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1. 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

3. 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

4. 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

8. 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

9. Practical management of ibrutinib in the real life: Focus on atrial fibrillation and bleeding

Author

Boriani, G, Corradini, P, Cuneo, A, Falanga, A, Foà, R, Gaidano, G, Ghia, P, Martelli, M, Marasca, R, Massaia, M, Mauro, F, Minotti, G, Molica, S, Montillo, M, Pinto, A, Tedeschi, A, Vitolo, U, Zinzani, P, Boriani G, Corradini P, Cuneo A, Falanga A, Foà R, Gaidano G, Ghia PP, Martelli M, Marasca R, Massaia M, Mauro FR, Minotti G, Molica S, Montillo M, Pinto A, Tedeschi A, Vitolo U, Zinzani PL, Boriani, G, Corradini, P, Cuneo, A, Falanga, A, Foà, R, Gaidano, G, Ghia, P, Martelli, M, Marasca, R, Massaia, M, Mauro, F, Minotti, G, Molica, S, Montillo, M, Pinto, A, Tedeschi, A, Vitolo, U, Zinzani, P, Boriani G, Corradini P, Cuneo A, Falanga A, Foà R, Gaidano G, Ghia PP, Martelli M, Marasca R, Massaia M, Mauro FR, Minotti G, Molica S, Montillo M, Pinto A, Tedeschi A, Vitolo U, and Zinzani PL

Abstract

The Bruton tyrosine kinase inhibitor ibrutinib (IB) has attained an important role in the treatment of patients with chronic lymphocytic leukaemia, mantle cell lymphoma, and Waldenström macroglobulinemia, significantly improving clinical outcomes. However, IB therapy has been associated with an increased risk of atrial fibrillation (AF) and bleeding. We report on the expert opinion that a group of Italian haematologists, cardiologists, and pharmacologists jointly released to improve the practical management of patients at risk for AF and bleeding during treatment with IB. A proper pretreatment assessment to identify patients who are at a higher risk, careful choice of concomitant drugs, regular monitoring, and multispecialist approach were characterized as the main principles of clinical management of these patients. For patients developing AF, anticoagulant and antiarrhythmic therapy must be guided by considerations about efficacy, safety, and risk of pharmacokinetic interactions with IB. For patients experiencing bleeding or requiring procedures that increase the risk of bleeding, considerations about platelet turnover, IB-related platelet dysfunctions, and bleeding worsening by concomitant anticoagulants or antiplatelet agents provide clues to manage bleeding. Overall, AF and bleeding are manageable clinical events in patients receiving IB, not requiring drug interruption in most cases. Preexisting AF should not represent an absolute contraindication to IB therapy. For each patient candidate for IB, strategies of risk assessment and mitigation may allow to exploit the life-saving effects of in chronic lymphocytic leukaemia and mantle cell lymphoma

Published
2018

10. FRONT-LINE THERAPY WITH FLUDARABINE, CYCLOPHOSPHAMIDE, OFATUMUMAB (FC-O2) IN YOUNG (<= 65 YRS) AND FIT CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS. RESULTS OF THE PROSPECTIVE PHASE 2 GIMEMA STUDY LLC0911

Author

Mauro, Fr, Molica, S, Zaja, F, Piciocchi, A, Ilariucci, F, Coscia, M, Carella, Am, Re, F, Liberati, Am, Tedeschi, A, Gozzetti, A, Cuneo, A, Cortelezzi, A, Baraldi, A, Del Poeta, G, Musolino, C, Battistini, R, De Propris, Ms, Della Starza, I, Raponi, S, Ilari, C, Cafforio, L, Nanni, M, Fazi, P, Vignetti, M, Russo, F, Porrazzo, M, Riemma, C, Specchia, G, Neri, A, Guarini, A, and Foa, R

Published
2017

12. Ibrutinib Treatment Mitigates Phenotypic Alterations of Non-Neoplastic Immune Cell Compartments in Chronic Lymphocytic Leukemia

Author

Griggio, V, Vitale, C, Todaro, M, Mauro, Fr, Salvetti, C, Pietrasanta, D, Vincelli, Id, Scarfo, L, Del Poeta, G, Gaidano, G, Gattei, V, Foà, R, Boccadoro, M, and Coscia, M

Subjects
Immunology, Cell Biology, Hematology, Biochemistry
Abstract

Background: Chronic lymphocytic leukemia (CLL) is characterized by phenotypic and functional defects of immune cells, which often emerge into increased susceptibility to infections and autoimmunity, and also contribute to immune evasion of cancer cells. Ibrutinib is a selective inhibitor of BTK that shows activity via its direct effects on crucial survival pathways in CLL cells. In addition to its anti-neoplastic effects, ibrutinib has also shown to have immunomodulatory properties. Currently available data are mainly limited to the activity exerted by ibrutinib on conventional T cells, whereas little is known on the effects induced on other non-neoplastic immune cell populations. Aim: The aim of this study was to evaluate the in vivo immunomodulatory effects of ibrutinib treatment on different immune compartments in patients with CLL Methods: We included 11 CLL patients with progressive disease (PD CLL) and eligible to ibrutinib therapy. PB samples were collected from patients at baseline and after 1, 6 and 12 months of treatment with ibrutinib. For comparison, we also analyzed 5 healthy donors (HD) and 6 treatment-naïve CLL patients with stable disease (SD CLL), who were not fulfilling criteria for treatment start. We assessed the percentages and the absolute numbers of CLL cells, T cells, γδ (Vδ1 and Vγ9Vδ2) T cells, T regulatory cells (Tregs), natural killer (NK) and NK-T cells by flow cytometry using population-specific markers. The expression of activation markers and immune checkpoint receptors (i.e. CD69, PD-1, CD96, TIGIT, NKG2D) was evaluated by flow cytometry as well. Results: Median age of patients was 69 years (range 44-75). The median lymphocyte count at study entry was 49 x 109/L (range 1,8-110) and the median number of previous treatment regimens was 2 (range 0-5). After 12 months of ibrutinib, 10 out of 11 (91%) patients achieved at least a partial response. The mean absolute number of CLL cells started to decrease by month 6 and became significantly lower than baseline value at 12 months of ibrutinib therapy. At the baseline, leukemic cells from PD CLL had significantly higher surface expression of the early activation marker CD69 and of the immune checkpoint molecule PD-1 compared to SD CLL and HD. After 6 months of treatment, the percentage of CLL cells expressing CD69 and PD-1 was normalized (reached values not significantly different from HD) (Fig 1A,B). We observed a gradual reduction of the total count of CD4+ and CD8+ T cells during ibrutinib treatment, becoming significant at 12 months. At the same timepoint, the expression of CD69, which was higher on T cells from PD CLL prior to therapy compared to SD CLL and HD, was normalized. Concurrently, a significant reduction in the surface levels of the inhibitory immune checkpoint molecule CD96 was observed (Fig 1C,D). Ibrutinib treatment had no impact on the absolute numbers of NK and NK-T cells. Compared to SD CLL and HD, NK cells from PD CLL showed a higher expression of CD69 before treatment start. In addition, they were characterized by increased levels of the immune checkpoints CD96 and TIGIT, and by reduced expression of the Fc receptor CD16, that is involved in the ADCC process, and the activating receptor NKG2D. After 6 months of treatment, the expression of CD69, CD16 and NKG2D on NK cells were restored (Fig 1E-G), whereas TIGIT and CD96 were not yet significantly modulated. Concerning the Tregs, a trend toward a reduction in the absolute number was detected after 12 months of ibrutinib treatment, compared to the baseline. The percentage of Tregs expressing the co-inhibitory molecule TIGIT was higher in PD CLL at the time of treatment start and was normalized by 12 months of ibrutinib therapy (Fig 1H). Lastly, we assessed ibrutinib effects on γδ T cells. The absolute numbers of both Vδ1 and Vγ9Vδ2 T cells remained unchanged during patients' treatment. Similar to conventional T lymphocytes, Vγ9Vδ2 T cells showed a decrease in the expression of CD96 after 12 months of ibrutinib administration (Fig 1I). Conclusions: our data suggest that the anti-tumor activity of ibrutinib is paralleled by a valuable immunomodulatory effect, leading to a partial recovery of phenotypic alterations that are hallmarks of immune exhaustion. Further studies to investigate the ability of ibrutinib to restore the functionality of the described immune cell compartments and to explore clinical correlations are currently ongoing on an enlarged cohort of treated patients. Figure 1. Figure 1. Disclosures Mauro: abbvie: Other: board member; janssen: Other: board member. Gaidano:Gilead: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Morphosys: Honoraria; Roche: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria. Foà:ABBVIE: Other: ADVISORY BOARD, Speakers Bureau; AMGEN: Other: ADVISORY BOARD; NOVARTIS: Speakers Bureau; JANSSEN: Other: ADVISORY BOARD, Speakers Bureau; ROCHE: Other: ADVISORY BOARD, Speakers Bureau; GILEAD: Speakers Bureau; INCYTE: Other: ADVISORY BOARD; CELGENE: Other: ADVISORY BOARD, Speakers Bureau; CELTRION: Other: ADVISORY BOARD. Boccadoro:AbbVie: Honoraria; Bristol-Myers Squibb: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Sanofi: Honoraria, Research Funding; Mundipharma: Research Funding; Novartis: Honoraria, Research Funding. Coscia:Janssen, Karyopharm: Research Funding; Abbvie, Gilead, Shire: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Published
2018

