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6. The first steps towards a diverse and inclusive EBMT: a position paper

Author

Montoto, S., Snowden, J. A., Chabannon, C., Corbacioglu, S., de la Camara, R., Dolstra, H., Greco, R., Gusi, A., Hamad, N., Kenyon, M., Kröger, N., Mohty, M., Murray, J., Mueller, A., Neven, B., Peffault de Latour, R., Peric, Z., Sánchez-Ortega, I., Sureda, A., Verhoeven, B., Villar, A., and Yakoub-Agha, I.

Published
2022
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7. Continuous and differential improvement in worldwide access to hematopoietic cell transplantation: activity has doubled in a decade with a notable increase in unrelated and non-identical related donors.

Author

Atsuta, Y, Baldomero, H, Neumann, D, Sureda, A, DeVos, JD, Iida, M, Karduss, A, Purtill, D, Elhaddad, AM, Bazuaye, NG, Bonfim, C, De la Camara, R, Chaudhri, NA, Ciceri, F, Correa, C, Frutos, C, Galeano, S, Garderet, L, Gonzalez-Ramella, O, Greco, R, Hamad, N, Hazenberg, MD, Horowitz, MM, Kalwak, K, Ko, B-S, Kodera, Y, Koh, MB, Liu, K, McLornan, DP, Moon, JH, Neven, B, Okamoto, S, Pasquini, MC, Passweg, JR, Paulson, K, Rondelli, D, Ruggeri, A, Seber, A, Snowden, JA, Srivastava, A, Szer, J, Weisdorf, D, Worel, N, Greinix, H, Saber, W, Aljurf, M, Niederwieser, D, Atsuta, Y, Baldomero, H, Neumann, D, Sureda, A, DeVos, JD, Iida, M, Karduss, A, Purtill, D, Elhaddad, AM, Bazuaye, NG, Bonfim, C, De la Camara, R, Chaudhri, NA, Ciceri, F, Correa, C, Frutos, C, Galeano, S, Garderet, L, Gonzalez-Ramella, O, Greco, R, Hamad, N, Hazenberg, MD, Horowitz, MM, Kalwak, K, Ko, B-S, Kodera, Y, Koh, MB, Liu, K, McLornan, DP, Moon, JH, Neven, B, Okamoto, S, Pasquini, MC, Passweg, JR, Paulson, K, Rondelli, D, Ruggeri, A, Seber, A, Snowden, JA, Srivastava, A, Szer, J, Weisdorf, D, Worel, N, Greinix, H, Saber, W, Aljurf, M, and Niederwieser, D

Abstract

Promoting access to and excellence in hematopoietic cell transplantation (HCT) by collecting and disseminating data on global HCT activities is one of the principal activities of the Worldwide Network for Blood and Marrow Transplantation, a non-Governmental organization in working relations with the World Health Organization. HCT activities are recorded annually by member societies, national registries and individual centers including indication, donor type (allogeneic/autologous), donor match and stem cell source (bone marrow/peripheral blood stem cells/cord blood). In 2018, 1,768 HCT teams in 89 countries (six WHO regions) reported 93,105 (48,680 autologous and 44,425 allogeneic) HCT. Major indications were plasma cell disorders and lymphoma for autologous, and acute leukemias and MDS/MPN for allogeneic HCT. HCT number increased from 48,709 in 2007. Notable increases were seen for autoimmune diseases in autologous and hemoglobinopathies in allogeneic HCT. The number of allogeneic HCT more than doubled with significant changes in donor match. While HCT from HLA identical siblings has seen only limited growth, HCT from non-identical related donors showed significant increase worldwide. Strongest correlation between economic growth indicator of gross national income/capita and HCT activity/ten million population was observed for autologous HCT (r=0.79). HCT from unrelated donors showed strong correlation (r=0.68), but only moderate correlation (r=0.51) was detected from related donors. The use of HCT doubled in about a decade worldwide at different speed and with significant changes regarding donor match as a sign of improved access to HCT worldwide. Although narrowing, significant gaps remain between developing and non-developing countries.

Published
2024

8. Cerebral Infectious Opportunistic Lesions in a Patient with Acute Myeloid Leukaemia: The Challenge of Diagnosis and Clinical Management

Author

Cavazza, G, Motto, C, Regna-Gladin, C, Travi, G, Di Gennaro, E, Peracchi, F, Monti, B, Corti, N, Greco, R, Minga, P, Riva, M, Rimoldi, S, Vecchi, M, Rogati, C, Motta, D, Pazzi, A, Vismara, C, Bandiera, L, Crippa, F, Mancini, V, Sessa, M, Oltolini, C, Cairoli, R, Puoti, M, Cavazza, Gabriele, Motto, Cristina, Regna-Gladin, Caroline, Travi, Giovanna, Di Gennaro, Elisa, Peracchi, Francesco, Monti, Bianca, Corti, Nicolò, Greco, Rosa, Minga, Periana, Riva, Marta, Rimoldi, Sara, Vecchi, Marta, Rogati, Carlotta, Motta, Davide, Pazzi, Annamaria, Vismara, Chiara, Bandiera, Laura, Crippa, Fulvio, Mancini, Valentina, Sessa, Maria, Oltolini, Chiara, Cairoli, Roberto, Puoti, Massimo, Cavazza, G, Motto, C, Regna-Gladin, C, Travi, G, Di Gennaro, E, Peracchi, F, Monti, B, Corti, N, Greco, R, Minga, P, Riva, M, Rimoldi, S, Vecchi, M, Rogati, C, Motta, D, Pazzi, A, Vismara, C, Bandiera, L, Crippa, F, Mancini, V, Sessa, M, Oltolini, C, Cairoli, R, Puoti, M, Cavazza, Gabriele, Motto, Cristina, Regna-Gladin, Caroline, Travi, Giovanna, Di Gennaro, Elisa, Peracchi, Francesco, Monti, Bianca, Corti, Nicolò, Greco, Rosa, Minga, Periana, Riva, Marta, Rimoldi, Sara, Vecchi, Marta, Rogati, Carlotta, Motta, Davide, Pazzi, Annamaria, Vismara, Chiara, Bandiera, Laura, Crippa, Fulvio, Mancini, Valentina, Sessa, Maria, Oltolini, Chiara, Cairoli, Roberto, and Puoti, Massimo

Abstract

Central nervous system (CNS) lesions, especially invasive fungal diseases (IFDs), in immunocompromised patients pose a great challenge in diagnosis and treatment. We report the case of a 48-year-old man with acute myeloid leukaemia and probable pulmonary aspergillosis, who developed hyposthenia of the left upper limb, after achieving leukaemia remission and while on voriconazole. Magnetic resonance imaging (MRI) showed oedematous CNS lesions with a haemorrhagic component in the right hemisphere with lepto-meningitis. After 2 weeks of antibiotics and amphotericin-B, brain biopsy revealed chronic inflammation with abscess and necrosis, while cultures were negative. Clinical recovery was attained, he was discharged on isavuconazole and allogeneic transplant was postponed, introducing azacitidine as a maintenance therapy. After initial improvement, MRI worsened; brain biopsy was repeated, showing similar histology; and 16S metagenomics sequencing analysis was positive (Veilonella, Pseudomonas). Despite 1 month of meropenem, MRI did not improve. The computer tomography and PET scan excluded extra-cranial infectious–inflammatory sites, and auto-immune genesis (sarcoidosis, histiocytosis, CNS vasculitis) was deemed unlikely due to the histological findings and unilateral lesions. We hypothesised possible IFD with peri-lesion inflammation and methyl-prednisolone was successfully introduced. Steroid tapering is ongoing and isavuconazole discontinuation is planned with close follow-up. In conclusion, the management of CNS complications in immunocompromised patients needs an interdisciplinary approach.

