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2. The time to first treatment is an independent predictor of overall survival in chronic lymphocytic leukemia

Author

Morabito, Francesco, Tripepi, G., Mauro, F. R., Laurenti, Luca, Reda, G., Moia, R., Condoluci, A., Vincelli, I., Chiarenza, A., Vigna, E., Martino, E. A., Bruzzese, Maria Antonella, Mezzatesta, S., Laureana, R., Cutrona, G., Di Raimondo, F., Fronza, G., Zucchetto, A., Bomben, R., Rossi, Federica Maria, Olivieri, J., Zaja, F., Rossi, Dario, Gaidano, G., Del Principe, M. I., Ilariucci, F., Del Poeta, G., Ferrarini, M., Neri, A., Gattei, V., Gentile, M., Morabito F., Laurenti L. (ORCID:0000-0002-8327-1396), Bruzzese A., Rossi F. M., Rossi D., Morabito, Francesco, Tripepi, G., Mauro, F. R., Laurenti, Luca, Reda, G., Moia, R., Condoluci, A., Vincelli, I., Chiarenza, A., Vigna, E., Martino, E. A., Bruzzese, Maria Antonella, Mezzatesta, S., Laureana, R., Cutrona, G., Di Raimondo, F., Fronza, G., Zucchetto, A., Bomben, R., Rossi, Federica Maria, Olivieri, J., Zaja, F., Rossi, Dario, Gaidano, G., Del Principe, M. I., Ilariucci, F., Del Poeta, G., Ferrarini, M., Neri, A., Gattei, V., Gentile, M., Morabito F., Laurenti L. (ORCID:0000-0002-8327-1396), Bruzzese A., Rossi F. M., and Rossi D.

Abstract

NA

Published
2023

3. Clinical impact of TP53 disruption in chronic lymphocytic leukemia patients treated with ibrutinib: a campus CLL study

Author

Bomben, R., Rossi, Federica Maria, Vit, F., Bittolo, T., Zucchetto, A., Papotti, R., Tissino, E., Pozzo, F., Degan, M., Polesel, J., Bulian, P., Marasca, R., Reda, G., Laurenti, Luca, Olivieri, J., Chiarenza, A., Laureana, R., Postorino, M., Del Principe, M. I., Cuneo, A., Gentile, M., Morabito, Francesco, Fronza, G., Tafuri, A., Zaja, F., Foa, Robin, Di Raimondo, F., Del Poeta, G., Gattei, V., Rossi F. M., Laurenti L. (ORCID:0000-0002-8327-1396), Morabito F., Foa R., Bomben, R., Rossi, Federica Maria, Vit, F., Bittolo, T., Zucchetto, A., Papotti, R., Tissino, E., Pozzo, F., Degan, M., Polesel, J., Bulian, P., Marasca, R., Reda, G., Laurenti, Luca, Olivieri, J., Chiarenza, A., Laureana, R., Postorino, M., Del Principe, M. I., Cuneo, A., Gentile, M., Morabito, Francesco, Fronza, G., Tafuri, A., Zaja, F., Foa, Robin, Di Raimondo, F., Del Poeta, G., Gattei, V., Rossi F. M., Laurenti L. (ORCID:0000-0002-8327-1396), Morabito F., and Foa R.

Abstract

NA

Published
2023

4. Immune thrombocytopenia

Author

Bussel J., Cooper N., Boccia R., Zaja F., Newland A., Bussel, J., Cooper, N., Boccia, R., Zaja, F., and Newland, A.

Subjects
Adult, corticosteroid, Purpura, Thrombocytopenic, Idiopathic, fostamatinib, Hematology, Thrombocytopenia, splenectomy, corticosteroids, Immune thrombocytopenia, guidelines, rituximab, thrombopoietin receptor agonists, Quality of Life, Splenectomy, Humans, Rituximab, guideline
Abstract

Introduction: Primary immune thrombocytopenia (ITP) is an autoimmune disorder characterized by a low platelet count (

Published
2021
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6. Role of bone marrow biopsy in staging of patients with classical Hodgkin’s lymphoma undergoing positron emission tomography/computed tomography

Author

Puccini, B ., Nassi, L., Minoia, C., Volpetti, S., Ciancia, R., Riccomagno, P. C., Di Rocco, A., Mulè, A., Toldo, C., Sassone, M. C., Guariglia, R., Filì, C., Finolezzi, E., Falorio, S., Zanon, S., Furlan, A., Doa, G., Zaja, F., and on behalf of the Fondazione Italiana Linfomi Postgraduate Master course

Published
2017
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10. COVID-19 elicits an impaired antibody response against SARS-CoV-2 in patients with haematological malignancies

