76 results on '"Buelli, M"'
Search Results
2. Carboplatin-Based High-Dose Therapy for Refractory Acute Myeloid Leukaemia
- Author
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Bassan, R., Lerede, T., Buelli, M., Rossi, A., Rambaldi, A., Borleri, G., Bellavita, P., Comotti, B., Cortelazzo, S., Viero, P., Barbui, T., Hiddemann, W., editor, Büchner, T., editor, Wörmann, B., editor, Ritter, J., editor, Creutzig, U., editor, Keating, M., editor, and Plunkett, W., editor
- Published
- 1998
- Full Text
- View/download PDF
3. Clinical outcome after autologous transplantation in non-Hodgkin’s lymphoma patients with high international prognostic index (IPI)
- Author
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Cortelazzo, S., Rossi, A., Bellavita, P., Oldani, E., Viero, P., Buelli, M., Rambaldi, A., and Barbui, T.
- Published
- 1999
- Full Text
- View/download PDF
4. Pneumocystis carinii pneumonia in patients with malignant haematological diseases: 10 years' experience of infection in GIMEMA centres
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Pagano, L., Fianchi, L., Mele, L., Girmenia, C., Offidani, M., Ricci, P, Mitra, M. E., Picardi, M., Caramatti, C., Piccaluga, P., Nosari, A., Buelli, M., Allione, B., Cortelezzi, A., Fabbiano, F., Milone, G., Invernizzi, R., Martino, B., Masini, L., Todeschini, G., Cappucci, M. A., Russo, Domenico, Corvatta, L., Martino, P., Del Favero, A., Pagano, L, Fianchi, L, Mele, L, Girmenia, C, Offidani, M, Ricci, P, Mitra, Me, Picardi, Marco, Caramatti, C, Piccaluga, P, Nosari, A, Buelli, M, Allione, B, Cortelezzi, A, Fabbiano, F, Milone, G, Invernizzi, R, Martino, B, Masini, L, Todeschini, G, Cappucci, Ma, Russo, D, Corvatta, L, Martino, P, and Del Favero, A.
- Subjects
Adult ,Male ,Adolescent ,Immunocompromised Host ,Anti-Infective Agents ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,Trimethoprim, Sulfamethoxazole Drug Combination ,Humans ,Lung ,Aged ,Retrospective Studies ,Lymphoma, Non-Hodgkin ,Pneumonia, Pneumocystis ,Middle Aged ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,Leukemia, Lymphocytic, Chronic, B-Cell ,Radiography ,Treatment Outcome ,Leukemia, Myeloid ,Primary Myelofibrosis ,Hematologic Neoplasms ,Myelodysplastic Syndromes ,Acute Disease ,Multivariate Analysis ,Thalassemia ,Female ,Multiple Myeloma ,Bronchoalveolar Lavage Fluid - Abstract
A retrospective survey was conducted over a 10-year period (1990-99) among 52 haematology divisions in order to evaluate the clinical and laboratory characteristics and outcome of patients with proven Pneumocystis carinii pneumonia (PCP) complicating haematological diseases. The study included 55 patients (18 with non-Hodgkin's lymphoma, 10 with acute lymphoblastic leukaemia, eight with acute myeloid leukaemia, five with chronic myeloid leukaemia, four with chronic lymphocytic leukaemia, four with multiple myeloma, three with myelodys-plastic syndrome, two with myelofibrosis and one with thalassemia) who developed PCP. Among these, 18 (33%) underwent stem cell transplantation; only two received an oral prophylaxis with trimethroprim/sulphamethoxazole. Twelve patients (22%) developed PCP despite protective isolation in a laminar airflow room. The most frequent symptoms were: fever (86%), dyspnoea (78%), non-productive cough (71%), thoracic pain (14%) and chills (5%); a severe hypoxaemia was present in 39 patients (71%). Chest radiography or computerized tomography showed interstitial infiltrates in 34 patients (62%), alveolar infiltrates in 12 patients (22%), and alveolar-interstitial infiltrates in nine patients (16%). Bronchoalveolar lavage was diagnostic in 47/48 patients, induced sputum in 9/18 patients and lung biopsy in 3/8 patients. The diagnosis was made in two patients at autopsy. All patients except one started a specific treatment (52 patients trimethroprim/sulphamethoxazole, one pentamidine and one dapsone). Sixteen patients (29%) died of PCP within 30 d of diagnosis. Multivariate analysis showed that prolonged steroid treatment (P < 0.006) and a radiological picture of diffuse lung involvement (P < 0.003) were negative diagnostic factors.
- Published
- 2002
5. Infections caused by filamentous fungi in patients with hematologic malignancies. A report of 391 cases by GIMEMA Infection Program
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Pagano L, Girmenia C, Mele L, Ricci P, Tosti ME, Nosari A, Buelli M, Allione B, Corvatta L, D'Antonio D, Montillo M, Melillo L, Chierichini A, Cenacchi A, Tonso A, Cudillo L, Candoni A, Savignano C, Bonini A, Martino P, Del Favero A, GIMEMA Infection Program, Gruppo Italiano Malattie Ematologiche dell'Adulto, PICARDI, MARCO, Pagano, L, Girmenia, C, Mele, L, Ricci, P, Tosti, Me, Nosari, A, Buelli, M, Picardi, Marco, Allione, B, Corvatta, L, D'Antonio, D, Montillo, M, Melillo, L, Chierichini, A, Cenacchi, A, Tonso, A, Cudillo, L, Candoni, A, Savignano, C, Bonini, A, Martino, P, Del Favero, A, GIMEMA Infection, Program, and Gruppo Italiano Malattie Ematologiche, Dell'Adulto
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Adult ,Aged, 80 and over ,Male ,Leukemia ,Adolescent ,Fungi ,Filamentous fungi infection ,Middle Aged ,Prognosis ,Survival Rate ,Aspergillus ,Treatment Outcome ,Mycoses ,Risk Factors ,Hematologic Neoplasms ,Humans ,Hematologic malignancies ,Female ,Prospective Studies ,Child ,Aged ,Retrospective Studies - Abstract
BACKGROUND AND OBJECTIVES: To evaluate the clinical characteristics of patients with hematologic malignancies developing a filamentous fungi infection (FFI) and to define the prognostic factors for their outcome. DESIGN AND METHODS: A retrospective study, conducted on patients admitted to 14 Hematology divisions of tertiary care or university hospitals, participating in the GIMEMA Infection Program, over a ten-year period (1988-1997). The study included patients with hematological malignancies and a histologically and/or microbiologically proven or probable FFI. RESULTS: We included 391 patients (male/female: 262/129, median age 49 years) with hematologic malignancies (225 acute myeloid leukemia, 67 acute lymphocytic leukemia, 30 chronic myeloid leukemia, 22 non-Hodgkin's lymphoma, 12 myelodysplastic syndrome, 10 aplastic anemia, 7 Hodgkin's disease, 8 chronic lymphocytic leukemia, 5 multiple myeloma, and 5 hairy cell leukemia) who developed a proven FFI. Eighty percent of the patients had been neutropenic for an average of 14 days before the infection, and 71% had an absolute neutrophil count lower than 0.5 x 10(9)/L at the time of FFI diagnosis. The primary sites of infection were: lungs (85%), nose and paranasal sinus (10%), and other sites (5%). The diagnosis was made while still alive in 310 patients (79%), and at autopsy in the remaining 81 patients (21%). Chest X-ray was diagnostic in 77% of patients with pulmonary FFI, while computed tomography (CT) scan of the thorax was positive in 95% of cases. A significant diagnostic advantage for CT scan was observed in 145 patients who had both a chest X-ray and CT scan. Aspergillus was identified as the cause of FFI in 296 patients, Mucorales in 45 patients, Fusarium in 6 patients and other filamentous fungi species in 4 patients, while in a further 40 patients no agent was identifiable. The overall mortality rate three months after the diagnosis of FFI was 74%, and fungal infection had been the cause of death in 51% of patients. INTERPRETATION AND CONCLUSIONS: Our retrospective study shows that FFI still remains a life-threatening complication in neutropenic patients. Despite appropriate treatment, half of the patients die due to this complication. The use of glucocorticoids and recovery from neutropenia are the most important prognostic factors. Mucorales infections are associated with a significantly poorer prognosis than those due to Aspergillus spp.
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- 2001
6. Risk of second cancer in nongastric marginal zone B-cell lymphomas of MALT: a population-based study from Northern Italy
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Arcaini, L., Burcheri, S., Rossi, A., Pascutto, C., Passamonti, Francesco, Brusamolino, E., Paulli, M., Orlandi, E., Buelli, M., Viero, P., Lucioni, M., Montanari, F., Merli, M., Cortelazzo, S., and Lazzarino, M.
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MALT ,marginal zone lymphoma ,second cancer - Published
- 2007
7. The Italian Way of Treating Acute Promyelocytic Leukemia (APL), Final Act
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Avvisati, G., Petti, M. C., LO COCO, F., Testi, A. M., Fazi, P., Specchia, G., Malagola, M., DI BONA, E., Recchia, A., Marmont, F., Buelli, M., Lazzarino, M., DI RAIMONDO, Francesco, Leoni, F., Kropp, M. G., Veneri, D., Micolis, I., Rossi, G., Venditti, A., and Mandelli, F.
