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2. Predictive value on advance hodgkin lymphoma treatment outcome of end-of treatment FDG PET/CT in the HD0607 clinical trial

Author

Biggi, A, Chauvie, S, Fallanca, F, Guerra, L, Bergesio, F, Menga, M, Bianchi, A, Gregianin, M, Chiaravalloti, A, Schillaci, O, Pavoni, C, Patti, C, Picardi, M, Romano, A, Schiavotto, C, Sorasio, R, Viviani, S, La Nasa, G, Trentin, L, Rambaldi, A, Gallamini, A, Biggi A., Chauvie S., Fallanca F., Guerra L., Bergesio F., Menga M., Bianchi A., Gregianin M., Chiaravalloti A., Schillaci O., Pavoni C., Patti C., Picardi M., Romano A., Schiavotto C., Sorasio R., Viviani S., La Nasa G., Trentin L., Rambaldi A., Gallamini A., Biggi, A, Chauvie, S, Fallanca, F, Guerra, L, Bergesio, F, Menga, M, Bianchi, A, Gregianin, M, Chiaravalloti, A, Schillaci, O, Pavoni, C, Patti, C, Picardi, M, Romano, A, Schiavotto, C, Sorasio, R, Viviani, S, La Nasa, G, Trentin, L, Rambaldi, A, Gallamini, A, Biggi A., Chauvie S., Fallanca F., Guerra L., Bergesio F., Menga M., Bianchi A., Gregianin M., Chiaravalloti A., Schillaci O., Pavoni C., Patti C., Picardi M., Romano A., Schiavotto C., Sorasio R., Viviani S., La Nasa G., Trentin L., Rambaldi A., and Gallamini A.

Abstract

The Lugano classification for response assessment in lymphoma recommends the use of the 5-point-scale Deauville Score (DS) to assess response evaluation of end-of-treatment FDG-PET/CT (eotPET) in Hodgkin Lymphoma (HL); nevertheless, there is a paucity of data on its accuracy and reproducibility. We focus here on the cohort of advanced stage IIb-IV HL patients enrolled in the HD0607 clinical trial (NCT identifier 00795613) that having had a negative interim PET performed 6 cycles of ABVD (Doxorubicin, Vinblastine, Vincristine and Dacarbazine) and then performed an eotPET. Negative patients were randomized to radiotherapy and no further treatment while positive patients were treated based on local policies. eotPET was re-evaluated independently by two readers evaluated and progression free survival was analysed (PFS). eotPET of 254 patients were analysed. The median follow-up was 43 months. The best receiver operator characteristics cut-off values to distinguish positive and negative patients was 4. The area-under-the-curve was 0.81 (95%CI, 0.70–0.91). Three-years PFS was 0.95 (95% CI 0.90–0.97) in eotPET negative and 0.22 (95% CI 0.11–0.43) in eotPET positive. DS demonstrated a good reproducibility of positivity/negativity between the readers consensus and local site evaluation where the agreement occurred on 95.0% of patients. The present study demonstrates that eotPET is an accurate tool to predict treatment outcome in HL and confirms the appropriateness of the Lugano classification for eotPET evaluation.

Published
2023

3. Integrating biological HLA-DPB1 mismatch models to predict survival after unrelated hematopoietic cell transplantation

