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1. Decoding the historical tale: COVID-19 impact on haematological malignancy patients—EPICOVIDEHA insights from 2020 to 2022

Author

Salmanton-Garcia, J., Marchesi, F., Farina, F., Weinbergerova, B., Itri, F., Davila-Valls, J., Martin-Perez, S., Glenthoj, A., Hersby, D. S., Gomes da Silva, M., Nunes Rodrigues, R., Lopez-Garcia, A., Cordoba, R., Bilgin, Y. M., Falces-Romero, I., El-Ashwah, S., Emarah, Z., Besson, C., Kohn, M., Van Doesum, J., Ammatuna, E., Marchetti, M., Labrador, J., Zambrotta, G. P. M., Verga, L., Jaksic, O., Nucci, M., Piukovics, K., Cabirta-Touzon, A., Jimenez, M., Arellano, E., Espigado, I., Blennow, O., Nordlander, A., Meers, S., van Praet, J., Aiello, T. F., Garcia-Vidal, C., Fracchiolla, N., Sciume, M., Seval, G. C., Zak, P., Buquicchio, C., Tascini, C., Grafe, S. K., Schonlein, M., Adzic-Vukicevic, T., Bonuomo, V., Cattaneo, C., Nizamuddin, S., Cernan, M., Plantefeve, G., Prin, R., Szotkovski, T., Collins, G. P., Dargenio, M., Petzer, V., Wolf, D., Colovic, N., Prezioso, L., Valkovic, T., Passamonti, F., Mendez, G. -A., Sili, U., Vena, A., Bavastro, M., Limongelli, A., Duarte, R. F., Ledoux, M. -P., Cvetanoski, M., Stojanoski, Z., Machado, M., Batinic, J., Magliano, G., Biernat, M. M., Pantic, N., Poulsen, C. B., Cuccaro, A., Del Principe, M. I., Kulasekararaj, A., Ormazabal-Velez, I., Busca, A., Demirkan, F., Ijaz, M., Klimko, N., Stoma, I., Khostelidi, S., Fernandez, N., Omrani, A. S., Bergantim, R., De Jonge, N., Fouquet, G., Navratil, M., Abu-Zeinah, G., Samarkos, M., Maertens, J., De Ramon, C., Guidetti, A., Magyari, F., Gonzalez-Lopez, T. J., Lahmer, T., Finizio, O., Ali, N., Pinczes, L. I., Lavilla-Rubira, E., Romano, A., Merelli, M., Delia, M., Calbacho, M., Meletiadis, J., Antic, D., Hernandez-Rivas, J. -A., Marques de Almeida, J., Al-Khabori, M., Hoenigl, M., Tisi, M. C., Khanna, N., Barac, A., Eisa, N., Di Blasi, R., Lievin, R., Miranda-Castillo, C., Bahr, N. C., Lamure, S., Papa, M. V., Yahya, A., Aujayeb, A., Novak, J., Erben, N., Fernandez-Galan, M., Ribera-Santa Susana, J. -M., Rinaldi, I., Fazzi, R., Piedimonte, M., Dulery, R., Gonzaga, Y., Soto-Silva, A., Sapienza, G., Serris, A., Drgona, Groh, A., Serrano, L., Gavriilaki, E., Tragiannidis, A., Prattes, J., Coppola, N., Otasevic, V., Mladenovic, M., Mitrovic, M., Miskovic, B., Jindra, P., Zompi, S., Sacchi, M. V., Krekeler, C., Infante, M. S., Garcia-Bordallo, D., Colak, G. M., Mayer, J., Nygaard, M., Hanakova, M., Racil, Z., Bonanni, Matteo, Koehler, P., Rahimli, L., Cornely, O. A., Pagano, Livio, Martin-Vallejo, F. J., Zdziarski, P., Zarrinfer, H., Wittig, J., Win, S., Wai-Man, V., Visek, B., Vinh, D. C., Vehreschild, M., Varricchio, G., Tsirigotis, P., Torres-Tienza, A., Tanase, A. D., Tafuri, A., Stamouli, M., Sramek, J., Soussain, C., Shirinova, A., Schubert, J., Schalk, E., Salehi, M. R., Saleh, M., Rosati, G., Roldan, E., Reizine, F., Rego, M., Regalado-Artamendi, I., Popova, M., Pinto, F., Philippe, L., Orth, H. M., Ommen, H. -B., Obr, A., Nunez-Martin-Buitrago, L., Noel, N., Neuhann, J., Nadali, G., Nacov, J. A., Munhoz Alburquerque, A. M., Mitra, M. E., Mikulska, M., Mellinghoff, S., Mechtel, B., Martin-Gonzalez, J. -A., Malak, S., Loureiro-Amigo, J., Lorenzo De La Pena, L., Liberti, G., Landau, M., Lacej, I., Kolditz, M., Kho, C. S., Khedr, R. A., Karthaus, M., Karlsson, L. K., Jimenez-Lorenzo, M. -J., Izuzquiza, M., Hoell-Neugebauer, B., Herbrecht, R., Heath, C. H., Guolo, F., Grothe, J., Giordano, A., Gerasymchuk, S., Garcia-Sanz, R., Garcia-Pouton, N., Funke, V. A. M., Fung, M., Flasshove, C., Fianchi, Luana, Essame, J., Egger, M., Drenou, B., Dragonetti, G., Desole, M., Della Pepa, R., Deau Fischer, B., De Kort, E., De Cabo, E., Danion, F., Daguindau, E., Cushion, T., Cremer, L., Criscuolo, Marianna, Cordini, G., Cingolani, Antonella, Ciceri, F., Chowdhury, F. R., Chelysheva, E., Chauchet, A., Chai, L. Y. A., Ceesay, M. M., Busch, E., Brehon, M., Borducchi, D. M. M., Booth, S., Bologna, S., Berg Venemyr, C., Bailen-Almorox, R., Antoniadou, A., Anastasopoulou, A. N., Altuntas, F., Bonanni M., Pagano L. (ORCID:0000-0001-8287-928X), Fianchi L., Criscuolo M., Cingolani A. (ORCID:0000-0002-3793-2755), Salmanton-Garcia, J., Marchesi, F., Farina, F., Weinbergerova, B., Itri, F., Davila-Valls, J., Martin-Perez, S., Glenthoj, A., Hersby, D. S., Gomes da Silva, M., Nunes Rodrigues, R., Lopez-Garcia, A., Cordoba, R., Bilgin, Y. M., Falces-Romero, I., El-Ashwah, S., Emarah, Z., Besson, C., Kohn, M., Van Doesum, J., Ammatuna, E., Marchetti, M., Labrador, J., Zambrotta, G. P. M., Verga, L., Jaksic, O., Nucci, M., Piukovics, K., Cabirta-Touzon, A., Jimenez, M., Arellano, E., Espigado, I., Blennow, O., Nordlander, A., Meers, S., van Praet, J., Aiello, T. F., Garcia-Vidal, C., Fracchiolla, N., Sciume, M., Seval, G. C., Zak, P., Buquicchio, C., Tascini, C., Grafe, S. K., Schonlein, M., Adzic-Vukicevic, T., Bonuomo, V., Cattaneo, C., Nizamuddin, S., Cernan, M., Plantefeve, G., Prin, R., Szotkovski, T., Collins, G. P., Dargenio, M., Petzer, V., Wolf, D., Colovic, N., Prezioso, L., Valkovic, T., Passamonti, F., Mendez, G. -A., Sili, U., Vena, A., Bavastro, M., Limongelli, A., Duarte, R. F., Ledoux, M. -P., Cvetanoski, M., Stojanoski, Z., Machado, M., Batinic, J., Magliano, G., Biernat, M. M., Pantic, N., Poulsen, C. B., Cuccaro, A., Del Principe, M. I., Kulasekararaj, A., Ormazabal-Velez, I., Busca, A., Demirkan, F., Ijaz, M., Klimko, N., Stoma, I., Khostelidi, S., Fernandez, N., Omrani, A. S., Bergantim, R., De Jonge, N., Fouquet, G., Navratil, M., Abu-Zeinah, G., Samarkos, M., Maertens, J., De Ramon, C., Guidetti, A., Magyari, F., Gonzalez-Lopez, T. J., Lahmer, T., Finizio, O., Ali, N., Pinczes, L. I., Lavilla-Rubira, E., Romano, A., Merelli, M., Delia, M., Calbacho, M., Meletiadis, J., Antic, D., Hernandez-Rivas, J. -A., Marques de Almeida, J., Al-Khabori, M., Hoenigl, M., Tisi, M. C., Khanna, N., Barac, A., Eisa, N., Di Blasi, R., Lievin, R., Miranda-Castillo, C., Bahr, N. C., Lamure, S., Papa, M. V., Yahya, A., Aujayeb, A., Novak, J., Erben, N., Fernandez-Galan, M., Ribera-Santa Susana, J. -M., Rinaldi, I., Fazzi, R., Piedimonte, M., Dulery, R., Gonzaga, Y., Soto-Silva, A., Sapienza, G., Serris, A., Drgona, Groh, A., Serrano, L., Gavriilaki, E., Tragiannidis, A., Prattes, J., Coppola, N., Otasevic, V., Mladenovic, M., Mitrovic, M., Miskovic, B., Jindra, P., Zompi, S., Sacchi, M. V., Krekeler, C., Infante, M. S., Garcia-Bordallo, D., Colak, G. M., Mayer, J., Nygaard, M., Hanakova, M., Racil, Z., Bonanni, Matteo, Koehler, P., Rahimli, L., Cornely, O. A., Pagano, Livio, Martin-Vallejo, F. J., Zdziarski, P., Zarrinfer, H., Wittig, J., Win, S., Wai-Man, V., Visek, B., Vinh, D. C., Vehreschild, M., Varricchio, G., Tsirigotis, P., Torres-Tienza, A., Tanase, A. D., Tafuri, A., Stamouli, M., Sramek, J., Soussain, C., Shirinova, A., Schubert, J., Schalk, E., Salehi, M. R., Saleh, M., Rosati, G., Roldan, E., Reizine, F., Rego, M., Regalado-Artamendi, I., Popova, M., Pinto, F., Philippe, L., Orth, H. M., Ommen, H. -B., Obr, A., Nunez-Martin-Buitrago, L., Noel, N., Neuhann, J., Nadali, G., Nacov, J. A., Munhoz Alburquerque, A. M., Mitra, M. E., Mikulska, M., Mellinghoff, S., Mechtel, B., Martin-Gonzalez, J. -A., Malak, S., Loureiro-Amigo, J., Lorenzo De La Pena, L., Liberti, G., Landau, M., Lacej, I., Kolditz, M., Kho, C. S., Khedr, R. A., Karthaus, M., Karlsson, L. K., Jimenez-Lorenzo, M. -J., Izuzquiza, M., Hoell-Neugebauer, B., Herbrecht, R., Heath, C. H., Guolo, F., Grothe, J., Giordano, A., Gerasymchuk, S., Garcia-Sanz, R., Garcia-Pouton, N., Funke, V. A. M., Fung, M., Flasshove, C., Fianchi, Luana, Essame, J., Egger, M., Drenou, B., Dragonetti, G., Desole, M., Della Pepa, R., Deau Fischer, B., De Kort, E., De Cabo, E., Danion, F., Daguindau, E., Cushion, T., Cremer, L., Criscuolo, Marianna, Cordini, G., Cingolani, Antonella, Ciceri, F., Chowdhury, F. R., Chelysheva, E., Chauchet, A., Chai, L. Y. A., Ceesay, M. M., Busch, E., Brehon, M., Borducchi, D. M. M., Booth, S., Bologna, S., Berg Venemyr, C., Bailen-Almorox, R., Antoniadou, A., Anastasopoulou, A. N., Altuntas, F., Bonanni M., Pagano L. (ORCID:0000-0001-8287-928X), Fianchi L., Criscuolo M., and Cingolani A. (ORCID:0000-0002-3793-2755)