- Published
- 2003
8. AIDA: The italian way of treating acute promyelocytic leukemia (APL): final act
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Avvisati, G, Petti, Mc, Lo Coco, F, Testi, Am, Fazi, P, Specchia, G, Malagola, Michele, Di Bona, E, Recchia, A, Marmont, F, Buelli, M, Lazzarino, M, Di Raimondo, F, Leoni, F, Kropp, Mg, Veneri, D, Miccolis, I, Rossi, G, Venditti, A, and Mandelli, F.
- Published
- 2003
9. Pneumocystis Carinii pneumonia in patients with hematological diseases:10 years experience in GIMEMA centers
- Author
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Pagano, L., Mele, L., Ricci C, P., Girmenia, Mitra, Me, Offidani, M., Fianchi, L., Piccaluga, P., Nosari, A., Buelli, M., Picardi, M, Allione, B., Rossi, G., Cortelezzi, A., Fabbiano, F., Milone, G., Caramatti, C., Invernizzi, R., Martini, B., Masini, L., and Todeschini, Giuseppe
- Published
- 2002
10. Split-Course High-Dose ARA-C Plus Idarubicin and Multidrug Blockade by short Cyclosporin-A Infusion for Refractory Acute Myeloid Leukemia
- Author
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T. Barbui, T. Lerede, B. Chiodini, R. Bassan, A. Rossi, and Buelli M
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Mitoxantrone ,business.industry ,Daunorubicin ,Myeloid leukemia ,Induction chemotherapy ,Pharmacology ,Carboplatin ,chemistry.chemical_compound ,Regimen ,chemistry ,Cyclosporin a ,medicine ,Idarubicin ,business ,medicine.drug - Abstract
Refractory acute myeloid leukemia (R-AML), defined as primary resistance to induction chemotherapy, early relapse (within 6-12 months from remission), and second or subsequent relapse, is typically a multidrugresistant illness, for which effective treatment is presently lacking. We have treated R-AML patients with a combination of intermediatedose ara-C, carboplatin and either mitoxantrone or idarubicin in a cross-over design, obtaining an encouraging response rate (46%) in a small group of 13 R-AML patients who were given an amended, low-toxicity regimen [1]. Five more patients were treated with a similar carboplatin-containing schedule delivered in a sequential manner, but only one remission was achieved, to an overall response rate of 33% (6/18). This result prompted a further change in retreatment strategy. In R-AML, clinical multidrug resistance is often associated with functional overexpression of the MDR1 drug efflux machinery and/or other mechanisms such as LRP (lung-related protein) and MRP (multidrug resistance-associated protein) [2-11]. Theoretically, in view of the high incidence of MDR1 activation in R-AML and its adverse clinical significance, functional MDR1 inhibition with cyclosporin A (CsA), verapamil, tamoxifen, PSC 833, quinine [12-19] or the use of drugs scarcely (Idarubicin=IDR) or not (high-dose ara-C=HiDAC, carboplatin) MDR1-sensitive could underlie therapeutic improvement. In preclinical in vitrostudies on a MDR1+ human leukemic cell line [20,21], we found that both cellular uptake and pro-apoptotic effects of IDR used at therapeutic concentration (50-100 ng/ml, corresponding to the ranges of peak plasma level obtainable after rapid intravenous administration of IDR 10-12 mg/m2) were significantly increased by co-incubation with CsA 1500 ng/ml. Interestingly, CsA enhanced IDR-related cytotoxicity only in the early phase of IDR-blast cell interaction while, contrary to daunorubicin, 12-hour IDR retention by blast cells was not modified by CsA. The study conclusion was that both cellular uptake of and related biologic effects from IDR can be upregulated by CsA in MDR1+ cells but, partly because IDR is highly lypophilic and partly because it is less vulnerable to MDR1, this effect does not require a prolonged CsA exposure. On this basis we initiated a new clinical study, using CsA and aiming to determine the upper IDR concentration tolerated by patients with R-AML. This new sequential regimen included HiDAC 3 g/m2 every 12 hours for two consecutive days followed by IDR 12.5 mg/m2 as starting dose level (both drugs were given for two times on days 1-3 and 8-10) together with CsA 6 mg/kg over 1 hour and then 7.5 mg/kg over 11 hours according to the List schedule [22]. IDR was delivered 4 hours after starting CsA. The three-day sequence was repeated on days 8-10. Recombinanat human granulocyte colony-stimulating factor (G-CSF) was administered from day 11 until response evaluation. We report the therapeutic results obtained in the first 10 patients, who received IDR from 12.5 to 17.5 mg/m2/dose.
- Published
- 2001
11. Itraconazole oral solution as prophylaxis for fungal infections in neutropenic patients with hematologic malignancies: A randomized, placebo- controlled, double-blind, multicenter trial
- Author
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Menichetti, F., Del Favero, A., Martino, P., Bucaneve, G., Micozzi, A., Girmenia, C., Barbabietola, G., Pagano, L., Leoni, P., Giorgina Specchia, Caiozzo, A., Raimondi, R., Mandelli, F., Cascavilla, N., Rigolin, G., Deliliers, G. L., Martino, B., Peta, A., Ricci P., Fanci, R., Plano, W., Sivera, P., Zagonel, V., Caramatti, C., Invernizzi, R., Buelli, M., Bernasconi, C., Carella, A., Damasio, E., Biasi, R., Chierichini, A., Galieni, P., Grasso, M., Jacopino, P., Morra, E., Porcellini, A., Resegotti, L., Ricciuti, F., Picardi, M., Ronconi, F., Cimino, R., Ferrandina, C., Gabbas, A., and Mettivier, V.
- Subjects
Oral ,Adult ,Male ,Microbiology (medical) ,medicine.medical_specialty ,Antifungal Agents ,Neutropenia ,Adolescent ,Itraconazole ,Placebo ,Aspergillosis ,Double-Blind Method ,Internal medicine ,Multicenter trial ,medicine ,Administration, Oral ,Aged ,Female ,Hematologic Neoplasms ,Humans ,Middle Aged ,Mycoses ,Patient Compliance ,Infectious Diseases ,Mycosis ,Fungemia ,business.industry ,medicine.disease ,Surgery ,Chemoprophylaxis ,Administration ,business ,medicine.drug - Abstract
To evaluate the efficacy and safety of itraconazole oral solution for preventing fungal infections, a randomized, placebo-controlled, double-blind, multicenter trial was conducted: 405 neutropenic patients with hematologic malignancies were randomly assigned to receive either itraconazole, 2.5 mg/kg every 12 hours (201 patients), or placebo (204 patients). Proven and suspected deep fungal infection occurred in 24% of itraconazole recipients and in 33% of placebo recipients, a difference of 9 percentage points (95% confidence interval [CI], 0.6% to 22.5%; P = .035). Fungemia due to Candida species was documented in 0.5% of itraconazole recipients and in 4% of placebo recipients, a difference of 3.5 percentage points (95% CI, 0.5% to 6%; P = .01). Deaths due to candidemia occurred in none of the itraconazole recipients compared with 4 placebo recipients, a difference of 2 percentage points (95% CI, 0.05% to 4%; P = .06). Aspergillus infection was documented in four itraconazole recipients (one death) and one placebo recipient (one death). Side effects causing drug interruption occurred in 18% of itraconazole recipients and 13% of placebo recipients. Itraconazole oral solution was well-tolerated and effectively prevented proven and suspected deep fungal infection as well as systemic infection and death due to Candida species.
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- 1999
12. Thrombotic Thrombocytopenic Purpura and High-Dose Immunoglobulin Treatment
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VIERO, P., CORTELAZZO, S., BUELLI, M., COMOTTI, B., MlNETTI, B., BASSAN, R., and BARBUI, T.
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- 1986
- Full Text
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13. Effects of teicoplanin and those of vancomycin in initial empirical antibiotic regimen for febrile neutropenia patients with hematologic malignancies
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Menichetti, F., Martino, Pietro, Bucaneve, G. P., Gentile, Giuseppe, D'Antonio, D., Liso, V., Ricci, P., Nosari, Am, Buelli, M., Carotenuto, M., Fasolo, G., Jacopino, P., Montillo, M., Barbabietola, G., Girmenia, C., Del Favero, A., and The GIMEMA Infection Program
- Published
- 1994
14. Optimum Offshore Development Schemes Selected with Computer Assistance
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De Ghetto, G., additional, D'Amato, M., additional, Buelli, M., additional, Negri, I., additional, Giacometti, L., additional, Bonuccelli, M., additional, Ferretti, C., additional, Basana, R., additional, and Berti, D., additional
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- 1998
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15. Granulocyte colony-stimulating factor following peripheral-blood progenitor-cell transplant in non-Hodgkin's lymphoma.
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Cortelazzo, S, primary, Viero, P, additional, Bellavita, P, additional, Rossi, A, additional, Buelli, M, additional, Borleri, G M, additional, Marziali, S, additional, Bassan, R, additional, Comotti, B, additional, and Rambaldi, A, additional
- Published
- 1995
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16. Effects of teicoplanin and those of vancomycin in initial empirical antibiotic regimen for febrile, neutropenic patients with hematologic malignancies. Gimema Infection Program
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Menichetti, F, primary, Martino, P, additional, Bucaneve, G, additional, Gentile, G, additional, D'Antonio, D, additional, Liso, V, additional, Ricci, P, additional, Nosari, A M, additional, Buelli, M, additional, and Carotenuto, M, additional
- Published
- 1994
- Full Text
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17. High risk of severe bleeding in aged patients with chronic idiopathic thrombocytopenic purpura
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Cortelazzo, S, primary, Finazzi, G, additional, Buelli, M, additional, Molteni, A, additional, Viero, P, additional, and Barbui, T, additional
- Published
- 1991
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18. Cancer Procoagulant in Acute Non Lymphoid Leukemia: Relationship of Enzyme Detection to Disease Activity
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Donati, M B, additional, Falanga, A, additional, Consonni, R, additional, Alessio, M G, additional, Bassan, R, additional, Buelli, M, additional, Borin, L, additional, Catani, L G, additional, Pogliani, E, additional, Gugliotta, L, additional, Masera, G, additional, and Barbui, T, additional
- Published
- 1990
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19. The management of acute myelogenous leukemia in the elderly: ten-year experience in 118 patients.