13. AB0150 Increased eryptosis levels in primary antiphospholipid syndrome patients

Author

Vomero, M, primary, Ceccarelli, F, additional, Finucci, A, additional, Pensa, C, additional, Barbati, C, additional, Colasanti, T, additional, Spinelli, FR, additional, Massaro, L, additional, Truglia, S, additional, Perricone, C, additional, Miranda, F, additional, Mauro, FR, additional, Foà, R, additional, Conti, F, additional, Valesini, G, additional, and Alessandri, C, additional

Published
2017
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16. MAKING THE RIGHT CHOICE: THE ROLE OF FITNESS STATUS IN THE MANAGEMENT OF FIRST-LINE TREATMENT IN CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS (CLL FITNESS STUDY)

Author

Scarfo, L, Quaresmini, G, Mauro, Fr, Orlandi, E, Reda, G, Laurenti, L, Coscia, Marta, Ambrosetti, A, Murru, R, Trentin, L, Guelill, A, Visco, C, Morabito, F, Frustaci, A, Ciolli, S, Rossini, F, Cuneo, A, Gozzetti, A, Scortechini, I, Pane, F, Zinzani, Pl, Ferrara, F, Mannina, D, Marasca, R, Pierri, I, Specchia, G, Chiarenza, A, Zallio, F, Molica, S, De Paoli, L, Torreggiani, A, Brugiatelli, M, Semenzato, G, Innocenti, I, Picardi, P, Pizzolo, G, Foa, R, Rambaldi, A, and Ghia, P.

Published
2015

17. A Molecular Model to Predict Durable Remission after First Line Fludarabine-Cyclophosphamide-Rituximab Treatment in Chronic Lymphocytic Leukemia

Author

Rossi, D, di Bergamo, Lt, Chiarenza, A, Bulian, P, Visco, C, Mauro, Fr, Morabito, F, Cortelezzi, A, Zaja, F, Forconi, F, Laurenti, L, Del Giudice, I, De Paoli, L, Vincelli, I, Rigolin, Gian Matteo, Marasca, R, Perbellini, O, Moreno, C, Del Poeta, G, Massaia, M, Zinzani, Pl, Montillo, M, Cuneo, Antonio, Foa, R, Gattei, V, and Gaidano, G.

Subjects
CLL, FCR, molecular analysis, FCR, molecular analysis, CLL, NO
Published
2014

18. Molecular prediction of durable remission after first-line fludarabine-cyclophosphamide-rituximab in chronic lymphocytic leukemia.

Author

Rossi, D, Terzi-di-Bergamo, L, De Paoli, Luigi, Cerri, Marco Vittorio, Ghilardi, Giampaolo, Chiarenza, A, Bulian, P, Visco, C, Mauro, Fr, Morabito, F, Cortelezzi, A, Zaja, F, Forconi, F, Laurenti, Luca, Del Giudice, I, Gentile, M, Vincelli, I, Motta, M, Coscia, M, Rigolin, Gm, Tedeschi, Alessandra, Neri, A, Marasca, R, Perbellini, O, Moreno, C, Del Poeta, G, Massaia, M, Zinzani, Pl, Montillo, M, Cuneo, A, Gattei, V, Foà, R, Gaidano, G, Laurenti L (ORCID:0000-0002-8327-1396), Rossi, D, Terzi-di-Bergamo, L, De Paoli, Luigi, Cerri, Marco Vittorio, Ghilardi, Giampaolo, Chiarenza, A, Bulian, P, Visco, C, Mauro, Fr, Morabito, F, Cortelezzi, A, Zaja, F, Forconi, F, Laurenti, Luca, Del Giudice, I, Gentile, M, Vincelli, I, Motta, M, Coscia, M, Rigolin, Gm, Tedeschi, Alessandra, Neri, A, Marasca, R, Perbellini, O, Moreno, C, Del Poeta, G, Massaia, M, Zinzani, Pl, Montillo, M, Cuneo, A, Gattei, V, Foà, R, Gaidano, G, and Laurenti L (ORCID:0000-0002-8327-1396)

Abstract

X

Published
2015

19. Diagnostic and prognostic role of PET/CT in patients with chronic lymphocytic leukemia and progressive disease.

Author

Mauro, Fr, Chauvie, S, Paoloni, F, Biggi, A, Cimino, G, Rago, A, Gentile, M, Morabito, F, Coscia, M, Bellò, M, Sacchetti, Gm, Rossi, D, Laurenti, Luca, Autore, Francesco, Campanelli, M, Trastulli, F, Nicolai, E, Riminucci, M, Gaidano, G, Guarini, A, Gallamini, A, Foà, R., Laurenti L (ORCID:0000-0002-8327-1396), Autore F, Mauro, Fr, Chauvie, S, Paoloni, F, Biggi, A, Cimino, G, Rago, A, Gentile, M, Morabito, F, Coscia, M, Bellò, M, Sacchetti, Gm, Rossi, D, Laurenti, Luca, Autore, Francesco, Campanelli, M, Trastulli, F, Nicolai, E, Riminucci, M, Gaidano, G, Guarini, A, Gallamini, A, Foà, R., Laurenti L (ORCID:0000-0002-8327-1396), and Autore F

Abstract

X

Published
2015

20. Bendamustine in combination with rituximab for elderly patients with previously untreated B-cell chronic lymphocytic leukemia: A retrospective analysis of real-life practice in Italian hematology departments.

Author

Laurenti, Luca, Innocenti, Idanna, Autore, Francesco, Vannata, Barbara, Efremov, Dg, Ciolli, S, Del Poeta, G, Mauro, Fr, Cortelezzi, A, Borza, Pa, Ghio, F, Mondello, P, Murru, R, Gozzetti, A, Cariccio, Mr, Piccirillo, Nicola, Boncompagni, R, Cantonetti, M, Principe, Mi, Reda, G, Bongarzoni, Velia, Cervetti, G, Pitini, V, Foa, Robin, Sica, Simona, D'Arena, G., Laurenti L (ORCID:0000-0002-8327-1396), Innocenti I, Autore F, Vannata B, Piccirillo N (ORCID:0000-0002-1688-1987), Sica S (ORCID:0000-0003-2426-3465), Laurenti, Luca, Innocenti, Idanna, Autore, Francesco, Vannata, Barbara, Efremov, Dg, Ciolli, S, Del Poeta, G, Mauro, Fr, Cortelezzi, A, Borza, Pa, Ghio, F, Mondello, P, Murru, R, Gozzetti, A, Cariccio, Mr, Piccirillo, Nicola, Boncompagni, R, Cantonetti, M, Principe, Mi, Reda, G, Bongarzoni, Velia, Cervetti, G, Pitini, V, Foa, Robin, Sica, Simona, D'Arena, G., Laurenti L (ORCID:0000-0002-8327-1396), Innocenti I, Autore F, Vannata B, Piccirillo N (ORCID:0000-0002-1688-1987), and Sica S (ORCID:0000-0003-2426-3465)

Abstract

X

Published
2015

21. Fludarabine + prednisone +/- alpha-interferon followed or not by alpha-interferon maintenance therapy for previously untreated patients with chronic lymphocytic leukemia: long term results of a randomized study

Author

Mauro, Fr, Zinzani, P, Zaja, Francesco, Gentile, M, Vegna, Ml, Stefoni, V, Marin, L, Fanin, Renato, Baccarani, M, Tura, S, Mandelli, F., Mauro, Fr, Zinzani, P, Zaja, Francesco, Gentile, M, Vegna, Ml, Stefoni, V, Marin, L, Fanin, Renato, Baccarani, M, Tura, S, and Mandelli, F.

