33 results on '"Bassan, R"'
Search Results
2. Mutations of TP53 gene in adult acute lymphoblastic leukemia at diagnosis do not affect the achievement of hematologic response but correlate with early relapse and very poor survival
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Salmoiraghi, S., primary, Montalvo, M. L. G., additional, Ubiali, G., additional, Tosi, M., additional, Peruta, B., additional, Zanghi, P., additional, Oldani, E., additional, Boschini, C., additional, Kohlmann, A., additional, Bungaro, S., additional, Intermesoli, T., additional, Terruzzi, E., additional, Angelucci, E., additional, Cavattoni, I., additional, Ciceri, F., additional, Bassan, R., additional, Rambaldi, A., additional, and Spinelli, O., additional
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- 2016
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3. Randomized trial of radiation-free central nervous system prophylaxis comparing intrathecal triple therapy with liposomal cytarabine in acute lymphoblastic leukemia
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Bassan, R., primary, Masciulli, A., additional, Intermesoli, T., additional, Audisio, E., additional, Rossi, G., additional, Pogliani, E. M., additional, Cassibba, V., additional, Mattei, D., additional, Romani, C., additional, Cortelezzi, A., additional, Corti, C., additional, Scattolin, A. M., additional, Spinelli, O., additional, Tosi, M., additional, Parolini, M., additional, Marmont, F., additional, Borlenghi, E., additional, Fumagalli, M., additional, Cortelazzo, S., additional, Gallamini, A., additional, Marfisi, R. M., additional, Oldani, E., additional, and Rambaldi, A., additional
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- 2015
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4. Short course infusional idarubicin plus intermittent cytarabine and etoposide for refractory hematologic malignancies: clinical and preliminary pharmacological results
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Bassan R, Chiodini B, Massimo Zucchetti, Lerede T, Pe, Cornelli, Cortelazzo S, and Barbui T
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Male ,Cytarabine ,Middle Aged ,Drug Administration Schedule ,Lymphoproliferative Disorders ,Drug Resistance, Neoplasm ,Child, Preschool ,Hematologic Neoplasms ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Female ,Idarubicin ,Aged ,Etoposide - Abstract
Idarubicin (IDA) is relatively immune to the multidrug resistance P-gp mechanism that is frequently expressed in recurrent and refractory hematologic malignancies. Owing to rapid metabolism in vivo, a continuous infusion (CI) of IDA might prolong exposure time to the parent drug rather than its more P-gp susceptible alcohol metabolite. For this reason we developed a brief retreatment schedule incorporating CI IDA in order to obtain clinical as well as preliminary pharmacological data in patients with refractory leukemias and lymphomas.Eligible patients had either advanced-stage acute myeloid or lymphoid leukemias (AML, ALL) or high-grade non-Hodgkin's lymphomas (NHL) which failed curative-intent frontline or salvage regimens in use at our institution during the study period (July-October 1992). CI IDA 5 mg/m2/d was employed together with intermittent (every 8 hours) intermediate-dose cytarabine (500 mg/m2) and etoposide (200 mg/m2); all drugs were given for 2-4 days. A preliminary pharmacokinetic evaluation of CI IDA was carried out in three patients, including a comparison with bolus delivery in one. The in vitro effects of CI-type vs bolus-type IDA delivery in terms of intracellular IDA accumulation and related pro-apoptotic activity were assessed in P-gp- and P-gp+ human leukemic CEM cells by means of cytofluorimetry (IDA fluorescence intensity = FI, annexin V expression), with and without the addition of P-gp inhibitor cyclosporin A (CsA).Complete (2) or partial (4) responses were achieved in a total of 12 patients (17% and 33%, respectively), despite prior treatments with anthracyclines (100% of cases) and cytarabine-etoposide (33% of cases). Hematological toxicity caused the duration of treatment to be reduced from 4 days to 2 days after the first 4 patients. The procedural death rate was 42% (5/12), which was probably related in part to the sum of adverse prognostic characteristics: median patient age 55 years, two-thirds of cases having previously failed second/third-line regimens. The pharmacokinetic study showed an increased plasma AUC value with CI IDA in one patient (2.9-fold increase vs bolus delivery) due to the prolonged presence of low IDA plasma levels (10-20 ng/mL vs 50 ng/mL), as seen in two other cases as well. On the other hand, the in vitro study did not prove to be in favor of CI IDA because the FI threshold (1500 units) associated with increased apoptosis of P-gp+ cells (10%) was achieved only with bolus-type IDA exposure (50 ng/mL for 30') plus CsA.This short regimen demonstrated activity against end-stage leukemias and lymphomas and might prove to be more effective and less toxic in younger patients and in those with less advanced disease. In view of the results from plasma pharmacokinetics and in vitro intracellular IDA accumulation and apoptosis assays in lymphoblastic CEM cells, CI IDA 5 mg/m2/day may not represent a better therapeutic option than a rapid bolus injection, particularly in P-gp+ neoplasms. If obtaining an adequate intracellular drug concentration is the primary treatment goal, a higher CI IDA dosage, the addition of a P-gp down-regulator such as CsA and others, and in vivo study focusing on tumor samples from patients could all be helpful.