Published
2024

13. Effects of peripheral FAAH blockade on NTG-induced hyperalgesia—evaluation of URB937 in an animal model of migraine

Author

Greco, R, Bandiera, T, Mangione, AS, Demartini, C, Siani, F, Nappi, G, Sandrini, G, Guijarro, A, Armirotti, A, Piomelli, D, and Tassorelli, C

Subjects
Migraines, Pain Research, Neurosciences, Chronic Pain, Headaches, Dental/Oral and Craniofacial Disease, Neurological, Amidohydrolases, Analgesics, Animals, Cannabinoids, Disease Models, Animal, Dose-Response Relationship, Drug, Hyperalgesia, Male, Nitroglycerin, Pain Perception, Rats, Rats, Sprague-Dawley, Treatment Outcome, Migraine, nitroglycerin, hyperalgesia, anandamide, URB937, Clinical Sciences, Neurology & Neurosurgery
Abstract

BackgroundSystemic nitroglycerin (NTG) activates brain nuclei involved in nociceptive transmission as well as in neuroendocrine and autonomic functions in rats. These changes are considered relevant for migraine because NTG consistently provokes spontaneous-like migraine attacks in migraineurs. Several studies have suggested a relationship between the endocannabinoid levels and pain mediation in migraine. URB937, a peripheral inhibitor of fatty acid amide hydrolase (FAAH)-the enzyme that degrades anandamide, produces analgesia in animal models of pain, but there is no information on its effects in migraine.AimWe evaluated whether URB937 alters nociceptive responses in the animal model of migraine based on NTG administration in male rats, using the tail flick test and the plantar and orofacial formalin tests, under baseline conditions and after NTG administration. Furthermore, we investigated whether URB937 affects NTG-induced c-Fos expression in the brain.ResultsDuring the tail flick test, URB937 showed an antinociceptive effect in baseline conditions and it blocked NTG-induced hyperalgesia. URB937 also proved effective in counteracting NTG-induced hyperalgesia during both the plantar and orofacial formalin tests. Mapping of brain nuclei activated by NTG indicates that URB937 significantly reduces c-Fos expression in the nucleus trigeminalis caudalis and the locus coeruleus.ConclusionsThe data suggest that URB937 is capable of changing, probably via indirect mechanisms, the functional status of central structures that are important for pain transmission in an animal model of migraine.

Published
2015

15. Progress towards fabrication of Th:229-doped high energy band-gap crystals for use as a solid-state optical frequency reference

Author

Rellergert, Wade G., Sullivan, Scott T., DeMille, D., Greco, R. R., Hehlen, M. P., Jackson, R. A., Torgerson, J. R., and Hudson, Eric R.

Subjects
Physics - Atomic Physics
Abstract

We have recently described a novel method for the construction of a solid-state optical frequency reference based on doping $^{229}$Th into high energy band-gap crystals. Since nuclear transitions are far less sensitive to environmental conditions than atomic transitions, we have argued that the $^{229}$Th optical nuclear transition may be driven inside a host crystal resulting in an optical frequency reference with a short-term stability of $3\times10^{-17}<\Delta f/f <1\times10^{-15}$ at 1 s and a systematic-limited repeatability of $\Delta f/f \sim 2 \times 10^{-16}$. Improvement by $10^2-10^3$ of the constraints on the variability of several important fundamental constants also appears possible. Here we present the results of the first phase of these experiments. Specifically, we have evaluated several high energy band-gap crystals (Th:NaYF, Th:YLF, Th:LiCAF, Na$_2$ThF$_6$, LiSAF) for their suitability as a crystal host by a combination of electron beam microprobe measurements, Rutherford Backscattering, and synchrotron excitation/fluorescence measurements. These measurements have shown LiCAF to be the most promising host crystal, and using a $^{232}$Th doped LiCAF crystal, we have performed a mock run of the actual experiment that will be used to search for the isomeric transition in $^{229}$Th. This data indicates that a measurement of the transition energy with a signal to noise ratio (SNR) greater than 30:1 can be achieved at the lowest expected fluorescence rate., Comment: Eurodim Conference Proceedings

Published
2010
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16. Optical transition of the $^{229}$Th nucleus in a solid-state environment

Author

Rellergert, Wade G., DeMille, D., Greco, R. R., Hehlen, M. P., Torgerson, J. R., and Hudson, Eric R.

Subjects
Physics - Atomic Physics
Abstract

We describe a novel approach to directly measure the energy of the narrow, low-lying isomeric state in $^{229}$Th. Since nuclear transitions are far less sensitive to environmental conditions than atomic transitions, we argue that the $^{229}$Th optical nuclear transition may be driven inside a host crystal with a high transition Q. This technique might also allow for the construction of a solid-state optical frequency reference that surpasses the precision of current optical clocks, as well as improved limits on the variability of fundamental constants. Based on analysis of the crystal lattice environment, we argue that a precision of $3\times10^{-17}<\Delta f/f <1\times10^{-15}$ after 1 s of photon collection may be achieved with a systematic-limited accuracy of $\Delta f/f \sim 2 \times 10^{-16}$. Improvement by $10^2-10^3$ of the constraints on the variability of several important fundamental constants also appears possible., Comment: 5 pages

Published
2009

22. A simplified approach for the hydrological simulation of urban drainage systems with SWMM

Author

Farina A., Di Nardo A., Gargano R., van der Werf J. A., Greco R., Farina, A., Di Nardo, A., Gargano, R., van der Werf, J. A., and Greco, R.

Subjects
Simplified hydrological modelling, Lumped hydrological model, Hydrological parameter
Abstract

The management of an Urban Drainage System (UDS) is a complex task, as it requires extensive knowledge about precipitation regime, hydrological features of the catchment, hydraulic characteristics of the drainage network, and information about the water use by the served inhabitants. Complex semi-distributed hydrological and physically based hydraulic models are nowadays available to summarise such information and run simulations. However, in many cases, the uncertainty of the available hydrological information hampers the use of complex models. Hence, simple models with few parameters and small computational effort may be preferable, especially for UDS management problems requiring the execution of many simulations. This paper proposes a convenient approach to define effective lumped Simplified Models (SMs) of UDSs, the parameters of which can be estimated directly from cartographic information. For several case studies of UDS with different morphological and topological characteristics, SMs were built, capable of reproducing the hydrographs provided by available semi-distributed Detailed Models (DMs), assumed as benchmark in absence of measured hydrographs. To this aim, the SWMM simulation software was used, and the SM lumped parameters were calibrated by maximising the goodness of fit between the hydrograph of the DM and of the SM. The results show that SMs satisfactorily predict the hydrographs for all the case studies, and that robust relationships between the calibrated parameters and morphological and topological characteristics of the UDS can be established. This suggests that SMs can be used by decision makers for preliminary design, planning studies and management problems of UDSs, as their parameters can be soundly estimated from cartographic information. An example of application of SMs to Combined Sewer Overflow prediction is also presented.

Published
2023

23. MIS-A: Beware of non-lymphoma

Author

Cantoni, S, Greco, R, Mancini, V, Russo, V, Capasso, A, Travi, G, Vanzulli, A, Cairoli, R, Cantoni, S, Greco, R, Mancini, V, Russo, V, Capasso, A, Travi, G, Vanzulli, A, and Cairoli, R

Subjects
Lymphoma, SARS-CoV-2, MIS-A
Published
2023

24. Haematopoietic stem cell transplantation for severe autoimmune diseases in children: A review of current literature, registry activity and future directions on behalf of the autoimmune diseases and paediatric diseases working parties of the European Society for Blood and Marrow Transplantation