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Bassan, Renato, Buelli, Maurizio, Viero, Piera, Minotti, Clara, Barbui, Tiziano, Bassan, R, Buelli, M, Viero, P, Minotti, C, and Barbui, T
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- 1992
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20. Intensive retreatment of adults and children with acute lymphoblastic leukemia.
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Bassan, Renato, Cornelli, Pier Emilio, Battista, Raffaele, Terzi, Fausto, Buelli, Maurizio, Rambaldi, Alessandro, Viero, Piera, D'Emilio, Anna, Dini, Enrico, Barbui, Tiziano, Bassan, R, Cornelli, P E, Battista, R, Terzi, F, Buelli, M, Rambaldi, A, Viero, P, D'Emilio, A, Dini, E, and Barbui, T
- Published
- 1992
- Full Text
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21. Fibrinogen Bergamo I (Aα16Arg → Cys): Susceptibility Towards Thrombin Following Aminoethylation, Methylation or Carboxamidomethylation of Cysteine Residues
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Reber, P, Furlan, M, Beck, E A, Finazzi, G, Buelli, M, and Barbui, T
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- 1985
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22. Cancer procoagulant in acute non lymphoid leukemia: Relationship of enzyme detection to disase activity
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Donati, M. B., Anna Falanga, Consonni, R., Alessio, M. G., Bassan, R., Buelli, M., Borin, L., Catani, L., Pogliani, E., Gugliotta, L., Masera, G., and Barbui, T.
23. Pneumocystis carinii pneumonia in patients with hematological diseases. A ten-years multicentric study
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Pagano, L., Fianchi, L., Corrado GIRMENIA, Mele, L., Offidani, M., Ricci, P., Mitra, Me, Picardi, M., Caramatti, C., Piccaluga, P., Nosari, A., Buelli, M., Allione, B., Rossi, G., Cortelezzi, A., Fabbiano, F., Milone, G., Invernizzi, R., Martino, B., Masini, L., Todeschini, G., Cappucci, Ma, Russo, D., Corvatta, L., Martino, P., and Del Favero, A.
24. Danazol for the Treatment of Idiopathic Thrombocytopenic Purpura
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Buelli, M., primary, Cortelazzo, S., additional, Viero, P., additional, Minetti, B., additional, Comotti, B., additional, Bassan, R., additional, and Barbui, T., additional
- Published
- 1985
- Full Text
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25. Prednisone Corrects the Prolonged Bleeding Time in Thrombocythaemia
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Viero, P, additional, Buelli, M, additional, Comotti, B, additional, Minetti, B, additional, Cortelazzo, S, additional, and Barbui, T, additional
- Published
- 1982
- Full Text
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26. Levofloxacin to prevent bacterial infection in patients with cancer and neutropenia.
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Bucaneve G, Micozzi A, Menichetti F, Martino P, Dionisi MS, Martinelli G, Allione B, D'Antonio D, Buelli M, Nosari AM, Cilloni D, Zuffa E, Cantaffa R, Specchia G, Amadori S, Fabbiano F, Deliliers GL, Lauria F, Foà R, and Del Favero A
- Published
- 2005
27. Risk of second cancer in nongastric marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue: a population-based study from northern Italy.
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Arcaini L, Burcheri S, Rossi A, Pascutto C, Passamonti F, Brusamolino E, Paulli M, Orlandi E, Buelli M, Viero P, Lucioni M, Montanari F, Merli M, Cortelazzo S, and Lazzarino M
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- Adult, Age Factors, Aged, Aged, 80 and over, Female, Humans, Italy, Male, Middle Aged, Risk, Time Factors, Treatment Outcome, Gastric Mucosa pathology, Lymphoma, B-Cell pathology, Lymphoma, B-Cell, Marginal Zone pathology, Neoplasms, Second Primary
- Abstract
Purpose: The aim of this study was to define the risk of second cancer in nongastric marginal zone lymphomas of mucosa-associated lymphoid tissue (MALT)., Experimental Design: We considered for the analysis 157 patients with a confirmed histology of marginal zone B-cell lymphoma of MALT, presenting with a clinically prevalent extranodal site of disease, except for stomach. All patients came from two hematologic institutions of Northern Italy. We compared the occurrence of second cancer with respect to the general population by calculating the standardized incidence ratio, with the age- and sex-specific incidence rates of a cancer registry of Northern Italy (Lombardia) as a reference., Results: A history of solid neoplasia was present in 29 (18%) patients for a total number of 30 neoplasms: 25 solid tumors, 2 hematologic diseases (1 Hodgkin's lymphoma and 1 essential thrombocythemia), and 3 nonmelanoma in situ skin cancers. In 4 patients, the site of cancer and lymphoma was the same. In 21 cases the solid tumor preceded the MALToma, in 3 the neoplasm was concomitant, whereas in 6 it was subsequent. For the entire group, the standardized incidence ratio of an additional malignancy was 0.8 [95% confidence interval (95% CI), 0.55-1.17; P = 0.2]. After excluding nonmelanoma skin cancer, the standardized incidence ratio of a second tumor was 0.75 (95% CI, 0.5-1.12; P = 0.2). After excluding all previous malignancies, the standardized incidence ratio of a second cancer was 1.32 (95% CI, 0.69-2.55; P = 0.4). The comparison of risks between males and females was not significant in each group analysis., Conclusions: Patients with nongastric MALT lymphomas are not at increased risk for other neoplasms compared with the general population of the same geographic area.
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- 2007
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28. Invasive infections caused by Trichosporon species and Geotrichum capitatum in patients with hematological malignancies: a retrospective multicenter study from Italy and review of the literature.
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Girmenia C, Pagano L, Martino B, D'Antonio D, Fanci R, Specchia G, Melillo L, Buelli M, Pizzarelli G, Venditti M, and Martino P
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- Adolescent, Adult, Aged, Child, Child, Preschool, Female, Geotrichosis epidemiology, Geotrichosis microbiology, Humans, Infant, Italy, Male, Middle Aged, Retrospective Studies, Trichosporon classification, Geotrichum pathogenicity, Hematologic Neoplasms complications, Mycoses microbiology, Trichosporon pathogenicity
- Abstract
Trichosporonosis is an uncommon but frequently fatal mycosis in immunocompromised patients. A multicenter retrospective study was conducted to characterize cases of proven or probable invasive trichosporonosis diagnosed over the past 20 years in Italian patients with hematological diseases. Of the 52 cases identified, 17 were classified as Trichosporon sp. infections and 35 were attributed to Geotrichum capitatum. Acute myeloid leukemia accounted for 65.4% of the cases. The incidence rates of Trichosporon sp. and G. capitatum infections in acute leukemia patients were 0.4 and 0.5%, respectively. Overall, 76.9% of cases had positive blood cultures. Pulmonary involvement was documented in 26.9% of cases. Death was reported for 57.1% of G. capitatum infections and for 64.7% of Trichosporon sp. infections. A literature review on trichosporonosis in patients with any underlying disease or condition reveals G. capitatum as a predominantly European pathogen, particularly in certain Mediterranean areas, while Trichosporon sp. infections are seen with similar frequencies on all continents. The majority of published Trichosporon sp. and G. capitatum infections occurred in patients with hematological diseases (62.8 and 91.7%, respectively). Well over half of these were suffering from acute leukemia (68 and 84% of patients with Trichosporon sp. and G. capitatum infections, respectively). Crude mortality rates were 77% for Trichosporon spp. and 55.7% for G. capitatum. The optimal therapy for trichosporonosis has yet to be identified; however, in vitro experiences are providing encouraging evidence of the potential role of the new triazoles, in particular, voriconazole.
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- 2005
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29. Gigantic cutaneous lymphoma following Di Bella's therapy.
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Bassan R, Reseghetti A, Cortelazzo S, Rossi A, Buelli M, Viero P, and Barbui T
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- Antineoplastic Combined Chemotherapy Protocols administration & dosage, Female, Humans, Italy, Lymphoma, B-Cell diagnosis, Lymphoma, Large B-Cell, Diffuse diagnosis, Malpractice, Middle Aged, Skin Neoplasms diagnosis, Complementary Therapies adverse effects, Lymphoma, B-Cell therapy, Lymphoma, Large B-Cell, Diffuse therapy, Skin Neoplasms therapy
- Published
- 2002
30. Phase I trial with escalating doses of idarubicin and multidrug resistance reversal by short-course cyclosporin A, sequential high-dose cytosine arabinoside, and granulocyte colony-stimulating factor for adult patients with refractory acute leukemia.
