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1. Gut microbiota diversity before allogeneic hematopoietic stem cell transplantation as a predictor of mortality in children

Author

Masetti, R., Leardini, D., Muratore, E., Fabbrini, M., D'Amico, F., Zama, D., Baccelli, F., Gottardi, F., Belotti, T., Ussowicz, M., Fraczkiewicz, J., Cesaro, S., Zecca, M., Merli, P., Candela, M., Pession, A., Locatelli, Franco, Prete, A., Brigidi, P., Turroni, S., Locatelli F. (ORCID:0000-0002-7976-3654), Masetti, R., Leardini, D., Muratore, E., Fabbrini, M., D'Amico, F., Zama, D., Baccelli, F., Gottardi, F., Belotti, T., Ussowicz, M., Fraczkiewicz, J., Cesaro, S., Zecca, M., Merli, P., Candela, M., Pession, A., Locatelli, Franco, Prete, A., Brigidi, P., Turroni, S., and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

The correlation existing between gut microbiota diversity and survival after allogeneic hematopoietic stem cell transplantation (allo-HSCT) has so far been studied in adults. Pediatric studies question whether this association applies to children as well. Stool samples from a multicenter cohort of 90 pediatric allo-HSCT recipients were analyzed using 16S ribosomal RNA amplicon sequencing to profile the gut microbiota and estimate diversity with the Shannon index. A global-to-local networking approach was used to characterize the ecological structure of the gut microbiota. Patients were stratified into higher- and lower-diversity groups at 2 time points: before transplantation and at neutrophil engraftment. The higher-diversity group before transplantation exhibited a higher probability of overall survival (88.9% ± 5.7% standard error [SE] vs 62.7% ± 8.2% SE; P = .011) and lower incidence of grade 2 to 4 and grade 3 to 4 acute graft-versus-host disease (aGVHD). No significant difference in relapse-free survival was observed between the 2 groups (80.0% ± 6.0% SE vs 55.4% ± 10.8% SE; P = .091). The higher-diversity group was characterized by higher relative abundances of potentially health-related microbial families, such as Ruminococcaceae and Oscillospiraceae. In contrast, the lower-diversity group showed an overabundance of Enterococcaceae and Enterobacteriaceae. Network analysis detected short-chain fatty acid producers, such as Blautia, Faecalibacterium, Roseburia, and Bacteroides, as keystones in the higher-diversity group. Enterococcus, Escherichia-Shigella, and Enterobacter were instead the keystones detected in the lower-diversity group. These results indicate that gut microbiota diversity and composition before transplantation correlate with survival and with the likelihood of developing aGVHD.

Published
2023

2. Multicenter Observational Retrospective Study on Febrile Events in Patients with Acute Myeloid Leukemia Treated with Cpx-351 in “Real-Life”: The SEIFEM Experience

Author

Fianchi, Luana, Guolo, F., Marchesi, F., Cattaneo, C., Gottardi, M., Restuccia, F., Candoni, A., Ortu La Barbera, E., Fazzi, R., Pasciolla, C., Finizio, O., Fracchiolla, N., Delia, M., Lessi, F., Dargenio, M., Bonuomo, V., Del Principe, M. I., Zappasodi, P., Picardi, M., Basilico, C., Piedimonte, M., Minetto, P., Giordano, A., Chiusolo, Patrizia, Prezioso, L., Buquicchio, C., Melillo, L. M. A., Zama, D., Farina, F., Mancini, V., Terrenato, I., Rondoni, M., Urbino, I., Tumbarello, Mario, Busca, A., Pagano, Livio, Fianchi L., Chiusolo P. (ORCID:0000-0002-1355-1587), Tumbarello M. (ORCID:0000-0002-9519-8552), Pagano L. (ORCID:0000-0001-8287-928X), Fianchi, Luana, Guolo, F., Marchesi, F., Cattaneo, C., Gottardi, M., Restuccia, F., Candoni, A., Ortu La Barbera, E., Fazzi, R., Pasciolla, C., Finizio, O., Fracchiolla, N., Delia, M., Lessi, F., Dargenio, M., Bonuomo, V., Del Principe, M. I., Zappasodi, P., Picardi, M., Basilico, C., Piedimonte, M., Minetto, P., Giordano, A., Chiusolo, Patrizia, Prezioso, L., Buquicchio, C., Melillo, L. M. A., Zama, D., Farina, F., Mancini, V., Terrenato, I., Rondoni, M., Urbino, I., Tumbarello, Mario, Busca, A., Pagano, Livio, Fianchi L., Chiusolo P. (ORCID:0000-0002-1355-1587), Tumbarello M. (ORCID:0000-0002-9519-8552), and Pagano L. (ORCID:0000-0001-8287-928X)

Abstract

In the present study, we aimed to evaluate the absolute risk of infection in the real-life setting of AML patients treated with CPX-351. The study included all patients with AML from 30 Italian hematology centers of the SEIFEM group who received CPX-351 from July 2018 to June 2021. There were 200 patients included. Overall, 336 CPX-351 courses were counted: all 200 patients received the first induction cycle, 18 patients (5%) received a second CPX-351 induction, while 86 patients (26%) proceeded with the first CPX-351 consolidation cycle, and 32 patients (10%) received a second CPX-351 consolidation. A total of 249 febrile events were recorded: 193 during the first or second induction, and 56 after the first or second consolidation. After the diagnostic work-up, 92 events (37%) were classified as febrile neutropenia of unknown origin (FUO), 118 (47%) were classifiable as microbiologically documented infections, and 39 (17%) were classifiable as clinically documented infections. The overall 30-day mortality rate was 14% (28/200). The attributable mortality–infection rate was 6% (15/249). A lack of response to the CPX-351 treatment was the only factor significantly associated with mortality in the multivariate analysis [p-value: 0.004, OR 0.05, 95% CI 0.01–0.39]. Our study confirms the good safety profile of CPX-351 in a real-life setting, with an incidence of infectious complications comparable to that of the pivotal studies; despite prolonged neutropenia, the incidence of fungal infections was low, as was infection-related mortality.

Published
2023

4. Global characteristics and outcomes of SARS-CoV-2 infection in children and adolescents with cancer (GRCCC): a cohort study

