61 results on '"Anna Maria Barbui"'
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2. FIRST REPORT OF THE REAL‐LIFE PROSPECTIVE OBSERVATIONAL STUDY 'CAR‐T CELL IN DIFFUSE LARGE B‐CELL AND PRIMARY MEDIASTINAL LYMPHOMAS' OF THE ITALIAN SOCIETY OF HEMATOLOGY
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Anna Guidetti, Maria Chiara Tisi, Rosalba Miceli, Matteo Carrabba, P. L. Zinzani, Patrizia Chiusolo, A. Di Rocco, Massimo Martino, Beatrice Casadei, Anna Maria Barbui, Paolo Corradini, Anna Dodero, C. Carniti, Annalisa Chiappella, Armando Santoro, and Stefania Bramanti
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Oncology ,Cancer Research ,medicine.medical_specialty ,Hematology ,business.industry ,General Medicine ,medicine.anatomical_structure ,Internal medicine ,medicine ,Observational study ,Car t cells ,business ,B cell - Published
- 2021
3. RE-MIND: Comparing Tafasitamab + Lenalidomide (L-MIND) with a real-world lenalidomide monotherapy cohort in relapsed or refractory diffuse large B-cell lymphoma
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Sumeet Ambarkhane, Mark Winderlich, Claudia Castellino, Sascha Tillmanns, Nathan Fowler, Erika Meli, Anna Maria Barbui, Nuwan C. Kurukulasuriya, Gilles Salles, Grzegorz S. Nowakowski, Maurizio Frezzato, Günter Fingerle-Rowson, Thomas D. Rodgers, Bruce Feinberg, Debarshi Dey, Pier Luigi Zinzani, Stephan Parche, Dario Marino, Zinzani P.L., Rodgers T., Marino D., Frezzato M., Barbui A.M., Castellino C., Meli E., Fowler N.H., Salles G., Feinberg B., Kurukulasuriya N.C., Tillmanns S., Parche S., Dey D., Fingerle-Rowson G., Ambarkhane S., Winderlich M., and Nowakowski G.S.
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Oncology ,Cancer Research ,medicine.medical_specialty ,Combination therapy ,Antibodies, Monoclonal, Humanized ,Retrospective Studie ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Clinical endpoint ,medicine ,Humans ,Refractory Diffuse Large B-Cell Lymphoma ,Lenalidomide ,Retrospective Studies ,Antineoplastic Combined Chemotherapy Protocol ,business.industry ,Retrospective cohort study ,Confidence interval ,Propensity score matching ,Cohort ,Lymphoma, Large B-Cell, Diffuse ,business ,medicine.drug ,Human - Abstract
Purpose: Tafasitamab, an Fc-modified, humanized, anti-CD19 monoclonal antibody, in combination with lenalidomide, demonstrated efficacy in transplant-ineligible patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL), in the single-arm, phase II L-MIND study (NCT02399085). RE-MIND, a retrospective observational study, generated a historic control for L-MIND to delineate the contribution of tafasitamab to the efficacy of the combination. Patients and Methods: Data were retrospectively collected from patients with R/R DLBCL treated with lenalidomide monotherapy for comparison with tafasitamab + lenalidomide–treated patients (L-MIND). Key eligibility criteria were aligned with L-MIND. Estimated propensity score–based Nearest Neighbor 1:1 Matching methodology balanced the cohorts for nine prespecified prognostic baseline covariates. The primary endpoint was investigator-assessed best overall response rate (ORR). Secondary endpoints included complete response (CR) rate, progression-free survival (PFS), and overall survival (OS). Results: Data from 490 patients going through lenalidomide monotherapy were collected; 140 qualified for matching with the L-MIND cohort. The primary analysis included 76 patients from each cohort who received a lenalidomide starting dose of 25 mg/day. Cohort baseline covariates were comparable. A significantly better ORR of 67.1% (95% confidence interval, 55.4–77.5) was observed for the combination therapy versus 34.2% (23.7–46.0) for lenalidomide monotherapy [odds ratio, 3.89 (1.90–8.14); P < 0.0001]. Higher CR rates were achieved with combination therapy compared with lenalidomide monotherapy [39.5% (28.4–51.4) vs. 13.2% (6.5–22.9)]. Survival endpoints favored combination therapy. Lenalidomide monotherapy outcomes were similar to previously published data. Conclusions: RE-MIND enabled the estimation of the additional treatment effect achieved by combining tafasitamab with lenalidomide in patients with R/R DLBCL.
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- 2021
4. Checkpoint Inhibition before Axicabtagene Ciloleucel Cell Therapy in Primary Mediastinal B-Cell Lymphoma (PMBCL) Treated in Real Life Setting
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Paolo Corradini, Chiara Monfrini, Federica Sorà, Stefania Bramanti, Filippo Bagnoli, Anna Guidetti, Vanessa Aragona, Cristiana Carniti, Anna Dodero, Annalisa Chiappella, Pier Luigi Zinzani, Matteo Carrabba, and Anna Maria Barbui
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medicine.medical_specialty ,Chemotherapy ,Intention-to-treat analysis ,business.industry ,medicine.medical_treatment ,Immunology ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Refractory ,Internal medicine ,Expanded access ,medicine ,Primary mediastinal B-cell lymphoma ,Nivolumab ,Adverse effect ,business ,Progressive disease - Abstract
Background: Eighty-five percent of PMBCL are cured by standard therapy, but the outcome of refractory/relapsed (R/R) PMBCL is very poor. Checkpoint inhibitors (CPIs) have shown promising activity in relapsed PMBCL. Axibactagene ciloleucel (axi-cel) CAR-T cell therapy, can induce durable responses and is currently approved for the treatment of adult patients with R/R PMBCL. Aims of this analysis were: to register all Italian PMBCL patients candidate to CAR-T in the 6 active centers;to evaluate the intention to treat overall response rate (ORR, complete [CR] and partial response [PR]) in patients treated with axi-cel and CPIs for salvage or bridging before CAR-T and for relapse after CAR-T;to evaluate cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Methods: In August 2019 the Italian Drug Agency (AIFA) approved axi-cel; before the reimbursement by AIFA, an expanded access program supported by Kite/Gilead started. One patient slot per month per qualified center was available. Patients were included in a large national CAR-T prospective observational study approved by ethics committees. Results: Since April 2019 to March 2020, 20 R/R PMBCL were evaluated and 18 were apheresized in order to receive axi-cel; 2 were excluded because active CNS disease in one, and eligibility to transplant, while in CR, in the second one. Their clinical characteristics were: median age 38 years (range 22-50), male 8 (44%), stage II 6 (33%), advanced stage III/IV 12 (66%), bulky disease 6 (33%); LDH upper than normal 3 (2%). Median number of prior lines was 3 (2-6); 5 patients (28%) had a previous autologous stem cell transplant and 12 (66%) received a prior radiotherapy. The majority of patients, 16 (89%) were refractory to the last treatment when they were evaluated for CAR-T eligibility; 9 of 18 patients had CPI exposure before leukoapheresis: 6 pembrolizumab and 3 nivolumab in combination with brentuximab-vedotin. No manufacturing failures were reported. Bridging therapy was performed in 16 of 18 patients (88%). Seventeen patients (94%) received lymphodepleting Flu-Cy chemotherapy and only 16 pts received CAR-T for central nervous system (CNS) progression during bridging therapy (n=1) and respiratory failure due to pneumonia (n=1); the 2 patient not infused were exposed to CPIs. Median vein to vein time was 40 days (30-79). Median follow-up time for infused patients was 209 days (9-444). CRS was observed in 12 of 16 infused patients: 5 grade 2 and 7 grade 1. ICANS (2 grade 1, 2 grade 2, 1 grade 3) was recorded in 5 patients. No differences regarding CRS and ICANS occurrence were observed in patients exposed or not to CPIs. At 30-days after the infusion, all the 16 infused patients were evaluable for response: 7 (44%) CR, 5 (31%) PR, with ORR 75%, 3 (19%) stable disease (SD) and 1 (6%) progressive disease (PD). Two patients in PR at 30 days converted to CR at 90 days, with continuous CR at 180 days; all the 3 patients in SD and 1 out of 5 in PR at 30 days progressed at 90 days. Considering the 9 patients exposed to CPIs before CAR-T, 7 out of 9 were infused and all the 7 infused were evaluable for response: 2 (29%) CR, 4 (57%) PR, with ORR 86%, and 1 (14%) died because of a rapid CNS progression after infusion. Two patients in PR at 30-days converted to CR at 90-days, one with continuous CR at 180 days after CAR-T. Conclusions: In our series of 16 infused patients, axi-cel was effective with an ORR of 75% (CR 44%) at 30-days after CAR-T infusion and ORR of 54% (CR 46%) in the 13 patients evaluable at the median follow-up time (180-days after CAR-T infusion). It is important to note the 4 patients from the original real life cohort never received axi-cel. It is noteworthy that ORR was 86% in patients receiving CPIs before CAR-T and 75% in those not exposed to CPIs. With the limitation of small number, the exposure of immune-checkpoint inhibitors seems not to affect negatively response rate and adverse events. Disclosures Chiappella: Janssen: Honoraria; Iqone: Honoraria; Servier: Honoraria; Roche: Honoraria; Celgene: Honoraria; Gilead-Kite: Honoraria; Takeda: Honoraria. Zinzani:Bayer: Consultancy. Corradini:BMS: Other; Sanofi: Consultancy, Honoraria; Servier: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Other; Amgen: Consultancy, Honoraria, Other: Travel and accommodations paid by for; AbbVie: Consultancy, Honoraria, Other: Travel and accommodations paid by for; KiowaKirin: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Other: Travel and accommodations paid by for; F. Hoffman-La Roche Ltd: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Incyte: Consultancy; Gilead: Consultancy, Honoraria, Other: Travel and accommodations paid by for; Daiichi Sankyo: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Other: Travel and accommodations paid by for; Kite: Consultancy, Honoraria.
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- 2020
5. O17-2 Tafasitamab + lenalidomide versus lenalidomide monotherapy in transplant-ineligible patients with R/R DLBCL (RE-MIND)
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Pier Luigi Zinzani, Bruce Feinberg, Maurizio Frezzato, Günter Fingerle-Rowson, Gilles Salles, Anna Maria Barbui, Nathan Fowler, Sumeet Ambarkhane, Dario Marino, Erika Meli, Sascha Tillmanns, Claudia Castellino, Stephan Parche, Grzegorz S. Nowakowski, Thomas D. Rodgers, and Mark Winderlich
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Oncology ,medicine.medical_specialty ,business.industry ,Internal medicine ,medicine ,Hematology ,business ,Transplant ineligible ,Lenalidomide ,medicine.drug - Published
- 2021
6. Evaluation of an antigen-based test for hospital point-of-care diagnosis of SARS-CoV-2 infection
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Cristina Costa, Maurizio Coggiola, Gabriele Bianco, Franco Riccardini, Matteo Boattini, Gitana Scozzari, Rossana Cavallo, Anna Maria Barbui, and Enrico Lupia
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Male ,0301 basic medicine ,Fluorescent Antibody Technique ,Antigen test ,Hospital screening ,COVID-19 Testing ,0302 clinical medicine ,80 and over ,Medicine ,Infection control ,Viral ,Prospective Studies ,030212 general & internal medicine ,Young adult ,Child ,Prospective cohort study ,Antigens, Viral ,Aged, 80 and over ,Middle Aged ,Infectious Diseases ,Point-of-Care Testing ,Child, Preschool ,Female ,medicine.symptom ,Adult ,medicine.medical_specialty ,Adolescent ,Short Communication ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Point-of-care testing ,030106 microbiology ,Sensitivity and Specificity ,Asymptomatic ,Young Adult ,03 medical and health sciences ,Antigen ,Virology ,Internal medicine ,parasitic diseases ,Humans ,Healthcare workers ,Antigens ,Diagnostic Errors ,Preschool ,Aged ,Point of care ,SARS-CoV-2 ,business.industry ,COVID-19 ,Infant ,Point-of-care-testing ,body regions ,business - Abstract
Background An accurate diagnosis is essential to identify and manage SARS-CoV-2 infected patients and implement infection control measures. Although real-time reverse transcription polymerase chain reaction (RT-PCR) is the current recommended laboratory method, several rapid antigen point-of-care tests (POCTs) were developed as frontline testing for SARS-CoV-2 infection diagnosis. Objectives The aim of this study was to assess a recently CE-approved POCT, SARS-CoV-2 Ag Test on the LumiraDx™ Platform (LumiraDx GmbH, Cologne, Germany) for the identification of SARS-COV-2 infected subjects at hospital setting. Methods LumiraDx POCT was implemented in three hospital settings: adult and pediatric emergency departments and occupational medicine department along two-month period during the second peak of Italian SARS-CoV-2 pandemic. Rapid antigen testing was performed on direct nasal swabs and results were compared with those obtained by Xpert Xpress SARS-CoV-2 assay. Results Overall sensitivity, specificity, NPV and PPV were 90.3%, 92.1%, 95.1%, and 84.9%, respectively, compared to reference method. Sensitivity, specificity, PPV and NPV for symptomatic group were 89.3% [95% IC 84.2-93.3], 88.2% [95% IC 72.5-96.7], 97.8% [95% IC 94.6-99.1], and 58.8% [95% IC 48.4-68.5], respectively. Sensitivity, specificity, PPV and NPV for asymptomatic group were 92.1% [95% IC 85-96.5], 92.3% [95% IC 89.9-94.4], 67.9% [95% IC 61.3-73.8], and 98.5% [95% IC 97.1-99.2], respectively. False positive and negative antigen testing results in both symptomatic and asymptomatic group were observed. Conclusion SARS-CoV-2 Ag POCT may represent an interesting tool to rapidly identify symptomatic or asymptomatic infected subjects. However, in hospital setting in which false negative or false positive results may have relevant implications, confirmatory NAAT always remains necessary for the appropriate management of patients.
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- 2021
7. ABCL-135: RE-MIND: A Comparison of Tafasitamab (MOR208) + Lenalidomide (L-MIND) Versus Lenalidomide Monotherapy (Real-World Data) in Transplant-Ineligible Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma
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Annarita Conconi, Mark Winderlich, Erika Meli, Anna Maria Barbui, Nathan Fowler, Thomas D. Rodgers, Gilles Salles, Pier Luigi Zinzani, Sumeet Ambarkhane, Maurizio Frezzato, Günter Fingerle-Rowson, Bruce Feinberg, Federica Cavallo, Dario Marino, Grzegorz S. Nowakowski, Sascha Tillmanns, Claudia Castellino, Stephan Parche, and Nicola Cascavilla
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Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Retrospective cohort study ,Context (language use) ,Hematology ,medicine.disease ,Regimen ,Autologous stem-cell transplantation ,Internal medicine ,Cohort ,Clinical endpoint ,medicine ,business ,Diffuse large B-cell lymphoma ,Lenalidomide ,medicine.drug - Abstract
Context: Tafasitamab (MOR208), a humanized anti-CD19 antibody, combined with lenalidomide (LEN) showed encouraging results in the Phase II, single-arm L-MIND study ( NCT02399085 ) of patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) ineligible for autologous stem cell transplantation (ASCT). Objective: To generate a LEN monotherapy matched comparator cohort for L-MIND using patient-level data to isolate the tafasitamab contribution to the efficacy of the tafasitamab + LEN combination. Design: RE-MIND ( NCT04150328 ), a retrospective observational study, used a Nearest Neighbor ePS-based 1:1 Matching methodology to balance the LEN monotherapy cohort (observational data) and combination cohort (derived from L-MIND) for nine prespecified baseline covariates: age, Ann Arbor stage, last therapy refractoriness, number of prior therapy lines, primary refractoriness, prior ASCT, LDH, neutropenia, and anemia. The primary analysis set included matched patients who received a LEN starting dose of 25 mg/day (as in L-MIND) with sufficient follow-up. Patients: LEN monotherapy-treated patients from the US and EU who met the L-MIND-aligned eligibility criteria: adult patients with R/R DLBCL; 1–3 prior systemic therapies, including 1 CD20-targeting regimen; ASCT-ineligible. Baseline characteristics, LEN dosing, and patient outcomes were collected retrospectively from health records. Main outcome measures: The primary endpoint was investigator-assessed best objective response rate (ORR). Secondary endpoints included overall survival (OS) and complete response (CR) rates. Results: 490 patients were enrolled, of which 140 fulfilled the ePS matching criteria. Following matching, the primary analysis set included 76 patients from each cohort. Baseline characteristics were comparable. The primary endpoint was met. Best ORR was significantly higher in the combination cohort (67.1%) versus the monotherapy cohort (34.2%) (odds ratio 3.89; 95% confidence interval [CI]: 1.90–8.14; p Conclusions: Significantly better ORR, CR, and OS indicate potential synergistic effects of the tafasitamab + LEN combination in ASCT-ineligible R/R DLBCL. RE-MIND demonstrates the utility of real-world data in interpreting non-randomized trials.