Subjects
Adult, Male, alpha-interferon, treatment, Remission Induction, fludarabine, Interferon-alpha, Neoplasms, Second Primary, Middle Aged, Prognosis, Leukemia, Lymphocytic, Chronic, B-Cell, Survival Analysis, Drug Administration Schedule, Treatment Outcome, Cause of Death, Antineoplastic Combined Chemotherapy Protocols, Disease Progression, Humans, Prednisone, chronic lymphocytic leukemia, Female, Life Tables, chronic lymphocytic leukemia, treatment, fludarabine, alpha-interferon, Vidarabine, Aged
Abstract

BACKGROUND AND OBJECTIVES: Fludarabine is an effective therapy for patients with chronic lymphocytic leukemia (CLL) and interferon-alpha (IFN-alpha) has been reported to have anti-leukemic activity in CLL patients. A randomized study was designed to evaluate whether the addition of IFN-alpha to a first-line treatment with fludarabine and prednisone could increase the response rate in patients with advanced CLL and whether IFN-alpha given as maintenance therapy could improve the duration of response. DESIGN AND METHODS: One hundred and thirty-three patients were randomized to receive fludarabine (25 mg/m2/i.v., days 9-13) and prednisone (20 mg/m2, days 1, 3, 5, 7 and 14 and 40 mg/m2, days 9-13) (arm A: 66 patients) or in addition to the same schedule, IFN-alpha (2 MUI/sc, days 1, 3, 5, 7, 9, 11, 13 and 15) (arm B: 67 patients). Seventy-eight patients responsive to therapy entered the post-remission phase of the study in which 41 patients were randomized to receive IFN-alpha (3 MUI three times a week) and 37 to clinical observation. RESULTS: A similar response rate (complete responses + partial responses) was observed in the 2 arms: 86% for arm A and 84% for arm B (p = 0.4). A longer response duration was observed in patients who achieved a complete response (p = 0.001) and in patients who received maintenance therapy with IFN-alpha (p < 0.05). However, the quality of response was the only significant and independent factor influencing response duration (p < 0.01). No benefits in terms of infection-related mortality and morbidity could be ascribed to IFN-alpha administration. INTERPRETATION AND CONCLUSIONS: In previously untreated CLL patients with advanced disease a high response rate is obtained from first-line fludarabine and prednisone and no benefit is derived from the addition of IFN-alpha to this regimen. The achievement of a good quality response to therapy was the only independent predictor of a prolonged response.

Published
2003

22. An Italian retrospective study on the routine clinical use of low-dose alemtuzumab in relapsed/refractory chronic lymphocytic leukaemia patients

Author

Cortelezzi, A, Gritti, G, Laurenti, L, Cuneo, Antonio, Ciolli, S, Di Renzo, N, Musto, P, Mauro, Fr, Cascavilla, N, Falchi, L, Zallio, F, Callea, V, Maura, F, Martinelli, S, Piciocchi, A, Reda, G, Foà, R, and on behalf of the GIMEMA Chronic Lymphoproliferative Disorders Working Party

Subjects
Chronic lymphocytic leukaemia, Alemtuzumab, Infection, Monoclonal antibodies
Published
2012

23. Behind the scenes of non-nodal MCL: downmodulation of genes involved in actin cytoskeleton organization, cell projection, cell adhesion, tumour invasion, TP53 pathway and mutated status of immunoglobulin heavy chain genes

Author

Del Giudice, I, Messina, M, Chiaretti, S, Santangelo, S, Tavolaro, S, De Propris MS, Nanni, M, Pescarmona, E, Mancini, F, Pulsoni, A, Martelli, M, Di Rocco, A, Finolezzi, E, Paoloni, F, Mauro, Fr, Cuneo, Antonio, Guarini, A, and Foà, R.

Subjects
Immunoglobulin heavy chain, Mantle cell lymphoma, Lymphoma, Gene expression profile, Non-nodal
Published
2012

25. Appropriate use of bendamustine in first-line therapy of chronic lymphocytic leukemia. Recommendations from SIE, SIES, GITMO Group

Author

Cuneo, A, Marchetti, M, Barosi, G, Billio, A, Brugiatelli, M, Ciolli, S, Laurenti, Luca, Mauro, Fr, Molica, S, Montillo, M, Zinzani, P, Tura, S., Laurenti, Luca (ORCID:0000-0002-8327-1396), Cuneo, A, Marchetti, M, Barosi, G, Billio, A, Brugiatelli, M, Ciolli, S, Laurenti, Luca, Mauro, Fr, Molica, S, Montillo, M, Zinzani, P, Tura, S., and Laurenti, Luca (ORCID:0000-0002-8327-1396)

Abstract

By using the GRADE system we produced the following recommendations for the use of bendamustine in the first-line treatment of CLL: (1) bendamustine with rituximab is recommended in elderly fit patients potentially eligible to FCR; (2) Bendamustine alone is recommended in patients who are candidate to chlorambucil alone; (3) Rituximab-bendamustine is recommended in patients not eligible to FCR, but suitable to receive rituximab. Consensus-based recommendations addressed evidence-orphan issues concerning the use of bendamustine in genetically-defined high-risk patients and the appropriate dose of bendamustine as single agent or in association with rituximab.

Published
2014

26. Fludarabine plus alemtuzumab (FA) front-line treatment in young patients with chronic lymphocytic leukemia (CLL) and an adverse biologic profile

Author

Mauro, Fr, Molica, S, Laurenti, Luca, Cortelezzi, A, Carella, Am, Zaja, F, Chiarenza, A, Angrilli, F, Nobile, F, Marasca, R, Musolino, C, Brugiatelli, M, Piciocchi, A, Vignetti, M, Fazi, P, Gentile, G, De Propris, M, Starza, Id, Marinelli, M, Chiaretti, S, Del Giudice, I, Nanni, M, Albano, F, Cuneo, A, Guarini, A, Foà, R., Laurenti, Luca (ORCID:0000-0002-8327-1396), Mauro, Fr, Molica, S, Laurenti, Luca, Cortelezzi, A, Carella, Am, Zaja, F, Chiarenza, A, Angrilli, F, Nobile, F, Marasca, R, Musolino, C, Brugiatelli, M, Piciocchi, A, Vignetti, M, Fazi, P, Gentile, G, De Propris, M, Starza, Id, Marinelli, M, Chiaretti, S, Del Giudice, I, Nanni, M, Albano, F, Cuneo, A, Guarini, A, Foà, R., and Laurenti, Luca (ORCID:0000-0002-8327-1396)

Abstract

In 45, ≤60 years old patients with CLL and an adverse biologic profile, a front-line treatment with Fludarabine and Campath (Alemtuzumab(®)) was given. The overall response rate was 75.5%, the complete response rate (CR) 24.4% with the lowest CR rates, 16.7% and 8.3%, in 11q and 17p deleted cases. The 3-year progression-free survival (PFS) and overall survival were 42.5% and 79.9%, respectively. PFS was significantly influenced by CLL duration, beta2-microglobulin, and improved by post-remissional stem cell transplantation. Front-line fludarabine and alemtuzumab showed a manageable safety profile and evidence of a benefit in a small series of CLL patients with adverse biologic features.

Published
2014

27. Bendamustine in combination with Ofatumumab in relapsed or refractory chronic lymphocytic leukemia: a GIMEMA Multicenter Phase II Trial

Author

Cortelezzi, A, Sciumè, M, Liberati, Am, Vincenti, D, Cuneo, A, Reda, G, Laurenti, Luca, Zaja, F, Marasca, R, Chiarenza, A, Gritti, G, Orsucci, L, Storti, S, Angelucci, E, Cascavilla, N, Gobbi, M, Mauro, Fr, Morabito, F, Fabris, S, Piciocchi, A, Vignetti, M, Neri, A, Rossi, D, Giannarelli, D, Guarini, A, Foà, R., Laurenti, Luca (ORCID:0000-0002-8327-1396), Cortelezzi, A, Sciumè, M, Liberati, Am, Vincenti, D, Cuneo, A, Reda, G, Laurenti, Luca, Zaja, F, Marasca, R, Chiarenza, A, Gritti, G, Orsucci, L, Storti, S, Angelucci, E, Cascavilla, N, Gobbi, M, Mauro, Fr, Morabito, F, Fabris, S, Piciocchi, A, Vignetti, M, Neri, A, Rossi, D, Giannarelli, D, Guarini, A, Foà, R., and Laurenti, Luca (ORCID:0000-0002-8327-1396)

Abstract

We conducted a phase II, noncomparative, open-label, multicenter GIMEMA (Gruppo Italiano Malattie EMatologiche dell'Adulto) study (CLL0809) to assess the efficacy and safety of bendamustine in combination with ofatumumab (BendOfa) in relapsed/refractory chronic lymphocytic leukemia (CLL). Forty-seven patients from 14 centers were evaluated. Therapy consisted of bendamustine (70 mg/m(2)) for 2 consecutive days every 28 days, and ofatumumab 300 mg on day 1 and 1000 mg on day 8 during the first cycle, and 1000 mg on day 1 subsequently. Treatment was administered up to six cycles. The overall response rate (ORR), as per intention-to-treat analysis, was 72.3% (95% confidence of interval (CI), 57-84%), with 17% complete responses. After a median follow-up of 24.2 months, the overall survival was 83.6% (95% CI, 73.0-95.7%) and the progression-free survival (PFS) was 49.6% (95% CI, 35.9-68.6%). The median PFS was 23.6 months. Univariate and multivariate analyses were used to identify clinical and biological characteristics associated with ORR and PFS. Myelosuppression was the most common toxicity; grade 3 neutropenia was observed in 61.7% of patients; however, grade 3 infections occurred in 6% of patients. BendOfa is feasible and effective in relapsed/refractory CLL patients, including patients with high-risk clinical and biological features.Leukemia advance online publication, 3 December 2013; doi:10.1038/leu.2013.334.