Author

Mukkada, S, Bhakta, N, Chantada, G, Chen, Y, Vedaraju, Y, Faughnan, L, Homsi, M, Muniz-Talavera, H, Ranadive, R, Metzger, M, Friedrich, P, Agulnik, A, Jeha, S, Lam, C, Dalvi, R, Hessissen, L, Moreira, D, Santana, V, Sullivan, M, Bouffet, E, Caniza, M, Devidas, M, Pritchard-Jones, K, Rodriguez-Galindo, C, Ribelles, A, Balduzzi, A, Elhaddad, A, Casanovas, A, Garcia Velazquez, A, Laptsevich, A, Chang, A, F. Sampaio A., L, Gonzalez Prieto, A, Lassaletta, A, Suarez M, A, Alcasabas, A, Colita, A, Morales La Madrid, A, Samudio, A, Tondo, A, Colombini, A, Kattamis, A, Lopez Facundo, N, Bhattacharyya, A, Alimi, A, Phulpin, A, Vakrmanova, B, Aksoy, B, Brethon, B, Kobuin, J, Nolasco Monteiro, C, Paillard, C, Vezina, C, Ceyhun, B, Hentea, C, Meazza, C, Ortiz-Morales, D, Solorzano, R, Arce Cabrera, D, Zama, D, Ghosh, D, Ramirez-Rivera, D, Calle Jara, D, Janic, D, Rey Helo, E, Gouache, E, Guerrero Quiroz, E, Lopez, E, Thebault, E, Maradiegue, E, de Berranger, E, Ebeid, F, Galaverna, F, Antillon-Klussmann, F, Espinoza Chacur, F, Negro, F, Carraro, F, Compagno, F, Barriga, F, Tamayo Pedraza, G, Sanchez Fernandez, G, Naidu, G, Tokuc, G, Alias, H, B Segocio, H, Boudiaf, H, Asetre Luna, I, Maia, I, Astigarraga, I, Maza, I, Montoya Vasquez, J, Jazbec, J, Lazic, J, Beck Dean, J, Rouger-Gaudichon, J, Contreras Gonzalez, J, Huerta Aragones, J, Fuster, J, Quintana, J, Palma, J, Svojgr, K, Quintero, K, Malic Tudor, K, Georgantzi, K, P Schultz, K, Urena Horno, L, Fraquelli, L, Meneghello, L, Shalaby, L, Macias Mora, L, A Renner, L, Nunes Silva, L, Sisinni, L, Hammad, M, Fernandez Sanmartin, M, Zubieta A, C, Drozdowski, M, Kourti, M, Palladino, M, Miranda Madrazo, M, Poiree, M, Popova, M, Melgar, M, Baragano, M, Aviles-Robles, M, Provenzi, M, Mendes Lins, M, Fatih Orhan, M, Villarroel, M, Jeronimo, M, Varas Palma, M, Rafie Raza, M, M Justin, M, Shaheen, N, Dominguez-Pinilla, N, Whipple, N, Andre, N, Hrusak, O, Velasco Puyo, P, Zacasa Vargas, P, Olate Mellado, P, Yola Gassant, P, Diaz Romero, P, De Santis, R, Kebudi, R, Boranbayeva, R, Vasquez, R, Segura, R, Rosado, R, Gomez, S, Raimbault, S, Gunasekera, S, Makkeyah, S, Buyukkapu Bay, S, M Gomez, S, Bouttefroy, S, Islam, S, Abouelnaga, S, Torres, S, Cesaro, S, Nunes, S, Rouxinol, S, Bhaumik, S, Saliyeva, S, Inostroza, T, Velasquez, T, Hnin, T, Noren-Nystrom, U, Baretta, V, Jimenez-Antolinez, Y, Perez Alonso, V, Ayer Miller, V, Gandemer, V, Lotero, V, Mishkova, V, Gomez-Garcia, W, Margaryan, Y, Syed, Y, Mukkada S., Bhakta N., Chantada G. L., Chen Y., Vedaraju Y., Faughnan L., Homsi M. R., Muniz-Talavera H., Ranadive R., Metzger M., Friedrich P., Agulnik A., Jeha S., Lam C., Dalvi R., Hessissen L., Moreira D. C., Santana V. M., Sullivan M., Bouffet E., Caniza M. A., Devidas M., Pritchard-Jones K., Rodriguez-Galindo C., Ribelles A. J., Balduzzi A., Elhaddad A., Casanovas A., Garcia Velazquez A., Laptsevich A., Chang A., F. Sampaio A. L., Gonzalez Prieto A., Lassaletta A., Suarez M A., Alcasabas A. P., Colita A., Morales La Madrid A., Samudio A., Tondo A., Colombini A., Kattamis A., Lopez Facundo N. A., Bhattacharyya A., Alimi A., Phulpin A., Vakrmanova B., Aksoy B. A., Brethon B., Kobuin J. B., Nolasco Monteiro C., Paillard C., Vezina C., Ceyhun B., Hentea C., Meazza C., Ortiz-Morales D., Solorzano R. D., Arce Cabrera D., Zama D., Ghosh D., Ramirez-Rivera D., Calle Jara D. A., Janic D., Rey Helo E., Gouache E., Guerrero Quiroz E., Lopez E., Thebault E., Maradiegue E., de Berranger E., Ebeid F. S. E., Galaverna F., Antillon-Klussmann F., Espinoza Chacur F., Negro F. D., Carraro F., Compagno F., Barriga F., Tamayo Pedraza G., Sanchez Fernandez G., Naidu G., Tokuc G., Alias H., B Segocio H. G., Boudiaf H., Asetre Luna I., Maia I., Astigarraga I., Maza I., Montoya Vasquez J. E., Jazbec J., Lazic J., Beck Dean J., Rouger-Gaudichon J., Contreras Gonzalez J. C., Huerta Aragones J., Fuster J. L., Quintana J., Palma J., Svojgr K., Quintero K., Malic Tudor K., Georgantzi K., P Schultz K. A., Urena Horno L., Fraquelli L., Meneghello L., Shalaby L., Macias Mora L. L., A Renner L., Nunes Silva L., Sisinni L., Hammad M., Fernandez Sanmartin M., Zubieta A C. M., Drozdowski M. C., Kourti M., Palladino M. M., Miranda Madrazo M. R., Poiree M., Popova M., Melgar M., Baragano M., Aviles-Robles M. J., Provenzi M., Mendes Lins M., Fatih Orhan M., Villarroel M., Jeronimo M., Varas Palma M., Rafie Raza M., M Justin M., Shaheen N., Dominguez-Pinilla N., Whipple N. S., Andre N., Hrusak O., Velasco Puyo P., Zacasa Vargas P., Olate Mellado P., Yola Gassant P., Diaz Romero P., De Santis R., Kebudi R., Boranbayeva R., Vasquez R., Segura R. A., Rosado R. E., Gomez S., Raimbault S., Gunasekera S., Makkeyah S. M., Buyukkapu Bay S., M Gomez S., Bouttefroy S., Islam S., Abouelnaga S., Torres S. F., Cesaro S., Nunes S., Rouxinol S., Bhaumik S., Saliyeva S., Inostroza T., Velasquez T., Hnin T. M., Noren-Nystrom U., Baretta V., Jimenez-Antolinez Y. V., Perez Alonso V., Ayer Miller V., Gandemer V., Lotero V., Mishkova V., Gomez-Garcia W., Margaryan Y., Syed Y., Mukkada, S, Bhakta, N, Chantada, G, Chen, Y, Vedaraju, Y, Faughnan, L, Homsi, M, Muniz-Talavera, H, Ranadive, R, Metzger, M, Friedrich, P, Agulnik, A, Jeha, S, Lam, C, Dalvi, R, Hessissen, L, Moreira, D, Santana, V, Sullivan, M, Bouffet, E, Caniza, M, Devidas, M, Pritchard-Jones, K, Rodriguez-Galindo, C, Ribelles, A, Balduzzi, A, Elhaddad, A, Casanovas, A, Garcia Velazquez, A, Laptsevich, A, Chang, A, F. Sampaio A., L, Gonzalez Prieto, A, Lassaletta, A, Suarez M, A, Alcasabas, A, Colita, A, Morales La Madrid, A, Samudio, A, Tondo, A, Colombini, A, Kattamis, A, Lopez Facundo, N, Bhattacharyya, A, Alimi, A, Phulpin, A, Vakrmanova, B, Aksoy, B, Brethon, B, Kobuin, J, Nolasco Monteiro, C, Paillard, C, Vezina, C, Ceyhun, B, Hentea, C, Meazza, C, Ortiz-Morales, D, Solorzano, R, Arce Cabrera, D, Zama, D, Ghosh, D, Ramirez-Rivera, D, Calle Jara, D, Janic, D, Rey Helo, E, Gouache, E, Guerrero Quiroz, E, Lopez, E, Thebault, E, Maradiegue, E, de Berranger, E, Ebeid, F, Galaverna, F, Antillon-Klussmann, F, Espinoza Chacur, F, Negro, F, Carraro, F, Compagno, F, Barriga, F, Tamayo Pedraza, G, Sanchez Fernandez, G, Naidu, G, Tokuc, G, Alias, H, B Segocio, H, Boudiaf, H, Asetre Luna, I, Maia, I, Astigarraga, I, Maza, I, Montoya Vasquez, J, Jazbec, J, Lazic, J, Beck Dean, J, Rouger-Gaudichon, J, Contreras Gonzalez, J, Huerta Aragones, J, Fuster, J, Quintana, J, Palma, J, Svojgr, K, Quintero, K, Malic Tudor, K, Georgantzi, K, P Schultz, K, Urena Horno, L, Fraquelli, L, Meneghello, L, Shalaby, L, Macias Mora, L, A Renner, L, Nunes Silva, L, Sisinni, L, Hammad, M, Fernandez Sanmartin, M, Zubieta A, C, Drozdowski, M, Kourti, M, Palladino, M, Miranda Madrazo, M, Poiree, M, Popova, M, Melgar, M, Baragano, M, Aviles-Robles, M, Provenzi, M, Mendes Lins, M, Fatih Orhan, M, Villarroel, M, Jeronimo, M, Varas Palma, M, Rafie Raza, M, M Justin, M, Shaheen, N, Dominguez-Pinilla, N, Whipple, N, Andre, N, Hrusak, O, Velasco Puyo, P, Zacasa Vargas, P, Olate Mellado, P, Yola Gassant, P, Diaz Romero, P, De Santis, R, Kebudi, R, Boranbayeva, R, Vasquez, R, Segura, R, Rosado, R, Gomez, S, Raimbault, S, Gunasekera, S, Makkeyah, S, Buyukkapu Bay, S, M Gomez, S, Bouttefroy, S, Islam, S, Abouelnaga, S, Torres, S, Cesaro, S, Nunes, S, Rouxinol, S, Bhaumik, S, Saliyeva, S, Inostroza, T, Velasquez, T, Hnin, T, Noren-Nystrom, U, Baretta, V, Jimenez-Antolinez, Y, Perez Alonso, V, Ayer Miller, V, Gandemer, V, Lotero, V, Mishkova, V, Gomez-Garcia, W, Margaryan, Y, Syed, Y, Mukkada S., Bhakta N., Chantada G. L., Chen Y., Vedaraju Y., Faughnan L., Homsi M. R., Muniz-Talavera H., Ranadive R., Metzger M., Friedrich P., Agulnik A., Jeha S., Lam C., Dalvi R., Hessissen L., Moreira D. C., Santana V. M., Sullivan M., Bouffet E., Caniza M. A., Devidas M., Pritchard-Jones K., Rodriguez-Galindo C., Ribelles A. J., Balduzzi A., Elhaddad A., Casanovas A., Garcia Velazquez A., Laptsevich A., Chang A., F. Sampaio A. L., Gonzalez Prieto A., Lassaletta A., Suarez M A., Alcasabas A. P., Colita A., Morales La Madrid A., Samudio A., Tondo A., Colombini A., Kattamis A., Lopez Facundo N. A., Bhattacharyya A., Alimi A., Phulpin A., Vakrmanova B., Aksoy B. A., Brethon B., Kobuin J. B., Nolasco Monteiro C., Paillard C., Vezina C., Ceyhun B., Hentea C., Meazza C., Ortiz-Morales D., Solorzano R. D., Arce Cabrera D., Zama D., Ghosh D., Ramirez-Rivera D., Calle Jara D. A., Janic D., Rey Helo E., Gouache E., Guerrero Quiroz E., Lopez E., Thebault E., Maradiegue E., de Berranger E., Ebeid F. S. E., Galaverna F., Antillon-Klussmann F., Espinoza Chacur F., Negro F. D., Carraro F., Compagno F., Barriga F., Tamayo Pedraza G., Sanchez Fernandez G., Naidu G., Tokuc G., Alias H., B Segocio H. G., Boudiaf H., Asetre Luna I., Maia I., Astigarraga I., Maza I., Montoya Vasquez J. E., Jazbec J., Lazic J., Beck Dean J., Rouger-Gaudichon J., Contreras Gonzalez J. C., Huerta Aragones J., Fuster J. L., Quintana J., Palma J., Svojgr K., Quintero K., Malic Tudor K., Georgantzi K., P Schultz K. A., Urena Horno L., Fraquelli L., Meneghello L., Shalaby L., Macias Mora L. L., A Renner L., Nunes Silva L., Sisinni L., Hammad M., Fernandez Sanmartin M., Zubieta A C. M., Drozdowski M. C., Kourti M., Palladino M. M., Miranda Madrazo M. R., Poiree M., Popova M., Melgar M., Baragano M., Aviles-Robles M. J., Provenzi M., Mendes Lins M., Fatih Orhan M., Villarroel M., Jeronimo M., Varas Palma M., Rafie Raza M., M Justin M., Shaheen N., Dominguez-Pinilla N., Whipple N. S., Andre N., Hrusak O., Velasco Puyo P., Zacasa Vargas P., Olate Mellado P., Yola Gassant P., Diaz Romero P., De Santis R., Kebudi R., Boranbayeva R., Vasquez R., Segura R. A., Rosado R. E., Gomez S., Raimbault S., Gunasekera S., Makkeyah S. M., Buyukkapu Bay S., M Gomez S., Bouttefroy S., Islam S., Abouelnaga S., Torres S. F., Cesaro S., Nunes S., Rouxinol S., Bhaumik S., Saliyeva S., Inostroza T., Velasquez T., Hnin T. M., Noren-Nystrom U., Baretta V., Jimenez-Antolinez Y. V., Perez Alonso V., Ayer Miller V., Gandemer V., Lotero V., Mishkova V., Gomez-Garcia W., Margaryan Y., and Syed Y.

