99 results on '"Filì, C"'
Search Results
52. Cytokine patterns and lymphocyte subsets in patients with chronic graft versus host disease after allogeneic stem cell transplantation with reduced intensity conditioning
- Author
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Skert, C, Damiani, D, Patriarca, F, Michelutti, A, Filì, C, Lucchi, P, Malagola, Michele, Bergonzi, C, Roccaro, Am, Ricotta, Doris, Caimi, Luigi, Fanin, R, and Russo, Domenico
- Published
- 2007
53. In vitro activity of tyrosine kinase, farnesyl transferase and AKT kinase inhibitors on c-kit positive/negative and ;DR-pgp positive/negative leukaemia tumor cell lines
- Author
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Malagola, Michele, Damiani, D, Michelutti, A, Martinelli, G, Ottaviani, E, Paolini, S, Piccaluga, Pp, Skert, C, Roccaro, A, Peli, A, Capuzzi, E, Filì, C, Bergonzi, C, Tiribelli, M, Fanin, R, Baccarani, M, and Russo, Domenico
- Published
- 2007
54. Impact of allogenenic HSC transplantation in normal karyotype adult acute myeloid leukemia and correlation with multodrug resistance proeitns expression
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Damiani, Daniela, Tiribelli, Mario, Geromin, A., Michelutti, A., Russo, D., Filì, C., and Fanin, R.
- Published
- 2007
55. Prognosis and treatment of MDR-Pgp positive Acute Myeloid Leukaemia
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Malagola, Michele, Bergonzi, C, Skert, C, Filì, C, Roccaro, A, Galletti, L, Peli, A, Capuzzi, E, and Russo, Domenico
- Published
- 2007
56. Clinical effects of 5-azacitidine five days/monthly schedale in three symptomatic low-risk (IPSS: 0 – 1) myelodisplastic patients
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Filì, C, Bergonzi, C, Skert, C, Malagola, Michele, Roccaro, Am, Peli, A, Capuzzi, E, and Russo, Domenico
- Published
- 2007
57. In vitro activity of tyrosine kinase, farnedyl trasferase, and AKT kinase inhibitors on c-kit positive/negative and MDR-PGP positive/negative leukemia tumor cell lines
- Author
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Malagola, M., Damiani, Daniela, Michelutti, A., Martienlli, G., Ottaviani, E., Paolini, S., Piccaluga, P. P., Skert, C., Roccaro, A., Peli, A., Capuzzi, E., Filì, C., Bergonzi, C., Fanin, R., Baccarani, M., and Russo, D.
- Published
- 2007
58. Sclerodermatous chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation: incidence, predictors and outcome
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Skert, C., Patriarca, F., Sperotto, A., Cerno, M., Filì, C., Zaja, F., Stocchi, R., Geromin, A., Daniela DAMIANI, Fanin, R., Skert, C, Patriarca, Francesca, Sperotto, A, Cerno, M, Fili, C, Zaja, Francesco, Stocchi, R, Geromin, A, Damiani, Daniela, and Fanin, Renato
- Abstract
Scleroderma may be one of the most severe forms of chronic graft-versus-host disease (GVHD). We retrospectively evaluated its incidence, predictor variables and outcome in 133 patients who survived at least 4 months after allogeneic hematopoietic stem cell transplantation. The 5-year cumulative incidence was 15.5% in patients with chronic GVHD. The generalized form had a progressive course despite immunosuppressive therapy. Eosinophilia, autoimmune markers, and previous skin involvement by chronic GVHD with disorders of pigmentation were significantly associated with an increased probability of developing scleroderma.
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- 2006
59. A specific Toll-like receptor profile on T lymphocytes and values of monocytes correlate with bacterial, fungal, and cytomegalovirus infections in the early period of allogeneic stem cell transplantation
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Skert, C., primary, Fogli, M., additional, Garrafa, E., additional, Perucca, S., additional, Fiorentini, S., additional, Cancelli, V., additional, Turra, A., additional, Ribolla, R., additional, Filì, C., additional, Malagola, M., additional, Bergonzi, C., additional, Cattina, F., additional, Bernardi, S., additional, Caruso, A., additional, Di Palma, A., additional, and Russo, D., additional
- Published
- 2014
- Full Text
- View/download PDF
60. Epigenetic regulation of nuclear PI-PLCbeta1 signaling pathway in low-risk MDS patients during azacitidine treatment
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Follo, M Y, primary, Russo, D, additional, Finelli, C, additional, Mongiorgi, S, additional, Clissa, C, additional, Filì, C, additional, Colombi, C, additional, Gobbi, M, additional, Manzoli, L, additional, Piazzi, M, additional, Martelli, A M, additional, and Cocco, L, additional
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- 2011
- Full Text
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61. 240 Effect of azacitidine on inositide-dependent signalling pathways in low-risk MDS patients
- Author
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Follo, M.Y., primary, Mongiorgi, S., additional, Clissa, C., additional, Filì, C., additional, Colombi, C., additional, Baccarani, M., additional, Martinelli, G., additional, Gobbi, M., additional, Manzoli, L., additional, Russo, D., additional, Finelli, C., additional, and Cocco, L., additional
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- 2011
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62. P153 Clinical effects of 5-azacitidine five days/monthly schedule in three symptomatic low-risk (IPSS: 0-1) myelodysplastic patients
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Fili, C., Bergonzi, C., Skert, C., Malagola, M., Roccaro, A.M., Peli, A., Capuzzi, E., and Russo, D.
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- 2007
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63. EARLY EXTRACORPOREAL PHOTOAPHERESIS FOR THE TREATMENT OF ACUTE GRAFT VERSUS HOST DISEASE (AGVHD)
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Michele Malagola, Ferremi Leali, P., Skert, C., Almici, C., Bergonzi, C., Filì, C., Alghisi, E., Simona Bernardi, Cancelli, V., Cattina, F., Di Palma, Andrea, Martinazzoli, D., Perucca, Simone, Ribolla, R., Turra, A., Marini, M., and Russo, Domenico
64. ACHIEVEMENT OF COMPLETE REMISSION WITH PONATINIB THERAPY FOR PHILADELPHIA ACUTE LYMPHOBLASTIC LEUKEMIA RELAPSED AFTER ALLOGENEIC STEM CELL TRANSPLANTATION: A CASE REPORT
- Author
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Turra, A., Michele Malagola, Bergonzi, C., Skert, C., Filì, C., Perucca, S., Ribolla, R., Cancelli, V., Di Palma, A., Alghisi, E., Cattina, F., Zedda, S., Simona Bernardi, and Russo, Domenico
65. PROGNOSTIC RELEVANCE OF WT1 MOLECULAR LEVELS IN PATIENTS WITH ACUTE MYELOID LEUKEMIA AFTER ALLOGENEIC STEM CELL TRANSPLANTATION
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Ribolla, R., Skert, C., Perucca, Simone, Michele Malagola, Filì, C., Bergonzi, C., Turra, A., Alghisi, E., Di Palma, Andrea, Cancelli, V., Cattina, F., Simona Bernardi, Borlenghi, E., Cattaneo, C., Antoniazzi, F., Ruggeri, G., Rossi, G., Luigi Caimi, and Russo, Domenico
66. Role of bone marrow biopsy in staging of patients with classical Hodgkin's lymphoma undergoing positron emission tomography/computed tomography
- Author
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A. Di Rocco, R. Guariglia, S. Falorio, P. C. Riccomagno, G. Doa, Benedetta Puccini, Erica Finolezzi, Rosanna Ciancia, A. Mulè, C. Filì, C. Toldo, S. Zanon, Stefano Volpetti, Carla Minoia, Francesco Zaja, A. Furlan, Marianna Sassone, Luca Nassi, Puccini, B., Nassi, L., Minoia, C., Volpetti, S., Ciancia, R., Riccomagno, P. C., Di Rocco, A., Mulè, A., Toldo, C., Sassone, M. C., Guariglia, R., Filì, C., Finolezzi, E., Falorio, S., Zanon, S., Furlan, A., Doa, G., and Zaja, F.
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Male ,Staging ,Biopsy ,Bone marrow biopsy ,Computed tomography ,Hodgkinâs lymphoma ,Positron emission tomography ,Adolescent ,Adult ,Aged ,80 and over ,Bone Marrow ,Bone Marrow Examination ,Female ,Hodgkin Disease ,Humans ,Middle Aged ,Neoplasm Staging ,Positron Emission Tomography Computed Tomography ,Reproducibility of Results ,Retrospective Studies ,Sensitivity and Specificity ,Young Adult ,Hematology ,0302 clinical medicine ,Retrospective Studie ,Positive predicative value ,Stage (cooking) ,Radiation treatment planning ,Hodgkinâ s lymphoma ,Aged, 80 and over ,medicine.diagnostic_test ,General Medicine ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Radiology ,Human ,medicine.medical_specialty ,Reproducibility of Result ,03 medical and health sciences ,medicine ,business.industry ,medicine.disease ,Hodgkin's lymphoma ,Lymphoma ,Bone marrow ,Nuclear medicine ,business ,Role of bone marrow biopsy in staging of patients with classical Hodgkin’s lymphoma undergoing positron emission tomography/computed tomography ,030215 immunology - Abstract
Several studies suggested that staging bone marrow biopsy (BMB) could be omitted in patients with classical Hodgkin's lymphoma (cHL) when a positron emission tomography/computed tomography (PET/CT) is performed at baseline.To address the concordance between BMB and PET/CT in the detection of bone marrow involvement (BMI) and the BMB role in determining the Ann Arbor stage, we retrospectively collected data on 1244 consecutive patients with cHL diagnosed from January 2007 to December 2013. One thousand eighty-five patients who had undergone both BMB and PET/CT were analyzed, comparing the Ann Arbor stage assessed with PET/CT only to that resulting from PET/CT combined with BMB.One hundred sixty-nine patients (16%) showed at least one focal skeletal lesion (FSL) at PET/CT evaluation. Only 55 patients had a positive BMB (5.1%); 34 of them presented at least one FSL at PET/CT. To the contrary, 895 out of 1030 patients with a negative BMB did not show any FSL (86.9%). Positive and negative predictive values of PET/CT for BMI were 20 and 98%, respectively; sensitivity and specificity were 62 and 87%, respectively. Fifty-four out of 55 patients with a positive BMB could have been evaluated as an advanced stage just after PET/CT; only one patient (0.1%) would have been differently treated without BMB.Our data showed a very high negative predictive value of PET/CT for BMI and a negligible influence of BMB on treatment planning, strengthening the recent indications that BMB could be safely omitted in cHL patients staged with PET/CT.