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- 1998
5. High cure rates in Burkitt lymphoma and leukemia: a Northern Italy Leukemia Group study of the German short intensive rituximab-chemotherapy program
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Intermesoli, T., primary, Rambaldi, A., additional, Rossi, G., additional, Delaini, F., additional, Romani, C., additional, Pogliani, E. M., additional, Pagani, C., additional, Angelucci, E., additional, Terruzzi, E., additional, Levis, A., additional, Cassibba, V., additional, Mattei, D., additional, Gianfaldoni, G., additional, Scattolin, A. M., additional, Di Bona, E., additional, Oldani, E., additional, Parolini, M., additional, Gokbuget, N., additional, and Bassan, R., additional
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- 2013
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6. CD20 expression has no prognostic role in Philadelphia-negative B-precursor acute lymphoblastic leukemia: new insights from the molecular study of minimal residual disease
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Mannelli, F., primary, Gianfaldoni, G., additional, Intermesoli, T., additional, Cattaneo, C., additional, Borlenghi, E., additional, Cortelazzo, S., additional, Cavattoni, I., additional, Pogliani, E. M., additional, Fumagalli, M., additional, Angelucci, E., additional, Romani, C., additional, Ciceri, F., additional, Corti, C., additional, Scattolin, A., additional, Cortelezzi, A., additional, Mattei, D., additional, Audisio, E., additional, Spinelli, O., additional, Oldani, E., additional, Bosi, A., additional, Rambaldi, A., additional, and Bassan, R., additional
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- 2011
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7. Clearance of minimal residual disease after allogeneic stem cell transplantation and the prediction of the clinical outcome of adult patients with high-risk acute lymphoblastic leukemia
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Spinelli, O., primary, Peruta, B., additional, Tosi, M., additional, Guerini, V., additional, Salvi, A., additional, Zanotti, M. C., additional, Oldani, E., additional, Grassi, A., additional, Intermesoli, T., additional, Mico, C., additional, Rossi, G., additional, Fabris, P., additional, Lambertenghi-Deliliers, G., additional, Angelucci, E., additional, Barbui, T., additional, Bassan, R., additional, and Rambaldi, A., additional
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- 2007
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8. Clinical significance of chromatin-spliceosome acute myeloid leukemia: a report from the Northern Italy Leukemia Group (NILG) randomized trial 02/06
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Anna Michelato, Fabio Ciceri, Dario Ferrero, Lorella De Paoli, Renato Bassan, Chiara Caprioli, Paolo Corradini, Silvia Salmoiraghi, Brunangelo Falini, Chiara Cattaneo, Giacomo Gianfaldoni, Agostino Cortelezzi, Federica Delaini, Alessandro Rambaldi, Francesco Mannelli, Leonardo Campiotti, Anna Maria Scattolin, Pamela Zanghì, Erika Borlenghi, Federico Lussana, Massimo Bernardi, Ksenija Buklijas, Daniele Mattei, Elena Oldani, Monica Tajana, Tamara Intermesoli, Roberta Cavagna, Anna De Grassi, Irene Cavattoni, Ernesta Audisio, Elisabetta Terruzzi, Orietta Spinelli, Lara Elidi, Elisabetta Todisco, Chiara Pavoni, Caprioli, C, Lussana, F, Salmoiraghi, S, Cavagna, R, Buklijas, K, Elidi, L, Zanghi', P, Michelato, A, Delaini, F, Oldani, E, Intermesoli, T, Grassi, A, Gianfaldoni, G, Mannelli, F, Ferrero, D, Audisio, E, Terruzzi, E, De Paoli, L, Cattaneo, C, Borlenghi, E, Cavattoni, I, Tajana, M, Scattolin, A, Mattei, D, Corradini, P, Campiotti, L, Ciceri, F, Bernardi, M, Todisco, E, Cortelezzi, A, Falini, B, Pavoni, C, Bassan, R, Spinelli, O, Rambaldi, A, Caprioli, Chiara, Lussana, Federico, Salmoiraghi, Silvia, Cavagna, Roberta, Buklijas, Ksenija, Elidi, Lara, Zanghi', Pamela, Michelato, Anna, Delaini, Federica, Oldani, Elena, Intermesoli, Tamara, Grassi, Anna, Gianfaldoni, Giacomo, Mannelli, Francesco, Ferrero, Dario, Audisio, Ernesta, Terruzzi, Elisabetta, De Paoli, Lorella, Cattaneo, Chiara, Borlenghi, Erika, Cavattoni, Irene, Tajana, Monica, Scattolin, Anna Maria, Mattei, Daniele, Corradini, Paolo, Campiotti, Leonardo, Ciceri, Fabio, Bernardi, Massimo, Todisco, Elisabetta, Cortelezzi, Agostino, Falini, Brunangelo, Pavoni, Chiara, Bassan, Renato, Spinelli, Orietta, and Rambaldi, Alessandro
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Acute Myeloid Leukemia ,Oncology ,medicine.medical_specialty ,Myeloid ,Cytogenetics and Molecular Genetics ,Myelodysplastic Syndromes ,Article ,law.invention ,Cytogenetics and Molecular Genetic ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,Secondary Acute Myeloid Leukemia ,Clinical significance ,Prospective Studies ,Prospective cohort study ,neoplasms ,Aged ,Myeloproliferative Disorders ,business.industry ,Myelodysplastic syndromes ,Myeloid leukemia ,Hematology ,Prognosis ,medicine.disease ,Chromatin ,Leukemia, Myeloid, Acute ,Leukemia ,medicine.anatomical_structure ,Spliceosomes ,business ,030215 immunology - Abstract
Secondary acute myeloid leukemia (sAML) after myelodysplastic or myeloproliferative disorders is a high-risk category currently identified by clinical history or specific morphological and cytogenetic abnormalities. However, in the absence of these features, uncertainties remain to identify the secondary nature of some cases otherwise defined as de novo AML. To test whether a chromatin-spliceosome (CS) mutational signature might better inform the definition of the de novo AML group, we analyzed a prospective cohort of 413 newly diagnosed AML patients enrolled into a randomized clinical trial (NILG AML 02/06) and provided with accurate cytogenetic and molecular characterization. Among clinically defined de novo AML, 17.6% carried CS mutations (CS-AML) and showed clinical characteristics closer to sAML (older age, lower white blood cell counts and higher rate of multilineage dysplasia). Outcomes in this group were adverse, more similar to those of sAML as compared to de novo AML (overall survival, 30% in CS-AML and 17% in sAML vs 61% in de novo AML, P
- Published
- 2020
9. Outcome of 421 adult patients with Philadelphia-negative acute lymphoblastic leukemia treated under an intensive program inspired by the GIMEMA LAL1913 clinical trial: a Campus ALL study.
