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3. L1CAM EXPRESSION IDENTIFIES DIFFERENT COLORECTAL TUMOR SUBGROUPS

Author

Cau, F., primary, Gerosa, C., additional, Ziranu, G., additional, Pretta, A., additional, Murru, R., additional, Fraschini, M., additional, Piras, M., additional, Eyken, P.V., additional, La Nasa, G., additional, Castagnola, M., additional, Coghe, F., additional, Orrù, G., additional, Zorcolo, L., additional, Fanni, D., additional, Scartozzi, M., additional, and Faa, G., additional

Published
2023
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4. Efficacy of front-line ibrutinib versus fludarabine, cyclophosphamide, and rituximab in patients with chronic lymphocytic leukemia: A retrospective multicenter “Real-World” study

Author

Levi, S., Bronstein, Y., Goldschmidt, N., Morabito, Francesco, Ziv-Baran, T., Del Poeta, G., Bairey, O., Del Principe, M. I., Fineman, R., Mauro, F. R., Gutwein, O., Reda, G., Ruchlemer, R., Sportoletti, P., Laurenti, Luca, Shvidel, L., Coscia, M., Tadmor, T., Varettoni, M., Aviv, A., Murru, R., Braester, A., Chiarenza, A., Visentin, A., Pietrasanta, D., Loseto, G., Zucchetto, A., Bomben, R., Olivieri, J., Neri, A., Rossi, Dario, Gaidano, G., Trentin, L., Foa, Robin, Cuneo, A., Perry, C., Gattei, V., Gentile, M., Herishanu, Y., Morabito F., Laurenti L. (ORCID:0000-0002-8327-1396), Rossi D., Foa R., Levi, S., Bronstein, Y., Goldschmidt, N., Morabito, Francesco, Ziv-Baran, T., Del Poeta, G., Bairey, O., Del Principe, M. I., Fineman, R., Mauro, F. R., Gutwein, O., Reda, G., Ruchlemer, R., Sportoletti, P., Laurenti, Luca, Shvidel, L., Coscia, M., Tadmor, T., Varettoni, M., Aviv, A., Murru, R., Braester, A., Chiarenza, A., Visentin, A., Pietrasanta, D., Loseto, G., Zucchetto, A., Bomben, R., Olivieri, J., Neri, A., Rossi, Dario, Gaidano, G., Trentin, L., Foa, Robin, Cuneo, A., Perry, C., Gattei, V., Gentile, M., Herishanu, Y., Morabito F., Laurenti L. (ORCID:0000-0002-8327-1396), Rossi D., and Foa R.

Abstract

NA

Published
2023

5. Human breast milk cells are positive for the pioneer transcription factor ISL1.

Author

PIRAS, M., CONI, P., PILUDU, M., CONI, S., LACHOWICZ, J. I., JAREMKO, M., FAA, G., CAU, F., SCANO, A., ORRÙ, G., MURRU, R., and PICHIRI, G.

Abstract

OBJECTIVE: ISL1 is a pioneer transcription factor that plays important roles in cell lineage specification and differentiation, by programming the epigenome and recruiting additional regulatory factors. The aim of this study is to determine whether the human breastmilk contains ISL1-positive stem cells, and, if so, to describe the subcellular localization of ISL1. MATERIALS AND METHODS: Breast milk was obtained from fourteen healthy females during the first 2-6 months of lactation. Cell morphology was examined in the breast milk with the automatic ThinPrep® processor (Hologic® Inc.) in commercial Cytological ThinPrep® solution (Hologic ® Inc.), followed by standard immunohistochemical staining of ISL1. RESULTS: ISL1 had a granular diffuse cytoplasmic localization, with varying intensity of staining in both single and grouped cells. Nuclear staining was also present, as was staining of intracellular and extracellular vesicles with ISL1 antibody. CONCLUSIONS: These preliminary results suggest that ISL1 could distinguish a readily available source of putative stem cells in human breast milk. These stem cells may complete the network created between the mother and the newborn during gestation, thereby improving the efficiency of programming and reprogramming postnatal events. [ABSTRACT FROM AUTHOR]

Published
2023

6. Chronic lymphocytic leukemia management in Italy during the COVID-19 pandemic: a Campus CLL report

Author

Cuneo, A., Scarfo, L., Reda, G., Varettoni, M., Quaglia, F. M., Marchetti, M., De Paoli, L., Re, F., Pietrasanta, D., Rigolin, G. M., Orsucci, L., Ibatici, A., Gattei, V., Mauro, F. R., Trentin, L., Laurenti, L., Marasca, R., Foa, R., Angeletti, I., Chiurazzi, F., Del Poeta, G., Rosaria De Paolis, M., Farina, L., Ferrari, A., Gentile, M., Gottardi, D., Gozzetti, A., Leone, M., Levato, L., Maccaferri, M., Malerba, L., Motta, M., Murru, R., Nocilli, L., Olivieri, J., Stefoni, V., Cuneo, A., Scarfo', L., Reda, G., Varettoni, M., Quaglia, F. M., Marchetti, M., De Paoli, L., Re, F., Pietrasanta, D., Rigolin, G. M., Orsucci, L., Ibatici, A., Gattei, V., Mauro, F. R., Trentin, L., Laurenti, L., Marasca, R., Foa, R., Angeletti, I., Chiurazzi, F., Del Poeta, G., Rosaria De Paolis, M., Farina, L., Ferrari, A., Gentile, M., Gottardi, D., Gozzetti, A., Leone, M., Levato, L., Maccaferri, M., Malerba, L., Motta, M., Murru, R., Nocilli, L., Olivieri, J., and Stefoni, V.