Author

Ruggeri, A, de Wreede, L, Muller, C, Crivello, P, Bonneville, E, Petersdorf, E, Socie, G, Dubois, V, Niittyvuopio, R, Perasaari, J, Yakoub-Agha, I, Cornelissen, J, Wieten, L, Gedde-Dahl, T, Forcade, E, Crawley, C, Marsh, S, Gandemer, V, Tholouli, E, Bulabois, C, Huynh, A, Choi, G, Deconinck, E, Itala-Remes, M, Lenhoff, S, Bengtsson, M, Johansson, J, van Gorkom, G, Hoogenboom, J, Vago, L, Rocha, V, Bonini, C, Chabannon, C, Fleischhauer, K, Clausen, J, Holter, W, Kalhs, P, Beguin, Y, Bron, D, Deeren, D, Lung, W, Kerre, T, Poire, X, Selleslag, D, Schroyens, W, Jindra, P, Mayer, J, Vydra, J, Zak, P, Nielsen, B, Sengeloev, H, Kaare, A, Partanen, A, Bay, J, Bertrand, Y, Blaise, D, Bourhis, J, Chevallier, P, Cluzeau, T, Damaj, G, Fegueux, N, Guyotat, D, Hunault-Berger, M, Labussiere-Wallet, H, Leleu, X, Lioure, B, Maury, S, Michel, G, Mohty, M, Rubio, M, Tilly, H, Turlure, P, Bethge, W, Casper, J, Einsele, H, Ganser, A, Kroger, N, Martin, S, Platzbecker, U, Reinhardt, C, Schafer-Eckart, K, Thurner, L, Valerius, T, Wulf, G, Karakasis, D, Spyridonidis, A, Hauser, P, Remenyi, P, Reykdal, S, Mousavi, A, Angelucci, E, Arcese, W, Benedetti, F, Bernasconi, P, Biondi, A, Bonifazi, F, Carella, A, Carluccio, P, Casini, M, Cavanna, L, Ciceri, F, Cimino, G, Corradini, P, Fanin, R, Galieni, P, Grillo, G, Iori, A, La Nasa, G, Locatelli, F, Marotta, G, Martino, M, Mazza, P, Mordini, N, Musso, M, Olivieri, A, Pavone, V, Pane, F, Petrini, M, Pioltelli, P, Rambaldi, A, Ruggeri, M, Saccardi, R, Santarone, S, Scime, R, Sica, S, Tarella, C, Velardi, A, Visani, G, Zecca, M, Tanase, A, Kulagin, A, Savchenko, V, Lopez, C, Amor, A, Lopez, J, Caballero, D, Duarte, R, Cascon, M, Porras, R, Perez-Simon, J, Rovira, M, Sanz, J, Carrete, J, Cammenga, J, Isaksson, C, Mielke, S, Chalandon, Y, Passweg, J, Schanz, U, Meijer, E, Kuball, J, Veelken, J, Apperley, J, Bloor, A, Byrne, J, Carpenter, B, Clark, A, Collin, M, Craddock, C, Gibson, B, Khan, A, Martin, M, Medd, P, Nicholson, E, Orchard, K, Patel, A, Peniket, A, Potter, V, Snowden, J, Wilson, K, Ruggeri A., de Wreede L. C., Muller C. R., Crivello P., Bonneville E. F., Petersdorf E. W., Socie G., Dubois V., Niittyvuopio R., Perasaari J., Yakoub-Agha I., Cornelissen J. J., Wieten L., Gedde-Dahl T., Forcade E., Crawley C. R., Marsh S. G. E., Gandemer V., Tholouli E., Bulabois C. -E., Huynh A., Choi G., Deconinck E., Itala-Remes M., Lenhoff S., Bengtsson M., Johansson J. -E., van Gorkom G., Hoogenboom J. D., Vago L., Rocha V., Bonini C., Chabannon C., Fleischhauer K., Clausen J., Holter W., Kalhs P., Beguin Y., Bron D., Deeren D., Lung W. K., Kerre T., Poire X., Selleslag D., Schroyens W., Jindra P., Mayer J., Vydra J., Zak P., Nielsen B., Sengeloev H., Kaare A., Partanen A., Bay J., Bertrand Y., Blaise D., Bourhis J. H., Chevallier P., Cluzeau T., Damaj G., Fegueux N., Guyotat D., Hunault-Berger M., Labussiere-Wallet H., Leleu X., Lioure B., Maury S., Michel G., Mohty M., Rubio M. T., Tilly H., Turlure P., Bethge W., Casper J., Einsele H., Ganser A., Kroger N., Martin S., Platzbecker U., Reinhardt C., Schafer-Eckart K., Thurner L., Valerius T., Wulf G. G., Karakasis D., Spyridonidis A., Hauser P., Remenyi P., Reykdal S., Mousavi A., Angelucci E., Arcese W., Benedetti F., Bernasconi P., Biondi A., Bonifazi F., Carella A. M., Carluccio P., Casini M., Cavanna L., Ciceri F., Cimino G., Corradini P., Fanin R., Galieni P., Grillo G., Iori A. P., La Nasa G., Locatelli F., Marotta G., Martino M., Mazza P., Mordini N., Musso M., Olivieri A., Pavone V., Pane F., Petrini M., Pioltelli P., Rambaldi A., Ruggeri M., Saccardi R., Santarone S., Scime R., Sica S., Tarella C., Velardi A., Visani G., Zecca M., Tanase A., Kulagin A., Savchenko V., Lopez C. A., Amor A. A., Lopez J. L. B., Caballero D., Duarte R., Cascon M. J. P., Porras R. P., Perez-Simon J. A., Rovira M., Sanz J., Carrete J. P. T., Cammenga J., Isaksson C., Mielke S., Chalandon Y., Passweg J., Schanz U., Meijer E., Kuball J., Veelken J. H., Apperley J., Bloor A., Byrne J., Carpenter B., Clark A., Collin M., Craddock C., Gibson B. E., Khan A., Martin M., Medd P., Nicholson E., Orchard K., Patel A., Peniket A., Potter V., Snowden J., Wilson K. M. O., Ruggeri, A, de Wreede, L, Muller, C, Crivello, P, Bonneville, E, Petersdorf, E, Socie, G, Dubois, V, Niittyvuopio, R, Perasaari, J, Yakoub-Agha, I, Cornelissen, J, Wieten, L, Gedde-Dahl, T, Forcade, E, Crawley, C, Marsh, S, Gandemer, V, Tholouli, E, Bulabois, C, Huynh, A, Choi, G, Deconinck, E, Itala-Remes, M, Lenhoff, S, Bengtsson, M, Johansson, J, van Gorkom, G, Hoogenboom, J, Vago, L, Rocha, V, Bonini, C, Chabannon, C, Fleischhauer, K, Clausen, J, Holter, W, Kalhs, P, Beguin, Y, Bron, D, Deeren, D, Lung, W, Kerre, T, Poire, X, Selleslag, D, Schroyens, W, Jindra, P, Mayer, J, Vydra, J, Zak, P, Nielsen, B, Sengeloev, H, Kaare, A, Partanen, A, Bay, J, Bertrand, Y, Blaise, D, Bourhis, J, Chevallier, P, Cluzeau, T, Damaj, G, Fegueux, N, Guyotat, D, Hunault-Berger, M, Labussiere-Wallet, H, Leleu, X, Lioure, B, Maury, S, Michel, G, Mohty, M, Rubio, M, Tilly, H, Turlure, P, Bethge, W, Casper, J, Einsele, H, Ganser, A, Kroger, N, Martin, S, Platzbecker, U, Reinhardt, C, Schafer-Eckart, K, Thurner, L, Valerius, T, Wulf, G, Karakasis, D, Spyridonidis, A, Hauser, P, Remenyi, P, Reykdal, S, Mousavi, A, Angelucci, E, Arcese, W, Benedetti, F, Bernasconi, P, Biondi, A, Bonifazi, F, Carella, A, Carluccio, P, Casini, M, Cavanna, L, Ciceri, F, Cimino, G, Corradini, P, Fanin, R, Galieni, P, Grillo, G, Iori, A, La Nasa, G, Locatelli, F, Marotta, G, Martino, M, Mazza, P, Mordini, N, Musso, M, Olivieri, A, Pavone, V, Pane, F, Petrini, M, Pioltelli, P, Rambaldi, A, Ruggeri, M, Saccardi, R, Santarone, S, Scime, R, Sica, S, Tarella, C, Velardi, A, Visani, G, Zecca, M, Tanase, A, Kulagin, A, Savchenko, V, Lopez, C, Amor, A, Lopez, J, Caballero, D, Duarte, R, Cascon, M, Porras, R, Perez-Simon, J, Rovira, M, Sanz, J, Carrete, J, Cammenga, J, Isaksson, C, Mielke, S, Chalandon, Y, Passweg, J, Schanz, U, Meijer, E, Kuball, J, Veelken, J, Apperley, J, Bloor, A, Byrne, J, Carpenter, B, Clark, A, Collin, M, Craddock, C, Gibson, B, Khan, A, Martin, M, Medd, P, Nicholson, E, Orchard, K, Patel, A, Peniket, A, Potter, V, Snowden, J, Wilson, K, Ruggeri A., de Wreede L. C., Muller C. R., Crivello P., Bonneville E. F., Petersdorf E. W., Socie G., Dubois V., Niittyvuopio R., Perasaari J., Yakoub-Agha I., Cornelissen J. J., Wieten L., Gedde-Dahl T., Forcade E., Crawley C. R., Marsh S. G. E., Gandemer V., Tholouli E., Bulabois C. -E., Huynh A., Choi G., Deconinck E., Itala-Remes M., Lenhoff S., Bengtsson M., Johansson J. -E., van Gorkom G., Hoogenboom J. D., Vago L., Rocha V., Bonini C., Chabannon C., Fleischhauer K., Clausen J., Holter W., Kalhs P., Beguin Y., Bron D., Deeren D., Lung W. K., Kerre T., Poire X., Selleslag D., Schroyens W., Jindra P., Mayer J., Vydra J., Zak P., Nielsen B., Sengeloev H., Kaare A., Partanen A., Bay J., Bertrand Y., Blaise D., Bourhis J. H., Chevallier P., Cluzeau T., Damaj G., Fegueux N., Guyotat D., Hunault-Berger M., Labussiere-Wallet H., Leleu X., Lioure B., Maury S., Michel G., Mohty M., Rubio M. T., Tilly H., Turlure P., Bethge W., Casper J., Einsele H., Ganser A., Kroger N., Martin S., Platzbecker U., Reinhardt C., Schafer-Eckart K., Thurner L., Valerius T., Wulf G. G., Karakasis D., Spyridonidis A., Hauser P., Remenyi P., Reykdal S., Mousavi A., Angelucci E., Arcese W., Benedetti F., Bernasconi P., Biondi A., Bonifazi F., Carella A. M., Carluccio P., Casini M., Cavanna L., Ciceri F., Cimino G., Corradini P., Fanin R., Galieni P., Grillo G., Iori A. P., La Nasa G., Locatelli F., Marotta G., Martino M., Mazza P., Mordini N., Musso M., Olivieri A., Pavone V., Pane F., Petrini M., Pioltelli P., Rambaldi A., Ruggeri M., Saccardi R., Santarone S., Scime R., Sica S., Tarella C., Velardi A., Visani G., Zecca M., Tanase A., Kulagin A., Savchenko V., Lopez C. A., Amor A. A., Lopez J. L. B., Caballero D., Duarte R., Cascon M. J. P., Porras R. P., Perez-Simon J. A., Rovira M., Sanz J., Carrete J. P. T., Cammenga J., Isaksson C., Mielke S., Chalandon Y., Passweg J., Schanz U., Meijer E., Kuball J., Veelken J. H., Apperley J., Bloor A., Byrne J., Carpenter B., Clark A., Collin M., Craddock C., Gibson B. E., Khan A., Martin M., Medd P., Nicholson E., Orchard K., Patel A., Peniket A., Potter V., Snowden J., and Wilson K. M. O.