- Published
- 2016
67. Prospective Phase II Study on 5-Days Azacitidine for Treatment of Symptomatic and/or Erythropoietin Unresponsive Patients with Low/INT-1–Risk Myelodysplastic Syndromes
- Author
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Ilaria Iacobucci, Carla Filì, Renato Fanin, Anna Candoni, Federica Cattina, Matilde Y. Follo, Cristina Clissa, Cristina Skert, Carlo Finelli, Pierangelo Spedini, Lucio Cocco, Marco De Gobbi, Michele Malagola, Marzia Defina, Lucia Manzoli, Monachia Bocchia, Domenico Russo, Giovanni Martinelli, Filì C, Malagola M, Follo MY, Finelli C, Iacobucci I, Martinelli G, Cattina F, Clissa C, Candoni A, Fanin R, Gobbi M, Bocchia M, Defina M, Spedini P, Skert C, Manzoli L, Cocco L, and Russo D.
- Subjects
Male ,Cancer Research ,phospholipase C beta1 ,Phospholipase C beta ,Phases of clinical research ,Gastroenterology ,granulocyte colony stimulating factor ,Cyclosporin a ,80 and over ,Prospective Studies ,Prospective cohort study ,Aged, 80 and over ,Hematologic Tests ,Single Nucleotide ,Middle Aged ,Hematologic Response ,Gene Expression Regulation, Neoplastic ,Treatment Outcome ,Oncology ,Aged ,Azacitidine ,Drug Administration Schedule ,Erythropoietin ,Female ,Humans ,Myelodysplastic Syndromes ,Polymorphism, Single Nucleotide ,Wnt1 Protein ,antianemic agent ,azacitidine ,cyclosporin A ,danazol ,erythropoietin ,granulocyte macrophage colony stimulating factor ,medicine.drug ,medicine.medical_specialty ,PI-PLCbeta1 ,Neutropenia ,Internal medicine ,medicine ,Polymorphism ,Biologic marker ,Neoplastic ,business.industry ,Myelodysplastic syndromes ,medicine.disease ,Surgery ,Gene Expression Regulation ,MYELODYSPLASTIC SYNDROMES (MDS) ,business - Abstract
Purpose: This phase II prospective study aimed to evaluate the efficacy and safety of 5-days azacytidine (5d-AZA) in patients with low-risk myelodysplastic syndromes (MDS). Second, single-nucleotide polymorphism (SNP) genetic profile and phosphoinositide-phospholipase C (PI-PLC) β1 levels were studied to evaluate possible biologic markers able to predict the hematologic response. Experimental Design: The study tested a lower intensity schedule of azacytidine. The treatment plan consisted of 75 mg/sqm/d subcutaneous administered for 5 days every 28 days, for a total of 8 cycles. Results: Thirty-two patients were enrolled in the study. The overall response rate was 47% (15 of 32) on intention-to-treat and 58% (15 of 26) for patients completing the treatment program. In this latter group, 5 (19%) achieved complete remission (CR) and 10 (38%) had hematologic improvement, according to the International Working Group (IWG) criteria. Three patients have maintained their hematologic improvement after 37, 34, and 33 months without other treatments. Moreover, 21 and 2 of 26 cases completing 8 cycles were transfusion-dependent for red blood cells and platelets at baseline, respectively. Of these, 7 (33%) and 2 (100%) became transfusion-independent at the end of the treatment program, respectively. Grade 3–4 neutropenia occurred in 28% of patients and 4 patients died early due to infections or hemorrhage. SNP results were not significantly correlated to the clinical outcome, whereas PI-PLCβ1 level anticipated either positive or negative clinical responses. Conclusions: 5d-AZA is safe and effective in a proportion of patients with low-risk MDS. PI-PLCβ1 gene expression is a reliable and dynamic marker of response that can be useful to optimize azacytidine therapy. Clin Cancer Res; 19(12); 3297–308. ©2013 AACR.
- Published
- 2013
68. Kinetics of Th1/Th2 cytokines and lymphocyte subsets to predict chronic GVHD after allo-SCT: results of a prospective study
- Author
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Francesca Patriarca, Michele Malagola, Michele Baccarani, Aldo M. Roccaro, Carla Filì, Luigi Caimi, Mario Arpinati, Cristina Skert, Daniela Damiani, R Fanin, Doris Ricotta, Angela Michelutti, Domenico Russo, P Lucchi, Cesare Bergonzi, Annalisa Peli, Skert C, Damiani D, Michelutti A, Patriarca F, Arpinati M, Filì C, Lucchi P, Malagola M, Bergonzi C, Roccaro A, Peli A, Ricotta D, Caimi L, Fanin R, Baccarani M, and Russo D.
- Subjects
Adult ,Male ,medicine.medical_specialty ,Transplantation Conditioning ,medicine.medical_treatment ,Graft vs Host Disease ,Pathogenesis ,Young Adult ,Immune system ,Th2 Cells ,immune system diseases ,T-Lymphocyte Subsets ,hemic and lymphatic diseases ,Internal medicine ,Immunopathology ,medicine ,Humans ,Prospective Studies ,Prospective cohort study ,Aged ,Transplantation ,Peripheral Blood Stem Cell Transplantation ,Hematology ,business.industry ,T lymphocyte ,Middle Aged ,Th1 Cells ,medicine.disease ,Graft-versus-host disease ,Cytokine ,Immunology ,Chronic Disease ,Cytokines ,Female ,business - Abstract
The role of different cytokines and cells of immune system in the pathogenesis of chronic GVHD (cGVHD) is still controversial. Earlier studies, which were either retrospective or analysed one or a few factors, did not show unequivocal results. We prospectively evaluated cytokine levels and lymphocyte subsets in 30 patients who underwent Allo-SCT to investigate their possible correlation with cGVHD. Levels of IL-4, IL-6, IL-10, IFN-gamma, tumour necrosis factor-alpha (TNF-alpha) and its soluble receptors were assessed by ELISA in 30 patients at different times after SCT. Lymphocyte subsets were evaluated by flow cytometry in peripheral blood at the same times as cytokines. A multivariate analysis was performed using principal component analysis and multi-factor ANOVA (analysis of variance). Eighteen patients developed cGVHD at a median time of 6 months (range, 5-9) after SCT. In multivariate analysis, we observed a correlation between cGVHD and clusters of cytokines and lymphocyte subsets from the third to the sixth month after SCT. These clusters changed their composition over time, but they constantly included natural killer (NK) and CD152+ T cells as negative predictors of cGVHD. TNF-alpha prevailed among other cytokines before the onset of cGVHD. This prevalence could be related partly to the defect of immunoregulatory cells.
- Published
- 2009
69. Incidence of bacterial and fungal infections in newly diagnosed acute myeloid leukaemia patients younger than 65 yr treated with induction regimens including fludarabine: Retrospective analysis of 224 cases
- Author
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Alfonso Zaccaria, Stefania Paolini, Aldo M. Roccaro, Luigi Gugliotta, Daniela Damiani, Alessandro Bonini, Monica Bocchia, Giancarla Priccolo, Renato Fanin, Anna Candoni, Pier Paolo Piccaluga, Cesare Bergonzi, Mario Tiribelli, Carla Filì, Marco De Gobbi, Annalisa Peli, Domenico Russo, Francesco Lauria, Michele Baccarani, Francesco De Rosa, Michele Malagola, Ivana Pierri, Giuseppe Visani, Cristina Skert, Eliana Zuffa, Giovanni Martinelli, Patrizio Mazza, Malagola M, Peli A, Damiani D, Candoni A, Tiribelli M, Martinelli G, Piccaluga PP, Paolini S, De Rosa F, Lauria F, Bocchia M, Gobbi M, Pierri I, Zaccaria A, Zuffa E, Mazza P, Priccolo G, Gugliotta L, Bonini A, Visani G, Skert C, Bergonzi C, Roccaro AM, Filì C, Fanin R, Baccarani M, and Russo D.
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Adult ,Male ,medicine.medical_specialty ,Fever ,medicine.medical_treatment ,Context (language use) ,Antineoplastic Agents ,Bacteremia ,Infections ,Acute leukaemia ,Induction ,Fludarabine ,Risk Factors ,Internal medicine ,hemic and lymphatic diseases ,Case fatality rate ,medicine ,Idarubicin ,Humans ,Gram-Positive Bacterial Infections ,Retrospective Studies ,Chemotherapy ,business.industry ,Incidence (epidemiology) ,Incidence ,Induction chemotherapy ,Hematology ,General Medicine ,Middle Aged ,Surgery ,Survival Rate ,Regimen ,Leukemia, Myeloid, Acute ,Mycoses ,Female ,ACUTE MYELOID LEUKEMIA ,FLUDARABINE ,business ,Gram-Negative Bacterial Infections ,Vidarabine ,medicine.drug - Abstract
Objectives: Infections are the major cause of morbidity and mortality in patients with acute myeloid leukaemia (AML). They primarily occur during the first course of induction chemotherapy and may increase the risk of leukaemia relapse, due to a significant delay in consolidation therapy. The intensification of induction chemotherapy and the use of non-conventional drugs such as fludarabine are considered responsible for the increased risk of infections. Methods: In this study, we retrospectively analysed the infections occurred in 224 newly diagnosed AML patients ≤65 yr, consecutively treated between 1997 and 2002 with an induction regimen including fludarabine, arabinosyl cytosine and idarubicin, with or without etoposide (FLAI/FLAIE), in the context of three multicentric prospective trials (AML97, AML99, AML02). Results: During the induction phase, 146 (65%) patients experienced fever of undetermined origin (FUO), 30 (13%) and 47 (21%) patients had Gram-negative and positive bacteremias, respectively, and 10 (4%) patients developed a probable/proven invasive fungal infection (IFI). The fatality rate for Gram-negative, Gram-positive bacteremias and probable/proven IFI was 10%, 8% and 60% respectively. During consolidation, 75 (35%) patients had FUO, 43 (20%) and 40 (19%) patients had Gram-negative and positive bacteremias, respectively, and 5 (2%) patients developed a probable/proven IFI. The fatality rate for Gram-negative, Gram-positive bacteremias and probable/proven IFI was 14%, 5% and 80% respectively. Interestingly, the overall incidence of microbiologically documented infections during induction was 38% and the incidence of probable/proven IFIs during the induction/consolidation programme was 7%. No infections caused by viruses or opportunistic pathogens were observed neither during induction, nor during consolidation. Conclusions: These data, although retrospectively collected, suggest that fludarabine-based chemotherapy is not associated with an increased incidence of infections, in particular IFIs, compared to conventional regimens commonly used for AML induction.