Author

Achini-Gutzwiller, F, Snowden, J, Corbacioglu, S, Greco, R, Alexander, T, Badoglio, M, Labopin, M, Abinun, M, Apte, S, Arnold, R, Domenech, A, Brierley, C, Burman, J, Castilla-Llorente, C, Cooper, N, Daghia, G, Daikeler, T, del Papa, N, de Vries-Bouwstra, J, Farge, D, Finke, J, Hagglund, H, Hawkey, C, Henes, J, Hiepe, F, Jessop, H, Kiely, D, Kazmi, M, Kirgizov, K, Kramer, E, Mancardi, G, Marjanovic, Z, Martin, R, Martin, T, Ma, D, Moore, J, Miller, P, Muraro, P, Oliveira, M, Polushin, A, Onida, F, Simoes, B, Puyade, M, Resnick, I, Ricart, E, Rovira, M, Saccardi, R, Saif, M, Sakellari, I, Sharrack, B, Snarski, E, Scherer, H, Sossa, C, Withers, B, Wulffraat, N, Zaccara, E, Amrolia, P, Ansari, M, Balduzzi, A, Dalassier, A, Dalle, J, Diaz, C, Feuchtinger, T, Locatelli, F, Lucchini, G, Galimard, J, Vincent, M, Handgretinger, R, Kleinschmidt, K, Lawitschka, A, Martinez, A, Peters, C, Rocha, V, Ruggeri, A, Sedlacek, P, Svec, P, Toporski, J, Yesilipek, A, Achini-Gutzwiller F. R., Snowden J. A., Corbacioglu S., Greco R., Alexander T., Snowden J., Badoglio M., Labopin M., Abinun M., Apte S., Arnold R., Domenech A., Brierley C., Burman J., Castilla-Llorente C., Cooper N., Daghia G., Daikeler T., del Papa N., de Vries-Bouwstra J., Farge D., Finke J., Hagglund H., Hawkey C., Henes J., Hiepe F., Jessop H., Kiely D., Kazmi M., Kirgizov K., Kramer E., Mancardi G., Marjanovic Z., Martin R., Martin T., Ma D., Moore J., Miller P., Muraro P., Oliveira M. -C., Polushin A., Onida F., Simoes B., Puyade M., Resnick I., Ricart E., Rovira M., Saccardi R., Saif M., Sakellari I., Sharrack B., Snarski E., Scherer H. U., Sossa C., Withers B., Wulffraat N., Zaccara E., Amrolia P., Ansari M., Balduzzi A., Dalassier A., Dalle J. -H., Diaz C. H., Feuchtinger T., Locatelli F., Lucchini G., Galimard J. -E., Vincent M. G., Handgretinger R., Kleinschmidt K., Lawitschka A., Martinez A. P., Peters C., Rocha V., Ruggeri A., Sedlacek P., Svec P., Toporski J., Yesilipek A., Achini-Gutzwiller, F, Snowden, J, Corbacioglu, S, Greco, R, Alexander, T, Badoglio, M, Labopin, M, Abinun, M, Apte, S, Arnold, R, Domenech, A, Brierley, C, Burman, J, Castilla-Llorente, C, Cooper, N, Daghia, G, Daikeler, T, del Papa, N, de Vries-Bouwstra, J, Farge, D, Finke, J, Hagglund, H, Hawkey, C, Henes, J, Hiepe, F, Jessop, H, Kiely, D, Kazmi, M, Kirgizov, K, Kramer, E, Mancardi, G, Marjanovic, Z, Martin, R, Martin, T, Ma, D, Moore, J, Miller, P, Muraro, P, Oliveira, M, Polushin, A, Onida, F, Simoes, B, Puyade, M, Resnick, I, Ricart, E, Rovira, M, Saccardi, R, Saif, M, Sakellari, I, Sharrack, B, Snarski, E, Scherer, H, Sossa, C, Withers, B, Wulffraat, N, Zaccara, E, Amrolia, P, Ansari, M, Balduzzi, A, Dalassier, A, Dalle, J, Diaz, C, Feuchtinger, T, Locatelli, F, Lucchini, G, Galimard, J, Vincent, M, Handgretinger, R, Kleinschmidt, K, Lawitschka, A, Martinez, A, Peters, C, Rocha, V, Ruggeri, A, Sedlacek, P, Svec, P, Toporski, J, Yesilipek, A, Achini-Gutzwiller F. R., Snowden J. A., Corbacioglu S., Greco R., Alexander T., Snowden J., Badoglio M., Labopin M., Abinun M., Apte S., Arnold R., Domenech A., Brierley C., Burman J., Castilla-Llorente C., Cooper N., Daghia G., Daikeler T., del Papa N., de Vries-Bouwstra J., Farge D., Finke J., Hagglund H., Hawkey C., Henes J., Hiepe F., Jessop H., Kiely D., Kazmi M., Kirgizov K., Kramer E., Mancardi G., Marjanovic Z., Martin R., Martin T., Ma D., Moore J., Miller P., Muraro P., Oliveira M. -C., Polushin A., Onida F., Simoes B., Puyade M., Resnick I., Ricart E., Rovira M., Saccardi R., Saif M., Sakellari I., Sharrack B., Snarski E., Scherer H. U., Sossa C., Withers B., Wulffraat N., Zaccara E., Amrolia P., Ansari M., Balduzzi A., Dalassier A., Dalle J. -H., Diaz C. H., Feuchtinger T., Locatelli F., Lucchini G., Galimard J. -E., Vincent M. G., Handgretinger R., Kleinschmidt K., Lawitschka A., Martinez A. P., Peters C., Rocha V., Ruggeri A., Sedlacek P., Svec P., Toporski J., and Yesilipek A.

Abstract

Although modern clinical management strategies have improved the outcome of paediatric patients with severe autoimmune and inflammatory diseases over recent decades, a proportion will experience ongoing or recurrent/relapsing disease activity despite multiple therapies often leading to irreversible organ damage, and compromised quality of life, growth/development and long-term survival. Autologous and allogeneic haematopoietic stem cell transplantation (HSCT) have been used successfully to induce disease control and often apparent cure of severe treatment-refractory autoimmune diseases (ADs) in children. However, transplant-related outcomes are disease-dependent and long-term outcome data are limited in respect to efficacy and safety. Moreover, balancing risks of HSCT against AD prognosis with continually evolving non-transplant options is challenging. This review appraises published literature on HSCT strategies and outcomes in individual paediatric ADs. We also provide a summary of the European Society for Blood and Marrow Transplantation (EBMT) Registry, where 343 HSCT procedures (176 autologous and 167 allogeneic) have been reported in 326 children (<18 years) for a range of AD indications. HSCT is a promising treatment modality, with potential long-term disease control or cure, but therapy-related morbidity and mortality need to be reduced. Further research is warranted to establish the position of HSCT in paediatric ADs via registries and prospective clinical studies to support evidence-based interspeciality guidelines and recommendations.

Published
2022

25. Diagnosis and management of urinary tract infections in children aged 2 months to 3 years in the Italian emergency units: the ItaUTI study