Published
2023

5. 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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6. Autoimmune liver disease triggered by SARS-CoV-2: a case report and review of the literature.

Author

FANNI, D., GEROSA, C., SERRA, G., MIGLIANTI, M., COGHE, F., VAN EYKEN, P., FAA, G., LA NASA, G., and GUIDO, M.

Abstract

BACKGROUND: An increasing number of coronavirus disease 2019 (COVID-19) related autoimmune hepatitis (AIH) and autoimmune liver disease (AILD) has been already described so far in the last three years. This rise has set up some diagnostic and therapeutic concerns, although steroid therapy has mostly been efficient, avoiding main significant side effects. CASE PRESENTATION: We report the case of a 52-year-old subject displaying liver function impairment at the laboratory tests while positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) swab. Needle liver biopsy showed severe portal inflammation, interface hepatitis, lobular inflammation, abundant plasma cells, bridging necrosis, endothelialitis, bile duct vanishing disease, and ductular reaction. The diagnosis of autoimmune liver disease (AILD) was performed. After a month of steroid and ursodeoxycholic acid medications, liver function fully recovered. Azathioprine was introduced, and steroids were gradually reduced. CONCLUSIONS: Probably triggered by the SARS-CoV-2-induced cytokine storm, the association between COVID-19 and autoimmune-related inflammatory injury may display a particular paradigm of AILD pathogenesis. [ABSTRACT FROM AUTHOR]

Published
2024

7. Integrating biological HLA-DPB1 mismatch models to predict survival after unrelated hematopoietic cell transplantation

Author

Ruggeri, A., de Wreede, L. C., Muller, C. R., Crivello, P., Bonneville, E. F., Petersdorf, E. W., Socie, G., Dubois, V., Niittyvuopio, R., Perasaari, J., Yakoub-Agha, I., Cornelissen, J. J., Wieten, L., Gedde-Dahl, T., Forcade, E., Crawley, C. R., Marsh, S. G. E., Gandemer, V., Tholouli, E., Bulabois, C. -E., Huynh, A., Choi, G., Deconinck, E., Itala-Remes, M., Lenhoff, S., Bengtsson, M., Johansson, J. -E., van Gorkom, G., Hoogenboom, J. D., Vago, L., Rocha, V., Bonini, C., Chabannon, C., Fleischhauer, K., Clausen, J., Holter, W., Kalhs, P., Beguin, Y., Bron, D., Deeren, D., Lung, W. K., Kerre, T., Poire, X., Selleslag, D., Schroyens, W., Jindra, P., Mayer, J., Vydra, J., Zak, P., Nielsen, B., Sengeloev, H., Kaare, A., Partanen, A., Bay, J., Bertrand, Y., Blaise, D., Bourhis, J. H., Chevallier, P., Cluzeau, T., Damaj, G., Fegueux, N., Guyotat, D., Hunault-Berger, M., Labussiere-Wallet, H., Leleu, X., Lioure, B., Maury, S., Michel, G., Mohty, M., Rubio, M. T., Tilly, H., Turlure, P., Bethge, W., Casper, J., Einsele, H., Ganser, A., Kroger, N., Martin, S., Platzbecker, U., Reinhardt, C., Schafer-Eckart, K., Thurner, L., Valerius, T., Wulf, G. G., Karakasis, D., Spyridonidis, A., Hauser, P., Remenyi, P., Reykdal, S., Mousavi, A., Angelucci, E., Arcese, W., Benedetti, F., Bernasconi, P., Biondi, A., Bonifazi, F., Carella, A. M., Carluccio, P., Casini, M., Cavanna, L., Ciceri, F., Cimino, G., Corradini, P., Fanin, R., Galieni, P., Grillo, G., Iori, A. P., La Nasa, G., Locatelli, Franco, Marotta, G., Martino, M., Mazza, P., Mordini, N., Musso, M., Olivieri, A., Pavone, V., Pane, F., Petrini, M., Pioltelli, P., Rambaldi, A., Ruggeri, M., Saccardi, R., Santarone, S., Scime, R., Sica, S., Tarella, C., Velardi, A., Visani, G., Zecca, M., Tanase, A., Kulagin, A., Savchenko, V., Lopez, C. A., Amor, A. A., Lopez, J. L. B., Caballero, D., Duarte, R., Cascon, M. J. P., Porras, R. P., Perez-Simon, J. A., Rovira, M., Sanz, J., Carrete, J. P. T., Cammenga, J., Isaksson, C., Mielke, S., Chalandon, Y., Passweg, J., Schanz, U., Meijer, E., Kuball, J., Veelken, J. H., Apperley, J., Bloor, A., Byrne, J., Carpenter, B., Clark, A., Collin, M., Craddock, C., Gibson, B. E., Khan, A., Martin, M., Medd, P., Nicholson, E., Orchard, K., Patel, A., Peniket, A., Potter, V., Snowden, J., Wilson, K. M. O., Locatelli F. (ORCID:0000-0002-7976-3654), Ruggeri, A., de Wreede, L. C., Muller, C. R., Crivello, P., Bonneville, E. F., Petersdorf, E. W., Socie, G., Dubois, V., Niittyvuopio, R., Perasaari, J., Yakoub-Agha, I., Cornelissen, J. J., Wieten, L., Gedde-Dahl, T., Forcade, E., Crawley, C. R., Marsh, S. G. E., Gandemer, V., Tholouli, E., Bulabois, C. -E., Huynh, A., Choi, G., Deconinck, E., Itala-Remes, M., Lenhoff, S., Bengtsson, M., Johansson, J. -E., van Gorkom, G., Hoogenboom, J. D., Vago, L., Rocha, V., Bonini, C., Chabannon, C., Fleischhauer, K., Clausen, J., Holter, W., Kalhs, P., Beguin, Y., Bron, D., Deeren, D., Lung, W. K., Kerre, T., Poire, X., Selleslag, D., Schroyens, W., Jindra, P., Mayer, J., Vydra, J., Zak, P., Nielsen, B., Sengeloev, H., Kaare, A., Partanen, A., Bay, J., Bertrand, Y., Blaise, D., Bourhis, J. H., Chevallier, P., Cluzeau, T., Damaj, G., Fegueux, N., Guyotat, D., Hunault-Berger, M., Labussiere-Wallet, H., Leleu, X., Lioure, B., Maury, S., Michel, G., Mohty, M., Rubio, M. T., Tilly, H., Turlure, P., Bethge, W., Casper, J., Einsele, H., Ganser, A., Kroger, N., Martin, S., Platzbecker, U., Reinhardt, C., Schafer-Eckart, K., Thurner, L., Valerius, T., Wulf, G. G., Karakasis, D., Spyridonidis, A., Hauser, P., Remenyi, P., Reykdal, S., Mousavi, A., Angelucci, E., Arcese, W., Benedetti, F., Bernasconi, P., Biondi, A., Bonifazi, F., Carella, A. M., Carluccio, P., Casini, M., Cavanna, L., Ciceri, F., Cimino, G., Corradini, P., Fanin, R., Galieni, P., Grillo, G., Iori, A. P., La Nasa, G., Locatelli, Franco, Marotta, G., Martino, M., Mazza, P., Mordini, N., Musso, M., Olivieri, A., Pavone, V., Pane, F., Petrini, M., Pioltelli, P., Rambaldi, A., Ruggeri, M., Saccardi, R., Santarone, S., Scime, R., Sica, S., Tarella, C., Velardi, A., Visani, G., Zecca, M., Tanase, A., Kulagin, A., Savchenko, V., Lopez, C. A., Amor, A. A., Lopez, J. L. B., Caballero, D., Duarte, R., Cascon, M. J. P., Porras, R. P., Perez-Simon, J. A., Rovira, M., Sanz, J., Carrete, J. P. T., Cammenga, J., Isaksson, C., Mielke, S., Chalandon, Y., Passweg, J., Schanz, U., Meijer, E., Kuball, J., Veelken, J. H., Apperley, J., Bloor, A., Byrne, J., Carpenter, B., Clark, A., Collin, M., Craddock, C., Gibson, B. E., Khan, A., Martin, M., Medd, P., Nicholson, E., Orchard, K., Patel, A., Peniket, A., Potter, V., Snowden, J., Wilson, K. M. O., and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