Abstract

Background: The COVID-19 pandemic heightened risks for individuals with hematological malignancies due to compromised immune systems, leading to more severe outcomes and increased mortality. While interventions like vaccines, targeted antivirals, and monoclonal antibodies have been effective for the general population, their benefits for these patients may not be as pronounced. Methods: The EPICOVIDEHA registry (National Clinical Trials Identifier, NCT04733729) gathers COVID-19 data from hematological malignancy patients since the pandemic's start worldwide. It spans various global locations, allowing comprehensive analysis over the first three years (2020–2022). Findings: The EPICOVIDEHA registry collected data from January 2020 to December 2022, involving 8767 COVID-19 cases in hematological malignancy patients from 152 centers across 41 countries, with 42% being female. Over this period, there was a significant reduction in critical infections and an overall decrease in mortality from 29% to 4%. However, hospitalization, particularly in the ICU, remained associated with higher mortality rates. Factors contributing to increased mortality included age, multiple comorbidities, active malignancy at COVID-19 onset, pulmonary symptoms, and hospitalization. On the positive side, vaccination with one to two doses or three or more doses, as well as encountering COVID-19 in 2022, were associated with improved survival. Interpretation: Patients with hematological malignancies still face elevated risks, despite reductions in critical infections and overall mortality rates over time. Hospitalization, especially in ICUs, remains a significant concern. The study underscores the importance of vaccination and the timing of COVID-19 exposure in 2022 for enhanced survival in this patient group. Ongoing monitoring and targeted interventions are essential to support this vulnerable population, emphasizing the critical role of timely diagnosis and prompt treatment in preventing severe

Published
2024

2. Prospective multicenter study on infectious complications and clinical outcome of 230 unfit acute myeloid leukemia patients receiving first-line therapy with hypomethylating agents alone or in combination with Venetoclax

Author

Candoni, A., Lazzarotto, D., Papayannidis, C., Piccini, M., Nadali, G., Dargenio, M., Riva, M., Fracchiolla, N., Mellillo, L., Dragonetti, Giulia, Del Principe, M. I., Cattaneo, C., Stulle, M., Pasciolla, C., De Marchi, R., Delia, M., Tisi, M. C., Bonuomo, V., Sciume, M., Spadea, A., Sartor, C., Griguolo, D., Buzzatti, E., Basilico, C. M., Sarlo, C., Piccioni, A. L., Cerqui, E., Lessi, F., Olivieri, A., Fanin, R., Luppi, M., Pagano, Livio, Dragonetti G., Pagano L. (ORCID:0000-0001-8287-928X), Candoni, A., Lazzarotto, D., Papayannidis, C., Piccini, M., Nadali, G., Dargenio, M., Riva, M., Fracchiolla, N., Mellillo, L., Dragonetti, Giulia, Del Principe, M. I., Cattaneo, C., Stulle, M., Pasciolla, C., De Marchi, R., Delia, M., Tisi, M. C., Bonuomo, V., Sciume, M., Spadea, A., Sartor, C., Griguolo, D., Buzzatti, E., Basilico, C. M., Sarlo, C., Piccioni, A. L., Cerqui, E., Lessi, F., Olivieri, A., Fanin, R., Luppi, M., Pagano, Livio, Dragonetti G., and Pagano L. (ORCID:0000-0001-8287-928X)

Abstract

no abstract

Published
2023

3. Clinical features and prognostic factors of Magnusiomyces (Saprochaete) infections in haematology. A multicentre study of SEIFEM/Fungiscope

Author

Del Principe, M. I., Seidel, D., Criscuolo, Marianna, Dargenio, M., Racil, Z., Piedimonte, M., Marchesi, F., Nadali, G., Koehler, P., Fracchiolla, N., Cattaneo, C., Klimko, N., Spolzino, A., Yilmaz Karapinar, D., Demiraslan, H., Duarte, R. F., Demeter, J., Stanzani, M., Melillo, L. M. A., Basilico, C., Cesaro, S., Paterno, G., Califano, C., Delia, M., Buzzatti, E., Busca, A., Alakel, N., Arsenijevi'C, V. A., Camus, V., Falces-Romero, I., Itzhak, L., Kouba, M., Martino, R., Sedlacek, P., Weinbergerova, B., Cornely, O. A., Pagano, Livio, Criscuolo M., Pagano L. (ORCID:0000-0001-8287-928X), Del Principe, M. I., Seidel, D., Criscuolo, Marianna, Dargenio, M., Racil, Z., Piedimonte, M., Marchesi, F., Nadali, G., Koehler, P., Fracchiolla, N., Cattaneo, C., Klimko, N., Spolzino, A., Yilmaz Karapinar, D., Demiraslan, H., Duarte, R. F., Demeter, J., Stanzani, M., Melillo, L. M. A., Basilico, C., Cesaro, S., Paterno, G., Califano, C., Delia, M., Buzzatti, E., Busca, A., Alakel, N., Arsenijevi'C, V. A., Camus, V., Falces-Romero, I., Itzhak, L., Kouba, M., Martino, R., Sedlacek, P., Weinbergerova, B., Cornely, O. A., Pagano, Livio, Criscuolo M., and Pagano L. (ORCID:0000-0001-8287-928X)

Abstract

Background: Our multicentre study aims to identify baseline factors and provide guidance for therapeutic decisions regarding Magnusiomyces-associated infections, an emerging threat in patients with haematological malignancies. Methods: HM patients with proven (Magnusiomyces capitatus) M. capitatus or (Magnusiomyces clavatus) M. clavatus (formerly Saprochaete capitata and Saprochaete clavata) infection diagnosed between January 2010 and December 2020 were recorded from the SEIFEM (Sorveglianza Epidemiologica Infezioni nelle Emopatie) group and FungiScope (Global Emerging Fungal Infection Registry). Cases of Magnusiomyces fungemia were compared with candidemia. Results: Among 90 Magnusiomyces cases (60 [66%] M. capitatus and 30 (34%) M. clavatus), median age was 50 years (range 2–78), 46 patients (51%) were female and 67 (74%) had acute leukaemia. Thirty-six (40%) of Magnusiomyces-associated infections occurred during antifungal prophylaxis, mainly with posaconazole (n = 13, 36%) and echinocandins (n = 12, 34%). Instead, the candidemia rarely occurred during prophylaxis (p <.0001). First-line antifungal therapy with azoles, alone or in combination, was associated with improved response compared to other antifungals (p =.001). Overall day-30 mortality rate was 43%. Factors associated with higher mortality rates were septic shock (HR 2.696, 95% CI 1.396–5.204, p =.003), corticosteroid treatment longer than 14 days (HR 2.245, 95% CI 1.151–4.376, p =.018) and lack of neutrophil recovery (HR 3.997, 95% CI 2.102–7.601, p <.001). The latter was independently associated with poor outcome (HR 2.495, 95% CI 1.192–5.222, p =.015). Conclusions: Magnusiomyces-associated infections are often breakthrough infections. Effective treatment regimens of these infections remain to be determined, but neutrophil recovery appears to play an important role in the favourable outcome.

Published
2023

4. Posaconazole and midostaurin in patients with FLT3-mutated acute myeloid leukemia: Pharmacokinetic interactions and clinical facts in a real life study

Author

Menna, P., Marchesi, F., Cattaneo, C., Candoni, A., Delia, M., Nadali, G., Vatteroni, A., Pasciolla, C., Perrone, S., Verga, L., Armiento, D., Delprincipe, M. I., Fracchiolla, N. S., Salvatorelli, E., Lupisella, S., Terrenato, I., Busca, A., Minotti, G., Pagano, Livio, Pagano L. (ORCID:0000-0001-8287-928X), Menna, P., Marchesi, F., Cattaneo, C., Candoni, A., Delia, M., Nadali, G., Vatteroni, A., Pasciolla, C., Perrone, S., Verga, L., Armiento, D., Delprincipe, M. I., Fracchiolla, N. S., Salvatorelli, E., Lupisella, S., Terrenato, I., Busca, A., Minotti, G., Pagano, Livio, and Pagano L. (ORCID:0000-0001-8287-928X)

Abstract

Midostaurin is used in combination with chemotherapy to treat patients with newly diagnosed FLT3-mutated acute myeloid leukemia. Chemotherapy-induced neutropenia exposes these patients to a significant risk of invasive fungal infections (IFIs). International guidelines recommend primary antifungal prophylaxis with posaconazole (PCZ) but nested analysis of a phase III trial showed that strong PCZ inhibition of CYP3A4 diminished midostaurin metabolism and increased midostaurin plasma levels; however, midostaurin-related adverse events (AEs) were only moderately exacerbated. We conducted a prospective multicenter real-life study to evaluate (i) how often concerns around PCZ-midostaurin interactions made the hematologist prescribe antifungals other than PCZ, (ii) how remarkably PCZ increased midostaurin plasma levels, and (iii) how significantly PCZ-midostaurin interactions influenced hematologic and safety outcomes of induction therapy. Although the hematologists were blinded to pharmacokinetic findings, as many as 16 of 35 evaluable patients were prescribed antifungal prophylaxis with micafungin, weak CYP3A4 inhibitor, in place of PCZ (p < 0.001 for deviation from guidelines). In the 19 patients managed as per guidelines, PCZ-midostaurin interactions were more remarkable than previously characterized, such that at the end of induction therapy midostaurin minimum plasma concentration (Cmin) was greater than three times higher than reported; moreover, midostaurin Cmin, maximum plasma concentration, and area under the curve were more than or equal to four times higher with PCZ than micafungin. Hematologic outcomes (complete remission and duration of severe neutropenia) and safety outcomes (midostaurin-related any grade or grade ≥3 AEs) were nonetheless similar for patients exposed to PCZ or micafungin, as was the number of breakthrough IFIs. In waiting for randomized phase III trials of new prophylaxis regimens, these findings show that PCZ should remain the antifunga

Published
2023

5. INTERIM RESULTS OF PROSPECTIVE OBSERVATIONAL SEIFEM STUDY ON CLINICAL OUTCOME AND INFECTIOUS COMPLICATIONS IN 230 UNFIT AML PATIENTS TREATED IN FIRST-LINE WITH HYPOMETHYLATING AGENTS ALONE OR IN COMBINATION WITH VENETOCLAX