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- 2020
8. Randomized Trial Comparing R-CHOP Versus High-Dose Sequential Chemotherapy in High-Risk Patients With Diffuse Large B-Cell Lymphomas
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Manuela Zanni, Alessandro Massimo Gianni, Massimo Di Nicola, Simona Falorio, Fabio Benedetti, Atto Billio, Cristina Boschini, Andrea Rossi, Valentina Tabanelli, Antonino Mulè, Andrés J.M. Ferreri, Federica Delaini, L. Flenghi, Alessandro Rambaldi, Giorgio La Nasa, Paolo Corradini, Arianna Masciulli, Marco Ladetto, Caterina Patti, Corrado Tarella, Andrea Piccin, Sergio Cortelazzo, Riccardo Bruna, Guido Gini, Claudia Castellino, Francesco Di Raimondo, Anna Maria Barbui, Livio Trentin, Giovanni Negri, Maurizio Frezzato, Stefano Pileri, Marco Chilosi, Giuseppe Gritti, and Valerio Zoli
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Male ,Cancer Research ,Lymphoma ,medicine.medical_treatment ,Gastroenterology ,FRONT-LINE THERAPY ,Antibodies, Monoclonal, Murine-Derived ,0302 clinical medicine ,International Prognostic Index ,ACVBP PLUS RITUXIMAB ,Prednisone ,Monoclonal ,Antineoplastic Combined Chemotherapy Protocols ,GENE-EXPRESSION ,Middle Aged ,OPEN-LABEL ,Combined Modality Therapy ,Diffuse ,Treatment Outcome ,Oncology ,Vincristine ,030220 oncology & carcinogenesis ,INTENSIFIED CHEMOTHERAPY ,YOUNG-PATIENTS ,Female ,Rituximab ,Lymphoma, Large B-Cell, Diffuse ,medicine.drug ,Adult ,Murine-Derived ,medicine.medical_specialty ,Adolescent ,Aged ,Cyclophosphamide ,Doxorubicin ,Humans ,Stem Cell Transplantation ,Young Adult ,NON-HODGKINS-LYMPHOMA ,BONE-MARROW-TRANSPLANTATION ,DETUDES DES LYMPHOMES ,POOR-PROGNOSIS ,Antibodies ,03 medical and health sciences ,Internal medicine ,Large B-Cell ,medicine ,Chemotherapy ,Intention-to-treat analysis ,business.industry ,Surgery ,Transplantation ,business ,030215 immunology - Abstract
Purpose The benefit of high-dose chemotherapy with autologous stem-cell transplantation (ASCT) as first-line treatment in patients with diffuse large B-cell lymphomas is still a matter of debate. To address this point, we designed a randomized phase III trial to compare rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP)-14 (eight cycles) with rituximab plus high-dose sequential chemotherapy (R-HDS) with ASCT. Patients and Methods From June 2005 to June 2011, 246 high-risk patients with a high-intermediate (56%) or high (44%) International Prognostic Index score were randomly assigned to the R-CHOP or R-HDS arm, and 235 were analyzed by intent to treat. The primary efficacy end point of the study was 3-year event-free survival, and results were analyzed on an intent-to-treat basis. Results Clinical response (complete response, 78% v 76%; partial response, 5% v 9%) and failures (no response, 15% v 11%; and early treatment-related mortality, 2% v 3%) were similar after R-CHOP versus R-HDS, respectively. After a median follow-up of 5 years, the 3-year event-free survival was 62% versus 65% ( P = .83). At 3 years, compared with the R-CHOP arm, the R-HDS arm had better disease-free survival (79% v 91%, respectively; P = .034), but this subsequently vanished because of late-occurring treatment-related deaths. No difference was detected in terms of progression-free survival (65% v 75%, respectively; P = .12), or overall survival (74% v 77%, respectively; P = .64). Significantly higher hematologic toxicity ( P < .001) and more infectious complications ( P < .001) were observed in the R-HDS arm. Conclusion In this study, front-line intensive R-HDS chemotherapy with ASCT did not improve the outcome of high-risk patients with diffuse large B-cell lymphomas.
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- 2016
9. Prolonged survival in the absence of disease-recurrence in advanced-stage follicular lymphoma following chemo-immunotherapy: 13-year update of the prospective, multicenter randomized GITMO-IIL trial
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Alessandro Rambaldi, Carola Boccomini, Atto Billio, Francesco Angrilli, Roberto Passera, Marco Ladetto, Francesco Zallio, Gianpietro Semenzato, Liliana Devizzi, Fabio Ciceri, Barbara Mantoan, Fausto Rossini, Alessandra Dondi, Alessandra Tucci, Fabio Benedetti, Caterina Stelitano, Delia Rota-Scalabrini, Valerio Zoli, Paolo Corradini, Riccardo Bruna, Corrado Tarella, Maurizio Musso, Franco Narni, Caterina Patti, Guido Gini, Claudia Castellino, Tommasina Perrone, Anna Maria Barbui, Francesco Lanza, Anna Marina Liberati, Guido Parvis, Francesco Di Raimondo, Alessandro Massimo Gianni, Alessandro Pulsoni, Angela Gueli, Bruna R., Benedetti F., Boccomini C., Patti C., Barbui A. M., Pulsoni A., Musso M., Liberati A. M., Gini G., Castellino C., Rossini F., Ciceri F., Rota-Scalabrini D., Stelitano C., Di Raimondo F., Tucci A., Devizzi L., Zoli V., Zallio F., Narni F., Dondi A., Parvis G., Semenzato G., Lanza F., Perrone T., Angrilli F., Billio A., Gueli A., Mantoan B., Rambaldi A., Massimo Gianni A., Corradini P., Passera R., Ladetto M., Tarella C., Bruna, R., Benedetti, F., Boccomini, C., Patti, C., Barbui, A. M., Pulsoni, A., Musso, M., Liberati, A. M., Gini, G., Castellino, C., Rossini, F., Ciceri, F., Rota-Scalabrini, D., Stelitano, C., Di Raimondo, F., Tucci, A., Devizzi, L., Zoli, V., Zallio, F., Narni, F., Dondi, A., Parvis, G., Semenzato, G., Lanza, F., Perrone, T., Angrilli, F., Billio, A., Gueli, A., Mantoan, B., Rambaldi, A., Massimo Gianni, A., Corradini, P., Passera, R., Ladetto, M., and Tarella, C.
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Male ,Oncology ,Lymphoma ,medicine.medical_treatment ,advanced-stage follicular lymphoma ,Follicular lymphoma ,Kaplan-Meier Estimate ,law.invention ,0302 clinical medicine ,Cancer immunotherapy ,Randomized controlled trial ,Recurrence ,immune system diseases ,law ,hemic and lymphatic diseases ,Antineoplastic Combined Chemotherapy Protocols ,Prospective cohort study ,Lymphoma, Follicular ,non-Hodgkin lymphoma ,Remission Induction ,Hematology ,Middle Aged ,Prognosis ,Combined Modality Therapy ,Treatment Outcome ,Italy ,chemoimmunotherapy ,Female ,Rituximab ,Adult ,Follow-Up Studies ,Humans ,Neoplasm Staging ,Proportional Hazards Models ,Young Adult ,medicine.drug ,medicine.medical_specialty ,Sudden death ,Article ,NO ,03 medical and health sciences ,Lymphoma, therapy, clinical trial ,Internal medicine ,medicine ,Cancer staging ,Chemotherapy ,business.industry ,Follicular ,medicine.disease ,business ,030215 immunology - Abstract
A prospective trial conducted in the period 2000-2005 showed no survival advantage for high-dose chemotherapy with rituximab and autograft (R-HDS) versus conventional chemotherapy with rituximab (CHOP-R) as first-line therapy in 134 high-risk follicular lymphoma patients aged
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- 2019
10. Allogeneic Stem Cell Transplantation in Mantle Cell Lymphoma in the Era of New Drugs and CAR-T Cell Therapy
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Miriam Marangon, Gerardo Musuraca, Sara Galimberti, Simone Ferrero, Alberto Fabbri, Stefano Luminari, Annalisa Chiappella, Anna Maria Barbui, Carlo Visco, Alessandro Re, Vittorio Ruggero Zilioli, and Marco Ladetto
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Oncology ,Cancer Research ,medicine.medical_specialty ,Allogeneic transplantation ,mantle cell lymphoma ,Car-T cell therapy ,Review ,lcsh:RC254-282 ,03 medical and health sciences ,0302 clinical medicine ,immune system diseases ,allogeneic stem cell transplantation ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Mantle cell lymphoma ,business.industry ,Allogeneic stem cell transplantation ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Transplantation ,030220 oncology & carcinogenesis ,CAR T-cell therapy ,Stem cell ,business ,030215 immunology - Abstract
Simple Summary Mantle Cell Lymphoma (MCL) is a lymphoproliferative disorder which represents less than 10% of all non-Hodgkin Lymphomas. The typical course of MCL is characterized by several relapses (“remitting-relapsing” course), and since its identification it has been considered an incurable disease. Allogeneic stem cell transplantation (allo-SCT) has represented in the past years the only treatment which could ensure prolonged remissions, at least in younger patients. In our paper, we critically revised the available data on the use of allo-SCT in MCL. The aim of our review is to identify the subgroups of patients who could best benefit from this therapeutic strategy, the optimal timing for transplantation and the best ways to bridge patients to allo-SCT, in an era in which many novel agents have been developed. Abstract MCL is an uncommon lymphoproliferative disorder that has been regarded as incurable since its identification as a distinct entity. Allogeneic transplantation for two decades has represented the only option capable of ensuring prolonged remissions and possibly cure. Despite its efficacy, its application has been limited by feasibility limitations and substantial toxicity, particularly in elderly patients. Nevertheless, the experience accumulated over time has been wide though often scattered among retrospective and small prospective studies. In this review, we aimed at critically revise and discuss available evidence on allogeneic transplantation in MCL, trying to put available evidence into the 2020 perspective, characterized by unprecedented development of novel promising therapeutic agents and regimens.
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- 2021
11. IMMUNOCHEMOTHERAPY WITH OBINUTUZUMAB OR RITUXIMAB IN PREVIOUSLY UNTREATED FOLLICULAR LYMPHOMA IN THE RANDOMISED PHASE III GALLIUM STUDY: ANALYSIS BY CHEMOTHERAPY REGIMEN
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Robert Marcus, Roswitha Forstpointner, Mark Hertzberg, John Radford, Günter Fingerle-Rowson, Anna Maria Barbui, P.K. Cannell, Graham P. Collins, M. Wolbers, Kensei Tobinai, Michael Herold, Wolfgang Hiddemann, Jan Dürig, M. A. Canales Albendea, A. Burciu, Magdalena Klanova, and Tina Nielsen
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Oncology ,Cancer Research ,medicine.medical_specialty ,Follicular lymphoma ,chemistry.chemical_element ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Obinutuzumab ,Internal medicine ,medicine ,030212 general & internal medicine ,Study analysis ,Gallium ,business.industry ,Hematology ,General Medicine ,medicine.disease ,Chemotherapy regimen ,chemistry ,030220 oncology & carcinogenesis ,Immunology ,Rituximab ,business ,medicine.drug - Published
- 2017
12. RE-MIND study: A propensity score-based 1:1 matched comparison of tafasitamab + lenalidomide (L-MIND) versus lenalidomide monotherapy (real-world data) in transplant-ineligible patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL)
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Pier Luigi Zinzani, Thomas D. Rodgers, Claudia Castellino, Guenter Fingerle-Rowson, Erika Meli, Mark Winderlich, Stephan Parche, Grzegorz S. Nowakowski, Maurizio Frezzato, Bruce A. Feinberg, Nathan Fowler, Anna Maria Barbui, Gilles Salles, Dario Marino, Sumeet Ambarkhane, and Sascha Tillmanns
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Oncology ,Cancer Research ,medicine.medical_specialty ,Poor prognosis ,business.industry ,medicine.disease ,Transplant ineligible ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,Propensity score matching ,Relapsed refractory ,medicine ,Stem cell ,business ,Real world data ,Diffuse large B-cell lymphoma ,030215 immunology ,Lenalidomide ,medicine.drug - Abstract
8020 Background: Patients with R/R DLBCL ineligible for autologous stem cell transplant (ASCT) have a poor prognosis. In these patients, tafasitamab (anti-CD19 antibody) plus lenalidomide (LEN) has shown encouraging results in the open-label, single-arm, phase II L-MIND study (n = 81; NCT02399085). To evaluate the contribution of tafasitamab to the activity of this doublet, we conducted a global, real-world study of patients treated with LEN monotherapy (RE-MIND; NCT04150328). Here we present the primary analysis of a 1:1 patient-level matched comparison between the L-MIND and RE-MIND cohorts. Methods: Patients treated with LEN monotherapy for R/R DLBCL were enrolled in the observational, retrospective RE-MIND cohort. As in L-MIND, patients had 1–3 prior systemic therapies, including ≥1 CD20-targeting regimen; were aged ≥18 years; and were not eligible for ASCT. A 1:1 estimated propensity score (ePS) matching methodology ensured balancing of nine pre-specified baseline covariates. The primary analysis set, Matched Analysis Set 25 (MAS25), included patients who received a LEN starting dose of 25 mg/day. The primary endpoint was investigator-assessed best objective response rate (ORR). Key secondary endpoints included overall survival (OS) and complete response (CR) rate. Results: 490 patients were enrolled in RE-MIND across 58 centers in the US and Europe, of which 140 fulfilled the ePS matching criteria. The MAS25 included 76 patients each from the two cohorts. Baseline characteristics between cohorts were comparable. The primary endpoint was met with a significantly better ORR of 67.1% (95% CI: 55.4–77.5) for the L-MIND cohort versus 34.2% (95% CI: 23.7–46.0) for the RE-MIND cohort (odds ratio 3.89; 95% CI: 1.90–8.14; p < 0.0001). The CR rate was 39.5% (95% CI: 28.4–51.4) in the L-MIND cohort and 13.2% (95% CI: 6.5–22.9) in the RE-MIND cohort. A significant difference in OS favored the L-MIND cohort (HR = 0.499; 95% CI: 0.317–0.785). ORR and CR outcomes in the RE-MIND cohort were similar to the published literature for LEN monotherapy in R/R DLBCL. Conclusions: Significantly better ORR, CR and OS indicate potential synergistic effects of the tafasitamab + LEN combination in ASCT-ineligible R/R DLBCL. ePS-based 1:1 matching allows robust estimation of the treatment effect of tafasitamab when added to LEN. RE-MIND demonstrates the utility of real-world data in interpreting non-randomized trials. Clinical trial information: NCT04150328 .