Subjects
Aged, Aged, 80 and over, Betacoronavirus, COVID-19, Coronavirus Infections, Disease Management, Humans, Italy, Leukemia, Lymphocytic, Chronic, B-Cell, Middle Aged, Pandemics, Pneumonia, Viral, SARS-CoV-2, Chronic lymphocytic leukemia, Biochemistry, chemistry.chemical_compound, Pandemic, 80 and over, Viral, Chronic, Disease management (health), Letter to Blood, Leukemia, Hematology, Lymphocytic, Ibrutinib, CLL, COVID-19, Campus CLL, medicine.medical_specialty, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Immunology, Cancer therapy, NO, Internal medicine, medicine, business.industry, B-Cell, Pneumonia, Cell Biology, Campus CLL, medicine.disease, Settore MED/15 - MALATTIE DEL SANGUE, chemistry, business, CLL
Published
2020

7. Do age, fitness, and concomitant medications influence management and outcomes of patients with CLL treated with ibrutinib?

Author

Tedeschi, A, Frustaci, A, Mauro, F, Chiarenza, A, Coscia, M, Ciolli, S, Reda, G, Laurenti, L, Varettoni, M, Murru, R, Barate, C, Sportoletti, P, Greco, A, Borella, C, Rossi, V, Deodato, M, Biagi, A, Zamprogna, G, Pelle, A, Lapietra, G, Vitale, C, Morelli, F, Cassin, R, Fresa, A, Cavalloni, C, Postorino, M, Ielo, C, Cairoli, R, Di Raimondo, F, Montillo, M, Del Poeta, G, Tedeschi A., Frustaci A. M., Mauro F. R., Chiarenza A., Coscia M., Ciolli S., Reda G., Laurenti L., Varettoni M., Murru R., Barate C., Sportoletti P., Greco A., Borella C., Rossi V., Deodato M., Biagi A., Zamprogna G., Pelle A. C., Lapietra G., Vitale C., Morelli F., Cassin R., Fresa A., Cavalloni C., Postorino M., Ielo C., Cairoli R., Di Raimondo F., Montillo M., Del Poeta G., Tedeschi, A, Frustaci, A, Mauro, F, Chiarenza, A, Coscia, M, Ciolli, S, Reda, G, Laurenti, L, Varettoni, M, Murru, R, Barate, C, Sportoletti, P, Greco, A, Borella, C, Rossi, V, Deodato, M, Biagi, A, Zamprogna, G, Pelle, A, Lapietra, G, Vitale, C, Morelli, F, Cassin, R, Fresa, A, Cavalloni, C, Postorino, M, Ielo, C, Cairoli, R, Di Raimondo, F, Montillo, M, Del Poeta, G, Tedeschi A., Frustaci A. M., Mauro F. R., Chiarenza A., Coscia M., Ciolli S., Reda G., Laurenti L., Varettoni M., Murru R., Barate C., Sportoletti P., Greco A., Borella C., Rossi V., Deodato M., Biagi A., Zamprogna G., Pelle A. C., Lapietra G., Vitale C., Morelli F., Cassin R., Fresa A., Cavalloni C., Postorino M., Ielo C., Cairoli R., Di Raimondo F., Montillo M., and Del Poeta G.

Abstract

Functional reserve of organs and systems is known to be relevant in predicting immunochemotherapy tolerance. Age and comorbidities, assessed by the cumulative illness rating scale (CIRS), have been used to address chemotherapy intensity. In the ibrutinib era, it is still unclear whether age, CIRS, and Eastern Cooperative Oncology Group performance status (ECOG-PS) retain their predictive role on treatment vulnerability. In this series of 712 patients with chronic lymphocytic leukemia (CLL) treated with ibrutinib outside clinical trials, baseline ECOG-PS and neutropenia resulted as the most accurate predictors of treatment feasibility and outcomes. Age did not independently influence survival and ibrutinib tolerance, indicating that not age per se, but age-related conditions, may affect drug management. We confirmed the role of CIRS . 6 as a predictor of a poorer progression- and event-free survival (PFS, EFS). The presence of a severe comorbidity was significantly associated with permanent dose reductions (PDRs), not translating into worse outcomes. As expected, del(17p) and/or TP53mut and previous therapies affected PFS, EFS, and overall survival. No study so far has analyzed the influence of concomitant medications and CYP3A inhibitors with ibrutinib. In our series, these factors had no impact, although CYP3A4 inhibitors use correlated with Cox regression analysis, with an increased risk of PDR. Despite the limitation of its retrospective nature, this large study confirmed the role of ECOG-PS as the most accurate predictor of ibrutinib feasibility and outcomes, and importantly, neutropenia emerged as a relevant tool influencing patients’ vulnerability. Although CIRS > 6 retained a significant impact on PFS and EFS, its value should be confirmed by prospective studies.

Published
2021

8. P660: SEROLOGIC RESPONSE TO THE SECOND AND THIRD DOSE OF THE SARS-COV-2 VACCINE IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA: RESULTS OF A PROSPECTIVE, CENTRALIZED, MULTICENTER STUDY.