NO ABSTRACT

Published
2023

8. Thiotepa-busulfan-fludarabine Compared to Treosulfan-based Conditioning for Haploidentical Transplant With Posttransplant Cyclophosphamide in Patients With Acute Myeloid Leukemia in Remission: A Study From the Acute Leukemia Working Party of the EBMT

Author

Saraceni, F., Labopin, M., Raiola, A. M., Blaise, D., Remenyi, P., Sora', Federica, Pavlu, J., Bramanti, S., Busca, A., Berceanu, A., Battipaglia, G., Visani, G., Socie, G., Bug, G., Mico, C., La Nasa, G., Musso, M., Olivieri, A., Spyridonidis, A., Savani, B., Ciceri, F., Nagler, A., Mohty, M., Sora' F. (ORCID:0000-0002-9607-5298), Saraceni, F., Labopin, M., Raiola, A. M., Blaise, D., Remenyi, P., Sora', Federica, Pavlu, J., Bramanti, S., Busca, A., Berceanu, A., Battipaglia, G., Visani, G., Socie, G., Bug, G., Mico, C., La Nasa, G., Musso, M., Olivieri, A., Spyridonidis, A., Savani, B., Ciceri, F., Nagler, A., Mohty, M., and Sora' F. (ORCID:0000-0002-9607-5298)

Abstract

We conducted a registry analysis including adult acute myeloid leukemia (AML) patients in remission who had received thiotepa, busulfan, and fludarabine (TBF) or treosulfan-based (Treo) conditioning for haplo-hematopoietic stem cell transplant (HSCT) with posttransplant cyclophosphamide (PTCy) between 2010 and 2020. A total of 1123 patients met the inclusion criteria (968 received TBF and 155 received Treo). A 1:1 matched-pair analysis was performed on 142 TBF and 142 Treo patients. In the Treo group, 68% of patients received treosulfan at a dose ≥36 g/m2 and 54% of patients received a second alkylator (thiotepa or melphalan). We observed a trend toward increased incidence of grade II-IV acute (a) graft-versus-host disease (GVHD) at 180 days in the TBF group compared with Treo (29% versus 20%; P = 0.08), while incidence of grade III-IV aGVHD was not statistically different. Similarly, the incidence of chronic (c) GVHD was not statistically different in the 2 groups. Incidence of nonrelapse mortality at 2 years was 19% in TBF and 14% in Treo (P = 0.4). Relapse incidence at 2 years was not statistically different in the 2 groups (16% and 18% in TBF and Treo, respectively; P = 0.9). Leukemia-free survival, overall survival, and GVHD-free, relapse-free survival was 65% versus 68% (P = 0.6), 73% versus 76% (P = 0.5), and 54% versus 53% (P = 0.8) in TBF versus Treo, respectively. In conclusion, we did not find a significant difference between the 2 conditioning in the present study; Treo and TBF represent 2 valid alternative regimens for haplo-HSCT with PTCy for AML in remission.

Published
2023

9. Accuracy of physician assessment of treatment preferences and health status in elderly patients with higher-risk myelodysplastic syndromes

Author

Caocci, G., Voso, M.T., Angelucci, E., Stauder, R., Cottone, F., Abel, G., Nguyen, K., Platzbecker, U., Beyne-Rauzy, O., Gaidano, G., Invernizzi, R., Molica, S., Criscuolo, M., Breccia, M., Lübbert, M., Sanpaolo, G., Buccisano, F., Ricco, A., Palumbo, G.A., Niscola, P., Zhang, H., Fenu, S., La Nasa, G., Mandelli, F., and Efficace, F.

Published
2015
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11. Long-term results of all-trans retinoic acid and arsenic trioxide in non-high-risk acute promyelocytic leukemia: update of the APL0406 Italian-German randomized trial

Author

Cicconi, L, Platzbecker, U, Avvisati, G, Paoloni, F, Thiede, C, Vignetti, M, Fazi, P, Ferrara, F, Divona, M, Albano, F, Efficace, F, Sborgia, M, Di Bona, E, Breccia, M, Borlenghi, E, Cairoli, R, Rambaldi, A, Melillo, L, La Nasa, G, Fiedler, W, Brossart, P, Hertenstein, B, Salih, H, Annibali, O, Wattad, M, Lubbert, M, Brandts, C, Hanel, M, Rollig, C, Schmitz, N, Lin, H, Frairia, C, Fozza, C, Maria D’Arco, A, Di Renzo, N, Cortelezzi, A, Fabbiano, F, Dohner, K, Ganser, A, Dohner, H, Amadori, S, Mandelli, F, Teresa Voso, M, Ehninger, G, Schlenk, R, Lo-Coco, F, Cicconi L, Platzbecker U, Avvisati G, Paoloni F, Thiede C, Vignetti M, Fazi P, Ferrara F, Divona M, Albano F, Efficace F, Sborgia M, Di Bona E, Breccia M, Borlenghi E, Cairoli R, Rambaldi A, Melillo L, La Nasa G, Fiedler W, Brossart P, Hertenstein B, Salih HR, Annibali O, Wattad M, Lubbert M, Brandts C, Hanel M, Rollig C, Schmitz N, Lin H, Frairia C, Fozza C, Maria D’Arco A, Di Renzo N, Cortelezzi A, Fabbiano F, Dohner K, Ganser A, Dohner H, Amadori S, Mandelli F, Teresa Voso M, Ehninger G, Schlenk RF, Lo-Coco F., Cicconi, L, Platzbecker, U, Avvisati, G, Paoloni, F, Thiede, C, Vignetti, M, Fazi, P, Ferrara, F, Divona, M, Albano, F, Efficace, F, Sborgia, M, Di Bona, E, Breccia, M, Borlenghi, E, Cairoli, R, Rambaldi, A, Melillo, L, La Nasa, G, Fiedler, W, Brossart, P, Hertenstein, B, Salih, H, Annibali, O, Wattad, M, Lubbert, M, Brandts, C, Hanel, M, Rollig, C, Schmitz, N, Lin, H, Frairia, C, Fozza, C, Maria D’Arco, A, Di Renzo, N, Cortelezzi, A, Fabbiano, F, Dohner, K, Ganser, A, Dohner, H, Amadori, S, Mandelli, F, Teresa Voso, M, Ehninger, G, Schlenk, R, Lo-Coco, F, Cicconi L, Platzbecker U, Avvisati G, Paoloni F, Thiede C, Vignetti M, Fazi P, Ferrara F, Divona M, Albano F, Efficace F, Sborgia M, Di Bona E, Breccia M, Borlenghi E, Cairoli R, Rambaldi A, Melillo L, La Nasa G, Fiedler W, Brossart P, Hertenstein B, Salih HR, Annibali O, Wattad M, Lubbert M, Brandts C, Hanel M, Rollig C, Schmitz N, Lin H, Frairia C, Fozza C, Maria D’Arco A, Di Renzo N, Cortelezzi A, Fabbiano F, Dohner K, Ganser A, Dohner H, Amadori S, Mandelli F, Teresa Voso M, Ehninger G, Schlenk RF, and Lo-Coco F.