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Bassan R, Lerede T, Borleri G, Chiodini B, Rossi A, Buelli M, Rambaldi A, Viero P, and Barbui T
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- Acute Disease, Adult, Antibiotics, Antineoplastic administration & dosage, Antineoplastic Combined Chemotherapy Protocols toxicity, Cyclosporine administration & dosage, Cytarabine administration & dosage, Dose-Response Relationship, Drug, Drug Resistance, Multiple, Female, Granulocyte Colony-Stimulating Factor administration & dosage, Humans, Idarubicin administration & dosage, Male, Maximum Tolerated Dose, Middle Aged, Salvage Therapy, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Leukemia drug therapy
- Abstract
Background and Objectives: Patients with refractory acute myeloid or lymphoid leukemia (AML, ALL) were treated with a high-dose regimen comprising idarubicin (IDR) plus short-course cyclosporin A (CsA) as multidrug resistance type-1 (MDR1) blocking agent. The principal aim was to define the maximum tolerated dose (MTD) of IDR, which is reported to be a less MDR1-sensitive anthracycline. The short CsA infusion was patterned after the results of a previous in vitro study., Design and Methods: This was a phase I trial, in which eligible patients received high-dose cytarabine (HDAC) 3 g/m(2)/bd on days 1, 2 and 8, 9, and IDR 12.5-20 mg/m(2)/d on days 3 and 10, with increments of 2.5 mg/m(2)/d from the baseline per treatment group. Intravenous CsA infusion started 4 hours before IDR and lasted 12 hours. Recombinant granulocyte colony-stimulating factor (G-CSF) was added from day 11. IDR MTD was evaluated through analysis of regimen-related toxicity (RRT)., Results: Eighteen patients were treated (16 AML, 2 ALL; MDR1+: 8/8 studied). Overall response rate was 61%. Toxicity was severe but manageable up to an IDR dose of 17.5 mg/m(2)/d, while grade 4 RRT developed with IDR 20 mg/m(2)/d. High-grade toxicity, not strictly regimen-related, was sometimes observed at lower IDR concentrations in patients with unresolved complications from prior extensive treatments. In keeping, the complete response (CR) rate was 92% (11/12) for patients with an ECOG performance score <2 compared to 0% (0/6) in the others (p=0.000). Apart from that, induction of markedly hypocellular, leukemia-free bone marrow on day 11 was associated with achievement of CR (13 evaluable: CR 8/10 vs 0/3, p=0.035)., Interpretation and Conclusions: IDR at 17.5 mg/m(2)/d (x2) can be associated with short-course CsA and HDAC for the management of refractory acute leukemias. While this regimen could deserve testing in a larger phase II trial, to document activity in MDR1+ disease, it remains important to select the most suitable patients in order to avoid the occurrence of life-threatening cumulative toxicity.
- Published
- 2002
31. Prolonged administration of all-trans retinoic acid in combination with intensive chemotherapy and G-CSF for adult acute myelogenous leukemia: single-centre pilot study in different risk groups.
- Author
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Bassan R, Chiodini B, Lerede T, Giussani U, Oldani E, Buelli M, Rossi A, Viero P, Rambaldi A, and Barbui T
- Subjects
- Acute Disease, Adolescent, Adult, Aged, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Antineoplastic Combined Chemotherapy Protocols adverse effects, Apoptosis drug effects, Cytarabine administration & dosage, Cytarabine adverse effects, Disease-Free Survival, Etoposide administration & dosage, Etoposide adverse effects, Female, Filgrastim, Granulocyte Colony-Stimulating Factor administration & dosage, Headache chemically induced, Humans, Idarubicin administration & dosage, Idarubicin adverse effects, Leukemia, Myeloid mortality, Leukemia, Myeloid pathology, Life Tables, Male, Middle Aged, Neoplastic Stem Cells drug effects, Patient Compliance, Pilot Projects, Recombinant Proteins, Remission Induction, Survival Analysis, Treatment Failure, Tretinoin administration & dosage, Tretinoin adverse effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Granulocyte Colony-Stimulating Factor therapeutic use, Leukemia, Myeloid drug therapy
- Abstract
Introduction: An exploratory trial was conducted to evaluate toxicity and potential therapeutic role of all trans-retinoic acid (ATRA) given long-term together with chemotherapy and G-CSF to adult patients with acute myelogenous leukemia (AML)., Materials and Methods: ATRA was administered orally at 45 mg/m(2)/day on days 1-14 and 25 mg/m(2)/day on days 15-28 of two standard cycles (idarubicin, etoposide, cytarabine, G-CSF) and of up to three high-dose courses (cytarabine, G-CSF). The results obtained in 19 patients enrolled in the ATRA trial were compared with those from 29 comparable cases treated with the same schedule without ATRA, according to patient risk class and an in vitro study., Results: ATRA was administered for a median of 52 days to the patients selected for study who achieved a remission. ATRA-related toxicity was mostly non-severe apart from high incidence of headache in conjunction with high-dose cytarabine. Complete remission (CR) rate after cycle 1 (54%), kinetics of hematological recovery, postremission treatment realization, disease-free survival (DFS 37.5% at three years) and overall survival (30% at three years) were not different between ATRA-treated and untreated patients. The only significant prognostic factor was the patient risk class, as defined by cytogenetics and other clinical criteria: DFS rate was 57% at three years in standard-risk cases compared to only 19% in the high-risk group, with no influx by ATRA in either category. The in vitro study, in patients with a definite clinical response, failed to document any inhibitory or pro-apoptotic effect of ATRA on AML blast cells., Conclusion: As a consequence to these results, the pilot ATRA phase was closed. This study does not suggest a significant role for the present ATRA schedule as an adjunct to standard antileukemic therapy in adult AML.
- Published
- 2002
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32. Outcome assessment of age group-specific (+/- 50 years) post-remission consolidation with high-dose cytarabine or bone marrow autograft for adult acute myelogenous leukemia.
- Author
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Bassan R, Raimondi R, Lerede T, D'emilio A, Buelli M, Borleri G, Personeni A, Bellavita P, Rodeghiero F, and Barbui T
- Subjects
- Dose-Response Relationship, Drug, Evaluation Studies as Topic, Female, Humans, Male, Middle Aged, Remission Induction, Transplantation, Autologous, Treatment Outcome, Bone Marrow Transplantation, Cytarabine therapeutic use, Leukemia, Myeloid, Acute therapy
- Abstract
Background and Objective: To assess outcome of an age-adapted post-remission strategy for adult patients with acute myelogenous leukemia (AML, FAB-M3 excluded), including autologous bone marrow transplantation (ABMT) or high-dose cytarabine (HIDAC) consolidation., Design and Methods: AML patients in first complete remission (CR) after doxorubicin-cytarabine-thioguanine (DoxAT) chemotherapy were scheduled to receive two identical early consolidation courses followed by HIDAC (1 g/m2/bd for 6 days), if aged > 50 years, or HiDAC plus total body irradiation (TBI) plus ABMT if aged < 50 years, the bone marrow being harvested prior to the HiDAC/TBI regimen and unpurged. Results were examined by treatment intention and in actual treatment groups, by selected pretreatment and therapy-related variables, and compared with age and disease matched historical patients treated with DoxAT consolidation without additional HIDAC or ABMT., Results: One-hundred and eight (70%) of 153 patients achieved a response and were evaluable after a follow-up of 3.3-8.8 years. According to treatment intention, long-term relapse-free survival (RFS) was significantly improved in both age groups compared with controls (< 50 years: 41% vs 15%, p < 0.05; > 50 years: 33% vs 22%, p < 0.005). Actually, 41 patients proceeded to ABMT and 24 to the HIDAC cycle (including 5 aged < 50 years), 23 had early consolidation only (1: refusal; 1: inadequate marrow harvest; 21: complications), 10 relapsed and 2 died very early into remission, 7 were submitted to an allogeneic BMT, and one denied any post-remission therapy. The long-term RFS rates for ABMT and HIDAC groups were 53% and 54% (47% for 19 patients aged > 50), respectively, significantly better than for historical patients or those unable to go beyond early consolidation (p < 0.005, adjusted for early adverse events). Overall 5-year survival rate was 40% (p < 0.0001), 54% for CR patients, 60% after ABMT, and 65% after HIDAC. Relative to the ABMT and HIDAC intensive treatment groups, only the presence of hepatosplenomegaly at diagnosis was associated with a significantly worse outcome like that of the control study., Interpretation and Conclusions: This age-adapted double post-remission consolidation strategy with ABMT (allo-BMT) or HIDAC was applicable to only about two thirds of responders and was effective in about half these cases, regardless of patient age or specific treatment modality. While the loss of CR patients from treatment realization was unrelated to the study design and depended mainly on recurrence of AML and toxic complication, the exact place of ABMT vs HIDAC consolidation remains unsettled, calling for a new study in comparable patient and risk groups.
- Published
- 1998
33. A new combination of carboplatin, high-dose cytarabine and cross-over mitoxantrone or idarubicin for refractory and relapsed acute myeloid leukemia.
