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1. Incidence, Risk Factors and Outcome of Pre-engraftment Gram-Negative Bacteremia After Allogeneic and Autologous Hematopoietic Stem Cell Transplantation: An Italian Prospective Multicenter Survey

Author

Girmenia, Corrado, Bertaina, Alice, Piciocchi, Alfonso, Perruccio, Katia, Algarotti, Alessandra, Busca, Alessandro, Cattaneo, Chiara, Raiola, Anna Maria, Guidi, Stefano, Iori, Anna Paola, Candoni, Anna, Irrera, Giuseppe, Milone, Giuseppe, Marcacci, Giampaolo, Scimè, Rosanna, Musso, Maurizio, Cudillo, Laura, Sica, Simona, Castagna, Luca, Corradini, Paolo, Marchesi, Francesco, Pastore, Domenico, Alessandrino, Emilio Paolo, Annaloro, Claudio, Ciceri, Fabio, Santarone, Stella, Nassi, Luca, Farina, Claudio, Viscoli, Claudio, Rossolini, Gian Maria, Bonifazi, Francesca, Rambaldi, Alessandro, Capria, Saveria, Bertaina, A., Mastronuzzi, Angela, Pagliara, Daria, Bernaschi, Paola, Amico, Lucia, Carotti, Alessandra, Mencacci, Antonella, Busca, A., Bruno, Benedetto, Costa, Cristina, Passi, Angela, Ravizzola, Giuseppe, Angelucci, Emanuele, Marchese, Anna, Pecile, Patrizia, Candoni, A., Ventura, Giovanna, Fanin, Renato, Scarparo, Claudio, Barbaro, Angelo, Milone, G., Leotta, Salvatore, Marchese, Anna Elisa, Marcacci, G., Becchimanzi, Cristina, Donnarumma, Daniela, Tringali, Stefania, Baldi, Maria Teresa, Scalone, Renato, Cudillo, L., Picardi, Alessandra, Arcese, William, Fontana, Carla, Sica, S., Giammarco, Sabrina, Spanu, Teresa, Castagna, L., Crocchiolo, Roberto, Casari, Erminia, Mussetti, Alberto, Conte, Eutilia, Ensoli, Fabrizio, Miragliotta, Giuseppe, Marone, Piero, Arghittu, Milena, Greco, Raffaella, Forcina, Alessandra, Chichero, Paola, Santarone, S., Di Bartolomeo, Paolo, Fazii, Paolo, Kroumova, Vesselina, Decembrino, Nunzia, Zecca, Marco, Pisapia, Giovanni, Palazzo, Giulia, Lanino, Edoardo, Faraci, Maura, Castagnola, Elio, Bandettini, Roberto, Pastano, Rocco, Sammassimo, Simona, Passerini, Rita, Stefani, Piero Maria, Gherlinzoni, Filippo, Rigoli, Roberto, Prezioso, Lucia, Cambò, Benedetta, Calderaro, Adriana, Carella, Angelo Michele, Cascavilla, Nicola, Labonia, Maria Teresa, Celeghini, Ivana, Mordini, Nicola, Piana, Federica, Vacca, Adriana, Sanna, Marco, Podda, Giovanni, Corsetti, Maria Teresa, Rocchetti, Andrea, Cilloni, Daniela, De Gobbi, Marco, Bianco, Ornella, Fagioli, Franca, Carraro, Francesca, De Intinis, Gianfranco, Severino, Alessandro, Proia, Anna, Parisi, Gabriella, Vallisa, Daniele, Confalonieri, Massimo, Russo, Domenico, Malagola, Michele, Galieni, Piero, Falcioni, Sadia, Travaglini, Valeria, Raimondi, Roberto, Borghero, Carlo, Pavan, Giacomina, Prete, Arcangelo, Belotti, Tamara, Ambretti, Simone, Imola, Manuela, Mianulli, Anna Maria, Pedna, Maria Federica, Cesaro, Simone, Lo Cascio, Giuliana, Ferrari, Antonella, Piedimonte, Monica, Santino, Iolanda, Calandrelli, Monica, Olivieri, Attilio, Orecchioni, Francesca, Mirabile, Milena, Centurioni, Riccardo, Gironacci, Luciana, Caravelli, Daniela, Gallo, Susanna, De Filippi, Marco, Cupelli, Luca, Dentamaro, Teresa, Falco, Silvana, Eugenio, Ospedale S, Marotta, Serena, Risitano, Antonio, Lula, Dora, Musto, Pellegrino, Pietrantuono, Giuseppe, Traficante, Antonio, Cerchiara, Elisabetta, Tirindelli, Maria Cristina, Dicuonzo, Giordano, Chierichini, Anna, Anaclerico, Barbara, Placanica, Paola, Girmenia, C, Bertaina, A, Piciocchi, A, Perruccio, K, Algarotti, A, Busca, A, Cattaneo, C, Raiola, Am, Guidi, S, Iori, Ap, Candoni, A, Irrera, G, Milone, G, Marcacci, G, Scimè, R, Musso, M, Cudillo, L, Sica, S, Castagna, L, Corradini, P, Marchesi, F, Pastore, D, Alessandrino, Ep, Annaloro, C, Ciceri, F, Santarone, S, Nassi, L, Farina, C, Viscoli, C, Rossolini, Gm, Bonifazi, F, Rambaldi, A, for the Gruppo Italiano Trapianto di Midollo Osseo, (GITMO), Associazione Microbiologi Clinici Italiani, (AMCLI), Girmenia, Corrado, Bertaina, Alice, Piciocchi, Alfonso, Perruccio, Katia, Algarotti, Alessandra, Busca, Alessandro, Cattaneo, Chiara, Raiola, Anna Maria, Guidi, Stefano, Iori, Anna Paola, Candoni, Anna, Irrera, Giuseppe, Milone, G., Marcacci, Giampaolo, Scimè, Rosanna, Musso, Maurizio, Cudillo, Laura, Sica, Simona, Castagna, Luca, Corradini, Paolo, Marchesi, Francesco, Pastore, Domenico, Alessandrino, Emilio Paolo, Annaloro, Claudio, Ciceri, Fabio, Santarone, Stella, Nassi, Luca, Farina, Claudio, Viscoli, Claudio, Rossolini, Gian Maria, Bonifazi, Francesca, Rambaldi, Alessandro, Capria, Saveria, Bertaina, A., Mastronuzzi, Angela, Pagliara, Daria, Bernaschi, Paola, Amico, Lucia, Carotti, Alessandra, Mencacci, Antonella, Busca, A., Bruno, Benedetto, Costa, Cristina, Passi, Angela, Ravizzola, Giuseppe, Angelucci, Emanuele, Marchese, Anna, Pecile, Patrizia, Candoni, A., Ventura, Giovanna, Fanin, Renato, Scarparo, Claudio, Barbaro, Angelo, Leotta, Salvatore, Marchese, Anna Elisa, Marcacci, G., Becchimanzi, Cristina, Donnarumma, Daniela, Tringali, Stefania, Baldi, Maria Teresa, Scalone, Renato, Cudillo, L., Picardi, Alessandra, Arcese, William, Fontana, Carla, Sica, S., Giammarco, Sabrina, Spanu, Teresa, Castagna, L., Crocchiolo, Roberto, Casari, Erminia, Mussetti, Alberto, Conte, Eutilia, Ensoli, Fabrizio, Miragliotta, Giuseppe, Marone, Piero, Arghittu, Milena, Greco, Raffaella, Forcina, Alessandra, Chichero, Paola, Santarone, S., Di Bartolomeo, Paolo, Fazii, Paolo, Kroumova, Vesselina, Decembrino, Nunzia, Zecca, Marco, Pisapia, Giovanni, Palazzo, Giulia, Lanino, Edoardo, Faraci, Maura, Castagnola, Elio, Bandettini, Roberto, Pastano, Rocco, Sammassimo, Simona, Passerini, Rita, Stefani, Piero Maria, Gherlinzoni, Filippo, Rigoli, Roberto, Prezioso, Lucia, Cambò, Benedetta, Calderaro, Adriana, Carella, Angelo Michele, Cascavilla, Nicola, Labonia, Maria Teresa, Celeghini, Ivana, Mordini, Nicola, Piana, Federica, Vacca, Adriana, Sanna, Marco, Podda, Giovanni, Corsetti, Maria Teresa, Rocchetti, Andrea, Cilloni, Daniela, De Gobbi, Marco, Bianco, Ornella, Fagioli, Franca, Carraro, Francesca, De Intinis, Gianfranco, Severino, Alessandro, Proia, Anna, Parisi, Gabriella, Vallisa, Daniele, Confalonieri, Massimo, Russo, Domenico, Malagola, Michele, Galieni, Piero, Falcioni, Sadia, Travaglini, Valeria, Raimondi, Roberto, Borghero, Carlo, Pavan, Giacomina, Prete, Arcangelo, Belotti, Tamara, Ambretti, Simone, Imola, Manuela, Mianulli, Anna Maria, Pedna, Maria Federica, Cesaro, Simone, Lo Cascio, Giuliana, Ferrari, Antonella, Piedimonte, Monica, Santino, Iolanda, Calandrelli, Monica, Olivieri, Attilio, Orecchioni, Francesca, Mirabile, Milena, Centurioni, Riccardo, Gironacci, Luciana, Caravelli, Daniela, Gallo, Susanna, De Filippi, Marco, Cupelli, Luca, Dentamaro, Teresa, Falco, Silvana, Eugenio, Ospedale S, Marotta, Serena, Risitano, Antonio, Lula, Dora, Musto, Pellegrino, Pietrantuono, Giuseppe, Traficante, Antonio, Cerchiara, Elisabetta, Tirindelli, Maria Cristina, Dicuonzo, Giordano, Chierichini, Anna, Anaclerico, Barbara, and Placanica, Paola