Published
2014

28. B-cell receptor configuration and adverse cytogenetics are associated with autoimmune hemolytic anemia in chronic lymphocytic leukemia

Author

Maura, F, Visco, C, Falisi, E, Reda, G, Fabris, S, Agnelli, L, Tuana, G, Lionetti, M, Guercini, N, Novella, E, Nichele, I, Montaldi, A, Autore, F, Gregorini, A, Barcellini, W, Callea, V, Mauro, Fr, Laurenti, Luca, Foà, R, Neri, A, Rodeghiero, F, Cortelezzi, A., Laurenti, Luca (ORCID:0000-0002-8327-1396), Maura, F, Visco, C, Falisi, E, Reda, G, Fabris, S, Agnelli, L, Tuana, G, Lionetti, M, Guercini, N, Novella, E, Nichele, I, Montaldi, A, Autore, F, Gregorini, A, Barcellini, W, Callea, V, Mauro, Fr, Laurenti, Luca, Foà, R, Neri, A, Rodeghiero, F, Cortelezzi, A., and Laurenti, Luca (ORCID:0000-0002-8327-1396)

Abstract

The development of autoimmune hemolytic anemia (AIHA) in patients with chronic lymphocytic leukemia (CLL) is associated with specific biological features. The occurrence of AIHA was hereby investigated in a retrospective series of 585 CLL patients with available immunoglobulin heavy chain variable (IGHV) gene status. AIHA occurred in 73 patients and was significantly associated with an IGHV unmutated (UM) status (P < 0.0001) and unfavorable [del(17)(p13) and del(11)(q23)] cytogenetic lesions (P < 0.0001). Stereotyped HCDR3 sequences were identified in 29.6% of cases and were similarly represented among patients developing or not AIHA; notably, subset #3 was associated with a significantly higher risk of AIHA than the other patients (P = 0.004). Multivariate analysis showed that UM IGHV, del(17)(p13) and del(11)(q23), but not stereotyped subset #3, were the strongest independent variables associated with AIHA. Based on these findings, we generated a biological risk score for AIHA development according to the presence of none (low risk), one (intermediated risk), or two (high risk) of the independent risk factors. Overall, our data indicate that UM IGHV status and/or unfavorable cytogenetic lesions are associated with the risk of developing secondary AIHA in CLL patients and suggest a possible role of specific stereotyped B-cell receptor subsets in a proportion of cases.

Published
2013

29. Reduced susceptibility to apoptosis correlates with kinetic quiescence in disease progression of chronic lymphocytic leukaemia

Author

Ricciardi, Mr, Petrucci, Mt, Gregorj, C, Ariola, C, Lemoli, ROBERTO MASSIMO, Fogli, M, Mauro, Fr, Cerretti, R, Foà, R, Mandelli, F, and Tafuri, A.

Subjects
Adult, Aged, 80 and over, B-Lymphocytes, p27(kip1), T-Lymphocytes, Tumor Suppressor Proteins, Blotting, Western, Cell Cycle, Apoptosis, Cell Cycle Proteins, apoptosis, cell cycle, chronic lymphocytic leukaemia, disease progression, p27 kip1, Middle Aged, Flow Cytometry, Leukemia, Lymphocytic, Chronic, B-Cell, Culture Media, Case-Control Studies, Disease Progression, Humans, Lymphocytes, Microtubule-Associated Proteins, Cells, Cultured, Cyclin-Dependent Kinase Inhibitor p27, Aged
Abstract

The role of apoptosis and cell kinetics in the mechanisms of disease progression of chronic lymphocytic leukaemia (CLL) is still unclear. In the present study, we investigated the susceptibility of leukaemic cells taken from 75 CLL patients with either stable (STD) or progressive disease (PRD) to enter apoptosis. Particular attention was paid to the relationship between cell cycle status and autologous serum (AS). The susceptibility to enter apoptosis was significantly greater in STD than in PRD, both in standard medium (mean = 23.62% +/- 14.7 versus 14.23% +/- 7.2; P = 0.02) and in the presence of AS (mean = 23.03% +/- 17.9 versus 11.27% +/- 7.6; P = 0.01). Furthermore, cell kinetics studies revealed a higher quiescence in PRD than in STD cases, both in terms of a lower RNA content (P = 0.04) and of higher expression of the negative cell cycle regulator p27kip1 (P = 0.03). These kinetic differences were confirmed by short-term in vitro culture both in fetal calf serum and in AS. The results of this study indicate that CLL cells from PRD cases are characterized by a higher degree quiescence and much lower susceptibility to apoptosis when compared with STD ones. In this context, AS does not appear to play a specific role. The association between these kinetic characteristics and disease progression in CLL prompts further studies to establish whether higher quiescence may be responsible for the decreased susceptibility of PRD cells to enter apoptosis.

Published
2001

30. The coexistence of chronic lymphocytic leukemia and myeloproliperative neoplasms: a retrospective multicentric GIMEMA experience

Author

Laurenti, Luca, Tarnani, Michela, Nichele, I, Ciolli, S, Cortelezzi, A, Forconi, F, Rossi, D, Mauro, Fr, D'Arena, G, Del Poeta, G, Montanaro, M, Morabito, F, Musolino, C, Callea, V, Falchi, L, Tedeschi, A, Ambrosetti, A, Gaidano, G, Leone, Giuseppe, Foà, R., Laurenti, Luca (ORCID:0000-0002-8327-1396), Laurenti, Luca, Tarnani, Michela, Nichele, I, Ciolli, S, Cortelezzi, A, Forconi, F, Rossi, D, Mauro, Fr, D'Arena, G, Del Poeta, G, Montanaro, M, Morabito, F, Musolino, C, Callea, V, Falchi, L, Tedeschi, A, Ambrosetti, A, Gaidano, G, Leone, Giuseppe, Foà, R., and Laurenti, Luca (ORCID:0000-0002-8327-1396)

Abstract

Although the coexistence of chronic lymphocytic leukemia (CLL) and myeloproliferative neoplasms (MPN) has been sporadically reported in the literature, no systematic studies on this disease association are available. We retrospectively analyzed 46 patients affected by CLL/MPN referred by 15 Italian GIMEMA centers. The aim of this retrospective multicenter study was to define the following: clinico-biological characteristics, possible familiarity, clinical course of both diseases, and influence of MPN chemotherapy on the course of CLL. Among 46 patients, 30 patients were males, 16 patients were females; median age was 71 years. Only one case had familiar CLL. Myeloproliferative disorders consisted of essential thrombocytemia in 18 cases, polycythemia vera in 10 cases, chronic myeloid leukemia in 9 cases, primary myelofibrosis in 6 cases, and MPN/myelodysplastic syndrome in 3 cases. The lymphoproliferative disorder was diagnosed as monoclonal B-cell lymphocytosis in 8 patients and as Binet Stage A CLL in 38 patients. After a median follow-up of 49 months, 9 patients experienced progressive CLL and only 6 patients required treatment after a median of 57.5 months. The biological profile confirmed a subset of low-risk CLL. Twenty patients received chemotherapy for MPN without influence on the course of CLL: lymphocyte counts remained unchanged after 3, 6, and 12 months of treatment. This series is the largest so far reported in literature. The diagnosis of concomitant CLL/MPN is a rare event and lymphoproliferative disorders present a clinical indolent course with a low-risk biological profile. MPN therapy does not interfere with the prognosis of patients with CLL.

Published
2011

32. Relationship between autoimmune phenomena and disease stage and therapy in B-cell chronic lymphocytic leukemia

Author

Barcellini, W, Capalbo, S, Agostinelli, R, Mauro, F, Ambrosetti, A, Calori, R, Cortelezzi, A, Laurenti, L, Pogliani, E, Pedotti, P, Liso, V, Girelli, G, Mandelli, F, Zanella, A, Agostinelli, RM, Mauro, FR, Zanella, A., POGLIANI, ENRICO MARIA, Barcellini, W, Capalbo, S, Agostinelli, R, Mauro, F, Ambrosetti, A, Calori, R, Cortelezzi, A, Laurenti, L, Pogliani, E, Pedotti, P, Liso, V, Girelli, G, Mandelli, F, Zanella, A, Agostinelli, RM, Mauro, FR, Zanella, A., and POGLIANI, ENRICO MARIA

Abstract

The aim of this multicenter GIMEMA study was to correlate autoimmune complications (AIC) in B-cell chronic lymphocytic leukemia (B-CLL) with stage and therapy. Autoimmune hemolytic anemia (129/194 cases) and autoimmune thrombocytopenia (35/194 cases) were typically present in advanced and multi-treated disease. Age over the median, stage C and first and second line therapy were identified as independent risk factors by multivariate analysis. In contrast, non-hematologic AIC (30/194 cases) and the presence of serological markers of autoimmunity were mostly observed in early B-CLL, suggesting different pathogenic mechanisms underlying hematologic and non-hematologic autoimmune phenomena in B-CLL.