Author

Passamonti, F, Romano, A, Salvini, M, Merli, F, Porta, M, Bruna, R, Coviello, E, Romano, I, Cairoli, R, Lemoli, R, Farina, F, Venditti, A, Busca, A, Ladetto, M, Massaia, M, Pinto, A, Arcaini, L, Tafuri, A, Marchesi, F, Fracchiolla, N, Bocchia, M, Armiento, D, Candoni, A, Krampera, M, Luppi, M, Cardinali, V, Galimberti, S, Cattaneo, C, La Barbera, E, Mina, R, Lanza, F, Visani, G, Musto, P, Petrucci, L, Zaja, F, Grossi, P, Bertu, L, Pagano, L, Corradini, P, Derenzini, E, Marchetti, M, Scattolin, A, Corso, A, Tosi, P, Gherlinzoni, F, Gambacorti Passerini, C, Cavo, M, Fava, C, Turrini, M, Visco, C, Zappasodi, P, Merli, M, Mora, B, Vannucchi, A, Passamonti F., Romano A., Salvini M., Merli F., Porta M. G. D., Bruna R., Coviello E., Romano I., Cairoli R., Lemoli R., Farina F., Venditti A., Busca A., Ladetto M., Massaia M., Pinto A., Arcaini L., Tafuri A., Marchesi F., Fracchiolla N., Bocchia M., Armiento D., Candoni A., Krampera M., Luppi M., Cardinali V., Galimberti S., Cattaneo C., La Barbera E. O., Mina R., Lanza F., Visani G., Musto P., Petrucci L., Zaja F., Grossi P. A., Bertu L., Pagano L., Corradini P., Derenzini E., Marchetti M., Scattolin A. M., Corso A., Tosi P., Gherlinzoni F., Gambacorti Passerini C., Cavo M., Fava C., Turrini M., Visco C., Zappasodi P., Merli M., Mora B., Vannucchi A. M., Passamonti, F, Romano, A, Salvini, M, Merli, F, Porta, M, Bruna, R, Coviello, E, Romano, I, Cairoli, R, Lemoli, R, Farina, F, Venditti, A, Busca, A, Ladetto, M, Massaia, M, Pinto, A, Arcaini, L, Tafuri, A, Marchesi, F, Fracchiolla, N, Bocchia, M, Armiento, D, Candoni, A, Krampera, M, Luppi, M, Cardinali, V, Galimberti, S, Cattaneo, C, La Barbera, E, Mina, R, Lanza, F, Visani, G, Musto, P, Petrucci, L, Zaja, F, Grossi, P, Bertu, L, Pagano, L, Corradini, P, Derenzini, E, Marchetti, M, Scattolin, A, Corso, A, Tosi, P, Gherlinzoni, F, Gambacorti Passerini, C, Cavo, M, Fava, C, Turrini, M, Visco, C, Zappasodi, P, Merli, M, Mora, B, Vannucchi, A, Passamonti F., Romano A., Salvini M., Merli F., Porta M. G. D., Bruna R., Coviello E., Romano I., Cairoli R., Lemoli R., Farina F., Venditti A., Busca A., Ladetto M., Massaia M., Pinto A., Arcaini L., Tafuri A., Marchesi F., Fracchiolla N., Bocchia M., Armiento D., Candoni A., Krampera M., Luppi M., Cardinali V., Galimberti S., Cattaneo C., La Barbera E. O., Mina R., Lanza F., Visani G., Musto P., Petrucci L., Zaja F., Grossi P. A., Bertu L., Pagano L., Corradini P., Derenzini E., Marchetti M., Scattolin A. M., Corso A., Tosi P., Gherlinzoni F., Gambacorti Passerini C., Cavo M., Fava C., Turrini M., Visco C., Zappasodi P., Merli M., Mora B., and Vannucchi A. M.

Abstract

COVID-19 is associated with high mortality in patients with haematological malignancies (HM) and rate of seroconversion is unknown. The ITA-HEMA-COV project (NCT04352556) investigated patterns of seroconversion for SARS-CoV-2 IgG in patients with HMs. A total of 237 patients, SARS-CoV-2 PCR-positive with at least one SARS-CoV-2 IgG test performed during their care, entered the analysis. Among these, 62 (26·2%) had myeloid, 121 (51·1%) lymphoid and 54 (22·8%) plasma cell neoplasms. Overall, 69% of patients (164 of 237) had detectable IgG SARS-CoV-2 serum antibodies. Serologically negative patients (31%, 73 of 237) were evenly distributed across patients with myeloid, lymphoid and plasma cell neoplasms. In the multivariable logistic regression, chemoimmunotherapy [odds ratio (OR), 3·42; 95% confidence interval (CI), 1·04–11·21; P = 0·04] was associated with a lower rate of seroconversion. This effect did not decline after 180 days from treatment withdrawal (OR, 0·35; 95% CI: 0·11–1·13; P = 0·08). This study demonstrates a low rate of seroconversion in HM patients and indicates that treatment-mediated immune dysfunction is the main driver. As a consequence, we expect a low rate of seroconversion after vaccination and thus we suggest testing the efficacy of seroconversion in HM patients.