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Lazzarotto D, Cerrano M, Papayannidis C, Chiaretti S, Mosna F, Fracchiolla N, Zappasodi P, Imbergamo S, Del Principe MI, Lunghi M, Lussana F, Piccini M, Fumagalli M, Dargenio M, Salutari P, Forghieri F, Da Molin TG, Bonifacio M, Olivi M, Giglio F, Trappolini S, Leoncin M, Mule A, Delia M, Pasciolla C, Grimaldi F, Cambo B, Santoro L, Guolo F, Minetto P, Defina M, Chiusolo P, Fanin M, Mauro E, Aprile L, Mazzone C, Trastulli F, Ciccone M, De Gobbi M, Cignetti A, De Bellis E, Mancini V, Piciocchi A, Vignetti M, Marsili G, Starza ID, Fanin R, Luppi M, Ferrara F, Pizzolo G, Bassan R, Foa R, and Candoni A
- Abstract
The introduction of pediatric-inspired regimens in adult Philadelphia-negative acute lymphoblastic leukemia (Ph-ALL) has significantly improved patients' prognosis. Within the Campus ALL network we analyzed the outcome of adult Ph-ALL patients treated according to the GIMEMA LAL1913 protocol outside the clinical trial, to compare the real-life data with the study results. We included 421 consecutive patients, with a median age of 42 years. The complete remission (CR) rate after the first course of chemotherapy was 94% and a measurable residual disease (MRD) negativity after the third course was achieved in 72% of patients. The 3-year overall survival (OS) and disease-free survival (DFS) were 67% and 57%, respectively. In a multivariate analysis, MRD positivity negatively influenced DFS. In a time-dependent analysis including only very high risk (VHR) and MRD positive cases, transplanted (HSCT) patients had a significantly better DFS than non-HSCT ones (P=0.0017). During induction, grade ≥2 pegaspargase-related hepato-toxicity was observed in 25% of patients (vs 12% in the GIMEMA LAL1913 trial, P=0.0003). In this large real-life cohort of Ph-ALL, we confirmed the very high CR rate and a superimposable OS and DFS compared to the GIMEMA LAL1913 clinical trial: CR rate after C1 94% vs 85%, P=0.0004; 3-year OS 67% vs 67%, P=0.94; 3-year DFS 57% vs 63%, P=0.17. HSCT confirms its important role in VHR and MRD-positive patients. The rate of pegaspargase-related toxicity was significantly higher in the real-life setting, emphasizing the importance of dose adjustment in the presence of risk factors to avoid excessive toxicity.
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- 2024
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10. Clinical significance of chromatin-spliceosome acute myeloid leukemia: a report from the Northern Italy Leukemia Group (NILG) randomized trial 02/06.
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Caprioli C, Lussana F, Salmoiraghi S, Cavagna R, Buklijas K, Elidi L, Zanghi' P, Michelato A, Delaini F, Oldani E, Intermesoli T, Grassi A, Gianfaldoni G, Mannelli F, Ferrero D, Audisio E, Terruzzi E, De Paoli L, Cattaneo C, Borlenghi E, Cavattoni I, Tajana M, Scattolin AM, Mattei D, Corradini P, Campiotti L, Ciceri F, Bernardi M, Todisco E, Cortelezzi A, Falini B, Pavoni C, Bassan R, Spinelli O, and Rambaldi A
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- Aged, Chromatin genetics, Humans, Prognosis, Prospective Studies, Spliceosomes, Leukemia, Myeloid, Acute diagnosis, Leukemia, Myeloid, Acute epidemiology, Leukemia, Myeloid, Acute genetics, Myeloproliferative Disorders
- Abstract
Secondary acute myeloid leukemia (sAML) after myelodysplastic or myeloproliferative disorders is a high-risk category currently identified by clinical history or specific morphological and cytogenetic abnormalities. However, in the absence of these features, uncertainties remain to identify the secondary nature of some cases otherwise defined as de novo AML. To test whether a chromatin-spliceosome (CS) mutational signature might better inform the definition of the de novo AML group, we analyzed a prospective cohort of 413 newly diagnosed AML patients enrolled into a randomized clinical trial (NILG AML 02/06) and provided with accurate cytogenetic and molecular characterization. Among clinically defined de novo AML, 17.6% carried CS mutations (CS-AML) and showed clinical characteristics closer to sAML (older age, lower white blood cell counts and higher rate of multilineage dysplasia). Outcomes in this group were adverse, more similar to those of sAML as compared to de novo AML (overall survival, 30% in CS-AML and 17% in sAML vs 61% in de novo AML, P<0.0001; disease free survival, 26% in CS-AML and 22% in sAML vs 54% of de novo AML, P<0.001) and independently confirmed by multivariable analysis. Allogeneic transplant in first complete remission improved survival in both sAML and CS-AML patients. In conclusion, these findings highlight the clinical significance of identifying CS-AML for improved prognostic prediction and potential therapeutic implications. (NILG AML 02/06: ClinicalTrials.gov Identifier: NCT00495287).