Author

Candoni, A, Piccin, M, Lazzarotto, D, Bonuomo, V, Fracchiolla, N, Dargenio, M, Riva, M, Melillo, L, Papayannidis, C, Stulle, M, Lessi, F, Dragonetti, G, Del Principe, M, Cerqui, E, Pasciolla, C, De Marchi, R, Delia, M, Tisi, M, Fanci, R, Nadali, G, Sciume, M, Di Renzo, N, Cairoli, R, Valente, D, Basilico, C, (, C., ), A, (, A., ), D, (, D., ), Pagano, L, Candoni A, Piccin M, Lazzarotto D, Bonuomo V, Fracchiolla N, Dargenio M, Riva M, Melillo L, Papayannidis C, Stulle M, Lessi F, Dragonetti G, Del Principe MI, Cerqui E, Pasciolla C, De Marchi R, Delia M, Tisi MC, Fanci R, Nadali G, Sciume M, Di Renzo N, Cairoli R, Valente D, C (Basilico, C.) 18 Spadea, A (Spadea, A.) 19 Sartor, C (Sartor, C.) 8 Griguolo, D (Griguolo, D.) 9 Sarlo, C (Sarlo, C.) 20 Olivieri, A (Olivieri, A.) 21 Piccioni AL, Pagano L, Candoni, A, Piccin, M, Lazzarotto, D, Bonuomo, V, Fracchiolla, N, Dargenio, M, Riva, M, Melillo, L, Papayannidis, C, Stulle, M, Lessi, F, Dragonetti, G, Del Principe, M, Cerqui, E, Pasciolla, C, De Marchi, R, Delia, M, Tisi, M, Fanci, R, Nadali, G, Sciume, M, Di Renzo, N, Cairoli, R, Valente, D, Basilico, C, (, C., ), A, (, A., ), D, (, D., ), Pagano, L, Candoni A, Piccin M, Lazzarotto D, Bonuomo V, Fracchiolla N, Dargenio M, Riva M, Melillo L, Papayannidis C, Stulle M, Lessi F, Dragonetti G, Del Principe MI, Cerqui E, Pasciolla C, De Marchi R, Delia M, Tisi MC, Fanci R, Nadali G, Sciume M, Di Renzo N, Cairoli R, Valente D, C (Basilico, C.) 18 Spadea, A (Spadea, A.) 19 Sartor, C (Sartor, C.) 8 Griguolo, D (Griguolo, D.) 9 Sarlo, C (Sarlo, C.) 20 Olivieri, A (Olivieri, A.) 21 Piccioni AL, and Pagano L

Published
2021

6. P517: PROSPECTIVE MULTICENTRIC STUDY ON INFECTIOUS COMPLICATIONS AND CLINICAL OUTCOME IN 230 UNFIT AML PATIENTS TREATED IN FIRST-LINE WITH HYPOMETHYLATING AGENTS ALONE OR IN COMBINATION WITH VENETOCLAX.

Author

Candoni, A., primary, Piccini, M., additional, Lazzarotto, D., additional, Bonuomo, V., additional, Dargenio, M., additional, Riva, M., additional, Mellillo, L., additional, Papayannidis, C., additional, Stulle, M., additional, Dragonetti, G., additional, Del Principe, M. I., additional, Cattaneo, C., additional, Pasciolla, C., additional, De Marchi, R., additional, Delia, M., additional, Tisi, M. C., additional, Zannier, M. E., additional, Nadali, G., additional, Sciumè, M., additional, Spadea, A., additional, Sartor, C., additional, Griguolo, D., additional, Buzzatti, E., additional, Basilico, C. M., additional, Sarlo, C., additional, Piccioni, A. L., additional, Cairoli, R., additional, Olivieri, A., additional, and Pagano, L., additional

Published
2022
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7. A High-Risk Profile for Invasive Fungal Infections Is Associated with Altered Nasal Microbiota and Niche Determinants

Author

Costantini, C., Nunzi, E., Spolzino, A., Merli, F., Facchini, L., Spadea, A., Melillo, L., Codeluppi, K., Marchesi, F., Marchesini, G., Valente, D., Dragonetti, Giulia, Nadali, G., Englmaier, L., Coufalikova, K., Spacil, Z., Bellet, M. M., Pariano, M., Renga, G., Stincardini, C., D'Onofrio, F., Bozza, S., Pagano, Livio, Aversa, F., Romani, L., Dragonetti G., Pagano L. (ORCID:0000-0001-8287-928X), Costantini, C., Nunzi, E., Spolzino, A., Merli, F., Facchini, L., Spadea, A., Melillo, L., Codeluppi, K., Marchesi, F., Marchesini, G., Valente, D., Dragonetti, Giulia, Nadali, G., Englmaier, L., Coufalikova, K., Spacil, Z., Bellet, M. M., Pariano, M., Renga, G., Stincardini, C., D'Onofrio, F., Bozza, S., Pagano, Livio, Aversa, F., Romani, L., Dragonetti G., and Pagano L. (ORCID:0000-0001-8287-928X)

Abstract

It is becoming increasingly clear that the communities of microorganisms that populate the surfaces exposed to the external environment, termed microbiota, are key players in the regulation of pathogen-host cross talk affecting the onset as well as the outcome of infectious diseases. We have performed a multicenter, prospective, observational study in which nasal and oropharyngeal swabs were collected for microbiota predicting the risk of invasive fungal infections (IFIs) in patients with hematological malignancies. Here, we demonstrate that the nasal and oropharyngeal microbiota are different, although similar characteristics differentiate high-risk from low-risk samples at both sites. Indeed, similar to previously published results on the oropharyngeal microbiota, high-risk samples in the nose were characterized by low diversity, a loss of beneficial bacteria, and an expansion of potentially pathogenic taxa, in the presence of reduced levels of tryptophan (Trp). At variance with oropharyngeal samples, however, low Trp levels were associated with defective host-derived kynurenine production, suggesting reduced tolerance mechanisms at the nasal mucosal surface. This was accompanied by reduced levels of the chemokine interleukin-8 (IL-8), likely associated with a reduced recruitment of neutrophils and impaired fungal clearance. Thus, the nasal and pharyngeal microbiomes of hematological patients provide complementary information that could improve predictive tools for the risk of IFI in hematological patients.

Published
2022

8. High Incidence of Invasive Fungal Diseases in Patients with FLT3-Mutated AML Treated with Midostaurin: Results of a Multicenter Observational SEIFEM Study

Author

Cattaneo, C., Marchesi, F., Terrenato, I., Bonuomo, V., Fracchiolla, N. S., Delia, M., Criscuolo, Marianna, Candoni, A., Prezioso, L., Facchinelli, D., Pasciolla, C., Del Principe, M. I., Dargenio, M., Buquicchio, C., Mitra, M. E., Farina, F., Borlenghi, E., Nadali, G., Gagliardi, V. P., Fianchi, Luana, Sciume, M., Menna, P., Busca, A., Rossi, G., Pagano, Livio, Criscuolo M., Fianchi L., Pagano L. (ORCID:0000-0001-8287-928X), Cattaneo, C., Marchesi, F., Terrenato, I., Bonuomo, V., Fracchiolla, N. S., Delia, M., Criscuolo, Marianna, Candoni, A., Prezioso, L., Facchinelli, D., Pasciolla, C., Del Principe, M. I., Dargenio, M., Buquicchio, C., Mitra, M. E., Farina, F., Borlenghi, E., Nadali, G., Gagliardi, V. P., Fianchi, Luana, Sciume, M., Menna, P., Busca, A., Rossi, G., Pagano, Livio, Criscuolo M., Fianchi L., and Pagano L. (ORCID:0000-0001-8287-928X)

Abstract

The potential drug-drug interactions of midostaurin may impact the choice of antifungal (AF) prophylaxis in FLT3-positive acute myeloid leukemia (AML) patients. To evaluate the incidence of invasive fungal diseases (IFD) during the treatment of FLT3-mutated AML patients and to correlate it to the different AF prophylaxis strategies, we planned a multicenter observational study involving 15 SEIFEM centers. One hundred fourteen patients treated with chemotherapy + midostaurin as induction/reinduction, consolidation or both were enrolled. During induction, the incidence of probable/proven and possible IFD was 10.5% and 9.7%, respectively; no statistically significant difference was observed according to the different AF strategy adopted. The median duration of neutropenia was similar in patients with or without IFD. Proven/probable and possible IFD incidence was 2.4% and 1.8%, respectively, during consolidation. Age was the only risk factor for IFD (OR, 95% CI, 1.10 [1.03–1.19]) and complete remission achievement after first induction the only one for survival (OR, 95% CI, 5.12 [1.93–13.60]). The rate of midostaurin discontinuation was similar across different AF strategies. The IFD attributable mortality during induction was 8.3%. In conclusion, the 20.2% overall incidence of IFD occurring in FLT3-mutated AML during induction with chemotherapy + midostaurin, regardless of AF strategy type, was noteworthy, and merits further study, particularly in elderly patients.

Published
2022

9. 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. INTERIM RESULTS OF PROSPECTIVE OBSERVATIONAL SEIFEM STUDY ON CLINICAL OUTCOME AND INFECTIOUS COMPLICATIONS IN 230 UNFIT AML PATIENTS TREATED IN FIRST-LINE WITH HYPOMETHYLATING AGENTS ALONE OR IN COMBINATION WITH VENETOCLAX

Author

Candoni A, Piccin M, Lazzarotto D, Bonuomo V, Fracchiolla N, Dargenio M, Riva M, Melillo L, Papayannidis C, Stulle M, Lessi F, Dragonetti G, Del Principe MI, Cerqui E, Pasciolla C, De Marchi R, Delia M, Tisi MC, Fanci R, Nadali G, Sciume M, Di Renzo N, Cairoli R, Valente D, Basilico, C (Basilico, C.) 18 Spadea, A (Spadea, A.) 19 Sartor, C (Sartor, C.) 8 Griguolo, D (Griguolo, D.) 9 Sarlo, C (Sarlo, C.) 20 Olivieri, A (Olivieri, A.) 21 Piccioni AL, Pagano L, Candoni, A, Piccin, M, Lazzarotto, D, Bonuomo, V, Fracchiolla, N, Dargenio, M, Riva, M, Melillo, L, Papayannidis, C, Stulle, M, Lessi, F, Dragonetti, G, Del Principe, M, Cerqui, E, Pasciolla, C, De Marchi, R, Delia, M, Tisi, M, Fanci, R, Nadali, G, Sciume, M, Di Renzo, N, Cairoli, R, Valente, D, Basilico, C,, C., ), A,, A., ), D,, D., ), and Pagano, L

Subjects
Hematology
Published
2021

11. COVID-19 infection in adult patients with hematological malignancies: a European Hematology Association Survey (EPICOVIDEHA)