- Published
- 2008
70. Earlier administration of Rituximab allows higher rate of long-lasting response in adult patients with autoimmune thrombocytopenia
- Author
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Marta Lisa Battista, Monica Tani, Francesca Patriarca, Renato Fanin, Michele Baccarani, Nicola Vianelli, Francesco Zaja, Carla Filì, Valentina Tomadini, Alessandra Sperotto, Zaja F, Vianelli N, Battista M, Sperotto A, Patriarca F, Tomadini V, Fili C, Tani M, Baccarani M, Fanin R., Zaja, Francesco, Vianelli, N, Battista, M, Sperotto, A, Patriarca, Francesca, Tomadini, V, Filì, C, Tani, M, Baccarani, M, and Fanin, Renato
- Subjects
Adult ,Cancer Research ,medicine.medical_specialty ,Immunology ,Neutropenia ,Biochemistry ,Gastroenterology ,Autoimmune thrombocytopenia ,Antibodies, Monoclonal, Murine-Derived ,hemic and lymphatic diseases ,Internal medicine ,Genetics ,medicine ,Humans ,Molecular Biology ,Purpura, Thrombocytopenic, Idiopathic ,Platelet Count ,business.industry ,Undifferentiated connective tissue disease ,Antibodies, Monoclonal ,Cell Biology ,Hematology ,Middle Aged ,medicine.disease ,Thrombocytopenic purpura ,Surgery ,Concomitant ,Toxicity ,Serum sickness ,Rituximab ,business ,medicine.drug - Abstract
Background Previous reports highlighted the potential short and mid-term therapeutic activity and safety of rituximab in adult patients with autoimmune thrombocytopenias. Objectives Primary objectives of this study were to evaluate the long-term efficacy and toxicity profile. Patients and methods From October 1999 to April 2005, 37 adults patients, median age 54 years, with active and symptomatic autoimmune thrombocytopenias (30 idiopathic thrombocytopenic purpura, 1 idiopathic thrombocytopenia and neutropenia, 4 thrombocytopenia and concomitant undifferentiated connective tissue disease, 2 thrombocytopenia and concomitant B-cell lymphoprolipherative disorders) that had relapsed or were refractory to at least a full course of steroid therapy received weekly infusions of rituximab 375 mg/m2 for 4 weeks. The median interval from diagnosis to rituximab was 34 months (1–264 months) and the platelets median count was 11 x 109/L. The following parameters of efficacy and toxicity were considered: rate of complete and partial response, time to initial and maximum response, relapse rate, relapse free survival, treatment free survival, short and long-term toxicity. The possible prognostic influence of some clinical and laboratory parameters on the patients outcome were also analyzed. Results Complete and partial response (platelets count ≥ 100 x 109/L and ≥ 50 x 109/L) were 20/37 (54%) and 7/37 (19%), respectively. In most of the patients the time to initial and maximum response was prompt, already before the second administration of rituximab. The median period of observation from treatment was 22 months (1–48 months). Nine out 27 responding patients relapsed; 18/37 patients (49%) remained relapse free and 20/37 (54%) did not necessitated further therapy. A shorter interval period from the time of diagnosis and rituximab administration (≤ vs > 36 months) was associated with a lower relapse free survival (p= 0.03). During the period of rituximab administration, 2 patients experienced short term toxicity with one case of serum sickness syndrome; no infectious or other significant long term toxic complications were documented.. Conclusion Rituximab administration may allow to achieve long-lasting remission in nearly 50% of patients suffering from autoimmune thrombocytopenia with good toxic profile. The possibility to achieved long lasting response appeared related with an earlier timing of administration.
- Published
- 2006
71. Endogenous endophthalmitis following disseminated fungemia due to Fusarium solani in a patient with acute myeloid leukemia
- Author
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Tiribelli, M., Zaja, F., Fili, C., Michelutti, T., Prosdocimo, S., Candoni, A., Fanin, R., Tiribelli, Mario, Zaja, Francesco, Filì, C, Michelutti, T, Prosdocimo, S, Candon, i A, and Fanin, Renato
- Subjects
Adult ,Male ,Endophthalmitis ,Acute myeloid leukemia ,Fatal Outcome ,Fusarium ,Mycoses ,Leukemia, Myeloid ,Acute Disease ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Fungemia ,Fusarium solani - Abstract
We report the case of a young man with a resistant acute myeloid leukemia (AML) who developed a disseminated fungemia due to Fusarium solani involving the skin and lungs, during the neutropenic phase following a chemotherapy course. Despite continuous therapy with liposomal amphotericin B, he developed a bilateral endophthalmitis that rapidly evolved to complete blindness. The patient underwent two procedures of vitrectomy, with detection of F. solani in the vitreous fluid, and continued antifungal therapy, without any recovery of visual acuity. When he eventually died due to recurrence of leukemia and hemorrhagic shock, autopsy revealed a diffuse fusarial involvement of the central nervous sysytem.
- Published
- 2002
72. Early chemosensitivity to VAD regimen predicts a favorable outcome after autologous stem cell transplantation in multiple myeloma
- Author
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Patriarca, F., Sperotto, A., Fili, C., Francesco Zaja, Prosdocimo, S., Fanin, R., Patriarca, Francesca, Sperotto, A, Filì, C, Zaja, Francesco, Prosdocimo, S, and Fanin, Renato
- Abstract
We report that early chemosensitivity, defined by a greater than 50% reduction of M-component and plasma-cell marrow infiltration, after 2 cycles of VAD was correlated with a favorable outcome following autologous stem cell transplantation in 46 patients with newly diagnosed multiple myeloma submitted to high-dose therapy.
- Published
- 2002
73. The triple A (AAA) model globally recapitulates adverse outcomes in essential thrombocythemia.
- Author
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Tosoni L, Morelli GL, Tomadini G, Lazzarotto D, Filì C, Simeone E, Zannier ME, Callegari C, Fanin M, Battaglia G, Bergnach M, Damiani D, Fanin R, and Tiribelli M
- Subjects
- Humans, Female, Male, Middle Aged, Aged, Janus Kinase 2 genetics, Prognosis, Thrombocythemia, Essential genetics
- Published
- 2024
- Full Text
- View/download PDF
74. Risk-adapted MRD-directed therapy for young adults with acute myeloid leukemia: 6-year update of the GIMEMA AML1310 trial.
- Author
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Venditti A, Piciocchi A, Candoni A, Arena V, Palmieri R, Filì C, Carella AM, Calafiore V, Cairoli R, de Fabritiis P, Storti G, Salutari P, Lanza F, Martinelli G, Curti A, Luppi M, Ingrosso C, Martelli MP, Cuneo A, Albano F, Mulè A, Tafuri A, Cudillo L, Tieghi A, Fracchiolla NS, Capelli D, Trisolini SM, Alati C, La Sala E, Maurillo L, Del Principe MI, Irno Consalvo MA, Divona MD, Ottone T, Cerretti R, Sconocchia G, Voso MT, Fazi P, Vignetti M, and Buccisano F
- Subjects
- Humans, Young Adult, Adult, Male, Female, Adolescent, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Leukemia, Myeloid, Acute therapy, Neoplasm, Residual
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- 2024
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75. Efficacy and safety of venetoclax plus hypomethylating agents in relapsed/refractory acute myeloid leukemia: a multicenter real-life experience.
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Angotzi F, Lessi F, Leoncin M, Filì C, Endri M, Lico A, Visentin A, Pravato S, Candoni A, Trentin L, and Gurrieri C
- Abstract
Venetoclax (VEN) has been shown to play a synergistic effect in combination with hypomethylating agents (HMAs) in the frontline treatment of acute myeloid leukemia (AML). However, the potential role of this therapy in the relapsed/refractory (R/R) AML setting, still needs to be further unveiled. The aim of the current study was to retrospectively outline the safety profile, response and survival outcomes of R/R AML patients treated with VEN in association with HMAs. Clinical, biological, and molecular data were collected from 57 patients with R/R AML treated with VEN combined with azacitidine or decitabine between 2018 and 2023. The median age of patients was 63 years, 38 (66.7%) received treatment for relapsed disease while 19 (33.3%) for refractory disease, 5 (8.7%) were treated for molecular relapse. A consistent proportion of the cohort was represented by patients with unfavorable prognostic factors such as complex karyotype (36.8%), secondary AML (29.8%), previous exposure to HMAs (38.6%), and relapse after allogeneic stem cell transplant (22.8%). A total of 14 patients achieved CR (24.6%), 3 (5.3%) CRi, 3 (5.3%) MLFS, and 3 (5.3%) PR, accounting for an ORR of 40.4%. The CR/CRi rate was higher in the group treated with azacitidine than in the group treated with decitabine (37.8% vs. 15%). The median OS was 8.2 months, reaching 20.1 months among responding patients. VEN-HMAs treatment allowed to bridge to allogeneic stem cell transplantation 11 (23.9%) of eligible patients, for which a median OS of 19.8 months was shown. On multivariate analysis, ECOG performance status ≥2, complex karyotype and not proceeding to allogeneic stem cell transplantation after therapy with VEN-HMAs were the factors independently associated with shorter OS. Patients treated with the azacitidine rather than the decitabine containing regimen generally displayed a trend toward superior outcomes. The major toxicities were prolonged neutropenia and infections. In conclusion, this study showed how VEN-HMAs could represent an effective salvage therapy in patients with R/R AML, even among some of those patients harboring dismal prognostic features, with a good toxicity profile. Further prospective studies are thus warranted., Competing Interests: LT received research funding from Abbvie, Gilead, Janssen, Astrazeneca, Takeda, and attended advisory boards by Janssen, Takeda, Abbvie, Astrazeneca, Beigene and Octapharma. AV attended advisory boards organized by Janssen, Astrazeneca, Beigene and CSL Behring. AC received honoraria from Incyte. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Angotzi, Lessi, Leoncin, Filì, Endri, Lico, Visentin, Pravato, Candoni, Trentin and Gurrieri.)