Published
2020

12. Busulfan–fludarabine- or treosulfan–fludarabine-based myeloablative conditioning for children with thalassemia major

Author

Luftinger, R., Zubarovskaya, N., Galimard, J. -E., Cseh, A., Salzer, E., Locatelli, Franco, Algeri, M., Yesilipek, A., de la Fuente, J., Isgro, A., Alseraihy, A., Angelucci, E., Smiers, F. J., La La Nasa, G., Zecca, M., Fisgin, T., Unal, E., Kleinschmidt, K., Peters, C., Lankester, A., Corbacioglu, S., Locatelli F. (ORCID:0000-0002-7976-3654), Luftinger, R., Zubarovskaya, N., Galimard, J. -E., Cseh, A., Salzer, E., Locatelli, Franco, Algeri, M., Yesilipek, A., de la Fuente, J., Isgro, A., Alseraihy, A., Angelucci, E., Smiers, F. J., La La Nasa, G., Zecca, M., Fisgin, T., Unal, E., Kleinschmidt, K., Peters, C., Lankester, A., Corbacioglu, S., and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

Significant advances in supportive care for patients with transfusion-dependent thalassemia major (TDT) have improved patients’ life expectancy. However, transfusion-associated iron overload remains a significant barrier to long-term survival with good quality of life. Today, allogeneic hematopoietic stem cell transplantation (HSCT) is the current curative standard of care. Alongside selection of the best available donor, an optimized conditioning regimen is crucial to maximize outcomes for patients with TDT undergoing HSCT. The aim of this retrospective analysis was to investigate the role of busulfan–fludarabine-based and treosulfan–fludarabine-based conditioning in TDT patients undergoing HSCT. We included 772 patients registered in the European Society for Blood and Marrow Transplantation (EBMT) database who underwent first HSCT between 2010 and 2018. Four hundred ten patients received busulfan–fludarabine-based conditioning (median age 8.6 years) and 362 patients received treosulfan–fludarabine-based conditioning (median age 5.7 years). Patient outcomes were retrospectively compared by conditioning regimen. Two-year overall survival was 92.7% (95% confidence interval: 89.3–95.1%) after busulfan–fludarabine-based conditioning and 94.7% (95% confidence interval: 91.7–96.6%) after treosulfan–fludarabine-based conditioning. There was a very low incidence of second HSCT overall. The main causes of death were infections, graft-versus-host disease, and rejection. In conclusion, use of busulfan or treosulfan as the backbone of myeloablative conditioning for patients with TDT undergoing HSCT resulted in comparably high cure rates. Long-term follow-up studies are warranted to address the important issues of organ toxicities and gonadal function.

Published
2022

13. The human carotid atherosclerotic plaque: an observational review of histological scoring systems.

Author

GEROSA, C., CERRONE, G., SURI, J. S., AIMOLA, V., CAU, F., CONI, P., PIRAS, M., CAU, R., BALESTRIERI, A., SCANO, A., ORRÙ, G., VAN EYKEN, P., LA NASA, G., COGHE, F., CASTAGNOLA, M., GIBO, Y., FANNI, D., and SABA, L.

Abstract

OBJECTIVE: The atherosclerotic plaque is a complex dynamic pathological lesion of the arterial wall, characterized by multiple elementary lesions of different diagnostic and prognostic significance. Fibrous cap thickness, lipid necrotic core dimension, inflammation, intra-plaque hemorrhage (IPH), plaque neovascularization and endothelial dysfunction (erosions) are generally considered the most relevant morphological details of plaque morphology. In this review, the most relevant features able to discriminate between stable and vulnerable plaques at histological level are discussed. SUBJECTS AND METHODS: Retrospectively, we have evaluated the laboratory results from one hundred old histological samples from patients treated with carotid endarterectomy. These results were analyzed to assess elementary lesions that characterize stable and unstable plaques. RESULTS: A thin fibrous cap (<65 micron), loss of smooth muscle cells, collagen depletion, a large lipid-rich necrotic core, infiltrating macrophages, IPH and intra-plaque vascularization are identified as the most important risk factors associated with plaque rupture. CONCLUSIONS: Immunohistochemistry for smooth muscle actin (smooth muscle cell marker) and for CD68 (marker of monocytes/macrophages) and glycophorin (marker of red blood cells) are suggested as useful tools for an in deep characterization of any carotid plaque and for distinguishing plaque phenotypes at histology. Since patients with a carotid vulnerable plaque are at higher risk of developing vulnerable plaques in other arteries as well, the definition of the vulnerability index is underlined, in order to stratify patients at higher risk for undergoing cardiovascular events. [ABSTRACT FROM AUTHOR]

Published
2023

14. 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

16. 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

17. VERY LONG-TERM RESULTS OF ALL-TRANS RETINOIC ACID AND ARSENIC TRIOXIDE IN NON-HIGH RISK ACUTE PROMYELOCYTIC LEUKEMIA: LATEST UPDATE OF THE ITALIAN-GERMAN APL0406 RANDOMIZED TRIAL

Author

Cicconi, L, Platzbecker, U, Avvisati, G, Paoloni, F, Thiede, C, Vignetti, M, Fazi, P, Ferrara, F, Divona, M, Albano, F, Efficace, F, Sborgia, M, Di Bona, E, Breccia, M, Borlenghi, E, Cairoli, R, Rambaldi, A, Melillo, L, La Nasa, G, Fiedler, W, Brossart, P, Hertenstein, B, Salih, H, Annibali, O, Wattad, M, Lubbert, M, Brandts, C, Hanel, M, Rollig, C, Schmitz, N, Lin, H, Frairia, C, Fozza, C, Maria D’Arco, A, Di Renzo, N, Cortelezzi, A, Fabbiano, F, Dohner, K, Ganser, A, Dohner, H, Amadori, S, Mandelli, F, Teresa Voso, M, Ehninger, G, Schlenk, R, Lo-Coco, F, Cicconi L, Platzbecker U, Avvisati G, Paoloni F, Thiede C, Vignetti M, Fazi P, Ferrara F, Divona M, Albano F, Efficace F, Sborgia M, Di Bona E, Breccia M, Borlenghi E, Cairoli R, Rambaldi A, Melillo L, La Nasa G, Fiedler W, Brossart P, Hertenstein B, Salih HR, Annibali O, Wattad M, Lubbert M, Brandts C, Hanel M, Rollig C, Schmitz N, Lin H, Frairia C, Fozza C, Maria D’Arco A, Di Renzo N, Cortelezzi A, Fabbiano F, Dohner K, Ganser A, Dohner H, Amadori S, Mandelli F, Teresa Voso M, Ehninger G, Schlenk RF, Lo-Coco F., Cicconi, L, Platzbecker, U, Avvisati, G, Paoloni, F, Thiede, C, Vignetti, M, Fazi, P, Ferrara, F, Divona, M, Albano, F, Efficace, F, Sborgia, M, Di Bona, E, Breccia, M, Borlenghi, E, Cairoli, R, Rambaldi, A, Melillo, L, La Nasa, G, Fiedler, W, Brossart, P, Hertenstein, B, Salih, H, Annibali, O, Wattad, M, Lubbert, M, Brandts, C, Hanel, M, Rollig, C, Schmitz, N, Lin, H, Frairia, C, Fozza, C, Maria D’Arco, A, Di Renzo, N, Cortelezzi, A, Fabbiano, F, Dohner, K, Ganser, A, Dohner, H, Amadori, S, Mandelli, F, Teresa Voso, M, Ehninger, G, Schlenk, R, Lo-Coco, F, Cicconi L, Platzbecker U, Avvisati G, Paoloni F, Thiede C, Vignetti M, Fazi P, Ferrara F, Divona M, Albano F, Efficace F, Sborgia M, Di Bona E, Breccia M, Borlenghi E, Cairoli R, Rambaldi A, Melillo L, La Nasa G, Fiedler W, Brossart P, Hertenstein B, Salih HR, Annibali O, Wattad M, Lubbert M, Brandts C, Hanel M, Rollig C, Schmitz N, Lin H, Frairia C, Fozza C, Maria D’Arco A, Di Renzo N, Cortelezzi A, Fabbiano F, Dohner K, Ganser A, Dohner H, Amadori S, Mandelli F, Teresa Voso M, Ehninger G, Schlenk RF, and Lo-Coco F.