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- 2021
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11. Philadelphia-like acute lymphoblastic leukemia is associated with minimal residual disease persistence and poor outcome. First report of the minimal residual disease-oriented GIMEMA LAL1913.
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Chiaretti S, Messina M, Della Starza I, Piciocchi A, Cafforio L, Cavalli M, Taherinasab A, Ansuinelli M, Elia L, Albertini Petroni G, La Starza R, Canichella M, Lauretti A, Puzzolo MC, Pierini V, Santoro A, Spinelli O, Apicella V, Capria S, Di Raimondo F, De Fabritiis P, Papayannidis C, Candoni A, Cairoli R, Cerrano M, Fracchiolla N, Mattei D, Cattaneo C, Vitale A, Crea E, Fazi P, Mecucci C, Rambaldi A, Guarini A, Bassan R, and Foà R
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- Acute Disease, Adult, Disease-Free Survival, Humans, Neoplasm, Residual, Prognosis, Precursor Cell Lymphoblastic Leukemia-Lymphoma diagnosis, Precursor Cell Lymphoblastic Leukemia-Lymphoma genetics, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy
- Abstract
Early recognition of Ph-like acute lymphoblastic leukemia cases could impact on the management and outcome of this subset of B-lineage ALL. To assess the prognostic value of the Ph-like status in a pediatric-inspired, minimal residual disease (MRD)-driven trial, we screened 88 B-lineage ALL cases negative for the major fusion genes (BCR-ABL1, ETV6-RUNX1, TCF3-PBX1 and KTM2Ar) enrolled in the GIMEMA LAL1913 front-line protocol for adult BCR/ABL1-negative ALL. The screening - performed using the BCR/ABL1-like predictor - identified 28 Ph-like cases (31.8%), characterized by CRLF2 overexpression (35.7%), JAK/STAT pathway mutations (33.3%), IKZF1 (63.6%), BTG1 (50%) and EBF1 (27.3%) deletions, and rearrangements targeting tyrosine kinases or CRLF2 (40%). The correlation with outcome highlighted that: i) the complete remission (CR) rate was significantly lower in Ph-like compared to non-Ph-like cases (74.1% vs 91.5%, p=0.044); ii) at time point 2 (TP2), decisional for transplant allocation, 52.9% of Ph-like cases vs 20% of non-Ph-like were MRD-positive (p=0.025); iii) the Ph-like profile was the only parameter associated with a higher risk of being MRD-positive at TP2 (p=0.014); iv) at 24 months, Ph-like patients had a significantly inferior event-free and disease-free survival compared to non-Ph-like patients (33.5% vs 66.2%, p=0.005 and 45.5% vs 72.3%, p=0.062, respectively). This study documents that Ph-like patients have a lower CR rate, EFS and DFS, as well as a greater MRD persistence also in a pediatric-oriented and MRD-driven adult ALL protocol, thus reinforcing that the early recognition of Ph-like ALL patients at diagnosis is crucial to refine risk-stratification and to optimize therapeutic strategies.
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- 2021
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12. A systematic literature review and meta-analysis of minimal residual disease as a prognostic indicator in adult B-cell acute lymphoblastic leukemia.
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Bassan R, Brüggemann M, Radcliffe HS, Hartfield E, Kreuzbauer G, and Wetten S
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- Adult, Humans, Neoplasm, Residual, Prognosis, Remission Induction, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma blood, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma diagnosis, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma therapy
- Abstract
Minimal (or 'measurable') residual disease in acute lymphoblastic leukemia appears to be a prognostic indicator, with potential value in informing individualized treatment decisions. Complete understanding of the strength of the association between minimal residual disease and long-term outcomes is, however, lacking. A systematic literature review and meta-analysis were performed to elucidate the clinical significance of minimal residual disease with respect to relapse-free survival and overall survival in precursor B-cell acute lymphoblastic leukemia. A total of 23 articles and abstracts, most published between 2012 and 2016, were identified for inclusion in the primary meta-analysis. Typically, patients were in their first complete remission at the time of minimal residual disease assessment; in two studies, all patients were in their second, or later, complete remission. The primary analysis revealed improved relapse-free survival across all studies for patients who achieved minimal residual disease negativity (random effects hazard ratio, 2.34; 95% confidence interval, 1.91-2.86). Improved overall survival for patients who achieved minimal residual disease negativity was also observed (hazard ratio, 2.19; 95% confidence interval, 1.63-2.94). There was no observed difference in the impact of minimal residual disease status in subgroups based on disease stage, minimal residual disease sensitivity threshold level, Philadelphia chromosome status, histological phenotype, risk group, minimal residual disease testing location, minimal residual disease timing after induction, or minimal residual disease detection method. Despite heterogeneity in study design and patient populations between the contributing studies, these data provide a compelling argument for minimal residual disease as a clinical tool for assessing prognosis and guiding treatment decisions in precursor B-cell acute lymphoblastic leukemia., (Copyright© 2019 Ferrata Storti Foundation.)
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- 2019
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13. CEBPA -double-mutated acute myeloid leukemia displays a unique phenotypic profile: a reliable screening method and insight into biological features.