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- 2024
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76. Correlation between IPSET-t risk at diagnosis and subsequent hemorrhage in patients with essential thrombocythemia; a single institution experience.
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Tosoni L, Liberi M, Morelli G, Zannier ME, Lazzarotto D, Filì C, Simeone E, Battaglia G, Callegari C, Fanin M, Damiani D, Fanin R, and Tiribelli M
- Subjects
- Humans, Retrospective Studies, Risk Factors, Prognosis, Hemorrhage etiology, Hemorrhage complications, Mutation, Janus Kinase 2 genetics, Calreticulin genetics, Thrombocythemia, Essential complications, Thrombocythemia, Essential diagnosis, Thrombocythemia, Essential genetics, Thrombosis epidemiology
- Abstract
Essential thrombocythemia (ET) is a myeloproliferative neoplasm characterized by an increased risk of thrombotic and hemorrhagic events, that represent the leading causes of mortality and morbidity. Currently, while thrombotic risk is assessed through the IPSET-t and r-IPSET scores, there is no specific prognostic tool used to predict hemorrhagic risk in ET. The aim of the study was to define incidence and risk factors connected to hemorrhagic events by retrospectively analyzing 308 ET patients diagnosed between 1996 and 2022 at the Division of Hematology of Udine and treated according to the current international guidelines. According to molecular status, 193 patients (62.7%) were JAK2 mutated, 66 (21.4%) had a CALR mutation, 14 (4.5%) had a MPL mutation, 21 patients (6.8%) were "triple negative," and 14 patients (4.5%) were not evaluable. According to IPSET-t score, 49.7% patients were at high, 24.3% at intermediate, and 26.0% at low-risk, respectively. Twelve (3.9%) patients experienced bleeding at ET diagnosis, while 24 (7.8%) had at least one hemorrhagic event during follow-up at a median time of 103 months (range: 1-309). Forty hemorrhagic events were totally recorded and defined as minor in 22 cases, moderate in 11 cases, and severe in 7 cases. Cumulative incidence (CI) of hemorrhage at 10 and 20 years was 6.0% and 12.0%, respectively. A statistically significant correlation between hemorrhagic risk and IPSET-t score emerged: 10 years hemorrhage CI was 3.2% for low-risk, 2.9% for intermediate-risk, and 9.8% for high-risk patients, respectively (p=0.002). We found no correlation between hemorrhagic risk and gender or mutational status. Results of our study highlight the validity of IPSET-t score in predicting individual hemorrhagic risk among ET patients, suggesting a possible role of IPSET-t scoring system as a global evaluator for vascular events in ET patients., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2024
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77. Correction to: Correlation between IPSET‑t risk at diagnosis and subsequent hemorrhage in patients with essential thrombocythemia; a single institution experience.
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Tosoni L, Liberi M, Morelli G, Zannier ME, Lazzarotto D, Filì C, Simeone E, Battaglia G, Callegari C, Fanin M, Damiani D, Fanin R, and Tiribelli M
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- 2024
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78. Pulmonary Actinomycosis by Actinomyces graevenitzii in Two Hematologic Patients.
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Facchin G, Battaglia G, Sartor A, Filì C, Zannier ME, Battista ML, Fanin R, and Candoni A
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Competing Interests: Competing interests: The authors declare no conflict of Interest.
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- 2023
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79. Effect of heparin treatment on pulmonary embolism and in-hospital death in unvaccinated COVID-19 patients without overt deep vein thrombosis.
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Bais B, Sozio E, De Silvestri D, Volpetti S, Zannier ME, Filì C, Bassi F, Alcaro L, Cotrufo M, Pagotto A, Giacinta A, Patruno V, Da Porto A, Sbrojavacca R, Curcio F, Tascini C, Sechi LA, and Colussi G
- Abstract
Background: Pulmonary embolism (PE) without overt deep vein thrombosis (DVT) was common in hospitalized coronavirus-induced disease (COVID)-19 patients and represented a diagnostic, prognostic, and therapeutic challenge. The aim of this study was to analyze the prognostic role of PE on mortality and the preventive effect of heparin on PE and mortality in unvaccinated COVID-19 patients without overt DVT., Methods: Data from 401 unvaccinated patients (age 68 ± 13 years, 33% females) consecutively admitted to the intensive care unit or the medical ward were included in a retrospective longitudinal study. PE was documented by computed tomography scan and DVT by compressive venous ultrasound. The effect of PE diagnosis and any heparin use on in-hospital death (primary outcome) was analyzed by a classical survival model. The preventive effect of heparin on either PE diagnosis or in-hospital death (secondary outcome) was analyzed by a multi-state model after having reclassified patients who started heparin after PE diagnosis as not treated., Results: Median follow-up time was 8 days (range 1-40 days). PE cumulative incidence and in-hospital mortality were 27% and 20%, respectively. PE was predicted by increased D-dimer levels and COVID-19 severity. Independent predictors of in-hospital death were age (hazards ratio (HR) 1.05, 95% confidence interval (CI) 1.03-1.08, p < 0.001), body mass index (HR 0.93, 95% CI 0.89-0.98, p = 0.004), COVID-19 severity (severe versus mild/moderate HR 3.67, 95% CI 1.30-10.4, p = 0.014, critical versus mild/moderate HR 12.1, 95% CI 4.57-32.2, p < 0.001), active neoplasia (HR 2.58, 95% CI 1.48-4.50, p < 0.001), chronic obstructive pulmonary disease (HR 2.47; 95% CI 1.15-5.27, p = 0.020), respiratory rate (HR 1.06, 95% CI 1.02-1.11, p = 0.008), heart rate (HR 1.03, 95% CI 1.01-1.04, p < 0.001), and any heparin treatment (HR 0.35, 95% CI 0.18-0.67, p = 0.001). In the multi-state model, preventive heparin at prophylactic or intermediate/therapeutic dose, compared with no treatment, reduced PE risk and in-hospital death, but it did not influence mortality of patients with a PE diagnosis., Conclusions: PE was common during the first waves pandemic in unvaccinated patients, but it was not a negative prognostic factor for in-hospital death. Heparin treatment at any dose prevented mortality independently of PE diagnosis, D-dimer levels, and disease severity., (© 2022. The Author(s).)
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- 2022
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80. Clinical characteristics and outcome of 125 polymicrobial bloodstream infections in hematological patients: an 11-year epidemiologic survey.
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Facchin G, Candoni A, Lazzarotto D, Zannier ME, Peghin M, Sozio E, Pellegrini N, Filì C, Sartor A, Tascini C, and Fanin R
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- Bacteria, Drug Resistance, Multiple, Bacterial, Humans, Retrospective Studies, Risk Factors, Bacteremia epidemiology, Bacterial Infections, Sepsis
- Abstract
Background: Polymicrobial bloodstream infections (pBSI) occurring in hematological patients are still poorly understood, and specific information are very limited., Objectives and Methods: In this epidemiologic survey, we describe clinical characteristics and outcome of 125 consecutive pBSI occurred in oncohematological patients. Polymicrobial bloodstream infections (pBSI) were defined with the isolation of 2 or more bacteria from blood culture specimens obtained within 72 h., Results: Over an 11-year period, we documented 500 bacterial bloodstream infections (BSI) in 4542 hospital admissions and 25% (125) of these were pBSI. Most common underlying hematological disease was acute myeloid leukemia and 89% of patients had severe neutropenia. Fifty pBSI (40%) occurred in patients undergoing a stem cell transplantation (SCT), mostly within 30 days from transplant (42/50-84%). Principal bacterial association was Gram-positive plus Gram-negative (57%). Resolution rate of pBSI was 82%, without differences between SCT and non-SCT cases. pBSI-related mortality was 15% (6% in SCT cases). Septic shock occurred in 16% of cases and septic shock-related mortality was 65% (75% in SCT cases and 63% in non-SCT cases; p = 0.6). Multidrug-resistant (MDR) bacteria were involved in 22% of pBSI and the MDR-pBSI-related mortality was significantly higher in SCT patients (p = 0.007)., Conclusions: This observational study highlights that pBSI is not a rare bloodstream infectious complication in oncohematological patients. pBSI-related mortality is lower than 20%, but, if septic shock occurs, mortality reaches 65%. MDR bacteria were involved in 22% of cases and pBSI-MDR-related mortality was significantly higher in SCT patients., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2022
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81. SARS-CoV-2 in Myelodysplastic Syndromes: A Snapshot From Early Italian Experience.
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Mossuto S, Attardi E, Alesiani F, Angelucci E, Balleari E, Bernardi M, Binotto G, Bosi C, Calvisi A, Capodanno I, Carbone A, Castelli A, Cerrano M, Ciancia R, Cilloni D, Clavio M, Clissa C, Crisà E, Crugnola M, Della Porta MG, Di Renzo N, Di Veroli A, Fattizzo R, Fava C, Fenu S, Ferrara IL, Fianchi L, Filì C, Finelli C, Giai V, Frattini F, Gaidano V, Guaragna G, Gumenyuk S, Latagliata R, Mancini S, Messa E, Molteni A, Musto P, Niscola P, Oliva E, Palumbo GA, Pelizzari A, Pilo F, Poloni A, Riva M, Rivellini F, Sarlo C, Sciumé M, Secchi R, Selleri C, Tafuri A, and Santini V
- Abstract
Competing Interests: The authors have no conflicts of interest to disclose.
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- 2020
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82. Population Pharmacokinetics of Continuous-Infusion Meropenem in Febrile Neutropenic Patients with Hematologic Malignancies: Dosing Strategies for Optimizing Empirical Treatment against Enterobacterales and P. aeruginosa .