Published
2019

20. 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

24. VERY LONG-TERM RESULTS OF ALL-TRANS RETINOIC ACID AND ARSENIC TRIOXIDE IN NON-HIGH RISK ACUTE PROMYELOCYTIC LEUKEMIA: LATEST UPDATE OF THE ITALIAN-GERMAN APL0406 RANDOMIZED TRIAL

Author

Cicconi L, Platzbecker U, Avvisati G, Paoloni F, Thiede C, Vignetti M, Fazi P, Ferrara F, Divona M, Albano F, Efficace F, Sborgia M, Di Bona E, Breccia M, Borlenghi E, Cairoli R, Rambaldi A, Melillo L, La Nasa G, Fiedler W, Brossart P, Hertenstein B, Salih HR, Annibali O, Wattad M, Lubbert M, Brandts C, Hanel M, Rollig C, Schmitz N, Lin H, Frairia C, Fozza C, Maria D’Arco A, Di Renzo N, Cortelezzi A, Fabbiano F, Dohner K, Ganser A, Dohner H, Amadori S, Mandelli F, Teresa Voso M, Ehninger G, Schlenk RF, Lo-Coco F., Cicconi, L, Platzbecker, U, Avvisati, G, Paoloni, F, Thiede, C, Vignetti, M, Fazi, P, Ferrara, F, Divona, M, Albano, F, Efficace, F, Sborgia, M, Di Bona, E, Breccia, M, Borlenghi, E, Cairoli, R, Rambaldi, A, Melillo, L, La Nasa, G, Fiedler, W, Brossart, P, Hertenstein, B, Salih, H, Annibali, O, Wattad, M, Lubbert, M, Brandts, C, Hanel, M, Rollig, C, Schmitz, N, Lin, H, Frairia, C, Fozza, C, Maria D’Arco, A, Di Renzo, N, Cortelezzi, A, Fabbiano, F, Dohner, K, Ganser, A, Dohner, H, Amadori, S, Mandelli, F, Teresa Voso, M, Ehninger, G, Schlenk, R, and Lo-Coco, F

Subjects
Hematology
Published
2019

25. 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

29. Hematopoietic stem cell transplantation for multiple sclerosis: A retrospective multicenter study

Author

Fassas, A.S., Passweg, J. R., Anagnostopoulos, A., Kazis, A., Kozak, T., Havrdova, E., Carreras, E., Graus, F., Kashyap, A., Openshaw, H., Schipperus, M., Deconinck, E., Mancardi, G., Marmont, A., Hansz, J., Rabusin, M., Zuazu Nagore, F. J., Besalduch, J., Dentamaro, T., Fouillard, L., Hertenstein, B., La Nasa, G., Musso, M., Papineschi, F., Rowe, J. M., Saccardi, R., Steck, A., Kappos, L., Gratwohl, A., Tyndall, A., and for the Autoimmune Disease Working Party of the EBMT (European Group for Blood and Marrow Transplantation)

Published
2002
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30. Strong ACE-2 expression in the choroidal vessels: do high choroid plexuses serve as a gateway for SARS-CoV-2 infection on the human brain?

Author

PIRAS, M., CAU, F., MANCHIA, M., PARIBELLO, P., SABA, L., SURI, J. S., FAA, G., PICHIRI, G., CERRONE, G., SCANO, A., ORRÙ, G., LA NASA, G., COGHE, F., CASTAGNOLA, M., FANNI, D., and GEROSA, C.

Abstract

OBJECTIVE: Previous studies have confirmed the key mechanism by which SARS-CoV-2 enters human cells. It is well established that ACE2 is the receptor that can mark the beginning of the infection. In light of this, the organs that express higher levels of ACE2 are generally considered at higher risk, while those with lower levels should be somehow more protected. This - if related to the scarcity of ace2-expressing cells in the brain - seems to contrast with the presence of a variety of neurological symptoms that follow infection with ace2. The aim of this work was to analyze ACE2 expression in the human brain, focusing on the choroid plexuses. PATIENTS AND METHODS: Twenty brain samples were obtained at autopsy from ten human fetuses and from ten adult subjects. All samples were selected to contain the choroid plexus. Specimens were fixed in 10% formalin, routinely processed and paraffin embedded. 5-micron sections were stained with Hematoxylin and Eosin (H&E) and immunostained with a commercial anti-human ACE2 rabbit monoclonal antibody at 1:100 dilution. RESULTS: We analyzed 20 samples by immunohistochemistry, and we noted that, as far as fetal samples are concerned, a strong reactivity for ACE2 was detected in the myxoid stroma of the choroid plexuses and in the endothelial cells in fetuses. The complete absence of the ACE2 marker was detected in epithelial cells, neurons and glial cells of the cerebral cortex, both in fetuses and in adults. Whereas a strong but selective reactivity for ACE2 was also detected in adult choroid plexuses, mainly localized in the endothelial cells of the choroid capillaries. CONCLUSIONS: Our study shows a strong expression of ACE in the fetal and adult brain choroid plexuses. This new histopathological finding may clarify the susceptibility of the human brain to SARS-COV-2 infection. Our data indicate the choroid plexus as the entry gate of virus for in the human brain; therefore, the entrance of SARS-CoV-2 into the cerebrospinal fluid through the choroid plexuses might represent the mechanism utilized by this coronavirus to cause direct injury to brain cells. [ABSTRACT FROM AUTHOR]

Published
2022

36. Lenalidomide treatment of myelodysplastic syndromes with chromosome 5q deletion: Results from the National Registry of the Italian Drug Agency