Author

Pagano, L., Salmanton-Garcia, J., Marchesi, F., Busca, A., Corradini, P., Hoenigl, M., Klimko, N., Koehler, P., Pagliuca, A., Passamonti, F., Verga, L., Visek, B., Ilhan, O., Nadali, G., Weinbergerova, B., Cordoba-Mascunano, R., Marchetti, M., Collins, G. P., Farina, F., Cattaneo, C., Cabirta, A., Gomes-Silva, M., Itri, F., van Doesum, J., Ledoux, M. -P., Cernan, M., Jaksic, O., Duarte, R. F., Magliano, G., Omrani, A. S., Fracchiolla, N. S., Kulasekararaj, A., Valkovic, T., Poulsen, C. B., Machado, M., Glenthoj, A., Stoma, I., Racil, Z., Piukovics, K., Navratil, M., Emarah, Z., Sili, U., Maertens, J., Blennow, O., Bergantim, R., Garcia-Vidal, C., Prezioso, L., Guidetti, A., del Principe, M. I., Popova, M., de Jonge, N., Ormazabal-Velez, I., Fernandez, N., Falces-Romero, I., Cuccaro, A., Meers, S., Buquicchio, C., Antic, D., Al-Khabori, M., Garcia-Sanz, R., Biernat, M. M., Tisi, M. C., Sal, E., Rahimli, L., Colovic, N., Schonlein, M., Calbacho, M., Tascini, C., Miranda-Castillo, C., Khanna, N., Mendez, G. -A., Petzer, V., Novak, J., Besson, C., Dulery, R., Lamure, S., Nucci, M., Zambrotta, G., Zak, P., Seval, G. C., Bonuomo, V., Mayer, J., Lopez-Garcia, A., Sacchi, M. V., Booth, S., Ciceri, F., Oberti, M., Salvini, M., Izuzquiza, M., Nunes-Rodrigues, R., Ammatuna, E., Obr, A., Herbrecht, R., Nunez-Martin-Buitrago, L., Mancini, V., Shwaylia, H., Sciume, M., Essame, J., Nygaard, M., Batinic, J., Gonzaga, Y., Regalado-Artamendi, I., Karlsson, L. K., Shapetska, M., Hanakova, M., El-Ashwah, S., Borbenyi, Z., Colak, G. M., Nordlander, A., Dragonetti, G., Maraglino, A. M. E., Rinaldi, A., De Ramon-Sanchez, C., Cornely, O. A., Finizio, O., Fazzi, R., Sapienza, G., Chauchet, A., Van Praet, J., Prattes, J., Dargenio, M., Rossi, C., Shirinova, A., Malak, S., Tafuri, A., Ommen, H. -B., Bologna, S., Khedr, R. A., Choquet, S., Joly, B., Ceesay, M. M., Philippe, L., Kho, C. S., Desole, M., Tsirigotis, P., Otasevic, V., Borducchi, D. M. M., Antoniadou, A., Gaziev, J., Almaslamani, M. A., Garcia-Pouton, N., Paterno, G., Torres-Lopez, A., Tarantini, G., Mellinghoff, S., Grafe, S., Borschel, N., Passweg, J., Merelli, M., Barac, A., Wolf, D., Shaikh, M. U., Thieblemont, C., Bernard, S., Funke, V. A. M., Daguindau, E., Khostelidi, S., Nucci, F. M., Martin-Gonzalez, J. -A., Landau, M., Soussain, C., Laureana, C., Lacombe, K., Kohn, M., Aliyeva, G., Piedimonte, M., Fouquet, G., Rego, M., Hoell-Neugebauer, B., Cartron, G., Pinto, F., Alburquerque, A. M., Passos, J., Yilmaz, A. F., Redondo-Izal, A. -M., Altuntas, F., Heath, C., Kolditz, M., Schalk, E., Guolo, F., Karthaus, M., Della Pepa, R., Vinh, D., Noel, N., Deau Fischer, B., Drenou, B., Mitra, M. E., Meletiadis, J., Bilgin, Y. M., Jindra, P., Espigado, I., Drgona, L., Serris, A., Di Blasi, R., Ali, N., Pagano L. (ORCID:0000-0001-8287-928X), Dragonetti G., Pagano, L., Salmanton-Garcia, J., Marchesi, F., Busca, A., Corradini, P., Hoenigl, M., Klimko, N., Koehler, P., Pagliuca, A., Passamonti, F., Verga, L., Visek, B., Ilhan, O., Nadali, G., Weinbergerova, B., Cordoba-Mascunano, R., Marchetti, M., Collins, G. P., Farina, F., Cattaneo, C., Cabirta, A., Gomes-Silva, M., Itri, F., van Doesum, J., Ledoux, M. -P., Cernan, M., Jaksic, O., Duarte, R. F., Magliano, G., Omrani, A. S., Fracchiolla, N. S., Kulasekararaj, A., Valkovic, T., Poulsen, C. B., Machado, M., Glenthoj, A., Stoma, I., Racil, Z., Piukovics, K., Navratil, M., Emarah, Z., Sili, U., Maertens, J., Blennow, O., Bergantim, R., Garcia-Vidal, C., Prezioso, L., Guidetti, A., del Principe, M. I., Popova, M., de Jonge, N., Ormazabal-Velez, I., Fernandez, N., Falces-Romero, I., Cuccaro, A., Meers, S., Buquicchio, C., Antic, D., Al-Khabori, M., Garcia-Sanz, R., Biernat, M. M., Tisi, M. C., Sal, E., Rahimli, L., Colovic, N., Schonlein, M., Calbacho, M., Tascini, C., Miranda-Castillo, C., Khanna, N., Mendez, G. -A., Petzer, V., Novak, J., Besson, C., Dulery, R., Lamure, S., Nucci, M., Zambrotta, G., Zak, P., Seval, G. C., Bonuomo, V., Mayer, J., Lopez-Garcia, A., Sacchi, M. V., Booth, S., Ciceri, F., Oberti, M., Salvini, M., Izuzquiza, M., Nunes-Rodrigues, R., Ammatuna, E., Obr, A., Herbrecht, R., Nunez-Martin-Buitrago, L., Mancini, V., Shwaylia, H., Sciume, M., Essame, J., Nygaard, M., Batinic, J., Gonzaga, Y., Regalado-Artamendi, I., Karlsson, L. K., Shapetska, M., Hanakova, M., El-Ashwah, S., Borbenyi, Z., Colak, G. M., Nordlander, A., Dragonetti, G., Maraglino, A. M. E., Rinaldi, A., De Ramon-Sanchez, C., Cornely, O. A., Finizio, O., Fazzi, R., Sapienza, G., Chauchet, A., Van Praet, J., Prattes, J., Dargenio, M., Rossi, C., Shirinova, A., Malak, S., Tafuri, A., Ommen, H. -B., Bologna, S., Khedr, R. A., Choquet, S., Joly, B., Ceesay, M. M., Philippe, L., Kho, C. S., Desole, M., Tsirigotis, P., Otasevic, V., Borducchi, D. M. M., Antoniadou, A., Gaziev, J., Almaslamani, M. A., Garcia-Pouton, N., Paterno, G., Torres-Lopez, A., Tarantini, G., Mellinghoff, S., Grafe, S., Borschel, N., Passweg, J., Merelli, M., Barac, A., Wolf, D., Shaikh, M. U., Thieblemont, C., Bernard, S., Funke, V. A. M., Daguindau, E., Khostelidi, S., Nucci, F. M., Martin-Gonzalez, J. -A., Landau, M., Soussain, C., Laureana, C., Lacombe, K., Kohn, M., Aliyeva, G., Piedimonte, M., Fouquet, G., Rego, M., Hoell-Neugebauer, B., Cartron, G., Pinto, F., Alburquerque, A. M., Passos, J., Yilmaz, A. F., Redondo-Izal, A. -M., Altuntas, F., Heath, C., Kolditz, M., Schalk, E., Guolo, F., Karthaus, M., Della Pepa, R., Vinh, D., Noel, N., Deau Fischer, B., Drenou, B., Mitra, M. E., Meletiadis, J., Bilgin, Y. M., Jindra, P., Espigado, I., Drgona, L., Serris, A., Di Blasi, R., Ali, N., Pagano L. (ORCID:0000-0001-8287-928X), and Dragonetti G.

Abstract

Background: Patients with hematological malignancies (HM) are at high risk of mortality from SARS-CoV-2 disease 2019 (COVID-19). A better understanding of risk factors for adverse outcomes may improve clinical management in these patients. We therefore studied baseline characteristics of HM patients developing COVID-19 and analyzed predictors of mortality. Methods: The survey was supported by the Scientific Working Group Infection in Hematology of the European Hematology Association (EHA). Eligible for the analysis were adult patients with HM and laboratory-confirmed COVID-19 observed between March and December 2020. Results: The study sample includes 3801 cases, represented by lymphoproliferative (mainly non-Hodgkin lymphoma n = 1084, myeloma n = 684 and chronic lymphoid leukemia n = 474) and myeloproliferative malignancies (mainly acute myeloid leukemia n = 497 and myelodysplastic syndromes n = 279). Severe/critical COVID-19 was observed in 63.8% of patients (n = 2425). Overall, 2778 (73.1%) of the patients were hospitalized, 689 (18.1%) of whom were admitted to intensive care units (ICUs). Overall, 1185 patients (31.2%) died. The primary cause of death was COVID-19 in 688 patients (58.1%), HM in 173 patients (14.6%), and a combination of both COVID-19 and progressing HM in 155 patients (13.1%). Highest mortality was observed in acute myeloid leukemia (199/497, 40%) and myelodysplastic syndromes (118/279, 42.3%). The mortality rate significantly decreased between the first COVID-19 wave (March–May 2020) and the second wave (October–December 2020) (581/1427, 40.7% vs. 439/1773, 24.8%, p value < 0.0001). In the multivariable analysis, age, active malignancy, chronic cardiac disease, liver disease, renal impairment, smoking history, and ICU stay correlated with mortality. Acute myeloid leukemia was a higher mortality risk than lymphoproliferative diseases. Conclusions: This survey confirms that COVID-19 patients with HM are at high risk of lethal complications. Ho

Published
2021

12. Pharyngeal microbial signatures are predictive of the risk of fungal pneumonia in hematologic patients

Author

Costantini, C., Nunzi, E., Spolzino, A., Palmieri, M., Renga, G., Zelante, T., Englmaier, L., Coufalikova, K., Spacil, Z., Borghi, M., Bellet, M. M., Acerbi, E., Puccetti, M., Giovagnoli, S., Spaccapelo, R., Talesa, V. N., Lomurno, G., Merli, F., Facchini, L., Spadea, A., Melillo, L., Codeluppi, K., Marchesi, F., Marchesini, G., Valente, D., Dragonetti, G., Nadali, G., Pagano, L., Aversa, F., Romani, L., Dragonetti G., Pagano L. (ORCID:0000-0001-8287-928X), Costantini, C., Nunzi, E., Spolzino, A., Palmieri, M., Renga, G., Zelante, T., Englmaier, L., Coufalikova, K., Spacil, Z., Borghi, M., Bellet, M. M., Acerbi, E., Puccetti, M., Giovagnoli, S., Spaccapelo, R., Talesa, V. N., Lomurno, G., Merli, F., Facchini, L., Spadea, A., Melillo, L., Codeluppi, K., Marchesi, F., Marchesini, G., Valente, D., Dragonetti, G., Nadali, G., Pagano, L., Aversa, F., Romani, L., Dragonetti G., and Pagano L. (ORCID:0000-0001-8287-928X)

Abstract

The ability to predict invasive fungal infections (IFI) in patients with hematological malignancies is fundamental for successful therapy. Although gut dysbiosis is known to occur in hematological patients, whether airway dysbiosis also contributes to the risk of IFI has not been investigated. Nasal and oropharyngeal swabs were collected for functional microbiota characterization in 173 patients with hematological malignancies recruited in a multicenter, prospective, observational study and stratified according to the risk of developing IFI. A lower microbial richness and evenness were found in the pharyngeal microbiota of high-risk patients that were associated with a distinct taxonomic and metabolic profile. A murine model of IFI provided biologic plausibility for the finding that loss of protective anaerobes, such as Clostridiales and Bacteroidetes, along with an apparent restricted availability of tryptophan, is causally linked to the risk of IFI in hematologic patients and indicates avenues for antimicrobial stewardship and metabolic reequilibrium in IFI.