- Author
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Bassan R, Lerede T, Buelli M, Borleri G, Bellavita P, Rambaldi A, and Barbui T
- Subjects
- Acute Disease, Adult, Aged, Carboplatin administration & dosage, Cross-Over Studies, Cytarabine administration & dosage, Dose-Response Relationship, Drug, Female, Humans, Idarubicin administration & dosage, Male, Middle Aged, Mitoxantrone administration & dosage, Recurrence, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Leukemia, Myeloid drug therapy
- Abstract
Background and Objective: High-dose cytarabine (HIDAC) and new anthracycline-type drugs (mitoxantrone, idarubicin) are the mainstay of several active regimens against relapsed and refractory acute myeloid leukemia (AML). The present study was undertaken to assess the feasibility, toxicity, and antileukemic activity of carboplatin (CBDCA) added to a combination of the two former agents., Design and Methods: Two regimens (R) of CBDCA plus HIDAC and either mitoxantrone or idarubicin (crossover) were sequentially evaluated. R-1 consisted of CBDCA 300 mg/m2/d (24-hour infusion) on days 1-4, HIDAC 1 g/m2/bd on days 1-5, and mitoxantrone/idarubicin 12/6 mg/m2/d on days 1-3, followed by granulocyte colony-stimulating factor (G-CSF). R-2, an attenuated-toxicity regimen, consisted of CBDCA and G-CSF as above, HIDAC on alternate days (1, 3, 5), and mitoxantrone/idarubicin 8/5 mg/m2/dose. Intended post-remission therapy included a similar, lower intensity course and a myeloablative phase supported by an allogeneic or autologous blood cell transplant., Results: Twenty-nine patients (median age 53 years, one child) formed the study group: 10 (34%) had a primary refractory disease (8 to idarubicin-cytarabine-etoposide, ICE), 6 (21%) were at second or subsequent relapse, and 5 (17%) had a first remission lasting < 12 months. In addition, 4 patients (14%) had received prior HIDAC and 10 (34%) were relapsing after a bone marrow/blood cell transplant. Twelve patients were treated with R-1 and 17 with R-2. The complete response rate was 25% with R-1 and 53% with R-2, due to a significantly lower death rate by pancytopenic complications (p = 0.023). The probability of response by risk class was: primary refractory 30% (43% with R-2), > 2nd relapse 33% (50% with R-2), 1st relapse < 12 months 40% (50% with R-2), 1st relapse > 12 months 50% (75% with R-2), prior HIDAC 75%, and prior transplant 30% (33% with R-2). Seven patients could undergo an autologous (n = 5) or allogeneic (n = 2) bone marrow/peripheral blood cell transplant after one consolidation cycle. Overall survival was 4.2 months, significantly longer in responders (complete and partial: median 11 months) than non-responders (p < 0.001). Median duration of complete remission was 10 months and 2-year probability 0.31, but no patient remained disease-free at 3 years., Interpretation and Conclusions: R-2 was well tolerated, exerted a significant activity in high-risk AML, and is amenable to further improvements. However, the lack of long-term disease-free survivors indicates the need for innovative post-remission strategies.
- Published
- 1998
34. Granulocyte colony-stimulating factor (G-CSF, filgrastim) after or during an intensive remission induction therapy for adult acute lymphoblastic leukaemia: effects, role of patient pretreatment characteristics, and costs.
- Author
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Bassan R, Lerede T, Di Bona E, Rossi G, Pogliani E, Rambaldi A, Buelli M, Viero P, Rodeghiero F, Izzi T, Corneo G, and Barbui T
- Subjects
- Adolescent, Adult, Asparaginase administration & dosage, Cost-Benefit Analysis, Female, Filgrastim, Granulocyte Colony-Stimulating Factor economics, Humans, Idarubicin administration & dosage, Male, Middle Aged, Patient Selection, Precursor Cell Lymphoblastic Leukemia-Lymphoma economics, Prednisolone administration & dosage, Prospective Studies, Recombinant Proteins, Remission Induction methods, Treatment Outcome, Vincristine administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Granulocyte Colony-Stimulating Factor therapeutic use, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy
- Abstract
An early intensive anthracycline therapy can improve therapeutic outcome in adult acute lymphoblastic leukaemia (ALL) but is usually associated with marked myelosuppressive effects and significant morbidity by infections. To reduce this risk, we employed granulocyte colony-stimulating factor (G-CSF, filgrastim 5 microg/kg/d) as an adjunct to a myelotoxic, 14-day long induction regimen with idarubicin-vincristine-L-asparaginase-prednisone (IVAP). Owing to changes in study design, patients received 'late' (n = 28) or 'early' (n = 37) G-CSF from days 15 or 4 of IVAP, respectively, until resolution of severe neutropenia. Study endpoints included time to recovery from neutropenic nadir, duration of neutropenia <0.5 x 10(9)/l, incidence of infectious complications, assessment of variables affecting G-CSF response, clinical outcome and costs. Sixty-five consecutive cases were evaluable. Patients in early G-CSF group recovered significantly faster from the neutropenic nadir (p < 0.002), contracted less infectious complications (p = 0.007), and required less intravenous antibiotic (p = 0.008) and antifungal (p = 0.002) medications. Although these reductions did not compensate for the increased G-CSF treatment cost, the overall supportive care cost was not significantly increased by early G-CSF. Interestingly, T-ALL phenotype (p = 0.02) and higher neutrophil presentation count (p = 0.03) were associated with a shorter neutropenic course even with late G-CSF. Early G-CSF may be a valid approach to mitigate chemotherapy-induced neutropenia of IVAP and other similarly myelosuppressive adult ALL regimens.
- Published
- 1997
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35. Therapeutic impact of adult-type acute lymphoblastic leukemia regimens in B-cell/L3 acute leukemia and advanced-stage Burkitt's lymphoma.
- Author
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Lerede T, Bassan R, Rossi A, Di Bona E, Rossi G, Pogliani EM, Motta T, Torri V, Buelli M, Comotti B, Viero P, Rambaldi A, Cortelazzo S, Rodeghiero F, and Barbui T
- Subjects
- Adolescent, Adult, Aged, Child, Female, Humans, Male, Middle Aged, Retrospective Studies, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Burkitt Lymphoma drug therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy
- Abstract
Background: Adult B/L3-ALL is a rare disease subset characterized by an aggressive clinical course and a poor response to conventional adult ALL-type chemotherapy. Recent data from the GMALL Group showed that prognosis can be improved with an innovative treatment regimen. In the current retrospective survey we focus on therapeutic results obtained at our Institutions during a 15-year period with ALL-type regimens in 34 adults with either B/L3-ALL or advanced-stage Burkitt's lymphoma., Methods: Five successive ALL treatment programs were developed. They included a homogeneous induction phase with early intrathecal chemoprophylaxis, multidrug postremission consolidation followed by cranial irradiation (4 trials), high-dose chemotherapy plus autografting (2 trials), late consolidation (2 trials), and variable-length maintenance (4 trials). Early response and prolonged disease-free survival rates were analyzed according to selected clinical and therapeutic variables., Results: Overall, a complete remission was achieved in 62%, with a median duration of 1.6 years and a 10-year remission rate of 49%. A diagnosis of B/L3-ALL (p = 0.007), the use of idarubicin instead of adriamycin during induction (p = 0.018), a serum creatinine < 1.6 mg/dL, and an uninvolved central nervous system were associated with higher response rates. As regards long-term disease-free survival, results were significantly better in patients with < 1 x 10(9)/L L3/blast cells in the peripheral blood (p = 0.0029) and/or aged < 50 years (p = 0.04), and in those consolidated with the most recent rotational high-dose plus peripheral blood stem cell autotransplant regimen., Conclusions: According to the results presented, ALL-like regimens may still represent a worthwhile therapeutic choice. The use of idarubicin during induction, the prognostic subclassification of patients, a careful control of dysmetabolic complications, the selection of the proper chemo-radioprevention for meningeal disease and perhaps the introduction of high-dose chemotherapy supported by autologous stem cell rescue appear to be the mainstay of further improvements.
- Published
- 1996
36. Localization of aspergillosis to the central nervous system among patients with acute leukemia: report of 14 cases. Gruppo Italiano Malattie Ematologiche dell'Adulto Infection Program.
- Author
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Pagano L, Ricci P, Montillo M, Cenacchi A, Nosari A, Tonso A, Cudillo L, Chierichini A, Savignano C, Buelli M, Melillo L, La Barbera EO, Sica S, Hohaus S, Bonini A, Bucaneve G, and Del Favero A
- Subjects
- Acute Disease, Adult, Aged, Aspergillosis diagnosis, Aspergillosis mortality, Central Nervous System Diseases diagnosis, Central Nervous System Diseases mortality, Female, Humans, Leukemia mortality, Male, Middle Aged, Retrospective Studies, Risk Factors, Survival Rate, Aspergillosis etiology, Central Nervous System Diseases etiology, Leukemia complications
- Abstract
We retrospectively studied a consecutive series of 100 patients with acute leukemia and aspergillosis to evaluate the clinical findings and risk factors for colonization of the central nervous system (CNS) by Aspergillus species. The diagnosis of CNS aspergillosis was made in 14 patients on the basis of the following criteria: neurological signs of CNS involvement (13 of 14 patients); cerebral CT scan findings (9 of 12); microbiological findings (6 of 12); and histological findings at autopsy (11 of 11). The majority of patients had severe neurological complications (i.e., hemiparesis or seizures), due mainly to brain abscesses or mycetomas. Autopsies were performed on 11 of 14 patients and provided evidence that CNS localization was secondary to invasive aspergillosis; in each case, the most likely primary focus of infection was the lung. Although all patients had received oral antimycotic prophylaxis and had received timely empirical antifungal treatment, they all died within a median time of 5 days from the onset of neurological symptoms. Analysis of the characteristics of patients with invasive aspergillosis did not reveal any difference between those with CNS localization and those without CNS localization.
- Published
- 1996
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37. Age-adapted moderate-dose induction and flexible outpatient postremission therapy for elderly patients with acute lymphoblastic leukemia.