Abstract

Background: Previous studies have shown that children and adolescents with COVID-19 generally have mild disease. Children and adolescents with cancer, however, can have severe disease when infected with respiratory viruses. In this study, we aimed to understand the clinical course and outcomes of SARS-CoV-2 infection in children and adolescents with cancer. Methods: We did a cohort study with data from 131 institutions in 45 countries. We created the Global Registry of COVID-19 in Childhood Cancer to capture de-identified data pertaining to laboratory-confirmed SARS-CoV-2 infections in children and adolescents (<19 years) with cancer or having received a haematopoietic stem-cell transplantation. There were no centre-specific exclusion criteria. The registry was disseminated through professional networks through email and conferences and health-care providers were invited to submit all qualifying cases. Data for demographics, oncological diagnosis, clinical course, and cancer therapy details were collected. Primary outcomes were disease severity and modification to cancer-directed therapy. The registry remains open to data collection. Findings: Of 1520 submitted episodes, 1500 patients were included in the study between April 15, 2020, and Feb 1, 2021. 1319 patients had complete 30-day follow-up. 259 (19·9%) of 1301 patients had a severe or critical infection, and 50 (3·8%) of 1319 died with the cause attributed to COVID-19 infection. Modifications to cancer-directed therapy occurred in 609 (55·8%) of 1092 patients receiving active oncological treatment. Multivariable analysis revealed several factors associated with severe or critical illness, including World Bank low-income or lower-middle-income (odds ratio [OR] 5·8 [95% CI 3·8–8·8]; p<0·0001) and upper-middle-income (1·6 [1·2–2·2]; p=0·0024) country status; age 15–18 years (1·6 [1·1–2·2]; p=0·013); absolute lymphocyte count of 300 or less cells per mm3 (2·5 [1·8–3·4]; p<0·0001), absolute neutrophil count

Published
2021

5. Prevalence of Immunological Defects in a Cohort of 97 Rubinstein–Taybi Syndrome Patients

Author

Saettini, F, Herriot, R, Prada, E, Nizon, M, Zama, D, Marzollo, A, Romaniouk, I, Lougaris, V, Cortesi, M, Morreale, A, Kosaki, R, Cardinale, F, Ricci, S, Dominguez-Garrido, E, Montin, D, Vincent, M, Milani, D, Biondi, A, Gervasini, C, Badolato, R, Saettini F., Herriot R., Prada E., Nizon M., Zama D., Marzollo A., Romaniouk I., Lougaris V., Cortesi M., Morreale A., Kosaki R., Cardinale F., Ricci S., Dominguez-Garrido E., Montin D., Vincent M., Milani D., Biondi A., Gervasini C., Badolato R., Saettini, F, Herriot, R, Prada, E, Nizon, M, Zama, D, Marzollo, A, Romaniouk, I, Lougaris, V, Cortesi, M, Morreale, A, Kosaki, R, Cardinale, F, Ricci, S, Dominguez-Garrido, E, Montin, D, Vincent, M, Milani, D, Biondi, A, Gervasini, C, Badolato, R, Saettini F., Herriot R., Prada E., Nizon M., Zama D., Marzollo A., Romaniouk I., Lougaris V., Cortesi M., Morreale A., Kosaki R., Cardinale F., Ricci S., Dominguez-Garrido E., Montin D., Vincent M., Milani D., Biondi A., Gervasini C., and Badolato R.

Abstract

Although recurrent infections in Rubinstein–Taybi syndrome (RSTS) are common, and probably multifactorial, immunological abnormalities have not been extensively described with only isolated cases or small case series of immune deficiency and dysregulation having been reported. The objective of this study was to investigate primary immunodeficiency (PID) and immune dysregulation in an international cohort of patients with RSTS. All published cases of RSTS were identified. The corresponding authors and researchers involved in the diagnosis of inborn errors of immunity or genetic syndromes were contacted to obtain up-to-date clinical and immunological information. Ninety-seven RSTS patients were identified. For 45 patients, we retrieved data from the published reports while for 52 patients, a clinical update was provided. Recurrent or severe infections, autoimmune/autoinflammatory complications, and lymphoproliferation were observed in 72.1%, 12.3%, and 8.2% of patients. Syndromic immunodeficiency was diagnosed in 46.4% of individuals. Despite the broad heterogeneity of immunodeficiency disorders, antibody defects were observed in 11.3% of subjects. In particular, these patients presented hypogammaglobulinemia associated with low B cell counts and reduction of switched memory B cell numbers. Immunoglobulin replacement therapy, antibiotic prophylaxis, and immunosuppressive treatment were employed in 16.4%, 8.2%, and 9.8% of patients, respectively. Manifestations of immune dysfunctions, affecting mostly B cells, are more common than previously recognized in patients with RSTS. Full immunological assessment is warranted in these patients, who may require detailed investigation and specific supportive treatment. [Figure not available: see fulltext.]