Published
2021

14. S136: CONSTITUTIVE VLA-4 ACTIVATION IN CHRONIC LYMPHOCYTIC LEUKEMIA. THE OTHER SIDE OF BCR AUTONOMOUS SIGNALING.

Author

Tissino, E., primary, Bomben, R., additional, Maity, P. C., additional, Pozzo, F., additional, Forestieri, G., additional, Nicolò, A., additional, Härzschel, A., additional, Bittolo, T., additional, Rossi, F. M., additional, Datta, M., additional, Zaja, F., additional, Capasso, G., additional, D’Arena, G., additional, Chiarenza, A., additional, Di Raimondo, F., additional, Jumaa, H., additional, Rossi, D., additional, Del Poeta, G., additional, Hartmann, T. N., additional, Zucchetto, A., additional, and Gattei, V., additional

Published
2022
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15. S292: SUSTAINED RESPONSE OFF TREATMENT IN ELTROMBOPAG-TREATED PATIENTS WITH ITP WHO ARE REFRACTORY OR RELAPSED AFTER FIRST-LINE STEROIDS: PRIMARY ANALYSIS OF THE PHASE II TAPER TRIAL

Author

Cooper, N., primary, Ghanima, W., additional, Vianelli, N., additional, Valcárcel, D., additional, Yavaşoğlu, I., additional, Melikyan, A., additional, Yañez Ruiz, E., additional, Haenig, J., additional, Lee, J., additional, Maier, J., additional, Zolkin, N., additional, and Zaja, F., additional

Published
2022
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16. PB2307: A MULTICENTER, RANDOMIZED, OPEN-LABEL STUDY OF ROMIPLOSTIM PLUS DEXAMETHASONE VS DEXAMETHASONE IN PATIENTS WITH NEWLY DIAGNOSED PRIMARY IMMUNE THROMBOCYTOPENIA

Author

Mingot Castellano, M. E., primary, Bradbury, C. A., additional, Rosso Fernández, C., additional, Thomas, I., additional, Alvarez-Román, M. T., additional, Canaro, M., additional, Caparrós Miranda, I. S., additional, Cappechi, M., additional, Carpenedo, M., additional, Evans, G., additional, González-Lopéz, J. T., additional, González-Porras, J. R., additional, Jarque Ramos, I., additional, Lozano-Almela, M. L., additional, Lopez Fernandez, M. F., additional, Lowe, G., additional, Lyall, H., additional, Pascual Izquierdo, C., additional, Pavord, S., additional, Rayment, R., additional, Roberts, P., additional, Rosique Cortina, P., additional, Sánchez-González, B., additional, Santoro, C., additional, Talks, K., additional, Valcarcel-Ferreiras, D., additional, and Zaja, F., additional

Published
2022
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18. P596: CLINICAL IMPACT OF TP53 DISRUPTION IN CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS TREATED WITH A BCR INHIBITOR. A CAMPUS CLL EXPERIENCE

Author

Bomben, R., primary, Rossi, F. M., additional, Vit, F., additional, Bittolo, T., additional, Zucchetto, A., additional, Papotti, R., additional, Tissino, E., additional, Pozzo, F., additional, Degan, M., additional, Zaina, E., additional, Cattarossi, I., additional, Nanni, P., additional, Marasca, R., additional, Reda, G., additional, Laurenti, L., additional, Olivieri, J., additional, Chiarenza, A., additional, Ballotta, L., additional, Cuneo, A., additional, Gentile, M., additional, Morabito, F., additional, Tafuri, A., additional, Zaja, F., additional, Foà, R., additional, Di Raimondo, F., additional, Del Poeta, G., additional, and Gattei, V., additional

Published
2022
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19. Efficacy and safety assessment of prolonged maintenance with subcutaneous rituximab in patients with relapsed or refractory indolent non-Hodgkin lymphoma: results of the phase Ill MabCute study

Author

Rule, S, Barreto, WG, Briones, J, Carella, AM, Casasnovas, O, Pocock, C, Wendtner, CM, Zaja, F, Robson, S, MacGregor, L, Tschopp, RR, Nick, S, and Dreyling, M

Abstract

Rituximab plus chemotherapy induction followed by rituximab maintenance for up to 2 years confers a long-term benefit in terms of progression-free survival in patients with indolent non-Hodgkin lymphoma. It is not known whether further prolonged maintenance with rituximab provides additional benefit. The phase III MabCute study enrolled 692 patients with relapsed or refractory indolent non-Hodgkin lymphoma. Patients who responded to induction with rituximab plus chemotherapy and were still responding after up to 2 years' initial maintenance with subcutaneous rituximab were randomized to extended maintenance with subcutaneous rituximab (n=138) or observation only (n=138). The primary endpoint of investigator-assessed progression-free survival in the randomized population was un-addressed by the end of study because of an insufficient number of events (129 events were needed for 80% power at 5% significance if approximately 330 patients were randomized). In total, there were 46 progression-free survival events, 19 and 27 in the rituximab and observation arms, respectively (P=0.410 by stratified log-rank test; hazard ratio 0.76 [95% confidence interval: 0.37-1.53]). The median progression-free survival was not reached in either randomized arm. There were no new safety signals; however, adverse events were seen slightly more frequently with rituximab than with observation during extended maintenance. Maintenance for up to 2 years with rituximab after response to initial induction therefore remains the standard of care in patients with relapsed or refractory indolent non-Hodgkin lymphoma.