- Published
- 2020
13. A phase II multicenter study of the anti-CD19 antibody drug conjugate coltuximab ravtansine (SAR3419) in patients with relapsed or refractory diffuse large B-cell lymphoma previously treated with rituximab-based immunotherapy
- Author
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Anna Guidetti, Martin J. S. Dyer, Marek Trnĕný, Massimo Di Nicola, Laure Siraudin, María José Terol, Andrea Janíková, Kazimierz Sulek, John Radford, Andres Lopez, Miguel Canales, Gregor Verhoef, Farrukh T. Awan, Anna Maria Barbui, Dina Ben Yehuda, Corina Oprea, Sandrine Schwab, Caterina Patti, Laurence Hatteville, Alessandro M. Gianni, and Paul G. Montgomery
- Subjects
0301 basic medicine ,Male ,Immunoconjugates ,CLINICAL ACTIVITY ,Gastroenterology ,0302 clinical medicine ,MOLECULAR SUBTYPES ,Refractory Diffuse Large B-Cell Lymphoma ,ELDERLY-PATIENTS ,Aged, 80 and over ,LENALIDOMIDE ,education.field_of_study ,Manchester Cancer Research Centre ,Hematology ,Middle Aged ,Treatment Outcome ,030220 oncology & carcinogenesis ,Rituximab ,Female ,Immunotherapy ,Lymphoma, Large B-Cell, Diffuse ,NON-HODGKIN-LYMPHOMA ,Life Sciences & Biomedicine ,medicine.drug ,Adult ,medicine.medical_specialty ,Non-Hodgkin Lymphoma ,Population ,Antigens, CD19 ,Antibodies, Monoclonal, Humanized ,Article ,PLUS CYCLOPHOSPHAMIDE ,03 medical and health sciences ,Refractory ,Internal medicine ,medicine ,Humans ,Maytansine ,education ,Adverse effect ,Survival analysis ,Aged ,Salvage Therapy ,Science & Technology ,TRANSPLANTATION ,business.industry ,ResearchInstitutes_Networks_Beacons/mcrc ,medicine.disease ,Survival Analysis ,Lymphoma ,INTRAVENOUS-INFUSION ,030104 developmental biology ,IMMUNOCONJUGATE ,Eye disorder ,INOTUZUMAB OZOGAMICIN ,business - Abstract
This phase II, single-arm, multicenter study examined the efficacy and safety of coltuximab ravtansine (an anti-CD19 antibody drug conjugate) in 61 patients with histologically documented (de novo or transformed) relapsed or refractory diffuse large B-cell lymphoma who had previously received rituximab-containing immuno-chemotherapy. Patients had received a median of 2.0 (range 0-9) prior treatment regimens for diffuse large B-cell lymphoma and almost half (45.9%) had bulky disease (≥1 lesion >5 cm) at trial entry. Patients received coltuximab ravtansine (55 mg/m2) in 4 weekly and 4 biweekly administrations until disease progression or unacceptable toxicity. Forty-one patients were eligible for inclusion in the per protocol population. Overall response rate (International Working Group criteria) in the per protocol population, the primary end point, was 18/41 [43.9%; 90% confidence interval (CI:) 30.6-57.9%]. Median duration of response, progression-free survival, and overall survival (all treated patients) were 4.7 (range 0.0-8.8) months, 4.4 (90%CI: 3.02-5.78) months, and 9.2 (90%CI: 6.57-12.09) months, respectively. Common non-hematologic adverse events included asthenia/fatigue (30%), nausea (23%), and diarrhea (20%). Grade 3-4 adverse events were reported in 23 patients (38%), the most frequent being hepatotoxicity (3%) and abdominal pain (3%). Eye disorders occurred in 15 patients (25%); all were grade 1-2 and none required a dose modification. Coltuximab ravtansine monotherapy was well tolerated and resulted in moderate clinical responses in pre-treated patients with relapsed/refractory diffuse large B-cell lymphoma. (Registered at: clinicaltrials.gov identifier: 01472887). ispartof: HAEMATOLOGICA vol:103 issue:8 pages:1351-1358 ispartof: location:Italy status: published
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- 2018
14. Immunochemotherapy With Obinutuzumab or Rituximab for Previously Untreated Follicular Lymphoma in the GALLIUM Study: Influence of Chemotherapy on Efficacy and Safety
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Jan Dürig, Marcel Wolbers, Miguel Canales, Roswitha Forstpointner, Tina Nielsen, Wolfgang Hiddemann, John Radford, John F. Seymour, Anna Maria Barbui, Günter Fingerle-Rowson, Graham P. Collins, Kensei Tobinai, Michael Herold, Magdalena Klanova, Robert Marcus, Mark Hertzberg, Paul Cannell, Alis Burciu, and Judith Trotman
- Subjects
Adult ,Male ,Bendamustine ,Cancer Research ,medicine.medical_specialty ,Vincristine ,Medizin ,Follicular lymphoma ,CHOP ,Antibodies, Monoclonal, Humanized ,Gastroenterology ,Young Adult ,03 medical and health sciences ,chemistry.chemical_compound ,Antineoplastic Agents, Immunological ,0302 clinical medicine ,International Prognostic Index ,Obinutuzumab ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Bendamustine Hydrochloride ,Humans ,Progression-free survival ,Cyclophosphamide ,Lymphoma, Follicular ,Aged ,Aged, 80 and over ,Manchester Cancer Research Centre ,business.industry ,ResearchInstitutes_Networks_Beacons/mcrc ,Middle Aged ,medicine.disease ,Progression-Free Survival ,Oncology ,chemistry ,Doxorubicin ,030220 oncology & carcinogenesis ,Prednisone ,Female ,Rituximab ,business ,030215 immunology ,medicine.drug - Abstract
Purpose The GALLIUM study ( ClinicalTrials.gov identifier: NCT01332968) showed that obinutuzumab (GA101; G) significantly prolonged progression-free survival (PFS) in previously untreated patients with follicular lymphoma relative to rituximab (R) when combined with cyclophosphamide (C), doxorubicin, vincristine (V), and prednisone (P; CHOP); CVP; or bendamustine. This report focuses on the impact of chemotherapy backbone on efficacy and safety. Patients and Methods A total of 1,202 patients with previously untreated follicular lymphoma (grades 1 to 3a), advanced disease (stage III or IV, or stage II with tumor diameter ≥ 7 cm), Eastern Cooperative Oncology Group performance status 0 to 2, and requiring treatment were randomly assigned 1:1 to G 1,000 mg on days 1, 8, and 15 of cycle 1 and day 1 of subsequent cycles or R 375 mg/m2 on day 1 of each cycle, for six to eight cycles, depending on chemotherapy (allocated nonrandomly by center). Responding patients received G or R for 2 years or until disease progression. Results Baseline Follicular Lymphoma International Prognostic Index risk, bulky disease, and comorbidities differed by chemotherapy. After 41.1 months median follow-up, PFS (primary end point) was superior for G plus chemotherapy (overall hazard ratio [HR], 0.68; 95% CI, 0.54 to 0.87; P = .0016), with consistent results across chemotherapy backbones (bendamustine: HR, 0.63; 95% CI, 0.46 to 0.88; CHOP: HR, 0.72; 95% CI, 0.48 to 1.10; CVP: HR, 0.79; 95% CI, 0.42 to 1.47). Grade 3 to 5 adverse events, notably cytopenias, were most frequent with CHOP. Grade 3 to 5 infections and second neoplasms were most frequent with bendamustine, which was associated with marked and prolonged reductions in T-cell counts. Fatal events were more frequent in patients treated with bendamustine, possibly reflecting differences in patient risk profiles. Conclusion Improved PFS was observed for G plus chemotherapy for all three chemotherapy backbones. Safety profiles differed, although comparisons are confounded by nonrandom chemotherapy allocation.
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- 2018
15. PS1257 LYMPHOCYTE TO MONOCYTE RATIO (LMR) PREDICTS PROGRESSION-FREE SURVIVAL INDEPENDENTLY FROM FLIPI AND IS USEFUL IN IDENTIFYING PATIENTS WITH EARLY DISEASE PROGRESSION
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Anna Maria Barbui, F. Delaini, Andrea Rossi, Giuseppe Gritti, C. Pavoni, S. Ferrari, A. Rambaldi, and Paola Stefanoni
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Oncology ,medicine.medical_specialty ,medicine.anatomical_structure ,business.industry ,Internal medicine ,Lymphocyte ,Monocyte ,Early disease ,medicine ,Hematology ,Progression-free survival ,business - Published
- 2019
16. Adrenal function and microbial DNA in noninfected cirrhotic patients with ascites: Relationship and effect on survival
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A. Morgando, Carlo Alessandria, Giovannino Ciccone, Alfredo Marzano, Lavinia Mezzabotta, Roberto Serra, Maurizio Spandre, Alida Andrealli, Chiara Elia, A. Risso, Andrea Evangelista, Anna Maria Barbui, Paola Di Luigi, and Mario Rizzetto
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DNA, Bacterial ,Liver Cirrhosis ,Male ,medicine.medical_specialty ,Cirrhosis ,Hydrocortisone ,Microbial DNA ,Gastroenterology ,End Stage Liver Disease ,Basal (phylogenetics) ,Liver disease ,Internal medicine ,Ascites ,Adrenal insufficiency ,medicine ,Humans ,Clinical significance ,DNA, Fungal ,Aged ,Hepatology ,business.industry ,Middle Aged ,medicine.disease ,Liver Transplantation ,Survival Rate ,Endocrinology ,Female ,Liver function ,medicine.symptom ,business ,Adrenal Insufficiency - Abstract
There are few data on clinical relevance of adrenal dysfunction and its relationship with occult microbial DNA in noninfected haemodynamically stable cirrhotic patients with ascites.The aim of this study was to evaluate prognostic role of adrenal dysfunction, microbial DNA, and their relationship.Adrenal function was assessed in 93 consecutive patients following a corticotropin stimulation test. Adrenal dysfunction was defined as: basal cortisol10 μg/dl, delta cortisol9 μg/dl, or peak cortisol18 μg/dl. Microbial DNA was assessed in blood and ascites of 54 consecutive patients. Patients were followed up until liver transplantation or death.Adrenal dysfunction was not significantly associated with mortality, while the risk of death rose significantly with an increase in basal cortisol values (HR 1.13 per 1-μl/dl increase; 95% CI 1.01-1.26). Microbial DNA was independently associated with reduced survival (HR 8.05, 95% CI 1.57-41.2). In microbial DNA-positive patients a significant correlation was found between Model for End-Stage Liver Disease (MELD) score and basal cortisol values (Pearson's r=0.5107; p=0.018).Microbial DNA and MELD score, but not adrenal function, were the best independent predictors of mortality in noninfected cirrhotic patients with ascites. High serum cortisol levels may be a systemic reaction to microbial translocation, increasing in parallel with deterioration of liver function.
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- 2015
17. Evaluation of tenascin-C by tenatumomab in T-cell non-Hodgkin lymphomas identifies a new target for radioimmunotherapy
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Andrea Rossi, Luigi Giusto Spagnoli, Laura Cattaneo, Rita De Santis, Silvia Ferrari, Giuseppe Gritti, Anna Maria Barbui, Chiara Pavoni, Andrea Gianatti, Riccardo L. Rossi, Alessandro Rambaldi, and Fiorella Petronzelli
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,Hematology ,biology ,business.industry ,medicine.medical_treatment ,Cutaneous T-cell lymphoma ,Tenascin C ,Cancer ,Correction ,medicine.disease ,Peripheral T-cell lymphoma ,Lymphoma ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,T-Cell Non-Hodgkin Lymphoma ,030220 oncology & carcinogenesis ,Internal medicine ,Radioimmunotherapy ,medicine ,biology.protein ,business - Abstract
// Giuseppe Gritti 1 , Andrea Gianatti 2 , Fiorella Petronzelli 3 , Rita De Santis 3 , Chiara Pavoni 1 , Riccardo Lorenzo Rossi 4 , Laura Cattaneo 2 , Luigi Giusto Spagnoli 5 , Silvia Ferrari 1 , Andrea Rossi 1 , Anna Maria Barbui 1 and Alessandro Rambaldi 1, 6 1 Hematology Unit, Ospedale Papa Giovanni XXIII, Bergamo, Italy 2 Pathology Unit, Ospedale Papa Giovanni XXII, Bergamo, Italy 3 Sigma Tau S.p.A. Biotech Products R and D, Pomezia, Italy 4 Bioinformatics, Istituto Nazionale Genetica Molecolare, Milan, Italy 5 Department of Biomedicine and Prevention, Universita di Roma Tor Vergata, Rome, Italy 6 Department of Oncology and Oncohematology, Universita degli Studi di Milano, Milan, Italy Correspondence to: Alessandro Rambaldi, email: alessandro.rambaldi@unimi.it Keywords: T-cell non-Hodgkin lymphoma; peripheral T-cell lymphoma; cutaneous T-cell lymphoma; tenascin-C; radioimmunotherapy Received: May 13, 2017 Accepted: November 03, 2017 Published: January 03, 2018 ABSTRACT The clinical outcome of T-cell non-Hodgkin lymphoma (NHL) is poor and innovative treatments are needed. Tenascin-C is a large extracellular glycoprotein not expressed under physiological conditions, but overexpressed in cancer. Aim of the study was to evaluate tenascin-C expression within pathologic tissue of T-cell NHL and determine its clinical significance. We used an immunohistochemistry approach using the anti-tenascin-C monoclonal antibody Tenatumomab in 75 systemic T-cell NHL (including 72 mature and 3 precursor T-cell NHL), and 25 primary cutaneous T-cell NHL. Data were analyzed in terms of staining intensity, proportion of involved areas and histologic pattern, and results were correlated with clinical characteristics and outcome. Ninety-three percent of the cases were tenascin-C positive and 59% of systemic diseases were characterized by a predominant involvement (>50%). Stromal expression was detected in all the cases while vascular and vascular plus cytoplasmic expression was present in 49% and 23%. The constant overexpression of the tenascin-C gene was observed in two independent publicly available T-cell NHL gene expression datasets. In conclusions, tenascin-C represents an attractive target that sets the rationale to investigate the therapeutic activity of radiolabeled Tenatumomab in T-cell NHL.
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- 2017
18. Subgingival Microbiota in White Patients With Desquamative Gingivitis: A Cross-Sectional Study
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Roberto Broccoletti, Luca Cricenti, Raffaella Cipriani, Federica Romano, Fulvio Ricceri, Paolo G. Arduino, Silvia Brossa, Marco Cabras, Mario Aimetti, Danilo Sasia, and Anna Maria Barbui
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Adult ,Male ,medicine.medical_specialty ,Erythema ,Gingiva ,Dentistry ,Aggregatibacter actinomycetemcomitans ,Polymerase Chain Reaction ,White People ,03 medical and health sciences ,Gingivitis ,0302 clinical medicine ,Eikenella corrodens ,medicine ,Odds Ratio ,cross-sectional study ,Humans ,Clinical significance ,Fusobacterium nucleatum ,PCR ,desquamative gingivitis ,Aged ,Aged, 80 and over ,biology ,Bacteria ,business.industry ,Microbiota ,030206 dentistry ,Middle Aged ,medicine.disease ,biology.organism_classification ,Dermatology ,Desquamative gingivitis ,Cross-Sectional Studies ,030220 oncology & carcinogenesis ,Case-Control Studies ,Periodontics ,Regression Analysis ,Oral lichen planus ,Female ,medicine.symptom ,business ,Gingival disease - Abstract
Presence of epithelial desquamation, erythema, and erosions on gingival tissue is usually described in the literature as desquamative gingivitis (DG). A wide range of autoimmune/dermatologic disorders can manifest as DG, although the two more common are oral lichen planus and mucous membrane pemphigoid. The aim of this study is to investigate prevalence of 11 periodontopathogenic microorganisms in patients with DG and to compare it with the microbiologic status of individuals affected by plaque-induced gingivitis (pGI).Cross-sectional clinical and microbiologic data were obtained from 66 patients (33 in each group). Subgingival plaque samples were analyzed using semiquantitative polymerase chain reaction analysis.Statistically significant difference, but with little clinical significance, was observed in gingival conditions between the two groups, probably due to the worse home control hygiene of patients with DG. Prevalence and levels of Aggregatibacter actinomycetemcomitans, Eikenella corrodens, and Fusobacterium nucleatum/periodonticum were statistically higher in samples from patients with DG than in those with pGI. In multivariate regression models, subgingival colonization of A. actinomycetemcomitans and F. nucleatum/periodonticum was not statistically associated with DG, whereas, high levels of E. corrodens were associated with 13-fold increased odds for DG.Microbiologic differences were found in subgingival plaque for patients with DG and pGI. This may suggest possible association between periodontal pathogens and DG.