Subjects
0301 basic medicine, Male, Transplantation Conditioning, Drug Resistance, Bacteremia, 0302 clinical medicine, epidemiology, Gram negative bacteremia, multidrug resistance, stem cell transplant, survival, Risk Factors, Drug Resistance, Multiple, Bacterial, Epidemiology, Medicine, Age Factor, Prospective Studies, Prospective cohort study, Child, Transplantation, Homologou, education.field_of_study, Incidence (epidemiology), Incidence, Bacterial, Age Factors, Hematopoietic Stem Cell Transplantation, Middle Aged, Transplantation, Autologou, surgical procedures, operative, Infectious Diseases, Italy, Child, Preschool, Female, medicine.symptom, Multiple, Autologous, Human, Homologous, Microbiology (medical), Adult, medicine.medical_specialty, Adolescent, 030106 microbiology, Population, Transplantation, Autologous, 03 medical and health sciences, Young Adult, Internal medicine, Gram-Negative Bacteria, Gram-Negative Bacterial Infection, Escherichia coli, Humans, Transplantation, Homologous, Preschool, education, Aged, Gram-Negative Bacterial Infections, Infant, Transplantation, business.industry, Risk Factor, medicine.disease, Prospective Studie, Carriage, Otitis, business, Settore MED/15 - Malattie del Sangue, 030215 immunology
Abstract