Published
2022

20. Corrigendum: 'Venetoclax in combination with hypomethylating agents in previously untreated patients with acute myeloid leukemia ineligible for intensive treatment: a real-life multicenter experience' (Leukemia Research (2022) 114, (106803), (S0145212622000297), (10.1016/j.leukres.2022.106803))

Author

De Bellis, E., Imbergamo, S., Candoni, A., Lico, A., Tanasi, I., Mauro, E., Mosna, F., Leoncin, M., Stulle, M., Griguolo, D., Pravato, S., Trentin, L., Lazzarotto, D., Di Bona, E., Sancetta, R., Lucchini, E., Poiani, M., Palmieri, C., and Zaja, F.

Published
2022

21. Corrigendum to 'Venetoclax in combination with hypomethylating agents in previously untreated patients with acute myeloid leukemia ineligible for intensive treatment: a real-life multicenter experience' [Leukemia Res. 114 (March 2022) 106803](S0145212622000297)(10.1016/j.leukres.2022.106803)

Author

De Bellis, E., Imbergamo, S., Candoni, A., Lico, A., Tanasi, I., Mauro, E., Mosna, F., Leoncin, M., Stulle, M., Griguolo, D., Pravato, S., Trentin, L., Lazzarotto, D., Di Bona, E., Sancetta, R., Lucchini, E., Poiani, M., Palmieri, C., and Zaja, F.

Published
2022

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

Author

Cortelezzi, A, Sciumè, M, Liberati, A M, Vincenti, D, Cuneo, A, Reda, G, Laurenti, L, Zaja, F, Marasca, R, Chiarenza, A, Gritti, G, Orsucci, L, Storti, S, Angelucci, E, Cascavilla, N, Gobbi, M, Mauro, F R, Morabito, F, Fabris, S, Piciocchi, A, Vignetti, M, Neri, A, Rossi, D, Giannarelli, D, Guarini, A, and Foà, R

Published
2014
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24. SF3B1-mutated chronic lymphocytic leukemia shows evidence of NOTCH1 pathway activation including CD20 downregulation

Author

Pozzo, F, Bittolo, T, Tissino, E, Vit, F, Vendramini, E, Laurenti, L, D'Arena, G, Olivieri, J, Pozzato, G, Zaja, F, Chiarenza, A, Di Raimondo, F, Zucchetto, A, Bomben, R, Rossi, Fm, Del Poeta, G, Dal Bo, M, Gattei, V., Pozzo, F, Bittolo, T, Tissino, E, Vit, F, Vendramini, E, Laurenti, L, D'Arena, G, Olivieri, J, Pozzato, G, Zaja, F, Chiarenza, A, Di Raimondo, F, Zucchetto, A, Bomben, R, Rossi, Fm, Del Poeta, G, Dal Bo, M, and Gattei, V.

Subjects
Down-Regulation, Article, NOTCH1, immune system diseases, hemic and lymphatic diseases, Humans, CD20, Receptor, Notch1, Antigens, Chronic, neoplasms, CLL, SF3B1, Notch1, Leukemia, B-Cell, Antigens, CD20, Phosphoproteins, Prognosis, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphocytic, Settore MED/15 - MALATTIE DEL SANGUE, embryonic structures, Mutation, cardiovascular system, RNA Splicing Factors, Receptor
Abstract

Chronic lymphocytic leukemia (CLL) is characterized by a low CD20 expression, in part explained by an epigenetic-driven downregulation triggered by mutations of the NOTCH1 gene. In the present study, by taking advantage of a wide and well-characterized CLL cohort (n=537), we demonstrate that CD20 expression is downregulated in SF3B1-mutated CLL in an extent similar to NOTCH1-mutated CLL. In fact, SF3B1-mutated CLL cells show common features with NOTCH1-mutated CLL cells, including a gene expression profile enriched of NOTCH1-related gene sets and elevated expression of the active intracytoplasmic NOTCH1. Activation of the NOTCH1 signaling and down-regulation of surface CD20 in SF3B1-mutated CLL cells correlate with over-expression of an alternatively spliced form of DVL2, a component of the Wnt pathway and negative regulator of the NOTCH1 pathway. These findings are confirmed by separately analyzing the CD20-dim and CD20-bright cell fractions from SF3B1-mutated cases as well as by DVL2 knock-out experiments in CLL-like cell models. Altogether, the clinical and biological features that characterize NOTCH1-mutated CLL may also be recapitulated in SF3B1-mutated CLL, contributing to explain the poor prognosis of this CLL subset and providing the rationale for expanding novel agents-based therapies to SF3B1-mutated CLL.