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- 2017
19. Time trend analysis (2009-2016) of antimicrobial susceptibility in Neisseria gonorrhoeae isolated in Italy following the introduction of the combined antimicrobial therapy
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Paola Stefanelli, Maria Fenicia Vescio, Maria Paola Landini, Ivano Dal Conte, Alberto Matteelli, Antonio Cristaudo, Marina Gaino, Marco Cusini, Anna Maria Barbui, Antonella Mencacci, Rosella De Nittis, Valeria Ghisetti, Elena Stroppiana, Anna Carannante, and Neisseria gonorrhoeae antimicrobials resistant Study Group
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0301 basic medicine ,Genetics and Molecular Biology (all) ,Male ,lcsh:Medicine ,medicine.disease_cause ,Azithromycin ,Pathology and Laboratory Medicine ,Biochemistry ,Geographical locations ,Men who have sex with men ,0302 clinical medicine ,Mathematical and Statistical Techniques ,Medicine and Health Sciences ,030212 general & internal medicine ,lcsh:Science ,Multidisciplinary ,Antimicrobials ,Drugs ,HIV diagnosis and management ,Antimicrobial ,Anti-Bacterial Agents ,Bacterial Pathogens ,Europe ,Adult ,Drug Therapy, Combination ,Female ,Humans ,Italy ,Microbial Sensitivity Tests ,Neisseria gonorrhoeae ,Young Adult ,Biochemistry, Genetics and Molecular Biology (all) ,Agricultural and Biological Sciences (all) ,Infectious Diseases ,Medical Microbiology ,Combination ,Physical Sciences ,Ceftriaxone ,Pathogens ,Neisseria ,Statistics (Mathematics) ,medicine.drug ,Research Article ,medicine.medical_specialty ,030106 microbiology ,Research and Analysis Methods ,Microbiology ,03 medical and health sciences ,Antibiotic resistance ,Drug Therapy ,Internal medicine ,Microbial Control ,medicine ,Sex organ ,European Union ,Statistical Methods ,Microbial Pathogens ,Pharmacology ,Treatment Guidelines ,Health Care Policy ,Bacteria ,business.industry ,lcsh:R ,Organisms ,Biology and Life Sciences ,Diagnostic medicine ,Health Care ,Co-Infections ,Multivariate Analysis ,lcsh:Q ,Antimicrobial Resistance ,People and places ,business ,Cefixime ,Mathematics - Abstract
Introduction Neisseria gonorrhoeae (NG) antimicrobial susceptibility trends to azithromycin, cefixime and ceftriaxone were analyzed, from 2009 to 2016, to monitor changing antimicrobial susceptibility concomitant with the change in prescribing practice in 2012 from cefixime, or ceftriaxone, to ceftriaxone plus azithromycin. Patient characteristics predictive to be infected by antibiotic resistant N. gonorrhoeae were estimated. Finally, the protocol for the treatment of gonorrhoea, in comparison with the international guidelines, was also evaluated. Materials and methods Data on NG antimicrobial resistance were obtained from a network of sexually transmitted diseases clinics and other laboratories in 12 cities in Italy. We tested the 1,433 gonococci for antimicrobial susceptibility to azithromycin, cefixime and ceftriaxone using a gradient diffusion method. Logistic-regression methods with cluster robust standard errors were used to investigate the association of resistance categories with demographic and clinical patient characteristics and to assess changes in prescribing practices. To minimize bias due to missing data, all statistical models were fitted to data with forty rounds of multiple imputation, using chained equations. Results The percentage of isolates resistant to cefixime was 17.10% in 2009 and declined up to 1.39% in 2016; at the same time, those resistant to azithromycin was 23.68% in 2009 and 3.00% in 2012. Starting from 2013, azithromycin resistant gonococci tended to increase up to 7.44% in 2016. No ceftriaxone resistant isolates were observed. By multivariate analysis, the men who have sex with women (MSW) and women had a proportional adjusted OR of resistance of 1.25 (95%CI: 0.90; 1.73) and 1.67 (95%CI: 1.16; 2.40), respectively, in comparison with men who have sex with men (MSM). An aOR of resistance of 0.48 (95%CI: 0.21; 1.12) among NG isolated in the pharynx, compared with those isolated in genital sites, was calculated. The proportional aOR of resistance was 0.58 (95%CI: 0.38; 0.89) for presence vs absence of co-infection and 2.00 (95%CI: 1.36; 2.96) for past history vs no history of gonorrhoea.Finally, at least for the period 2013–2016, the older, subjects with anorectal or pharyngeal gonorrhoea infection, subjects with a co-infection, subjects with a previous gonorrhoea infection were not always correctly treated. Conclusions Overall, our findings suggest the shifts in N. gonorrhoeae susceptibility to cefixime and azithromycin in the time frame period. First of all, the increasing rate of azithromycin resistance in 2015–2016 in NG isolated in the country need to be monitor in the future. Finally, extensive information on treatment regimens may be useful to asses treatment adherence particularly for the older subjects, subjects with an anorectal or pharyngeal infection, subjects with a co-infection and subjects with a previous history of gonorrhoea. Gonorrhoea treatment strategy should be based on the evidence obtained by the local antimicrobial surveillance system and data about treatment failures.
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- 2017
20. Rhino-Orbital-Cerebral Mucormycosis after Allogeneic Hematopoietic Stem Cell Transplantation and Isavuconazole Therapeutic Drug Monitoring during Intestinal Graft versus Host Disease
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Giacomo Andreani, Valentina Monticone, Daniela Cilloni, Gian Luca Fadda, Antonio D'Avolio, Marco De Gobbi, Alessandro Morotti, Angelo Guerrasio, Dario Gned, Anna Maria Barbui, Giovanni Cavallo, and Matteo Dragani
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0301 basic medicine ,medicine.medical_specialty ,medicine.medical_treatment ,030106 microbiology ,Liposomal amphotericin B ,Case Report ,Hematopoietic stem cell transplantation ,Therapeutic drug monitoring ,Gastroenterology ,Rhino-orbital-cerebral mucormycosis, Isavuconazole, Liposomal amphotericin B, Therapeutic drug monitoring, Deferasirox ,03 medical and health sciences ,Rhino orbital cerebral mucormycosis ,0302 clinical medicine ,Internal medicine ,otorhinolaryngologic diseases ,Medicine ,Secondary Acute Myeloid Leukemia ,030212 general & internal medicine ,Deferasirox ,Isavuconazole ,Rhino-orbital-cerebral mucormycosis ,medicine.diagnostic_test ,lcsh:RC633-647.5 ,business.industry ,Mucormycosis ,lcsh:Diseases of the blood and blood-forming organs ,Hematology ,medicine.disease ,Infectious Diseases ,Intestinal Graft Versus Host Disease ,business ,Intestinal GVHD ,medicine.drug - Abstract
A diagnosis of rhino-orbital-cerebral mucormycosis was made in a 59-year-old man with a secondary acute myeloid leukemia a few days after hematopoietic stem cell transplantation. Prompt treatment with combined antifungal therapy (liposomal amphotericin B and isavuconazole) followed by a procedure of endoscopic sinus surgery resulted in the resolution of the infection. Therapeutic drug monitoring of isavuconazole was performed during the year of treatment showing an increment of plasma concentrations in correspondence with the improvement of intestinal GvHD, thus suggesting that in this or similar conditions TDM for isavuconazole can be of value. A literature review of cases of rhino-orbital-cerebral and rhino-cerebral mucormycosis in allogeneic hematopoietic stem cell transplant recipients was performed.
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- 2019
21. Moxifloxacin for the treatment of pulmonary tuberculosis in children: A single center experience
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Irene Raffaldi, Silvia Garazzino, Anna Maria Barbui, Pier-Angelo Tovo, Carlo Scolfaro, and Luigi Luccoli
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Pulmonary and Respiratory Medicine ,Psychomotor learning ,Pediatrics ,medicine.medical_specialty ,business.industry ,Medical record ,Arthritis ,medicine.disease ,Single Center ,QT interval ,Regimen ,Tolerability ,Moxifloxacin ,Pediatrics, Perinatology and Child Health ,medicine ,business ,medicine.drug - Abstract
Objective To report our experience on the safety and tolerability of moxifloxacin for treating children affected by pulmonary TB. Study Design Children receiving a moxifloxacin-containing anti-TB regimen were included in the study. Their medical records were revised at the end of follow-up. Methods We describe nine children treated with moxifloxacin for pulmonary TB at Regina Margherita Children's Hospital (Turin, Italy) between 2007 and 2012. Moxifloxacin was administered orally at 10 mg/kg/day once daily (maximum dose = 400 mg/day) following World Health Organization indications. During treatment, patients were systematically assessed for the development of side effects. Results Eight children were considered cured at the end of treatment; one child was lost to follow-up after 3 months of treatment. Two children had side effects during treatment: one developed arthritis of the ankle; the other had liver toxicity, whose relationship with moxifloxacin could not be ruled out. We did not observe any case of QT prolongation, central nervous system disorders, growth defects or gastrointestinal disturbances. Conclusions A moxifloxacin-containing regimen might be considered for the treatment of TB in children, especially for drug-resistant and extensive forms. However, vigilance for possible side effects is recommended, especially if other drugs are concomitantly used. Studies on wider populations are needed to better define the impact of long-term treatments with quinolones on children's growth and psychomotor development and to outline regulatory indications on moxifloxacin use in the pediatric setting. Pediatr Pulmonol. 2014; 49:372–376. © 2013 Wiley Periodicals, Inc.
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- 2013
22. Caulobacter spp: A Rare Pathogen Responsible for Paucisintomatic Persisitant Meningitis in a Glioblastoma Patient
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Silvia Brossa, Rossana Cavallo, Anna Maria Barbui, Federica Penner, Francesco Zenga, and Alessandro Ducati
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0301 basic medicine ,Wound site ,Male ,medicine.medical_specialty ,Complications ,Caulobacter ,030106 microbiology ,Neurosurgery ,Microbial Sensitivity Tests ,Microbiology ,Meningitis, Bacterial ,Glioblastoma ,Meningitis ,Postoperative meningitis ,Aged ,Brain Neoplasms ,Cerebrospinal Fluid ,Gram-Negative Bacterial Infections ,Humans ,Postoperative Complications ,Thienamycins ,Virulence ,Surgery ,Neurology (clinical) ,03 medical and health sciences ,0302 clinical medicine ,Cerebrospinal fluid ,medicine ,Pathogen ,business.industry ,Bacterial ,Meropenem ,medicine.disease ,030220 oncology & carcinogenesis ,business ,Surgical site infection - Abstract
Background Caulobacter spp. are Gram-negative bacteria that have rarely been found to be pathogenic in humans. Case Description This report describes the first case, to our knowledge, of meningitis in an adult patient caused by Caulobacter spp. A 75-year-old man was operated for a glioblastoma with no evident signs of primary infection in the wound site. Eight days after surgery, the patient developed signs and symptoms of meningitis. Caulobacter was then isolated on 3 separate occasions in the patient's cerebrospinal fluid. Thereafter, specific antibiotic therapy began. After 2 weeks of therapy, the patient was discharged with complete resolution of any related symptoms. Conclusions Caulobacter spp. can cause adult meningitis even where there is no evidence of surgical site infection.
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- 2016
23. Louseborne relapsing fever among East African refugees, Italy, 2015
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Filippo Lipani, Andrea Calcagno, Anna Lucchini, Mariaelisabetta Scarvaglieri, Ivano Dal Conte, Valeria Ghisetti, Giovanni Di Perri, Sabrina Audagnotto, Pietro Caramello, Anna Maria Barbui, Silvia Brossa, C. Costa, Sinibaldo Carosella, and Rosanna Balbiano
- Subjects
Microbiology (medical) ,medicine.medical_specialty ,relapsing fever ,Epidemiology ,Refugee ,Expedited ,Relapsing fever ,030231 tropical medicine ,vector-borne infections ,lcsh:Medicine ,Black People ,Borrelia recurrentis ,East Africa ,Italy ,bacteria ,lice ,refugees ,Infectious Diseases ,lcsh:Infectious and parasitic diseases ,03 medical and health sciences ,0302 clinical medicine ,RNA, Ribosomal, 16S ,Louseborne Relapsing Fever among East African Refugees, Italy, 2015 ,East africa ,Medicine ,Humans ,lcsh:RC109-216 ,030212 general & internal medicine ,Louse-Borne Relapsing Fever ,RNA RIBOSOMAL 16S ,biology ,business.industry ,Borrelia ,lcsh:R ,Dispatch ,biology.organism_classification ,medicine.disease ,Immunology ,business ,Disease transmission ,Demography - Abstract
During June 9–September 30, 2015, five cases of louseborne relapsing fever were identified in Turin, Italy. All 5 cases were in young refugees from Somalia, 2 of whom had lived in Italy since 2011. Our report seems to confirm the possibility of local transmission of louse-borne relapsing fever.
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- 2016
24. Diagnosis of invasive fungal infections
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Corrado Girmenia, Anna Maria Barbui, and Giorgio Limerutti
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medicine.medical_specialty ,Immune status ,Hematology ,business.industry ,Diagnostic marker ,General Medicine ,Disease ,Medical decision making ,Diagnostic strategy ,Surgery ,Invasive fungal infections ,Diagnosis ,Underlying disease ,Internal medicine ,medicine ,Infectivology ,Stage (cooking) ,Intensive care medicine ,business - Abstract
A proper diagnostic strategy of invasive fungal infections (IFI) is a very important component in the management of infectious complications in hematological patients. A good diagnostic approach should be adapted to the patient in relation to the underlying disease, stage of disease, localization of infection and immune status. None of the diagnostic markers can be entirely adopted for medical decision making, and sometimes it’s useful to use the combination of several microbiological tests.The diagnosis of IFI must therefore have a multidisciplinary approach that includes clinical suspicion, microbiological results and radiological evidence.
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- 2012
25. Prognostic role of gender in diffuse large B-cell lymphoma treated with rituximab containing regimens: a Fondazione Italiana Linfomi/Grupo de Estudos em Moléstias Onco-Hematológicas retrospective study
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Gianluca Gaidano, Benedetta Puccini, Annalisa Chiappella, Angelo Michele Carella, Caterina Stelitano, Andrea Rossi, Eliana C M Miranda, Marina Cesaretti, Luigi Marcheselli, Carmino Antonio De Souza, Annalisa Guida, Francesco Merli, Stefan Hohaus, Alice Di Rocco, Michele Spina, Massimo Federico, Luigi Rigacci, Stefano Luminari, and Anna Maria Barbui
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Male ,Oncology ,Cancer Research ,Lymphoma ,Antibodies, Monoclonal, Murine-Derived ,International Prognostic Index ,Prednisone ,hemic and lymphatic diseases ,Monoclonal ,Antineoplastic Combined Chemotherapy Protocols ,Adolescent ,Adult ,Aged ,Aged, 80 and over ,Cyclophosphamide ,Doxorubicin ,Female ,Humans ,Lymphoma, Large B-Cell, Diffuse ,Middle Aged ,Neoplasm Staging ,Prognosis ,Retrospective Studies ,Sex Factors ,Treatment Outcome ,Vincristine ,Young Adult ,80 and over ,Medicine ,Univariate analysis ,Hazard ratio ,Hematology ,Diffuse ,Rituximab ,medicine.drug ,Murine-Derived ,medicine.medical_specialty ,Diffuse Large B cell lymphoma ,Antibodies ,Internal medicine ,Large B-Cell ,business.industry ,Retrospective cohort study ,medicine.disease ,Surgery ,Settore MED/15 - MALATTIE DEL SANGUE ,business ,Diffuse large B-cell lymphoma - Abstract
Male gender was recently reported as an adverse prognostic factor in patients with diffuse large B-cell lymphoma (DLBCL) treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone). We conducted a retrospective study of adult patients with DLBCL initially treated with rituximab containing regimens between 2001 and 2007. Patients were identified from the clinical archives of 43 Italian and Brazilian institutions. The principal endpoint was overall survival (OS). One thousand seven hundred and ninety-three patients were fully eligible for the study. Thirty-eight percent, 27%, 22% and 12% of patients had an International Prognostic Index (IPI) score of 0-1, 2, 3 and 4-5, respectively; 53% were males. After a median follow-up of 36 months (1-106), the 5-year OS was 76% (95% confidence interval 74-78%). In univariate analysis, male gender was an adverse prognostic factor with a hazard ratio of 1.52. In multivariate analysis, when adjusted by IPI, again gender maintained its prognostic relevance, showing an independent additive effect. In conclusion, in patients with DLBCL treated with rituximab containing regimens, gender may increase the predictive power of the IPI. Based on these results, given possible differences in blood clearance of rituximab between males and females, the benefit of higher doses of rituximab in males should be explored.
- Published
- 2012
26. Persistent occurrence of serogroup Y/sequence type (ST)-23 complex invasive meningococcal disease among patients aged five to 14 years, Italy, 2007 to 2013
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Iolanda Santino, Caterina Vocale, Raffaele Antonetti, Paola Stefanelli, Laura Daprai, Paola Vacca, Cecilia Fazio, Lucia Rossi, Anna Maria Barbui, Carlo Tascini, Arianna Neri, Giovanna Renna, and Paolo Lanzafame
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Male ,Serotype ,medicine.medical_specialty ,Adolescent ,Genotype ,Epidemiology ,Porins ,Biology ,medicine.disease_cause ,Molecular typing ,Bacterial Proteins ,Virology ,Internal medicine ,medicine ,Humans ,Serotyping ,Child ,meningococcal disease ,Incidence ,Neisseria meningitidis ,Incidence (epidemiology) ,Public Health, Environmental and Occupational Health ,Odds ratio ,Meningococcal Infections ,Molecular Typing ,Italy ,Invasive meningococcal disease ,Child, Preschool ,Female ,Neisseria meningitidis, Serogroup Y ,Acyltransferases ,Bacterial Outer Membrane Proteins - Abstract
In Italy, the incidence of invasive meningococcal disease (IMD) has remained stable since 2007 (around 0.3 cases/100,000 inhabitants). However, as reported for other European countries, an increase of serogroup Y Neisseria meningitidis has been observed. In this study we report IMD cases from 2007 to 2013 in Italy and investigate the clinical and epidemiological features of cases affected by serogroup Y. Molecular characteristics of serogroup Y strains are also described. During the study period, the proportion of IMD cases due to serogroup Y increased, ranging from 2% in 2007 to 17% in 2013 (odds ratio (OR): 8.8), whereby the five to 14 years age group was mostly affected (p lpxL1 gene; however, no associations among lpxL1 mutations, ST and age group were identified. Overall, these findings generate scientific evidence for the use of the quadrivalent meningococcal conjugate vaccine in the five to 14 years age group.