Background Gram-negative bacteremia (GNB) is a major cause of illness and death after hematopoietic stem cell transplantation (HSCT), and updated epidemiological investigation is advisable. Methods We prospectively evaluated the epidemiology of pre-engraftment GNB in 1118 allogeneic HSCTs (allo-HSCTs) and 1625 autologous HSCTs (auto-HSCTs) among 54 transplant centers during 2014 (SIGNB-GITMO-AMCLI study). Using logistic regression methods. we identified risk factors for GNB and evaluated the impact of GNB on the 4-month overall-survival after transplant. Results The cumulative incidence of pre-engraftment GNB was 17.3% in allo-HSCT and 9% in auto-HSCT. Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa were the most common isolates. By multivariate analysis, variables associated with GNB were a diagnosis of acute leukemia, a transplant from a HLA-mismatched donor and from cord blood, older age, and duration of severe neutropenia in allo-HSCT, and a diagnosis of lymphoma, older age, and no antibacterial prophylaxis in auto-HSCT. A pretransplant infection by a resistant pathogen was significantly associated with an increased risk of posttransplant infection by the same microorganism in allo-HSCT. Colonization by resistant gram-negative bacteria was significantly associated with an increased rate of infection by the same pathogen in both transplant procedures. GNB was independently associated with increased mortality at 4 months both in allo-HSCT (hazard ratio, 2.13; 95% confidence interval, 1.45–3.13; P Conclusions Pre-engraftment GNB is an independent factor associated with increased mortality rate at 4 months after auto-HSCT and allo-HSCT. Previous infectious history and colonization monitoring represent major indicators of GNB. Clinical Trials registration NCT02088840.

Published
2017

2. Unrelated cord blood transplantation for adult patients with acute myeloid leukemia: higher incidence of acute graft-versus-host disease and lower survival in male patients transplanted with female unrelated cord blood--a report from Eurocord, the Acute Leukemia Working Party, and the Cord Blood Committee of the Cellular Therapy and Immunobiology Working Party of the European Group for Blood and Marrow Transplantation

Author

Baron, Frédéric, Labopin, Myriam, Ruggeri, Annalisa, Mohty, Mohamad, Sanz, Guillermo, Milpied, Noel, Bacigalupo, Andrea, Rambaldi, Alessandro, Bonifazi, Francesca, Bosi, Alberto, Sierra, Jorge, Yakoub-Agha, Ibrahim, Ribera, Jose-Maria, Gluckman, Eliane, Nagler, Arnon, Universitat Autònoma de Barcelona, Service d'Hématologie, Université de Liège-CHU Sart-Tilman, Centre International des greffes [CHU Saint-Antoine] (EBMT), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Eurocord, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7), Servicio de Hematologia, Hospital Universitari i Politècnic La Fe, Service d'Hématologie et Thérapie Cellulaire, CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Department of Haematology II, Ospedale San Martino, Hematology and Bone Marrow Transplant Unit, Azienda Ospedaliera Papa Giovanni XXIII, Institute of Hematology and Medical, Oncology L and A Seràgnoli, Policlinico S. Orsola - Malpighi, Bone Marrow Transplant Unit (BMT), Azienda Ospedaliera Careggi, Hematology Department, Hospital de la Santa Creu i Sant Pau, Unités d'Activité Médicale [Lille] (UAM), Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Jose Carreras Research Institute, Hospital Universitari Germans Trias i Pujol, France Monacord, Centre Scientifique de Monaco (CSM), Division of Hematology and Bone Marrow Transplantation, The Chaim Sheba Medical Center at Tel hashomer, Hospital Universitari i Politècnic La Fe = University and Polytechnic Hospital La Fe, BMC, BMC, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut Universitaire d'Hématologie (IUH), and Hôpital Claude Huriez-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)

Subjects
Male, Cancer Research, [SDV]Life Sciences [q-bio], GVHD, Graft vs Host Disease, Blood Donors, 0302 clinical medicine, AML, Risk Factors, hemic and lymphatic diseases, Medicine, 0303 health sciences, Acute leukemia, Hematology, Incidence, Hazard ratio, Middle Aged, 3. Good health, Europe, Survival Rate, [SDV] Life Sciences [q-bio], Leukemia, surgical procedures, operative, Oncology, Leukemia, Myeloid, 030220 oncology & carcinogenesis, Cord blood, Acute Disease, Female, Cord Blood Stem Cell Transplantation, Adult, medicine.medical_specialty, Adolescent, 03 medical and health sciences, Young Adult, Sex Factors, Unrelated cord blood, Sang fetal, Internal medicine, Humans, Survival rate, Molecular Biology, 030304 developmental biology, Aged, Retrospective Studies, Transplantation, business.industry, Research, medicine.disease, Survival Analysis, Surgery, Multivariate Analysis, business
Abstract

Background In the setting of allogeneic human leukocyte antigen (HLA)-matched bone marrow transplantation, transplanting male patients with grafts from female donors has been associated with a higher incidence of graft-versus-host disease (GVHD) and of nonrelapse mortality (NRM). The aim of the current analysis was to compare transplantation outcomes in male patients given female unrelated cord blood (UCB) versus other gender combinations. Patients and methods Data from 552 consecutive patients with acute myeloid leukemia (AML) given a single UCB transplantation between 2000 and 2014 were included. Results In comparison with other gender combination, male patients given female UCB (n = 131) had a trend for a higher incidence of grades II–IV acute GVHD (33 versus 25 %, P = 0.08), a trend for a higher incidence of NRM (41 versus 33 %, P = 0.06), and a lower leukemia-free (LFS, 30 versus 41 %, P = 0.01) and overall survival (OS, 33 versus 45 %, P = 0.008). In multivariate analyses, taking into consideration all patients for which data on HLA-matching and cell dose transplanted were fully available (n = 363), male patients transplanted with a female UCB had a trend for a higher incidence of grade III–IV acute GVHD (hazard ratio (HR) = 2.0, P = 0.06), a trend for a higher NRM (HR = 1.5, P = 0.06), and a worse LFS (HR = 1.4, P = 0.04) and OS (HR = 1.3, P = 0.06). Conclusions Our data suggest that male patients transplanted with female UCB might have higher risk of acute GVHD and of NRM leading to worse LFS and OS. These results should be confirmed in other large cohorts of patients before used for determining the choice of an UCB unit. Electronic supplementary material The online version of this article (doi:10.1186/s13045-015-0207-4) contains supplementary material, which is available to authorized users.