Published
2020

25. COVID-19 elicits an impaired antibody response against SARS-CoV-2 in patients with haematological malignancies

Author

Passamonti, F., Romano, A., Salvini, M., Merli, F., Porta, M. G. D., Bruna, R., Coviello, E., Romano, I., Cairoli, R., Lemoli, R., Farina, F., Venditti, A., Busca, A., Ladetto, M., Massaia, M., Pinto, A., Arcaini, L., Tafuri, A., Marchesi, F., Fracchiolla, N., Bocchia, M., Armiento, D., Candoni, A., Krampera, M., Luppi, M., Cardinali, V., Galimberti, S., Cattaneo, C., La Barbera, E. O., Mina, R., Lanza, F., Visani, G., Musto, P., Petrucci, L., Zaja, F., Grossi, P. A., Bertu, L., Pagano, Livio, Corradini, P., Derenzini, E., Marchetti, M., Scattolin, A. M., Corso, A., Tosi, P., Gherlinzoni, F., Passerini, C. G., Cavo, M., Fava, C., Turrini, M., Visco, C., Zappasodi, P., Merli, M., Mora, B., Vannucchi, A. M., Pagano L. (ORCID:0000-0001-8287-928X), Passamonti, F., Romano, A., Salvini, M., Merli, F., Porta, M. G. D., Bruna, R., Coviello, E., Romano, I., Cairoli, R., Lemoli, R., Farina, F., Venditti, A., Busca, A., Ladetto, M., Massaia, M., Pinto, A., Arcaini, L., Tafuri, A., Marchesi, F., Fracchiolla, N., Bocchia, M., Armiento, D., Candoni, A., Krampera, M., Luppi, M., Cardinali, V., Galimberti, S., Cattaneo, C., La Barbera, E. O., Mina, R., Lanza, F., Visani, G., Musto, P., Petrucci, L., Zaja, F., Grossi, P. A., Bertu, L., Pagano, Livio, Corradini, P., Derenzini, E., Marchetti, M., Scattolin, A. M., Corso, A., Tosi, P., Gherlinzoni, F., Passerini, C. G., Cavo, M., Fava, C., Turrini, M., Visco, C., Zappasodi, P., Merli, M., Mora, B., Vannucchi, A. M., and Pagano L. (ORCID:0000-0001-8287-928X)

Abstract

COVID-19 is associated with high mortality in patients with haematological malignancies (HM) and rate of seroconversion is unknown. The ITA-HEMA-COV project (NCT04352556) investigated patterns of seroconversion for SARS-CoV-2 IgG in patients with HMs. A total of 237 patients, SARS-CoV-2 PCR-positive with at least one SARS-CoV-2 IgG test performed during their care, entered the analysis. Among these, 62 (26·2%) had myeloid, 121 (51·1%) lymphoid and 54 (22·8%) plasma cell neoplasms. Overall, 69% of patients (164 of 237) had detectable IgG SARS-CoV-2 serum antibodies. Serologically negative patients (31%, 73 of 237) were evenly distributed across patients with myeloid, lymphoid and plasma cell neoplasms. In the multivariable logistic regression, chemoimmunotherapy [odds ratio (OR), 3·42; 95% confidence interval (CI), 1·04–11·21; P = 0·04] was associated with a lower rate of seroconversion. This effect did not decline after 180 days from treatment withdrawal (OR, 0·35; 95% CI: 0·11–1·13; P = 0·08). This study demonstrates a low rate of seroconversion in HM patients and indicates that treatment-mediated immune dysfunction is the main driver. As a consequence, we expect a low rate of seroconversion after vaccination and thus we suggest testing the efficacy of seroconversion in HM patients.

Published
2021

29. RESPONSE ADAPTED POST INDUCTION THERAPY IN FOLLICULAR LYMPHOMA: UPDATED RESULTS OF THE FOLL12 TRIAL BY THE FONDAZIONE ITALIANA LINFOMI (FIL)

Author

Luminari, S., primary, Galimberti, S., additional, Versari, A., additional, Tucci, A., additional, Boccomini, C., additional, Farina, L., additional, Zaja, F., additional, Marcheselli, L., additional, Ferrero, S., additional, Arcaini, L., additional, Pulsoni, A., additional, Musuraca, G., additional, Califano, C., additional, Merli, M., additional, Bari, A., additional, Conconi, A., additional, Giudice, I. del, additional, Re, F., additional, Stefani, P. M., additional, Usai, S. V., additional, Perrone, T., additional, Gini, G., additional, Falini, B., additional, Gattei, V., additional, Manni, M., additional, Ladetto, M., additional, Mannina, D., additional, and Federico, M., additional

Published
2021
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30. Alternate use of thrombopoietin receptor agonists in adult primary immune thrombocytopenia patients: A retrospective collaborative survey from Italian hematology centers