- Author
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Bassan R, Di Bona E, Lerede T, Pogliani E, Rossi G, D'Emilio A, Buelli M, Rambaldi A, Viero P, Rodeghiero F, and Barbui T
- Subjects
- Aged, Antineoplastic Combined Chemotherapy Protocols adverse effects, Asparaginase administration & dosage, Dose-Response Relationship, Drug, Drug Administration Schedule, Female, Granulocyte Colony-Stimulating Factor administration & dosage, Humans, Idarubicin administration & dosage, Male, Middle Aged, Outpatients, Prednisolone administration & dosage, Vincristine administration & dosage, Aging physiology, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy
- Abstract
We report the results of a recent trial in elderly acute lymphoblastic leukemia (ALL) patients (> or = 60 years). Initial chemotherapy consisted of one 14-day course with single-dose idarubicin plus vincristine-prednisone-L-asparaginase. Idarubicin was preferred to other anthracyclines because of its shorter time to response. Sequential outpatient postremission therapy included single-dose idarubicin plus vincristine-cyclophosphamide-L-asparaginase pulses, cranial irradiation with intrathecal methotrexate-cytarabine, flexible weekly vincristine-cyclophosphamide alternating with cytarabine-teniposide, and two-year standard maintenance with mercaptopurine-methotrexate. Granulocyte colony-stimulating factor (G-CSF) was added to induction and early consolidation courses. Twenty-two patients mainly with high-risk features entered the study: median age was 64 years (60-73), 40% of cases were CD10- B-lineage and T-lineage ALL, 38% of CD10+ B-lineage ALL carried a BCR-ABL rearrangement, while 23% coexpressed myeloid antigen, 86% had L2 morphology, 50% had a blast count greater than 10 x 10(9)/1, 54% had hepato-splenomegaly and lymphadenopathy. The complete remission (CR) rate after induction therapy was 59%. A partial remission was obtained in two cases. There were four early deaths (18%) and three refractory ALL (14%). Median time to response was 21 days. With G-CSF, the median duration of absolute neutropenia was 10.5 days. Flexible postremission therapy was very well tolerated, causing no major toxicity. With a median follow-up of 2.6 years, 3 patients remain alive in first CR (23%), 2 of whom at 21.3 months and 39.6 months, respectively. Median survival of responders was 12 months compared to only 1.2 months for nonresponders (p < 0.001). This moderate-dose idarubicin-containing and G-CSF-supported regimen was associated with a high early remission rate in elderly ALL. Postremission therapy results were modest, though not appreciably different from the general experience in this patient population. Because further escalation of drug intensity appears unjustified, attempts to document and reverse drug resistance patterns and restore a dysregulated apoptosis must be considered.
- Published
- 1996
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38. G-CSF-mobilized peripheral blood progenitor cells for allogeneic transplantation of resistant or relapsing acute leukemias.
- Author
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Rambaldi A, Viero P, Bassan R, Buelli M, Rossi A, Bellavita P, Spinelli O, Amaru R, Micheletti M, Borleri G, Cortelazzo S, Comotti B, and Barbui T
- Subjects
- Adolescent, Adult, Blood Cells transplantation, Drug Resistance, Neoplasm, Female, Graft vs Host Disease etiology, Hematopoietic Stem Cells drug effects, Humans, Leukemia drug therapy, Leukemia mortality, Male, Middle Aged, Recombinant Proteins pharmacology, Salvage Therapy, Transplantation, Homologous, Bone Marrow drug effects, Granulocyte Colony-Stimulating Factor pharmacology, Hematopoietic Stem Cell Transplantation adverse effects, Leukemia therapy
- Abstract
Peripheral blood progenitor cells (PBPC) were mobilized by G-CSF in normal HLA identical siblings and used for allogeneic transplantation in eight patients with refractory or relapsed acute leukemias. G-CSF administration was well tolerated and no significant side-effects were registered. The number of circulating WBC peaked at day 5 after G-CSF (range: 22.6-74.6 x 10(9)/l) with a median of 65 CD34+ cells/microl (38-155). As a consequence of leukaphereses, platelets progressively decreased, reaching the nadir after the last procedure (84-205 x 10(9)/l). A mean of two aphereses (1-3) were performed between day +4 and +7 during which 10 liters of blood were processed each time by a cell separator. Conditioning regimens were: fractionated total body irradiation (FTBI) plus either HDAra-C (2 g/m2 x 2/day for 6 days) (n=5) or melphalan (110 mg/m2) (n= 1) and busulfan (4 mg/kg/day for 4 days) and melphalan (110 mg/m2) in two patients relapsed after a previous FTBI-based allogeneic or autologous BMT. At transplantation, a median of 6.9 x 10(6) CD34+ cells/kg (4.2-16.5) and 279 x 10(6) CD3+ cells/kg (161-786) were infused. Engraftment of both neutrophils (> or v=1.5 x 10(9)/l) and platelets (> or v=20 x 10(9)/l) was observed in all patients after a median time of 18 days (range: 11-20 and 10-26, respectively). The evaluation of engraftment after transplantation was accomplished by PCR analysis of four hypervariable genomic regions (VNTR) (ApoB, ApoC2, YNZ-22, and MCT 118) which allowed to demonstrate the condition of donor chimaera in all patients after transplantation. As far as the clinical outcome, two patients died of interstitial pneumonitis at day +243 and +69 and two patients died at day +62 and +152 of pulmonary aspergillosis. Four patients remain alive in remission between day +88 and +287 with grade 0-l GVHD. Allogeneic PBPC transplantation is associated with a complete hematologic recovery and despite the infusion of a large amount of mature CD3+ lymphocytes, apparently acute GVHD is not worse than expected after transplantation of bone marrow progenitors.
- Published
- 1996
39. Factors for rapid and sustained hematopoietic reconstitution by circulating progenitor-cell transplantation in non-Hodgkin's lymphoma.
- Author
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Barbui T, Cortelazzo S, Rossi A, Viero P, Bellavita P, Buelli M, Fracassetti D, Bassan R, Comotti B, Marchioli R, Marfisi RM, and Rambaldi A
- Subjects
- Adolescent, Adult, Aged, Antigens, CD34 administration & dosage, Carmustine therapeutic use, Cytarabine therapeutic use, Etoposide therapeutic use, Female, Humans, Male, Melphalan therapeutic use, Middle Aged, Prognosis, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Granulocyte Colony-Stimulating Factor administration & dosage, Hematopoiesis, Hematopoietic Stem Cell Transplantation, Lymphoma, Non-Hodgkin therapy
- Abstract
Circulating progenitor cells (CPCs) mobilized from bone marrow will replace the use of bone marrow transplantation because hematopoietic reconstitution is more rapid using the former technique. We report on early and late recovery of hematopoiesis after CPC transplantation in patients with non-Hodgkin's lymphoma (NHL) and analyze the role of variables possibly influencing engraftment. From December 1992 through September 1995, 57 consecutive NHL patients were enrolled in this study. Patients could be divided into 2 groups: the first comprised 32 patients with untreated diffuse large-cell lymphoma and unfavorable prognostic factors; the second comprised 25 patients with resistant or relapsing NHL of low-and high-grade histology. All patients received high-dose chemotherapy (carmustine, cytarabine, etoposide, and melphalan; BEAM) followed by CPC transplantation. In all, 25 patients were treated with granulocyte colony-stimulating factor (G-CSF) after CPC administration. The time to short-and long-term hematologic engraftment and variables correlating with multilineage long-term reconstitution were examined. The time to bilineage (neutrophils and platelets) hematopoietic reconstitution did not differ in G-CSF-treated and-untreated patients. In contrast, the time taken to reach a neutrophil count of 0.5 x 10(9)/1 and a WBC of 1 x 10(9)/1 was significantly shorter in G-CSF-treated patients. Overall, 33 patients achieved long-term, complete trilineage engraftment after a median of 117 days from CPC transplantation. The leukocyte count was the first parameter to reach full engraftment and hemoglobin was the last. According to Kaplan-Meier analysis, 80% of the patients are projected to reconstitute fully at 12 months after transplantation. Univariate and multivariate analyses showed that sustained, long-term hematopoiesis was significantly related to a younger age, an early bilineage reconstitution, and the quantity of CD34+ cells infused.
- Published
- 1996
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40. The use of anthracyclines in adult acute lymphoblastic leukemia.
- Author
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Bassan R, Lerede T, Rambaldi A, Buelli M, Viero P, and Barbui T
- Subjects
- Adult, Humans, Remission Induction, Antibiotics, Antineoplastic therapeutic use, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy
- Abstract
A critical review of the role of anthracyclines in the management of adult patients with acute lymphoblastic leukemia was performed to define current indications for their use. Major pertinent clinical series were reviewed with reference to anthracycline type, cumulative dosage and dose intensity, and administration schedule during both induction therapy and postremission consolidation, comparing results, whenever possible, with non-anthracycline treatment groups. A subgroup analysis was performed to evidentiate disease subtypes likely associated with a favorable outcome to anthracycline treatment. The results indicated that anthracyclines may still play a primary role in this setting. In particular, anthracyclines should be used at full therapeutic doses, especially during induction and early consolidation; idarubicin could be a better choice than daunorubicin or adriamycin; finally, an early brief intensive treatment with anthracyclines may provide an excellent probability of long-term disease-free survival in CD10+ t(9;22)-negative B-precursor adult ALL, obviating the need for prolonged maintenance or late reinduction therapy.