Published
2006

36. (Title Page to) Mappemonde dress es en 1450, par Fra Mauro cosmographe Venetien. Par order d'Alphonse V. Roide Portugal. Publiee pour la premiere fois de la grandeur de l'original avec toutes les Legendes par Le Vicomte de Santarem, 1854. J. J. Feuquieres, lith. Schwaerzle Sculp. Pl. V.

Author

Santarem, Manuel Francisco de. and Mauro, Fra

Subjects
World
Abstract

Large circular planisphere on 6 sheets, 85x107 or smaller. Title from sheet 5. Reproduced and printed for the first time at the size of the original with all the legends and notations by Viscount of Santarém in 1854. The original 1450 map was fully described and reproduced in manuscript for the first time by William Frazer in 1804, Manuscript on vellum, BL Add. MS 1126. This was deposited at the British Museum in 1807 by William Vincent, dean of Westminster. Vincent wrote a short account of this process in 1807 in his "The Commerce and Navigation of the Ancients in the Indian Ocean," 2 vols. London: Cadell and Davies, 1807, in an appendix = 2:661–79. Matthew Edney states "Santarém took his facsimile from a tracing of Frazer’s manuscript at the BM, as indicated by the placement of Eden in the lower-right corner, rather than in the lower-left where it actually sits: see: Cattaneo, Angelo. “L’Atlas del visconte de Santarém: Una storia culturale europa tra erudizione orientalismo e colonialismo,” in “A história da cartografia na obra do 2.º visconde de Santarém. Exposição cartobibliográfica, 24 de Novembro de 2006 a 10 de Fevereiro de 2007”, edited by João Carlos García, and Maria Joaquina Feijoo, 17–49. Lisbon: Biblioteca Nacional, 2006." Fra Mauro's map was also reproduced by Placido Zurla in II Mappamondo di Fra Mauro Camaldolese, 1818 in Venice ( see our copy), and later again by Santarem in his facsimile Atlas of 1849, "Atlas de Vicomte de Santarem," see lower left sheet 5. Unusual for medieval European maps, it is oriented with South at the top (Indian Ocean, top left; Mediterranean, right center) and so meticulously drawn and full of detail and legends that it has been described as a “medieval cosmography of no small extent, a conspectus of 15th century geographical knowledge cast in medieval form.” The coasts are drawn in a style recalling that of nautical charts. Includes 4 insets at each corner, numerous note boxes on the map and explanatory text at the margins. Shows place names, rivers, mountains, lakes, etc. Landmarks shown pictorially. Text and place names in Italian, publication information in French. Relief shown pictorially.

Published
1450

37. Mappemonde dress es en 1450, par Fra Mauro cosmographe Venetien. Par order d'Alphonse V. Roide Portugal. Publiee pour la premiere fois de la grandeur de l'original avec toutes les Legendes par Le Vicomte de Santarem, 1854. J. J. Feuquieres, lith. Schwaerzle Sculp. Pl. VI.

Author

Santarem, Manuel Francisco de. and Mauro, Fra

Subjects
World
Abstract

Large circular planisphere on 6 sheets, 85x107 or smaller. Title from sheet 5. Reproduced and printed for the first time at the size of the original with all the legends and notations by Viscount of Santarém in 1854. The original 1450 map was fully described and reproduced in manuscript for the first time by William Frazer in 1804, Manuscript on vellum, BL Add. MS 1126. This was deposited at the British Museum in 1807 by William Vincent, dean of Westminster. Vincent wrote a short account of this process in 1807 in his "The Commerce and Navigation of the Ancients in the Indian Ocean," 2 vols. London: Cadell and Davies, 1807, in an appendix = 2:661–79. Matthew Edney states "Santarém took his facsimile from a tracing of Frazer’s manuscript at the BM, as indicated by the placement of Eden in the lower-right corner, rather than in the lower-left where it actually sits: see: Cattaneo, Angelo. “L’Atlas del visconte de Santarém: Una storia culturale europa tra erudizione orientalismo e colonialismo,” in “A história da cartografia na obra do 2.º visconde de Santarém. Exposição cartobibliográfica, 24 de Novembro de 2006 a 10 de Fevereiro de 2007”, edited by João Carlos García, and Maria Joaquina Feijoo, 17–49. Lisbon: Biblioteca Nacional, 2006." Fra Mauro's map was also reproduced by Placido Zurla in II Mappamondo di Fra Mauro Camaldolese, 1818 in Venice ( see our copy), and later again by Santarem in his facsimile Atlas of 1849, "Atlas de Vicomte de Santarem," see lower left sheet 5. Unusual for medieval European maps, it is oriented with South at the top (Indian Ocean, top left; Mediterranean, right center) and so meticulously drawn and full of detail and legends that it has been described as a “medieval cosmography of no small extent, a conspectus of 15th century geographical knowledge cast in medieval form.” The coasts are drawn in a style recalling that of nautical charts. Includes 4 insets at each corner, numerous note boxes on the map and explanatory text at the margins. Shows place names, rivers, mountains, lakes, etc. Landmarks shown pictorially. Text and place names in Italian, publication information in French. Relief shown pictorially.

Published
1450

38. Mappemonde dress es en 1450, par Fra Mauro cosmographe Venetien. Par order d'Alphonse V. Roide Portugal. Publiee pour la premiere fois de la grandeur de l'original avec toutes les Legendes par Le Vicomte de Santarem, 1854. J. J. Feuquieres, lith. Schwaerzle Sculp. Pl. III.

Author

Santarem, Manuel Francisco de. and Mauro, Fra

Subjects
World
Abstract

Large circular planisphere on 6 sheets, 85x107 or smaller. Title from sheet 5. Reproduced and printed for the first time at the size of the original with all the legends and notations by Viscount of Santarém in 1854. The original 1450 map was fully described and reproduced in manuscript for the first time by William Frazer in 1804, Manuscript on vellum, BL Add. MS 1126. This was deposited at the British Museum in 1807 by William Vincent, dean of Westminster. Vincent wrote a short account of this process in 1807 in his "The Commerce and Navigation of the Ancients in the Indian Ocean," 2 vols. London: Cadell and Davies, 1807, in an appendix = 2:661–79. Matthew Edney states "Santarém took his facsimile from a tracing of Frazer’s manuscript at the BM, as indicated by the placement of Eden in the lower-right corner, rather than in the lower-left where it actually sits: see: Cattaneo, Angelo. “L’Atlas del visconte de Santarém: Una storia culturale europa tra erudizione orientalismo e colonialismo,” in “A história da cartografia na obra do 2.º visconde de Santarém. Exposição cartobibliográfica, 24 de Novembro de 2006 a 10 de Fevereiro de 2007”, edited by João Carlos García, and Maria Joaquina Feijoo, 17–49. Lisbon: Biblioteca Nacional, 2006." Fra Mauro's map was also reproduced by Placido Zurla in II Mappamondo di Fra Mauro Camaldolese, 1818 in Venice ( see our copy), and later again by Santarem in his facsimile Atlas of 1849, "Atlas de Vicomte de Santarem," see lower left sheet 5. Unusual for medieval European maps, it is oriented with South at the top (Indian Ocean, top left; Mediterranean, right center) and so meticulously drawn and full of detail and legends that it has been described as a “medieval cosmography of no small extent, a conspectus of 15th century geographical knowledge cast in medieval form.” The coasts are drawn in a style recalling that of nautical charts. Includes 4 insets at each corner, numerous note boxes on the map and explanatory text at the margins. Shows place names, rivers, mountains, lakes, etc. Landmarks shown pictorially. Text and place names in Italian, publication information in French. Relief shown pictorially.

Published
1450

39. Abbozzo Del Mappamondo Di F: Mauro Camaldolese Cosmografo Incomparabile alla Meta del Sec. XV. Gia' Esistnet Neall Bilblioteca Di S. Michele Di Murano Ora Nella Marciana. (to accompany) Sulle antiche mappe idro - geografiche lavorate in Venezia.