Author

Mauro, F. R., primary, Giannarelli, D., additional, Galluzzo, C., additional, Visentin, A., additional, Frustaci, A. M., additional, Sportoletti, P., additional, Vitale, C., additional, Reda, G., additional, Gentile, M., additional, Levato, L., additional, Murru, R., additional, Armiento, D., additional, Ielo, C., additional, Maglione, R., additional, Crisanti, E., additional, Cipiciani, A., additional, Mattiello, V., additional, Gianfelici, V., additional, Barabino, L., additional, Amici, R., additional, Coscia, M., additional, Tedeschi, A., additional, Trentin, L., additional, and Baroncelli, S., additional

Published
2022
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9. How Age, Comorbidities and Concomitant Medications Influence Ibrutinib Management and Survival in Waldenstrom Macroglobulinemia

Author

Frustaci, A, Piazza, F, Ferrero, S, Reda, G, Rizzi, R, Orsucci, L, Ferrarini, I, Deodato, M, Laurenti, L, Puccini, B, Barate, C, Varettoni, M, Merli, M, Cencini, E, Greco, A, Gini, G, Ferrari, A, Borella, C, Lista, E, Gentile, M, Murru, R, Motta, M, Rezzonico, F, Tani, M, Sportoletti, P, Zamprogna, G, Torri, V, Cairoli, R, Tedeschi, A, Frustaci, A, Piazza, F, Ferrero, S, Reda, G, Rizzi, R, Orsucci, L, Ferrarini, I, Deodato, M, Laurenti, L, Puccini, B, Barate, C, Varettoni, M, Merli, M, Cencini, E, Greco, A, Gini, G, Ferrari, A, Borella, C, Lista, E, Gentile, M, Murru, R, Motta, M, Rezzonico, F, Tani, M, Sportoletti, P, Zamprogna, G, Torri, V, Cairoli, R, and Tedeschi, A

Published
2022

10. Thrombotic and bleeding complications in patients with chronic lymphocytic leukemia and severe COVID-19: a study of ERIC, the European Research Initiative on CLL

Author

Antic, D., Milic, N., Chatzikonstantinou, T., Scarfo, L., Otasevic, V., Rajovic, N., Allsup, D., Alonso Cabrero, A., Andres, M., Baile Gonzales, M., Capasso, A., Collado, R., Cordoba, R., Cuellar-Garcia, C., Correa, J. G., De Paoli, L., De Paolis, M. R., Del Poeta, G., Dimou, M., Doubek, M., Efstathopoulou, M., El-Ashwah, S., Enrico, A., Espinet, B., Farina, L., Ferrari, A., Foglietta, M., Lopez-Garcia, A., Garcia-Marco, J. A., Garcia-Serra, R., Gentile, Marino, Gimeno, E., da Silva, M. G., Gutwein, O., Hakobyan, Y. K., Herishanu, Y., Hernandez-Rivas, J. A., Herold, T., Itchaki, G., Jaksic, O., Janssens, A., Kalashnikova, O. B., Kalicinska, E., Kater, A. P., Kersting, S., Koren-Michowitz, M., Labrador, J., Lad, D., Laurenti, Luca, Fresa, Alberto, Levin, M. -D., Mayor Bastida, C., Malerba, L., Marasca, R., Marchetti, M., Marquet, J., Mihaljevic, B., Milosevic, I., Miras, F., Morawska, M., Motta, M., Munir, T., Murru, R., Nunes, R., Olivieri, J., Pavlovsky, M. A., Piskunova, I., Popov, V. M., Quaglia, F. M., Quaresmini, G., Reda, G., Rigolin, G. M., Shrestha, A., Simkovic, M., Smirnova, S., Spacek, M., Sportoletti, P., Stanca, O., Stavroyianni, N., Te Raa, D., Tomic, K., Tonino, S., Trentin, L., Van Der Spek, E., van Gelder, M., Varettoni, M., Visentin, A., Vitale, C., Vukovic, Vladimir, Wasik-Szczepanek, E., Wrobel, T., Segundo, L. Y. S., Yassin, M., Coscia, M., Rambaldi, A., Montserrat, E., Foa, Robin, Cuneo, A., Carrier, M., Ghia, P., Stamatopoulos, K., Gentile M., Laurenti L. (ORCID:0000-0002-8327-1396), Fresa A., Vukovic V. (ORCID:0000-0002-9561-7825), Foa R., Antic, D., Milic, N., Chatzikonstantinou, T., Scarfo, L., Otasevic, V., Rajovic, N., Allsup, D., Alonso Cabrero, A., Andres, M., Baile Gonzales, M., Capasso, A., Collado, R., Cordoba, R., Cuellar-Garcia, C., Correa, J. G., De Paoli, L., De Paolis, M. R., Del Poeta, G., Dimou, M., Doubek, M., Efstathopoulou, M., El-Ashwah, S., Enrico, A., Espinet, B., Farina, L., Ferrari, A., Foglietta, M., Lopez-Garcia, A., Garcia-Marco, J. A., Garcia-Serra, R., Gentile, Marino, Gimeno, E., da Silva, M. G., Gutwein, O., Hakobyan, Y. K., Herishanu, Y., Hernandez-Rivas, J. A., Herold, T., Itchaki, G., Jaksic, O., Janssens, A., Kalashnikova, O. B., Kalicinska, E., Kater, A. P., Kersting, S., Koren-Michowitz, M., Labrador, J., Lad, D., Laurenti, Luca, Fresa, Alberto, Levin, M. -D., Mayor Bastida, C., Malerba, L., Marasca, R., Marchetti, M., Marquet, J., Mihaljevic, B., Milosevic, I., Miras, F., Morawska, M., Motta, M., Munir, T., Murru, R., Nunes, R., Olivieri, J., Pavlovsky, M. A., Piskunova, I., Popov, V. M., Quaglia, F. M., Quaresmini, G., Reda, G., Rigolin, G. M., Shrestha, A., Simkovic, M., Smirnova, S., Spacek, M., Sportoletti, P., Stanca, O., Stavroyianni, N., Te Raa, D., Tomic, K., Tonino, S., Trentin, L., Van Der Spek, E., van Gelder, M., Varettoni, M., Visentin, A., Vitale, C., Vukovic, Vladimir, Wasik-Szczepanek, E., Wrobel, T., Segundo, L. Y. S., Yassin, M., Coscia, M., Rambaldi, A., Montserrat, E., Foa, Robin, Cuneo, A., Carrier, M., Ghia, P., Stamatopoulos, K., Gentile M., Laurenti L. (ORCID:0000-0002-8327-1396), Fresa A., Vukovic V. (ORCID:0000-0002-9561-7825), and Foa R.