- Published
- 1995
41. Fatal haemoptysis in pulmonary filamentous mycosis: an underevaluated cause of death in patients with acute leukaemia in haematological complete remission. A retrospective study and review of the literature. Gimema Infection Program (Gruppo Italiano Malattie Ematologiche dell'Adulto)
- Author
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Pagano L, Ricci P, Nosari A, Tonso A, Buelli M, Montillo M, Cudillo L, Cenacchi A, Savignana C, and Melillo L
- Subjects
- Acute Disease, Adult, Aged, Aspergillosis complications, Female, Hemoptysis diagnostic imaging, Humans, Leukemia drug therapy, Lung diagnostic imaging, Lung Diseases, Fungal diagnostic imaging, Male, Middle Aged, Mucormycosis complications, Opportunistic Infections diagnostic imaging, Radiography, Remission Induction, Retrospective Studies, Hemoptysis etiology, Leukemia complications, Lung Diseases, Fungal complications, Opportunistic Infections complications
- Abstract
A retrospective study on a consecutive series of 116 patients affected by acute leukaemia with documented pulmonary filamentous mycosis (FM) admitted between 1987 and 1992 to 14 tertiary-care hospitals in Italy was made in order to evaluate the characteristics of those patients who developed fatal massive haemoptysis. In 59/116 cases of pulmonary FM the infection was the principal cause of death and in 12 of these patients a massive haemoptysis was responsible for death. The diagnosis of FM infection was made ante-mortem in only four out of these 12 patients. The autopsy was performed in 11/12 patients and documented a FM infection. The mycetes isolated were: Hyphomycetes spp. (three patients), Mucorales spp. (two patients), Aspergillus spp. (seven patients). At the time of the massive haemoptysis the mean neutrophil count was 7.2 x 10(9)/l, and no patient had relevant thrombocytopenia (mean 184 x 10(9)/l, range 28-350) or coagulative abnormalities. The mean time which elapsed between resolution of chemotherapy-induced neutropenia (WBC < 10(9)/l) and occurrence of haemoptysis was 7 d. No signs or symptoms predictive of this fatal complication were identified. Massive haemoptysis can be the cause of death in patients with acute leukaemia and pulmonary FM which in the majority of patients was not diagnosed in vivo. This complication occurs most frequently shortly after the recovery from chemotherapy-induced aplasia. The mechanism of lesion is unknown, but it may involve the vascular tropism of FM and the release of leucocyte enzymes. Better preventive and therapeutic antifungal treatments are needed to avoid this serious, albeit rare, complication.
- Published
- 1995
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42. Short-term treatment for adult hypergranular and microgranular acute promyelocytic leukemia.
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Bassan R, Battista R, Viero P, d'Emilio A, Buelli M, Montaldi A, Rambaldi A, Tremul L, Dini E, and Barbui T
- Subjects
- Adolescent, Adult, Age Factors, Bone Marrow Transplantation, Combined Modality Therapy, Cytarabine administration & dosage, Cytoplasmic Granules ultrastructure, Disease-Free Survival, Disseminated Intravascular Coagulation etiology, Doxorubicin administration & dosage, Female, Hemorrhage etiology, Hemorrhage mortality, Humans, Leukemia, Promyelocytic, Acute blood, Leukemia, Promyelocytic, Acute classification, Leukemia, Promyelocytic, Acute complications, Leukemia, Promyelocytic, Acute mortality, Leukemia, Promyelocytic, Acute therapy, Life Tables, Male, Middle Aged, Prospective Studies, Remission Induction, Survival Analysis, Thioguanine administration & dosage, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Leukemia, Promyelocytic, Acute drug therapy
- Abstract
A high hemorrhagic risk and a complete response to the differentiative agent all-trans-retinoic acid (ATRA) are the main clinical features of acute promyelocytic leukemia (APL), two distinct subtypes of which have been recognized, the common hypergranular leukopenic form (M3) and a microgranular hyperleukocytic variant (M3v). We analyzed, with emphasis on both disease- and therapy-related prognostic factors, the results from a 9-year trial in 65 adults with M3 and M3v APL, treated homogenously with a short-term therapy (STT) program excluding maintenance. STT comprised a maximum of six courses with doxorubicin, cytosine arabinoside (ara-C), and 6-thioguanine. Sixty-five APL patients formed the study group, M3v accounting for 25% of cases. In M3v, the absolute blast cell count was significantly higher (p < 0.0001) and early hemorrhagic deaths were more frequent (p = 0.05). The blast count correlated inversely with the probability of remission (p = 0.005), poor-risk patients being those with > 10 x 10(9)/l blast cells. During the study, the median survival improved from 0.1 to 2.7 years (p = < 0.005). In first place, response to chemotherapy increased from 42 to 84% (p = 0.006), by giving daily prophylactic platelet transfusions (to > 30 x 10(9)/l) and no heparin (course I), and by avoiding too toxic high-dose ara-C and deferring treatment in infected/neutropenic patients showing the atypical differentiative bone marrow pattern (course II). Secondly, the probability of first unmaintained remission differed significantly between patients given intentionally more than four total chemotherapy courses or intermediate/high-dose ara-C consolidation (0.59 at 5 years) and those treated less intensively (0.21) (p < 0.005). Intensive STT was very effective for the management of adult APL patients at standard hemorrhagic risk and receiving optimal supportive care. In high-risk patients with hyperleukocytosis and M3v, induction results could be improved by the concomitant use of ATRA. M3v in adults must be recognized promptly because of the very high early hemorrhagic risk.
- Published
- 1995
43. Intensive therapy for adult acute lymphoblastic leukemia: preliminary results of the idarubicin/vincristine/L-asparaginase/prednisolone regimen.
- Author
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Bassan R, Battista R, Viero P, Pogliani E, Rossi G, Lambertenghi-Deliliers G, Rambaldi A, D'Emilio A, Buelli M, and Borleri G
- Subjects
- Adolescent, Adult, Aged, Antineoplastic Combined Chemotherapy Protocols adverse effects, Asparaginase administration & dosage, Bone Marrow Transplantation, Child, Combined Modality Therapy, Female, Granulocyte Colony-Stimulating Factor therapeutic use, Humans, Idarubicin administration & dosage, Immunophenotyping, Male, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma immunology, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy, Prednisolone administration & dosage, Recombinant Proteins therapeutic use, Remission Induction, Vincristine administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy
- Abstract
Between June 1991 and September 1992, 80 patients with adult acute lymphoblastic leukemia (ALL) (newly diagnosed, n = 68; relapsed or refractory ALL, n = 7; lymphoid blast transformation of Philadelphia chromosome-positive chronic myelogenous leukemia [LT-CML], n = 5) were managed with a combination regimen consisting of idarubicin 36, 20, or 10 mg/m2 plus vincristine, L-asparaginase, and prednisolone (IVAP-1, -2, -3). Three patients with LT-CML and four with relapsing ALL had a complete remission. In the group of newly diagnosed patients aged 15 to 60 years treated with IVAP-1, the complete remission rate was only 44% due to the high incidence of toxic deaths. In contrast, 39 of 44 cases who subsequently received IVAP-2 achieved a complete remission (89%, P = .001), as did 62% of elderly patients who received IVAP-3. Hematologic and nonhematologic toxicity was significantly reduced with IVAP-2 compared with IVAP-1. The use of recombinant human granulocyte colony-stimulating factor in 24 patients was not associated with a reduced duration of granulocytopenia less than 0.5 x 10(9)/L, although there was a lower incidence of documented infections in patients receiving granulocyte colony-stimulating factor than in controls. Post-remission intensification with idarubicin-based courses, high-dose therapy with autologous bone marrow stem cell rescue, and rotational weekly therapy was feasible and its toxicity was manageable. These preliminary findings indicate that IVAP-2 (idarubicin 20 mg/m2) is a highly effective and well-tolerated regimen for remission induction of adult ALL.
- Published
- 1993
44. Reinforced HEAV'D therapy for adult acute lymphoblastic leukemia: improved results and revised prognostic criteria.
- Author
-
Bassan R, Battista R, Montaldi A, Rambaldi A, D'Emilio A, Viero P, Borleri G, Buelli M, Dini E, and Barbui T
- Subjects
- Adolescent, Adult, Chromosome Aberrations, Female, Humans, Male, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma genetics, Precursor Cell Lymphoblastic Leukemia-Lymphoma mortality, Prognosis, Survival Rate, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy
- Abstract
Thirty-six adults with acute lymphoblastic leukemia (ALL) were treated with adriamycin, vincristine, prednisolone, and asparaginase for remission induction, followed by vincristine-adriamycin-cyclophosphamide consolidation courses, cranial irradiation, a short ara-C plus VM-26 pulse, and vincristine plus cyclophosphamide rotating weekly with ara-C plus VM-26 for three months (reinforced HEAV'D). Thirty-one patients achieved a complete remission (86 per cent). Compared with historical results from a prior study, age > 30 years, absolute blast count > 15 x 10(9)/l, and CD10-negative immunophenotype were not associated with higher relapse rate and shorter survival, suggesting a positive effect from intensification therapy with ara-C and VM-26 in these poor prognostic categories. However, patients with an abnormal karyotypic pattern or a positive molecular study for BCR-ABL rearrangement detecting t(9;22) had a far greater likelihood of treatment failure (probability of remission at 3 years 0.10) than those with normal karyotype or negative molecular study (probability 0.70), and those not studied or with insufficient methaphases (probability 0.50) (p < 0.05 by log-rank test). These results underline the prognostic importance of chromosomal abnormalities and the usefulness of ara-C and VM-26 in the management of adult ALL.