Author

Zurla, Placido, 1769-1834 and Mauro, Fra

Subjects
Exploration
Abstract

Uncolored circular planisphere world map of Fra Mauro Camaldolese. Described and illustrated by Placido Zurla, the map is believed to have been made around 1450 by the Venetian monk Fra Mauro, one of the few extent early facsimiles of early world maps. Fra Mauro's pre-Columbian World map is considered the greatest memorial of medieval cartography. The original Mauro map was discovered in the monastery of San Michel in Isola, Murano, where the Camaldolese cartographer had his studio. Relief shown pictorially. Includes 4 circular insets., An ancient hydro-geographical work in Venice, by Placido Zurla in 96 pages of descriptive text, and three uncolored maps. Including: 1- Abbozzo della mappa dei viaggi di Marco Polo ... 2- Carta Da Navegar De Nicolo et Antonio Zeni Fvrono In Tramontana Lano M.CCC. LXXX. 3- Abbozzo Del Mappamondo Di F: Mauro Camaldolese Cosmografo Incomparabile alla Meta del Sec. XV. Text and maps includes: Marco Polo's travels, map showing his exploration routes in East Asia, also shows northern part of America, Sierra Nevada, etc., voyages of Nicolo and Antonio Zeno in North Atlantic, map showing North Atlantic, Greenland, Iceland and Lapland, etc., and the last map is a circular planisphere map of the world, made by Fra Mauro.

Published
1806

40. (Composite map) Mappemonde dress es en 1450, par Fra Mauro cosmographe Venetien. Par order d'Alphonse V. Roide Portugal. Publiee pour la premiere fois de la grandeur de l'original avec toutes les Legendes par Le Vicomte de Santarem, 1854. J. J. Feuquieres, lith. Schwaerzle Sculp. Pl. I-VI.

Author

Santarem, Manuel Francisco de. and Mauro, Fra

Subjects
Data Visualization, Re-Mapping Sovereignty
Abstract

Large circular planisphere on 6 sheets, 85x107 or smaller. Title from sheet 5. Reproduced and printed for the first time at the size of the original with all the legends and notations by Viscount of Santarém in 1854. The original 1450 map was fully described and reproduced in manuscript for the first time by William Frazer in 1804, Manuscript on vellum, BL Add. MS 1126. This was deposited at the British Museum in 1807 by William Vincent, dean of Westminster. Vincent wrote a short account of this process in 1807 in his "The Commerce and Navigation of the Ancients in the Indian Ocean," 2 vols. London: Cadell and Davies, 1807, in an appendix = 2:661–79. Matthew Edney states "Santarém took his facsimile from a tracing of Frazer’s manuscript at the BM, as indicated by the placement of Eden in the lower-right corner, rather than in the lower-left where it actually sits: see: Cattaneo, Angelo. “L’Atlas del visconte de Santarém: Una storia culturale europa tra erudizione orientalismo e colonialismo,” in “A história da cartografia na obra do 2.º visconde de Santarém. Exposição cartobibliográfica, 24 de Novembro de 2006 a 10 de Fevereiro de 2007”, edited by João Carlos García, and Maria Joaquina Feijoo, 17–49. Lisbon: Biblioteca Nacional, 2006." Fra Mauro's map was also reproduced by Placido Zurla in II Mappamondo di Fra Mauro Camaldolese, 1818 in Venice ( see our copy), and later again by Santarem in his facsimile Atlas of 1849, "Atlas de Vicomte de Santarem," see lower left sheet 5. Unusual for medieval European maps, it is oriented with South at the top (Indian Ocean, top left; Mediterranean, right center) and so meticulously drawn and full of detail and legends that it has been described as a “medieval cosmography of no small extent, a conspectus of 15th century geographical knowledge cast in medieval form.” The coasts are drawn in a style recalling that of nautical charts. Includes 4 insets at each corner, numerous note boxes on the map and explanatory text at the margins. Shows place names, rivers, mountains, lakes, etc. Landmarks shown pictorially. Text and place names in Italian, publication information in French. Relief shown pictorially.

Published
1450

41. Cartographie du Moyen-Age. (contents:) Mappemonde de Fra Mauro, 1457. Peinte a Venise dans le Couent des Camaldules, reduite au 1/8e de la grandeur de l'original, d'apres la reproduction photographiee de Munster . Carte catalane, 1375. La Mediterranee des portulans, carte d'Andreas Benincasa d'Anone, 1476. Dessine par Vivien de Saint Martin. Imp. Fraillery. Histoire de la geographie. Atlas pl. VII. Librairie Hachette et Cie. (1874)

Author

Benincasa, Andrea, Mauro, fra, Vivien de Saint-Martin, M., Imp. Fraillery, and Imprimerie Simon Racon et Cie.

Subjects
Historical
Abstract

Three color maps. Facsimiles. Relief shown pictorially., P264, World 679.

Published
1874

42. Efficacy of recombinant erythropoietin in autoimmune hemolytic anemia:a multicenter international study

Author

Francesca Romana Mauro, Bruno Fattizzo, Wilma Barcellini, Anita J. Hill, Marc Michel, Josephine M.I. Vos, Francesco Zaja, Henrik Frederiksen, Bernd Jilma, Sigbjørn Berentsen, Anna Zaninoni, Andrea Patriarca, Stephanie Guillet, Juri Alessandro Giannotta, Fattizzo, B, Michel, M, Zaninoni, A, Giannotta, J, Guillet, S, Frederiksen, H, Vos, Jmi, Mauro, Fr, Jilma, B, Patriarca, A, Zaja, F, Hill, A, Berentsen, S, Barcellini, W., General Internal Medicine, Clinical Haematology, and AII - Inflammatory diseases

Subjects
Anemia, Hemolytic, business.industry, cold agglutinin disease, Hematology, medicine.disease, Recombinant Proteins, cytokines, bone marrow response, erythropoietin, warm autoimmune hemolytic anemia, N/A, Immunology, medicine, Humans, Anemia, Hemolytic, Autoimmune, Autoimmune hemolytic anemia, Letters to the Editor, Recombinant erythropoietin, business
Abstract

N/A

Published
2021

43. High rate of MRD-responses in young and fit patients with IGHV mutated chronic lymphocytic leukemia treated with front-line fludarabine, cyclophosphamide, and intensified dose of ofatumumab (FCO2)

Author

Caterina Musolino, Francesco Albano, Emanuele Angelucci, Francesca Romana Mauro, Fiorella Ilariucci, Alessandra Tedeschi, Sara Raponi, Roberta Battistini, Antonio Cuneo, Francesco Zaja, Stefano Soddu, Gianluigi Reda, Alessandro Gozzetti, Alfonso Piciocchi, Marta Coscia, Antonino Neri, Francesca Re, Anna Marina Liberati, Daniela Pietrasanta, Mauro Nanni, Anna Guarini, Maria Stefania De Propris, Robin Foà, Irene Della Starza, Ilaria Del Giudice, Stefano Molica, Marco Vignetti, Giovanni Del Poeta, Mauro, Fr, Molica, S, Soddu, S, Ilariucci, F, Coscia, M, Zaja, F, Angelucci, E, Re, F, Liberati, Am, Tedeschi, A, Reda, G, Pietrasanta, D, Gozzetti, A, Battistini, R, Del Poeta, G, Musolino, C, Nanni, M, Piciocchi, A, Vignetti, M, Neri, A, Albano, F, Cuneo, A, Del Giudice, I, Della Starza, I, De Propris, M, Raponi, S, Guarini, Ar, and Foà, R.

Subjects
Oncology, medicine.medical_specialty, Cyclophosphamide, Chronic lymphocytic leukemia, Lymphoproliferative disorders, Ofatumumab, Antibodies, Monoclonal, Humanized, NO, chemistry.chemical_compound, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Chronic Lymphocytic Leukemia, Letters to the Editor, Minimal Residual Disease, Lymphoproliferative Disorders, business.industry, Front line, Hematology, medicine.disease, Settore MED/15, Minimal residual disease, Leukemia, Lymphocytic, Chronic, B-Cell, Fludarabine, Treatment Outcome, chemistry, N/A, Chronic Lymphocytic Leukemia, Lymphoproliferative Disorders, IGHV@, business, Rituximab, Vidarabine, medicine.drug
Abstract

N/A

Published
2020

44. Familial cancer associated with a polymorphism in ARLTS1.

Author

Calin GA, Trapasso F, Shimizu M, Dumitru CD, Yendamuri S, Godwin AK, Ferracin M, Bernardi G, Chatterjee D, Baldassarre G, Rattan S, Alder H, Mabuchi H, Shiraishi T, Hansen LL, Overgaard J, Herlea V, Mauro FR, Dighiero G, and Movsas B

Published
2005

45. Appropriate use of bendamustine in first-line therapy of chronic lymphocytic leukemia. Recommendations from SIE, SIES, GITMO Group

Author

Atto Billio, Stefano Molica, Luca Laurenti, Pier Luigi Zinzani, Maura Brugiatelli, Antonio Cuneo, Monia Marchetti, Marco Montillo, Giovanni Barosi, Stefania Ciolli, Francesca Romana Mauro, Sante Tura, and Cuneo A, Marchetti M, Barosi G, Billio A, Brugiatelli M, Ciolli S, Laurenti L, Mauro FR, Molica S, Montillo M, Zinzani P, Tura S.