- Published
- 2015
27. Repeated infusions of donor-derived cytokine-induced killer cells in patients relapsing after allogeneic stem cell transplantation: a phase I study
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Ettore Biagi, Anna Grassi, Enrico Pogliani, Giovanna D'Amico, Tiziano Barbui, Alessandro Rambaldi, Martino Introna, Erica Dander, Raewyn Broady, Marta Franceschetti, Josée Golay, Elena Conti, Orietta Spinelli, Gianmaria Borleri, Donatella Baronciani, Andrea Biondi, Matteo Parma, Giuseppe Gaipa, Anna Maria Barbui, Introna, M, Borleri, G, Conti, E, Franceschetti, M, Barbui, A, Broady, R, Dander, E, Gaipa, G, D'Amico, G, Biagi, E, Parma, M, Pogliani, E, Spinelli, O, Baronciani, D, Grassi, A, Golay, J, Barbui, T, Biondi, A, and Rambaldi, A
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Adult ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Chronic myelomonocytic leukemia ,Hematopoietic stem cell transplantation ,Gastroenterology ,CIK, BMT, cell therapy ,Recurrence ,Internal medicine ,medicine ,Humans ,Transplantation, Homologous ,Salvage Therapy ,Chemotherapy ,Cytokine-induced killer cell ,business.industry ,Hematopoietic Stem Cell Transplantation ,Hematology ,Middle Aged ,medicine.disease ,Donor Lymphocytes ,Killer Cells, Natural ,Transplantation ,Haematopoiesis ,Leukemia ,Hematologic Neoplasms ,Lymphocyte Transfusion ,Immunology ,Cytokines ,Female ,business - Abstract
BACKGROUND AND OBJECTIVES: Cytokine-induced killer (CIK) cells have shown anti-leukemic activity and little graft-versus-host disease (GVHD) in several animal models. The safety of these cells in autologous settings has been shown. We performed a phase I study of allogeneic (donor's) CIK cells in patients relapsing after allogeneic haematopoietic stem cell transplantation (HSCT). DESIGN AND METHODS: Eleven patients with acute myelogenous leukemia (n=4), Hodgkin's disease (n=3), chronic myelomonocytic leukemia, (n=1), pre-B acute lymphoblastic leukemia (n=1) and myelodysplasia (n=2), all of whom had relapsed after sibling (n=6) or matched unrelated donor (n=5) HSCT, entered this study. RESULTS: Before CIK administration, six patients had received other salvage treatments including chemotherapy (n=5), radiotherapy (n=1) and unmanipulated donor lymphocytes (n=6) without any significant tumor response. The median number of CIK infusions was two (range 1-7) and the median number of total CIK cells was 12.4x106/kg (range 7.2-87.4). The infusions were well tolerated and no acute or late infusion-related reactions were recorded. Acute GVHD (grade I and II) was observed in four patients, 30 days after the last CIK infusion, and progressed into extensive chronic GVHD in two cases. Disease progression and death occurred in six patients. One patient had stable disease, one had hematologic improvement and three achieved complete responses. INTERPRETATION AND CONCLUSIONS: This study shows that the production of allogeneic CIK cells is feasible under clinical-grade conditions, well tolerated and may contribute to clinical responses.
- Published
- 2007
28. Primary treatment response rather than front line stem cell transplantation is crucial for long term outcome of peripheral T-cell lymphomas
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Giuseppe Gritti, Anna De Grassi, Caterina Micò, Alessandro Rambaldi, Cristina Boschini, Federica Delaini, Rosangela Trezzi, Andrea Rossi, Andrea Gianatti, Anna Maria Barbui, and Alessandra Algarotti
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Oncology ,Adult ,Male ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,lcsh:Medicine ,Hematopoietic stem cell transplantation ,Single Center ,Young Adult ,Internal medicine ,hemic and lymphatic diseases ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,lcsh:Science ,Survival analysis ,Aged ,Retrospective Studies ,Aged, 80 and over ,Chemotherapy ,Multidisciplinary ,business.industry ,lcsh:R ,Hematopoietic Stem Cell Transplantation ,Lymphoma, T-Cell, Peripheral ,Retrospective cohort study ,Middle Aged ,medicine.disease ,Prognosis ,Combined Modality Therapy ,Survival Analysis ,Peripheral T-cell lymphoma ,Surgery ,Transplantation ,Treatment Outcome ,Cohort ,Female ,lcsh:Q ,business ,Research Article - Abstract
Outcome of systemic peripheral T-cell lymphomas (PTCL) is unsatisfactory and no controlled clinical study guides the therapy. Phase II studies suggest to consolidate response achieved after front-line treatment with stem cell transplant (SCT). We retrospectively evaluate the impact of front-line SCT consolidation in a single Center cohort of 209 patients treated during the last two decades. Median age was 49 years (range 15-85) with a prevalence of male sex (61%), advanced stage (68%) while IPI was >2 in 44%. Primary treatment was MACOP-B (39%) CHO(E)P (39%), intensive regimens (18%) or others (4%). Complete response to primary treatment (i.e. before SCT) was 60% (5% partial remission). Forty-four patients further proceeded to SCT while 92 did not receive consolidation. Outcome of primary responders was good, with a 3-year overall survival of 74% (82% in ALCL ALK+ and 69% for the other histologies). By multivariate analysis a better overall survival was significantly associated with IPI
- Published
- 2015
29. Usefulness of Sequential Aspergillus galactomannan Antigen Detection Combined With Early Radiologic Evaluation for Diagnosis of Invasive Pulmonary Aspergillosis in Patients Undergoing Allogeneic Stem Cell Transplantation
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Francesco Locatelli, Giorgio Limerutti, Alessandro Busca, Roberto Serra, Anna Maria Barbui, Michele Falda, and Daniela Libertucci
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Adult ,Lung Diseases ,medicine.medical_specialty ,Antigens, Fungal ,Gastroenterology ,Mannans ,Galactomannan ,chemistry.chemical_compound ,Neoplasms ,Internal medicine ,Amphotericin B ,medicine ,Aspergillosis ,Humans ,Transplantation, Homologous ,Fever of unknown origin ,skin and connective tissue diseases ,Mycosis ,Aged ,Retrospective Studies ,Cause of death ,Transplantation ,business.industry ,Respiratory disease ,Galactose ,Middle Aged ,bacterial infections and mycoses ,medicine.disease ,Surgery ,Aspergillus ,Treatment Outcome ,chemistry ,Hematologic Neoplasms ,Caspofungin ,business ,Stem Cell Transplantation ,medicine.drug - Abstract
Background Early diagnosis of invasive pulmonary aspergillosis (IPA) is important as prompt treatment with antifungal drugs may increase patient survival. Our study investigated the efficiency of routine testing of the Aspergillus galactomannan antigen (AGA) test in combination with chest CT scans for IPA diagnosis. Patients and Methods From February 2002 to June 2004, 74 hemato-oncologic patients undergoing allogeneic stem cell transplantation were prospectively studied with serum AGA twice weekly from admission until death or discharge and weekly afterward when possible. Chest CT scans were performed when fever of unknown origin had lasted beyond 3 days of antibacterial therapy. Results Seven patients were classified with possible IPA and two patients, proven IPA. Fourteen patients showed positive results for AGA (OD index ≥ 1.0 on two subsequent sera). The sensitivity and specificity of the test were 100% and 93%, respectively; the positive and negative predictive values were 64% and 100%, respectively. All patients with possible/proven IPA showed abnormal CT signs; in four cases, imaging signs followed AGA positivity (median 5 days), whereas in five cases they preceded serologic positivity (median, 8 days). In the nine patients with IPA, antifungal therapy was promptly instituted, including lipid formulations of amphotericin B (n = 5) or caspofungin (n = 4). In only two of the nine patients (22%) with IPA, the primary cause of death was fungal infection. Conclusions The combination of AGA detection and early chest CT scans might be considered useful tools to detect minimal changes of IPA. Based on these findings, aggressive antifungal therapy should be initiated.
- Published
- 2006
30. Intermediate-dose melphalan improves survival of myeloma patients aged 50 to 70: results of a randomized controlled trial
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Patrizia Falco, Cecilia Rus, Mariella Grasso, Vito Michele Lauta, Maria Teresa Petrucci, Angelo Michele Carella, Martina Nunzi, Antonio Capaldi, Tommaso Caravita, Anna Maria Barbui, Federica Cavallo, Fausto Rossini, Pellegrino Musto, Vincenzo Callea, Alessandra Bertola, Franco Mandelli, Massimo Massaia, Giovannino Ciccone, Mario Boccadoro, Sara Bringhen, Antonio Palumbo, Tommasina Guglielmelli, Franco Dammacco, Anna Marina Liberati, Patrizia Pregno, Cesare Bergonzi, Enrico Pogliani, Palumbo, A, Bringhen, S, Petrucci, M, Musto, P, Rossini, F, Nunzi, M, Lauta, V, Bergonzi, C, Barbui, A, Caravita, T, Capaldi, A, Pregno, P, Guglielmelli, T, Grasso, M, Callea, V, Bertola, A, Cavallo, F, Falco, P, Rus, C, Massaia, M, Mandelli, F, Carella, A, Pogliani, E, Liberati, A, Dammacco, F, Ciccone, G, and Boccadoro, M
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Male ,Melphalan ,medicine.medical_treatment ,DIAGNOSED MULTIPLE-MYELOMA ,COMBINATION CHEMOTHERAPY ,Salvage therapy ,THERAPY ,Biochemistry ,Gastroenterology ,MED/15 - MALATTIE DEL SANGUE ,Prednisone ,FINAL ANALYSIS ,Medicine ,Multiple myeloma ,Standard treatment ,Hematology ,Middle Aged ,Chemotherapy regimen ,Treatment Outcome ,STEM-CELL TRANSPLANTATION ,AUTOLOGOUS TRANSPLANTATION ,INTENSIVE MELPHALAN ,TANDEM TRANSPLANTS ,STAGING SYSTEM ,200 MG/M(2) ,Female ,Survival Analysi ,Multiple Myeloma ,Human ,medicine.drug ,medicine.medical_specialty ,Immunology ,Disease-Free Survival ,Follow-Up Studie ,Internal medicine ,Humans ,Antineoplastic Agents, Alkylating ,Aged ,Salvage Therapy ,Chemotherapy ,business.industry ,Cell Biology ,medicine.disease ,Survival Analysis ,Surgery ,Regimen ,business ,Follow-Up Studies - Abstract
High-dose therapy is an effective standard treatment for multiple myeloma patients. Evidence that intermediate-dose therapy improves survival is limited. At diagnosis, about 70% of patients are older than 65. Intermediate-dose regimen is very well tolerated in older patients. In a multicenter study, 194 patients were randomized to receive at diagnosis either conventional chemotherapy (6 courses of oral melphalan and prednisone [MP]) or intermediate-dose therapy (2 courses of melphalan at 100 mg/m(2) [MEL100]) with stem cell support. Response rate was higher after MEL100. Near-complete remission (nCR) was 6% after MP and 25% after MEL100 (P = .0002). At 3 years, MEL100 increased event-free survival (EFS) from 16% to 37% and overall survival (OS) from 62% to 77% (P < .001). Similar results were observed in patients aged 65 to 70: nCR was 8% after MP and 25% after MEL100 (P = .05); at 3 years, MEL100 improved EFS from 18% to 31% (P = .01) and OS from 58% to 73% (P = .01). Patients aged 65 to 70 had a median OS of 37.2 months (MP) versus 58 months (MEL100). Intermediate-dose melphalan improves response rate, EFS, and OS in myeloma patients, specifically in those aged 65 to 70. It constitutes a more effective first-line regimen than standard treatment for elderly patients.
- Published
- 2004
31. Infectious complications following nonmyeloablative allogeneic hematopoietic stem cell transplantation
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R. Serra, Michele Falda, Daniela Maria Cirillo, Valeria Ghisetti, Alessandro Busca, Ernesta Audisio, Anna Maria Barbui, and Francesco Locatelli
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Human cytomegalovirus ,Transplantation ,medicine.medical_specialty ,Leukopenia ,business.industry ,medicine.medical_treatment ,Hematopoietic stem cell transplantation ,Neutropenia ,medicine.disease ,medicine.disease_cause ,Gastroenterology ,Herpesviridae ,Surgery ,Infectious Diseases ,Internal medicine ,Bacteremia ,medicine ,medicine.symptom ,business ,Mycosis ,Cause of death - Abstract
Nonmyeloablative hematopoietic stem cell transplantation (NST) has been explored in hematological malignancies and solid tumors in an attempt to minimize treatment-related toxicity. Whether this approach is associated with reduced risk of infectious complications is unclear. The aim of the current study was to evaluate the infectious complications in a series of 32 consecutive adult patients who received NSTat our institution. Peripheral blood stem cell grafts (n = 30) or marrow grafts (n = 2) were infused from human leukocyte antibody (HLA)-matched sibling (n = 30), partially matched related (n = 1), or unrelated (n = 1) donors. Neutropenia developed in two-thirds of patients and lasted 16 days. Acute graft-versus-host disease (GVHD) grade II to IV was observed in 25% of patients, whereas 35% of patients had signs of extensive chronic GVHD. Twenty-two patients (69%) had at least one significant infectious episode. Bacteremia occurred in 19% of patients (n = 5 gram-positive, n = 1 gram-negative microorganisms). Cytomegalovirus (CMV) infection was observed in 10 out of 28 (36%) evaluable patients; 4 of these had recurrent or persistent CMVantigenemia requiring a second-line treatment, but eventually the viremia cleared. No patients experienced CMV disease. Fungal infections were documented in five (16%) patients, comprising invasive fungal infections in two cases and mucosal fungal infections in three. Four patients died of transplant-related causes, and three of these died before day +100. Infection was considered the primary cause of death in one patient (pulmonary aspergillosis) and contributed to death in another two. The actuarial probability of nonrelapse mortality at 100 days was 10% (95% confidence interval, 3-26%). Our preliminary results suggest that NST is associated to a low incidence of bacteremia or fungal and viral infections. Whether these findings would translate into an improved overall survival needs to be confirmed in larger prospective studies.
- Published
- 2003
32. Negative selection of peripheral blood stem cells to support a tandem autologous transplantation programme in multiple myeloma
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Nadia Belli, Gianmaria Borleri, Giovanna Gritti, Anna Maria Barbui, Monica Galli, Gianpietro Dotti, Piera Viero, Tiziano Barbui, Piermario Bellavita, Alessandro Rambaldi, and B Comotti
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Oncology ,medicine.medical_specialty ,medicine.medical_treatment ,CD34 ,Hematology ,Hematopoietic stem cell transplantation ,Biology ,medicine.disease ,Debulking ,Minimal residual disease ,Internal medicine ,Immunology ,medicine ,Autologous transplantation ,Stem cell ,Survival rate ,Multiple myeloma - Abstract
We recently described a two-step negative selection procedure whereby peripheral blood stem cells (PBSCs) were efficiently purged of contaminating neoplastic cells by a combination of monoclonal antibodies. Here, we report 60 newly diagnosed multiple myeloma (MM) patients treated with a double transplant programme and randomized to receive either unmanipulated or in vitro purged PBSCs. We demonstrated that this technique is feasible and safe without significant loss of either CD34+ or CD3+ cells. Haematological engraftment and immunological reconstitution were rapid without treatment-related mortality. Using polymerase chain reaction (PCR), we compared the level of minimal residual disease (MRD) in PBSC before and after in vitro purging and in vivo after transplant. A median of one tumour cell per 10(2) normal cells (range 10(1)-10(5)) was seen in the unmanipulated aphereses with a 3-4 log reduction after manipulation in vitro. However, despite this tumour debulking, all patients remained PCR positive in vivo. At 3 years, the estimated event-free survival was 40% in the control arm and 72% in the experimental arm (P = 0.05), whereas the estimated overall survival was 83% in both arms. This suggests that autologous transplantation using efficiently purged PBSCs can be performed safely, but confirms the need for innovative protocols for MRD eradication in vivo.