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Cojutti PG, Candoni A, Lazzarotto D, Filì C, Zannier M, Fanin R, and Pea F
- Abstract
A population pharmacokinetic analysis of continuous infusion (CI) meropenem was conducted in a prospective cohort of febrile neutropenic (FN) patients with hematologic malignancies. A non-parametric approach with Pmetrics was used for pharmacokinetic analysis and covariate evaluation. Monte Carlo simulations were performed for identifying the most appropriate dosages for empirical treatment against common Enterobacterales and P. aeruginosa. The probability of target attainment (PTA) of steady-state meropenem concentration (Css)-to-minimum inhibitory concentration (MIC) ratio (Css/MIC) ≥1 and ≥4 at the European Committee on Antimicrobial Susceptibility Testing (EUCAST) clinical breakpoint of 2 mg/L were calculated. Cumulative fraction of response (CFR) against Enterobacterales and P. aeruginosa were assessed as well. PTAs and CFRs ≥ 90% were considered optimal. A total of 61 patients with 178 meropenem Css were included. Creatinine clearance (CL
CR ) was the only covariate associated with meropenem clearance. Monte Carlo simulations showed that dosages of meropenem ranging between 1 g q8h and 1.25 g q6h by CI may grant optimal PTAs of Css/MIC ≥4 at the EUCAST clinical breakpoint. Optimal CFRs may be granted with these dosages against the Enterobacterales at Css/MIC ≥ 4 and against P. aeruginosa at Css/MIC ≥ 1. When dealing against P. aeruginosa at Css/MIC ≥ 4, only a dosage of 1.5 g q6h by CI may grant quasi-optimal CFR (around 80-87%). In conclusion, our findings suggest that dosages of meropenem ranging between 1 g q8h and 1.25 g q6h by CI may maximize empirical treatment against Enterobacterales and P. aeruginosa among FN patients with hematologic malignancies having different degree of renal function.- Published
- 2020
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83. Real-world experience with decitabine as a first-line treatment in 306 elderly acute myeloid leukaemia patients unfit for intensive chemotherapy.
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Bocchia M, Candoni A, Borlenghi E, Defina M, Filì C, Cattaneo C, Sammartano V, Fanin R, Sciumè M, Sicuranza A, Imbergamo S, Riva M, Fracchiolla N, Latagliata R, Caizzi E, Mazziotta F, Alunni G, Di Bona E, Crugnola M, Rossi M, Consoli U, Fontanelli G, Greco G, Nadali G, Rotondo F, Todisco E, Bigazzi C, Capochiani E, Molteni A, Bernardi M, Fumagalli M, Rondoni M, Scappini B, Ermacora A, Simonetti F, Gottardi M, Lambertenghi Deliliers D, Michieli M, Basilico C, Galeone C, Pelucchi C, and Rossi G
- Subjects
- Aged, Aged, 80 and over, Antimetabolites, Antineoplastic adverse effects, Antimetabolites, Antineoplastic therapeutic use, Cause of Death, Decitabine adverse effects, Disease Progression, Female, Humans, Infections etiology, Kaplan-Meier Estimate, Leukemia, Myeloid, Acute mortality, Male, Multicenter Studies as Topic statistics & numerical data, Observational Studies as Topic statistics & numerical data, Prognosis, Proportional Hazards Models, Risk Factors, Treatment Outcome, Decitabine therapeutic use, Leukemia, Myeloid, Acute drug therapy
- Abstract
Despite widespread use of decitabine to treat acute myeloid leukaemia (AML), data on its effectiveness and safety in the real-world setting are scanty. Thus, to analyze the performance of decitabine in clinical practice, we pooled together patient-level data of three multicentric observational studies conducted since 2013 throughout Italy, including 306 elderly AML patients (median age 75 years), unfit for intensive chemotherapy, treated with first-line decitabine therapy at the registered schedule of 20 mg/m
2 /iv daily for 5 days every 4 weeks. Overall response rate (ORR), overall survival (OS) curves, and multivariate hazard ratios (HRs) of all-cause mortality were computed. Overall, 1940 cycles of therapy were administered (median, 5 cycles/patient). A total of 148 subjects were responders and, therefore, ORR was 48.4%. Seventy-one patients (23.2%) had complete remission, 32 (10.5%) had partial remission, and 45 (14.7%) had haematologic improvement. Median OS was 11.6 months for patients with favourable-intermediate cytogenetic risk and 7.9 months for those with adverse cytogenetic risk. Median relapse-free survival after CR was 10.9 months (95% confidence interval [CI]: 8.7-16.0). In multivariate analysis, mortality was higher in patients with adverse cytogenetic risk (HR=1.58; 95% CI: 1.13-2.21) and increased continuously with white blood cell (WBC) count (HR=1.12; 95% CI: 1.06-1.18). A total of 183 infectious adverse events occurred in 136 patients mainly (>90%) within the first five cycles of therapy. This pooled analysis of clinical care studies confirmed, outside of clinical trials, the effectiveness of decitabine as first-line therapy for AML in elderly patients unfit for intensive chemotherapy. An adverse cytogenetic profile and a higher WBC count at diagnosis were, in this real life setting, unfavourable predictors of survival., (© 2019 John Wiley & Sons, Ltd.)- Published
- 2019
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84. Efficacy and toxicity of Decitabine in patients with acute myeloid leukemia (AML): A multicenter real-world experience.
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Filì C, Candoni A, Zannier ME, Olivieri J, Imbergamo S, Caizzi M, Nadali G, Di Bona E, Ermacora A, Gottardi M, Facchinelli D, Ciancia R, Lazzarotto D, Dubbini MV, Festini G, Gherlinzoni F, Michieli MG, Semenzato G, and Fanin R
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- Adult, Aged, Aged, 80 and over, Antimetabolites, Antineoplastic administration & dosage, Antimetabolites, Antineoplastic adverse effects, Decitabine administration & dosage, Decitabine adverse effects, Female, Humans, Italy, Leukemia, Myeloid, Acute diagnosis, Leukemia, Myeloid, Acute mortality, Male, Middle Aged, Proportional Hazards Models, Remission Induction, Retrospective Studies, Treatment Outcome, Antimetabolites, Antineoplastic therapeutic use, Decitabine therapeutic use, Leukemia, Myeloid, Acute drug therapy
- Abstract
Background: The hypomethylating agent Decitabine (DAC) is a valuable treatment option in acute myeloid leukemia (AML), particularly in elderly patients (pts) not suitable for intensive chemotherapy (CHT). However, limited data are available about efficacy and safety of DAC in clinical practice., Patients and Methods: We retrospectively reviewed data of 104 AML pts treated with DAC in eight Italian Hematological Centers from 2015 to 2017. The objective of this study was to evaluate the efficacy and safety of DAC in older AML pts outside of clinical trial. Seventy-five (75%) pts received DAC as first line treatment (Cohort 1) and 29 pts as salvage therapy (Cohort 2). All pts received a DAC schedule of 20 mg/sqm IV for 5-days, every 28 days. The median age was 72.5 years (74 in cohort 1 and 66 in cohort 2) and 16% of pts had an ECOG performance status >2 at the start of DAC treatment (with non-significant difference in the two cohorts). The cumulative illness rating scale (CIRS) was > 6 in 27% of pts. Forty-five pts (43%) had secondary AML. Bone marrow blast count was > 30% in 64% of patients (67/104). In the relapsed cohort 17/29 (59%) patients were treated with DAC after conventional CHT, 5/29 (17%) after allo-SCT and 7/29 (24%) after azacitidine therapy., Results: A total of 469 DAC cycles were given to the 104 pts with a median of 3 cycles (range 1-21) and 45/104 (43%) pts received > 4 cycles. The Overall Response Rate (ORR = Complete Remission-CR plus Partial Remission-PR) was 33%, significantly higher in Cohort 1 (42%) compared to Cohort 2 (14%) (p = 0.009). The median duration of response was 6 months (range 1-20). In Cohort 1 the best response (CR or PR) was obtained between 3th and 6th cycle. In multivariate Cox regression analysis, achievement of CR or PR (HR = 0.78; p = 0.0004), CIRS < 6 (HR = 0.9; p = 0.04) and complex karyotype (HR = 0.8; p = 0.03) were significant predictors of better overall survival (OS). Median OS from the start of DAC therapy was 11 months for the whole population with a significant OS advantage in Cohort 1 (median OS 12.7 mths vs 6.3 mths; p = 0.003); median OS was significantly longer in responders compared to non-responders (22.6 mths vs 5.7 mths; p < 0.0001). At the last follow-up, 56 patients (54%) are still alive and 48 (46%) are dead (71% due to disease progression). The most common toxicities were myelosuppression and documented infectious complications that occurred mainly during the first 4 cycles., Conclusion: These data confirm the efficacy (ORR 33%) and the acceptable safety profile of DAC in the real life management of AML in elderly pts unsuitable for intensive CHT, with a significant better performance in first line therapy (ORR 42%, median OS 12.7 mths). The efficacy of DAC, both in first line and as salvage therapy, may probably be improved with combined treatment strategies and/or with different DAC schedules that could increase its anti-leukemic effect., (Copyright © 2018 Elsevier Ltd. All rights reserved.)
- Published
- 2019
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85. High prognostic value of pre-allogeneic stem cell transplantation minimal residual disease detection by WT1 gene expression in AML transplanted in cytologic complete remission.