Published
2015

3. Additional file 1: of Unrelated cord blood transplantation for adult patients with acute myeloid leukemia: higher incidence of acute graft-versus-host disease and lower survival in male patients transplanted with female unrelated cord bloodâ a report from Eurocord, the Acute Leukemia Working Party, and the Cord Blood Committee of the Cellular Therapy and Immunobiology Working Party of the European Group for Blood and Marrow Transplantation

Author

FrĂŠdĂŠric Baron, Labopin, Myriam, Ruggeri, Annalisa, Mohty, Mohamad, Sanz, Guillermo, Milpied, Noel, Bacigalupo, Andrea, Rambaldi, Alessandro, Bonifazi, Francesca, Bosi, Alberto, Sierra, Jorge, Yakoub-Agha, Ibrahim, Santasusana, Josep, Gluckman, Eliane, and Nagler, Arnon

Abstract

List of institutions reporting data in this study.

Published
2015
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4. Reduced Relapse and Improved Survival in Chemosensitive Hodgkin Lymphoma Patients Undergoing Haploidentical Related Donor Compared to HLA-Identical Donor Transplantation

Author

Castagna, Luca, Bramanti, Stefania, Busca, Alessandro, Malagola, Michele, Ciceri, Fabio, Arcese, William, Vallisa, Daniele, Patriarca, Francesca, Specchia, Giorgina, Raimondi, Roberto, Devillier, Raynier, Furst, Sabine, Giordano, Laura, Sarina, Barbara, Morabito, Lucio, Jacopo Mariotti, Granata, Angela, Bouabdallah, Reda, Carlo-Stella, Carmelo, Rambaldi, Alessandro, Santoro, Armando, Bacigalupo, Andrea, Corradini, Paolo, Bonifazi, Francesca, and Blaise, Didier

5. Allogeneic Hematopoietic Stem Cell Transplantation Provides Cure for Adult Patients with Hemophagocytic Lymphohistiocytosis (HLH): A Retrospective Study of The Chronic Malignancies and Inborn ErrorsWorking Parties (CMWP and IEWP) of The EBMT

Author

Machowcz, Rafal, Suarez, Felipe, Wiktor-Jedrzejczak, Wieslaw, Eikema, Diderik-Jan, Wreede, Liesbeth, Blok, Henric-Jan, Isaksson, Cecilia, Poire, Xavier, Nikolousis, Manos, Kobbe, Guido, Einsele, Herman, Arnold, Renate, Bonifazi, Francesca, Mcquacker, Grant, Lenhoff, Stig, Rohrlich, Pierre-Simon, Theobald, Matthias, Ljungman, Per, Schaap, Nicolaas, Collin, Matthew, Albert, Michael, Finke, Juergen, Ehninger, Gerhard, Carlson, Kristina, Kazimierz Halaburda, Johansson, Jan-Erik, Zecca, Marco, Diez-Martin, J., Lehmberg, Kai, Schoenland, Stefan, Lankester, Arjan, Gennery, Andrew, and Kroger, Nicolaus

6. TREATMENT OF STEROID RESISTANT ACUTE GRAFT VERSUS HOST DISEASE WITH AN ANTI-CD26 MONOCLONAL ANTIBODY- BEGELOMAB

Author

Metafuni, Elisabetta, Gualandi, Francesca, Raiola, Anna Maria, Riccardo Varaldo, Di Grazia, Carmen, Angelucci, Emanuele, Benedetti, Edoardo, Locatelli, Franco, Risitano, Antonio, Musso, Maurizio, Zallio, Francesco, Ciceri, Fabio, Chiusolo, Patrizia, Rambaldi, Alessandro, Bonifazi, Francesca, Parma, Matteo, Martino, Massimo, Onida, Francesco, Iori, Anna Paola, Selleri, Carmine, Borghero, Carlo, Bertaina, Alice, Lint, Maria Teresa, and Bacigalupo, Andrea

7. Outcomes of Cord Blood Transplantation for Adult Patients with Hodgkin Lymphoma, a Eurocord and EBMT Lymphoma Working Party Study

Author

Paviglianiti, Annalisa, Tozatto-Maio, Karina, Rocha, Vanderson, Gehlkopf, Eve, Milpied, Noel, Esquirol, Albert, Chevallier, Patrice, Didier Blaise, Damaj, Gandhi, Nguyen-Quoc, Stephanie, Cahn, Jean Yves, Abecasis, Manuel, Zuckerman, Tsila, Schouten, Harry C., Gurman, Gunhan, Rubio, Marie Therese, Beguin, Yves, Corral, Lucia Lopez, Nagler, Arnon, Snowden, John A., Yener, Koc, Mordini, Nicola, Bonifazi, Francesca, Fanin, Renato, Volt, Fernanda, Kenzey, Chantal, Robinson, Stephen, Montoto, Silvia, Gluckman, Eliane, and Ruggeri, Annalisa

8. Outcome of allogeneic-HSCT in adult patients with PH-positive-all in the era of TKI: A retrospective analysis of the Italian blood and marrow transplantation society (GITMO)