- Published
- 2002
33. Rate of Primary Refractory Disease in B and T-Cell Non-Hodgkin’s Lymphoma: Correlation with Long-Term Survival
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Federica Delaini, Marco Ruella, Daniele Caracciolo, Cristina Boschini, Roberto Passera, Alessandro Rambaldi, Angela Gueli, Riccardo Bruna, Daniela Gottardi, Andrea Rossi, Giuseppe Gritti, Corrado Tarella, and Anna Maria Barbui
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Oncology ,Male ,medicine.medical_treatment ,lcsh:Medicine ,CHOP ,Follicular lymphoma ,hemic and lymphatic diseases ,lcsh:Science ,Non-Hodgkin lymphoma ,Aged, 80 and over ,Multidisciplinary ,Hematology ,Diffuse large B-cell lymphoma ,Middle Aged ,Rituximab ,Lymphomas ,Female ,medicine.drug ,Research Article ,Adult ,medicine.medical_specialty ,Lymphoma, B-Cell ,Adolescent ,Antineoplastic Agents ,Lymphoma, T-Cell ,Young Adult ,Refractory ,Internal medicine ,medicine ,Humans ,Survival analysis ,Aged ,Retrospective Studies ,Medicine and health sciences ,Chemotherapy ,business.industry ,lcsh:R ,Peripheral T-cell lymphoma ,medicine.disease ,Long-Term Care ,Survival Analysis ,Non-Hodgkin's lymphoma ,Lymphoma ,Health Care ,Drug Resistance, Neoplasm ,Immunology ,Hematologic cancers and related disorders ,Multivariate Analysis ,lcsh:Q ,business ,Progressive disease - Abstract
BACKGROUND: Primary refractory disease is a main challenge in the management of non-Hodgkin's Lymphoma (NHL). This survey was performed to define the rate of refractory disease to first-line therapy in B and T-cell NHL subtypes and the long-term survival of primary refractory compared to primary responsive patients. METHODS: Medical records were reviewed of 3,106 patients who had undergone primary treatment for NHL between 1982 and 2012, at the Hematology Centers of Torino and Bergamo, Italy. Primary treatment included CHOP or CHOP-like regimens (63.2%), intensive therapy with autograft (16.9%), or other therapies (19.9%). Among B-cell NHL, 1,356 (47.8%) received first-line chemotherapy with rituximab. Refractory disease was defined as stable/progressive disease, or transient response with disease progression within six months. RESULTS: Overall, 690 (22.2%) patients showed primary refractory disease, with a higher incidence amongst T-cell compared to B-cell NHL (41.9% vs. 20.5%, respectively, p
- Published
- 2014
34. Genetic PTX3 deficiency and aspergillosis in stem-cell transplantation
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Fernando Rodrigues, Luigina Romani, Alessandro Busca, Alberto Mantovani, Antonio Inforzato, Johan Maertens, Alain S. Bell, Giovanni Salvatori, Agostinho Carvalho, João F. Lacerda, Oliver Kurzai, Morena Caira, Pedro Santos e Sousa, Cristina Cunha, Livio Pagano, Bruno Almeida, Elisa Barbati, Anna Maria Barbui, Matthias Grube, Leonardo Potenza, Andrea Velardi, Franco Aversa, Jürgen Löffler, Mario Luppi, and Universidade do Minho
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Oncology ,Adult ,Male ,medicine.medical_specialty ,Neutrophils ,medicine.medical_treatment ,Hematopoietic stem cell transplantation ,Aspergillosis ,Internal medicine ,medicine ,Humans ,Innate ,Cumulative incidence ,Genetic Predisposition to Disease ,Polymorphism ,Science & Technology ,biology ,business.industry ,Hazard ratio ,C-reactive protein ,Immunity ,Hematopoietic Stem Cell Transplantation ,General Medicine ,Odds ratio ,Single Nucleotide ,medicine.disease ,3. Good health ,pendraxine ,Transplantation ,Serum Amyloid P-Component ,Settore MED/15 - MALATTIE DEL SANGUE ,C-Reactive Protein ,allotransplantation ,Female ,Haplotypes ,Immunity, Innate ,Polymorphism, Single Nucleotide ,Immunology ,biology.protein ,business ,Allotransplantation - Abstract
BACKGROUND: The soluble pattern-recognition receptor known as long pentraxin 3 (PTX3) has a nonredundant role in antifungal immunity. The contribution of single-nucleotide polymorphisms (SNPs) in PTX3 to the development of invasive aspergillosis is unknown. METHODS: We screened an initial cohort of 268 patients undergoing hematopoietic stem-cell transplantation (HSCT) and their donors for PTX3 SNPs modifying the risk of invasive aspergillosis. The analysis was also performed in a multicenter study involving 107 patients with invasive aspergillosis and 223 matched controls. The functional consequences of PTX3 SNPs were investigated in vitro and in lung specimens from transplant recipients. RESULTS: Receipt of a transplant from a donor with a homozygous haplotype (h2/h2) in PTX3 was associated with an increased risk of infection, in both the discovery study (cumulative incidence, 37% vs. 15%; adjusted hazard ratio, 3.08; P=0.003) and the confirmation study (adjusted odds ratio, 2.78; P=0.03), as well as with defective expression of PTX3. Functionally, PTX3 deficiency in h2/h2 neutrophils, presumably due to messenger RNA instability, led to impaired phagocytosis and clearance of the fungus. CONCLUSIONS: Genetic deficiency of PTX3 affects the antifungal capacity of neutrophils and may contribute to the risk of invasive aspergillosis in patients treated (Funded by the European Society of Clinical Microbiology and Infectious Diseases and others) .with HSCT., Supported by grants from the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) (to Dr. Carvalho); the German Ministry for Education and Science (03Z2JN21, to Dr. Kurzai); the European Commission (FP7-HEALTH-2009-260338, to Dr. Romani; FP7-HEALTH-2011-280873, to Dr. Mantovani), the European Research Council (ERC-2008-AdG-233417, to Dr. Mantovani; ERC-2011-AdG-293714, to Dr. Romani), Associazione Italiana per la Ricerca sul Cancro (99629, to Dr. Mantovani); and Fundacao para a Ciencia e Tecnologia, Portugal (SFRH/BPD/46292/2008, to Dr. Carvalho; SFRH/BD/65962/2009, to Dr. Cunha; and SFRH/BPD/70783/2010, to Dr. Almeida).
- Published
- 2014
35. Tenascin-C Is Highly Expressed in T-Cell Non-Hodgkin Lymphomas and Represents an Attractive Target for Radioimmunotherapy
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Cristina Boschini, Fiorella Petronzelli, Giuseppe Gritti, Andrea Gianatti, Alessandro Rambaldi, Anna Maria Barbui, Riccardo L. Rossi, Rosangela Trezzi, and Andrea Rossi
- Subjects
Mycosis fungoides ,Pathology ,medicine.medical_specialty ,CD30 ,medicine.medical_treatment ,Immunology ,Tenascin C ,Cell Biology ,Hematology ,Biology ,medicine.disease ,Biochemistry ,Lymphoma ,hemic and lymphatic diseases ,Radioimmunotherapy ,medicine ,biology.protein ,Immunohistochemistry ,Anaplastic large-cell lymphoma ,Tenatumomab - Abstract
Introduction: Tenascins are a family of large glycoproteins present in extracellular matrix, overexpressed in tumors compared to healthy tissues. Tenatumomab (ST2146) is an anti tenascin-C monoclonal antibody that is currently under development for radio immunotherapy (RIT) in tenascin-C expressing cancer. T-cell non-Hodgkin lymphomas (T-NHL) are a heterogeneous and rare group of poor prognosis malignancies lacking of standard treatments. Aim of the study was to evaluate the expression of tenascin-C in a cohort of T-NHL. Material and Methods: Under an IRB-approved protocol, 100 patients with a diagnosis of T-NHL in charge at the Hematology Unit of "Papa Giovanni XXII" Hospital were included in the study. Paraffin-embedded tumor samples were investigated using standard immunohistochemistry (IHC) for tenascin-C expression using tenatumomab antibody. Slides were assessed by two independent investigators. Staining was scored using the four different levels "no staining", "weak", "moderate" and "strong" (0-3). A grading system was used to express the proportion of involved areas in each case, as follows: 0 (0% to 25%), 1 (26% to 50%), 2 (51% to 75%), 3 (76% to 100%). Pattern of expression (stromal, vascular and/or cytoplasmic) was as well recorded. Tenascin C gene expression data were extracted from publicly available datasets. Association among variables was assessed with Chi square or Fisher exact test. Results:Of the 100 patients evaluated, 75 cases were peripheral T-NHL (PTCL) and 25 cutaneous T-NHL (CTCL). Specific diagnosis was, anaplastic large cell lymphoma (ALCL) ALK negative (n=21) or positive (n=19), PTCL-not otherwise specified (NOS, n=20), mycosis fungoides (n=13), angioimmunoblastic T-cell lymphoma (AITL, n=9), CD30+ primary cutaneous T-NHL (n=6) and other subtypes (n=12). Tenatumomab revealed the expression of tenascin-C in all the patients, with a staining that was weak, moderate and strong in 21, 51 and 28 of the cases. There was no significant different distribution among histologies (P=0.334). A high (>50%, grade 2-3) proportion of involved areas in pathologic samples were shown in half of the patients and this proportion was higher in ALCL ALK- (81%), AITL (78%) and ALCL ALK+ (58%) while was lower for PTCL NOS (30%) and CTCL (24%) (P=0.0019). A stromal pattern of expression was present in all the cases, vasculature was stained in 47 patients while in 21 tenascin-C was as well cytoplasmic. Vascular pattern was revealed in 56% of PTCL and 20% of CTCL (P=0.0018). To further evaluate the presence of tenascin C in T-NHL, gene expression datasets from published reports were retrieved and expression values of tenascin-C gene were extracted. Significant overexpression was present in T-NHL compared to normal tissues in both of the two considered datasets (Piccaluga et al., 2007 and Iqbal et al., 2010). Conclusions: Tenatumomab revealedthat tenascin-C is uniformly present in T-NHL with a high proportion of cases showing a strong and diffuse expression. Thus, tenascin-C represent an attractive target for RIT in this category of poor prognosis rare diseases. Disclosures Petronzelli: Sigma Tau S.p.A: Employment.
- Published
- 2016
36. Prevention of invasive fungal infections in patients with acute myeloid leukaemia: results of a single centre retrospective observational study with the use of posaconazole versus conventional mould-active azoles
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Alessandro Busca, Bernardino Allione, Sara Manetta, Chiara Frairia, Semra Aydin, Filippo Marmont, Ernesta Audisio, Umberto Vitolo, Stefano D'Ardia, Anna Maria Barbui, Michele Falda, Clara Pecoraro, Francesco Giuseppe De Rosa, and Chiara Dellacasa
- Subjects
Oral ,Myeloid ,Adult ,Male ,medicine.medical_specialty ,Posaconazole ,Antifungal Agents ,Adolescent ,Itraconazole ,Administration, Oral ,Aged ,Cohort Studies ,Female ,Humans ,Leukemia, Myeloid, Acute ,Middle Aged ,Mycoses ,Retrospective Studies ,Triazoles ,Young Adult ,Acute ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Pharmacology (medical) ,Young adult ,Intensive care medicine ,Pharmacology ,Leukemia ,business.industry ,Induction chemotherapy ,Retrospective cohort study ,Transplantation ,surgical procedures, operative ,Infectious Diseases ,Oncology ,Administration ,Myeloid leukaemia ,business ,medicine.drug ,Cohort study - Abstract
Patients with acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) during induction chemotherapy and those receiving allogeneic stem-cell transplantation (HSCT) are at high risk of inva...
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- 2013
37. The lymphocyte to monocyte ratio improves the IPI-risk definition of diffuse large B-cell lymphoma when rituximab is added to chemotherapy
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Liliana Devizzi, Federica Delaini, Daniele Caracciolo, Alberto De Crescenzo, Cristina Boschini, Alessandro Rambaldi, Angela Gueli, Alessandro Massimo Gianni, Elena Oldani, Marco Ladetto, Anna Maria Barbui, Caterina Patti, Roberto Passera, Andrea Rossi, Corrado Tarella, and Giuseppe Gritti
- Subjects
Oncology ,Male ,Pathology ,medicine.medical_treatment ,Kaplan-Meier Estimate ,Severity of Illness Index ,Monocytes ,Antibodies, Monoclonal, Murine-Derived ,Leukocyte Count ,International Prognostic Index ,hemic and lymphatic diseases ,Antineoplastic Combined Chemotherapy Protocols ,Medicine ,Stage (cooking) ,Aged, 80 and over ,Hematology ,Middle Aged ,Prognosis ,Combined Modality Therapy ,Treatment Outcome ,Vincristine ,Rituximab ,Female ,Lymphoma, Large B-Cell, Diffuse ,medicine.drug ,Adult ,medicine.medical_specialty ,Adolescent ,Young Adult ,Internal medicine ,Biomarkers, Tumor ,Humans ,Lymphocyte Count ,Cyclophosphamide ,Aged ,Retrospective Studies ,Chemotherapy ,Performance status ,L-Lactate Dehydrogenase ,business.industry ,medicine.disease ,Lymphoma ,Radiation therapy ,ROC Curve ,Doxorubicin ,Prednisone ,Radiotherapy, Adjuvant ,business ,Diffuse large B-cell lymphoma ,Follow-Up Studies - Abstract
The peripheral blood lymphocyte to monocyte ratio (LMR) at diagnosis can be clinically relevant in patients with diffuse large B-cell lymphoma (DLBCL). We reviewed the outcome of 1,057 DLBCL patients followed from 1984 to 2012 at four centers. LMR was analyzed as a clinical biomarker by receiver-operating characteristic (ROC) analysis and Harrell's C-statistics. Patients were characterized by a median age of 61 years, International Prognostic Index (IPI) score of >2 in 39%, and were treated with a rituximab-containing chemotherapy in 66%. LMR proved strongly predictive for survival in patients treated with rituximab-based programs, but not in those receiving chemotherapy alone. Additionally, an LMR value of ≤2.6 (as determined by ROC analysis) was associated with a worst performance status, a higher lactate dehydrogenase (LDH) level, an advanced clinical stage, and a higher IPI score (P = 0.000). In patients treated with rituximab-supplemented chemotherapy programs, an LMR value of
- Published
- 2013
38. SIMIFF study: Italian fungal registry of mold infections in hematological and non-hematological patients
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Vittorio Sambri, Teresa Santantonio, Livio Pagano, Stefano Andreoni, Filomena Puntillo, F. Di Bernardo, C Coretti, Claudio Viscoli, Maurizio Sanguinetti, Patrizia Pecile, Lucia Pitzurra, O De Giglio, Giorgina Specchia, Malgorzata Mikulska, Domenico Martinelli, G. Lombardi, Anna Candoni, Giuseppina Caggiano, Ercole Concia, G Lovero, Mario Delia, Domenico D'Antonio, R. Masciari, Claudio Farina, Maria Teresa Montagna, Morena Caira, Natalia Maximova, Anna Maria Barbui, G. Lo Cascio, Salvatore Massimo Oliveri, Mario Venditti, Francesco Barchiesi, Pierluigi Viale, M. T. Montagna, G. Lovero, C. Coretti, D. Martinelli, M. Delia, O. D. Giglio, M. Caira, F. Puntillo, D. D'Antonio, M. Venditti, V. Sambri, F. D. Bernardo, A. Barbui, G. L. Cascio, E. Concia, M. Mikulska, C. Viscoli, N. Maximova, A. Candoni, S. Oliveri, G. Lombardi, L. Pitzurra, M. Sanguinetti, R. Masciari, T. Santantonio, S. Andreoni, F. Barchiesi, P. Pecile, C. Farina, P. Viale, G. Specchia, G. Caggiano, and L. Pagano
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Male ,Microbiological Techniques ,Hematological patients ,Prevalence ,Aspergillosis ,80 and over, Diagnostic Test ,Non-hematological patients ,Epidemiology ,Filamentous fungal infections ,Italian survey ,80 and over ,aspergillosis ,Prospective Studies ,Registries ,Prospective cohort study ,Aged, 80 and over ,General Medicine ,Middle Aged ,Hospitals ,Infectious Diseases ,Treatment Outcome ,Italy ,Hematologic Neoplasms ,Female ,Microbiology (medical) ,Adult ,medicine.medical_specialty ,methods, Middle Aged, Mycose ,Adolescent ,Neutropenia ,Clinical and Epidemiological Study ,Young Adult ,Pharmacotherapy ,Diagnostic Tests ,Internal medicine ,medicine ,Humans ,Routine, Female, Fungi ,Routine ,epidemiology, Male, Microbiological Technique ,Aged ,complications, Hospitals, Humans, Italy ,classification/isolation /&/ purification, Hematologic Neoplasm ,business.industry ,Diagnostic Tests, Routine ,fungal infection ,Mucormycosis ,Fungi ,hematological patients ,italian survey ,hematological and non-hematological patients ,non-hematological patients ,filamentous fungal infections ,italy ,fungal infections ,medicine.disease ,Survival Analysis ,diagnosis/epidemiology/microbiology/mortality, Prospective Studies, Registries, Survival Analysis, Treatment Outcome, Young Adult ,Settore MED/15 - MALATTIE DEL SANGUE ,Mycoses ,Adolescent, Adult, Aged, Aged ,Immunology ,Etiology ,business - Abstract
Purpose We compared the risk factors, the diagnostic tools and the outcome of filamentous fungal infections (FFIs) in hematological patients (HAEs) and non-hematological patients (non-HAEs). Methods Prospective surveillance (2009–2011) of proven and probable FFIs was implemented in 23 Italian hospitals. Results Out of 232 FFIs, 113 occurred in HAEs and 119 in non-HAEs. The most frequent infection was invasive aspergillosis (76.1 % for HAEs, 56.3 % for non-HAEs), and the localization was principally pulmonary (83.2 % for HAEs, 74.8 % for non-HAEs). Neutropenia was a risk factor for 89.4 % HAEs; the main underlying condition was corticosteroid treatment (52.9 %) for non-HAEs. The distribution of proven and probable FFIs was different in the two groups: proven FFIs occurred more frequently in non-HAEs, whereas probable FFIs were correlated with the HAEs. The sensitivity of the galactomannan assay was higher for HAEs than for non-HAEs (95.3 vs. 48.1 %). The overall mortality rate was 44.2 % among the HAEs and 35.3 % among the non-HAEs. The etiology influenced the patient outcomes: mucormycosis was associated with a high mortality rate (57.1 % for HAEs, 77.8 % for non-HAEs). Conclusions The epidemiological and clinical data for FFIs were not identical in the HAEs and non-HAEs. The differences should be considered to improve the management of FFIs according to the patients’ setting.