Published
2020

6. Antibiotic prophylaxis and management of infections in pediatric hematopoietic stem cell transplantation: a survey from the Stem Cell Transplant and the Infectious Disease Working Groups of the AIEOP network

Author

Zama, D., Masetti, R., Baccelli, F., Leardini, D., Muratore, E., Abram, N., Vendemini, F., Biffi, A., Perruccio, K., D'Amico, M. R., Faraci, M., Tintori, V., Spirito, A., Lo Nigro, L., Locatelli, Franco, Luksch, R., Saglio, F., Santoro, N., Soncini, E., Zecca, M., Ziino, O., Prete, A., Pagliara, D., Cesaro, S., Locatelli F. (ORCID:0000-0002-7976-3654), Zama, D., Masetti, R., Baccelli, F., Leardini, D., Muratore, E., Abram, N., Vendemini, F., Biffi, A., Perruccio, K., D'Amico, M. R., Faraci, M., Tintori, V., Spirito, A., Lo Nigro, L., Locatelli, Franco, Luksch, R., Saglio, F., Santoro, N., Soncini, E., Zecca, M., Ziino, O., Prete, A., Pagliara, D., Cesaro, S., and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

NO ABSTRACT

Published
2022

7. Invasive aspergillosis in relapsed/refractory acute myeloid leukaemia patients: Results from SEIFEM 2016-B survey

Author

Del Principe, M. I., Dragonetti, Giulia, Conti, A., Verga, L., Ballanti, S., Fanci, R., Candoni, A., Marchesi, F., Cattaneo, C., Lessi, F., Fracchiolla, N., Spolzino, A., Prezioso, L., Delia, M., Potenza, L., Decembrino, N., Castagnola, C., Nadali, G., Picardi, M., Zama, D., Orciulo, E., Veggia, B., Garzia, M., Dargenio, M., Melillo, L., Manetta, S., Russo, D., Mancini, V., Piedimonte, M., Tisi, M. C., Toschi, N., Busca, A., Pagano, Livio, Dragonetti G., Pagano L. (ORCID:0000-0001-8287-928X), Del Principe, M. I., Dragonetti, Giulia, Conti, A., Verga, L., Ballanti, S., Fanci, R., Candoni, A., Marchesi, F., Cattaneo, C., Lessi, F., Fracchiolla, N., Spolzino, A., Prezioso, L., Delia, M., Potenza, L., Decembrino, N., Castagnola, C., Nadali, G., Picardi, M., Zama, D., Orciulo, E., Veggia, B., Garzia, M., Dargenio, M., Melillo, L., Manetta, S., Russo, D., Mancini, V., Piedimonte, M., Tisi, M. C., Toschi, N., Busca, A., Pagano, Livio, Dragonetti G., and Pagano L. (ORCID:0000-0001-8287-928X)

Abstract

Background: In patients with relapsed/refractory acute myeloid leukaemia (R/R AML) who received salvage chemotherapy, limited and not updated studies explored the incidence of invasive aspergillosis (IA) and the role of antifungal prophylaxis (AP). The aims of this multicentre retrospective ‘SEIFEM 2016-B’ study were as follows: (1) to evaluate the current rate and the outcome of proven/probable IA and (2) to assess the efficacy of AP, in a large ‘real life’ series of patient with R/R AML submitted to salvage chemotherapy. Results: Of 2250 R/R AML patients, a total of 74 cases of IA (5.1%) were recorded as follows: 10 (0.7%) proven and 64 (4.3%) probable. Information about AP were available in 73/74 (99%) patients. Fifty-eight (79%) breakthrough infections occurred, mainly during AP with posaconazole [25 (43%)]. The patients who received AP during salvage chemotherapy showed a benefit from antifungal therapy (AT) than patients who did not received AP [43 (86%) vs 7 (14%); p <.033]. In a multivariate analysis, AP and absence of severe mucositis had a significant favourable effect on overall response rate. Conclusion: Our data demonstrated that the incidence of IA during the salvage chemotherapy is similar to the past. Nevertheless, the attributable mortality rate (AMR) appears to be lower than that previously reported in R/R AML. Further prospective studies should be performed to confirm our preliminary observation and understand and the why a decreased AMR is reported in this setting of high-risk patients.

Published
2022

10. Fungal infections of the central nervous system and paranasal sinuses in onco-haematologic patients. Epidemiological study reporting the diagnostic-therapeutic approach and outcome in 89 cases

Author

Candoni A, Klimko N, Busca A, Di Blasi R, Shadrivova O, Cesaro S, Zannier ME, Verga L, Forghieri F, Calore E, Nadali G, Simonetti E, Muggeo P, Quinto AM, Castagnola C, Cellini M, Del Principe MI, Fracchiolla N, Melillo L, Piedimonte M, Zama D, Farina F, Giusti D, Mosna F, Capelli D, Delia M, Picardi M, Decembrino N, Perruccio K, Vallero S, Aversa F, Fanin R, Pagano L, SEIFEM Group (Epidemiological Surveillance of Infections in Haematological Diseases), Candoni, A., Klimko, N., Busca, A., Di Blasi, R., Shadrivova, O., Cesaro, S., Zannier, M. E., Verga, L., Forghieri, F., Calore, Aldo, Nadali, G., Simonetti, E., Muggeo, P., Quinto, A. M., Castagnola, C., Cellini, M., Del Principe, M. I., Fracchiolla, N., Melillo, L., Piedimonte, M., Zama, D., Farina, F., Giusti, D., Mosna, F., Capelli, D., Delia, M., Picardi, M., Decembrino, N., Perruccio, K., Vallero, S., Aversa, F., Fanin, R., Pagano, L., Candoni A, Klimko N, Busca A, Di Blasi R, Shadrivova O, Cesaro S, Zannier ME, Verga L, Forghieri F, Calore E, Nadali G, Simonetti E, Muggeo P, Quinto AM, Castagnola C, Cellini M, Del Principe MI, Fracchiolla N, Melillo L, Piedimonte M, Zama D, Farina F, Giusti D, Mosna F, Capelli D, Delia M, Picardi M, Decembrino N, Perruccio K, Vallero S, Aversa F, Fanin R, Pagano L, and SEIFEM Group (Epidemiological Surveillance of Infections in Haematological Diseases)

Subjects
0301 basic medicine, Male, Antifungal Agents, haematological disease, Aspergillosis, fungal CNS infectious, haematological diseases, leukaemia, neurologic complications, Zygomicosis, 030207 dermatology & venereal diseases, 0302 clinical medicine, Central Nervous System Fungal Infections, Epidemiology, Paranasal Sinuses, Sinusitis, Child, Adolescent, Adult, Aged, Cerebrospinal Fluid, Child, Preschool, Epidemiologic Studies, Female, Fungi, Hematologic Neoplasms, Humans, Middle Aged, Survival Analysis, Treatment Outcome, Young Adult, Debridement, medicine.diagnostic_test, aspergillosis, fungal cns infectious, zygomicosis, neurologic complication, General Medicine, medicine.anatomical_structure, Infectious Diseases, Cohort, medicine.drug, medicine.medical_specialty, fungal CNS infectiou, Aspergillosi, 030106 microbiology, Dermatology, 03 medical and health sciences, Internal medicine, Biopsy, medicine, Preschool, Invasive fungal infection, central nervous system, onco-haematologic patients, Survival analysis, Voriconazole, business.industry, Zygomicosi, medicine.disease, Paranasal sinuses, 2708, business, Settore MED/15 - Malattie del Sangue
Abstract

Invasive fungal infections (IFI) of the Central Nervous System (IFI-CNS) and Paranasal Sinuses (IFI-PS) are rare, life-threatening infections in haematologic patients, and their management remains a challenge despite the availability of new diagnostic techniques and novel antifungal agents. In addition, analyses of large cohorts of patients focusing on these rare IFI are still lacking. Between January 2010 and December 2016, 89 consecutive cases of Proven (53) or Probable (36) IFI-CNS (71/89) and IFI-PS (18/89) were collected in 34 haematological centres. The median age was 40 years (range 5-79); acute leukaemia was the most common underlying disease (69%) and 29% of cases received a previous allogeneic stem cell transplant. Aspergillus spp. were the most common pathogens (69%), followed by mucormycetes (22%), Cryptococcus spp. (4%) and Fusarium spp. (2%). The lung was the primary focus of fungal infection (48% of cases). The nervous system biopsy was performed in 10% of IFI-CNS, and a sinus biopsy was performed in 56% of IFI-PS (P = 0.03). The Galactomannan test on cerebrospinal fluid has been performed in 42% of IFI-CNS (30/71), and it was positive in 67%. Eighty-four pts received a first-line antifungal therapy with Amphotericine B in 58% of cases, Voriconazole in 31% and both in 11%. Moreover, 58% of patients received 2 or more lines of therapy and 38% were treated with a combination of 2 or more antifungal drugs. The median duration of antifungal therapy was 60 days (range 5-835). A surgical intervention was performed in 26% of cases but only 10% of IFI-CNS underwent neurosurgical intervention. The overall response rate to antifungal therapy (complete or partial response) was 57%, and 1-year overall survival was 32% without significant differences between IFI-CNS and IFI-PS. The overall mortality was 69% but the IFI attributable mortality was 33%. Mortality of IFI-CNS/PS remains high but, compared to previous historical data, it seems to be reduced probably due to the availability of newer antifungal drugs. The results arising from this large contemporary cohort of cases may allow a more effective diagnostic and therapeutic management of these very rare IFI complications in haematologic patients.