Author

Cenzato, F, Milani, G, Amigoni, A, Sperotto, F, Bianchetti, M, Agostoni, C, Montini, G, Farello, G, Chiarelli, F, Greco, R, Di Lollo, F, Rocco Forte, F, Manieri, S, Carpino, L, Caloiero, M, Cirisano, A, Bragho, S, Della Casa, R, Nunziata, F, Pecoraro, C, Pacifico, R, Lanari, M, Ghizzi, C, Serra, L, Stella, M, Maggiore, G, Fiorini, R, Dodi, I, Morelli, A, Lughetti, L, Cella, A, Vergine, G, De Fanti, A, Dragovic, D, Santori, D, Cozzi, G, Cogo, P, Raponi, M, Lubrano, R, de Martinis, M, Gatto, A, Barbieri, M, Reale, A, Bracaglia, G, Piccotti, E, Borea, R, Gaiero, A, Martelli, L, Arrighini, A, Cianci, P, Cavalli, C, De Santis, L, Pietra, B, Biondi, A, Sala, M, Pogliani, L, Cherubini, S, Bellini, M, Bruni, P, Traina, G, Tommasi, P, Del Barba, P, Arrigoni, S, Salvini, F, Bernardo, L, Bertolozzi, G, Fasoli, S, Marseglia, G, Palumbo, E, Bosco, A, Mirri, G, Fabiani, E, Ruffini, E, Pieragostini, L, Fornaro, M, Ripanti, G, Pannoni, D, Enrico, F, Perona, A, Tappi, E, Nis Haitink, O, Rabbone, I, Capalbo, P, Urbino, A, Guala, A, Cosi, G, Barracchia, M, Martire, B, Cardinale, F, Moramarco, F, Perrone, C, Campanozzi, A, Cecinati, V, Canetto, A, Clemente, C, Cualbu, A, Narducci, F, Mula, G, Bulciolu, P, Antonucci, R, Gramaglia, G, Cavaleri, G, Salpietro, C, Corsello, G, Salvo, R, Palmeri, M, Vitale, M, Morgano, A, Falorni, S, Peroni, D, Masi, S, Bertini, A, Vaccaro, A, Vasarri, P, Reinstadler, P, Soffiati, M, Stefanelli, M, Verrotti di Pianella, A, Bertone, C, Marzini, S, Da Dalt, L, Rugolotto, S, Scozzola, F, Ecclesio Livio, L, Cinquetti, M, Silvagni, D, Bellettato, M, Cenzato F., Milani G. P., Amigoni A., Sperotto F., Bianchetti M. G., Agostoni C., Montini G., Farello G., Chiarelli F., Greco R., Di Lollo F., Rocco Forte F., Manieri S., Carpino L., Caloiero M., Cirisano A., Bragho S., Della Casa R., Nunziata F., Pecoraro C., Pacifico R., Lanari M., Ghizzi C., Serra L., Stella M., Maggiore G., Fiorini R., Dodi I., Morelli A., Lughetti L., Cella A., Vergine G., De Fanti A., Dragovic D., Santori D., Cozzi G., Cogo P., Raponi M., Lubrano R., de Martinis M., Gatto A., Barbieri M. A., Reale A., Bracaglia G., Piccotti E., Borea R., Gaiero A., Martelli L., Arrighini A., Cianci P., Cavalli C., De Santis L., Pietra B. C., Biondi A., Sala M., Pogliani L. M., Cherubini S., Bellini M., Bruni P., Traina G., Tommasi P., Del Barba P., Arrigoni S., Salvini F. M., Bernardo L., Bertolozzi G., Fasoli S., Marseglia G. L., Palumbo E., Bosco A., Mirri G., Fabiani E., Ruffini E., Pieragostini L., Fornaro M., Ripanti G., Pannoni D., Enrico F., Perona A., Tappi E., Nis Haitink O., Rabbone I., Capalbo P. T., Urbino A., Guala A., Cosi G., Barracchia M. G., Martire B., Cardinale F., Moramarco F., Perrone C., Campanozzi A., Cecinati V., Canetto A., Clemente C., Cualbu A., Narducci F., Mula G., Bulciolu P., Antonucci R., Gramaglia G., Cavaleri G., Salpietro C., Corsello G., Salvo R., Palmeri M., Vitale M. A., Morgano A., Falorni S., Peroni D., Masi S., Bertini A., Vaccaro A., Vasarri P., Reinstadler P., Soffiati M., Stefanelli M., Verrotti di Pianella A., Bertone C., Marzini S., Da Dalt L., Rugolotto S., Scozzola F., Ecclesio Livio L., Cinquetti M., Silvagni D., Bellettato M., Cenzato, F, Milani, G, Amigoni, A, Sperotto, F, Bianchetti, M, Agostoni, C, Montini, G, Farello, G, Chiarelli, F, Greco, R, Di Lollo, F, Rocco Forte, F, Manieri, S, Carpino, L, Caloiero, M, Cirisano, A, Bragho, S, Della Casa, R, Nunziata, F, Pecoraro, C, Pacifico, R, Lanari, M, Ghizzi, C, Serra, L, Stella, M, Maggiore, G, Fiorini, R, Dodi, I, Morelli, A, Lughetti, L, Cella, A, Vergine, G, De Fanti, A, Dragovic, D, Santori, D, Cozzi, G, Cogo, P, Raponi, M, Lubrano, R, de Martinis, M, Gatto, A, Barbieri, M, Reale, A, Bracaglia, G, Piccotti, E, Borea, R, Gaiero, A, Martelli, L, Arrighini, A, Cianci, P, Cavalli, C, De Santis, L, Pietra, B, Biondi, A, Sala, M, Pogliani, L, Cherubini, S, Bellini, M, Bruni, P, Traina, G, Tommasi, P, Del Barba, P, Arrigoni, S, Salvini, F, Bernardo, L, Bertolozzi, G, Fasoli, S, Marseglia, G, Palumbo, E, Bosco, A, Mirri, G, Fabiani, E, Ruffini, E, Pieragostini, L, Fornaro, M, Ripanti, G, Pannoni, D, Enrico, F, Perona, A, Tappi, E, Nis Haitink, O, Rabbone, I, Capalbo, P, Urbino, A, Guala, A, Cosi, G, Barracchia, M, Martire, B, Cardinale, F, Moramarco, F, Perrone, C, Campanozzi, A, Cecinati, V, Canetto, A, Clemente, C, Cualbu, A, Narducci, F, Mula, G, Bulciolu, P, Antonucci, R, Gramaglia, G, Cavaleri, G, Salpietro, C, Corsello, G, Salvo, R, Palmeri, M, Vitale, M, Morgano, A, Falorni, S, Peroni, D, Masi, S, Bertini, A, Vaccaro, A, Vasarri, P, Reinstadler, P, Soffiati, M, Stefanelli, M, Verrotti di Pianella, A, Bertone, C, Marzini, S, Da Dalt, L, Rugolotto, S, Scozzola, F, Ecclesio Livio, L, Cinquetti, M, Silvagni, D, Bellettato, M, Cenzato F., Milani G. P., Amigoni A., Sperotto F., Bianchetti M. G., Agostoni C., Montini G., Farello G., Chiarelli F., Greco R., Di Lollo F., Rocco Forte F., Manieri S., Carpino L., Caloiero M., Cirisano A., Bragho S., Della Casa R., Nunziata F., Pecoraro C., Pacifico R., Lanari M., Ghizzi C., Serra L., Stella M., Maggiore G., Fiorini R., Dodi I., Morelli A., Lughetti L., Cella A., Vergine G., De Fanti A., Dragovic D., Santori D., Cozzi G., Cogo P., Raponi M., Lubrano R., de Martinis M., Gatto A., Barbieri M. A., Reale A., Bracaglia G., Piccotti E., Borea R., Gaiero A., Martelli L., Arrighini A., Cianci P., Cavalli C., De Santis L., Pietra B. C., Biondi A., Sala M., Pogliani L. M., Cherubini S., Bellini M., Bruni P., Traina G., Tommasi P., Del Barba P., Arrigoni S., Salvini F. M., Bernardo L., Bertolozzi G., Fasoli S., Marseglia G. L., Palumbo E., Bosco A., Mirri G., Fabiani E., Ruffini E., Pieragostini L., Fornaro M., Ripanti G., Pannoni D., Enrico F., Perona A., Tappi E., Nis Haitink O., Rabbone I., Capalbo P. T., Urbino A., Guala A., Cosi G., Barracchia M. G., Martire B., Cardinale F., Moramarco F., Perrone C., Campanozzi A., Cecinati V., Canetto A., Clemente C., Cualbu A., Narducci F., Mula G., Bulciolu P., Antonucci R., Gramaglia G., Cavaleri G., Salpietro C., Corsello G., Salvo R., Palmeri M., Vitale M. A., Morgano A., Falorni S., Peroni D., Masi S., Bertini A., Vaccaro A., Vasarri P., Reinstadler P., Soffiati M., Stefanelli M., Verrotti di Pianella A., Bertone C., Marzini S., Da Dalt L., Rugolotto S., Scozzola F., Ecclesio Livio L., Cinquetti M., Silvagni D., and Bellettato M.

Abstract

Urinary tract infections (UTIs) are among the most frequent bacterial diseases in infants and children. Physician adherence to recommendations is notoriously often poor, but no data are available on UTIs management in the emergency setting. In this multicenter national study, we investigated the policies regarding UTIs management in children aged 2 months to 3 years in Italian emergency units. Between April and June 2021, directors of the emergency units were invited to answer an online survey on the following items: diagnostic approach to children with fever without an apparent source, therapeutic approach to UTIs, the use of kidney and urinary tract ultrasound, and the criteria for hospitalization. A total of 121 (89%) out of 139 of invited units participated in the study. Overall, units manage children with a suspected or confirmed UTI according to available recommendations for most of the items. However, in almost 80% (n = 94) of units, a sterile perineal bag is used to collect urine for culture. When urine is collected by cathether, heterogeneity exists on the threshold of bacterial load considered for UTI diagnosis. Conclusions: Available recommendations on UTIs in children are followed by Italian emergency units for most of the items. However, the methods to collect urine specimens for culture, one of the crucial steps of the diagnostic work-up, often do not align with current recommendations and CFU thresholds considered for diagnosis largely vary among centers. Efforts should be addressed to validate and implement new child and family friendly urine collection techniques.What is Known:• Several guidelines are published on the management of children with suspected or confirmed urinary tract infection.• No data are available on the management of pediatric urinary tract infections in the emergency setting.What is New:• Almost 80% of the Italian emergency units employ a sterile perineal bag to collect urine for culture.• Diagnostic

Published
2022

28. Topic: AS01-Diagnosis/AS01c-Molecular aberrations (cytogenetic, genetic, gene expression): A CARTOGRAPHY OF UBA1 GENE TESTING, EPIDEMIOLOGY AND CLINICAL-GENOMIC CHARACTERISTICS: THE VEXAS/MDS ITALIAN EXPERIENCE

Author

Gurnari, C., primary, Pascale, M.R., additional, Vitale, A., additional, Diral, E., additional, Galossi, E., additional, Falconi, G., additional, Bruno, A., additional, Crisafulli, F., additional, Frassi, M., additional, Cattaneo, C., additional, Bertoli, D., additional, Bernardi, M., additional, Condorelli, A., additional, Morsia, E., additional, Crisà, E., additional, Triggianese, P., additional, Brussino, L., additional, Battipaglia, G., additional, Bindoli, S., additional, Sfriso, P., additional, Caroni, F., additional, Olivieri, A., additional, Kordasti, S., additional, Albano, F., additional, Pane, F., additional, Musto, P., additional, Bocchia, M., additional, Lugli, E., additional, Rambaldi, A., additional, Greco, R., additional, Franceschini, F., additional, Ciceri, F., additional, Cantarini, L., additional, and Voso, M.T., additional

Published
2023
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29. Hematopoietic cell transplantation and cellular therapies in Europe 2021. The second year of the SARS-CoV-2 pandemic. A Report from the EBMT Activity Survey.