- Published
- 1993
- Full Text
- View/download PDF
45. Infection and hemorrhage in elderly acute myeloblastic leukemia and primary myelodysplasia.
- Author
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Barbui T, Cortelazzo S, Viero P, Buelli M, and Bassan R
- Subjects
- Aged, Anti-Bacterial Agents therapeutic use, Bacterial Infections drug therapy, Bacterial Infections etiology, Hemorrhage etiology, Humans, Incidence, Leukemia, Myeloid, Acute physiopathology, Middle Aged, Myelodysplastic Syndromes physiopathology, Palliative Care, Prevalence, Retrospective Studies, Treatment Outcome, Bacterial Infections epidemiology, Hemorrhage epidemiology, Leukemia, Myeloid, Acute complications, Leukemia, Myeloid, Acute therapy, Myelodysplastic Syndromes complications, Myelodysplastic Syndromes therapy
- Published
- 1993
46. Treatment of adult acute lymphoblastic leukaemia (ALL) over a 16 year period.
- Author
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Bassan R, Battista R, Rohatiner AZ, Love S, Carter M, Buelli M, Viero P, D'Emilio A, MacCallum P, and Amess J
- Subjects
- Adolescent, Adult, Aged, Asparaginase administration & dosage, Cytarabine administration & dosage, Doxorubicin administration & dosage, Drug Administration Schedule, Female, Follow-Up Studies, Humans, Male, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma mortality, Prednisolone administration & dosage, Recurrence, Remission Induction, Survival Analysis, Vincristine administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy
- Abstract
Between 1972 and 1988 269 newly diagnosed adolescents and adults (age range 14-78 years) with ALL were managed with three protocols of increasing intensity (OPAL, HEAV'D, OPAL-HDAraC). The complete remission (CR) rate in 212 patients treated with OPAL and HEAV'D was 151/212 (71%), the median CR duration was 1.9 years. With a median follow-up of 9 years, 49 patients remain free of disease. On multivariate analysis age, blast cell count, and immunophenotype were found to correlate significantly with CR rate, remission duration and survival. CR was achieved in 38/57 (67%) patients subsequently treated with OPAL-HDAraC; however, although remission duration was longer in 'high risk' patients (T, B and Null phenotype irrespective of blast cout, cALLA+ve with blast count greater than 10 x 10(9)/l) as compared to the results achieved in similar patients with OPAL/HEAV'D, overall, the results were no better than those achieved previously. Indeed, patients in the 'standard risk' category (cALLA+ve, blast count less than 10 x 10(9)/l) fared better previously. Subsequently, neither treatment according to prognostic variables, or the addition of different pairs of drugs in rotation, to HEAV'D, have improved outcome in 63 other patients. Currently, further intensification of the early treatment is being evaluated.
- Published
- 1992
47. Short term therapy (STT) for acute myelogenous leukaemia (AML).
- Author
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Rohatiner AZ, Battista R, Bassan R, Love S, Oza AM, Whelan JS, Lim J, Buelli M, Viero P, and D'Emillio A
- Subjects
- Adolescent, Adult, Combined Modality Therapy, Cytarabine administration & dosage, Doxorubicin administration & dosage, Humans, Leukemia, Myeloid, Acute mortality, Middle Aged, Remission Induction, Survival Analysis, Thioguanine administration & dosage, Whole-Body Irradiation, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Bone Marrow Transplantation, Leukemia, Myeloid, Acute therapy
- Abstract
Between 1978 and 1988 (median follow up 5 1/2 years), 396 newly diagnosed adults with AML (age range 14-59 years, median 44) received STT comprising daily Adriamycin: 25mg/m2 for 3 days, Cytosine arabinoside (ara-C): 100mg/m2 bd and 6-thioguanine: 100mg/m2 bd, each for 7 days. A maximum of 6 cycles was administered with as short an intercycle time as possible. No further treatment was given. Complete remission (CR) was achieved in 243/396 patients (62%), 71 patients (18%) having resistant leukaemia and 82 (21%) dying within 6 weeks. Antecedent myelodysplasia and advanced age correlated unfavourably with achievement of CR (p = less than 0.001 and 0.005 respectively). Sixty nine patients continue in first remission between 2 1/2 and 12 years; the median duration of remission was 1 year. M3 morphology (p = 0.005) and absence of hepatosplenomegaly (p = 0.001) correlated favourably with duration of remission. Ninety one patients remain alive with an actuarial survival of 22% at 5 years. More recently, additional consolidation comprising high-dose ara-C and total body irradiation (TBI) with autologous bone marrow transplantation (ABMT) has been evaluated in an open study. CR has been achieved in 41/66 patients under the age of 50 but only 19/41 have proceeded to ara-C + TBI + ABMT. Twenty two have not (early recurrence 10, allogeneic BMT 4, debility 6, refusal 2). 11/19 who proceeded to ablative therapy continue in remission (4 treatment related deaths, 4 recurrences) as compared to 9/22 who did not. Currently the overall median duration of remission for the 41 patients intended to proceed is identical to that of age-matched historical controls illustrating the difficulties inherent in demonstrating benefit for the use of myeloablative therapy and ABMT in patients with AML in first remission.
- Published
- 1992
48. Pure white cell aplasia treated by high dose intravenous immunoglobulin.
- Author
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Barbui T, Bassan R, Viero P, Minetti B, Comotti B, and Buelli M
- Subjects
- Humans, Male, Middle Aged, Agranulocytosis therapy, Immunization, Passive
- Published
- 1984
- Full Text
- View/download PDF
49. Fibrinogen Bergamo I (A alpha 16Arg----Cys): susceptibility towards thrombin following aminoethylation, methylation or carboxamidomethylation of cysteine residues.
- Author
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Reber P, Furlan M, Beck EA, Finazzi G, Buelli M, and Barbui T
- Subjects
- Amino Acids analysis, Aziridines, Blood Coagulation Disorders genetics, Blood Coagulation Tests, Female, Fibrinogen genetics, Fibrinogen isolation & purification, Fibrinopeptide A isolation & purification, Fibrinopeptide A metabolism, Fibrinopeptide B isolation & purification, Fibrinopeptide B metabolism, Humans, Male, Mercaptoethanol, Methylation, Blood Coagulation Disorders blood, Cysteine, Fibrinogen metabolism, Fibrinogens, Abnormal, Thrombin pharmacology
- Abstract
An abnormal fibrinogen, denoted as "fibrinogen Bergamo I", has been characterized. Its defect consists in an exchange of arginine by cysteine in position 16 of the A alpha-chain, thus corresponding to that found in a number of other fibrinogen variants. The abnormal fibrinopeptide A cannot be split off by thrombin from intact fibrinogen Bergamo I. We describe three different chemical modifications of the cysteine A alpha 16, i.e. aminoethylation, methylation and carboxamidomethylation, and their effects on the susceptibility of fibrinogen Bergamo I towards thrombin attack. S-aminoethylation of the A alpha 16Cys renders the peptide bond A alpha 16-17 cleavable by thrombin. Following methylation or carboxamidomethylation, the A alpha 19-arginyl bond becomes accessible for thrombin. The chemically modified extended fibrinopeptide A can be readily separated from the normal fibrinopeptide A by HPLC. The latter two modifications are suitable alternative procedures for detecting the molecular defect A alpha 16Arg----Cys of fibrinogen.
- Published
- 1985
50. Aspirin and risk of bleeding in patients with thrombocythemia.
- Author
-
Barbui T, Buelli M, Cortelazzo S, Viero P, and De Gaetano G
- Subjects
- 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid, Adolescent, Adult, Aged, Bleeding Time, Blood Platelets analysis, Female, Humans, Hydroxyeicosatetraenoic Acids blood, Male, Middle Aged, Myeloproliferative Disorders blood, Myeloproliferative Disorders complications, Myeloproliferative Disorders drug therapy, Polycythemia Vera blood, Polycythemia Vera complications, Polycythemia Vera drug therapy, Risk, Serotonin blood, Thrombocythemia, Essential etiology, Thromboxane B2 blood, Time Factors, von Willebrand Factor analysis, Aspirin adverse effects, Thrombocythemia, Essential blood
- Abstract
Thirty-two patients with thrombocythemia associated with myeloproliferative syndromes were selected on the basis of normal bleeding time and absence of hemorrhagic or thrombotic history. Twenty-five control subjects were studied simultaneously. They were all given a single intravenous infusion of 500 mg of aspirin (lysine acetylsalicylate), and bleeding time was measured two hours later. Both in the control group and in the patient group, aspirin significantly prolonged the bleeding time, but the average prolongation was significantly more pronounced in the patients. In comparison with the control subjects, the patients had a statistically significant reduction of platelet serotonin content and no difference in the production of platelet lipoxygenase derivative 12-HETE or plasma von Willebrand factor properties. Fourteen patients had abnormal platelet aggregation in response to adenosine diphosphate, adrenaline (epinephrine), or collagen. In six of them, all with very low serotonin content, the bleeding time was prolonged above the upper limit of the post-aspirin values in the control group. Thus, cyclooxygenase inhibition by aspirin unmasked a bleeding tendency in patients with a severe reduction in platelet dense bodies content. These findings might be relevant in relation to the use of antiplatelet drugs.
- Published
- 1987
- Full Text
- View/download PDF
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