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Candoni A, De Marchi F, Zannier ME, Lazzarotto D, Filì C, Dubbini MV, Rabassi N, Toffoletti E, Lau BW, and Fanin R
- Subjects
- Adolescent, Adult, Aged, Biomarkers, Tumor genetics, Female, Follow-Up Studies, Humans, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute therapy, Male, Middle Aged, Neoplasm Recurrence, Local genetics, Neoplasm Recurrence, Local therapy, Neoplasm, Residual genetics, Neoplasm, Residual therapy, Prognosis, Remission Induction, Survival Rate, Transplantation, Homologous, WT1 Proteins genetics, Young Adult, Biomarkers, Tumor metabolism, Leukemia, Myeloid, Acute pathology, Neoplasm Recurrence, Local pathology, Neoplasm, Residual pathology, Stem Cell Transplantation, WT1 Proteins metabolism
- Abstract
We analyzed the outcome of allogeneic stem cell transplantation (allo-SCT) in acute myeloid leukemia (AML) patients according to molecular Minimal Residual Disease (MRD) status prior to allo-SCT. MRD was assessed by the quantitative expression of the pan-leukemic marker Wilms' tumor (WT1) gene, according to the validated LeukemiaNet method. Between 2005 and 2016, 122 consecutive AML patients, WT1 positive at diagnosis, received allo-SCT in cytologic complete remission (cCR). The median age at SCT was 53 years (range 18-70). Quantitative analysis of WT1 gene expression (bone marrow samples) was available in all cases both at diagnosis (100% of samples overexpressed WT1 with a mean of 8607±8187 copies/10
4 Abelson) and immediately before allo-SCT. Eighty one cases (66%) were MRD-WT1 negative (WT1 <250 copies) and 41/122 (44%) cases were MRD-WT1 positive (WT1 >250 copies) prior to allo-SCT. We evaluated post-SCT overall survival (OS), disease free survival (DFS) and relapse rate (RR), according to MRD-WT1 status pre-SCT. Both post-allo-SCT OS and DFS were significantly improved in patients who were MRD-WT1 negative at the time of SCT compared with those who were MRD-WT1 positive, with a median OS and DFS not reached in the MRD-WT1 negative group and 9 and 8 months, respectively, in the WT1 positive group (OS log-rank p<0.0001; hazard ratio [HR] 3.9, 95% confidence interval [95% CI] 2.0-7.38; DFS log-rank p<0.0001; HR 3.73, 95% CI 2.0-6.72). The RR after SCT was 15% (12/81) in pre-SCT MRD-WT1 negative cases and 44% (18/41) in MRD-WT1 positive cases (p=0.00073). Univariate analysis showed that MRD-WT1 negativity pre-SCT and grade <2 acute GVHD were significant prognostic factors for improved OS and DFS. However multivariate analysis showed MRD-WT1 negativity pre-SCT was the only independent prognostic factor for improved OS and DFS. These data show that pre allo-SCT molecular MRD evaluation using WT1 expression is a powerful predictor of post allo-SCT outcomes in AML undergoing SCT in cCR. Patients with both cCR and MRD-WT1 negativity before SCT have a very good outcome with lower RR and improved OS. The pre allo-SCT MRD-WT1 stratification in AML is a valuable tool to identify patients at high risk of post-SCT relapse, and can influence conditioning regimen intensification and/or post-SCT preemptive strategies., (Copyright © 2017 Elsevier Ltd. All rights reserved.)- Published
- 2017
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86. Predictive value of pretransplantation molecular minimal residual disease assessment by WT1 gene expression in FLT3-positive acute myeloid leukemia.
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Candoni A, De Marchi F, Zanini F, Zannier ME, Simeone E, Toffoletti E, Chiarvesio A, Cerno M, Filì C, Patriarca F, and Fanin R
- Subjects
- Adult, Allografts, Disease-Free Survival, Female, Humans, Male, Middle Aged, Neoplasm, Residual, Predictive Value of Tests, Remission Induction, Survival Rate, Biomarkers, Tumor biosynthesis, Gene Expression Regulation, Leukemic, Leukemia, Myeloid, Acute metabolism, Leukemia, Myeloid, Acute mortality, Leukemia, Myeloid, Acute pathology, Leukemia, Myeloid, Acute therapy, Preoperative Period, Stem Cell Transplantation, WT1 Proteins biosynthesis, fms-Like Tyrosine Kinase 3 biosynthesis
- Abstract
The FMS-like tyrosine kinase 3 (FLT3) mutation in acute myeloid leukemia (AML) is a negative prognostic factor and, in these cases, allogeneic stem cell transplantation (allo-SCT) can represent an important therapeutic option, especially if performed in complete remission (CR). However, it is increasingly clear that not all cytological CRs (cCRs) are the same and that minimal residual disease (MRD) before allo-SCT could have an impact on AML outcome. Unfortunately, FLT3, due its instability of expression, is still not considered a good molecular MRD marker. We analyzed the outcome of allo-SCT in a population of FLT3-positive AML patients according to molecular MRD at the pretransplantation workup, assessed by the quantitative expression evaluation of the panleukemic marker Wilms' tumor (WT1) gene. Sixty-two consecutive AML FLT3-positive patients received allo-SCT between 2005 and 2016 in our center. The median age at transplantation was 55 years. The quantitative analysis of the WT1 gene expression (bone marrow samples) was available in 54 out of 62 (87%) cases, both at diagnosis (100% overexpressing WT1 with a mean of 9747 ± 8064 copies) and before allo-SCT (33 WT1-negative and 21 WT1-positive cases at the pretransplantation workup). Of these cases, 33/54 (61%) were both in cCR and molecular remission (WT1-negative) at the time of transplantation, 13/54 (24%) were in cCR but not in molecular remission (WT1-positive), and 8/54 (15%) showed a cytological evidence of disease (relapsed or refractory). Both post-allo-SCT overall survival (OS) and disease-free survival (DFS) were significantly better in patients who were WT1-negative (WT1 <250 copies) at the time of transplantation compared with those who were WT1-positive (WT1 >250 copies), with a median OS and DFS not reached in the WT1-negative group and 10.2 and 5.5 months, respectively, in the WT1-positive group (OS log-rank p = 0.0005; hazard ratio [HR] = 3.7, 95% confidence interval [95% CI] = 1.5-9; DFS log-rank p = 0.0001; HR = 4.38, 95% CI = 1.9-10). Patients with cCR who were WT1-positive had the same negative outcome as those with a cytological evidence of disease. The relapse rate after allo-SCT was 9% (3/33) in pre-allo-SCT WT1-negative cases and 54% (7/13) in WT1-positive cases (p = 0.002). At multivariate analysis, WT1 negativity before allo-SCT and grade <2 acute graft versus host disease were the only independent prognostic factors for improved OS and DFS. These data show that pre-allo-SCT molecular MRD evaluation through WT1 expression is a powerful predictor of posttransplantation outcomes (OS, DFS, relapse rate). Patients with both cCR and a WT1-negative marker before allo-SCT have a very good outcome with very low relapse rate; conversely, patients with positive molecular MRD and refractory/relapsed patients have a negative outcome. The WT1 MRD stratification in FLT3-positive AML is a valuable tool with which to identify patients who are at high risk of relapse and that could be considered from post-allo-SCT prophylaxis with FLT3 inhibitors or other strategies (donor lymphocyte infusion, tapering of immunosuppression, azacitidine)., (Copyright © 2017 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2017
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87. Clinical outcome of myeloid sarcoma in adult patients and effect of allogeneic stem cell transplantation. Results from a multicenter survey.
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Lazzarotto D, Candoni A, Filì C, Forghieri F, Pagano L, Busca A, Spinosa G, Zannier ME, Simeone E, Isola M, Borlenghi E, Melillo L, Mosna F, Lessi F, and Fanin R
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Disease-Free Survival, Female, Humans, Male, Middle Aged, Retrospective Studies, Sarcoma, Myeloid mortality, Stem Cell Transplantation adverse effects, Survival Rate, Transplantation, Homologous, Treatment Outcome, Young Adult, Sarcoma, Myeloid therapy, Stem Cell Transplantation methods
- Abstract
Introduction: Myeloid Sarcoma (MS) is a rare hematologic myeloid neoplasm that can involve any site of the body. It can occur as an exclusively extramedullary form or it can be associated with an acute myeloid leukemia (AML), a chronic myeloproliferative neoplasm (MPN) or a myelodysplastic syndrome (MDS) at onset or at relapse. The rarity of MS does not enable prospective clinical trials and therefore a specific multicenter register can be useful for the clinical and biological studies of this rare disease., Patients and Results: we report the clinical characteristics and outcome of 48 histologically confirmed MS, diagnosed and treated in 9 Italian Hematological Centers in the last 10 years. The patient's median age was 46 years. There were 9/48 de novo extramedullary MS, 24/48 de novo AML-related MS and 15/48 were secondary AML-related MS. The most common extramedullary anatomic sites of disease were: skin, lymph nodes and soft tissues. Forty-three patients (90%) underwent a program of intensive chemotherapy including FLAI, HDAC-IDA, HyperCVAD and MEC schemes, with a DDI of 5% and a CR Rate of 45%. Twenty-two (46%) patients underwent Allogeneic SCT, 13 from a MUD, 8 from an HLA-identical sibling donor and 1 from an haploidentical donor. The median OS of the whole population (48 pts) was 16.7 months. The OS probability at 1, 2 and 5 years was 64%, 39% and 33%, respectively. The OS was better in patients that underwent an intensive therapeutic program (median OS: 18 months vs 5 months). Among the intensively treated patients, in univariate analysis, the OS was better in young patients (P=0,008), in patients that underwent Allo-SCT (P=0,009) and in patients that achieved a CR during treatment (P=0,001), and was worse in pts with secondary AML-related MS (P=0,007). Age, response to intensive chemotherapy and Allo-SCT were the only three variables that significantly influenced DFS (P=0,02, P=0,01 and P=0,04, respectively). In multivariable analysis, Allo-SCT and response to intensive chemotherapy remained significant in predicting a better OS (P=0,04 and P=0,001, respectively), and response to intensive chemotherapy was the only significant variable in predicting DFS (P=0,01). After Allo-SCT we observe a survival advantage in patients who achieved a pre-transplant CR (P=0,008) and in those who developed a chronic GvHD (P=0,05)., Conclusions: Patients with MS, both with de novo and secondary forms, still have a very unfavorable outcome and require an intensive therapeutic program, that includes Allo-SCT whenever possible. The outcome after Allo-SCT is positively influenced by the development of chronic GvHD suggesting a Graft versus MS effect., (Copyright © 2016 Elsevier Ltd. All rights reserved.)
- Published
- 2017
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88. Treatment of chronic myeloid leukemia elderly patients in the tyrosine kinase inhibitor era.