Author

Passweg, J.R., Baldomero, H., Ciceri, F., Corbacioglu, S., Cámara, R. de la, Dolstra, H., Glass, B., Greco, R., McLornan, D.P., Neven, B., Latour, R.P. de, Perić, Z., Ruggeri, A., Snowden, J.A., Sureda, A., Passweg, J.R., Baldomero, H., Ciceri, F., Corbacioglu, S., Cámara, R. de la, Dolstra, H., Glass, B., Greco, R., McLornan, D.P., Neven, B., Latour, R.P. de, Perić, Z., Ruggeri, A., Snowden, J.A., and Sureda, A.

Abstract

01 juni 2023, Item does not contain fulltext, In 2021, 47,412 HCT (19,806 (42%) allogeneic and 27,606 (58%) autologous) in 43,109 patients were reported by 694 European centers. 3494 patients received advanced cellular therapies, 2524 of which were CAR-T treatments, an additional 3245 received DLI. Changes compared to the previous year were CAR-T treatment (+35%), allogeneic HCT +5.4%, autologous HCT +3.9%, more pronounced in non-malignant disorders. Main indications for allogeneic HCT were myeloid malignancies 10,745 (58%), lymphoid malignancies 5127 (28%) and non-malignant disorders 2501 (13%). Main indications for autologous HCT were lymphoid malignancies 22,129 (90%) and solid tumors 1635 (7%). In allogeneic HCT, use of haploidentical donors decreased by -0.9% while use of unrelated and sibling donors increased by +4.3% and +9%. Cord blood HCT decreased by -5.8%. Pediatric HCT increased overall by +5.6% (+6.9% allogeneic and +1.6% autologous). Increase in the use of CAR-T was mainly restricted to high-income countries. The drop in HCT activity reported in 2020 partially recovered in 2021, the second year of the SARS-CoV-2 pandemic. The transplant community confronted with the pandemic challenge, continued in providing patients access to treatment. This annual EBMT report reflects current activities useful for health care resource planning.

Published
2023

30. Practice harmonization workshops of EBMT: an expert-based approach to generate practical and contemporary guidelines within the arena of hematopoietic cell transplantation and cellular therapy.

Author

Yakoub-Agha, I., Greco, R., Onida, F., Cámara, R. de la, Ciceri, F., Corbacioglu, S., Dolstra, H., Glass, B., Kenyon, M., McLornan, D.P., Neven, B., Latour, R.P. de, Peric, Z., Ruggeri, A., Snowden, J.A., Sureda, A., Sánchez-Ortega, I., Yakoub-Agha, I., Greco, R., Onida, F., Cámara, R. de la, Ciceri, F., Corbacioglu, S., Dolstra, H., Glass, B., Kenyon, M., McLornan, D.P., Neven, B., Latour, R.P. de, Peric, Z., Ruggeri, A., Snowden, J.A., Sureda, A., and Sánchez-Ortega, I.

Abstract

01 juni 2023, Item does not contain fulltext, For hematopoietic cell transplantation (HCT) and cellular therapy (CT), clinical patient care is localized, and practices may differ between countries and from center to center even within the same country. Historically, international guidelines were not always adapted to the changing daily clinical practice and practical topics there were not always addressed. In the absence of well-established guidelines, centers tended to develop local procedures/policies, frequently with limited communication with other centers. To try to harmonize localized clinical practices for malignant and non-malignant hematological disorders within EBMT scope, the practice harmonization and guidelines (PH&G) committee of the EBMT will co-ordinate workshops with topic-specific experts from interested centers. Each workshop will discuss a specific issue and write guidelines/recommendations that practically addresses the topic under review. To provide clear, practical and user-friendly guidelines when international consensus is lacking, the EBMT PH&G committee plans to develop European guidelines by HCT and CT physicians for peers' use. Here, we define how workshops will be conducted and guidelines/recommendations produced, approved and published. Ultimately, there is an aspiration for some topics, where there is sufficient evidence base to be considered for systematic reviews, which are a more robust and future-proofed basis for guidelines/recommendations than consensus opinion.

Published
2023

31. Benchmarking of survival outcomes following Haematopoietic Stem Cell Transplantation (HSCT): an update of the ongoing project of the European Society for Blood and Marrow Transplantation (EBMT) and Joint Accreditation Committee of ISCT and EBMT (JACIE).

Author

Saccardi, R., Putter, H., Eikema, D.J., Busto, M.P., McGrath, E., Middelkoop, B., Adams, G., Atlija, M., Ayuk, F.A., Baldomero, H., Beguin, Y., Cámara, R. de la, Cedillo, Á., Balari, A.M.S., Chabannon, C., Corbacioglu, S., Dolstra, H., Duarte, R.F., Dulery, R., Greco, R., Gusi, A., Hamad, N., Kenyon, M., Kröger, N., Labopin, M., Lee, J., Ljungman, P., Manson, L., Mensil, F., Milpied, N., Mohty, M., Oldani, E., Orchard, K., Passweg, J., Pearce, R., Latour, R.P. de, Poirel, H.A., Rintala, T., Rizzo, J.D., Ruggeri, A., Sanchez-Martinez, C., Sanchez-Guijo, F., Sánchez-Ortega, I., Trnková, M., Ferreiras, D.V., Wilcox, L., Wreede, L.C. de, Snowden, J.A., Saccardi, R., Putter, H., Eikema, D.J., Busto, M.P., McGrath, E., Middelkoop, B., Adams, G., Atlija, M., Ayuk, F.A., Baldomero, H., Beguin, Y., Cámara, R. de la, Cedillo, Á., Balari, A.M.S., Chabannon, C., Corbacioglu, S., Dolstra, H., Duarte, R.F., Dulery, R., Greco, R., Gusi, A., Hamad, N., Kenyon, M., Kröger, N., Labopin, M., Lee, J., Ljungman, P., Manson, L., Mensil, F., Milpied, N., Mohty, M., Oldani, E., Orchard, K., Passweg, J., Pearce, R., Latour, R.P. de, Poirel, H.A., Rintala, T., Rizzo, J.D., Ruggeri, A., Sanchez-Martinez, C., Sanchez-Guijo, F., Sánchez-Ortega, I., Trnková, M., Ferreiras, D.V., Wilcox, L., Wreede, L.C. de, and Snowden, J.A.

Abstract

01 juni 2023, Item does not contain fulltext, From 2016 EBMT and JACIE developed an international risk-adapted benchmarking program of haematopoietic stem cell transplant (HSCT) outcome to provide individual EBMT Centers with a means of quality-assuring the HSCT process and meeting FACT-JACIE accreditation requirements relating to 1-year survival outcomes. Informed by previous experience from Europe, North America and Australasia, the Clinical Outcomes Group (COG) established criteria for patient and Center selection, and a set of key clinical variables within a dedicated statistical model adapted to the capabilities of the EBMT Registry. The first phase of the project was launched in 2019 to test the acceptability of the benchmarking model through assessment of Centers' performance for 1-year data completeness and survival outcomes of autologous and allogeneic HSCT covering 2013-2016. A second phase was delivered in July 2021 covering 2015-2019 and including survival outcomes. Reports of individual Center performance were shared directly with local principal investigators and their responses were assimilated. The experience thus far has supported the feasibility, acceptability and reliability of the system as well as identifying its limitations. We provide a summary of experience and learning so far in this 'work in progress', as well as highlighting future challenges of delivering a modern, robust, data-complete, risk-adapted benchmarking program across new EBMT Registry systems.