Published
2021

13. Infections in patients with lymphoproliferative diseases treated with targeted agents: SEIFEM multicentric retrospective study

Author

Marchesini, G., Nadali, G., Facchinelli, D., Candoni, A., Cattaneo, C., Laurenti, Luca, Fanci, R., Farina, F., Lessi, F., Visentin, A., Marchesi, F., Prezioso, L., Spolzino, A., Tisi, Maria Chiara, Trastulli, F., Picardi, Stefano Maria, Verga, L., Dargenio, M., Busca, A., Pagano, Livio, Laurenti L. (ORCID:0000-0002-8327-1396), Tisi M. C., Picardi M., Pagano L. (ORCID:0000-0001-8287-928X), Marchesini, G., Nadali, G., Facchinelli, D., Candoni, A., Cattaneo, C., Laurenti, Luca, Fanci, R., Farina, F., Lessi, F., Visentin, A., Marchesi, F., Prezioso, L., Spolzino, A., Tisi, Maria Chiara, Trastulli, F., Picardi, Stefano Maria, Verga, L., Dargenio, M., Busca, A., Pagano, Livio, Laurenti L. (ORCID:0000-0002-8327-1396), Tisi M. C., Picardi M., and Pagano L. (ORCID:0000-0001-8287-928X)

Abstract

We describe the opportunistic infections occurring in 362 patients with lymphoproliferative disorders treated with ibrutinib and idelalisib in clinical practice. Overall, 108 of 362 patients (29·8%) developed infections, for a total of 152 events. Clinically defined infections (CDI) were 49·3% (75/152) and microbiologically defined infections (MDI) were 50·7% (77/152). Among 250 patients treated with ibrutinib, 28·8% (72/250) experienced one or more infections, for a total of 104 episodes. MDI were 49% (51/104). Bacterial infections were 66·7% (34/51), viral 19·6% (10/51) and invasive fungal diseases (IFD) 13·7% (7/51). Among the 112 patients treated with idelalisib, 32·1% (36/112) experienced one or more infections, for a total of 48 episodes. MDI were 54·2% (26/48). Bacterial infections were 34·6% (9/26), viral 61·5% (16/26) and IFD 3·8% (1/26). With ibrutinib, the rate of bacterial infections was significantly higher compared to idelalisib (66·7% vs. 34·6%; P = 0·007), while viral infections were most frequent in idelalisib (61·5% vs. 19·6%; P < 0·001). Although a higher rate of IFD was observed in patients treated with ibrutinib, the difference was not statistically significant (13·7% vs. 3·8% respectively; P = 0·18). Bacteria are the most frequent infections with ibrutinib, while viruses are most frequently involved with idelalisib.

Published
2021

14. Considerations on antimicrobial prophylaxis in patients with lymphoproliferative diseases: A SEIFEM group position paper

Author

Busca, A., Cattaneo, C., De Carolis, Elena, Nadali, G., Offidani, M., Picardi, M., Candoni, A., Ceresoli, E., Criscuolo, Marianna, Delia, M., Della Pepa, R., Del Principe, I., Fanci, R. R., Farina, F., Fracchiolla, N., Giordano, C., Malagola, M., Marchesi, F., Piedimonte, M., Prezioso, L., Quinto, A. M., Spolzino, A., Tisi, M. C., Trastulli, F., Trecarichi, E. M., Zappasodi, P., Tumbarello, Mario, Pagano, Livio, De Carolis E. (ORCID:0000-0003-4757-7256), Criscuolo M., Tumbarello M. (ORCID:0000-0002-9519-8552), Pagano L. (ORCID:0000-0001-8287-928X), Busca, A., Cattaneo, C., De Carolis, Elena, Nadali, G., Offidani, M., Picardi, M., Candoni, A., Ceresoli, E., Criscuolo, Marianna, Delia, M., Della Pepa, R., Del Principe, I., Fanci, R. R., Farina, F., Fracchiolla, N., Giordano, C., Malagola, M., Marchesi, F., Piedimonte, M., Prezioso, L., Quinto, A. M., Spolzino, A., Tisi, M. C., Trastulli, F., Trecarichi, E. M., Zappasodi, P., Tumbarello, Mario, Pagano, Livio, De Carolis E. (ORCID:0000-0003-4757-7256), Criscuolo M., Tumbarello M. (ORCID:0000-0002-9519-8552), and Pagano L. (ORCID:0000-0001-8287-928X)

Abstract

The therapeutic armamentarium for the treatment of patients with lymphoproliferative diseases has grown considerably over the most recent years, including a large use of new immunotherapeutic agents. As a consequence, the epidemiology of infectious complications in this group of patients is poorly documented, and even more importantly, the potential benefit of antimicrobial prophylaxis remains a matter of debate when considering the harmful effect from the emergence of multidrug resistant pathogens. The present position paper is addressed to all hematologists treating patients affected by lymphoproliferative malignancies with the aim to provide clinicians with a useful tool for the prevention of bacterial, fungal and viral infections.

Published
2021

15. Do high MICs predict the outcome in invasive fusariosis?

Author

Nucci, M., Jenks, J., Thompson, G. R., Hoenigl, M., Dos Santos, M. C., Forghieri, F., Rico, J. C., Bonuomo, V., Lopez-Soria, L., Lass-Florl, C., Candoni, A., Garcia-Vidal, C., Cattaneo, C., Buil, J., Rabagliati, R., Roiz, M. P., Gudiol, C., Fracchiolla, N., Campos-Herrero, M. I., Delia, M., Farina, F., Fortun, J., Nadali, G., Sastre, E., Colombo, A. L., Perez Nadales, E., Alastruey-Izquierdo, A., Pagano, Livio, Pagano L. (ORCID:0000-0001-8287-928X), Nucci, M., Jenks, J., Thompson, G. R., Hoenigl, M., Dos Santos, M. C., Forghieri, F., Rico, J. C., Bonuomo, V., Lopez-Soria, L., Lass-Florl, C., Candoni, A., Garcia-Vidal, C., Cattaneo, C., Buil, J., Rabagliati, R., Roiz, M. P., Gudiol, C., Fracchiolla, N., Campos-Herrero, M. I., Delia, M., Farina, F., Fortun, J., Nadali, G., Sastre, E., Colombo, A. L., Perez Nadales, E., Alastruey-Izquierdo, A., Pagano, Livio, and Pagano L. (ORCID:0000-0001-8287-928X)

Abstract

BACKGROUND: Invasive fusariosis (IF) affects mostly severely immunocompromised hosts and is associated with poor outcome. Since Fusarium species exhibit high MICs for most antifungal agents, this could explain the poor prognosis. However, a clear-cut correlation between MIC and outcome has not been established. OBJECTIVE: To evaluate the correlation between MIC and outcome (6 week death rate) in patients with IF. METHODS: We performed a multicentre retrospective study of patients with IF who received treatment and had MIC levels determined by EUCAST or CLSI for the drug(s) used during treatment. We compared the MIC50 and MIC distribution among survivors and patients who died within 6 weeks from the diagnosis of IF. RESULTS: Among 88 patients with IF, 74 had haematological diseases. Primary treatment was monotherapy in 52 patients (voriconazole in 27) and combination therapy in 36 patients (liposomal amphotericin B + voriconazole in 23). The MIC50 and range for the five most frequent agents tested were: voriconazole 8 mg/L (range 0.5-64), amphotericin B 2 mg/L (range 0.25-64), posaconazole 16 mg/L (range 0.5-64), itraconazole 32 mg/L (range 4-64), and isavuconazole 32 mg/L (range 8-64). There was no difference in MIC50 and MIC distribution among survivors and patients who died. By contrast, persistent neutropenia and receipt of corticosteroids were strong predictors of 6 week mortality. CONCLUSIONS: Our study did not show any correlation between MIC and mortality at 6 weeks in patients with IF.

Published
2021

16. 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

17. Candidaemia in haematological malignancy patients from a SEIFEM study: Epidemiological patterns according to antifungal prophylaxis

Author

Posteraro, Brunella, De Carolis, Elena, Criscuolo, Marianna, Ballanti, S., De Angelis, Giulia, Del Principe, M. I., Delia, M., Fracchiolla, N., Marchesi, F., Nadali, G., Picardi, Stefano Maria, Piccioni, A. L., Verga, L., Candoni, A., Busca, A., Sanguinetti, Maurizio, Pagano, Livio, Muggeo, P., Stanzani, M., Cattaneo, C., Russo, D., Vacca, A., Fanci, R., De Paolis, M. R., Mancini, V., Lessi, F., Rossetti, E., Decembrino, N., Facchini, L., Dragonetti, Giulia, Ferrari, A., Vallero, S., Posteraro B. (ORCID:0000-0002-1663-7546), De Carolis E. (ORCID:0000-0003-4757-7256), Criscuolo M., De Angelis G. (ORCID:0000-0002-7087-7399), Picardi M., Sanguinetti M. (ORCID:0000-0002-9780-7059), Pagano L. (ORCID:0000-0001-8287-928X), Dragonetti G., Posteraro, Brunella, De Carolis, Elena, Criscuolo, Marianna, Ballanti, S., De Angelis, Giulia, Del Principe, M. I., Delia, M., Fracchiolla, N., Marchesi, F., Nadali, G., Picardi, Stefano Maria, Piccioni, A. L., Verga, L., Candoni, A., Busca, A., Sanguinetti, Maurizio, Pagano, Livio, Muggeo, P., Stanzani, M., Cattaneo, C., Russo, D., Vacca, A., Fanci, R., De Paolis, M. R., Mancini, V., Lessi, F., Rossetti, E., Decembrino, N., Facchini, L., Dragonetti, Giulia, Ferrari, A., Vallero, S., Posteraro B. (ORCID:0000-0002-1663-7546), De Carolis E. (ORCID:0000-0003-4757-7256), Criscuolo M., De Angelis G. (ORCID:0000-0002-7087-7399), Picardi M., Sanguinetti M. (ORCID:0000-0002-9780-7059), Pagano L. (ORCID:0000-0001-8287-928X), and Dragonetti G.

Abstract

Background: Candidaemia is an important infectious complication for haematological malignancy patients. Antifungal prophylaxis reduces the incidence of candidaemia but may be associated with breakthrough candidaemia. Objective: To analyse the Candida species’ distribution and relative antifungal susceptibility profiles of candidaemia episodes in relation to the use of antifungal prophylaxis among Italian SEIFEM haematology centres. Methodology: This multicentre retrospective observational SEIFEM study included 133 single-species candidaemia episodes of haematological malignancy patients for whom antifungal susceptibility testing results of blood Candida isolates were available between 2011 and 2015. Each participating centre provided both clinical and microbiological data. Results: Non-Candida albicans Candida (NCAC) species were the mostly isolated species (89, 66.9%), which accounted for C parapsilosis (35, 26.3%), C glabrata (16, 12.0%), C krusei (14, 10.5%), C tropicalis (13, 9.8%) and uncommon species (11, 8.3%). C albicans caused the remaining 44 (33.1%) episodes. Excluding 2 C albicans isolates, 23 of 25 fluconazole-resistant isolates were NCAC species (14 C krusei, 6 C glabrata, 2 C parapsilosis and 1 C tropicalis). Fifty-six (42.1%) of 133 patients developed breakthrough candidaemia. Systemic antifungal prophylaxis consisted of azoles, especially fluconazole and posaconazole, in 50 (89.3%) of 56 patients in whom a breakthrough candidaemia occurred. Interestingly, all these patients tended to develop a C krusei infection (10/56, P =.02) or a fluconazole-resistant isolate’s infection (14/50, P =.04) compared to patients (4/77 and 10/77, respectively) who did not have a breakthrough candidaemia. Conclusions: Optimisation of prophylactic strategies is necessary to limit the occurrence of breakthrough candidaemia and, importantly, the emergence of fluconazole-resistant NCAC isolates’ infections in

Published
2020

18. Central nervous system fungal infections in allogeneic stem cell transplantation. Outcome of 24 recent cases and literature review

Author

Candoni, A., Facchin, G., Busca, A., Lazzarotto, D., Cattaneo, C., Nadali, G., Klimko, N., Del Principe, M. I., Castagnola, C., Verga, L., Zannier, M. E., Calore, E., Capelli, D., Perruccio, K., Melillo, L., Fanin, R., Pagano, Livio, Pagano L. (ORCID:0000-0001-8287-928X), Candoni, A., Facchin, G., Busca, A., Lazzarotto, D., Cattaneo, C., Nadali, G., Klimko, N., Del Principe, M. I., Castagnola, C., Verga, L., Zannier, M. E., Calore, E., Capelli, D., Perruccio, K., Melillo, L., Fanin, R., Pagano, Livio, and Pagano L. (ORCID:0000-0001-8287-928X)

Abstract

nd

Published
2020

19. Evaluation on ‘real life’ prescriptions of antifungal prophylaxis in acute myeloid leukemia: Final results from a prospective survey: C12-3

Author

Caira, M., Busca, A., Candoni, A., Melillo, L., Blasi, R. Di, Cuccaro, A., Caramatti, C., Specchia, G., Fanci, R., Rossi, G., Vacca, A., Quintavalle, C., Picardi, M., Mitra, M. E., Delia, M., Landini, B., Aversa, F., Gasbarrino, C., Invernizzi, R., Salutari, P., Martino, B., Garzia, M. G., Chierichini, A., Caprio, L. Di, Vianelli, N., Nadali, G., Luppi, M., Nosari, A., and Pagano, L.