Abstract

Background: Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to COVID-19 related poor outcomes, including thrombosis and death, due to the advanced age, the presence of comorbidities, and the disease and treatment-related immune deficiency. The aim of this study was to assess the risk of thrombosis and bleeding in patients with CLL affected by severe COVID-19. Methods: This is a retrospective multicenter study conducted by ERIC, the European Research Initiative on CLL, including patients from 79 centers across 22 countries. Data collection was conducted between April and May 2021. The COVID-19 diagnosis was confirmed by the real-time polymerase chain reaction (RT-PCR) assay for SARS-CoV-2 on nasal or pharyngeal swabs. Severe cases of COVID-19 were defined by hospitalization and the need of oxygen or admission into ICU. Development and type of thrombotic events, presence and severity of bleeding complications were reported during treatment for COVID-19. Bleeding events were classified using ISTH definition. STROBE recommendations were used in order to enhance reporting. Results: A total of 793 patients from 79 centers were included in the study with 593 being hospitalized (74.8%). Among these, 511 were defined as having severe COVID: 162 were admitted to the ICU while 349 received oxygen supplementation outside the ICU. Most patients (90.5%) were receiving thromboprophylaxis. During COVID-19 treatment, 11.1% developed a thromboembolic event, while 5.0% experienced bleeding. Thrombosis developed in 21.6% of patients who were not receiving thromboprophylaxis, in contrast to 10.6% of patients who were on thromboprophylaxis. Bleeding episodes were more frequent in patients receiving intermediate/therapeutic versus prophylactic doses of low-molecular-weight heparin (LWMH) (8.1% vs. 3.8%, respectively) and in elderly. In multivariate analysis, peak D-dimer level and C-reactive protein to albumin ratio were poor prognostic factors for thrombosis occu

Published
2022

11. Obinutuzumab plus chlorambucil versus ibrutinib in previously untreated chronic lymphocytic leukemia patients without TP53 disruptions: A real-life CLL campus study

Author

Visentin, A., Mauro, F. R., Catania, G., Fresa, Alberto, Vitale, C., Sanna, A., Mattiello, V., Cibien, F., Sportoletti, P., Gentile, M., Rigolin, G. M., Quaglia, F. M., Murru, R., Gozzetti, A., Molica, Serena, Marchetti, M., Pravato, S., Angotzi, F., Cellini, A., Scarfo, L., Reda, G., Coscia, M., Laurenti, Luca, Ghia, P., Foa, Robin, Cuneo, A., Trentin, L., Fresa A., Molica S., Laurenti L. (ORCID:0000-0002-8327-1396), Foa R., Visentin, A., Mauro, F. R., Catania, G., Fresa, Alberto, Vitale, C., Sanna, A., Mattiello, V., Cibien, F., Sportoletti, P., Gentile, M., Rigolin, G. M., Quaglia, F. M., Murru, R., Gozzetti, A., Molica, Serena, Marchetti, M., Pravato, S., Angotzi, F., Cellini, A., Scarfo, L., Reda, G., Coscia, M., Laurenti, Luca, Ghia, P., Foa, Robin, Cuneo, A., Trentin, L., Fresa A., Molica S., Laurenti L. (ORCID:0000-0002-8327-1396), and Foa R.

Abstract

One of the main issues in the treatment of patients with chronic lymphocytic leukemia (CLL) deals with the choice between continuous or fixed-duration therapy. Continuous ibrutinib (IB), the first-in-class BTK inhibitor, and obinutuzumab-chlorambucil (G-CHL) are commonly used therapies for elderly and/or comorbid patients. No head-to-head comparison has been carried out. Within the Italian campus CLL network, we performed a retrospective study on CLL patients without TP53 disruption treated with IB or G-CHL as first-line therapy. Patients in the G-CHL arm had a higher CIRS score and the worst renal function. The overall response rates between the G-CHL and IB arms were similar, but more complete remissions (CRs) were achieved with G-CHL (p = 0.0029). After a median follow-up of 30 months, the progression-free survival (PFS, p = 0.0061) and time to next treatment (TTNT, p = 0.0043), but not overall survival (OS, p = 0.6642), were better with IB than with G-CHL. Similar results were found after propensity score matching and multivariate analysis. While PFS and TTNT were longer with IB than with G-CHL in IGHV unmutated patients (p = 0.0190 and 0.0137), they were superimposable for IGHV mutated patients (p = 0.1900 and 0.1380). In the G-CHL arm, the depth of response (79% vs. 68% vs. 38% for CR, PR and SD/PD; p < 0.0001) and measurable residual disease (MRD) influenced PFS (78% vs. 53% for undetectable MRD vs. detectable MRD, p = 0.0203). Hematological toxicities were common in the G-CHL arm, while IB was associated with higher costs. Although continuous IB provides better disease control in CLL, IGHV mutated patients and those achieving an undetectable MRD show a marked clinical and economic benefit from a fixed-duration obinutuzumab-based treatment.

Published
2022

12. Clinical course and features of persistent polyclonal B-cell lymphocytosis with BCL-6 amplification during pregnancy.