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Russo D, Malagola M, Skert C, Filì C, Bergonzi C, Cancelli V, and Cattina F
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- Age Factors, Antineoplastic Agents adverse effects, Antineoplastic Agents chemistry, Drug Design, Humans, Leukemia, Myelogenous, Chronic, BCR-ABL Positive enzymology, Leukemia, Myelogenous, Chronic, BCR-ABL Positive mortality, Leukemia, Myelogenous, Chronic, BCR-ABL Positive pathology, Medication Adherence, Molecular Targeted Therapy, Patient Selection, Protein Kinase Inhibitors adverse effects, Protein Kinase Inhibitors chemistry, Protein-Tyrosine Kinases metabolism, Signal Transduction drug effects, Treatment Outcome, Antineoplastic Agents therapeutic use, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Protein Kinase Inhibitors therapeutic use, Protein-Tyrosine Kinases antagonists & inhibitors
- Abstract
The prevalence of chronic myeloid leukemia (CML) is expected to double in the next 15 years. The introduction of imatinib significantly changed the prognosis of CML, challenging the concept of a fatal disease. Nowdays, imatinib, nilotinib and dasatinib are registered for first-line treatment of CML patients in chronic phase (CP). Considering elderly patients, the most extensively studied TKI is imatinib, that induces a rate of cytogenetic and molecular responses comparable between the younger and the elderly patients. Once a CCgR with imatinib is achieved, the probability to be alive and disease free at 8 years is more than 80%. These results confirm that imatinib has to be considered the first-line treatment for the elderly and that the CCgR is the guide parameter for treatment modulation and the most solid marker of long term outcome. Nevertheless, older patients tolerate imatinib worse in comparison to the younger, and this causes a higher rate of therapy discontinuation and less adherence to chronic treatment. Thus, the toxic profile of each TKI is one of the most important factors driving the choice of the best drug. Another important factor is the potency of the TKI. Since nilotinib and dasatinib are more potent than imatinib in inducing cytogenetic and molecular responses, they could be preferred for increasing the proportion of patients who can achieve deeper molecular responses, allowing treatment discontinuation. This approach is intriguing, but it is still experimental. Another therapeutic strategy could be the identification of the minimal effective dose of TKI in order to maintain the CCgR, but also this approach is under clinical investigation.
- Published
- 2013
- Full Text
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89. Prospective phase II Study on 5-days azacitidine for treatment of symptomatic and/or erythropoietin unresponsive patients with low/INT-1-risk myelodysplastic syndromes.
- Author
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Filì C, Malagola M, Follo MY, Finelli C, Iacobucci I, Martinelli G, Cattina F, Clissa C, Candoni A, Fanin R, Gobbi M, Bocchia M, Defina M, Spedini P, Skert C, Manzoli L, Cocco L, and Russo D
- Subjects
- Aged, Aged, 80 and over, Drug Administration Schedule, Erythropoietin metabolism, Female, Gene Expression Regulation, Neoplastic, Hematologic Tests, Humans, Male, Middle Aged, Myelodysplastic Syndromes genetics, Myelodysplastic Syndromes pathology, Polymorphism, Single Nucleotide, Prospective Studies, Treatment Outcome, Azacitidine administration & dosage, Myelodysplastic Syndromes drug therapy, Phospholipase C beta genetics, Wnt1 Protein genetics
- Abstract
Purpose: This phase II prospective study aimed to evaluate the efficacy and safety of 5-days azacytidine (5d-AZA) in patients with low-risk myelodysplastic syndromes (MDS). Second, single-nucleotide polymorphism (SNP) genetic profile and phosphoinositide-phospholipase C (PI-PLC) β1 levels were studied to evaluate possible biologic markers able to predict the hematologic response., Experimental Design: The study tested a lower intensity schedule of azacytidine. The treatment plan consisted of 75 mg/sqm/d subcutaneous administered for 5 days every 28 days, for a total of 8 cycles., Results: Thirty-two patients were enrolled in the study. The overall response rate was 47% (15 of 32) on intention-to-treat and 58% (15 of 26) for patients completing the treatment program. In this latter group, 5 (19%) achieved complete remission (CR) and 10 (38%) had hematologic improvement, according to the International Working Group (IWG) criteria. Three patients have maintained their hematologic improvement after 37, 34, and 33 months without other treatments. Moreover, 21 and 2 of 26 cases completing 8 cycles were transfusion-dependent for red blood cells and platelets at baseline, respectively. Of these, 7 (33%) and 2 (100%) became transfusion-independent at the end of the treatment program, respectively. Grade 3-4 neutropenia occurred in 28% of patients and 4 patients died early due to infections or hemorrhage. SNP results were not significantly correlated to the clinical outcome, whereas PI-PLCβ1 level anticipated either positive or negative clinical responses., Conclusions: 5d-AZA is safe and effective in a proportion of patients with low-risk MDS. PI-PLCβ1 gene expression is a reliable and dynamic marker of response that can be useful to optimize azacytidine therapy.
- Published
- 2013
- Full Text
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90. Profile of toll-like receptors on peripheral blood cells in relation to acute graft-versus-host disease after allogeneic stem cell transplantation.
- Author
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Skert C, Fogli M, Perucca S, Garrafa E, Fiorentini S, Filì C, Bergonzi C, Malagola M, Turra A, Colombi C, Cattina F, Alghisi E, Caruso A, and Russo D
- Subjects
- Acute Disease, Adolescent, Adult, Enzyme-Linked Immunosorbent Assay, Female, Flow Cytometry, Humans, Male, Middle Aged, Monocytes metabolism, T-Lymphocytes metabolism, Transplantation, Homologous, Young Adult, Graft vs Host Disease blood, Stem Cell Transplantation, Toll-Like Receptors blood
- Abstract
Toll-like receptors (TLRs) play a key role in the cross-talk between the innate and adaptive immune systems. Previous studies investigating associations between certain TLRs and acute graft-versus-host disease (aGVHD) have reported contrasting results, and no studies relating aGVHD to the expression and function of all human TLRs together have been published to date. We prospectively evaluated the expression of 9 TLRs on T lymphocytes and monocytes by flow cytometry in relation to aGVHD in 34 patients. Induction of TNF-α, IL-4, IFN-γ, and monocyte chemotactic protein 1 on TLR activation was assessed by ELISA on cell supernatants. Nineteen patients developed aGVHD, at a median time of 28 days (range, 20-50 days) after transplantation. A 2-step multivariate analysis was performed using principal component analysis and multifactor analysis of variance. The levels of TLR-5 expression on monocytes and T lymphocytes were positively correlated to aGVHD (P = .01), whereas levels of TLR-1 and -9 were negative predictors (P = .03 and .01, respectively). This profile of TLR-1, -5, and -9 can promote an overall immunostimulatory/proinflammatory response. If our findings are confirmed by further studies, this TLR profile could be a useful biomarker of aGVHD., (Copyright © 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2013
- Full Text
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91. Incidence of bacterial and fungal infections in newly diagnosed acute myeloid leukaemia patients younger than 65 yr treated with induction regimens including fludarabine: retrospective analysis of 224 cases.
- Author
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Malagola M, Peli A, Damiani D, Candoni A, Tiribelli M, Martinelli G, Piccaluga PP, Paolini S, De Rosa F, Lauria F, Bocchia M, Gobbi M, Pierri I, Zaccaria A, Zuffa E, Mazza P, Priccolo G, Gugliotta L, Bonini A, Visani G, Skert C, Bergonzi C, Roccaro AM, Filì C, Fanin R, Baccarani M, and Russo D
- Subjects
- Adult, Antineoplastic Agents administration & dosage, Bacteremia chemically induced, Bacteremia mortality, Female, Fever chemically induced, Fever mortality, Gram-Negative Bacterial Infections chemically induced, Gram-Positive Bacterial Infections chemically induced, Humans, Incidence, Leukemia, Myeloid, Acute drug therapy, Male, Middle Aged, Mycoses chemically induced, Retrospective Studies, Risk Factors, Survival Rate, Vidarabine administration & dosage, Vidarabine adverse effects, Antineoplastic Agents adverse effects, Gram-Negative Bacterial Infections mortality, Gram-Positive Bacterial Infections mortality, Leukemia, Myeloid, Acute mortality, Mycoses mortality, Vidarabine analogs & derivatives
- Abstract
Objectives: Infections are the major cause of morbidity and mortality in patients with acute myeloid leukaemia (AML). They primarily occur during the first course of induction chemotherapy and may increase the risk of leukaemia relapse, due to a significant delay in consolidation therapy. The intensification of induction chemotherapy and the use of non-conventional drugs such as fludarabine are considered responsible for the increased risk of infections., Methods: In this study, we retrospectively analysed the infections occurred in 224 newly diagnosed AML patients =65 yr, consecutively treated between 1997 and 2002 with an induction regimen including fludarabine, arabinosyl cytosine and idarubicin, with or without etoposide (FLAI/FLAIE), in the context of three multicentric prospective trials (AML97, AML99, AML02)., Results: During the induction phase, 146 (65%) patients experienced fever of undetermined origin (FUO), 30 (13%) and 47 (21%) patients had Gram-negative and positive bacteremias, respectively, and 10 (4%) patients developed a probable/proven invasive fungal infection (IFI). The fatality rate for Gram-negative, Gram-positive bacteremias and probable/proven IFI was 10%, 8% and 60% respectively. During consolidation, 75 (35%) patients had FUO, 43 (20%) and 40 (19%) patients had Gram-negative and positive bacteremias, respectively, and 5 (2%) patients developed a probable/proven IFI. The fatality rate for Gram-negative, Gram-positive bacteremias and probable/proven IFI was 14%, 5% and 80% respectively. Interestingly, the overall incidence of microbiologically documented infections during induction was 38% and the incidence of probable/proven IFIs during the induction/consolidation programme was 7%. No infections caused by viruses or opportunistic pathogens were observed neither during induction, nor during consolidation., Conclusions: These data, although retrospectively collected, suggest that fludarabine-based chemotherapy is not associated with an increased incidence of infections, in particular IFIs, compared to conventional regimens commonly used for AML induction.
- Published
- 2008
- Full Text
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92. Earlier administration of Rituximab allows higher rate of long-lasting response in adult patients with autoimmune thrombocytopenia.
- Author
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Zaja F, Vianelli N, Battista M, Sperotto A, Patriarca F, Tomadini V, Filì C, Tani M, Baccarani M, and Fanin R
- Subjects
- Adult, Antibodies, Monoclonal therapeutic use, Antibodies, Monoclonal, Murine-Derived, Humans, Middle Aged, Platelet Count, Rituximab, Antibodies, Monoclonal administration & dosage, Purpura, Thrombocytopenic, Idiopathic drug therapy
- Published
- 2006
- Full Text
- View/download PDF
93. The development of autoantibodies after allogeneic stem cell transplantation is related with chronic graft-vs-host disease and immune recovery.