Author

Candoni, Anna, Fanin, Renato, Rambaldi, Alessandro, Velardi, Andrea, Arcese, William, Ciceri, Fabio, Lazzarotto, Davide, Lussana, Federico, Jacopo Olivieri, Grillo, Giovanni, Parma, Matteo, Bruno, Benedetto, Sora, Federica, Bernasconi, Paolo, Saccardi, Riccardo, Foa, Roberto, Sessa, Mariarosa, Bresciani, Paola, Giglio, Fabio, Cerretti, Raffaella, Busca, Alessandro, Sica, Simona, Diral, Elisa, Colombo, Anna Amelia, Tringali, Stefano, Santarone, Stella, Irrera, Giuseppe, Mancini, Stefano, Zallio, Francesco, Malagola, Michele, Albano, Francesco, Carella, Angelo Michele, Olivieri, Attilio, Tecchio, Cristina, Dominietto, Alida, Vacca, Adriana, Sorasio, Roberto, Orciuolo, Enrico, Risitano, Antonio Maria, Cortelezzi, Agostino, Mammoliti, Sonia, Oldani, Elena, and Bonifazi, Francesca

9. Case report: Senescence as mechanism of resistance to Pembrolizumab in a Lymphoma patient who failed CD19-Targeted CAR-T cell therapy

Author

Serena De Matteis, Beatrice Casadei, Ginevra Lolli, Michele Dicataldo, Francesco Barbato, Elisa Dan, Andrea Paccagnella, Barbara Sinigaglia, Clara Bertuzzi, Annalisa Arcari, Luca Zazzeroni, Patrizia Bernuzzi, Noemi Laprovitera, Gianluca Storci, Salvatore Nicola Bertuccio, Manuela Ferracin, Massimiliano Bonafè, Pier Luigi Zinzani, Francesca Bonifazi, De Matteis, Serena, Casadei, Beatrice, Lolli, Ginevra, Dicataldo, Michele, Barbato, Francesco, Dan, Elisa, Paccagnella, Andrea, Sinigaglia, Barbara, Bertuzzi, Clara, Arcari, Annalisa, Zazzeroni, Luca, Bernuzzi, Patrizia, Laprovitera, Noemi, Storci, Gianluca, Bertuccio, Salvatore Nicola, Ferracin, Manuela, Bonafe, Massimiliano, Zinzani, Pier Luigi, and Bonifazi, Francesca

Subjects
senescence, Receptors, Chimeric Antigen, Antigens, CD19, Immunology, Receptors, Antigen, T-Cell, Cell- and Tissue-Based Therapy, lymphoma, CD8-Positive T-Lymphocyte, chimeric antigen receptor (CAR T), Immunotherapy, Adoptive, resistance, exhaustion, Immunology and Allergy, pembrolizumab, Lymphoma, Large B-Cell, Diffuse, Human
Abstract

BackgroundT cells engineered to target CD19 antigen on neoplastic B cells represent the most striking example of CAR-T cell therapy. The success rate of this therapy is affected by several limitations: target antigen loss, and/or acquisition of a senescent/exhausted phenotype by CAR and non-CAR T cells.Case presentationWe report on a patient affected by refractory Diffuse Large B-cell Lymphoma who was resistant to CAR T-cell therapy and to two cycles post CAR-T of pembrolizumab (PBZ) due to the evolution into a B-cell Hodgkin-like lymphoma. Owing to the CD30 expression and the Hodgkin-like phenotype, the patient was ultimately treated with Brentuximab-Vedotin and finally underwent remission. Upon PBZ treatment, 100% of circulating CAR-T+ cells showed a persistent CD8+ senescent/exhausted phenotype, while an increase in the percentage of senescent cells was found in the non-CAR CD8+ T cells compartment.ConclusionsPBZ is not able to reinvigorate exhausted CAR+ T cells and to confer durable clinical response. We hypothesize that the phenomenon is due to the senescent phenotype of CAR+ T cells, which did not allow PBZ-induced reactivation and proliferative rescue. The phenomenon, together with the loss of CAR-T target CD19 and the shift of non-CAR CD8+ T cells towards a senescent phenotype likely contributed to set up an immune landscape with poor antitumor capacity.

Published
2022

10. Classification and Personalized Prognostic Assessment on the Basis of Clinical and Genomic Features in Myelodysplastic Syndromes

Author

Andrea Bacigalupo, Pierre Fenaux, Alberto Termanini, Marianna Rossi, Lucio Morabito, Niccolo Bolli, Massimo Bernardi, Victor Savevski, Manja Meggendorfer, Daniel Remondini, Tommaso Matteuzzi, Torsten Haferlach, Luciano Milanesi, Matteo G. Della Porta, Ettore Mosca, Gastone Castellani, Valeria Santini, Alessandro Rambaldi, Giulia Maggioni, Guillermo Sanz, Claudia Sala, Wolfgang Kern, Marta Ubezio, Matteo Zampini, Emanuele Angelucci, Armando Santoro, Laura Palomo, Noemi Di Nanni, Lorenza Borin, Erica Travaglino, Alessia Campagna, Maria Teresa Voso, Francesc Solé, Francesca Bonifazi, Shahram Kordasti, Uwe Platzbecker, Matteo Bersanelli, Matteo Gnocchi, Esther Oliva, Marta Riva, Benedetto Bruno, Fabio Ciceri, Francesco Passamonti, Claudia Saitta, Enrico Giampieri, Chiara Chiereghin, Bersanelli, Matteo, Travaglino, Erica, Meggendorfer, Manja, Matteuzzi, Tommaso, Sala, Claudia, Mosca, Ettore, Chiereghin, Chiara, Di Nanni, Noemi, Gnocchi, Matteo, Zampini, Matteo, Rossi, Marianna, Maggioni, Giulia, Termanini, Alberto, Angelucci, Emanuele, Bernardi, Massimo, Borin, Lorenza, Bruno, Benedetto, Bonifazi, Francesca, Santini, Valeria, Bacigalupo, Andrea, Voso, Maria Teresa, Oliva, Esther, Riva, Marta, Ubezio, Marta, Morabito, Lucio, Campagna, Alessia, Saitta, Claudia, Savevski, Victor, Giampieri, Enrico, Remondini, Daniel, Passamonti, Francesco, Ciceri, Fabio, Bolli, Niccolò, Rambaldi, Alessandro, Kern, Wolfgang, Kordasti, Shahram, Sole, Francesc, Palomo, Laura, Sanz, Guillermo, Santoro, Armando, Platzbecker, Uwe, Fenaux, Pierre, Milanesi, Luciano, Haferlach, Torsten, Castellani, Gastone, and Della Porta, Matteo G