Author

Arcioni, F., Roncadori, A., Di Battista, V., Tura, S., Covezzoli, A., Cundari, S., Mecucci, C., Abbadessa, A., Alterini, R., Santini, V., Cantonetti, M., Buccisano, F., Bacigalupo, A., Sessarego, M., Tonso, A., Ferrero, D., D'Ardia, S., Tarella, C., Cascavilla, N., Bassan, R., Sancetta, R., Cortelezzi, A., Reda, G., Maria D'Arco, A., De Fabritiis, P., Di Renzo, N., Falini, B., Alimena, G., Avanzini, P., Ilariucci, F., Iuliano, F., La Nasa, G., Caocci, G., Defina, M., Latte, G., Palmas, A., Levis, A., Leone, G., Teresa Voso, M., Leoni, P., Poloni, A., Fozza, C., Crugnola, M., Montanaro, M., Spedini, P., Lanza, F., Pizzuti, M., Pane, F., Paolini, R., Borin, L., Rambaldi, A., Rossi, G., Maria Pelizzari, A., Russo, D., D'Emilio, A., Ruggeri, M., Semenzato, G., Specchia, G., Tagariello, G., Sartori, R., Testore, F., Ciravegna, G., Marasca, R., Cimarosto, L., Fontanive, O., Visani, G., Arcioni, F., Roncadori, A., Di Battista, V., Tura, S., Covezzoli, A., Cundari, S., Mecucci, C., Abbadessa, A., Alterini, R., Santini, V., Cantonetti, M., Buccisano, F., Bacigalupo, A., Sessarego, M., Tonso, A., Ferrero, D., D'Ardia, S., Tarella, C., Cascavilla, N., Bassan, R., Sancetta, R., Cortelezzi, A., Reda, G., Maria D'Arco, A., De Fabritiis, P., Di Renzo, N., Falini, B., Alimena, G., Avanzini, P., Ilariucci, F., Iuliano, F., La Nasa, G., Caocci, G., Defina, M., Latte, G., Palmas, A., Levis, A., Leone, G., Teresa Voso, M., Leoni, P., Poloni, A., Fozza, C., Crugnola, M., Montanaro, M., Spedini, P., Lanza, F., Pizzuti, M., Pane, F., Paolini, R., Borin, L., Rambaldi, A., Rossi, G., Maria Pelizzari, A., Russo, D., D'Emilio, A., Ruggeri, M., Semenzato, G., Specchia, G., Tagariello, G., Sartori, R., Testore, F., Ciravegna, G., Marasca, R., Cimarosto, L., Fontanive, O., and Visani, G.

Subjects
Oncology, Myeloid, Male, Group B, Immunologic Factor, 0302 clinical medicine, Retrospective Studie, hemic and lymphatic diseases, del(5q), Prospective Studies, Registries, Prospective cohort study, Hematology, Leukemia, registry study, Standard treatment, Remission Induction, General Medicine, Middle Aged, lenalidomide, myelodysplastic syndromes, Aged, Chromosomes, Human, Pair 5, Disease Progression, Female, Humans, Immunologic Factors, Italy, Karyotyping, Lenalidomide, Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Retrospective Studies, Thalidomide, Chromosome Deletion, 030220 oncology & carcinogenesis, Pair 5, medicine.drug, Human, medicine.medical_specialty, Myelodysplastic Syndrome, Acute, Chromosomes, NO, 03 medical and health sciences, Internal medicine, medicine, business.industry, Myelodysplastic syndromes, Retrospective cohort study, medicine.disease, Settore MED/15, Prospective Studie, business, 030215 immunology
Abstract

Objective The most typical cytogenetic aberration in myelodysplastic syndromes is del(5q), which, when isolated, is associated with refractory anaemia and good prognosis. Based on high rates of erythroid response and transfusion independence, Lenalidomide (LEN) became the standard treatment. This multi-centre study was designed to supplement Italian Registry data on LEN by addressing prescription, administration appropriateness, haematological and cytogenetic responses and disease evolution. Methods MORE study was an observational, non-interventional, multi-centre, retrospective and prospective study. Cases were recruited from 45 Haematological Centres throughout Italy. Data were collected from the Italian National Registry for Lenalidomide administration and supplemented by a MORE data form. Results Data from 190/213 patients were analysed. In all, 149 had been diagnosed by conventional cytogenetics (GROUP A) and 41 only by FISH (GROUP B). Overall erythroid response was obtained in 92.8% of cases. Overall cytogenetic remission was achieved in 22.6% of cases. Disease progression occurred in 15.6% of cases. Clonal cytogenetic evolution characterised progression to AML but not to higher risk MDS. Conclusions Erythroid response to Lenalidomide was similar in MDS with isolated del(5q) and with del(5q) plus one anomaly. Progression to AML or higher risk MDS showed different cytogenetic features.

Published
2018

37. Improved outcomes with retinoic acid and arsenic trioxide compared with retinoic acid and chemotherapy in non-high-risk acute promyelocytic leukemia: Final results of the randomized Italian-German APL0406 trial

Author

Platzbecker, U, Avvisati, G, Cicconi, L, Thiede, C, Paoloni, F, Vignetti, M, Ferrara, F, Divona, M, Albano, F, Efficace, F, Fazi, P, Sborgia, M, Di Bona, E, Breccia, M, Borlenghi, E, Cairoli, R, Rambaldi, A, Melillo, L, La Nasa, G, Fiedler, W, Brossart, P, Hertenstein, B, Salih, H, Wattad, M, Lübbert, M, Brandts, C, Hänel, M, Röllig, C, Schmitz, N, Link, H, Frairia, C, Pogliani, E, Fozza, C, D'Arco, A, Di Renzo, N, Cortelezzi, A, Fabbiano, F, Döhner, K, Ganser, A, Döhner, H, Amadori, S, Mandelli, F, Ehninger, G, Schlenk, R, Lo-Coco, F, Platzbecker U, Avvisati G, Cicconi L, Thiede C, Paoloni F, Vignetti M, Ferrara F, Divona M, Albano F, Efficace F, Fazi P, Sborgia M, Di Bona E, Breccia M, Borlenghi E, Cairoli R, Rambaldi A, Melillo L, La Nasa G, Fiedler W, Brossart P, Hertenstein B, Salih HR, Wattad M, Lübbert M, Brandts CH, Hänel M, Röllig C, Schmitz N, Link H, Frairia C, Pogliani EM, Fozza C, D'Arco AM, Di Renzo N, Cortelezzi A, Fabbiano F, Döhner K, Ganser A, Döhner H, Amadori S, Mandelli F, Ehninger G, Schlenk RF, Lo-Coco F., Platzbecker, U, Avvisati, G, Cicconi, L, Thiede, C, Paoloni, F, Vignetti, M, Ferrara, F, Divona, M, Albano, F, Efficace, F, Fazi, P, Sborgia, M, Di Bona, E, Breccia, M, Borlenghi, E, Cairoli, R, Rambaldi, A, Melillo, L, La Nasa, G, Fiedler, W, Brossart, P, Hertenstein, B, Salih, H, Wattad, M, Lübbert, M, Brandts, C, Hänel, M, Röllig, C, Schmitz, N, Link, H, Frairia, C, Pogliani, E, Fozza, C, D'Arco, A, Di Renzo, N, Cortelezzi, A, Fabbiano, F, Döhner, K, Ganser, A, Döhner, H, Amadori, S, Mandelli, F, Ehninger, G, Schlenk, R, Lo-Coco, F, Platzbecker U, Avvisati G, Cicconi L, Thiede C, Paoloni F, Vignetti M, Ferrara F, Divona M, Albano F, Efficace F, Fazi P, Sborgia M, Di Bona E, Breccia M, Borlenghi E, Cairoli R, Rambaldi A, Melillo L, La Nasa G, Fiedler W, Brossart P, Hertenstein B, Salih HR, Wattad M, Lübbert M, Brandts CH, Hänel M, Röllig C, Schmitz N, Link H, Frairia C, Pogliani EM, Fozza C, D'Arco AM, Di Renzo N, Cortelezzi A, Fabbiano F, Döhner K, Ganser A, Döhner H, Amadori S, Mandelli F, Ehninger G, Schlenk RF, and Lo-Coco F.