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Patriarca F, Skert C, Sperotto A, Zaja F, Falleti E, Mestroni R, Kikic F, Calistri E, Filì C, Geromin A, Cerno M, and Fanin R
- Subjects
- Adult, Chronic Disease, Female, Humans, Male, Middle Aged, Autoantibodies biosynthesis, Graft vs Host Disease immunology, Stem Cell Transplantation
- Abstract
Objective: Chronic graft-vs-host disease (GVHD) has certain similarities with autoimmune diseases and is associated with the development of various autoantibodies in some patients. In this study, we analyzed the occurrence of autoantibodies in 63 patients surviving longer than 3 months after an allogeneic haematopoietic stem cell transplantation (HSCT), with the aim of detecting a possible association between occurrence of autoantibodies and development of chronic GVHD and immune recovery after HSCT., Patients and Methods: The patients were screened every 3 months for the occurrence of the following autoantibodies: anti-nuclear (ANA), anti-mitochondrial (AMA), anti-smooth muscle (ASMA), anti-cardiolipin (ACLA), anti-liver-kidney microsomal (LKM), anti-DNA, anti-neutrophil cytoplasmatic (ANCA), and anti-thyroid antibodies. Peripheral blood immunophenotyping with anti-CD3, CD4, CD8, CD19, CD20, CD16, and CD56 antibodies was evaluated at the same intervals., Results: Autoantibodies were not found in 18 patients (29%), at least in one screening in 29 patients (46%), and in all screenings in 16 patients (25%). ANA were found in 41 patients (65%), AMA in 4 (6%), ASMA in 4 (6%), ANCA in 7 (11%), ACLA in 1 (2%), anti-thyroid antibodies in 3 (5%), and anti-DNA in 2 (3%). More than one antibody occurred in 16/63 (25%) positive patients. ANA was significantly more frequent in patients with chronic GVHD and, among these, in those with the extensive form. The nucleolar pattern of immunofluorescence of ANA but not its titer was correlated with the extension of chronic GVHD. Patients who developed autoantibodies had higher CD20(+) cell blood counts than negative patients in the third month (p=0.006), ninth month (p=0.061), and twelfth month (p=0.043)., Conclusion: We conclude that patients with chronic GVHD, particularly those with an extensive involvement, were likely to develop autoantibodies and have a faster B-cell recovery, suggesting a role of B cells in the pathogenesis of chronic GVHD.
- Published
- 2006
- Full Text
- View/download PDF
94. Sclerodermatous chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation: incidence, predictors and outcome.
- Author
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Skert C, Patriarca F, Sperotto A, Cerno M, Filì C, Zaja F, Stocchi R, Geromin A, Damiani D, and Fanin R
- Subjects
- Adolescent, Adult, Aged, Chronic Disease, Female, Graft vs Host Disease etiology, Humans, Incidence, Male, Middle Aged, Retrospective Studies, Risk Factors, Transplantation, Homologous, Treatment Outcome, Graft vs Host Disease pathology, Hematopoietic Stem Cell Transplantation adverse effects, Scleroderma, Systemic etiology
- Abstract
Scleroderma may be one of the most severe forms of chronic graft-versus-host disease (GVHD). We retrospectively evaluated its incidence, predictor variables and outcome in 133 patients who survived at least 4 months after allogeneic hematopoietic stem cell transplantation. The 5-year cumulative incidence was 15.5% in patients with chronic GVHD. The generalized form had a progressive course despite immunosuppressive therapy. Eosinophilia, autoimmune markers, and previous skin involvement by chronic GVHD with disorders of pigmentation were significantly associated with an increased probability of developing scleroderma.
- Published
- 2006
95. Abdominal abscess and Hafnia alvei septicemia occurring during the aplastic phase after autologous stem-cell transplantation in a patient with diffuse large B-cell lymphoma.
- Author
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Candoni A, Trevisan R, Filì C, Tiribelli M, and Fanin R
- Subjects
- Enterobacteriaceae Infections microbiology, Female, Hepatitis C complications, Humans, Lymphoma, Large B-Cell, Diffuse therapy, Middle Aged, Transplantation, Autologous adverse effects, Abdominal Abscess microbiology, Bacteremia microbiology, Hafnia alvei isolation & purification, Lymphoma, B-Cell therapy, Stem Cell Transplantation adverse effects
- Abstract
Hafnia alvei is a motile gram-negative bacterium that is rarely isolated from human specimens, but that sometimes can be found as part of the gastrointestinal flora. Here we report a rare case of Hafnia alvei septicemia with an abdominal abscess in a 60-year-old woman with diffuse large B-cell lymphoma involving the spleen, liver, and then lymph nodes. She initially received a splenectomy, and, over a 2-year period, four courses of chemotherapy. After achieving complete remission status, she underwent autologous peripheral blood stem-cell transplantation (PBSCT). During the aplastic phase following transplantation, the patient developed fever, diarrhea, and abdominal pain, with blood cultures positive for Hafnia alvei and an abscess in the splenic recess. Considering the high surgical risk, the infection was treated, successfully, with antibiotics (imipenem/cilastatin), without surgery or computed tomography (CT)-guided percutaneous drainage. Infections due to Hafnia alvei are rare, and this is the first reported case of Hafnia alvei septicemia in an adult hematologic patient undergoing a stem-cell transplantation procedure.
- Published
- 2004
- Full Text
- View/download PDF
96. Autologus stem cell transplantation as postremission therapy for acute myeloid leukemia. Risk factors at diagnosis can predict the outcome.
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Candoni A, Sperotto A, Tomadini V, Filì C, Damiani D, and Fanin R
- Subjects
- Female, Humans, Leukemia, Myeloid, Acute mortality, Male, Predictive Value of Tests, Retrospective Studies, Risk Factors, Stem Cell Transplantation adverse effects, Survival Analysis, Tissue and Organ Harvesting methods, Transplantation, Autologous adverse effects, Transplantation, Autologous methods, Treatment Outcome, Leukemia, Myeloid, Acute therapy, Stem Cell Transplantation methods
- Published
- 2003
- Full Text
- View/download PDF
97. Early chemosensitivity to VAD regimen predicts a favorable outcome after autologous stem cell transplantation in multiple myeloma.
- Author
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Patriarca F, Sperotto A, Filì C, Zaja F, Prosdocimo S, and Fanin R
- Subjects
- Antineoplastic Combined Chemotherapy Protocols administration & dosage, Cytarabine administration & dosage, Dexamethasone administration & dosage, Humans, Multiple Myeloma diagnosis, Prognosis, Retrospective Studies, Survival Analysis, Time Factors, Transplantation, Autologous, Treatment Outcome, Vincristine administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Multiple Myeloma mortality, Multiple Myeloma therapy, Stem Cell Transplantation
- Abstract
We report that early chemosensitivity, defined by a greater than 50% reduction of M-component and plasma-cell marrow infiltration, after 2 cycles of VAD was correlated with a favorable outcome following autologous stem cell transplantation in 46 patients with newly diagnosed multiple myeloma submitted to high-dose therapy.
- Published
- 2002
98. Activity of all-trans-retinoic acid in a case of central nervous system extramedullary relapse of acute promyelocytic leukemia.
- Author
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Patriarca F, Filì C, Geromin A, Sperotto A, Prosdocimo S, and Fanin R
- Subjects
- Cell Differentiation drug effects, Central Nervous System Neoplasms pathology, Cerebrospinal Fluid cytology, Humans, Leukemia, Promyelocytic, Acute pathology, Male, Middle Aged, Myeloid Cells, Recurrence, Tretinoin pharmacology, Central Nervous System Neoplasms drug therapy, Leukemia, Promyelocytic, Acute drug therapy, Tretinoin administration & dosage
- Abstract
We describe a patient with an acute promyelocytic leukemia (APL) previously treated with two courses of cytarabin, idarubicin and all-trans retinoic acid (ATRA), who presented a medullary and meningeal relapse after 8 months of complete remission. A diagnosis of central nervous system (CNS) involvement was based on the appearance of APL blasts in the cerebrospinal fluid (CSF); magnetic resonance (MR) imaging was negative. The neurological symptoms were not evident at the time of recognition of the medullary recurrence, but appeared a few days later, when the patient had already received a reinduction treatment. When the CSF was first examined, showing atypical promyelocytes, there was no excess of blasts on bone-marrow examination. The patient was treated with ATRA and intrathecal administrations of cytoxic drugs, achieving a complete long-lasting CNS remission. The appearance of mature myeloid cells in the CSF during this treatment suggested a possible differentiating effect of ATRA towards extramedullary relapse.
- Published
- 2002
- Full Text
- View/download PDF
99. Endogenous endophthalmitis following disseminated fungemia due to Fusarium solani in a patient with acute myeloid leukemia.
- Author
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Tiribelli M, Zaja F, Filì C, Michelutti T, Prosdocimo S, Candoni A, and Fanin R
- Subjects
- Acute Disease, Adult, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Antineoplastic Combined Chemotherapy Protocols toxicity, Endophthalmitis drug therapy, Fatal Outcome, Fungemia drug therapy, Fungemia pathology, Humans, Leukemia, Myeloid drug therapy, Male, Endophthalmitis microbiology, Fungemia chemically induced, Fusarium, Leukemia, Myeloid complications, Mycoses
- Abstract
We report the case of a young man with a resistant acute myeloid leukemia (AML) who developed a disseminated fungemia due to Fusarium solani involving the skin and lungs, during the neutropenic phase following a chemotherapy course. Despite continuous therapy with liposomal amphotericin B, he developed a bilateral endophthalmitis that rapidly evolved to complete blindness. The patient underwent two procedures of vitrectomy, with detection of F. solani in the vitreous fluid, and continued antifungal therapy, without any recovery of visual acuity. When he eventually died due to recurrence of leukemia and hemorrhagic shock, autopsy revealed a diffuse fusarial involvement of the central nervous system.
- Published
- 2002
- Full Text
- View/download PDF
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