Subjects
Male, Cancer Research, SCORING SYSTEM, MODELS, disease classification, MEDLINE, ACUTE MYELOID-LEUKEMIA, Computational biology, 03 medical and health sciences, 0302 clinical medicine, Text mining, hemic and lymphatic diseases, MDS, medicine, CRITERIA, Humans, NGS, somatic mutations, myelodysplastic syndromes, prognosis, 030304 developmental biology, Retrospective Studies, 0303 health sciences, GENETIC LESIONS, business.industry, Myelodysplastic syndromes, Disease classification, Retrospective cohort study, SOMATIC MUTATIONS, Genomics, MDS, Artificial Intekkìlligence, machine learning, Settore MED/15, medicine.disease, Prognosis, 3. Good health, Oncology, 030220 oncology & carcinogenesis, Myelodysplastic Syndromes, Female, prognostication, business
Abstract

PURPOSE Recurrently mutated genes and chromosomal abnormalities have been identified in myelodysplastic syndromes (MDS). We aim to integrate these genomic features into disease classification and prognostication. METHODS We retrospectively enrolled 2,043 patients. Using Bayesian networks and Dirichlet processes, we combined mutations in 47 genes with cytogenetic abnormalities to identify genetic associations and subgroups. Random-effects Cox proportional hazards multistate modeling was used for developing prognostic models. An independent validation on 318 cases was performed. RESULTS We identify eight MDS groups (clusters) according to specific genomic features. In five groups, dominant genomic features include splicing gene mutations ( SF3B1, SRSF2, and U2AF1) that occur early in disease history, determine specific phenotypes, and drive disease evolution. These groups display different prognosis (groups with SF3B1 mutations being associated with better survival). Specific co-mutation patterns account for clinical heterogeneity within SF3B1- and SRSF2-related MDS. MDS with complex karyotype and/or TP53 gene abnormalities and MDS with acute leukemia–like mutations show poorest prognosis. MDS with 5q deletion are clustered into two distinct groups according to the number of mutated genes and/or presence of TP53 mutations. By integrating 63 clinical and genomic variables, we define a novel prognostic model that generates personally tailored predictions of survival. The predicted and observed outcomes correlate well in internal cross-validation and in an independent external cohort. This model substantially improves predictive accuracy of currently available prognostic tools. We have created a Web portal that allows outcome predictions to be generated for user-defined constellations of genomic and clinical features. CONCLUSION Genomic landscape in MDS reveals distinct subgroups associated with specific clinical features and discrete patterns of evolution, providing a proof of concept for next-generation disease classification and prognosis.

Published
2021

11. Steroid treatment of acute graft- versus -host disease grade I: a randomized trial

Author

Franca Fagioli, Anna Maria Raiola, Patrizia Chiusolo, Carmine Selleri, Antonio M. Risitano, Stella Santarone, Giuseppe Milone, Maria Pia Sormani, Andrea Bacigalupo, Alessandra Cupri, Maria Teresa Van Lint, Sonia Mammoliti, Simona Sica, Roberto Sorasio, Massimo Berger, Antonio Severino, Alessio Signori, Francesca Gualandi, Francesca Bonifazi, Daniela Massi, Bacigalupo, Andrea, Milone, Giuseppe, Cupri, Alessandra, Severino, Antonio, Fagioli, Franca, Berger, Massimo, Santarone, Stella, Chiusolo, Patrizia, Sica, Simona, Mammoliti, Sonia, Sorasio, Roberto, Massi, Daniela, Van Lint, Maria Teresa, Raiola, Anna Maria, Gualandi, Francesca, Selleri, Carmine, Sormani, Maria Pia, Signori, Alessio, Risitano, Antonio, and Bonifazi, Francesca

Subjects
medicine.medical_treatment, Graft vs Host Disease, Hematopoietic stem cell transplantation, Gastroenterology, law.invention, 0302 clinical medicine, Randomized controlled trial, immune system diseases, law, Clinical endpoint, Cumulative incidence, Young adult, Child, Acute Disease, Adolescent, Adult, Aged, Child, Preschool, Disease Progression, Hematopoietic Stem Cell Transplantation, Humans, Infant, Infant, Newborn, Methylprednisolone, Middle Aged, Prognosis, Steroids, Survival Analysis, Young Adult, Hematology, surgical procedures, operative, 030220 oncology & carcinogenesis, Survival Analysi, Human, medicine.drug, medicine.medical_specialty, Randomization, Prognosi, Article, 03 medical and health sciences, Cell Therapy & Immunotherapy, Internal medicine, medicine, Preschool, Steroid, Survival analysis, business.industry, Newborn, Surgery, Settore MED/15 - MALATTIE DEL SANGUE, business, 030215 immunology
Abstract