Published
2012

22. '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 MI, Dragonetti, G, Verga, L, Candoni, A, Marchesi, F, Cattaneo, C, Delia, M, Potenza, L, Farina, F, Ballanti, S, Decembrino, N, Castagnola, C, Nadali, G, Fanci, R, Orciulo, E, Veggia, B, Offidani, M, Melillo, L, Manetta, S, Tumbarello, M, Venditti, A, Busca, A, Aversa, F, and Pagano, L

Subjects
antifungal prophylaxis , consolidation therapy. AML
Published
2019

27. Bloodstream infections caused by Escherichia coli in onco-haematological patients: Risk factors and mortality in an Italian prospective survey

Author

Trecarichi, Enrico Maria, Giuliano, Gabriele, Cattaneo, C., Ballanti, S., Criscuolo, Marianna, Candoni, A., Marchesi, F., Laurino, M., Dargenio, M., Fanci, R., Cefalo, M., Delia, M., Spolzino, A., Maracci, L., Nadali, G., Busca, A., Del Principe, M. I., Daffini, R., Simonetti, E., Dragonetti, G., Zannier, M. E., Pagano, Livio, Tumbarello, Mario, Trecarichi E. M., Criscuolo M., Pagano L. (ORCID:0000-0001-8287-928X), Tumbarello M. (ORCID:0000-0002-9519-8552), Trecarichi, Enrico Maria, Giuliano, Gabriele, Cattaneo, C., Ballanti, S., Criscuolo, Marianna, Candoni, A., Marchesi, F., Laurino, M., Dargenio, M., Fanci, R., Cefalo, M., Delia, M., Spolzino, A., Maracci, L., Nadali, G., Busca, A., Del Principe, M. I., Daffini, R., Simonetti, E., Dragonetti, G., Zannier, M. E., Pagano, Livio, Tumbarello, Mario, Trecarichi E. M., Criscuolo M., Pagano L. (ORCID:0000-0001-8287-928X), and Tumbarello M. (ORCID:0000-0002-9519-8552)

Abstract

Bloodstream infections (BSIs) remain life-threatening complications in the clinical course of patients with haematological malignancies (HM) and Escherichia coli represent one of the most frequent cause of such infections. In this study, we aimed to describe risk factors for resistance to third generation cephalosporins and prognostic factors, including the impact of third generation cephalosporins resistance, in patients with HM and BSIs caused by E. coli. Three hundred forty-two cases of E. coli BSIs were collected during the study period (from January 2016 to December 2017). The percentage of resistance to third generation cephalosporins was 25.7%. In multivariate analysis, the variables recent endoscopic procedures, culture-positive surveillance rectal swabs for multidrug-resistant bacteria, antibiotic prophylaxis with fluoroquinolones, and prolonged neutropenia were independently associated with bloodstream infections caused by a third generation cephalosporins resistant E. coli. The overall 30-day mortality rate was 7.1%. Cox regression revealed that significant predictors of mortality were acute hepatic failure, septic shock, male sex, refractory/relapsed HM, and third generation cephalosporins resistance by E. coli isolate. In conclusion, resistance to third generation cephalosporins adversely affected the outcomes of bloodstream infections caused by E. coli in our cohort of HM patients. We also found a significant correlation between prophylaxis with fluoroquinolones and resistance to third generation cephalosporins by E. coli isolates.

Published
2019

28. 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

31. PS1267 ISAVUCONAZOLE IN HEMATOLOGICAL PATIENTS: FINAL RESULTS OF A REAL-LIFE MULTICENTER SEIFEM (SORVEGLIANZA EPIDEMIOLOGICA DELLE INFEZIONI NELLE EMOPATIE) STUDY

Author

Cattaneo, C., primary, Gramegna, D., additional, Busca, A., additional, Farina, F., additional, Candoni, A., additional, Piedimonte, M., additional, Fracchiolla, N.S., additional, Pagani, C., additional, Principe, M.I. Del, additional, Tisi, M.C., additional, Maracci, L., additional, Fanci, R., additional, Ballanti, S., additional, Spolzino, A., additional, Criscuolo, M., additional, Marchesi, F., additional, Nadali, G., additional, Delia, M., additional, Picardi, M., additional, Sciumé, M., additional, Tumbarello, M., additional, Rossi, G., additional, and Pagano, L., additional

Published
2019
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32. PS1276 EPIDEMIOLOGY AND CLINICAL OUTCOME OF FUNGAL INFECTIONS OF THE CENTRAL NERVOUS SYSTEM IN ALLOGENEIC STEM CELL TRANSPLANTATION RECIPIENTS

Author

Facchin, G., primary, Candoni, A., additional, Busca, A., additional, Lazzarotto, D., additional, Cattaneo, C., additional, Nadali, G., additional, Klimko, N., additional, Principe, M.I. Del, additional, Castagnola, C., additional, Verga, L., additional, Calore, E., additional, Capelli, D., additional, Perruccio, K., additional, Melillo, L., additional, and Pagano, L., additional

Published
2019
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35. Bloodstream infections in haematological cancer patients colonized by multidrug-resistant bacteria

Author

Cattaneo, C., Di Blasi, R., Skert, C., Candoni, A., Martino, B., Di Renzo, N., Delia, M., Ballanti, S., Marchesi, F., Mancini, V., Orciuolo, E., Cesaro, S., Prezioso, L., Fanci, R., Nadali, G., Chierichini, A., Facchini, L., Picardi, M., Malagola, M., Orlando, V., Trecarichi, E. M., Tumbarello, M., Aversa, F., Rossi, G., Pagano, L., Passi, Angela, Gramegna, Doriana, Russo, Domenico, Lazzarotto, Davide, Rotilio, Domenico, De Paolis, Maria Rosaria, Simonetti, Edoardo, Innocente, Maria Alessandra, Spadea, Antonio, Mazziotta, Francesco, Pegoraro, Anna, Spolzino, Angelica, Turri, Gloria, Veggia, Barbara, Tumbarello, M. (ORCID:0000-0002-9519-8552), Pagano, L. (ORCID:0000-0001-8287-928X), Cattaneo, C., Di Blasi, R., Skert, C., Candoni, A., Martino, B., Di Renzo, N., Delia, M., Ballanti, S., Marchesi, F., Mancini, V., Orciuolo, E., Cesaro, S., Prezioso, L., Fanci, R., Nadali, G., Chierichini, A., Facchini, L., Picardi, M., Malagola, M., Orlando, V., Trecarichi, E. M., Tumbarello, M., Aversa, F., Rossi, G., Pagano, L., Passi, Angela, Gramegna, Doriana, Russo, Domenico, Lazzarotto, Davide, Rotilio, Domenico, De Paolis, Maria Rosaria, Simonetti, Edoardo, Innocente, Maria Alessandra, Spadea, Antonio, Mazziotta, Francesco, Pegoraro, Anna, Spolzino, Angelica, Turri, Gloria, Veggia, Barbara, Tumbarello, M. (ORCID:0000-0002-9519-8552), and Pagano, L. (ORCID:0000-0001-8287-928X)

Abstract

Infections by multidrug-resistant (MDR) bacteria are a worrisome phenomenon in hematological patients. Data on the incidence of MDR colonization and related bloodstream infections (BSIs) in haematological patients are scarce. A multicentric prospective observational study was planned in 18 haematological institutions during a 6-month period. All patients showing MDR rectal colonization as well as occurrence of BSI at admission were recorded. One-hundred forty-four patients with MDR colonization were observed (6.5% of 2226 admissions). Extended spectrum beta-lactamase (ESBL)-producing (ESBL-P) enterobacteria were observed in 64/144 patients, carbapenem-resistant (CR) Gram-negative bacteria in 85/144 and vancomycin-resistant enterococci (VREs) in 9/144. Overall, 37 MDR-colonized patients (25.7%) developed at least one BSI; 23 of them (62.2%, 16% of the whole series) developed BSI by the same pathogen (MDRrel BSI), with a rate of 15.6% (10/64) for ESBL-P enterobacteria, 14.1% (12/85) for CR Gram-negative bacteria and 11.1% (1/9) for VRE. In 20/23 cases, MDRrel BSI occurred during neutropenia. After a median follow-up of 80 days, 18 patients died (12.5%). The 3-month overall survival was significantly lower for patients colonized with CR Gram-negative bacteria (83.6%) and VRE (77.8%) in comparison with those colonized with ESBL-P enterobacteria (96.8%). CR-rel BSI and the presence of a urinary catheter were independent predictors of mortality. MDR rectal colonization occurs in 6.5% of haematological inpatients and predicts a 16% probability of MDRrel BSI, particularly during neutropenia, as well as a higher probability of unfavourable outcomes in CR-rel BSIs. Tailored empiric antibiotic treatment should be decided on the basis of colonization.