Author

GALITZIA, A., MURRU, R., CAOCCI, G., BARABINO, L., AZZENA, A., LICHERI, V. M., GRECO, M., and LA NASA, G.

Abstract

BACKGROUND: Persistent polyclonal B-cell lymphocytosis is a rare nonmalignant disorder characterized by mild persistent lymphocyte proliferation with possible evolution to aggressive lymphoma. Its biology is not well known, but it is characterized by a specific immunophenotype with rearrangement of the BCL-2/IGH gene, whereas amplification of the BCL-6 gene has rarely been reported. Given the paucity of reports, it has been hypothesized that this disorder is associated with poor pregnancy outcomes. CASE REPORT: To our knowledge, only two successful pregnancies have been described in women with this condition. We report the third successful pregnancy in a patient with PPBL and the first with amplification of the BCL-6 gene. CONCLUSIONS: PPBL is still a poorly understood clinical condition with insufficient data to demonstrate an adverse effect on pregnancy. The role of BCL-6 dysregulation in the pathogenesis of PPBL and its prognostic significance are still unknown. Evolution into aggressive clonal lymphoproliferative disorders is possible and prolonged hematologic follow-up is warranted in patients with this rare clinical disorder. [ABSTRACT FROM AUTHOR]

Published
2023

14. Thrombotic and bleeding complications in patients with chronic lymphocytic leukemia and severe COVID-19: a study of ERIC, the European Research Initiative on CLL

Author

Antic D, Milic N, Chatzikonstantinou T, Scarfò L, Otasevic V, Rajovic N, Allsup D, Alonso Cabrero A, Andres M, Baile Gonzales M, Capasso A, Collado R, Cordoba R, Cuéllar-García C, Correa JG, De Paoli L, De Paolis MR, Del Poeta G, Dimou M, Doubek M, Efstathopoulou M, El-Ashwah S, Enrico A, Espinet B, Farina L, Ferrari A, Foglietta M, Lopez-Garcia A, García-Marco JA, García-Serra R, Gentile M, Gimeno E, da Silva MG, Gutwein O, Hakobyan YK, Herishanu Y, Hernández-Rivas JÁ, Herold T, Itchaki G, Jaksic O, Janssens A, Kalashnikova OB, Kalicińska E, Kater AP, Kersting S, Koren- Michowitz M, Labrador J, Lad D, Laurenti L, Fresa A, Levin MD, Mayor Bastida C, Malerba L, Marasca R, Marchetti M, Marquet J, Mihaljevic B, Milosevic I, Mirás F, Morawska M, Motta M, Munir T, Murru R, Nunes R, Olivieri J, Pavlovsky MA, Piskunova I, Popov VM, Quaglia FM, Quaresmini G, Reda G, Rigolin GM, Shrestha A, Šimkovič M, Smirnova S, Špaček M, Sportoletti P, Stanca O, Stavroyianni N, Te Raa D, Tomic K, Tonino S, Trentin L, Van Der Spek E, van Gelder M, Varettoni M, Visentin A, Vitale C, Vukovic V, Wasik-Szczepanek E, Wróbel T, Segundo LYS, Yassin M, Coscia M, Rambaldi A, Montserrat E, Foà R, Cuneo A, Carrier M, Ghia P, Stamatopoulos K.

Subjects
Age, Anticoagulation therapy, Bleeding, CLL, COVID-19, D-dimer, LMWH, Thromboprophylaxis, Thrombosis
Abstract

Background: Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to COVID-19 related poor outcomes, including thrombosis and death, due to the advanced age, the presence of comorbidities, and the disease and treatment- related immune deficiency. The aim of this study was to assess the risk of thrombosis and bleeding in patients with CLL affected by severe COVID-19. Methods: This is a retrospective multicenter study conducted by ERIC, the European Research Initiative on CLL, including patients from 79 centers across 22 countries. Data collection was conducted between April and May 2021. The COVID-19 diagnosis was confirmed by the real-time polymerase chain reaction (RT-PCR) assay for SARS- CoV-2 on nasal or pharyngeal swabs. Severe cases of COVID-19 were defined by hospitalization and the need of oxygen or admission into ICU. Development and type of thrombotic events, presence and severity of bleeding complications were reported during treatment for COVID-19. Bleeding events were classified using ISTH definition. STROBE recommendations were used in order to enhance reporting. Results: A total of 793 patients from 79 centers were included in the study with 593 being hospitalized (74.8%). Among these, 511 were defined as having severe COVID: 162 were admitted to the ICU while 349 received oxygen supplementation outside the ICU. Most patients (90.5%) were receiving thromboprophylaxis. During COVID-19 treatment, 11.1% developed a thromboembolic event, while 5.0% experienced bleeding. Thrombosis developed in 21.6% of patients who were not receiving thromboprophylaxis, in contrast to 10.6% of patients who were on thromboprophylaxis. Bleeding episodes were more frequent in patients receiving intermediate/therapeutic versus prophylactic doses of low-molecular-weight heparin (LWMH) (8.1% vs. 3.8%, respectively) and in elderly. In multivariate analysis, peak D-dimer level and C- reactive protein to albumin ratio were poor prognostic factors for thrombosis occurrence (OR = 1.022, 95%CI 1.007‒1.038 and OR = 1.025, 95%CI 1.001‒1.051, respectively), while thromboprophylaxis use was protective (OR = 0.199, 95%CI 0.061‒0.645). Age and LMWH intermediate/therapeutic dose administration were prognostic factors in multivariate model for bleeding (OR = 1.062, 95%CI 1.017-1.109 and OR = 2.438, 95%CI 1.023-5.813, respectively). Conclusions: Patients with CLL affected by severe COVID-19 are at a high risk of thrombosis if thromboprophylaxis is not used, but also at increased risk of bleeding under the LMWH intermediate/therapeutic dose administration.