Subjects
Oncology, Bendamustine, Cancer Research, medicine.medical_specialty, Chronic lymphocytic leukemia, Guidelines, therapeutic use, Humans, Leukemia, Appropriate use, Antineoplastic Agent, First line therapy, immune system diseases, hemic and lymphatic diseases, Internal medicine, medicine, Bendamustine Hydrochloride, Humans, Single agent, Chronic, Antineoplastic Agents, Alkylating, drug therapy, Nitrogen Mustard Compound, Chlorambucil, business.industry, Grade system, B-Cell, First line treatment, Hematology, medicine.disease, Alkylating, Bendamustine, Chronic lymphocytic leukemia, First line treatment, Guidelines, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphocytic, Settore MED/15 - MALATTIE DEL SANGUE, therapeutic use, Immunology, Nitrogen Mustard Compounds, Rituximab, business, medicine.drug
Abstract

By using the GRADE system we produced the following recommendations for the use of bendamustine in the first-line treatment of CLL: (1) bendamustine with rituximab is recommended in elderly fit patients potentially eligible to FCR; (2) Bendamustine alone is recommended in patients who are candidate to chlorambucil alone; (3) Rituximab–bendamustine is recommended in patients not eligible to FCR, but suitable to receive rituximab. Consensus-based recommendations addressed evidence-orphan issues concerning the use of bendamustine in genetically-defined high-risk patients and the appropriate dose of bendamustine as single agent or in association with rituximab.

Published
2014

46. Bendamustine in combination with Ofatumumab in relapsed or refractory chronic lymphocytic leukemia: a GIMEMA Multicenter Phase II Trial

Author

Daniele Vincenti, Nicola Cascavilla, Francesca Romana Mauro, Agostino Cortelezzi, Francesco Zaja, Antonino Neri, Marco Gobbi, Mariarita Sciumè, Anna Marina Liberati, Davide Rossi, Anna Guarini, Sonia Fabris, Giuseppe Gritti, Marco Vignetti, Fortunato Morabito, Sergio Storti, Robin Foà, Gianluigi Reda, Diana Giannarelli, Emanuele Angelucci, Roberto Marasca, Alfonso Piciocchi, Luca Laurenti, Antonio Cuneo, Annalisa Chiarenza, L. Orsucci, Cortelezzi, A, Sciumè, M, Liberati, Am, Vincenti, D, Cuneo, A, Reda, G, Laurenti, L, Zaja, Francesco, Marasca, R, Chiarenza, A, Gritti, G, Orsucci, L, Storti, S, Angelucci, E, Cascavilla, N, Gobbi, M, Mauro, Fr, Morabito, F, Fabris, S, Piciocchi, A, Vignetti, M, Neri, A, Rossi, D, Giannarelli, D, Guarini, A, Foà, R., Liberati, A, Zaja, F, Mauro, F, and Foà, R

Subjects
Male, Cancer Research, Chronic lymphocytic leukemia, Gastroenterology, chemistry.chemical_compound, Recurrence, Monoclonal, Antineoplastic Combined Chemotherapy Protocols, Bendamustine Hydrochloride, Chronic, Relapse, Nitrogen Mustard Compound, Leukemia, Hematology, Refractory CLL, Antibodies, Monoclonal, Lymphocytic, Oncology, Nitrogen Mustard Compounds, Bendamustine, Toxicity, bendamustine, ofatumumab, chronic lymphocytic leukemia, relapse, Female, Refractory Chronic Lymphocytic Leukemia, Human, medicine.drug, medicine.medical_specialty, Author Keywords:bendamustine, ofatumumab, chronic lymphocytic leukemia, relapse KeyWords Plus:FLUDARABINE PLUS CYCLOPHOSPHAMIDE, INDEPENDENT PREDICTOR, PROGRESSION-FREE, RITUXIMAB, MUTATIONS, THERAPY, SURVIVAL, QUANTIFICATION, CHLORAMBUCIL, EXPRESSION, Neutropenia, Antibodies, Monoclonal, Humanized, Ofatumumab, Antibodies, NO, Internal medicine, medicine, Humans, Aged, Antineoplastic Combined Chemotherapy Protocol, business.industry, B-Cell, Leukemia, Lymphocytic, Chronic, B-Cell, medicine.disease, Surgery, Settore MED/15 - MALATTIE DEL SANGUE, Anesthesiology and Pain Medicine, chemistry, INGLESE, business
Abstract

We conducted a phase II, noncomparative, open-label, multicenter GIMEMA (Gruppo Italiano Malattie EMatologiche dell'Adulto) study (CLL0809) to assess the efficacy and safety of bendamustine in combination with ofatumumab (BendOfa) in relapsed/refractory chronic lymphocytic leukemia (CLL). Forty-seven patients from 14 centers were evaluated. Therapy consisted of bendamustine (70 mg/m 2) for 2 consecutive days every 28 days, and ofatumumab 300 mg on day 1 and 1000 mg on day 8 during the first cycle, and 1000 mg on day 1 subsequently. Treatment was administered up to six cycles. The overall response rate (ORR), as per intention-to-treat analysis, was 72.3% (95% confidence of interval (CI), 57-84%), with 17% complete responses. After a median follow-up of 24.2 months, the overall survival was 83.6% (95% CI, 73.0-95.7%) and the progression-free survival (PFS) was 49.6% (95% CI, 35.9-68.6%). The median PFS was 23.6 months. Univariate and multivariate analyses were used to identify clinical and biological characteristics associated with ORR and PFS. Myelosuppression was the most common toxicity; grade ≥3 neutropenia was observed in 61.7% of patients; however, grade ≥3 infections occurred in 6% of patients. BendOfa is feasible and effective in relapsed/refractory CLL patients, including patients with high-risk clinical and biological features. © 2014 Macmillan Publishers Limited.

Published
2014

47. Fludarabine plus alemtuzumab (FA) front-line treatment in young patients with chronic lymphocytic leukemia (CLL) and an adverse biologic profile

Author

Mauro Francesca, R, Molica, Stefano, Laurenti, Luca, Cortelezzi, Agostino, Carella Angelo, M., Zaja, Francesco, Chiarenza, Annalisa, Angrilli, Francesco, Nobile, Francesco, Marasca, Roberto, Musolino, Caterina, Brugiatelli, Maura, Piciocchi, Alfonso, Vignetti, Marco, Fazi, Paola, Gentile, Giuseppe, De Propris Maria, S., Starza Irene Della, Marinelli, Marilisa, Chiaretti, Sabina, Del Giudice Ilaria, Nanni, Mauro, Albano, Francesco, Cuneo, Antonio, Guarini, Anna, Foà, Robin, per il gruppo GIMEMA Working Party Chronic Lymph, Massaia, M., Mauro, Fr, Molica, S, Laurenti, L, Cortelezzi, A, Carella, Am, Zaja, Francesco, Chiarenza, A, Angrilli, F, Nobile, F, Marasca, R, Musolino, C, Brugiatelli, M, Piciocchi, A, Vignetti, M, Fazi, P, Gentile, G, De Propris, M, Della Starza, I, Marinelli, M, Chiaretti, S, Del Giudice, I, Nanni, M, Albano, F, Cuneo, A, Guarini, A, and Foà, R.

Subjects
Oncology, Male, Cancer Research, medicine.medical_treatment, Chronic lymphocytic leukemia, THERAPY, Fludarabine, Monoclonal, Antineoplastic Combined Chemotherapy Protocols, Medicine, Chronic, Alemtuzumab, Humanized, Vidarabine, Neoadjuvant therapy, Hematology, Leukemia, STEM CELL TRANSPLANTATION, Medicine (all), Middle Aged, Lymphocytic, Neoadjuvant Therapy, Treatment Outcome, Female, PHASE-II TRIAL, medicine.drug, EXPRESSION, Adult, medicine.medical_specialty, Young, Biology, CLL, Antibodies, Monoclonal, Humanized, Humans, Leukemia, Lymphocytic, Chronic, B-Cell, Survival Analysis, Antibodies, Chronic lymphocytic leukemia, CLL, Young, Biology, Fludarabine, Alemtuzumab, STEM CELL TRANSPLANTATION, PHASE-II TRIAL, TERM FOLLOW UP, SUBCUTANEOUS ALEMTUZUMAB, DISEASE PROGRESSION, POOR PROGNOSIS, FREE SURVIVAL, EXPRESSION, RITUXIMAB, THERAPY, Internal medicine, SUBCUTANEOUS ALEMTUZUMAB, RITUXIMAB, Survival analysis, business.industry, DISEASE PROGRESSION, B-Cell, medicine.disease, Transplantation, Settore MED/15 - MALATTIE DEL SANGUE, POOR PROGNOSIS, Immunology, TERM FOLLOW UP, FREE SURVIVAL, business
Abstract

In 45, ≤ 60 years old patients with CLL and an adverse biologic profile, a front-line treatment with Fludarabine and Campath (Alemtuzumab(®)) was given. The overall response rate was 75.5%, the complete response rate (CR) 24.4% with the lowest CR rates, 16.7% and 8.3%, in 11q and 17p deleted cases. The 3-year progression-free survival (PFS) and overall survival were 42.5% and 79.9%, respectively. PFS was significantly influenced by CLL duration, beta2-microglobulin, and improved by post-remissional stem cell transplantation. Front-line fludarabine and alemtuzumab showed a manageable safety profile and evidence of a benefit in a small series of CLL patients with adverse biologic features.