Published
2018

15. 'Real-life' analysis of the role of antifungal prophylaxis in preventing invasive aspergillosis in AML patients undergoing consolidation therapy: Sorveglianza Epidemiologica Infezioni nelle Emopatie (SEIFEM) 2016 study

Author

Del Principe, Maria Ilaria, Dragonetti, Giulia, Verga, Luisa, Candoni, Anna, Marchesi, Francesco, Cattaneo, Chiara, Delia, Mario, Potenza, Leonardo, Farina, Francesca, Ballanti, Stelvio, Decembrino, Nunzia, Castagnola, Carlo, Nadali, Gianpaolo, Fanci, Rosa, Orciulo, Enrico, Veggia, Barbara, Offidani, Massimo, Melillo, Lorella, Manetta, Sara, Tumbarello, Mario, Venditti, Adriano, Busca, Alessandro, Aversa, Franco, Pagano, Livio, Picardi, M, Della Pepa, R, Ferrari, A, Piedimonte, M, Fracchiolla, Ns, Sciumè, M, Lessi, F, Prezioso, L, Spolzino, A, Rambaldi, B, Russo, D, Maracci, L, di Ematologia, C, Sarlo, C, Annibali, O, Cefalo, M, Zizzari, A, Di Blasi, R, di Ematologia, I, Zama, D, Mancini, V, Salutari, P, Cesaro, S, Chiara Tisi, M, Garzia, Mg, Vacca, A, Dargenio, M, Invernizzi, R, Perruccio, K, Mitra, Me, Quinto, Am, Chierichini, A, and Spadea, A.

Subjects
0301 basic medicine, Microbiology (medical), Adult, Male, medicine.medical_specialty, Antifungal Agents, AML, SEIFEM, Invasive Aspergillosis, consolidation therapy, antifumgal prophylaxis, antifungal therapy, 030106 microbiology, SEIFEM, antifumgal prophylaxis, Comorbidity, Aspergillosis, 03 medical and health sciences, 0302 clinical medicine, AML, Risk Factors, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, Prospective cohort study, Aged, Pharmacology, business.industry, Incidence (epidemiology), Mortality rate, Consolidation Chemotherapy, Induction Chemotherapy, Middle Aged, medicine.disease, antifungal therapy, Leukemia, Myeloid, Acute, Infectious Diseases, Number needed to treat, Cytarabine, Invasive Aspergillosis, Female, business, consolidation therapy, Settore MED/15 - Malattie del Sangue, Invasive Fungal Infections, medicine.drug
Abstract

Background We evaluated the incidence of proven/probable invasive aspergillosis (IA) and the role of antifungal prophylaxis (AP) in a 'real-life' setting of patients with AML receiving intensive consolidation therapy. Methods Cases of IA, observed during consolidation in adult/paediatric patients with AML between 2011 and 2015, were retrospectively collected in a multicentre Italian study. Results Of 2588 patients, 56 (2.2%) developed IA [43 probable (1.7%) and 13 proven (0.5%)]. IA was diagnosed in 34 of 1137 (2.9%) patients receiving no AP and in 22 of 1451 (1.5%) who were given AP (P = 0.01). Number-needed-to-treat calculation indicates that, on average, 71 patients should have received AP (instead of no AP) for one additional patient to not have IA. Initial antifungal therapy was 'pre-emptive' in 36 (64%) patients and 'targeted' in 20 (36%) patients. A good response to first-line therapy was observed in 26 (46%) patients, mainly those who received AP [16 of 22 (73%) versus 10 of 34 (29%); P = 0.001]. The overall mortality rate and the mortality rate attributable to IA by day 120 were 16% and 9%, respectively. In multivariate analysis, age ≥60 years (OR = 12.46, 95% CI = 1.13-136.73; P = 0.03) and high-dose cytarabine treatment (OR = 10.56, 95% CI = 1.95-116.74; P = 0.04) independently affected outcome. Conclusions In our experience, AP appears to prevent IA from occurring during consolidation. However, although the incidence of IA was low, mortality was not negligible among older patients. Further prospective studies should be carried out particularly in elderly patients treated with high-dose cytarabine to confirm our data and to identify subsets of individuals who may require AP.

Published
2019

16. Early gut microbiota signature of aGvHD in children given allogeneic hematopoietic cell transplantation for hematological disorders

Author

Biagi, E., Zama, D., Rampelli, S., Turroni, S., Brigidi, P., Consolandi, C., Severgnini, M., Picotti, E., Gasperini, P., Merli, P., Decembrino, N., Zecca, M., Cesaro, S., Faraci, M., Prete, A., Locatelli, Franco, Pession, A., Candela, M., Masetti, R., Locatelli F. (ORCID:0000-0002-7976-3654), Biagi, E., Zama, D., Rampelli, S., Turroni, S., Brigidi, P., Consolandi, C., Severgnini, M., Picotti, E., Gasperini, P., Merli, P., Decembrino, N., Zecca, M., Cesaro, S., Faraci, M., Prete, A., Locatelli, Franco, Pession, A., Candela, M., Masetti, R., and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

Background: The onset of acute Graft-versus-Host Disease (aGvHD) has been correlated with the gut microbiota (GM) composition, but experimental observations are still few, mainly involving cohorts of adult patients. In the current scenario where fecal microbiota transplantation has been used as a pioneer therapeutic approach to treat steroid-refractory aGvHD, there is an urgent need to expand existing observational studies of the GM dynamics in Hematopoietic Stem Cell Transplantation (HSCT). Aim of the present study is to explore the GM trajectory in 36 pediatric HSCT recipients in relation to aGvHD onset. Methods: Thirty-six pediatric patients, from four transplantation centers, undergoing HSCT were enrolled in the study. Stools were collected at three time points: before HSCT, at time of engraftment and > 30 days following HSCT. Changes in the GM phylogenetic structure were studied by 16S rRNA gene Illumina sequencing and phylogenetic assignation. Results: Children developing gut aGvHD had a dysbiotic GM layout before HSCT occurred. This putative aGvHD-predisposing ecosystem state was characterized by (i) reduced diversity, (ii) lower Blautia content, (iii) increase in Fusobacterium abundance. At time of engraftment, the GM structure underwent a deep rearrangement in all patients but, regardless of the occurrence of aGvHD and its treatment, it reacquired a eubiotic configuration from day 30. Conclusions: We found a specific GM signature before HSCT predictive of subsequent gut aGvHD occurrence. Our data may open the way to a GM-based stratification of the risk of developing aGvHD in children undergoing HSCT, potentially useful also to identify patients benefiting from prophylactic fecal transplantation.

Published
2019

17. Fungal infections of the central nervous system and paranasal sinuses in onco-haematologic patients. Epidemiological study reporting the diagnostic-therapeutic approach and outcome in 89 cases

Author

Candoni, A., Klimko, N., Busca, A., Di Blasi, Roberta, Shadrivova, O., Cesaro, S., Zannier, M. E., Verga, L., Forghieri, F., Calore, E., Nadali, G., Simonetti, E., Muggeo, P., Quinto, A. M., Castagnola, C., Cellini, M., Del Principe, M. I., Fracchiolla, N., Melillo, L., Piedimonte, M., Zama, D., Farina, F., Giusti, D., Mosna, F., Capelli, D., Delia, M., Picardi, M., Decembrino, N., Perruccio, K., Vallero, S., Aversa, F., Fanin, R., Pagano, Livio, Di Blasi, R., Pagano, L. (ORCID:0000-0001-8287-928X), Candoni, A., Klimko, N., Busca, A., Di Blasi, Roberta, Shadrivova, O., Cesaro, S., Zannier, M. E., Verga, L., Forghieri, F., Calore, E., Nadali, G., Simonetti, E., Muggeo, P., Quinto, A. M., Castagnola, C., Cellini, M., Del Principe, M. I., Fracchiolla, N., Melillo, L., Piedimonte, M., Zama, D., Farina, F., Giusti, D., Mosna, F., Capelli, D., Delia, M., Picardi, M., Decembrino, N., Perruccio, K., Vallero, S., Aversa, F., Fanin, R., Pagano, Livio, Di Blasi, R., and Pagano, L. (ORCID:0000-0001-8287-928X)

Abstract

Invasive fungal infections (IFI) of the Central Nervous System (IFI-CNS) and Paranasal Sinuses (IFI-PS) are rare, life-threatening infections in haematologic patients, and their management remains a challenge despite the availability of new diagnostic techniques and novel antifungal agents. In addition, analyses of large cohorts of patients focusing on these rare IFI are still lacking. Between January 2010 and December 2016, 89 consecutive cases of Proven (53) or Probable (36) IFI-CNS (71/89) and IFI-PS (18/89) were collected in 34 haematological centres. The median age was 40 years (range 5-79); acute leukaemia was the most common underlying disease (69%) and 29% of cases received a previous allogeneic stem cell transplant. Aspergillus spp. were the most common pathogens (69%), followed by mucormycetes (22%), Cryptococcus spp. (4%) and Fusarium spp. (2%). The lung was the primary focus of fungal infection (48% of cases). The nervous system biopsy was performed in 10% of IFI-CNS, and a sinus biopsy was performed in 56% of IFI-PS (P = 0.03). The Galactomannan test on cerebrospinal fluid has been performed in 42% of IFI-CNS (30/71), and it was positive in 67%. Eighty-four pts received a first-line antifungal therapy with Amphotericine B in 58% of cases, Voriconazole in 31% and both in 11%. Moreover, 58% of patients received 2 or more lines of therapy and 38% were treated with a combination of 2 or more antifungal drugs. The median duration of antifungal therapy was 60 days (range 5-835). A surgical intervention was performed in 26% of cases but only 10% of IFI-CNS underwent neurosurgical intervention. The overall response rate to antifungal therapy (complete or partial response) was 57%, and 1-year overall survival was 32% without significant differences between IFI-CNS and IFI-PS. The overall mortality was 69% but the IFI attributable mortality was 33%. Mortality of IFI-CNS/PS remains high but, compared to previous historical data, it seems to be reduced probably due