Author

Cantoni, S, Carpenedo, M, Mazzucconi, M, De Stefano, V, Carrai, V, Ruggeri, M, Specchia, G, Vianelli, N, Pane, F, Consoli, U, Artoni, A, Zaja, F, D'Adda, M, Visentin, A, Ferrara, F, Barcellini, W, Caramazza, D, Baldacci, E, Rossi, E, Ricco, A, Ciminello, A, Rodeghiero, F, Nichelatti, M, Cairoli, R, Cantoni S, Carpenedo M, Mazzucconi MG, De Stefano V, Carrai V, Ruggeri M, Specchia G, Vianelli N, Pane F, Consoli U, Artoni A, Zaja F, D'adda M, Visentin A, Ferrara F, Barcellini W, Caramazza D, Baldacci E, Rossi E, Ricco A, Ciminello A, Rodeghiero F, Nichelatti M, Cairoli R, Cantoni, S, Carpenedo, M, Mazzucconi, M, De Stefano, V, Carrai, V, Ruggeri, M, Specchia, G, Vianelli, N, Pane, F, Consoli, U, Artoni, A, Zaja, F, D'Adda, M, Visentin, A, Ferrara, F, Barcellini, W, Caramazza, D, Baldacci, E, Rossi, E, Ricco, A, Ciminello, A, Rodeghiero, F, Nichelatti, M, Cairoli, R, Cantoni S, Carpenedo M, Mazzucconi MG, De Stefano V, Carrai V, Ruggeri M, Specchia G, Vianelli N, Pane F, Consoli U, Artoni A, Zaja F, D'adda M, Visentin A, Ferrara F, Barcellini W, Caramazza D, Baldacci E, Rossi E, Ricco A, Ciminello A, Rodeghiero F, Nichelatti M, and Cairoli R

Abstract

Sequential use of the TPO-RAs romiplostim and eltrombopag in ITP patients failing either agent was retrospectively evaluated to assess efficacy and impact of clinical characteristics on outcome. Patients were grouped into 5 categories: efficacy issues: 1st TPO-RA failure; loss of response; non-efficacy issues: platelet fluctuations; patient's preference; adverse event development. Either one TPO-RA sequence was analyzed at 3 month and at last follow-up. 106/546 patients on TPO-RA underwent switch and 65% achieved, regained or maintained a short- term response independent of switch sequence, gender or age; lower response rates were associated with lines of previous therapy; disease duration lowers probability to respond. Clinically, patients switched for efficacy issue did not differ from those switched for non-efficacy issues. Response was achieved/regained in 57.8% of patients switched for efficacy issues, the lowest response rates were observed in non-responders to 1st TPO-RA; 80% of patients switched for non-efficacy issues maintained a response. Platelet fluctuation resolved in 44.4%. Of the 49 patients evaluable for long-term outcome, 27 were in response on therapy; 16 discontinued the TPO-RA for reasons other than efficacy, while only 6 were non responders. We confirm the efficacy of TPO-RA switch; once achieved, response to the 2nd TPO-RA seems durable.

Published
2018

32. SF3B1-mutated chronic lymphocytic leukemia shows evidence of NOTCH1 pathway activation including CD20 downregulation

Author

Pozzo, F., Bittolo, T., Tissino, E., Vit, F., Vendramini, E., Laurenti, Luca, D'Arena, G., Olivieri, J., Pozzato, G., Zaja, F., Chiarenza, A., Di Raimondo, F., Zucchetto, A., Bomben, R., Rossi, Federica Maria, Del Poeta, G., Dal Bo, M., Gattei, V., Laurenti L. (ORCID:0000-0002-8327-1396), Rossi F. M., Pozzo, F., Bittolo, T., Tissino, E., Vit, F., Vendramini, E., Laurenti, Luca, D'Arena, G., Olivieri, J., Pozzato, G., Zaja, F., Chiarenza, A., Di Raimondo, F., Zucchetto, A., Bomben, R., Rossi, Federica Maria, Del Poeta, G., Dal Bo, M., Gattei, V., Laurenti L. (ORCID:0000-0002-8327-1396), and Rossi F. M.

Abstract

Chronic lymphocytic leukemia (CLL) is characterized by a low CD20 expression, in part explained by an epigenetic-driven downregulation triggered by mutations of the NOTCH1 gene. In the present study, by taking advantage of a wide and well-characterized CLL cohort (n=537), we demonstrate that CD20 expression is downregulated in SF3B1-mutated CLL in an extent similar to NOTCH1-mutated CLL. In fact, SF3B1-mutated CLL cells show common features with NOTCH1-mutated CLL cells, including a gene expression profile enriched of NOTCH1-related gene sets and elevated expression of the active intracytoplasmic NOTCH1. Activation of the NOTCH1 signaling and down-regulation of surface CD20 in SF3B1-mutated CLL cells correlate with over-expression of an alternatively spliced form of DVL2, a component of the Wnt pathway and negative regulator of the NOTCH1 pathway. These findings are confirmed by separately analyzing the CD20-dim and CD20-bright cell fractions from SF3B1-mutated cases as well as by DVL2 knock-out experiments in CLL-like cell models. Altogether, the clinical and biological features that characterize NOTCH1-mutated CLL may also be recapitulated in SF3B1-mutated CLL, contributing to explain the poor prognosis of this CLL subset and providing the rationale for expanding novel agents-based therapies to SF3B1-mutated CLL.