Published
2023

32. Cu-based Z-schemes family photocatalysts for solar H₂ production

Author

Greco, R. (Rossella), Botella, R. (Romain), Fernández-Catalá, J. (Javier), Greco, R. (Rossella), Botella, R. (Romain), and Fernández-Catalá, J. (Javier)

Abstract

Solar photocatalytic H₂ production has drawn an increasing amount of attention from the scientific community, industry, and society due to its use of green solar energy and a photocatalyst (semiconductor material) to produce green H₂. Cu-based semiconductors are interesting as photocatalysts for H₂ production because Cu is earth-abundant, cheap, and the synthesis of its copper-containing semiconductors is straightforward. Moreover, Cu-based semiconductors absorb visible light and present an adequate redox potential to perform water splitting reaction. Nevertheless, pristine Cu-based semiconductors exhibit low photoactivity due to the rapid recombination of photo-induced electron-hole (e⁻-h⁺) pairs and are subject to photo corrosion. To remedy these pitfalls, the Cu semiconductor-based Z-scheme family (Z-schemes and S-schemes) presents great interest due to the charge carrier mechanism involved. Due to the interest of Z-scheme photocatalysts in this issue, the basic concepts of the Z-scheme focusing on Cu-based semiconductors are addressed to obtain novel systems with high H₂ photo-catalytic activity. Focusing on H₂ production using Cu-based Z-schemes photocatalyst, the most representative examples are included in the main text. To conclude, an outlook on the future challenges of this topic is addressed.

Published
2023

33. Decrease of lethal infectious complications in the context of causes of death (COD) after hematopoietic cell transplantation: COD-2 and COD-1 study of the Infectious Diseases Working Party EBMT.

Author

Styczynski, J., Tridello, G., Koster, L, Knelange, N., Wendel, L., Biezen, A. van, Werf, S. van der, Mikulska, M., Gil, L., Cordonnier, C., Ljungman, P., Averbuch, D., Cesaro, S., Baldomero, H., Chabannon, C., Corbacioglu, S., Dolstra, H., Glass, B., Greco, R., Kröger, N., Latour, R.P. de, Mohty, M., Neven, B., Peric, Z., Snowden, J.A., Sureda, A., Yakoub-Agha, I., Camara, R. de la, Styczynski, J., Tridello, G., Koster, L, Knelange, N., Wendel, L., Biezen, A. van, Werf, S. van der, Mikulska, M., Gil, L., Cordonnier, C., Ljungman, P., Averbuch, D., Cesaro, S., Baldomero, H., Chabannon, C., Corbacioglu, S., Dolstra, H., Glass, B., Greco, R., Kröger, N., Latour, R.P. de, Mohty, M., Neven, B., Peric, Z., Snowden, J.A., Sureda, A., Yakoub-Agha, I., and Camara, R. de la

Abstract

01 augustus 2023, Item does not contain fulltext, We previously analyzed trends in incidence and factors associated with lethal complications in ALL/AML/CML patients (causes of deaths; COD-1 study). The objective of this study was the analysis of incidence and specific causes of death after HCT, with focus on infectious deaths in two time periods, 1980-2001 (cohort-1) and 2002-2015 (cohort-2). All patients with HCT for lymphoma, plasma cell disorders, chronic leukemia (except CML), myelodysplastic/myeloproliferative disorders, registered in the EBMT-ProMISe-database were included (n = 232,618) (COD-2 study). Results were compared to those in the ALL/AML/CML COD-1 study. Mortality from bacterial, viral, fungal, and parasitic infections decreased in very early, early and intermediate phases. In the late phase, mortality from bacterial infections increased, while mortality from fungal, viral, or unknown infectious etiology did not change. This pattern was similar for allo- and auto-HCT in COD-1 and COD-2 studies, with a distinct and constant lower incidence of all types of infections at all phases, after auto-HCT. In conclusion, infections were the main cause of death before day +100, followed by relapse. Mortality from infectious deaths significantly decreased, except late phase. Post-transplant mortality has significantly decreased in all phases, from all causes after auto-HCT; it has decreased in all phases after allo-HCT except late phase.

Published
2023

34. Multiparametric Flow Cytometry-MRD Assay: Lesson from Phase II Trail REL AML 001

Author

Gatti, A, Veronese, S, Grillo, G, Di Camillo, B, Fumagalli, M, Krampera, M, Zappasodi, P, Borlenghi, E, Todisco, E, Ubezio, M, Bernardi, M, Molteni, A, Basilico, C, Turrini, M, Greco, R, Mancini, V, Riva, M, Magliano, G, Stefanucci, M, Brando, B, Beghini, A, Cairoli, R, Gatti, Arianna, Veronese, Silvio, Grillo, Giovanni, Di Camillo, Barbara, Fumagalli, Monica, Krampera, Mauro, Zappasodi, Patrizia, Borlenghi, Erika, Todisco, Elisabetta, Ubezio, Marta, Bernardi, Massimo, Molteni, Alfredo, Basilico, Claudia, Turrini, Mauro, Greco, Rosa, Mancini, Valentina, Riva, Marta, Magliano, Gabriele, Stefanucci, Marta Rachele, Brando, Bruno, Beghini, Alessandro, Cairoli, Roberto, Gatti, A, Veronese, S, Grillo, G, Di Camillo, B, Fumagalli, M, Krampera, M, Zappasodi, P, Borlenghi, E, Todisco, E, Ubezio, M, Bernardi, M, Molteni, A, Basilico, C, Turrini, M, Greco, R, Mancini, V, Riva, M, Magliano, G, Stefanucci, M, Brando, B, Beghini, A, Cairoli, R, Gatti, Arianna, Veronese, Silvio, Grillo, Giovanni, Di Camillo, Barbara, Fumagalli, Monica, Krampera, Mauro, Zappasodi, Patrizia, Borlenghi, Erika, Todisco, Elisabetta, Ubezio, Marta, Bernardi, Massimo, Molteni, Alfredo, Basilico, Claudia, Turrini, Mauro, Greco, Rosa, Mancini, Valentina, Riva, Marta, Magliano, Gabriele, Stefanucci, Marta Rachele, Brando, Bruno, Beghini, Alessandro, and Cairoli, Roberto