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- 2013
39. Erratum to: MagicplexTM Sepsis Real-Time test to improve bloodstream infection diagnostics in children
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Carmelina Calitri, Silvia Brossa, Anna Maria Barbui, Pier-Angelo Tovo, Carlo Scolfaro, Silvia Garazzino, Sara Colombo, and Marco Denina
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0301 basic medicine ,medicine.medical_specialty ,business.industry ,Published Erratum ,MEDLINE ,medicine.disease ,Test (assessment) ,Sepsis ,03 medical and health sciences ,030104 developmental biology ,Bloodstream infection ,Pediatrics, Perinatology and Child Health ,medicine ,Intensive care medicine ,business - Published
- 2016
40. Impact of Comorbidity Burden in Treatment and Outcome of Older Patients with Indolent Non-Hodgkin Lymphomas
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Andrea Rossi, Paola Stefanoni, Giuseppe Gritti, Cristina Boschini, Alessandro Rambaldi, and Anna Maria Barbui
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medicine.medical_specialty ,Chlorambucil ,business.industry ,Proportional hazards model ,Immunology ,Cell Biology ,Hematology ,CHOP ,medicine.disease ,Biochemistry ,Comorbidity ,Surgery ,Exact test ,Internal medicine ,Cohort ,medicine ,Rituximab ,Progression-free survival ,business ,medicine.drug - Abstract
Introduction: Despite the growing interest about the optimal treatment of older patients with cancer, only few data are available for indolent non-Hodgkin lymphomas (NHL). Aim of the study was to evaluate the impact of comorbidities on treatment choice and survival in a cohort of older indolent NHL patients. Material and Methods: In an IRB-approved protocol, we reviewed the records of 742 patients with age≥60 years diagnosed of indolent NHL between January 1990 to December 2012 at our Center. Patients not receiving a treatment (N=177) and those treated with local therapy for stage I disease (N=138) were excluded from the analysis. Clinical information was gathered from the electronic charts, comorbidity was assessed using the cumulative illness rating scale-geriatrics (CIRS-G). Association between categorical variables was assessed with chi-squared test or Fisher's exact test. Overall survival (OS) and progression free survival (PFS) were the end-point of the study, defined respectively as the time from diagnosis to death or last visit and time to death or relapse/progression, which one occurred first, or last visit. Differences among groups in terms of OS and PFS were verified with both log-rank test in univariate setting and Cox proportional hazard model in multivariable analysis. Results: A total of 427 patients with a median follow-up of 4.04 years (range 0.1-20) were evaluated in the study. Patients were diagnosed as follicular NHL (n=207), marginal zone NHL (MALT N=93, splenic N=32, nodal N=38) and lymphocytic NHL (N=57). Median age was 69.9 years (range 60-93.9) with 11% of the patients older than 80 years, M/F ratio was 0.81. At least one comorbidity were present in 363 patients (85%), CIRS total score 2 was recorded in 161 patients (38%). At least one score 3-4 comorbidity was present in 176 (41%) and the most frequent categories involved were vascular (N=191, 45%), metabolic/endocrine/breast (N=102, 24%) and heart (N=71, 17%). Patients were further categorized in fit (N=224, 52%) or unfit/frail (N=203, 48%) on the basis of age (>80 years) and CIRS parameters (>1 grade 3-4 or >4 grade 2 categories). Patients categorized according these comorbidity scores were balanced for main clinical factors, with the exception of age. First line treatment was CHOP/CHOP-like (N=179, 42%), CVP (N=112, 26%), chlorambucil (N=104, 24%) or other (N=32, 7%) with the addition of rituximab in 53% of the cases. Severity index>2 (P=0.0146), presence of >1 score 3-4 category (P=0.0167) and frail/unfit status (P2 (P=0.0310), presence of >1 score 3-4 category (P=0.0239) and frail/unfit status (P Conclusions: Age and comorbidity scores influenced treatment intensity as well as the decision to add rituximab, this was associated to a significant impact on overall outcome of indolent NHL. Figure 1. Figure 1. Disclosures Rambaldi: Celgene: Research Funding; Amgen: Honoraria; Novartis: Honoraria; Roche: Honoraria; Pierre Fabre: Honoraria.
- Published
- 2015
41. Life Expectancy in Follicular Lymphoma Is Mainly Determined By Response to First LINE Treatment: A LONG-TERM Survey on 597 Patients
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Giuseppe Gritti, Federica Delaini, Andrea Rossi, Corrado Tarella, Roberto Passera, Riccardo Bruna, Safaa M. Ramadan, Daniela Gottardi, Alessandro Rambaldi, Daniele Caracciolo, Angela Gueli, and Anna Maria Barbui
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medicine.medical_specialty ,Univariate analysis ,business.industry ,Proportional hazards model ,Immunology ,Hazard ratio ,Follicular lymphoma ,Aggressive lymphoma ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Surgery ,International Prognostic Index ,Internal medicine ,Medicine ,Rituximab ,business ,Progressive disease ,medicine.drug - Abstract
BACKGROUND Follicular lymphoma (FL) is the most common indolent form of non-Hodgkin's lymphoma. However, FL is a heterogeneous disorder and in a proportion of patients, the disease is very resistant to standard frontline therapies. In the current analysis clinical features and outcome to primary treatment were evaluated in a large series of FL patients who were consecutively treated at the Hematology Centers of Bergamo and Torino, Italy between 1976 and 2012. The aim of the study was to define the rate of refractory disease and the long term survival of patients according to response to their primary treatment. METHODS Medical records of 597 FL patients were reviewed. In front line therapy, rituximab was employed in 330 patients (55%), front-line high dose therapy with autograft (HDS) was administered in 58 patients (9.7%). Primary refractory disease was defined as full refractoriness (stable or progressive disease) or progressive disease within six months after initial response. Univariate analysis was done for prognostic factors including gender, age at diagnosis (age≤60 and >60 years), histological grade, IPI score (low=0-2 versus high=3-5), bone marrow (BM) involvement, rituximab administration in 1st line treatment, lymphocyte to monocyte ratio at diagnosis (>2.6 vs ≤2.6), presence of primary refractory disease, and the administration of front-line HDS. Cox model was also used for multivariate analysis. RESULTS: A total of 375 patients (63%) were older than 60 years (range: 18-88) and 49% were males. There were 476 patients (79.7%) with stage III-IV, 286 patients (48%) with BM involvement, 185 (31%) had a high IPI score and 28 patients (5%) presented with high histological grade. Eighty-seven patients (13%) displayed primary refractory disease. At a median follow-up of 8 years, median overall survival (OS) was 25 years for all patients, 32.6 years for responsive patients compared to 5 years for primary refractory patients (p= CONCLUSION: FL patients who display responsive disease to their primary treatment have a very long life expectancy with median survival of 32.6 yrs. Similarly to the aggressive lymphoma subtypes, primary refractory disease is of major concern also for FL. Research studies should be focused on the early identification of primary refractory patients to promptly institute adapted therapy for this unfavorable subgroup, and possibly optimize treatment strategies for patients with high-risk FL. Table 1. Multivariate analysis for overall survival Parameter Hazard Ratio (95% Confidence interval) p-value Age (yrs): >60 vs. ≤ 60 1.54 (1.5-2.3) .03 Histologic grade: 1-2 vs 3 2.25 (0.5-9.1) .3 IPI *Score: low (0-2) vs high(3-5) 0.59 (0.4-0.9) .009 Primary Refractory: yes vs no 4.40 (3.0-6.5) < .0001 Rituximab 1st line: yes vs no 0.56 (0.4-0.8) .005 BM# involvement: yes vs no 1.44 (1.0-2.1) .06 *International prognostic index was used to have a uniform prognostic factors scoring system for patients treated over the three decades of the survey. # Bone marrow Figure 1. Overall Survival in 597 follicular lymphoma patients according to response to primary treatment Figure 1. Overall Survival in 597 follicular lymphoma patients according to response to primary treatment Disclosures No relevant conflicts of interest to declare.
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- 2015
42. Risk factors for the development of secondary malignancy after high-dose chemotherapy and autograft, with or without rituximab: a 20-year retrospective follow-up study in patients with lymphoma
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Alessandro Rambaldi, Valerio Zoli, Marco Sorio, Anna Maria Barbui, Antonino Mulè, Daniele Caracciolo, Andrea Rossi, Corrado Tarella, Sergio Cortelazzo, Michele Magni, Roberto Passera, Andrea Gallamini, Alessandra Carobbio, Fabio Benedetti, Guido Parvis, Paolo Corradini, Marco Bosa, Alessandro M. Gianni, Angela Gueli, Caterina Patti, Fabio Ciceri, Massimo Di Nicola, Tarella, C, Passera, R, Magni, M, Benedetti, F, Rossi, A, Gueli, A, Patti, C, Parvis, G, Ciceri, Fabio, Gallamini, A, Cortelazzo, S, Zoli, V, Corradini, P, Carobbio, A, Mule, A, Bosa, M, Barbui, A, Di Nicola, M, Sorio, M, Caracciolo, D, Gianni, Am, and Rambaldi, A.
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Male ,Oncology ,Cancer Research ,Time Factors ,Lymphoma ,medicine.medical_treatment ,Kaplan-Meier Estimate ,Cohort Studies ,Antibodies, Monoclonal, Murine-Derived ,hemic and lymphatic diseases ,Antineoplastic Combined Chemotherapy Protocols ,Neoplasms, Second Primary ,Middle Aged ,Combined Modality Therapy ,Hodgkin Disease ,Treatment Outcome ,Female ,Rituximab ,medicine.drug ,Adult ,medicine.medical_specialty ,Lymphoma, B-Cell ,Adolescent ,Lymphoma, T-Cell ,Risk Assessment ,Transplantation, Autologous ,Disease-Free Survival ,Statistics, Nonparametric ,Young Adult ,Internal medicine ,medicine ,Humans ,Immunologic Factors ,Risk factor ,Survival analysis ,Aged ,Proportional Hazards Models ,Retrospective Studies ,Chemotherapy ,Dose-Response Relationship, Drug ,business.industry ,Retrospective cohort study ,medicine.disease ,Survival Analysis ,Surgery ,Transplantation ,Multivariate Analysis ,Cytarabine ,business ,Follow-Up Studies ,Stem Cell Transplantation - Abstract
Purpose High-dose chemotherapy with peripheral blood progenitor cell (PBPC) autograft is effective in high-risk lymphoma, particularly with the addition of rituximab; however, it is associated with risk of secondary malignancy. These issues have been addressed in a series of 1,347 patients with lymphoma treated with a high-dose sequential (HDS) program. Patients and Methods A total of 1,024 patients with B-cell lymphoma, 234 patients with Hodgkin's lymphoma, and 89 patients with T-cell lymphoma were treated with HDS between 1985 and 2005 at 11 Gruppo Italiano Terapie Innovative Linfomi centers. HDS was given as salvage treatment to 707 patients (52%); 655 patients (49%) received a modified HDS, with high-dose cytarabine and two consecutive PBPC harvests. Rituximab-supplemented HDS was given to 523 patients (39%). Results At a median follow-up of 7 years, the median overall survival (OS) was 16.2 years; in B-cell lymphoma the OS was significantly superior with rituximab HDS compared to HDS alone. The cumulative incidence at 5 and 10 years of secondary myelodysplasia/acute leukemia (sMDS/AL) were 3.09% and 4.52%, respectively, that of solid tumors were 2.54% and 6.79%, respectively. Factors associated with sMDS/AL were male sex and use of the second harvest PBPC for the graft; factors found to be associated with solid tumor were advanced age, post-HDS radiotherapy, and rituximab addition to HDS. Despite the increased risk of solid tumors, rituximab addition to HDS was still associated with survival advantages. Conclusion This analysis has relevant implications for the design and use of intensive chemoimmunotherapy with autograft. In addition, it offers useful insights toward the understanding and prevention of tumor development.
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- 2011
43. Combination antifungal treatment of pseudomembranous tracheobronchial invasive aspergillosis: a case report
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Pierpaolo Terragni, Anna C. Trompeo, V. Marco Ranieri, Anna Maria Barbui, Rosario Urbino, Daniela Pasero, Francesco Giuseppe De Rosa, Giovanni Di Perri, De Rosa, F.G., Terragni, P., Pasero, D., Trompeo, A.C., Urbino, R., Barbui, A., Perri, G.D., and Marco Ranieri, V.
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Male ,bronchoscopy ,Antifungal Agents ,anamnesi ,vancomycin ,Critical Care and Intensive Care Medicine ,Aspergillosis ,law.invention ,computer assisted tomography ,chemistry.chemical_compound ,Tracheobronchitis ,meropenem ,law ,caspofungin ,Enterocolitis, Pseudomembranous ,combination chemotherapy ,artificial ventilation ,drotrecogin ,Middle Aged ,continuous infusion ,liver toxicity ,Intensive care unit ,amphotericin B ,Treatment Outcome ,drug withdrawal ,laboratory test ,Drug Therapy, Combination ,medicine.drug ,voriconazole, adult ,medicine.medical_specialty ,lung biopsy ,lung aspergillosi ,Critical Care ,Pulmonary Aspergillosi ,Itraconazole ,septic shock, Antifungal Agent ,ciprofloxacin ,Intensive care ,Internal medicine ,medicine ,case report ,Humans ,human ,Intensive care medicine ,Mycosis ,Enterocolitis, Pseudomembranou ,business.industry ,Intensive Care ,Aspergillu ,medicine.disease ,human tissue ,clinical feature ,Transplantation ,chemistry ,Aspergillus fumigatu ,Pulmonary Aspergillosis ,Caspofungin ,business ,note - Abstract
Invasive aspergillosis (IA) is increasingly recognized in the intensive care unit (ICU), and new risk factors associated with respiratory colonization or infection by Aspergillus spp. include steroid treatment and chronic lung obstructive disease [1, 2]. In a review of 289 autopsies in the ICU, IA was the leading cause of Goldman class I discrepancy (a missed major diagnosis with major impact on patient management and survival) [3]. The epidemiology of IA indicates an increasing number of infections in immunosuppressed patients/individuals undergoing transplantation of bone marrow, hematopoietic stem cells, or organ transplantations, and those receiving intensive chemotherapy or other immunosuppressive treatments. A broad group of patients who are admitted to ICU also have some form of immunosupppression and may be susceptible to invasive mould infections. For various reasons, figures about the true incidence of IA in ICU are difficult to generate. The most important reason is the difficulty encountered in making a definite diagnosis of IA (lack of sensitivity and specificity with regard to culture and radiology) [4]. Recently, galactomannan (GM) in bronchoalveolar lavage (BAL) fluid appears to be a promising tool for early diagnosis in non-neutropenic critically ill patients and has been associated in proven cases with sensitivity and specificity of 88 and 87%, respectively [5]. Pseudomembranous and obstructive Aspergillus tracheobronchitis are still considered to have a fatal outcome and have been reported in a wide variety of patients [6]. There has been only one report in a patient with diabetes which was treated by deoxycholate amphotericin B (AmB) and subsequent addition of oral itraconazole [7]. In this paper, we report a pseudomembranous and obstructive tracheobronchitis in a diabetic patient successfully treated with caspofungin and AmB.