Published
2022

15. Chronic graft vs. host disease and hypogammaglobulinemia predict a lower immunological response to the BNT162b2 mRNA COVID-19 vaccine after allogeneic hematopoietic stem cell transplantation.

Author

BARABINO, L., GALITZIA, A., MURRU, R., CAOCCI, G., TARGHETTA, C., GRECO, M., ANGIONI, G., MULAS, O., VACCA, A., PIRAS, E., FRAU, V., COSTA, A., and LA NASA, G.

Abstract

OBJECTIVE: Due to the high mortality rate of COVID-19, the assessment of BNT162b2 SARS-CoV-2 mRNA vaccine (Pfizer-BioNTech) efficacy in allogeneic hematopoietic stem cell transplant (HSCT) recipients is mandatory. PATIENTS AND METHODS: We conducted a single-center pilot study with the main objective of evaluating the immunogenicity of the BNT162b2 mRNA vaccine in 31 hematological patients who underwent hematopoietic stem cell transplantation within the previous 12 months and/or were affected by chronic graftvs.-host-disease (cGVHD), by the assessment of antibody levels at 30-45 days after the second dose of vaccine. RESULTS: After the second dose of vaccine, 23 out of 31 patients (74%) showed a positive immune response. The presence of severe cGVHD or Ig deficiency identified 7 out of 8 (85%) of non-responders. The median absolute cluster of differentiation 19 (CD19) count was significantly lower in non-responders vs. responders (109/µl vs. 351/µl). Underlying pathology, comorbidities, type of donor, time intervals from transplant and cluster of differentiation 3/cluster of differentiation 4/cluster of differentiation 8 (CD3/CD4/CD8) subsets were not significantly associated with an effective immune response to vaccination. CONCLUSIONS: Despite the limited sample of patients enrolled, our findings suggest that hypogammaglobulinemia and cGVHD could be associated with poor humoral response to the BNT162b2. [ABSTRACT FROM AUTHOR]

Published
2022

19. Expression of L1 Cell Adhesion Molecule (L1CAM) in extracellular vesicles in the human spinal cord during development.

Author

CAU, F., FANNI, D., MANCHIA, M., GEROSA, C., PIRAS, M., MURRU, R., PARIBELLO, P., CONGIU, T., CONI, P., PICHIRI, G., PILUDU, M., VAN EYKEN, P., GIBO, Y., LA NASA, G., ORRÙ, G., SCANO, A., COGHE, F., SABA, L., CASTAGNOLA, M., and FAA, G.

Abstract

OBJECTIVE: L1 cell adhesion molecule (L1CAM) is a glycoprotein characterized by three components: an extracellular region, a transmembrane segment, and a cytoplasmic tail. L1CAM is expressed in multiple human cells, including neurons. The neural cell adhesion molecule L1 has been implicated in a variety of neurologic processes, including neuritogenesis and cerebellar cell migration. The presence of L1CAM on the surface of nerve cells allows the adhesion of neurons among them. Furthermore, when it is bound to itself or to other proteins, L1-CAM induces signals inside the cell. The aim of this work was to study L1CAM expression in the human spinal cord during development, at different gestational ages, through immunohistochemistry. MATERIALS AND METHODS: Immunohistochemical analysis for L1CAM was performed in five human spinal cord samples, including three embryos and two fetuses of different gestational ages, ranging from 8 to 12 weeks. RESULTS: L1CAM expression was detected in all 5 spinal cords examined in this study. The adhesion molecule was found in the vast majority of cells. The highest levels of immunoreactivity for L1CAM were detected at the periphery of the developing organs, in the spinal cord zones occupied by sensory and motor fibers. In the alar and basal columns, immunoreactivity for L1CAM was characterized by a reticular pattern, being mainly expressed in axons. Strong reactivity of L1CAM was also found in extracellular vesicles. This extracellular localization might indicate the ability of L1CAM to mediate the transduction of extracellular signals that support axon outgrowth. CONCLUSIONS: The high reactivity of L1cam in the axons of developing neurons in the fetal spinal cord confirms previous studies on the ability of L1CAM to promote axon sprouting and branching in the developing nervous system. In this work, a new actor is reported to have a role in the complex field of human spinal cord development: L1CAM, whose expression is highly found in the developing neuronal and glial precursors. [ABSTRACT FROM AUTHOR]

Published
2022

20. EFFICACY AND DISCONTINUATION RATE OF IBRUTINIB IN TREATMENT NAIVE CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS WITH TP53 ABNORMALITIES. A REAL‐LIFE CAMPUS CLL STUDY

Author

Visentin, A., primary, Mauro, F. R., additional, Cibien, F., additional, Vitale, C., additional, Reda, G., additional, Fresa, A., additional, Ciolli, S., additional, Pietrasanta, D., additional, Marchetti, M., additional, Murru, R., additional, Gentile, M., additional, Rigolin, G. M., additional, Quaglia, F. M., additional, Scarfò, L., additional, Sportoletti, P., additional, Pravato, S., additional, Romano Gargarella, L., additional, Facco, M., additional, Piazza, F., additional, Coscia, M., additional, Laurenti, L., additional, Molica, S., additional, Pizzolo, G., additional, Foà, R., additional, Cuneo, A., additional, and Trentim, L., additional

Published
2021
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21. Efficacy of idelalisib and rituximab in relapsed/refractory chronic lymphocytic leukemia treated outside of clinical trials. A report of the Gimema Working Group