Published
2018

36. 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

38. Pre-chemotherapy risk factors for invasive fungal diseases: prospective analysis of 1,192 patients with newly diagnosed acute myeloid leukemia (SEIFEM 2010-a multicenter study)

Author

Caira, M., Candoni, A., Verga, L., Busca, A., Delia, M., Nosari, A., Caramatti, C., Castagnola, C., Cattaneo, C., Fanci, R., Chierichini, A., Melillo, L., Mitra, M. E., Picardi, M., Potenza, L., Salutari, P., Vianelli, N., Facchini, L., Cesarini, M., De Paolis, M. R., Di Blasi, R., Farina, F., Venditti, A., Ferrari, A., Garzia, M., Gasbarrino, C., Invernizzi, R., Lessi, F., Manna, A., Martino, B., Nadali, G., Offidani, M., Paris, L., Pavone, V., Rossi, G., Spadea, A., Specchia, G., Trecarichi, E. M., Vacca, A., Cesaro, S., Perriello, V., Aversa, F., Tumbarello, M., Pagano, L., Ragionieri, R., Orsola Malpighi, O. S., Antoniazzi, F., Storti, S., Luppi, M., Pagliuca, S., Rossetti, E., Da Vià, M., Di Caprio, L., Majolino, I., Cascavilla, N., Turri, G., Fanin, Renato, Sorveglianza Epidemiologica Infezioni Fungine in Emopatie Maligne, Caira, Morena, Candoni, Anna, Verga, Luisa, Busca, Alessandro, Delia, Mario, Nosari, Annamaria, Caramatti, Cecilia, Castagnola, Carlo, Cattaneo, Chiara, Fanci, Rosa, Chierichini, Anna, Melillo, Lorella, Mitra, Maria Enza, Picardi, Marco, Potenza, Leonardo, Salutari, Prassede, Vianelli, Nicola, Facchini, Luca, Cesarini, Monica, De Paolis, Maria Rosaria, Di Blasi, Roberta, Farina, Francesca, Venditti, Adriano, Ferrari, Antonella, Garzia, Mariagrazia, Gasbarrino, Cristina, Invernizzi, Rosangela, Lessi, Federica, Manna, Annunziata, Martino, Bruno, Nadali, Gianpaolo, Offidani, Massimo, Paris, Laura, Pavone, Vincenzo, Rossi, Giuseppe, Spadea, Antonio, Specchia, Giorgina, Trecarichi, Enrico Maria, Vacca, Adriana, Cesaro, Simone, Perriello, Vincenzo, Aversa, Franco, Tumbarello, Mario, and Pagano, Livio

Subjects
Myeloid, Male, Antifungal Agents, invasive fungal diseases, Mycose, Risk Factors, Epidemiology, Antineoplastic Combined Chemotherapy Protocols, Antifungal Agent, Prospective Studies, Prospective cohort study, Univariate analysis, leukemia, Myeloid leukemia, Hematology, Environmental exposure, Articles, Middle Aged, Prognosis, Survival Rate, Leukemia, Leukemia, Myeloid, Acute, Female, Case-Control Studie, Human, Adult, medicine.medical_specialty, Prognosi, risk factors, acute myeloid leukemia, Neutropenia, Acute, Settore MED/17 - MALATTIE INFETTIVE, Aged, Case-Control Studies, Follow-Up Studies, Humans, Mycoses, Neoplasm Staging, Immunocompromised Host, Follow-Up Studie, Internal medicine, medicine, Antineoplastic Combined Chemotherapy Protocol, Performance status, business.industry, Risk Factor, medicine.disease, Surgery, Prospective Studie, Settore MED/15 - MALATTIE DEL SANGUE, Fungal Disease, business
Abstract

Correct definition of the level of risk of invasive fungal infections is the first step in improving the targeting of preventive strategies. We investigated the potential relationship between pre-hospitalization exposure to sources of fungi and the development of invasive fungal infections in adult patients with newly diagnosed acute myeloid leukemia after their first course of chemotherapy. From January 2010 to April 2012, all consecutive acute myeloid leukemia patients in 33 Italian centers were prospectively registered. Upon first admission, information about possible pre-chemotherapy risk factors and environmental exposure was collected. We recorded data regarding comorbid conditions, employment, hygienic habits, working and living environment, personal habits, hobbies, and pets. All invasive fungal infections occurring within 30 days after the first course of chemotherapy were recorded. Of the 1,192 patients enrolled in this study, 881 received intensive chemotherapy and were included in the present analysis. Of these, 214 developed an invasive fungal infection, including 77 proven/probable cases (8.7%). Of these 77 cases, 54 were proven/probable invasive mold infections (6.1%) and 23 were proven yeast infections (2.6%). Upon univariate analysis, a significant association was found between invasive mold infections and age, performance status, diabetes, chronic obstructive pulmonary disease, smoking, cocaine use, job, hobbies, and a recent house renovation. Higher body weight resulted in a reduced risk of invasive mold infections. Multivariate analysis confirmed the role of performance status, job, body weight, chronic obstructive pulmonary disease, and house renovation. In conclusion, several hospital-independent variables could potentially influence the onset of invasive mold infections in patients with acute myeloid leukemia. Investigation of these factors upon first admission may help to define a patient's risk category and improve targeted prophylactic strategies. (Clinicaltrial.gov: NCT01315925)

Published
2015

39. Molecular analysis of PDGFRA and PDGFRB genes by rapid single-strand conformation polymorphism (SSCP) in patients with core-binding factor leukaemias with KIT or FLT3 mutation

Author

Trojani, A, Ripamonti, C, Penco, S, Beghini, A, Nadali, G, Di Bona, E, Viola, A, Castagnola, C, Colapietro, P, Grillo, G, Pezzetti, L, Ravelli, E, Patrosso, M, Marocchi, A, Cuneo, A, Ferrara, F, Lazzarino, M, Pizzolo, G, Cairoli, R, Morra, E, Trojani A, Ripamonti CB, Penco S, Beghini A, Nadali G, Di Bona E, Viola A, Castagnola C, Colapietro P, Grillo G, Pezzetti L, Ravelli E, Patrosso MC, Marocchi A, Cuneo A, Ferrara F, Lazzarino M, Pizzolo G, Cairoli R, Morra E., Trojani, A, Ripamonti, C, Penco, S, Beghini, A, Nadali, G, Di Bona, E, Viola, A, Castagnola, C, Colapietro, P, Grillo, G, Pezzetti, L, Ravelli, E, Patrosso, M, Marocchi, A, Cuneo, A, Ferrara, F, Lazzarino, M, Pizzolo, G, Cairoli, R, Morra, E, Trojani A, Ripamonti CB, Penco S, Beghini A, Nadali G, Di Bona E, Viola A, Castagnola C, Colapietro P, Grillo G, Pezzetti L, Ravelli E, Patrosso MC, Marocchi A, Cuneo A, Ferrara F, Lazzarino M, Pizzolo G, Cairoli R, and Morra E.

Abstract

Background: Mutations involving KIT and FLT3 genes, encoding tyrosine kinase (TK) membrane receptors, are detected in core-binding factor leukaemia (CBFL) patients. PDFGRA and PDGFRB encode class III TK receptors and are involved both in physiological processes and in the pathogenesis of haematological and solid tumours. The aim of this study was to investigate if PDGFR mutations are involved in CBFL. Patients and Methods: In order to detect PDGFR mutations in CBFL, 35 patients without KIT or FLT3 mutations patients were screened by rapid and sensitive single-strand conformation polymorphism (SSCP) analysis. Sequence analysis was performed in polymerase chain reaction (PCR) products showing altered mobility in SSCP analysis in order to determine the nucleotide changes. Results: Three types of single-nucleotide polymorphism (SNP) were detected in the PDGFRA gene (exon 12, exon 13 and exon 18) while no mutation of PDGFRB was detected in the tested CBFLs. Conclusion: These data showed that no pathogenic mutations in PDGFRA and PDGFRB were detected in the context of CBFL without KIT and FLT3 mutations. Thus, PDGFR genes do not seem to be involved in CBFL and future studies are needed to establish the genetic causes of the disease in these particular patients.

Published
2008

40. Prognostic impact of c-KIT mutations in core binding factor leukemias: an Italian retrospective study

Author

Cairoli, R, Beghini, A, Grillo, G, Nadali, G, Elice, F, Ripamonti, C, Colapietro, P, Nichelatti, M, Pezzetti, L, Lunghi, M, Cuneo, A, Viola, A, Ferrara, F, Lazzarino, M, Rodeghiero, F, Pizzolo, G, Larizza, L, Morra, E, Cairoli R, Beghini A, Grillo G, Nadali G, Elice F, Ripamonti CB, Colapietro P, Nichelatti M, Pezzetti L, Lunghi M, Cuneo A, Viola A, Ferrara F, Lazzarino M, Rodeghiero F, Pizzolo G, Larizza L, Morra E, Cairoli, R, Beghini, A, Grillo, G, Nadali, G, Elice, F, Ripamonti, C, Colapietro, P, Nichelatti, M, Pezzetti, L, Lunghi, M, Cuneo, A, Viola, A, Ferrara, F, Lazzarino, M, Rodeghiero, F, Pizzolo, G, Larizza, L, Morra, E, Cairoli R, Beghini A, Grillo G, Nadali G, Elice F, Ripamonti CB, Colapietro P, Nichelatti M, Pezzetti L, Lunghi M, Cuneo A, Viola A, Ferrara F, Lazzarino M, Rodeghiero F, Pizzolo G, Larizza L, and Morra E

Abstract

Distinct forms of tyrosine kinase domain (TKD), juxtamembrane domain, exon 8, and internal tandem duplication (ITD) mutations of c-KIT, were observed in about 46% of core binding factor leukemia (CBFL) patients. To evaluate their prognostic significance, 67 adult patients with CBFL were analyzed to ascertain the c-KIT mutation status. In acute myeloid leukemia (AML) with t(8;21), the presence of c-KIT TKD mutation at codon 816 (TKD816) was associated with a high white blood cell count at diagnosis (median, 29.60 × 10 9/L) and a higher incidence (33%) of extramedullary leukemia (EML) during the course of the disease. Data also showed that the TKD816 mutated patients (n = 12) had a significantly higher incidence of relapse and a lower overall survival (OS) at 24 months, compared with the 17 c-KIT unmutated (c-KIT-) patients (90% vs 35.3%, P = .002; 25% vs 76.5%, P = .006, respectively). No difference in relapse incidence (P = .126) and OS (P = .474) was observed between the c-KIT mutated other than TKD816 (n = 7) and the c-KIT- patients. These findings indicate that c-KIT TKD 816 mutation has a negative impact on the outcome of AML with t(8;21).

Published
2006

41. Studio prospettico, multicentrico, osservazionale sugli eventi febbrili nelle leucemie linfoblastiche acute

Author

Di Blasi, R, Lewis, Re, Busca, A, Candoni, A, Caramatti, C, Cattaneo, C, Cesarini, M, Cesaro, Simone, Delia, M, Dragonetti, G, Fanci, R, Garzia, Mg, Giordano, A, Martino, B, Melillo, L, Nadali, G, Offidani, M, Perriello, V, Picardi, M, Quinro, Am, Salutari, P, Vacca, A, Vetro, C, Zancanella, M, and Pagano, L.

Subjects
neutropenia febbrile, neutropenia febbrile, terapia empirica, leucemia, terapia empirica, leucemia
Published
2014

42. Studio prospettico, multicentrico, osservazionale sugli eventi febbrili fungini nelle leucemie linfoblastiche acute

Author

Di Blasi, R., Lewis, R. E., Busca, A., Candoni, A., Caramatti, C., Cattaneo, C., Cesarini, M., Cesaro, Simone, Delia, M., Dragonetti, G., Fanci, R., Garzia, M. G., Giordano, A., Martino, B., Melillo, L., Nadali, G., Offidani, M., Perriello, V., Picardi, M., Quinto, A. M., Salutari, P., Vacca, A., Vetro, C., Zancanella, M., and Pagano, L.