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Mannelli F, Ponziani V, Bencini S, Bonetti MI, Benelli M, Cutini I, Gianfaldoni G, Scappini B, Pancani F, Piccini M, Rondelli T, Caporale R, Gelli AM, Peruzzi B, Chiarini M, Borlenghi E, Spinelli O, Giupponi D, Zanghì P, Bassan R, Rambaldi A, Rossi G, and Bosi A
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- Adolescent, Adult, Aged, Aged, 80 and over, Biomarkers, Tumor, Bone Marrow pathology, CCAAT-Enhancer-Binding Protein-alpha metabolism, Cluster Analysis, Cytogenetic Analysis, DNA Mutational Analysis, Female, Genetic Association Studies, Genotype, Humans, Immunophenotyping, Kaplan-Meier Estimate, Leukemia, Myeloid, Acute mortality, Male, Middle Aged, Prognosis, Reproducibility of Results, Sensitivity and Specificity, Young Adult, CCAAT-Enhancer-Binding Protein-alpha genetics, Leukemia, Myeloid, Acute diagnosis, Leukemia, Myeloid, Acute genetics, Mutation, Phenotype
- Abstract
Mutations in CCAAT/enhancer binding protein α ( CEBPA ) occur in 5-10% of cases of acute myeloid leukemia. CEBPA -double-mutated cases usually bear biallelic N- and C-terminal mutations and are associated with a favorable clinical outcome. Identification of CEBPA mutants is challenging because of the variety of mutations, intrinsic characteristics of the gene and technical issues. Several screening methods (fragment-length analysis, gene expression array) have been proposed especially for large-scale clinical use; although efficient, they are limited by specific concerns. We investigated the phenotypic profile of blast and maturing bone marrow cell compartments at diagnosis in 251 cases of acute myeloid leukemia. In this cohort, 16 (6.4%) patients had two CEBPA mutations, whereas ten (4.0%) had a single mutation. First, we highlighted that the CEBPA -double-mutated subset displays recurrent phenotypic abnormalities in all cell compartments. By mutational analysis after cell sorting, we demonstrated that this common phenotypic signature depends on CEBPA -double-mutated multi-lineage involvement. From a multidimensional study of phenotypic data, we developed a classifier including ten core and widely available parameters. The selected markers on blasts (CD34, CD117, CD7, CD15, CD65), neutrophil (SSC, CD64), monocytic (CD14, CD64) and erythroid (CD117) compartments were able to cluster CEBPA -double-mutated cases. In a validation set of 259 AML cases from three independent centers, our classifier showed excellent performance with 100% specificity and 100% sensitivity. We have, therefore, established a reliable screening method, based upon multidimensional analysis of widely available phenotypic parameters. This method provides early results and is suitable for large-scale detection of CEBPA -double-mutated status, allowing gene sequencing to be focused in selected cases., (Copyright© Ferrata Storti Foundation.)
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- 2017
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14. CD20 expression has no prognostic role in Philadelphia-negative B-precursor acute lymphoblastic leukemia: new insights from the molecular study of minimal residual disease.
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Mannelli F, Gianfaldoni G, Intermesoli T, Cattaneo C, Borlenghi E, Cortelazzo S, Cavattoni I, Pogliani EM, Fumagalli M, Angelucci E, Romani C, Ciceri F, Corti C, Scattolin A, Cortelezzi A, Mattei D, Audisio E, Spinelli O, Oldani E, Bosi A, Rambaldi A, and Bassan R
- Subjects
- Adolescent, Adult, Aged, Gene Expression, Humans, Middle Aged, Neoplasm, Residual, Philadelphia Chromosome, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma mortality, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma therapy, Survival Analysis, Treatment Outcome, Young Adult, Antigens, CD20 genetics, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma genetics
- Abstract
The prognostic significance of CD20 expression in acute lymphoblastic leukemia has been investigated in children and adults but is still a subject of debate. The aim of our study was to correlate CD20 expression with clinical-biological characteristics and outcome in 172 Philadelphia chromosome negative patients prospectively treated in a multicenter trial introducing the molecular evaluation of minimal residual disease for therapeutic purposes. We considered 20% as the threshold for CD20 positivity. Complete remission rate, minimal residual disease negativity rate at weeks 10, 16 and 22, and disease-free and overall survival were similar among CD20-positive and -negative patients, even considering minimal residual disease results and related therapeutic choices. Our study failed to demonstrate any prognostic significance for CD20 expression in Philadelphia chromosome negative acute lymphoblastic leukemia. This conclusion is supported for the first time by a comparable minimal residual disease response rate among CD20-positive and -negative and positive patients.
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- 2012
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15. Liposomal cytarabine is effective and tolerable in the treatment of central nervous system relapse of acute lymphoblastic leukemia and very aggressive lymphoma.