- Published
- 2009
44. High Response Rate with Favorable Survival Projections in High-Risk Patients with Diffuse Large B-Cell Lymphoma (DLBCL) Receiving R-CHOP-14 or Early Intensified Chemotherapy with Rituximab and Autograft (R-HDS): Results of the Interim Analysis of A GITIL Prospective Multicenter Phase III Study
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Annalisa Chiarenza, Giovanni Pizzolo, Ignazio Majolino, Antonino Mulè, Angela Gueli, Tiziano Barbui, Guido Gini, Roberto Marchioli, Andrés J.M. Ferreri, Francesco Rodeghiero, Paolo Corradini, Pietro Leoni, Massimo Di Nicola, Sergio Cortelazzo, Alessandro Rambaldi, Giorgio La Nasa, Alessandro M. Gianni, Livio Trentin, Francesco Di Raimondo, Atto Billio, Marco Ladetto, Manuela Zanni, Corrado Tarella, Andrea Gallamini, Caterina Patti, Fabio Benedetti, and Anna Maria Barbui
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Melphalan ,medicine.medical_specialty ,business.industry ,Immunology ,Phases of clinical research ,Aggressive lymphoma ,Cell Biology ,Hematology ,Interim analysis ,medicine.disease ,Biochemistry ,Chemotherapy regimen ,Gastroenterology ,Surgery ,Regimen ,Internal medicine ,medicine ,Rituximab ,business ,Diffuse large B-cell lymphoma ,medicine.drug - Abstract
Abstract 1220 Poster Board I-242 Background The outcome of B-cell diffuse large B-cell lymphoma (DLB-CL) patients has definitely improved since the introduction of therapeutic programs combining chemotherapy and the anti CD20 rituximab. However, the outcome of patients with adverse prognostic factors still needs a substantial improvement and intensive therapy with autologous stem cell transplantation (ASCT) may represent a feasible option. In a previous Phase II study the combination of rituximab and high-dose (HD) sequential chemotherapy, delivered with multiple autologous peripheral blood progenitor cell (PBPC) support (R-HDS regimen), proved effective and well tolerated in previously untreated patients with DLB-CL and age-adjusted International Prognostic Score (aaIPI) score 2-3 (Tarella et al.: Leukemia 2007). Based on this study, a multicenter Phase III study was planned to compare the R-HDS regimen to a standard dose dense, rituximab supplemented R-CHOP-14 chemotherapy program. Patients and Methods The multicenter phase III trial R-HDS 0305 (Clinical Trials.gov.number NCT00355199) was planned to include 240 patients with DLBCL without CNS with stage '2 II B, bulk, age 18-60 years, with ECOG-PS=0-3 and aaIPI 2-3 or age 61-65 years with ECOG-PS=0-2 and IPI 3-5. The control group received 8 courses of R-CHOP-14, supported by GCSF ± involved field radiotherapy (IFRT), if they achieved at least a PR after 4 cycles. Cases refractory to R-CHOP-14 were rescued with R-HDS. Experimental arm (RHDS) included: 3 courses of doxorubicin-containing chemotherapy (APO), followed by sequential administration of cyclophosphamide (CTX) 7 g/sqm, Cytarabine (Ara-C) 2g/sqm every 12 hours for 6 days, etoposide 2 g/sqm plus cisplatin 100 mg/sqm; the program was completed by mitoxantrone plus melphalan (60 and 180 mg/sqm) or BEAM conditioning regimen with ASCT± IFRT. Rituximab (375 mg/sqm) was given for a total of 6 doses, twice after CTX and Ara-C, as in vivo purging before CD 34+ cells harvest, and twice after ASCT. The primary outcomes of the study were CR, DFS, OS, EFS and toxicity. From June 2005 to February 2009, 165 patients were enrolled in the study (R-CHOP-14=83; RHDS=82). The planned interim analysis has been carried out on 119 patients who have been randomized up to March 2008. Results The median age was 49 years (range, 18-65), 11 patients (9.2%) were> 60 years and the M/F was 1.38. Patients in two arms presented with comparable adverse features such as advanced stage (87%), BM infiltration (24%), bulky disease (67%), elevated LDH (81%) and beta 2-microglobulin (mean 3.9 mg/dl, SD = 4.5), poor ECOG-PS (60%), B-symptoms (62%), and ≥1 extranodal site (63%). Until now 10 patients (8%) did not complete the planned program because of toxicity or PD, 6 and 4 cases, respectively. One patient resistant to R-CHOP-14 was shifted to R-HDS. Overall, 24 patients (20%) deceased during the course of the study, 20 (17%) died from lymphoma, 2 (2%) due to therapy complications and 2 (2%) from hepatitis B reactivation. Moreover, 6 patients (5%) recovered from severe adverse events: 1 interstitial pneumonia, 1 graft failure, 1 sepsis, 1 colon diverticulitis, 1 shock, 1 prolonged aplasia. The main G>2 hematological toxicity were: anemia, granulocytopenia and thrombocytopenia, in 42%, 60 % and 45 % of patients, respectively. Grade >2 gastrointestinal, hepatic and infectious toxicity were recorded in 32 %, 11 % and 20% of patients, respectively. One-hundred and eight of 119 patients (91%) were alive and assessable for the response rate and clinical outcome at final restaging. Eighty-nine patients (82%) achieved CR, 8 PR and 7 had SD or PD. With a median follow up of 18.1 months (SD= 9.3, range 0.3–40.6 months) the 2year OS, DFS and EFS of the 119 evaluable patients are 80%, 84% and 74%, respectively. Conclusion This interim analysis shows that in high-risk DLBCL patients aged =/ Disclosures No relevant conflicts of interest to declare.
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- 2009
45. Combined antifungal therapy, iron chelation and surgical resection as treatment of hepatic zygomycosis in a patient with haematological malignancy
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Damiano Patrono, Alessandro Busca, Maria Teresa Sorrentino, Giorgio Limerutti, Francesco Giuseppe De Rosa, Mauro Salizzoni, Ezio David, Anna Maria Barbui, Franco Locatelli, and Filippo Marmont
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Posaconazole ,medicine.medical_specialty ,Combination therapy ,business.industry ,Deferasirox ,Dermatology ,General Medicine ,medicine.disease ,Surgery ,Transplantation ,Infectious Diseases ,Pharmacotherapy ,Amphotericin B ,Medicine ,Zygomycosis ,business ,Febrile neutropenia ,medicine.drug - Abstract
We describe the case of a 19-year-old boy with acute leukaemia who developed primary hepatic zygomycosis. The patient presented with febrile neutropenia and severe abdominal tenderness. Despite the administration of antibiotics and liposomal Amphotericin-B (L-AmB), the CT scan demonstrated an increase in the size of liver lesions. A wide surgical resection was carried out and liver specimens demonstrated a branching, filamentous fungus that was identified as Rhizomucor pusillus by both phenotypic and molecular methods. The patient was treated with L-AmB combined with posaconazole, and deferasirox was subsequently added given the potential synergistic effect of this iron chelator in combination with L-AmB. Three months after surgical intervention, an allogeneic stem-cell transplantation was successfully carried out. The present case confirms that an early surgical management combined with antifungal agents is crucial to optimise the outcome of patients with zygomycosis and the use of deferasirox is a promising alternative.
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- 2009
46. Multiple myeloma: comparison of two dose-intensive melphalan regimens (100 vs 200 mg/m(2))
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Mario Boccadoro, Pellegrino Musto, Tommaso Caravita, Alessandra Bertola, Benedetto Bruno, Antonio Palumbo, M Vignetti, Fausto Rossini, Sara Bringhen, Federica Cavallo, Massimo Massaia, Patrizia Falco, Cecilia Rus, Anna Maria Barbui, and Norbert Pescosta
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Melphalan ,Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Antineoplastic Agents ,administration /&/ dosage/adverse effects ,Gastroenterology ,Drug Administration Schedule ,Dose-Response Relationship ,Internal medicine ,Immunopathology ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,drug therapy/mortality ,Stage (cooking) ,administration /&/ dosage ,Antineoplastic Agents, Alkylating ,Multiple myeloma ,Aged ,Alkylating ,Drug ,Female ,Middle Aged ,Multiple Myeloma ,Neoplasm Staging ,Survival Rate ,Hematology ,Dose-Response Relationship, Drug ,M.2 ,business.industry ,medicine.disease ,Surgery ,Regimen ,Oncology ,Toxicity ,business ,medicine.drug - Abstract
Several trials have shown the superior impact of high-dose melphalan (usually 200 mg/m(2), MEL200) vs standard therapy in myeloma patients. Intermediate-dose melphalan (100 mg/m(2), MEL100) is also superior to the standard dose, but has not been clinically compared with MEL200. A total of 90 patients at diagnosis were treated with two MEL100 courses. Their clinical outcome was compared with that of a control group of 90 pair mates matched for serum beta2-microglobulin levels and Durie and Salmon clinical stage. These patients were treated at diagnosis with two MEL200 courses. Patient characteristics were similar in both groups except that the median age of the MEL100 group was significantly higher (P0.0001). Complete remission was 35% after MEL100 and 48% after MEL200 (P=0.08). Median event-free survival (EFS) was 32 months in the MEL100 group and 42 months in the MEL200 group (P0.005), but overall survival (OS) was not different. Transplant-related mortality was not significantly different. Haematological and extra-haematological toxicity was significantly reduced after MEL100. Despite the significant age difference, tandem MEL100 was less toxic than tandem MEL200, and MEL100 was inferior to MEL200 in terms of EFS but not in terms of OS. The intensified nonmyeloablative MEL100 regimen is an effective first-line treatment.
- Published
- 2004
47. Treatment of recurrent hepatitis C in liver transplants: efficacy of a six versus a twelve month course of interferon alfa 2b with ribavirin
- Author
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Fausto Zamboni, Ezio David, Adriana Bobbio, Maurizio Fadda, B. Lavezzo, Anna Maria Barbui, Mario Rizzetto, Mauro Salizzoni, Alessandro Franchello, Maria Torrani, Antonio Ottobrelli, and A. Smedile
- Subjects
Adult ,Male ,medicine.medical_specialty ,Combination therapy ,medicine.medical_treatment ,Biopsy ,Alpha interferon ,Liver transplantation ,Interferon alpha-2 ,Gastroenterology ,Antiviral Agents ,chemistry.chemical_compound ,Postoperative Complications ,Predictive Value of Tests ,Recurrence ,Internal medicine ,Ribavirin ,Medicine ,Humans ,Interferon alfa ,Hepatitis ,Hepatology ,business.industry ,virus diseases ,Interferon-alpha ,Hepatitis C ,Hepatitis C, Chronic ,Middle Aged ,medicine.disease ,digestive system diseases ,Recombinant Proteins ,Surgery ,Liver Transplantation ,Transplantation ,Treatment Outcome ,chemistry ,Liver ,Drug Therapy, Combination ,Female ,business ,medicine.drug - Abstract
Background/Aims : Interferon (IFN) with ribavirin combination therapy (CT) was proposed for the treatment of hepatitis C recurring in liver transplants. We assessed the efficacy of two protocols of CT in transplanted patients with recurrent severe hepatitis C virus (HCV) hepatitis. Methods : Fifty-seven patients (68% genotype 1b) were treated with IFN alfa-2b 3 million units three times weekly and oral ribavirin 800mg/die for 6 or 12 months. Study end-points were the end of treatment (ETVR) and the 12-month post-therapy sustained virologic response (SVR; negative HCV-RNA). Results : ETVR was induced in 9/27 (33%) and in 7/30 patients (23%) treated, respectively, for 6 and 12 months ( P =0.4); a SVR was induced in six (22%) of the former and five (17%) of the latter ( P =0.4). HCV genotype non-1 patients responded better than genotype 1 (SVR: 43% in genotype non-1 versus 12% in genotype 1, P : 0.02). In ETV responders the hepatitis activity index improved by >2 points in biopsies taken after therapy compared to pre-therapy biopsies. Anemia and leukopenia required reduction of therapy in 51% of the patients. Conclusions : CT is efficacious in controlling HCV disease in about 20% of transplants with recurrent hepatitis C. Six months of therapy are as efficacious as 12 months.
- Published
- 2002
48. Starlyte phase II study of coltuximab ravtansine (CoR, SAR3419) single agent: Clinical activity and safety in patients (pts) with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL; NCT01472887)
- Author
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John Radford, Farrukh T. Awan, Anna Maria Barbui, Laurence Hatteville, Laure Siraudin, Andrea Janíková, Kazimierz Sulek, Sandrine Schwab, Miguel Canales, Caterina Patti, Martin J. S. Dyer, Dina Ben Yehuda, Corina Oprea, Alessandro M. Gianni, Gregor Verhoef, María José Terol, Marek Trneny, Paul G. Montgomery, and Andres Lopez
- Subjects
Cancer Research ,Pathology ,medicine.medical_specialty ,Phases of clinical research ,chemical and pharmacologic phenomena ,Maytansinoid ,CD19 ,chemistry.chemical_compound ,immune system diseases ,hemic and lymphatic diseases ,Medicine ,In patient ,B cell ,biology ,business.industry ,hemic and immune systems ,medicine.disease ,medicine.anatomical_structure ,Oncology ,chemistry ,Cancer research ,biology.protein ,Antibody ,business ,Diffuse large B-cell lymphoma ,Conjugate - Abstract
8506 Background: CoR is an anti-CD19 antibody maytansinoid conjugate. CD19 is expressed in the majority of B cell lymphomas. Phase I program showed clinical activity in pts with both indolent and a...
- Published
- 2014
49. Long-term results of the phase III GITMO/FIL trial of CHOP-R versus R-HDS plus autograft in high-risk follicular lymphoma (FL) at diagnosis
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Roberto Passera, Maurizio Musso, Angela Gueli, Riccardo Bruna, Fausto Rossini, Michele Magni, Fabio Benedetti, Alessandro Pulsoni, Caterina Stelitano, Caterina Patti, Anna Marina Liberati, Corrado Tarella, Valerio Zoli, Anna Maria Barbui, Guido Gini, Claudia Castellino, Tommasina Perrone, Carola Boccomini, Marco Ladetto, and Paolo Corradini
- Subjects
Cancer Research ,medicine.medical_specialty ,Intention-to-treat analysis ,business.industry ,Follicular lymphoma ,Long term results ,CHOP ,medicine.disease ,Minimal residual disease ,Disease control ,Gastroenterology ,Surgery ,Oncology ,Early results ,Internal medicine ,Clinical endpoint ,Medicine ,business - Abstract
8531 Background: Early results of a randomized phase III GITMO/FIL study (www.clinicaltrials.gov NCT00435955) comparing CHOP-R vs. R-HDS + ASCT as primary treatment in134 FL pts, aged ≤60 yrs with aaIPI>1/IIL score>2, showed superior disease control with R-HDS but no OS advantage (Ladetto et al, Blood 2008). We here present an updated analysis from July 2013 at a median follow-up (MFU) of 9.5 yr including 125 pts of 134 originally randomized pts (61 CHOP-R/64 of R-HDS). Methods: Clinical features (CF) and treatment schedules have been already reported. Briefly, median age was 51 yrs. (22-60), M/F ratio 74/51, aaIPI 2-3 90%, retrospective FLIPI >2 60%, high LDH 49%, bulky disease 62%, B-symptoms 45%, BM+ 86%. CF were balanced among the two arms. Analysis was intention to treat and EFS the primary endpoint. Minimal residual disease was done by nested and RQ-PCR. Results: CR rate was 70.4% (57% with CHOP-R and 83% with R-HDS, p < .001); 64% patients achieved a Molecular Remission (MR). At MFU, 88 patients (7...
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- 2014
50. Prevention of hepatitis B virus recurrence after liver transplantation in cirrhotic patients treated with lamivudine and passive immunoprophylaxis
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Alessia Ciancio, Alfredo Marzano, Mario Rizzetto, Alessandro Franchello, Francesco Negro, W. Debernardi-Venon, Mauro Salizzoni, Antonina Smedile, Anna Maria Barbui, Piantino P, Ezio David, and Elena Gentilcore
- Subjects
Hepatitis B virus ,medicine.medical_specialty ,Cirrhosis ,Hepatology ,business.industry ,medicine.medical_treatment ,Lamivudine ,Hepatitis B ,Liver transplantation ,medicine.disease_cause ,medicine.disease ,Gastroenterology ,Transplantation ,Internal medicine ,Immunology ,Chemoprophylaxis ,Medicine ,Viral disease ,business ,medicine.drug - Abstract
Background/Aims : Treatment with hepatitis B virus immune globulins (HBIG) or lamivudine has reduced the rate of hepatitis B recurrence after liver transplantation to approximately 50%. Methods : To further decrease hepatitis B recurrence, 33 hepatitis B virus (HBV)-related cirrhotic patients were treated with lamivudine before liver transplantation and with lamivudine together with low-dose HBIG (46 500 IU the first month followed by 5000 IU/monthly) after surgery. Results : While on lamivudine, serum HBV DNA level decreased significantly in all patients and in 11 (33%) the Child–Pugh score improved. Twenty-six patients were transplanted. Among the 25 who survived for longer than 12 months, only one (4%) experienced a hepatitis B recurrence over an average follow-up of 31 months, a rate significantly lower ( P =0.0002) than the 50% recurrence rate among a historical control group of 12 patients. However, low-level HBV replication was detected sporadically throughout the follow-up in 64% of patients. Conclusions : Over the medium-term, combined prophylaxis with lamivudine and HBIG significantly decreases the risk of hepatitis B recurrence after liver transplantation. Though low-level HBV infection recurred in two thirds of patients, the pathogenic expression of HBV was prevented.
- Published
- 2001
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