Published
2019

18. A survey on hematology-oncology pediatric AIEOP centres: The challenge of posterior reversible encephalopathy syndrome

Author

Zama D, Gasperini P, Berger M, Petris M, De Pasquale MD, Cesaro S, Guerzoni ME, Mastrodicasa E, Savina F, Ziino O, Kiren V, Muggeo P, Mura RM, Melchionda F, Zanazzo GA, Supportive Therapy Working Group of Italian Pediatric Haematology and Oncology Association (AIEOP)., Zama D, Gasperini P, Berger M, Petris M, De Pasquale MD, Cesaro S, Guerzoni ME, Mastrodicasa E, Savina F, Ziino O, Kiren V, Muggeo P, Mura RM, Melchionda F, Zanazzo GA, and Supportive Therapy Working Group of Italian Pediatric Haematology and Oncology Association (AIEOP).

Subjects
Diagnostic Imaging, Male, Pediatrics, medicine.medical_specialty, posterior reversible encephalopathy syndrome, Adolescent, Neurological complication, medicine.medical_treatment, Hematopoietic stem cell transplantation, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Outcome Assessment, Health Care, medicine, Prevalence, Humans, In patient, Child, Chemotherapy, Hematology, business.industry, Incidence (epidemiology), and hematology, Incidence, Disease Management, Infant, Posterior reversible encephalopathy syndrome, General Medicine, pediatric oncology, medicine.disease, Health Surveys, children, hematology-oncology, posterior reversible encephalopathy syndrome, Italy, 030220 oncology & carcinogenesis, Child, Preschool, pediatric oncology, and hematology, Female, Posterior Leukoencephalopathy Syndrome, Symptom Assessment, business, Hematology+Oncology, 030217 neurology & neurosurgery
Abstract

Objectives Posterior reversible encephalopathy syndrome (PRES) is one of the most common neurological complications in hematology-oncology pediatric patients. Despite an increasingly recognized occurrence, no clear consensus exists regarding how best to manage the syndrome, because most cases of PRES have reported in single case reports or small series. Aim of this paper is to identify incidence, clinical features, management and outcome of PRES in a large series of hematology-oncology pediatric patients Methods The cases of PRES occurred in twelve centres of the Italian Association of Pediatric Haematology and Oncology were reported Results 124 cases of PRES in 112 pediatric patients were recorded with an incidence of 2.1% and 4.7% respectively in acute lymphoblastic leukemia in first complete remission and hematopoietic stem cell transplantation (HSCT). The majority of cases occurred after a cycle of chemotherapy rather than after stem cell transplant. PRES after chemotherapy significantly differs from that after HSCT for diagnosis, time of presentation, risk factors, management and outcome Conclusions This study demonstrates that PRES is a common neurological complication and occurring preferentially in course of induction treatment of some hematologic malignancies, as ALL and after HSCT. It also highlights great clinical differences in the management and outcome in patients with PRES occurring after chemotherapy or after HSCT This article is protected by copyright. All rights reserved.

Published
2017

19. Fungaemia in haematological malignancies: SEIFEM-2015 survey

Author

Criscuolo, M., Marchesi, F., Candoni, A., Cattaneo, C., Nosari, A., Veggia, B., Verga, L., Fracchiolla, N., Vianelli, N., Del Principe, M. I., Picardi, M., Tumbarello, M., Aversa, F., Busca, A., Pagano, L., Dragonetti, G., Ballanti, S., Delia, M., Nadali, G., Sciume, M., Castagnola, C., Ferrari, A., Mancini, V., Decembrino, N., Spolzino, A., Iovino, L., Martino, B., Vacca, A., Calore, E., Fanci, R., Lessi, F., Vallero, S., Zama, D., Cesaro, S., De Paolis, M. R., Facchini, L., Muggeo, P., Offidani, M., Perruccio, K., Russo, D., Criscuolo M, Marchesi F, Candoni A, Cattaneo C, Nosari A, Veggia B, Verga L, Fracchiolla N, Vianelli N, Del Principe MI, Picardi M, Tumbarello M, Aversa F, Busca A, Pagano L, SEIFEM Group: Giulia Dragonetti, Stelvio Ballanti, Mario Delia, Gianpaolo Nadali, Sciumè M, Castagnola C, Ferrari A, Mancini V, Decembrino N, Spolzino A, Iovino L, Martino B, Vacca A, Calore E, Fanci R, Lessi F, Vallero S, Zama D, Cesaro S, De Paolis M, Facchini L, Muggeo P, Offidani M, Perruccio K, Russo D., Criscuolo, Marianna, Marchesi, Francesco, Candoni, Anna, Cattaneo, Chiara, Nosari, Annamaria, Veggia, Barbara, Verga, Luisa, Fracchiolla, Nicola, Vianelli, Nicola, Del Principe, Maria Ilaria, Picardi, Marco, Tumbarello, Mario, Aversa, Franco, Busca, Alessandro, and Pagano, Livio

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, medicine.medical_treatment, Clinical Biochemistry, Prevalence, 030204 cardiovascular system & hematology, Biochemistry, Young Adult, 03 medical and health sciences, acute leukaemias, candidemia, fungaemia, 0302 clinical medicine, Risk Factors, Yeasts, Internal medicine, acute leukemias, Epidemiology, Fungemia, Hematological malignancies, medicine, Aged, Candidemia, Child, Female, Fungemia, Hematologic Neoplasms, Humans, Italy, Middle Aged, Prognosis, Retrospective Studies, acute leukemia, 030212 general & internal medicine, Cause of death, Hematology, business.industry, Septic shock, Mortality rate, General Medicine, bacterial infections and mycoses, medicine.disease, Settore MED/15 - MALATTIE DEL SANGUE, fungemia, business, Central venous catheter
Abstract

BACKGROUND: Fungal infections are still a relevant challenge for clinicians involved in the cure of patients with cancer. We retrospectively reviewed charts of hospitalized patients with hematological malignancies (HMs), in which a documented fungemia was diagnosed between January 2011 and December 2015 at 28 adult and 6 pediatric Italian Hematology Departments. METHODS: During the study period we recorded 215 fungal blood stream infections (BSI). Microbiological analyses documented that BSI was due to molds in 17 patients (8%) and yeasts in 198 patients (92%), being Candida spp identified in 174 patients (81%). RESULTS: Mortality rates were 70% and 39% for mold and yeast infections, respectively. Infection was the main cause of death in 53% of the mold and 18% of the yeast groups. At the multivariate analysis, ECOG ≥2 and septic shock were significantly associated with increased mortality, and removal of CVC survival was found to be protective. When considering patients with candidemia only, ECOG >2 and removal of CVC were statistically associated with overall mortality. CONCLUSIONS: Although candidemia represents a group of BSI with a good prognosis, its risk factors largely overlap with those identified for all fungemias, even though the candidemia-related mortality is lower when compared to other fungal BSI. Management of fungal BSI is still a complex issue, in which both patients and disease characteristics should be focused to address a personalized approach. This article is protected by copyright. All rights reserved.

Published
2019

21. ll microbiota intestinale come fattore di rischio dello sviluppo di aGVHD gastrointestinale in pazienti pediatrici sottoposti a trapianto allogenico di cellule staminali ematopoietiche

Author

Zama, D., Biagi, E., Rampelli, S., Turroni, S., Brigidi, P., Consolandi, C., Severgnini, M., Landi, E., Bossu, G., Carella, M., Merli, P., Decembrino, N., Zecca, M., Cesaro, S., Faraci, M., Prete, A., Locatelli, F., Pession, A., Candela, M., and R. Masetti. I.

Subjects
complicanze intestinali, microbiota, trapianto, microbiota, complicanze intestinali, trapianto
Published
2018

22. Identification of the NUP98-PHF23 fusion gene in pediatric cytogenetically normal acute myeloid leukemia by whole-transcriptome sequencing

Author

Togni, M, Masetti, R, Pigazzi, M, Astolfi, A, Zama, D, Indio, V, Serravalle, S, Manara, E, Bisio, V, Rizzari, C, Basso, G, Pession, A, Locatelli, F, Togni M., Masetti R., Pigazzi M., Astolfi A., Zama D., Indio V., Serravalle S., Manara E., Bisio V., Rizzari C., Basso G., Pession A., Locatelli F., Togni, M, Masetti, R, Pigazzi, M, Astolfi, A, Zama, D, Indio, V, Serravalle, S, Manara, E, Bisio, V, Rizzari, C, Basso, G, Pession, A, Locatelli, F, Togni M., Masetti R., Pigazzi M., Astolfi A., Zama D., Indio V., Serravalle S., Manara E., Bisio V., Rizzari C., Basso G., Pession A., and Locatelli F.