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Gökbuget N, Hartog CM, Bassan R, Derigs HG, Dombret H, Greil R, Hernández-Rivas JM, Huguet F, Intermesoli T, Jourdan E, Junghanss C, Leimer L, Moreno MJ, Reichle A, Ribera J, Schmid M, Serve H, Stelljes M, Stuhlmann R, and Hoelzer D
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Burkitt Lymphoma complications, Central Nervous System Neoplasms etiology, Female, Humans, International Agencies, Liposomes, Male, Maximum Tolerated Dose, Middle Aged, Neoplasm Recurrence, Local diagnosis, Precursor Cell Lymphoblastic Leukemia-Lymphoma complications, Prospective Studies, Risk Factors, Survival Rate, Treatment Outcome, Young Adult, Antimetabolites, Antineoplastic therapeutic use, Burkitt Lymphoma drug therapy, Central Nervous System Neoplasms drug therapy, Cytarabine therapeutic use, Neoplasm Recurrence, Local drug therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy
- Abstract
Background: Treatment of central nervous system relapse in adult acute lymphoblastic leukemia is a challenge and outcome is poor. Liposomal cytarabine has a prolonged half-life and, given intrathecally, has produced high response rates in patients with central nervous system relapse of non-Hodgkin's lymphoma. The aim of this study was to evaluate the efficacy and tolerability of liposomal cytarabine in central nervous system relapse of acute lymphoblastic leukemia or Burkitt's lymphoma/leukemia., Design and Methods: Liposomal cytarabine (50 mg) was given intrathecally together with systemic or intrathecal dexamethasone once every 2 weeks in a phase II European trial. The primary end-point, cytological response in the cerebrospinal fluid after one or two cycles, was evaluated at the time of next treatment., Results: Nineteen heavily pretreated patients (median age, 53 years; range 24-76 years) were evaluable: 14 with acute lymphoblastic leukemia and 5 with Burkitt's lymphoma/leukemia). Complete cytological remission as best response after two cycles of liposomal cytarabine was confirmed in 74% of the patients: 86% of those with acute lymphoblastic leukemia and 40% of those with Burkitt's lymphoma/leukemia). Nine of the 14 patients who achieved complete remission relapsed after a median of 7 months. The median overall survival was 11 months. Adverse events were observed in 89% of the patients (57% of cycles). Grade III-IV events with potential correlation to liposomal cytarabine occurred in 32% of the patients. The most frequent adverse event was headache. One patient developed severe neurological complications with loss of vision and a conus syndrome., Conclusions: Overall, liposomal cytarabine showed excellent antileukemic activity. Toxicity was acceptable but appeared to increase with the number of cycles. Future evaluation in prophylaxis is of interest.
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- 2011
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16. The European LeukemiaNet: achievements and perspectives.
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Hehlmann R, Grimwade D, Simonsson B, Apperley J, Baccarani M, Barbui T, Barosi G, Bassan R, Béné MC, Berger U, Büchner T, Burnett A, Cross NC, de Witte TJ, Döhner H, Dombret H, Einsele H, Engelich G, Foà R, Fonatsch C, Gökbuget N, Gluckman E, Gratwohl A, Guilhot F, Haferlach C, Haferlach T, Hallek M, Hasford J, Hochhaus A, Hoelzer D, Kiladjian JJ, Labar B, Ljungman P, Mansmann U, Niederwieser D, Ossenkoppele G, Ribera JM, Rieder H, Serve H, Schrotz-King P, Sanz MA, and Saussele S
- Subjects
- Europe, Humans, International Cooperation, Societies, Medical organization & administration, Biomedical Research organization & administration, Leukemia, Medical Oncology organization & administration
- Abstract
The only way to cure leukemia is by cooperative research. To optimize research, the European LeukemiaNet integrates 105 national leukemia trial groups and networks, 105 interdisciplinary partner groups and about 1,000 leukemia specialists from 175 institutions. They care for tens of thousands of leukemia patients in 33 countries across Europe. Their ultimate goal is to cure leukemia. Since its inception in 2002, the European LeukemiaNet has steadily expanded and has unified leukemia research across Europe. The European LeukemiaNet grew from two major roots: 1) the German Competence Network on Acute and Chronic Leukemias; and 2) the collaboration of European Investigators on Chronic Myeloid Leukemia. The European LeukemiaNet has improved leukemia research and management across Europe. Its concept has led to funding by the European Commission as a network of excellence. Other sources (European Science Foundation; European LeukemiaNet-Foundation) will take over when the support of the European Commission ends.
- Published
- 2011
- Full Text
- View/download PDF
17. The sensitivity of acute lymphoblastic leukemia cells carrying the t(12;21) translocation to campath-1H-mediated cell lysis.
- Author
-
Golay J, Cortiana C, Manganini M, Cazzaniga G, Salvi A, Spinelli O, Bassan R, Barbui T, Biondi A, Rambaldi A, and Introna M
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Alemtuzumab, Antibodies, Monoclonal, Humanized, Cell Death drug effects, Cell Death physiology, Cell Line, Tumor, Child, Child, Preschool, Dose-Response Relationship, Drug, Humans, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma metabolism, Translocation, Genetic physiology, Antibodies, Monoclonal pharmacology, Antibodies, Neoplasm pharmacology, Precursor Cell Lymphoblastic Leukemia-Lymphoma genetics, Precursor Cell Lymphoblastic Leukemia-Lymphoma pathology, Translocation, Genetic drug effects
- Abstract
Background and Objectives: Campath-1H is used in conditioning regimens and more recently as an anti-leukemic therapy in acute lymphoblastic leukemias (ALL). We therefore investigated CD52 expression and campath-1H-mediated lysis of ALL cells in vitro., Design and Methods: Complement-mediated cytotoxicity assays were performed on freshly isolated neoplastic cells and cell lines using human serum. Antibody-dependent cellular cytotoxicity (ADCC) was performed by calcein-AM release assays., Results: CD52 was expressed in four out of eight ALL cell lines studied. Among 61 freshly isolated ALL samples CD52 was expressed at varying levels in 87% of cases. Whereas ADCC was equivalent in different CD52+ lines, complement-dependent cytotoxicity (CDC) was variable. The REH cell line bearing the t(12;21) translocation showed 47-60% lysis when treated with 10 microg/mL campath-1H compared to 0-6% for the other cell lines expressing equivalent amounts of CD52. Furthermore all nine ALL samples with t(12;21) showed very high CDC (mean 97%) compared to the other 24 CD52+cases (mean 24%)(p<0.0001). In t(12;21) samples, efficient CDC was obtained with as little as 1 microg/mL campath-1H. CDC correlated in part with CD52 levels, suggesting that CD52 expression and other yet undefined factors contribute to the particular sensitivity of t(12;21) cells. The resistance of non t(12;21) ALL cases could be overcome to a limited extent by increasing the concentration of campath-1H, blocking the CD55 and CD59 complement inhibitors, and more effectively by combining campath-1H with fludarabine., Interpretation and Conclusions: We conclude that most ALL samples express CD52 to a variable level and that campath-1H has cytotoxic activity against CD52+ALL, alone or in combination with cytotoxic drugs.
