shorter OS. Grade 3-5 infections were recorded in 6.3% of patients. A matched-adjusted indirect comparison with ibrutinib given second-line within Named Patient Programs in the United Kingdom and in Italy was carried out with OS as objective end point. When restricting the analysis to patients with intact 17p who had received chemoimmunotherapy in first line, there was no difference in OS between patients treated with ibrutinib (63% alive at 36 months) and patients treated with BR (74.4% alive at 36 months). BR is an efficacious first salvage regimen in CLL in a real-life population, including the elderly and unfit patients. BR and ibrutinib may be equally effective in terms of OS when used as first salvage treatment in patients without 17p deletion. (Registered at clinicaltrials.gov identifier: 02491398)

Published
2018

94. PF392 MONOCLONAL GAMMOPATHY AND HYPOGAMMAGLOBULINEMIA AS INDEPENDENT PROGNOSTIC FACTORS IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA: A RETROSPECTIVE MULTICENTRIC EXPERIENCE

Author

Corbingi, A., primary, Innocenti, I., additional, Tomasso, A., additional, Pasquale, R., additional, Visentin, A., additional, Varettoni, M., additional, Autore, F., additional, Morelli, F., additional, Trentin, L., additional, Reda, G., additional, and Laurenti, L., additional

Published
2019
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95. CONSOLIDATION RADIOTHERAPY COULD BE OMITTED IN ADVANCED HODGKIN LYMPHOMA WITH LARGE NODAL MASS IN COMPLETE METABOLIC RESPONSE AFTER ABVD. FINAL ANALYSIS OF THE RANDOMIZED HD0607 TRIAL

Author

Gallamini, A., primary, Rossi, A., additional, Patti, C., additional, Picardi, M., additional, Romano, A., additional, Cantonetti, M., additional, Oppi, S., additional, Viviani, S., additional, Bolis, S., additional, Trentin, L., additional, Gini, G., additional, Battistini, R., additional, Chauvie, S., additional, Bertolotti, L., additional, Pavoni, C., additional, Parvis, G., additional, Zanotti, R., additional, Gavarotti, P., additional, Cimminiello, M., additional, Schiavotto, C., additional, Viero, P., additional, Avigdor, A., additional, Tarella, C., additional, and Rambaldi, A., additional

Published
2019
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96. PF375 IBRUTINIB AND RITUXIMAB AS FRONT-LINE TREATMENT FOR UNFIT PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA (CLL). PRELIMINARY RESULTS FROM THE GIMEMA LLC1114 STUDY

Author

Mauro, F.R., primary, Molica, S., additional, Paoloni, F., additional, Reda, G., additional, Trentin, L., additional, Marchetti, M., additional, Pietrasanta, D., additional, Coscia, M., additional, Marasca, R., additional, Sportoletti, P., additional, Gaidano, G., additional, Orsucci, L., additional, Stelitano, C., additional, Di Renzo, N., additional, Liberati, A.M., additional, Gottardi, D., additional, Re, F., additional, Ilariucci, F., additional, Zinzani, P., additional, Mannina, D., additional, Gozzetti, A., additional, Molinari, A.L., additional, Gentile, M., additional, Consoli, U., additional, Laurenti, L., additional, Arcaini, L., additional, Ibatici, A., additional, Murru, R., additional, Tani, M., additional, De Propris, M.S., additional, Del Giudice, I., additional, Della Starza, I., additional, Raponi, S., additional, Nanni, M., additional, Fazi, P., additional, Crea, E., additional, Neri, A., additional, Specchia, G., additional, Guarini, A.R., additional, Cuneo, A., additional, and Foà, R., additional

Published
2019
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97. PS1152 THE USE OF THE BCL-2 INHIBITOR IN CLL PATIENTS WHO PROGRESSED AFTER B-CELL-RECEPTOR INHIBITORS: A RETROSPECTIVE MULTICENTER ITALIAN EXPERIENCE

Author

Innocenti, I., primary, Morelli, F., additional, Autore, F., additional, Piciocchi, A., additional, Frustaci, A., additional, Mauro, F.R., additional, Schiattone, L., additional, Trentin, L., additional, Poeta, G. Del, additional, Reda, G., additional, Rigolin, G.M., additional, Ibatici, A., additional, Ciolli, S., additional, Coscia, M., additional, Sportoletti, P., additional, Murru, R., additional, Levato, L., additional, Gentile, M., additional, D’Arena, G., additional, Villa, M.R., additional, Fontana, R., additional, Tedeschi, A., additional, Scarfò, L., additional, Cuneo, A., additional, Foà, R., additional, and Laurenti, L., additional

Published
2019
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