Abstract

The genomic landscape of children with acute myeloid leukemia (AML) who do not carry any cytogenetic abnormality (CN-AML) is particularly heterogeneous and challenging, being characterized by different clinical outcomes. To provide new genetic insights into this AML subset, we analyzed through RNA-seq 13 pediatric CN-AML cases, corroborating our findings in an independent cohort of 168 AML patients enrolled in the AIEOP AML 2002/01 study. We identified a chimeric transcript involving NUP98 and PHF23, resulting from a cryptic t(11;17)(p15;p13) translocation, demonstrating, for the first time, that NUP98-PHF23 is a novel recurrent (2.6 %) abnormality in pediatric CN-AML.

Published
2015

23. Protective Effect of Green Tea (Camellia sinensis (L.) Kuntze) against Prostate Cancer: From in Vitro Data to Algerian Patients

Author

Lassed S., Deus C., Djebbari R., Zama D., Oliveira P., Rizvanov A., Dahdouh A., Benayache F., and Benayache S.

Abstract

© 2017 Somia Lassed et al.Green tea (GT) has been studied for its effects as antioxidant and cancer-preventive agent. Epidemiological studies showed that GT consumption decreases the risk for prostate cancer (PC). To investigate whether erythrocyte oxidative stress (OS) is associated with PC and whether daily consumption of GT improves the oxidative phenotype, we performed a study in a group of Algerian PC patients, preceded by an in vitro study to characterize composition and antioxidant/antiproliferative activities of the GT used. This contained a high content of phenolic and flavonoid compounds, demonstrating in vitro antioxidant activity and significant antiproliferative effect on human prostate cancer PC-3 cell line. Seventy PC patients and 120 age-matched healthy subjects participated in the study, with glutathione (GSH), malondialdehyde (MDA), and catalase activity evaluated before and after GT consumption. The results showed a reduced GSH and catalase activity and a high level of MDA in erythrocytes from PC patients. The consumption of 2-3 cups per day of GT during 6 months significantly increased GSH concentration and catalase activity and decreased MDA concentration. In conclusion, GT significantly decreased OS in Algerian PC patients. Regular consumption of GT for a long period may prevent men from developing PC or at least delay its progression.

Published
2017

25. Gonadal tumors

Author

Masetti R, Zama D, Vendemini F, Pession A., Masetti R, Zama D, Vendemini F, and Pession A.

Subjects
Gonadal tumors, children
Abstract

This encompassing volume gathers contributions by renowned experts in the field of pediatric urology to offer a systematic and complete review of the field. The book opens with a general section covering the basis of renal function from the fetus to adulthood, diagnostic imaging, anesthesia and infections. In subsequent sections on the kidneys, upper urinary tract, bladder, urethra and genitalia, specific anomalies are described in depth, from embryological, clinical and diagnostic aspects through to surgical treatment options. Detailed attention is devoted to the role of new technologies such as endoscopic and robotic surgery, but without disregarding the classical principles of pediatric urologic surgery. Urogenital tumors are fully covered and the book closes with a large chapter on renal transplantation. Numerous black and white and color illustrations will assist the reader in better understanding the various anomalies and the surgical procedures.

Published
2015

27. Studio Osservazionale retrospettivo AIEOP sulla Sindrome da encefalopatia posteriore reversibile in età pediatrica: risultati. XLI Annual Congress of AIEOP (Italian Association of Pediatric Hematology Oncology)

Author

Zama, D., Melchionda, F., Berger, M., Petris, M. G., De Pasquale, M. D., Cesaro, Simone, Guerzoni, M. E., Mastrodicasa, E., Savina, F., Ziino, O., Ferraro, F., Kiren, V., Muggeo, P., and Zanazzo, G.

Subjects
convulsioni, PRES, pazienti immunodepressi, convulsioni, pazienti immunodepressi, PRES
Published
2016

29. Diet, Lifestyles, Family History, and Prostate Cancer Incidence in an East Algerian Patient Group

Author

Lassed S., Deus C., Lourenço N., Dahdouh A., Rizvanov A., Oliveira P., and Zama D.

Abstract

© 2016 Somia Lassed et al.Prostate cancer (PC) is the fourth most common cancer in men and the sixth leading cause of death in Algeria. To examine the relationship between lifestyle factors, including diet, and family history and PC risk, a case-control study was performed in an eastern Algerian population, comprising 90 patients with histologically confirmed PC and 190 controls. Data collection was carried out through a structured questionnaire and statistical analysis was performed to evaluate the different variables. The data showed that consumption of lamb and beef meat and high intake of animal fat and dairy products increased PC risk. Seven to thirteen vegetables servings per week and fourteen or more servings decreased PC risk by 62% and 96%, respectively. Seven to fourteen fruit servings per week decrease PC risk by 98%. Green tea consumption reduced the risk of PC but the results were statistically borderline. Increased risk was observed for individuals with family history of PC in first and in second degree. A positive strong association was also found for alcohol and smoking intake and a dose-response relationship existed for quantity and history of smoking. This study suggests that dietary habits, lifestyle factors, and family history have influence on the development of PC in Algerian population.

Published
2016

30. Chlorpyrifos-induced oxidative stress and tissue damage in the liver, kidney, brain and fetus in pregnant rats: The protective role of the butanolic extract of Paronychia argentea L

Author

Zama, D., Meraihi, Z., Tebibel, S., Benayssa, W., Benayache, F., Benayache, S., and Vlietinck, A.

Subjects
Pesticides -- Physiological aspects -- Research -- Health aspects, Materia medica, Vegetable -- Physiological aspects -- Research -- Health aspects, Rats -- Research -- Health aspects -- Physiological aspects, Rattus -- Research -- Health aspects -- Physiological aspects, Plant extracts -- Physiological aspects -- Research -- Health aspects, Health
Abstract

Byline: D. Zama, Z. Meraihi, S. Tebibel, W. Benayssa, F. Benayache, S. Benayache, A. Vlietinck Objective : Toxicity of pesticides is thought to be due to reactive oxygen species (ROS). [...]

Published
2007

31. A New Formulation of an Old Drug: A Potential New Therapy in the Management of Oral cGvHD

Author

Bertelli, L, Di Nardo, G, Zama, D, Bardasi, G, Morello, W, Masetti, R, Belotti, T, Forchielli, M, Prete, A, Pession, A, Bertelli, Luca, Di Nardo, Giovanni, Zama, Daniele, Bardasi, Giulia, Morello, William, Masetti, Riccardo, Belotti, Tamara, Forchielli, Maria Luisa, Prete, Arcangelo, Pession, Andrea, Bertelli, L, Di Nardo, G, Zama, D, Bardasi, G, Morello, W, Masetti, R, Belotti, T, Forchielli, M, Prete, A, Pession, A, Bertelli, Luca, Di Nardo, Giovanni, Zama, Daniele, Bardasi, Giulia, Morello, William, Masetti, Riccardo, Belotti, Tamara, Forchielli, Maria Luisa, Prete, Arcangelo, and Pession, Andrea

Abstract

Oral chronic graft versus host disease (cGVHD) is often refractory to systemic therapies. Additional topical treatment is commonly required. The potency of the agent, the vehicle and formulation in which it is delivered are all critical factors in determining the effectiveness of topical therapies. High potency of budesonide, combined with its very low bioavailability when absorbed through mucosal surfaces, increased the potential role in topical application for oral cGVHD. Viscous formulation increases mucosal contact time resulting in a greater decrease in mucosal inflammation. This short communication suggests that oral viscous budesonide should be considered as a potential new therapy in the management of oral cGVHD.

Published
2016

34. Acute myeloid leukemia in infants: Biology and treatment

Author

Masetti, R., Vendemini, F., Zama, D., Biagi, C., Pession, A., Locatelli, Franco, Locatelli F. (ORCID:0000-0002-7976-3654), Masetti, R., Vendemini, F., Zama, D., Biagi, C., Pession, A., Locatelli, Franco, and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

Children aged 0-2 years (i.e., infants) with acute myeloid leukemia (AML) are a peculiar subgroup of patients in the childhood AML scenario. They present with distinctive biological and clinical characteristics, including a high prevalence of prognostically unfavorable risk factors and an increased susceptibility to therapy-related toxicity. Remarkable improvements have been achieved over the last two decades in the treatment of these patients and their outcome is becoming superimposable to that of the older age groups. In this review, we will focus on peculiarities of this young subgroup of children with AML, describing their clinical presentation, the biology of disease, and factors influencing outcome. Treatment results and toxicity data reported by major collaborative groups are also summarized and compared.