Author

Rigolin, G. M., Cavazzini, F., Piciocchi, A., Arena, V., Visentin, A., Reda, G., Zamprogna, G., Cibien, F., Vitagliano, O., Coscia, M., Farina, L., Gaidano, G., Murru, R., Varettoni, M., Paolini, R., Sportoletti, P., Pietrasanta, D., Molinari, A. L., Quaglia, F. M., Laurenti, L., Marasca, R., Marchetti, M., Mauro, F. R., Crea, E., Vignetti, M., Gentile, M., Montillo, M., Foa, R., Cuneo, A., Chiarenza, A., Perbellini, O., Mannina, D., Sancetta, R., Olivieri, A., Molica, S., Pane, F., Patti, C., Iliariucci, F., Gozzetti, A., Califano, C., Galieni, P., Augello, A. F., Vallisa, D., Cura, F., Frustaci, A. M., Fazi, P., Trentin, L., and Ferrara, F.

Subjects
Male, Oncology, Cancer Research, idelalisib, law.invention, 0302 clinical medicine, Randomized controlled trial, Recurrence, law, Original Research Articles, Antineoplastic Combined Chemotherapy Protocols, 80 and over, Original Research Article, Chronic, Aged, 80 and over, Leukemia, real‐world evidence, Hematology, General Medicine, Middle Aged, Lymphocytic, Survival Rate, 030220 oncology & carcinogenesis, Female, Rituximab, Refractory Chronic Lymphocytic Leukemia, Idelalisib, chronic lymphocytic leukemia, real-world evidence, Aged, Disease-Free Survival, Humans, Leukemia, Lymphocytic, Chronic, B-Cell, Purines, Quinazolinones, medicine.drug, medicine.medical_specialty, NO, 03 medical and health sciences, Internal medicine, medicine, Survival rate, Performance status, business.industry, B-Cell, Clinical trial, Settore MED/15 - MALATTIE DEL SANGUE, Regimen, business, 030215 immunology
Abstract

Because the efficacy of new drugs reported in trials may not translate into similar results when used in the real‐life, we analyzed the efficacy of idelalisib and rituximab (IR) in 149 patients with relapsed/refractory chronic lymphocytic leukemia treated at 34 GIMEMA centers. Median progression‐free survival (PFS) and overall survival were 22.9 and 44.5 months, respectively; performance status (PS) ≥2 and ≥3 previous lines of therapy were associated with shorter PFS and overall survival (OS). 48% of patients were on treatment at 12 months; the experience of the centers (≥5 treated patients) and PS 0–1 were associated with a significantly longer treatment duration (p = 0.015 and p = 0.002, respectively). TP53 disruption had no prognostic significance. The overall response rate to subsequent treatment was 49.2%, with median OS of 15.5 months and not reached in patients who discontinued, respectively, for progression and for toxicity (p

Published
2021

22. 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

23. 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

24. 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

25. 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

26. 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

27. Survival risk score for real-life relapsed/refractory chronic lymphocytic leukemia patients receiving ibrutinib. A campus CLL study

Author

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

Abstract

N/A

Published
2021

28. 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

29. Interindividual variability in L1CAM expression in the human kidney during development: are there implications for fetal programming of kidney diseases presenting in adulthood?

Author

CAU, F., GEROSA, C., MURRU, R., PICHIRI, G., CONI, P., PIRAS, M., SCANO, A., ORRÙ, G., LA NASA, G., COGHE, F., CASTAGNOLA, M., VAN EYKEN, P., SABA, L., FANNI, D., and FAA, G.

Abstract

OBJECTIVE: L1 cell adhesion molecule (L1CAM) is a member of the immunoglobulin superfamily of cell adhesion molecules. The present study investigated the expression of L1CAM during the development in the fetal human kidney at different gestational ages, to reach a better knowledge on the role of L1CAM in renal morphogenesis. MATERIALS AND METHODS: The immunohistochemical analysis for L1CAM was performed in 24 fetal kidneys of different gestational ages, ranging from 10 to 38 weeks. L1CAM expression was observed in all 24 kidneys examined. RESULTS: Immunoreactivity for L1CAM was restricted to the collecting tubules, of the developing fetal kidneys. Moreover, L1CAM was detected in the ureteric bud tips, near the subcapsular metanephric mesenchymal stem/progenitor cells. L1CAM was also expressed in the collecting tubules undergoing fusion with the distal tubules of the developing nephrons. L1CAM was mainly expressed along the cell membrane. In fetal kidneys in which the renal pelvis was observed, epithelial cells of the renal pelvis showed strong membranous reactivity for L1CAM. CONCLUSIONS: Our study shows that L1CAM is expressed in all stages of human kidney nephrogenesis, being restricted to the renal structures derived from the ureteric bud. The expression of L1CAM in the cells of the ureteric bud tips suggests a major role for this adhesion molecule in the induction of metanephric mesenchymal cells to undergo mesenchymal-to-epithelial transition and differentiation into new nephrons. The interindividual variability in L1CAM expression observed in this study might be related to different levels of nephrogenesis, suggesting L1CAM involvement in the fetal programming of adult kidney diseases. [ABSTRACT FROM AUTHOR]

Published
2022

30. 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

33. 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

34. Acyl-CoA binding protein (ACBP) is highly expressed in the developing human kidney.

Author

PIRAS, M., GEROSA, C., FANNI, D., CAU, F., CONI, P., MURRU, R., DENOTTI, G., ORRÙ, G., SCANO, A., LEDDA, F., VAN EYKEN, P., COGHE, F., FAA, G., and CASTAGNOLA, M.