Published
2020

33. CD49d promotes disease progression in chronic lymphocytic leukemia: New insights from CD49d bimodal expression

Author

Tissino, E., Pozzo, F., Benedetti, D., Caldana, C., Bittolo, T., Rossi, Federica Maria, Bomben, R., Nanni, P., Chivilo, H., Cattarossi, I., Zaina, Elisabetta, Norris, K., Polesel, J., Gentile, Marino, Tripepi, G., Moia, R., Santinelli, E., Innocenti, Idanna, Olivieri, J., D'Arena, G., Laurenti, Luca, Zaja, F., Pozzato, G., Chiarenza, A., Di Raimondo, F., Rossi, Dario, Pepper, C., Hartmann, T. N., Gaidano, G., Del Poeta, G., Gattei, V., Zucchetto, A., Rossi F. M., Zaina E., Gentile M., Innocenti I., Laurenti L. (ORCID:0000-0002-8327-1396), Rossi D., Tissino, E., Pozzo, F., Benedetti, D., Caldana, C., Bittolo, T., Rossi, Federica Maria, Bomben, R., Nanni, P., Chivilo, H., Cattarossi, I., Zaina, Elisabetta, Norris, K., Polesel, J., Gentile, Marino, Tripepi, G., Moia, R., Santinelli, E., Innocenti, Idanna, Olivieri, J., D'Arena, G., Laurenti, Luca, Zaja, F., Pozzato, G., Chiarenza, A., Di Raimondo, F., Rossi, Dario, Pepper, C., Hartmann, T. N., Gaidano, G., Del Poeta, G., Gattei, V., Zucchetto, A., Rossi F. M., Zaina E., Gentile M., Innocenti I., Laurenti L. (ORCID:0000-0002-8327-1396), and Rossi D.

Abstract

CD49d is a remarkable prognostic biomarker of chronic lymphocytic leukemia (CLL). The cutoff value for the extensively validated 30% of positive CLL cells is able to separate CLL patients into 2 subgroups with different prognoses, but it does not consider the pattern of CD49d expression. In the present study, we analyzed a cohort of 1630 CLL samples and identified the presence of ∼20% of CLL cases (n 5 313) characterized by a bimodal expression of CD49d, that is, concomitant presence of a CD49d1 subpopulation and a CD49d2 subpopulation. At variance with the highly stable CD49d expression observed in CLL patients with a homogeneous pattern of CD49d expression, CD49d bimodal CLL showed a higher level of variability in sequential samples, and an increase in the CD49d1 subpopulation over time after therapy. The CD49d1 subpopulation from CD49d bimodal CLL displayed higher levels of proliferation compared with the CD49d2 cells; and was more highly represented in the bone marrow compared with peripheral blood (PB), and in PB CLL subsets expressing the CXCR4dim/CD5bright phenotype, known to be enriched in proliferative cells. From a clinical standpoint, CLL patients with CD49d bimodal expression, regardless of whether the CD49d1 subpopulation exceeded the 30% cutoff or not, experienced clinical behavior similar to CD49d1 CLL, both in chemoimmunotherapy (n 5 1522) and in ibrutinib (n 5 158) settings. Altogether, these results suggest that CD49d can drive disease progression in CLL, and that the pattern of CD49d expression should also be considered to improve the prognostic impact of this biomarker in CLL.

Published
2020

39. Effect of Recombinant Zoster Vaccine on Incidence of Herpes Zoster After Autologous Stem Cell Transplantation A Randomized Clinical Trial

Author

Bastidas, A, de la Serna, J, El Idrissi, M, Oostvogels, L, Quittet, P, Lopez-Jimenez, J, Vural, F, Pohlreich, D, Zuckerman, T, Issa, NC, Gaidano, G, Lee, JJ, Abhyankar, S, Solano, C, de Oteyza, JP, Satlin, MJ, Schwartz, S, Campins, M, Rocci, A, Llamas, CV, Lee, DG, Tan, SM, Johnston, AM, Grigg, A, Boeckh, MJ, Campora, L, Lopez-Fauqued, M, Heineman, TC, Stadtmauer, EA, Sullivan, KM, Alonso, AA, Anagnostopoulos, A, Andreadis, C, Angelopoulou, M, Anttila, VJ, Aoun, M, Barista, I, Berkahn, L, Bloor, AJC, Broady, R, Brossart, P, Buadi, FK, Bulabois, CE, Cantin, G, Cellini, C, Chandrasekar, PH, Chauncey, T, Cuneo, A, Dadwal, SS, Dickinson, M, Eom, H, Sanfeliu, AE, Coll, CF, Flomenberg, PR, Gonzalez-Rodriguez, AP, Gottlieb, DJ, Grisariu, S, Guenther, A, Gutman, J, Hahn, U, Heinz, WJ, Heras, I, Ikeda, T, Jarque, I, Karthaus, M, Kerre, T, Kiani, A, Klein, AK, Kofla, G, Kryuchkova, IV, Kuo, CY, Kuruvilla, J, Kuvshinov, A, Kwak, JY, Lee, JH, Lepretre, S, Lie, AKW, Lucchesi, A, Maertens, J, Marijt, EWA, Munoz, CM, Michieli, M, Milliken, ST, Milpied, N, Coll, JM, Mossad, SB, Murphy, J, Matilla, MBN, Novak, J, Olney, HJ, Navarrete, RO, Cascon, MJP, Peniket, A, Penka, G, Piatkowska-Jakubas, B, Zarzuela, MP, Quiel, D, Rowley, SD, Sabry, W, Salmi, TM, Selleslag, DLD, Shea, TC, Silling, G, Sinisalo, UM, Sohn, SK, Staib, P, Szer, J, Theunissen, K, Topcuoglu, P, Tyurina, NG, Uvarov, M, Wahid, FSA, San Segundo, LY, Yegin, ZA, Yeh, SP, Yip, SF, Yoon, SS, Young, JAH, Zachee, P, Zaja, F, and ZOE-HSCT Study Grp Collaborators