Published
2023

35. Immune effector cell–associated hematotoxicity: EHA/EBMT consensus grading and best practice recommendations

Author

Rejeski, K, Subklewe, M, Aljurf, M, Bachy, E, Balduzzi, A, Barba, P, Bruno, B, Benjamin, R, Carrabba, M, Chabannon, C, Ciceri, F, Corradini, P, Delgado, J, Di Blasi, R, Greco, R, Houot, R, Iacoboni, G, Jaeger, U, Kersten, M, Mielke, S, Nagler, A, Onida, F, Peric, Z, Roddie, C, Ruggeri, A, Sanchez-Guijo, F, Sánchez-Ortega, I, Schneidawind, D, Schubert, M, Snowden, J, Thieblemont, C, Topp, M, Zinzani, P, Gribben, J, Bonini, C, Sureda Balari, A, Yakoub-Agha, I, Rejeski, Kai, Subklewe, Marion, Aljurf, Mahmoud, Bachy, Emmanuel, Balduzzi, Adriana Cristina, Barba, Pere, Bruno, Benedetto, Benjamin, Reuben, Carrabba, Matteo Giovanni, Chabannon, Christian, Ciceri, Fabio, Corradini, Paolo, Delgado, Julio, Di Blasi, Roberta, Greco, Raffaella, Houot, Roch, Iacoboni, Gloria, Jaeger, Ulrich, Kersten, Marie José, Mielke, Stephan, Nagler, Arnon, Onida, Francesco, Peric, Zinaida, Roddie, Claire, Ruggeri, Annalisa, Sanchez-Guijo, Fermin M, Sánchez-Ortega, Isabel, Schneidawind, Dominik, Schubert, Maria-Luisa, Snowden, John, Thieblemont, Catherine, Topp, Max S, Zinzani, Pierluigi Luigi, Gribben, John G, Bonini, Chiara, Sureda Balari, Anna, Yakoub-Agha, Ibrahim, Rejeski, K, Subklewe, M, Aljurf, M, Bachy, E, Balduzzi, A, Barba, P, Bruno, B, Benjamin, R, Carrabba, M, Chabannon, C, Ciceri, F, Corradini, P, Delgado, J, Di Blasi, R, Greco, R, Houot, R, Iacoboni, G, Jaeger, U, Kersten, M, Mielke, S, Nagler, A, Onida, F, Peric, Z, Roddie, C, Ruggeri, A, Sanchez-Guijo, F, Sánchez-Ortega, I, Schneidawind, D, Schubert, M, Snowden, J, Thieblemont, C, Topp, M, Zinzani, P, Gribben, J, Bonini, C, Sureda Balari, A, Yakoub-Agha, I, Rejeski, Kai, Subklewe, Marion, Aljurf, Mahmoud, Bachy, Emmanuel, Balduzzi, Adriana Cristina, Barba, Pere, Bruno, Benedetto, Benjamin, Reuben, Carrabba, Matteo Giovanni, Chabannon, Christian, Ciceri, Fabio, Corradini, Paolo, Delgado, Julio, Di Blasi, Roberta, Greco, Raffaella, Houot, Roch, Iacoboni, Gloria, Jaeger, Ulrich, Kersten, Marie José, Mielke, Stephan, Nagler, Arnon, Onida, Francesco, Peric, Zinaida, Roddie, Claire, Ruggeri, Annalisa, Sanchez-Guijo, Fermin M, Sánchez-Ortega, Isabel, Schneidawind, Dominik, Schubert, Maria-Luisa, Snowden, John, Thieblemont, Catherine, Topp, Max S, Zinzani, Pierluigi Luigi, Gribben, John G, Bonini, Chiara, Sureda Balari, Anna, and Yakoub-Agha, Ibrahim

Abstract

Hematological toxicity is the most common adverse event after chimeric antigen receptor (CAR) T-cell therapy. Cytopenias can be profound and long-lasting and can predispose for severe infectious complications. In a recent worldwide survey, we demonstrated that there remains considerable heterogeneity in regard to current practice patterns. Here, we sought to build consensus on the grading and management of immune effector cell–associated hematotoxicity (ICAHT) after CAR T-cell therapy. For this purpose, a joint effort between the European Society for Blood and Marrow Transplantation (EBMT) and the European Hematology Association (EHA) involved an international panel of 36 CAR T-cell experts who met in a series of virtual conferences, culminating in a 2-day meeting in Lille, France. On the basis of these deliberations, best practice recommendations were developed. For the grading of ICAHT, a classification system based on depth and duration of neutropenia was developed for early (day 0-30) and late (after day +30) cytopenia. Detailed recommendations on risk factors, available preinfusion scoring systems (eg, CAR-HEMATOTOX score), and diagnostic workup are provided. A further section focuses on identifying hemophagocytosis in the context of severe hematotoxicity. Finally, we review current evidence and provide consensus recommendations for the management of ICAHT, including growth factor support, anti-infectious prophylaxis, transfusions, autologous hematopoietic stem cell boost, and allogeneic hematopoietic cell transplantation. In conclusion, we propose ICAHT as a novel toxicity category after immune effector cell therapy, provide a framework for its grading, review literature on risk factors, and outline expert recommendations for the diagnostic workup and short- and long-term management.

Published
2023

36. Neural stem cell transplantation in patients with progressive multiple sclerosis: an open-label, phase 1 study

Author

Genchi, A, Brambilla, E, Sangalli, F, Radaelli, M, Bacigaluppi, M, Furlan, R, Andolfo, A, Drago, D, Magagnotti, C, Scotti, G, Greco, R, Vezzulli, P, Ottoboni, L, Bonopane, M, Capilupo, D, Ruffini, F, Belotti, D, Cabiati, B, Cesana, S, Matera, G, Leocani, L, Martinelli, V, Moiola, L, Vago, L, Panina-Bordignon, P, Falini, A, Ciceri, F, Uglietti, A, Sormani, M, Comi, G, Battaglia, M, Rocca, M, Storelli, L, Pagani, E, Gaipa, G, Martino, G, Genchi, Angela, Brambilla, Elena, Sangalli, Francesca, Radaelli, Marta, Bacigaluppi, Marco, Furlan, Roberto, Andolfo, Annapaola, Drago, Denise, Magagnotti, Cinzia, Scotti, Giulia Maria, Greco, Raffaella, Vezzulli, Paolo, Ottoboni, Linda, Bonopane, Marco, Capilupo, Daniela, Ruffini, Francesca, Belotti, Daniela, Cabiati, Benedetta, Cesana, Stefania, Matera, Giada, Leocani, Letizia, Martinelli, Vittorio, Moiola, Lucia, Vago, Luca, Panina-Bordignon, Paola, Falini, Andrea, Ciceri, Fabio, Uglietti, Anna, Sormani, Maria Pia, Comi, Giancarlo, Battaglia, Mario Alberto, Rocca, Maria A, Storelli, Loredana, Pagani, Elisabetta, Gaipa, Giuseppe, Martino, Gianvito, Genchi, A, Brambilla, E, Sangalli, F, Radaelli, M, Bacigaluppi, M, Furlan, R, Andolfo, A, Drago, D, Magagnotti, C, Scotti, G, Greco, R, Vezzulli, P, Ottoboni, L, Bonopane, M, Capilupo, D, Ruffini, F, Belotti, D, Cabiati, B, Cesana, S, Matera, G, Leocani, L, Martinelli, V, Moiola, L, Vago, L, Panina-Bordignon, P, Falini, A, Ciceri, F, Uglietti, A, Sormani, M, Comi, G, Battaglia, M, Rocca, M, Storelli, L, Pagani, E, Gaipa, G, Martino, G, Genchi, Angela, Brambilla, Elena, Sangalli, Francesca, Radaelli, Marta, Bacigaluppi, Marco, Furlan, Roberto, Andolfo, Annapaola, Drago, Denise, Magagnotti, Cinzia, Scotti, Giulia Maria, Greco, Raffaella, Vezzulli, Paolo, Ottoboni, Linda, Bonopane, Marco, Capilupo, Daniela, Ruffini, Francesca, Belotti, Daniela, Cabiati, Benedetta, Cesana, Stefania, Matera, Giada, Leocani, Letizia, Martinelli, Vittorio, Moiola, Lucia, Vago, Luca, Panina-Bordignon, Paola, Falini, Andrea, Ciceri, Fabio, Uglietti, Anna, Sormani, Maria Pia, Comi, Giancarlo, Battaglia, Mario Alberto, Rocca, Maria A, Storelli, Loredana, Pagani, Elisabetta, Gaipa, Giuseppe, and Martino, Gianvito

Abstract

Innovative pro-regenerative treatment strategies for progressive multiple sclerosis (PMS), combining neuroprotection and immunomodulation, represent an unmet need. Neural precursor cells (NPCs) transplanted in animal models of multiple sclerosis have shown preclinical efficacy by promoting neuroprotection and remyelination by releasing molecules sustaining trophic support and neural plasticity. Here we present the results of STEMS, a prospective, therapeutic exploratory, non-randomized, open-label, single-dose-finding phase 1 clinical trial (NCT03269071, EudraCT 2016-002020-86), performed at San Raffaele Hospital in Milan, Italy, evaluating the feasibility, safety and tolerability of intrathecally transplanted human fetal NPCs (hfNPCs) in 12 patients with PMS (with evidence of disease progression, Expanded Disability Status Scale ≥6.5, age 18–55 years, disease duration 2–20 years, without any alternative approved therapy). The safety primary outcome was reached, with no severe adverse reactions related to hfNPCs at 2-year follow-up, clearly demonstrating that hfNPC therapy in PMS is feasible, safe and tolerable. Exploratory secondary analyses showed a lower rate of brain atrophy in patients receiving the highest dosage of hfNPCs and increased cerebrospinal fluid levels of anti-inflammatory and neuroprotective molecules. Although preliminary, these results support the rationale and value of future clinical studies with the highest dose of hfNPCs in a larger cohort of patients.