Published
2014

48. Histopathological and molecular features of persistent polyclonal B-cell lymphocytosis (PPBL) with progressive splenomegaly

Author

Robin Foà, Francesca Romana Mauro, Daniele Armiento, Elena Sabattini, Francesca Mancini, Paola Gesuiti, Luisa Quattrocchi, Irene Della Starza, Ilaria Del Giudice, Maria Stefania De Propris, Maura Rossi, Maria Paola Perrone, Stefano Pileri, Angela Amendola, Cristina Campidelli, Agostino Tafuri, Anna Guarini, Del Giudice I, Pileri SA, Rossi M, Sabattini E, Campidelli C, Starza ID, De Propris MS, Mancini F, Perrone MP, Gesuiti P, Armiento D, Quattrocchi L, Tafuri A, Amendola A, Mauro FR, Guarini A, and Foà R.

Subjects
Adult, Male, Pathology, medicine.medical_specialty, Lymphocytosis, Adolescent, histopathology, lymphoproliferative disease, mzl, ppbl, splenectomy, Immunoglobulin D, Polymerase Chain Reaction, Immunophenotyping, Young Adult, immune system diseases, Bone Marrow, medicine, Humans, Lymphocyte Count, Gene Rearrangement, B-Lymphocytes, biology, business.industry, Smoking, Hematology, HLA-DR Antigens, medicine.disease, CD79A, Lymphoma, medicine.anatomical_structure, Proto-Oncogene Proteins c-bcl-2, Splenomegaly, biology.protein, Red pulp, Splenectomy, Female, Bone marrow, Splenic disease, medicine.symptom, business, Immunoglobulin Heavy Chains, Spleen, Follow-Up Studies, HLA-DRB1 Chains
Abstract

Five cases of persistent polyclonal B-cell lymphocytosis (PPBL) with progressive splenomegaly are reported; three were splenectomized. BCL2/ IGH rearrangements were found in three cases; HLA-DRB1*07 in all. Bone marrow (BM) trephines showed a moderate lymphoid infiltrate with intrasinusoidal distribution resembling a splenic marginal-zone lymphoma. Splenic white pulp revealed an enlargement of the marginal-zone area; red pulp was infiltrated by the same lymphocytes engulfing the sinuses. Splenic and BM B-lymphocytes were CD79a + /CD20 + /IgM + /IgD + /bcl-2 + /CD27 + / DBA.44 - /CD31 - and polyclonal by immunophenotype/polymerase chain reaction. PPBL features an expansion of splenic marginal-zone B-lymphocytes, which infiltrate BM sinusoids and circulate in the blood with no evidence of clonality, even in cases with progressive splenomegaly.

Published
2009

49. Management of chronic lymphocytic leukemia: practice guidelines from the Italian Society of Hematology, the Italian Society of Experimental Hematology and the Italian Group for Bone Marrow Transplantation

Author

Brugiatelli, M., Bandini, G., Barosi, G., Lauria, F., Liso, V., Marchetti, M., Mauro, F. R., Meloni, G., PIER LUIGI ZINZANI, Tura, S., Brugiatelli M, Bandini G, Barosi G, Lauria F, Liso V, Marchetti M, Mauro FR, Meloni G, Zinzani PL, and Tura S

Subjects
chemotherapy, chronic lymphocytic leukemia, clinical practice guidelines, systematic review, Italy, Disease Management, Humans, Leukemia, Lymphocytic, Chronic, B-Cell | Patients | Therapeutics, Hematology, Leukemia, Lymphocytic, Chronic, B-Cell, Societies, Medical, Bone Marrow Transplantation
Abstract

The Italian Society of Hematology (SIE) and two affiliate societies (SIES and GITMO) commissioned a project to develop clinical practice guidelines for the treatment of chronic lymphocytic leukemia (CLL). METHODS: Key questions in the management of patients with CLL were formulated by an Advisory Committee and approved by an Expert Panel of eight senior hematologists. After a systematic review of the literature, recommendations for disease-specific and supportive therapies were formulated and graded according to the supporting evidence. Explicit consensus methods were used for providing recommendations for questions with incomplete or potentially biased evidence. RESULTS: It is recommended that therapy is commenced in patients with CLL when at least one of the following are present: B-symptoms, progressive/obstructive lymphadenopathy or organomegaly, rapid lymphocyte doubling time, anemia or thrombocytopenia (of new onset, worsening or steroid-resistant). It is recommended that patients without co-morbidity should receive fludarabine plus cyclophosphamide, whereas elderly patients with co-morbidity should receive oral chlorambucil. Younger patients with unfavorable biological risk factors should be considered for high-dose chemotherapy and autologous or allogeneic stem cell transplantation within approved clinical trials. Patients either relapsing rapidly after, or non-responsive to, first-line chlorambucil should receive fludarabine-containing regimens. Patients either relapsing soon after or not responding to fludarabine-based chemotherapy should be considered for schedules including non-cross-reactive agents, such as alemtuzumab, possibly followed by high-dose chemotherapy and autologous transplantation in the context of a clinical trial or by allogeneic stem cell transplantation. CONCLUSIONS: We describe the results of a systematic literature review and an explicit approach to consensus techniques which resulted in recommendations for the key therapeutic decisions in patients with CLL.

Published
2006

50. Alpha-interferon as maintenance drug after initial fludarabine therapy for patients with chronic lymphocytic leukemia and low-grade non-Hodgkin's lymphoma

Author

Zinzani, P. L., Levrero, M. G., Lauria, F., Rondelli, D., Francesco Zaja, Russo, D., Fanin, R., Rossi, G., Mauro, F. R., Bendandi, M., Gozzetti, A., Dianzani, F., Mandelli, F., Tura, S., Zinzani, Pl, Levrero, Mg, Lauria, F, Rondelli, D, Zaja, Francesco, Russo, D, Fanin, Renato, De Rossi, G, Mauro, Fr, Bendandi, M, Gozzetti, A, Dianzani, F, Mandelli, F, and Tura, S.

Subjects
Adult, Male, Neutropenia, Lymphoma, Aged, Antineoplastic Combined Chemotherapy Protocols, Female, Humans, Interferon-alpha, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Non-Hodgkin, Middle Aged, Remission Induction, Treatment Outcome, Vidarabine, Non-Hodgkin, LG-NHL, MAINTENANCE TREATMENT, Chronic, Leukemia, B-CLL, LG-NHL, FLUDARABINE, ALPHA-IFN, MAINTENANCE TREATMENT, B-Cell, B-CLL, Lymphocytic, FLUDARABINE, ALPHA-IFN
Abstract

BACKGROUND: Fludarabine monophosphate (FLU) is an adenine nucleoside analogue with promising therapeutic activity in lymphoproliferative disorders. In addition, the effectiveness of alpha-interferon (alpha-IFN) in low-grade non-Hodgkin's lymphoma (LG-NHL) and B-cell chronic lymphocytic leukemia (B-CLL) has been demonstrated in several clinical trials. METHODS: In a phase II study of 45 patients with B-CLL and 28 with LG-NHL, we used FLU as second and third-line chemotherapy. Dosages of 25 mg/m2 were given in 30-minute infusions for 5 consecutive days. Treatment was repeated every 28 days depending on patients' clinical status for a maximum of 6 cycles. Entrance in the human lymphoblastoid alpha-IFN maintenance portion of the study depended on response to initial FLU. Following randomization we administered alpha-IFN, or no therapy at all, to patients who obtained a complete or a partial response after FLU therapy. The alpha-IFN dose was 3 x 10(6) U three times per week until disease progression. RESULTS: Twenty-one B-CLL patients achieved major responses, as did 17 of those with LG-NHL. Twenty-four of the former group and 11 of the latter failed to respond or obtained only a minor response. The 38 patients who responded well and entered the second part of the trial showed significant prolongation of remission duration with maintenance alpha-IFN. CONCLUSIONS: In consideration of its significant activity, the role of FLU in the management of lymphoproliferative disorders needs to be evaluated further; at the same time, this preliminary analysis seems to indicate that maintenance alpha-IFN may extend remission duration in B-CLL and LG-NHL.

Published
1994

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