Abstract

IMPORTANCE Herpes zoster, a frequent complication following autologous hematopoietic stem cell transplantation (HSCT), is associated with significant morbidity. A nonlive adjuvanted recombinant zoster vaccine has been developed to prevent posttransplantation zoster. OBJECTIVE To assess the efficacy and adverse event profile of the recombinant zoster vaccine in immunocompromised autologous HSCT recipients. DESIGN, SETTING, AND PARTICIPANTS Phase 3, randomized, observer-blinded study conducted in 167 centers in 28 countries between July 13, 2012, and February 1, 2017, among 1846 patients aged 18 years or older who had undergone recent autologous HSCT. INTERVENTIONS Participants were randomized to receive 2 doses of either recombinant zoster vaccine (n=922) or placebo (n=924) administered into the deltoid muscle; the first dose was given 50 to 70 days after transplantation and the second dose 1 to 2 months thereafter. MAIN OUTCOMES AND MEASURES The primary end point was occurrence of confirmed herpes zoster cases. RESULTS Among 1846 autologous HSCT recipients (mean age, 55 years; 688 [37%] women) who received 1 vaccine or placebo dose, 1735 (94%) received a second dose and 1366 (74%) completed the study. During the 21-month median follow-up, at least 1 herpes zoster episode was confirmed in 49 vaccine and 135 placebo recipients (incidence, 30 and 94 per 1000 person-years, respectively), an incidence rate ratio (IRR) of 0.32 (95% CI, 0.22-0.44; P

Published
2019

43. Rituximab-responsive CIDP

Author

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

Published
2004

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

Author

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

Subjects
Hematology
Published
2017

48. S104 THE BRAF INHIBITOR VEMURAFENIB COMBINED WITH RITUXIMAB PRODUCES A HIGH RATE OF DEEP AND DURABLE REMISSIONS IN RELAPSED OR REFRACTORY HAIRY CELL LEUKEMIA: UPDATED RESULTS OF A PHASE-2 TRIAL

Author

Tiacci, E., primary, De Carolis, L., additional, Simonetti, E., additional, Zaja, F., additional, Capponi, M., additional, Ambrosetti, A., additional, Lucia, E., additional, Antolino, A., additional, Pulsoni, A., additional, Ferrari, S., additional, Zinzani, P. L., additional, Rigacci, L., additional, Gaidano, G., additional, Della Seta, R., additional, Frattarelli, N., additional, Falcucci, P., additional, Visani, G., additional, Foà, R., additional, and Falini, B., additional

Published
2019
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49. PS1127 SF3B1 MUTATIONS ASSOCIATE WITH LOW CD20 EXPRESSION IN CLL: ANOTHER NOTCH1-DEPENDENT MECHANISM?

Author

Pozzo, F., primary, Bittolo, T., additional, Bomben, R., additional, Zucchetto, A., additional, Vendramini, E., additional, Laurenti, L., additional, D’Arena, G., additional, Raimondo, F. Di, additional, Chiarenza, A., additional, Zaja, F., additional, Pozzato, G., additional, Poeta, G. Del, additional, Bo, M. Dal, additional, and Gattei, V., additional

Published
2019
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50. PF695 ELTROMBOPAG AS SECOND LINE THERAPY IN ADULT PATIENTS WITH PRIMARY IMMUNE THROMBOCYTOPENIA (ITP) IN ATTEMPT TO TREATMENT-FREE REMISSION. UPDATED RESULTS OF A PHASE II PROSPECTIVE STUDY BY GIMEMA GROUP

Author

Lucchini, E., primary, Palandri, F., additional, Volpetti, S., additional, Vianelli, N., additional, Auteri, G., additional, Rossi, E., additional, Patriarca, A., additional, Carli, G., additional, Barcellini, W., additional, Rotondo, F., additional, Consoli, U., additional, Valeri, F., additional, Santoro, C., additional, Crea, E., additional, Vignetti, M., additional, Boggio, E., additional, Dianzani, U., additional, Giardini, I., additional, Carpenedo, M., additional, Rodeghiero, F., additional, Fanin, R., additional, and Zaja, F., additional

Published
2019
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