Patients with acute graft-versus-host disease (GvHD) grade I were randomized to an observation arm (n=85) or to a treatment arm (n=86) consisting of 6-methylprednisolone 1 mg/kg/day, after stratification for age and donor type. The primary end point was development of grade II–IV GvHD. The cumulative incidence of grade II–IV GvHD was 50% in the observation arm and 33% in the treatment arm (P=0.005). However, grade III–IV GvHD was comparable (13% vs. 10%, respectively; P=0.6), and this was true for sibling and alternative donor transplants. Moderate/severe chronic GvHD was also comparable (17% vs. 9%). In multivariate analysis, an early interval between transplant and randomization (

Published
2017

12. Intrabone transplant provides full stemness of cord blood stem cells with fast hematopoietic recovery and low GVHD rate: results from a prospective study

Author

Francesca Bonifazi, Valeria Giudice, Maria Rosa Motta, Gianluca Storci, Mariarosaria Sessa, Viviana Guadagnuolo, Martina Ferioli, Simonetta Rizzi, Elisa Dan, Michele Cavo, Barbara Sinigaglia, Massimiliano Bonafè, Sabrina De Carolis, Giovanni Martinelli, Andrea Bontadini, Myriam Labopin, Mario Arpinati, Alma Mater Studiorum Universita' di Bologna, DIPARTIMENTO DI MEDICINA SPECIALISTICA, DIAGNOSTICA E SPERIMENTALE, DIPARTIMENTO DI SCIENZE MEDICHE E CHIRURGICHE, Facolta' di MEDICINA e CHIRURGIA, Bonifazi, Francesca, Dan, Elisa, Labopin, Myriam, Sessa, Mariarosaria, Guadagnuolo, Viviana, Ferioli, Martina, Rizzi, Simonetta, De Carolis, Sabrina, Sinigaglia, Barbara, Motta, Maria Rosa, Bontadini, Andrea, Giudice, Valeria, Martinelli, Giovanni, Arpinati, Mario, Cavo, Michele, Bonafé, Massimiliano, and Storci, Gianluca

Subjects
Oncology, Adult, Male, medicine.medical_specialty, Adolescent, Graft vs Host Disease, Cell Count, Diseases, Cord Blood Stem Cell Transplantation, Human leukocyte antigen, Umbilical cord, CXCR4, Article, 03 medical and health sciences, 0302 clinical medicine, Medical research, Internal medicine, medicine, Humans, Cumulative incidence, hematopoietic malignancies, Prospective Studies, Transplantation, Umbilical Cord Blood, business.industry, Stem Cells, Hematology, Recovery of Function, Middle Aged, Hematopoiesis, Haematopoiesis, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Cord blood, Hematologic Neoplasms, Umbilical Cord Blood, hematopoietic malignancies, Female, Stem cell, business, 030215 immunology
Abstract

open 17 no We thank Rita Bertoni and Antonella Orlando for the technical assistance. This work has been supported by Bologna AIL (Italian Association against Leukemia, Lymphoma and Myeloma), Roberto and Cornelia Pallotti Legacy for Cancer Research (University of Bologna) to M.B., and REUSE with Love ONLUS, Bologna, Italy. Umbilical Cord Blood (UCB) represents a valid option for patients with hematopoietic malignancies lacking an HLA matched donor. To overcome the limitation of the low stem cell dose of UCB, the intrabone (IB) route has been proposed. We report the results of a prospective study on a poor-prognosis cohort of 23 patients receiving intrabone single UCB transplant (Clinicaltrials.gov NCT00886522). Cumulative incidence of hematological recovery at day 90 was 82 ± 9% (ANC > 0.5 × 109/L) and 70 ± 10% (platelet > 50 × 109/L) and correlated with CD34 + cells in the graft. NRM was 20 ± 9%. No severe aGVHD and only one extensive cGVHD occurred, with fast immune reconstitution. To test the hypothesis that the direct IB injection could affect the expression of stem cells regulatory pathways, CD34 + cells from BM aspirates at day + 10, + 20, + 30, processed in hypoxic conditions mimicking the BM-microenvironment (7%pO2), were studied for the expression of c-Mpl, Notch1 and CXCR4. We found that the expression of c-Mpl in CD34 + cells at day + 10 significantly correlated with hematological recovery. In conclusion, IB-UCB transplant success is associated with low incidence of GVHD and high-speed platelet recovery; intrabone route may preserve full hematopoietic stemness by direct delivery of UCB stem cells into the hypoxic HSC niche. none none Bonifazi, Francesca; Dan, Elisa; Labopin, Myriam; Sessa, Mariarosaria; Guadagnuolo, Viviana; Ferioli, Martina; Rizzi, Simonetta; De Carolis, Sabrina; Sinigaglia, Barbara; Motta, Maria Rosa; Bontadini, Andrea; Giudice, Valeria; Martinelli, Giovanni; Arpinati, Mario; Cavo, Michele; Bonafé, Massimiliano; Storci, Gianluca Bonifazi, Francesca; Dan, Elisa; Labopin, Myriam; Sessa, Mariarosaria; Guadagnuolo, Viviana; Ferioli, Martina; Rizzi, Simonetta; De Carolis, Sabrina; Sinigaglia, Barbara; Motta, Maria Rosa; Bontadini, Andrea; Giudice, Valeria; Martinelli, Giovanni; Arpinati, Mario; Cavo, Michele; Bonafé, Massimiliano; Storci, Gianluca

Published
2018

13. New drugs and allogeneic hematopoietic stem cell transplantation for hematological malignancies: do they have a role in bridging, consolidating or conditioning transplantation treatment?