Published
2023

39. Haematopoietic stem cell transplantation for severe autoimmune diseases in children : a review of current literature, registry activity and future directions on behalf of the autoimmune diseases and paediatric diseases working parties of the European Society for Blood and Marrow Transplantation

Author

Achini‐Gutzwiller, FR, Snowden, JA, Corbacioglu, S, Greco, R, Alexander, T, Snowden, J, Badoglio, M, Labopin, M, Abinun, M, Apte, S, Arnold, R, Domenech, A, Brierley, C, Burman, J, Castilla‐Llorente, C, Cooper, N, Daghia, G, Daikeler, T, del Papa, N, de Vries‐Bouwstra, J, Farge, D, Finke, J, Hagglund, H, Hawkey, C, Henes, J, Hiepe, F, Jessop, H, Kiely, D, Kazmi, M, Kirgizov, K, Kramer, E, Mancardi, G, Marjanovic, Z, Martin, R, Martin, T, Ma, D, Moore, J, Miller, P, Muraro, P, Oliveira, M, Polushin, A, Onida, F, Simoes, B, Puyade, M, Resnick, I, Ricart, E, Rovira, M, Saccardi, R, Saif, M, Sakellari, I, Sharrack, B, Snarski, E, Scherer, HU, Sossa, C, Withers, B, Wulffraat, N, Zaccara, E, Amrolia, P, Ansari, M, Balduzzi, A, Dalassier, A, Dalle, J, Diaz, CH, Feuchtinger, T, Locatelli, F, Lucchini, G, Galimard, J, Vincent, MG, Handgretinger, R, Kleinschmidt, K, Lawitschka, A, Martinez, AP, Peters, C, Rocha, V, Ruggeri, A, Sedlacek, P, Svec, P, Toporski, J, Yesilipek, A, Achini-Gutzwiller, F, Snowden, J, Corbacioglu, S, Greco, R, Alexander, T, Badoglio, M, Labopin, M, Abinun, M, Apte, S, Arnold, R, Domenech, A, Brierley, C, Burman, J, Castilla-Llorente, C, Cooper, N, Daghia, G, Daikeler, T, del Papa, N, de Vries-Bouwstra, J, Farge, D, Finke, J, Hagglund, H, Hawkey, C, Henes, J, Hiepe, F, Jessop, H, Kiely, D, Kazmi, M, Kirgizov, K, Kramer, E, Mancardi, G, Marjanovic, Z, Martin, R, Martin, T, Ma, D, Moore, J, Miller, P, Muraro, P, Oliveira, M, Polushin, A, Onida, F, Simoes, B, Puyade, M, Resnick, I, Ricart, E, Rovira, M, Saccardi, R, Saif, M, Sakellari, I, Sharrack, B, Snarski, E, Scherer, H, Sossa, C, Withers, B, Wulffraat, N, Zaccara, E, Amrolia, P, Ansari, M, Balduzzi, A, Dalassier, A, Dalle, J, Diaz, C, Feuchtinger, T, Locatelli, F, Lucchini, G, Galimard, J, Vincent, M, Handgretinger, R, Kleinschmidt, K, Lawitschka, A, Martinez, A, Peters, C, Rocha, V, Ruggeri, A, Sedlacek, P, Svec, P, Toporski, J, and Yesilipek, A

Subjects
autoimmune diseases, haematopoietic stem cell transplantation, paediatric, ddc:610, paediatric, surgical procedures, operative, Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA, haematopoietic stem cell transplantation, 610 Medizin, autoimmune diseases, autoimmune disease, Hematology
Abstract

Although modern clinical management strategies have improved the outcome of paediatric patients with severe autoimmune and inflammatory diseases over recent decades, a proportion will experience ongoing or recurrent/relapsing disease activity despite multiple therapies often leading to irreversible organ damage, and compromised quality of life, growth/development and long-term survival. Autologous and allogeneic haematopoietic stem cell transplantation (HSCT) have been used successfully to induce disease control and often apparent cure of severe treatment-refractory autoimmune diseases (ADs) in children. However, transplant-related outcomes are disease-dependent and long-term outcome data are limited in respect to efficacy and safety. Moreover, balancing risks of HSCT against AD prognosis with continually evolving non-transplant options is challenging. This review appraises published literature on HSCT strategies and outcomes in individual paediatric ADs. We also provide a summary of the European Society for Blood and Marrow Transplantation (EBMT) Registry, where 343 HSCT procedures (176 autologous and 167 allogeneic) have been reported in 326 children (

Published
2022

40. Z-scheme Bi₂O₃/Bi/ZnIn₂S₄ photocatalyst for enhancing the removal performance of Cr(VI), 2,4-dinitrophenol and tetracycline

Author

Luo, J. (Jing), Shi, Z. (Zhaoxia), Meng, J. (Jiefeng), Li, F. (Feng), Li, T. (Taohai), Zhang, M. (Meng), Greco, R. (Rossella), and Cao, W. (Wei)

Subjects
Synthesis, Bi₂O₃/Bi/ZnIn₂S₄, Photocatalysis, Z-scheme heterojunction
Abstract

Construction of heterojunctions is conventionally regarded as the prevailing technique to enhance solar-driven photocatalytic water splitting and photodegradation of pollutants. Herein, we report a novel design of a ternary Bi₂O₃/Bi/ZnIn₂S₄ system, which was facilely synthesized to satisfy these stringent criteria for sunlight photocatalytic removal of organic and ionic pollutants and hydrogen evolution. Bi₂O₃/Bi/ZnIn₂S₄ could degrade 2,4-dinitrophenol (94.6%), tetracycline (96.5%), and Cr⁶⁺ (96.3%) effectively under visible light and give a hydrogen production rate of 482.5 μmol·g⁻¹·h⁻¹ under visible light. Based on first-principles calculations and electrochemical results, our system could be identified as a Z-scheme. Photocorrosion of the sulfide is prohibited while the catalytic capabilities are simultaneously benefited due to lowered bandgap in light harvesting, internal electric fields in charge separations, and surface plasmonic resonance enhanced electron boost.

Published
2023

42. P013 - Topic: AS01-Diagnosis/AS01c-Molecular aberrations (cytogenetic, genetic, gene expression): A CARTOGRAPHY OF UBA1 GENE TESTING, EPIDEMIOLOGY AND CLINICAL-GENOMIC CHARACTERISTICS: THE VEXAS/MDS ITALIAN EXPERIENCE

Author

Gurnari, C., Pascale, M.R., Vitale, A., Diral, E., Galossi, E., Falconi, G., Bruno, A., Crisafulli, F., Frassi, M., Cattaneo, C., Bertoli, D., Bernardi, M., Condorelli, A., Morsia, E., Crisà, E., Triggianese, P., Brussino, L., Battipaglia, G., Bindoli, S., Sfriso, P., Caroni, F., Olivieri, A., Kordasti, S., Albano, F., Pane, F., Musto, P., Bocchia, M., Lugli, E., Rambaldi, A., Greco, R., Franceschini, F., Ciceri, F., Cantarini, L., and Voso, M.T.

Published
2023
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48. Quantitative polymerase chain reaction-based chimerism in bone marrow or peripheral blood to predict acute myeloid leukemia relapse in high-risk patients: Results from the KIM-PB prospective study

Author

Gambacorta, V, Parolini, R, Xue, E, Greco, R, Bouwmans, E, Toffalori, C, Giglio, F, Assanelli, A, Stanghellini, M, Ambrosi, A, Mazzi, B, Mulder, W, Corti, C, Peccatori, J, Ciceri, F, Vago, L, Gambacorta V., Parolini R., Xue E., Greco R., Bouwmans E. E., Toffalori C., Giglio F., Assanelli A., Stanghellini M. T. L., Ambrosi A., Mazzi B., Mulder W., Corti C., Peccatori J., Ciceri F., Vago L., Gambacorta, V, Parolini, R, Xue, E, Greco, R, Bouwmans, E, Toffalori, C, Giglio, F, Assanelli, A, Stanghellini, M, Ambrosi, A, Mazzi, B, Mulder, W, Corti, C, Peccatori, J, Ciceri, F, Vago, L, Gambacorta V., Parolini R., Xue E., Greco R., Bouwmans E. E., Toffalori C., Giglio F., Assanelli A., Stanghellini M. T. L., Ambrosi A., Mazzi B., Mulder W., Corti C., Peccatori J., Ciceri F., and Vago L.

Published
2021

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