Abstract

OBJECTIVE: Acyl-CoA-binding protein (ACBP), also known as diazepam binding inhibitor (DBI), is a small phylogenetically conserved protein. This ancestral peptide is multifunctional, performing intracellular activities as ACBP protein or extracellular roles as DBI. Several studies showed its endless facets, including a relevant activity as appetite stimulator and as anabolic factor. High levels of ACBP have been described in erythrocytes, liver, kidney, and gut cells. The aim of this study was to analyze, at immunohistochemical level, the expression of ACBP in fetal human tissues during development, focusing on the developing kidney. MATERIALS AND METHODS: Immunohistochemistry for ACBP was performed on 30 human fetal kidneys, from 15 fetuses of gestational age ranging from 13 to 19 weeks. At autopsy, all kidney samples were 10% formalin-fixed, routinely processed and paraffin-embedded. Five micron-thick paraffin sections were stained with Hematoxylin and Eosin and PAS stain for a morphological examination. RESULTS: ACBP was detected in all 30 kidneys analyzed in this study. No significant changes in ACBP expression were observed at different gestational ages. Immunostaining for ACBP was restricted to the epithelium covering the renal pelvis, the papillae, the collecting tubules, and the proximal and distal tubules. On the other hand, medullary regions and in the metanephric mesenchymal stem/progenitor cells did not show any reactivity for ACBP. CONCLUSIONS: According to our findings, ACBP should be considered as a new player in the complex field of human nephrogenesis, given that it was detected in all fetal kidneys immunostained. Its preferential localization in the renal structures derived from the Wolf duct, such as pelvis epithelium and collecting ducts, suggests a major role for ACBP in the induction of the metanephric mesenchymal cells toward the differentiation into glomerular structures. ACBP expression in proximal and distal tubules, two structures originating from the metanephric mesenchyme, indicates a further role of this protein in nephron development. In conclusion, ACBP should be added to the multiple molecules involved in human nephrogenesis. [ABSTRACT FROM AUTHOR]

Published
2022

40. 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

42. 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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44. 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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47. LDH AS PREDICTIVE PARAMETER IN TREATMENT-NAIVE PATIENTS WITH TRISOMY 12 CHRONIC LYMPHOCYTIC LEUKEMIA

Author

Autore, F., Strati, P., Innocenti, I., Corrente, F., Trentin, L., Cortelezzi, A., Visco, C., Coscia, M., Cuneo, A., Gozzetti, A., Mauro, F. R., Montillo, M., Gentile, M., Morabito, F., Molica, S., Falcucci, P., D Arena, G., Murru, R., Vincelli, D., Galieni, P., Reda, G., Maria Chiara Tisi, Vitale, C., Rigolin, G. M., Ferrajoli, A., and Laurenti, L.

Subjects
trisomy 12, LDH, prognosis, CLL, trisomy 12, prognosis, LDH, CLL, NO
Published
2017

48. The burden of multiple sclerosis variants in continental Italians and Sardinians

Author

Barizzone N, Zara I, Sorosina M, Lupoli S, Porcu E, Pitzalis M, Zoledziewska M, Esposito F, Leone M, Mulas A, Cocco E, Ferrigno P, Guerini FR, Brambilla P, Farina G, Murru R, Deidda F, Sanna S, Loi A, Barlassina C, Vecchio D, Zauli A, Clarelli F, Braga D, Poddie F, Cantello R, Martinelli V, Frau J, Lorefice L, Pugliatti M, Rosati G, PROGEMUS Consortium PROGRESSO Consortium, Melis M, Marrosu MG, Cusi D, Cucca F, Martinelli Boneschi F, D'Alfonso S., COMI , GIANCARLO, Barizzone, N, Zara, I, Sorosina, M, Lupoli, S, Porcu, E, Pitzalis, M, Zoledziewska, M, Esposito, F, Leone, M, Mulas, A, Cocco, E, Ferrigno, P, Guerini, Fr, Brambilla, P, Farina, G, Murru, R, Deidda, F, Sanna, S, Loi, A, Barlassina, C, Vecchio, D, Zauli, A, Clarelli, F, Braga, D, Poddie, F, Cantello, R, Martinelli, V, Comi, Giancarlo, Frau, J, Lorefice, L, Pugliatti, M, Rosati, G, PROGEMUS Consortium PROGRESSO, Consortium, Melis, M, Marrosu, Mg, Cusi, D, Cucca, F, Martinelli Boneschi, F, and D'Alfonso, S.

Published
2015

49. MARGINAL ZONE LYMPHOMA INTERNATIONAL PROGNOSTIC INDEX (MZL‐IPI): A PROGNOSTIC SCORE FOR THE ENTIRE SPECTRUM OF MARGINAL ZONE LYMPHOMAS. A FIL AND SPORE‐MER STUDY.

Author

Luminari, S., Bommier, C., Fabbri, N., Nizzoli, M. E., Maurer, M. J., Tarantino, V., Ferrero, S., Rattotti, S., Merli, M., Ferrari, A., Murru, R., Khurana, A., Mwangi, R., Deodato, M., Del Giudice, I., Cencini, E., Re, F., Visco, C., Feldman, A. L., and Link, B. K.

Subjects
MUCOSA-associated lymphoid tissue lymphoma, LYMPHOMAS, LYMPHOPENIA
Abstract

In the validation using the MER cohort of 192 MZL patients, 5y PFS was 57% (95% CI 51-64). Applying the MZL-IPI to the MER, 41(21%), 113 (59%), and 38 (20%) patients were classified as LRG, IRG, and HRG, respectively. B Conclusions: b MZL-IPI is a new validated prognostic score for all patients with MZL who are considered for systemic treatment. [Extracted from the article]

Published
2023
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