- Published
- 2006
18. Evolving strategies for the management of high-risk adult acute lymphoblastic leukemia.
- Author
-
Bassan R
- Subjects
- Adult, Antineoplastic Agents therapeutic use, Clinical Trials, Phase III as Topic methods, Disease Management, Humans, Precursor Cell Lymphoblastic Leukemia-Lymphoma blood, Precursor Cell Lymphoblastic Leukemia-Lymphoma genetics, Stem Cell Transplantation methods, Transplantation, Autologous, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy
- Published
- 2005
19. Immunophenotypic evaluation of circulating T-cell clones in hypereosinophilic syndromes with or without abnormal CD3 and CD4 lymphocytes.
- Author
-
Bassan R, Locatelli G, Borleri G, Salvi A, and Barbui T
- Subjects
- Adult, Aged, Aged, 80 and over, Antigens, CD analysis, Chronic Disease, Clone Cells immunology, Clone Cells pathology, Disease Progression, Eosinophilia complications, Eosinophilia pathology, Female, Gene Rearrangement, beta-Chain T-Cell Antigen Receptor, Humans, Hypereosinophilic Syndrome complications, Hypereosinophilic Syndrome pathology, Immunophenotyping, Lymphocytosis complications, Male, Middle Aged, Myelodysplastic Syndromes complications, T-Lymphocyte Subsets immunology, Eosinophilia immunology, Hypereosinophilic Syndrome immunology, T-Lymphocyte Subsets pathology
- Published
- 2004
20. Gigantic cutaneous lymphoma following Di Bella's therapy.
- Author
-
Bassan R, Reseghetti A, Cortelazzo S, Rossi A, Buelli M, Viero P, and Barbui T
- Subjects
- 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
21. 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.
- Author
-
Bassan R, Lerede T, Borleri G, Chiodini B, Rossi A, Buelli M, Rambaldi A, Viero P, and Barbui T
- Subjects
- 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
22. Fractionated cyclophosphamide added to the IVAP regimen (idarubicin-vincristine-L-asparaginase-prednisone) could lower the risk of primary refractory disease in T-lineage but not B-lineage acute lymphoblastic leukemia: first results from a phase II clinical study.
- Author
-
Bassan R, Pogliani E, Lerede T, Fabris P, Rossi G, Morandi S, Casula P, Lambertenghi-Deliliers G, Vespignani M, Izzi T, Coser P, Corneo G, and Barbui T
- Subjects
- Adolescent, Adult, Aged, Asparaginase administration & dosage, Burkitt Lymphoma drug therapy, Burkitt Lymphoma prevention & control, Female, Humans, Idarubicin administration & dosage, Leukemia-Lymphoma, Adult T-Cell drug therapy, Leukemia-Lymphoma, Adult T-Cell prevention & control, Male, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma prevention & control, Prednisolone administration & dosage, Vincristine administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Cyclophosphamide administration & dosage, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy
- Abstract
Background and Objective: In a prior study, primary resistant acute lymphoblastic leukemia (RES-ALL) was observed in 11 of 176 (6%) adult patients treated with a four drug regimen (IVAP), its incidence being higher in T-cell or Philadelphia (Ph) chromosome/BCR-ABL rearrangement positive ALL cases with a blast cell count >25x10(9)/L (RES-ALL rate 19%, p=0.04). Aiming to minimize this percentage of resistant disease, fractionated cyclophosphamide (f-CY) was then added to the IVAP regimen., Design and Methods: Study 08-96 was a prospective, collaborative phase II trial carried out at eight general hospital centers specialized in the care of hematologic malignancies. Historical IVAP-treated patients served as a retrospective control group. All consecutive, untreated patients (>15 years) with a diagnosis of ALL or advanced-stage lymphoblastic lymphoma (LBL) were eligible. RES-ALL was defined as the persistence of >5% ALL cells in the bone marrow 28-40 days after the start of the IVAP regimen (idarubicin 10 mg/m(2)/d on days 1 and 2; vincristine 2 mg on days 1, 8 and 15; L-asparaginase 6,000 U/m(2) on alternate days 3 6 from day 8; prednisone 60 mg/m(2)/d on days 1-21). In the new study, two f-CY schedules were sequentially adopted: CY 150 or 75 mg/m(2)/bd, given for 4 consecutive days before IVAP (f-CY 1200 or 600, expressing total CY dose in mg/m(2))., Results: Eighty-eight patients were evaluable (age range 15-74 years, blast count 0-240x10(9)/L, 14 T-lineage, 74 B-lineage, 13 Ph/BCR-ABL+). The first 39 patients received the f-CY 1200 schedule, 22 patients received f-CY 600, and the last 27 patients were not given any f-CY. These changes were dictated by the results of interim analyses of the f-CY groups (RES-ALL rate not reduced, myelotoxicity increased). Altogether, compared with the historical IVAP and no f-CY groups, the incidence of RES-ALL was not decreased by the addition of f-CY 1200/600 in B-lineage ALL, regardless of Ph/BCR-ABL expression and blast count. However, none of 14 T-ALL cases in the new study had RES-ALL (8 in f-CY groups, 5 of whom with >25x10(9)/L blast cells), compared to 5/39 (13%, overall) or 4/21 (19%, with >25x10(9)/L blast cells) among the control cases. Owing to small sample size, this difference was not statistically significant., Interpretation and Conclusions: This preliminary experience suggests that T-ALL may be more sensitive than B-lineage ALL to an early therapy including f-CY. The hypothesis could be tested in a larger clinical trial.