Published
2015

35. Identification of the NUP98-PHF23 fusion gene in pediatric cytogenetically normal acute myeloid leukemia by whole-transcriptome sequencing

Author

Togni, M., Masetti, R., Pigazzi, M., Astolfi, A., Zama, D., Indio, V., Serravalle, S., Manara, E., Bisio, V., Rizzari, C., Basso, G., Pession, A., Locatelli, Franco, Locatelli F. (ORCID:0000-0002-7976-3654), Togni, M., Masetti, R., Pigazzi, M., Astolfi, A., Zama, D., Indio, V., Serravalle, S., Manara, E., Bisio, V., Rizzari, C., Basso, G., Pession, A., Locatelli, Franco, and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

The genomic landscape of children with acute myeloid leukemia (AML) who do not carry any cytogenetic abnormality (CN-AML) is particularly heterogeneous and challenging, being characterized by different clinical outcomes. To provide new genetic insights into this AML subset, we analyzed through RNA-seq 13 pediatric CN-AML cases, corroborating our findings in an independent cohort of 168 AML patients enrolled in the AIEOP AML 2002/01 study. We identified a chimeric transcript involving NUP98 and PHF23, resulting from a cryptic t(11;17)(p15;p13) translocation, demonstrating, for the first time, that NUP98-PHF23 is a novel recurrent (2.6 %) abnormality in pediatric CN-AML.

Published
2015

36. Impact of inflammatory cytokine gene polymorphisms on developing acute graft-versus-host disease in children undergoing allogeneic hematopoietic stem cell transplantation

Author

Masetti, R, Zama, D, Urbini, M, Astolfi, A, Libri, V, Vendemini, F, Morello, W, Rondelli, R, Prete, A, Pession, A, Masetti, Riccardo, Zama, Daniele, Urbini, Milena, Astolfi, Annalisa, Libri, Virginia, Vendemini, Francesca, Morello, William, Rondelli, Roberto, Prete, Arcangelo, Pession, Andrea, Masetti, R, Zama, D, Urbini, M, Astolfi, A, Libri, V, Vendemini, F, Morello, W, Rondelli, R, Prete, A, Pession, A, Masetti, Riccardo, Zama, Daniele, Urbini, Milena, Astolfi, Annalisa, Libri, Virginia, Vendemini, Francesca, Morello, William, Rondelli, Roberto, Prete, Arcangelo, and Pession, Andrea

Abstract

Single nucleotide polymorphisms (SNPs) in gene encoding pro-and anti-inflammatory factors have been associated with the occurrence of aGvHD. We retrospectively tested a wide panel of 38 polymorphisms in 19 immunoregulatory genes, aiming to first establish, in a pediatric HSCT setting, which SNPs were significantly associated with the development of aGvHD. A significant association was found between aGvHD grades II-IV and SNPs of donor IL10-1082GG, and Fas-670CC + CT and recipient IL18-607 TT + TG genotype. aGvHD grades III-IV resulted associated with donor IL10-1082GG, Fas-670CC + CT, and TLR4-3612TT as well as the use of peripheral CD34+ cells as stem cell source. The multivariate analysis confirmed the association between donor IL10-1082GG and Fas-670CC + CT and aGvHD grades II-IV and between donor IL10-1082GG and TLR4-3612TT and aGvHD grades III-IV. In conclusion we found an association between IL10, FAS, and TLR4 in the donor and IL18 in the recipient and an increased risk of developing aGvHD in transplanted children. Knowledge of the SNPs of cytokine genes associated with aGvHD represents a useful tool for an integrated pretransplantation risk assessment and could guide the physicians to an optimal and more accurate HSCT planning.

Published
2015

37. Inflammatory disease of the central nervous system induced by anti-GD2 monoclonal antibody in a patient with high risk neuroblastoma

Author

Zama, D, Morello, W, Masetti, R, Cordelli, D, Massaccesi, E, Prete, A, Pession, A, Zama, Daniele, Morello, William, Masetti, Riccardo, Cordelli, Duccio Maria, Massaccesi, Erika, Prete, Arcangelo, Pession, Andrea, Zama, D, Morello, W, Masetti, R, Cordelli, D, Massaccesi, E, Prete, A, Pession, A, Zama, Daniele, Morello, William, Masetti, Riccardo, Cordelli, Duccio Maria, Massaccesi, Erika, Prete, Arcangelo, and Pession, Andrea

Published
2014

39. Focal nodular hyperplasia of the liver in children after hematopoietic stem cell transplantation

Author

Masetti, R, Zama, D, Gasperini, P, Morello, W, Prete, A, Colecchia, A, Festi, D, Pession, A, Masetti, Riccardo, Zama, Daniele, Gasperini, Pietro, Morello, William, Prete, Arcangelo, Colecchia, Antonio, Festi, Davide, Pession, Andrea, Masetti, R, Zama, D, Gasperini, P, Morello, W, Prete, A, Colecchia, A, Festi, D, Pession, A, Masetti, Riccardo, Zama, Daniele, Gasperini, Pietro, Morello, William, Prete, Arcangelo, Colecchia, Antonio, Festi, Davide, and Pession, Andrea

Abstract

FNH is a non-malignant neoplasia of the liver rarely described in children. A significant percentage of the pediatric cases have been reported in patients with a history of malignant disease treated with chemo-radiation therapy and in children who were given HSCT. Little is known about the pathogenesis of FNH in transplanted children, but many risk factors linked to the HSCT procedure have been hypothesized. The detection of hepatic nodules, particularly in children who underwent HSCT for a previous malignancy, always raises a diagnostic dilemma. To help the physicians in the diagnostic management of this rare entity, we have retrospectively evaluated a series of transplanted children diagnosed with FNH in our Center over the last 15 yr. In this period, we found 10 new diagnoses of FNH. The diagnostic work-up included CEUS, abdominal CT, and MRI. A liver biopsy was performed in two patients. The median FUP time after diagnosing FNH was 3.8 yr, with an abdominal US and no malignant transformation were observed. Possible risk factors and indications for the management of FNH in transplanted children are reported and discussed in a comprehensive review of the literature. © 2013 John Wiley & Sons A/S.

Published
2013

40. Retinoids in pediatric onco-hematology: The model of acute promyelocytic leukemia and neuroblastoma

Author

Masetti, R, Biagi, C, Zama, D, Vendemini, F, Martoni, A, Morello, W, Gasperini, P, Pession, A, Masetti, Riccardo, Biagi, Carlotta, Zama, Daniele, Vendemini, Francesca, Martoni, Anna, Morello, William, Gasperini, Pietro, Pession, Andrea, Masetti, R, Biagi, C, Zama, D, Vendemini, F, Martoni, A, Morello, W, Gasperini, P, Pession, A, Masetti, Riccardo, Biagi, Carlotta, Zama, Daniele, Vendemini, Francesca, Martoni, Anna, Morello, William, Gasperini, Pietro, and Pession, Andrea

Abstract

Retinoids are lipophilic compounds derived from vitamin A, which have been extensively studied in cancer prevention and therapy. In pediatric oncology, they are successfully used for the treatment of acute promyelocytic leukemia (APL) and high-risk neuroblastoma (HR-NBL). APL is a subtype of acute myeloid leukemia (AML) clinically characterized by a severe bleeding tendency with a highrisk of fatal hemorrhage. The molecular hallmark of this disease is the presence of the promyelocytic leukemia (PML)-retinoic acid receptor-a (RAR a) gene fusion that plays a critical role in promyelocytic leukemogenesis and represents the target of retinoid therapy. The introduction in the late 1980s of all-trans retinoic acid (ATRA) into the therapy of APL radically changed the management and the outcome of this disease. Presently, the standard front-line therapeutic approach for pediatric APL includes anthracycline-based chemotherapy and ATRA, leading to a complete remission in almost 90% of the patients. Neuroblastoma (NBL) is an aggressive childhood tumor derived from the peripheral neural crest. More than half of patients have a high-risk disease, with a poor outcome despite intensive multimodal treatment. Although the exact mechanism of action remains unclear, the introduction of 13-cis-retinoic acid (13-cis-RA) in the therapy of NBL has improved the prognosis of this disease. Currently, the standard treatment for HR-NBL consists of myeloablative therapy followed by autologous hematopoietic stem cell transplantation (HSCT) and maintenance with 13-cis-RA for the treatment of minimal residual disease, leading to a 3-year disease-free survival rate (DFS) of about 50%. In this paper the authors provide a review of the peer-reviewed literature on the role of retinoids in the treatment of pediatric APL and HR-NBL, summarizing the most relevant clinical trial results of the last decades, analyzing the ongoing trials, and investigating future therapeutic perspectives of children affecte

Published
2012

48. Effet hépatoprotecteur et antiradicalaire d'un extrait butanolique de Rhantherium suaveolens.

Author

Amrani, A., Benaissa, O., Boubekri, N., Zama, D., Biod, K., Beroal, N., Benayache, F., Benayache, S., and Bettuzzi, S.

Abstract

Copyright of Phytothérapie is the property of John Libbey Eurotext Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Published
2014
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