Abstract

Purpose: The initial results of the APL0406 trial showed that the combination of all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) is at least not inferior to standard ATRA and chemotherapy (CHT) in first-line therapy of low- or intermediate-risk acute promyelocytic leukemia (APL). We herein report the final analysis on the complete series of patients enrolled onto this trial. Patients and Methods: The APL0406 study was a prospective, randomized, multicenter, open-label, phase III noninferiority trial. Eligible patients were adults between 18 and 71 years of age with newly diagnosed, low- or intermediate-risk APL (WBC at diagnosis ≤ 10 × 109/L). Overall, 276 patients were randomly assigned to receive ATRA-ATO or ATRA-CHT between October 2007 and January 2013. Results: Of 263 patients evaluable for response to induction, 127 (100%) of 127 patients and 132 (97%) of 136 patients achieved complete remission (CR) in the ATRA-ATO and ATRA-CHT arms, respectively (P = .12). After a median follow-up of 40.6 months, the event-free survival, cumulative incidence of relapse, and overall survival at 50 months for patients in the ATRA-ATO versus ATRA-CHT arms were 97.3% v 80%, 1.9% v 13.9%, and 99.2% v 92.6%, respectively (P < .001, P = .0013, and P = .0073, respectively). Postinduction events included two relapses and one death in CR in the ATRA-ATO arm and two instances of molecular resistance after third consolidation, 15 relapses, and five deaths in CR in the ATRA-CHT arm. Two patients in the ATRA-CHT arm developed a therapy-related myeloid neoplasm. Conclusion: These results show that the advantages of ATRA-ATO over ATRA-CHT increase over time and that there is significantly greater and more sustained antileukemic efficacy of ATO-ATRA compared with ATRA-CHT in low- and intermediate-risk APL.

Published
2017

41. Ultrastructural findings of lung injury due to Vaccine-induced Immune Thrombotic Thrombocytopenia (VITT) following COVID-19 vaccination: a scanning electron microscopic study.

Author

CONGIU, T., FANNI, D., PIRAS, M., GEROSA, C., CAU, F., BARCELLONA, D., D'ALOJA, E., DEMONTIS, R., CHIGHINE, F., NIOI, M., CONI, P., RAVARINO, A., CERRONE, G., AIMOLA, V., BOTTA, C., SCANO, A., ORRÙ, G., COGHE, F., VAN EYKEN, P., and LA NASA, G.

Abstract

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare new syndrome occurring after the ChAdOx1 nCoV-19 vaccine immunization. Patients with VITT are characterized by a variable clinical presentation, likewise also the outcome of these patients is very variable. Here we report the lung ultrastructural findings in the course of VITT of a 58-year-old male patient. Alveoli were mainly dilated, irregular in shape, and occupied by a reticular network of fibrin, while interalveolar septa appeared thickened. The proliferation of small capillaries gave rise to plexiform structures and pulmonary capillary hemangiomatosis-like features. Near the alveoli occupied by a dense fibrin network, the medium-sized arteries showed a modi- fied wall and an intraluminal thrombus. This scenario looks quite similar to that found during COVID-19, where the lungs suffer from the attack of the antigen-antibodies complexes and the virus respectively. In both diseases, the final outcome is a severe inflammation, activation of the haemostatic system and fibrinolysis. [ABSTRACT FROM AUTHOR]

Published
2022

48. Results of a Multicentre, Randomized, Controlled Open-Label Study on the Use of Anti-T-Lymphocyte Globulin (ATLG) and Rituximab for Immunomodulation of Graft-Versus-Host Disease (GvHD) and Graft Failure (GF) in Patients with Non-Malignant Disorders.

Author

Algeri, M, Galimberti, S, Bernardo, M, Rovelli, A, Zecca, M, La Nasa, G, Marktel, S, Merli, P, Bertaina, A, Pagliara, D, Boccieri, E, Del Bufalo, F, Gaspari, S, Ruggeri, A, Capitoli, G, Valsecchi, M, Locatelli, F, Bernardo, ME, Valsecchi, MG, Algeri, M, Galimberti, S, Bernardo, M, Rovelli, A, Zecca, M, La Nasa, G, Marktel, S, Merli, P, Bertaina, A, Pagliara, D, Boccieri, E, Del Bufalo, F, Gaspari, S, Ruggeri, A, Capitoli, G, Valsecchi, M, Locatelli, F, Bernardo, ME, and Valsecchi, MG

Published
2019

49. Fetal programming of atherosclerosis: may the barker hypothesis explain the susceptibility of a subset of patients to develop stroke or cardiac infarct?

Author

GEROSA, C., FAA, G., FANNI, D., CERRONE, G., SURI, J. S., BARCELLONA, D., CONI, P., CONGIU, T., LAI, M. L., PIRAS, M., CAU, F., COGHE, F., BALESTRIERI, A., CAU, R., ORRU', G., SCANO, A., VAN EYKEN, P., LA NASA, G., CAMPAGNA, M., and CASTAGNOLA, M.

Abstract

The risk stratification of young adults between subjects who will develop a mild form of atherosclerosis and subjects who will undergo a severe disease remains inaccurate. In the eighties of the previous century, David JP Barker has demonstrated the relationship between fetal conditions and occurrence of pathologies in adulthood. In this paper, the multiple evidence that might explain the increased susceptibility to severe forms of atherosclerosis, including stroke and cardiac infarct, in subjects who underwent intrauterine growth restriction (IUGR) will be analyzed. Specifically, we will review those inter-connected data indicating an association between a low weight at birth and an adult phenotype which might favor a severe outcome of atherosclerosis. Young and adult subjects born too small (IUGR) or too early (pre-terms) might represent a subgroup of "at risk subjects", more susceptible toward severe forms of atherosclerosis. Given that low birth weight (LBW) may be considered a surrogate of IUGR, this phenotypic feature could be considered among those indispensable clinical data collected in every patient presenting with atherosclerosis, irrespectively of age. According to the hypothesis that structural arterial changes might represent the link between LBW and susceptibility to atherosclerosis later in life, we suggest that the prevention of atherosclerosis should begin at birth. Regenerative and physiological substances such as thymosin Beta-4 could be challenged for a new "arterial regenerative medicine" in the perinatal period. The goal of this new approach should be the reinforcement of the structure of the arterial wall, allowing LBW newborns to avoid the most severe complications of atherosclerosis later in life: a dream that our research could contribute to bringing to life. [ABSTRACT FROM AUTHOR]

Published
2021

50. Aortic vulnerability to COVID-19: is the microvasculature of vasa vasorum a key factor? A case report and a review of the literature.

Author

FAA, G., GEROSA, C., FANNI, D., BARCELLONA, D., CERRONE, G., ORRÙ, G., SCANO, A., MARONGIU, F., SURI, J., DEMONTIS, R., NIOI, M., D'ALOJA, E., LA NASA, G., and SABA, L.

Abstract

Arterial thromboembolic complications reported in patients with COVID-19 infection suggested that SARS-CoV-2 can trigger atherosclerotic plaque vulnerability. While endothelial cells in healthy subjects protect against thrombus formation, after injury they show prothrombotic activity. In addition, it has been hypothesized that "cytokine storm" might stimulate the production of neo-platelets triggering an abnormal "immunothrombosis" responsible for the hypercoagulable state induced in COVID-19 patients. The aim of this study is to report a case of severe COVID-19 infection characterized by the occurrence of microthrombosis in the vasa vasorum of the aorta. A 67-year-old male patient, in good health status and without comorbidities, who underwent a severe COVID-19 infection with fatal outcome, showed scattered aortic atherosclerotic plaques, characterized by multiple occlusive micro-thromboses in the vasa vasorum, spread out lymphocytic infiltrates and foci of endotheliitis and endothelial detachment. This case report confirms the previously described thrombotic involvement of vasa vasorum in COVID-19. The occurrence of the synchronous damage involving both the lumen surface (endothelial dysfunction, endotheliitis and endothelial detachment) and the adventitia (inflammation and occlusive thrombosis of vasa vasorum) could be the key points related to the fatal outcome of the SARS-CoV-2 patients. In our opinion, vasa vasorum thrombosis may thus initiate an atherogenic process that could be characterized by a much more rapid development. [ABSTRACT FROM AUTHOR]

Published
2021

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