- Published
- 1999
23. 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
-
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
24. A new combination of carboplatin, high-dose cytarabine and cross-over mitoxantrone or idarubicin for refractory and relapsed acute myeloid leukemia.
- Author
-
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
25. Randomized clinical trials in adult acute lymphoblastic leukemia: which is the question?
- Author
-
Bassan R
- Subjects
- Adult, Clinical Trials, Phase III as Topic, Humans, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy, Randomized Controlled Trials as Topic
- Published
- 1998
26. Therapeutic impact of adult-type acute lymphoblastic leukemia regimens in B-cell/L3 acute leukemia and advanced-stage Burkitt's lymphoma.
- Author
-
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
27. Strategies for the treatment of recurrent acute lymphoblastic leukemia in adults.
- Author
-
Bassan R, Lerede T, and Barbui T
- Subjects
- Adolescent, Adult, Humans, Middle Aged, Recurrence, Risk Factors, Antineoplastic Agents therapeutic use, Bone Marrow Transplantation, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy
- Abstract
Bone marrow recurrence of adult acute lymphoblastic leukemia is typically an aggressive and most often rapidly fatal condition, an ideal setting for testing the latest research developments and experimental therapeutic options. Here we review recurrence mechanisms and treatment possibilities in order to identify the most appropriate clinical conduct. Choice of retreatment drugs and their dosages, related or unrelated donor bone marrow transplants, autologous peripheral blood stem cell transplants, immune manipulations, reversal of drug resistance, and restoration of apoptosis are all part of an integrated short-term therapeutic and decisional network to be developed for specific patient and disease prognostic subgroups.
- Published
- 1996
28. The use of anthracyclines in adult acute lymphoblastic leukemia.
- Author
-
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
29. Remission induction therapy for adults with acute myelogenous leukemia: towards the ICE age?
- Author
-
Bassan R and Barbui T
- Subjects
- Adult, Clinical Trials as Topic, Cytarabine therapeutic use, Etoposide therapeutic use, Humans, Idarubicin therapeutic use, Remission Induction, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Leukemia, Myeloid, Acute drug therapy
- Abstract
The primary goal of acute myeloid leukemia chemotherapy is to obtain a complete remission. In adults with de novo disease, response rates reach between sixty and seventy per cent with classical '3 + 7' or DAT schemes. Curative postinduction treatments are now available for responsive patients, which makes it mandatory to look for more effective modalities of induction therapy. Experience gathered in recent years shows that idarubicin, cytosine arabinoside, and etoposide together might contribute to the modeling of an improved remission induction regimen: ICE. Because ICE and similar programs are being used with increasing frequency worldwide, we decided to review critically the underlying issues and the evidence supporting this change.
- Published
- 1995
30. Platelet function after busulphan in chronic myeloproliferative disorders.
- Author
-
Barbui T, Bassan R, Viero P, Cortelazzo S, and Dini E
- Subjects
- Humans, Myeloproliferative Disorders blood, Platelet Aggregation, Platelet Count drug effects, Blood Platelets drug effects, Busulfan therapeutic use, Myeloproliferative Disorders drug therapy
- Published
- 1983
31. Surface immunoglobulin intensivity and p67 (CD5) antigen expression define different forms of B-cell chronic lymphocytic leukaemia.
- Author
-
Bassan R, Pronesti M, Buzzetti M, Viero P, Minetti B, Comotti B, Buelli M, and Barbui T
- Subjects
- Antigens, Neoplasm analysis, Antigens, Surface analysis, Humans, Leukemia, Lymphoid classification, Receptors, Antigen, B-Cell analysis, B-Lymphocytes immunology, Leukemia, Lymphoid immunology
- Published
- 1987
32. The chronic proliferative disease of large granular lymphocytes.
- Author
-
Bassan R, Rambaldi A, and Barbui T
- Subjects
- Antigens, Differentiation, T-Lymphocyte analysis, Arthritis, Rheumatoid complications, Autoimmune Diseases etiology, B-Lymphocytes pathology, Diagnosis, Differential, Pancytopenia etiology, T-Lymphocytes classification, Lymphoproliferative Disorders diagnosis, Lymphoproliferative Disorders genetics, Lymphoproliferative Disorders immunology, Lymphoproliferative Disorders pathology, T-Lymphocytes pathology
- Abstract
This review deals with the chronic lymphoproliferative disease of large granular lymphocytes endowed with T and natural killer cell characteristics. The disease is sufficiently characterized to allow its distinction from other lymphoproliferative disorders of the T cell type. The heterogeneous clinical course and laboratory findings illustrate the complexity of the interaction between proliferating large granular lymphocytes and other haematopoietic cells.
- Published
- 1989
33. Integrated use of morphology, cytochemistry, and immune marker analysis to identify acute leukaemia subtypes.
- Author
-
Bassan R, Rambaldi A, Viero P, Borleri G, and Barbui T
- Subjects
- Acute Disease, Adolescent, Adult, Aged, Child, Child, Preschool, Female, Histocytochemistry, Humans, Immunologic Techniques, Male, Middle Aged, Antigens, Differentiation analysis, Leukemia classification
- Abstract
One hundred and thirty-three acute leukaemia cases were evaluated by using a simplified sequence of morphological, cytochemical, and immunological investigations in order to obtain a correct leukaemia characterization that could have clinical relevance, rather than look for FAB-immunophenotype correlates. This approach offered an effective support to immediate therapeutic decisions and further investigations.
- Published
- 1989
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