Subjects
leucemia linfoblastica acuta, Febbre, Infezioni fungine
Published
2014

43. IMPACT OF KIT MUTATIONS IN ACUTE MYELOID LEUKAEMIA WITH INV(16)

Author

Cairoli, R, Beghini, A, Ripamonti, CB, Grillo, G, Nadali, G, Di Bona, E, Colapietro, P, Bertani, GB, Ravelli, E, Nador, G, Castagnola, C, Cattaneo, C, Ottaviani, E, Pioltelli, P, Viola, A, Cuneo, A, Ferrara, F, Martinelli, G, Lazzarino, M, Rossi, G, Pizzolo, G, Morra, E, Cairoli, R, Beghini, A, Ripamonti, C, Grillo, G, Nadali, G, Di Bona, E, Colapietro, P, Bertani, G, Ravelli, E, Nador, G, Castagnola, C, Cattaneo, C, Ottaviani, E, Pioltelli, P, Viola, A, Cuneo, A, Ferrara, F, Martinelli, G, Lazzarino, M, Rossi, G, Pizzolo, G, and Morra, E

Subjects
Hematology
Published
2008

44. Prevalence and prognostic impact of KIT mutations in acute myeloid leukaemia with INV(16)

Author

Cairoli, R, Beghini, A, Ripamonti, CB, Grillo, G, Nadali, G, Di Bona, E, Colapietro, P, Nichelatti, M, Ravelli, E, Nador, G, Cuneo, A, Castagnola, C, Viola, A, Ottaviani, E, Colarossi, S, Cattaneo, C, Parma, M, Pioltelli, P, Ferrara, F, Lazzarino, M, Rossi, G, Rodeghiero, F, Pizzolo, G, Martinelli, G, Morra, E, Cairoli, R, Beghini, A, Ripamonti, C, Grillo, G, Nadali, G, Di Bona, E, Colapietro, P, Nichelatti, M, Ravelli, E, Nador, G, Cuneo, A, Castagnola, C, Viola, A, Ottaviani, E, Colarossi, S, Cattaneo, C, Parma, M, Pioltelli, P, Ferrara, F, Lazzarino, M, Rossi, G, Rodeghiero, F, Pizzolo, G, Martinelli, G, and Morra, E

Subjects
Hematology
Published
2007

45. Pre-chemotherapy risk factors for invasive fungal diseases: prospective analysis of 1,192 patients with newly diagnosed acute myeloid leukemia (SEIFEM 2010-a multicenter study)

Author

CAIRA, MORENA, Candoni, A, Verga, L, Busca, A, Delia, M, Nosari, A, Caramatti, C, Castagnola, C, Cattaneo, C, Fanci, R, Chierichini, A, Melillo, L, Mitra, ME, Picardi, M, Potenza, L, Salutari, P, Vianelli, N, Facchini, L, Cesarini, M, De Paolis, MR, Di Blasi, R, Farina, F, Venditti, A, Ferrari, A, Garzia, M, Gasbarrino, C, Invernizzi, R, Lessi, F, Manna, A, Martino, B, Nadali, G, Offidani, M, Paris, L, Pavone, V, Rossi, G, Spadea, A, Specchia, G, Trecarichi, EM, Vacca, A, Cesaro, S, Perriello, V, Aversa, F, TUMBARELLO, MARIO, PAGANO, LIVIO, CAIRA, MORENA, Candoni, A, Verga, L, Busca, A, Delia, M, Nosari, A, Caramatti, C, Castagnola, C, Cattaneo, C, Fanci, R, Chierichini, A, Melillo, L, Mitra, ME, Picardi, M, Potenza, L, Salutari, P, Vianelli, N, Facchini, L, Cesarini, M, De Paolis, MR, Di Blasi, R, Farina, F, Venditti, A, Ferrari, A, Garzia, M, Gasbarrino, C, Invernizzi, R, Lessi, F, Manna, A, Martino, B, Nadali, G, Offidani, M, Paris, L, Pavone, V, Rossi, G, Spadea, A, Specchia, G, Trecarichi, EM, Vacca, A, Cesaro, S, Perriello, V, Aversa, F, TUMBARELLO, MARIO, and PAGANO, LIVIO

Published
2015

46. Risk of invasive fungal infection in patients affected by acute promyelocytic leukaemia. A report by the SEIFEM-D registry

Author

Pagano, Livio, Stamouli, M, Tumbarello, Mario, Verga, L, Candoni, A, Cattaneo, C, Nadali, G, Mitra, Me, Mancini, V, Nosari, A, Garzia, Mg, Delia, M, Storti, S, Spadea, A, Caramatti, C, Perriello, V, Sanna, M, Vacca, A, De Paolis, Mr, Potenza, L, Salutari, P, Castagnola, C, Fanci, R, Chierichini, A, Melillo, L, Picardi, M, Facchini, L, Martino, B, Di Blasi, R, Cesarini, M, Offidani, M, Vianelli, N, Caira, M, Lessi, F, Ferrari, A, Venditti, A, Pavone, V, Lo Coco, F, Aversa, F, Busca, A., Pagano, Livio (ORCID:0000-0001-8287-928X), Tumbarello, Mario (ORCID:0000-0002-9519-8552), Storti, S (ORCID:0000-0002-4374-3985), Pagano, Livio, Stamouli, M, Tumbarello, Mario, Verga, L, Candoni, A, Cattaneo, C, Nadali, G, Mitra, Me, Mancini, V, Nosari, A, Garzia, Mg, Delia, M, Storti, S, Spadea, A, Caramatti, C, Perriello, V, Sanna, M, Vacca, A, De Paolis, Mr, Potenza, L, Salutari, P, Castagnola, C, Fanci, R, Chierichini, A, Melillo, L, Picardi, M, Facchini, L, Martino, B, Di Blasi, R, Cesarini, M, Offidani, M, Vianelli, N, Caira, M, Lessi, F, Ferrari, A, Venditti, A, Pavone, V, Lo Coco, F, Aversa, F, Busca, A., Pagano, Livio (ORCID:0000-0001-8287-928X), Tumbarello, Mario (ORCID:0000-0002-9519-8552), and Storti, S (ORCID:0000-0002-4374-3985)

Published
2015

47. Pre-chemotherapy risk factors for invasive fungal diseases: prospective analysis of 1,192 patients with newly diagnosed acute myeloid leukemia (SEIFEM 2010-a multicenter study)

Author

Caira, M, Candoni, A, Verga, L, Busca, A, Delia, M, Nosari, A, Caramatti, C, Castagnola, C, Cattaneo, C, Fanci, R, Chierichini, A, Melillo, L, Mitra, Me, Picardi, M, Potenza, L, Salutari, P, Vianelli, N, Facchini, L, Cesarini, M, De Paolis, Mr, Di Blasi, R, Farina, F, Venditti, A, Ferrari, A, Garzia, M, Gasbarrino, C, Invernizzi, R, Lessi, F, Manna, A, Martino, B, Nadali, G, Offidani, M, Paris, L, Pavone, V, Rossi, G, Spadea, A, Specchia, G, Trecarichi, Em, Vacca, A, Cesaro, S, Perriello, V, Aversa, F, Tumbarello, Mario, Pagano, Livio, Tumbarello, M (ORCID:0000-0002-9519-8552), Pagano, Livio (ORCID:0000-0001-8287-928X), Caira, M, Candoni, A, Verga, L, Busca, A, Delia, M, Nosari, A, Caramatti, C, Castagnola, C, Cattaneo, C, Fanci, R, Chierichini, A, Melillo, L, Mitra, Me, Picardi, M, Potenza, L, Salutari, P, Vianelli, N, Facchini, L, Cesarini, M, De Paolis, Mr, Di Blasi, R, Farina, F, Venditti, A, Ferrari, A, Garzia, M, Gasbarrino, C, Invernizzi, R, Lessi, F, Manna, A, Martino, B, Nadali, G, Offidani, M, Paris, L, Pavone, V, Rossi, G, Spadea, A, Specchia, G, Trecarichi, Em, Vacca, A, Cesaro, S, Perriello, V, Aversa, F, Tumbarello, Mario, Pagano, Livio, Tumbarello, M (ORCID:0000-0002-9519-8552), and Pagano, Livio (ORCID:0000-0001-8287-928X)

Abstract

Correct definition of the level of risk of invasive fungal infections is the first step in improving the targeting of preventive strategies. We investigated the potential relationship between pre-hospitalization exposure to sources of fungi and the development of invasive fungal infections in adult patients with newly diagnosed acute myeloid leukemia after their first course of chemotherapy. From January 2010 to April 2012, all consecutive acute myeloid leukemia patients in 33 Italian centers were prospectively registered. Upon first admission, information about possible pre-chemotherapy risk factors and environmental exposure was collected. We recorded data regarding comorbid conditions, employment, hygienic habits, working and living environment, personal habits, hobbies, and pets. All invasive fungal infections occurring within 30 days after the first course of chemotherapy were recorded. Of the 1,192 patients enrolled in this study, 881 received intensive chemotherapy and were included in the present analysis. Of these, 214 developed an invasive fungal infection, including 77 proven/probable cases (8.7%). Of these 77 cases, 54 were proven/probable invasive mold infections (6.1%) and 23 were proven yeast infections (2.6%). Upon univariate analysis, a significant association was found between invasive mold infections and age, performance status, diabetes, chronic obstructive pulmonary disease, smoking, cocaine use, job, hobbies, and a recent house renovation. Higher body weight resulted in a reduced risk of invasive mold infections. Multivariate analysis confirmed the role of performance status, job, body weight, chronic obstructive pulmonary disease, and house renovation. In conclusion, several hospital-independent variables could potentially influence the onset of invasive mold infections in patients with acute myeloid leukemia. Investigation of these factors upon first admission may help to define a patient's risk category and improve targeted prophylactic stra

Published
2015

48. KIT activating mutations: Incidence in adult and pediatric acute myeloid leukemia, and identification of an internal tandem duplication

Author

Beghini A, Cb, Ripamonti, Cairoli R, Giovanni Cazzaniga, Colapietro P, Elice F, Nadali G, Grillo G, Oa, Haas, Biondi A, Morra E, Larizza L, Beghini, A, Ripamonti, C, Cairoli, R, Cazzaniga, G, Colapietro, P, Elice, F, Nadali, G, Grillo, G, Haas, O, Biondi, A, Morra, E, and Larizza, L

Subjects
Adult, 21), Core Binding Factors, DNA Mutational Analysis, KIT mutation, Polymerase Chain Reaction, Childhood AML, Gene Expression Regulation, Neoplastic, Leukemia, Myeloid, Acute, Proto-Oncogene Proteins c-kit, Gene Duplication, Core binding factor leukemia, Trisomy 4, Humans, Inv(16), Child, T(8
Abstract

Background and Objectives. Mutations of KIT receptor tyrosine kinase are involved in the constitutive activation and development of human hematologic malignancies. Gain-of-function mutations in the second intracellular kinase domain (TK2) and in the juxtamembrane domain are described in patients with core binding factor acute myeloid leukemia (CBFL) and are associated with leukocytosis. We evaluated the incidence of KIT mutation in 52 adult patients with de novo CBFL and in 49 FLT3/ITD-negative childhood patients with de novo acute myeloid leukemia (AML), excluding cases of acute promyelocytic leukemia. Design and Methods. In order to analyze the role of KIT in CBFL we examined the KIT mutations in 52 adult CBFL, including 15 previously reported patients, and in 49 non-APL childhood AML patients using sensitive detection methods. We correlated our findings with the presence of trisomy 4 and investigated the relationship of the extra chromosome 4 with KIT mutations. Results. Several kinds of gain-of-function KIT mutations were found in 24 of the 52 (46.1%) adult CBFL cases and 6 of the 49 (12.2%) non-APL childhood AML patients. KIT mutations were detected in 4 of the 8 adult patients and one childhood AML case bearing trisomy of chromosome 4 as either the sole cytogenetic aberration or a karyotypic aberration additional to t(8;21). In three of the trisomy 4 cases we demonstrated that trisomy 4 leads to duplication of the KIT mutated allele. Interpretation and Conclusions. These results underline that the KIT gene is activated in AML characterized by distinct cytogenetic and molecular genetic patterns and represents the most frequently mutated target in adult CBFL.

Published
2004

49. Linfomi maligni

Author

Ambrosetti, Achille and Nadali, G.

Subjects
non-Hodgkin's lymphoma, Hodgkin's lymphoma, lymphoma
Published
2011

50. Leucemie

Author

Ambrosetti, Achille, Meneghini, V, and Nadali, G.

Subjects
chronic myeloid leukemia, Acute non-lymphoblastic leukaemia, lymphocytic leukemia, acute lymphoblastic leukemia
Published
2011

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