Author

Fabio Ciceri, Paolo Corradini, Renato Fanin, Renato Bassan, Stefano Volpetti, Antonio M. Risitano, Elena Maino, Benedetto Bruno, Nicola Mordini, Francesco Onida, Francesca Bonifazi, Raffaella Greco, Francesca Patriarca, Barbara Sarina, Luca Castagna, Jacopo Peccatori, Vittorio Montefusco, Michele Baccarani, Luisa Giaccone, Francesco Zaja, Alberto Mussetti, Moreno Festuccia, Alessandro Rambaldi, Patriarca, Francesca, Giaccone, Luisa, Onida, Francesco, Castagna, Luca, Sarina, Barbara, Montefusco, Vittorio, Mussetti, Alberto, Mordini, Nicola, Maino, Elena, Greco, Raffaella, Peccatori, Jacopo, Festuccia, Moreno, Zaja, Francesco, Volpetti, Stefano, Risitano, Antonio, Bassan, Renato, Corradini, Paolo, Ciceri, Fabio, Fanin, Renato, Baccarani, Michele, Rambaldi, Alessandro, Bonifazi, Francesca, Bruno, Benedetto, and Risitano, ANTONIO MARIA

Subjects
Oncology, medicine.medical_specialty, medicine.drug_class, medicine.medical_treatment, Clinical Biochemistry, Pharmaceutical Science, Salvage therapy, Allogeneic stem cell transplantation, graft-versus-tumor, monoclonal antibodies, new drugs, targeted therapy, Pharmacology, Drug Discovery3003 Pharmaceutical Science, Graft vs Host Disease, Antineoplastic Agents, Disease, Hematopoietic stem cell transplantation, Monoclonal antibody, Targeted therapy, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Drug Discovery, medicine, Humans, Transplantation, Homologous, Single agent, monoclonal antibodie, Protein Kinase Inhibitors, Salvage Therapy, new drug, business.industry, Hematopoietic Stem Cell Transplantation, Antibodies, Monoclonal, Transplantation, surgical procedures, operative, 030220 oncology & carcinogenesis, Hematologic Neoplasms, Immunology, Stem cell, business, 030215 immunology
Abstract

Introduction: Novel targeted therapies and monoclonal antibodies can be combined with allogeneic stem cell transplantation (allo-SCT) at different time-points: 1) before the transplant to reduce tumour burden, 2) as part of the conditioning in place of or in addition to conventional agents 3) after the transplant to allow long-term disease control. Areas covered: This review focuses on the current integration of new drugs with allo-SCT for the treatment of major hematological malignancies for which allo-SCT has been a widely-adopted therapy. Expert opinion: After having been used as single agent salvage treatments in relapsed patients after allo-SCT or in combination with donor lymphocyte infusions, many new drugs have also been safely employed before allo-SCT as a bridge to transplantation or after it as planned consolidation/maintenance. This era of new drugs has opened new important opportunities to ‘smartly’ combine ‘targeted drugs and cell therapies’ in new treatment paradigms that may lead to higher cure rates or longer disease control in patients with hematological malignancies.

Published
2017

14. Dry Eye Disease Is Already Present in Hematological Patients Before Hematopoietic Stem Cell Transplantation

Author

Giuseppe Giannaccare, Giuseppe Bandini, Mario Arpinati, Francesca Bonifazi, Piera Versura, Mariarosaria Sessa, Michela Fresina, Giannaccare, Giuseppe, Bonifazi, Francesca, Sessa, Mariarosaria, Fresina, Michela, Arpinati, Mario, Bandini, Giuseppe, and Versura, Piera

Subjects
0301 basic medicine, chronic lymphoproliferative disorder, medicine.medical_treatment, Dry Eye Syndromes, Hematopoietic stem cell transplantation, Fluorophotometry, dry eye, 0302 clinical medicine, Retrospective Studie, Surveys and Questionnaires, Prevalence, Medicine, Surveys and Questionnaire, Ocular Surface Disease Index, Prospective Studies, Prospective cohort study, Transplantation, Homologou, Hematopoietic Stem Cell Transplantation, Middle Aged, early diagnosi, Lymphoproliferative Disorder, Human, Adult, medicine.medical_specialty, Adolescent, Malignancy, 03 medical and health sciences, Young Adult, stem cell malignancie, Internal medicine, Humans, Transplantation, Homologous, Aged, Retrospective Studies, business.industry, Retrospective cohort study, Odds ratio, medicine.disease, eye diseases, Lymphoproliferative Disorders, Transplantation, Prospective Studie, Ophthalmology, 030104 developmental biology, Immunology, Chronic Disease, 030221 ophthalmology & optometry, hematological stem cell transplantation, business, Dry Eye Syndrome
Abstract

Purpose To analyze ocular surface parameters in patients before hematopoietic stem cell transplantation (HSCT) and to correlate them with hematological characteristics. Methods This is a retrospective analysis of prospectively collected data from 203 patients undergoing HSCT. Demographic data and hematological parameters (disorder type and stage) were collected from clinical charts. Ocular surface parameters (ocular surface disease index; Schirmer test I; tear film break-up time; corneal esthesiometry; and corneal and conjunctival staining) were analyzed the day before beginning the conditioning treatment for HSCT preparation. Results A high prevalence of dry eye (DE) was found: 116 patients (57.2%) were diagnosed as not suffering from DE, whereas 87 patients (42.8%) were diagnosed as having DE. Of these, 26 were classified as dry eye workshot (DEWS) severity score 1, 46 as DEWS score 2, and 15 as DEWS score 3. Tear film break-up time was found to be the only parameter statistically worse in the chronic lymphoproliferative disorder group compared with the stem cell malignancy group. Older age [odds ratio (OR) 1.03], female sex (OR 2.03), advanced stage of hematological disease (OR 1.4), and previous auto- or allo-HSCT (OR 1.9) showed a significant positive association in predicting DE onset before transplantation. Conclusions DE was already present in a significant number of patients suffering from hematological disease before HSCT. Some hematological parameters seemed to influence this percentage. These results highlight the role of ocular surface examination by an ophthalmologist in hematological patients before HSCT, with the aim of diagnosing and, if necessary, treating DE patients early.

Published
2016

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