77 results on '"Morra, Enrica"'
Search Results
2. Response Assessment in Waldenström's Macroglobulinaemia.
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Kimby, Eva, Owen, Roger G., and Morra, Enrica
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- 2017
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3. Wide-transcriptome analysis and cellularity of bone marrow CD34+/lin- cells of patients with chronic-phase chronic myeloid leukemia at diagnosis vs. 12 months of first-line nilotinib treatment.
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Trojani, Alessandra, Pungolino, Ester, Rossi, Giuseppe, D'Adda, Mariella, Lodola, Milena, Di Camillo, Barbara, Perego, Alessandra, Turrini, Mauro, Orlandi, Ester, Borin, Lorenza, Iurlo, Alessandra, Malato, Simona, Spina, Francesco, Latargia, Maria Luisa, Lanza, Francesco, Artale, Salvatore, Anghilieri, Michela, Carraro, Maria Cristina, De Canal, Gabriella, and Morra, Enrica
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BONE marrow ,CHRONIC myeloid leukemia ,NILOTINIB ,MYELOPROLIFERATIVE neoplasms ,GENE expression ,PROTEIN-tyrosine kinase inhibitors ,DIAGNOSIS ,THERAPEUTICS - Abstract
BACKGROUND: Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder with heterogeneous biological and clinical features. The biomolecular mechanisms of CML response to tyrosine-kinase inhibitors are not fully defined. OBJECTIVE: We undertook a gene expression profiling (GEP) study of selected bone marrow (BM) CD34+/lin- cells of chronic-phase CML patients at diagnosis and after 12 months of TKI nilotinib to investigate molecular signatures characterizing both conditions. METHODS:We selected and counted BM CD34+/lin- cells of 30 CML patients at diagnosis and during 3, 6 and 12 months of first-line nilotinib treatment. GEP was performed between CD34+/lin- cells of patients at diagnosis and the same patients after 12 months of nilotinib. RESULTS: The number of BM CD34+/lin- cells dramatically decreased after 3, 6 and 12 months of nilotinib. GEP detected 264 statistically significant differentially expressed genes at diagnosis vs. 12 months of nilotinib. Functional enrichment analysis revealed groups of genes belonging to 14 pathways differentially active during nilotinib treatment. CONCLUSIONS: In conclusion, lipid, glucose and sphingolipid metabolism, insulin resistance, complement and coagulation, platelet activation, cytoscheleton, cell adhesion, transport, B cell differentiation, RAS-signaling pathway, proliferation, growth factors, and apoptosis were significantly deregulated between CML patients at diagnosis and after 12 months of nilotinib. [ABSTRACT FROM AUTHOR]
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- 2017
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4. Recommendations for the diagnosis and initial evaluation of patients with Waldenström Macroglobulinaemia: A Task Force from the 8th International Workshop on Waldenström Macroglobulinaemia.
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Castillo, Jorge J., Garcia‐Sanz, Ramon, Hatjiharissi, Evdoxia, Kyle, Robert A., Leleu, Xavier, McMaster, Mary, Merlini, Giampaolo, Minnema, Monique C., Morra, Enrica, Owen, Roger G., Poulain, Stephanie, Stone, Marvin J., Tam, Constantine, Varettoni, Marzia, Dimopoulos, Meletios A., Treon, Steven P., and Kastritis, Efstathios
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WALDENSTROM'S macroglobulinemia ,BONE marrow examination ,NEEDLE biopsy ,AMYLOIDOSIS ,BLOOD hyperviscosity syndrome ,DIAGNOSIS - Abstract
The diagnosis of Waldenström macroglobulinaemia ( WM) can be challenging given the variety of signs and symptoms patients can present. Furthermore, once the diagnosis of WM is established, the initial evaluation should be thorough as well as appropriately directed. During the 8th International Workshop for WM in London, United Kingdom, a multi-institutional task force was formed to develop consensus recommendations for the diagnosis and initial evaluation of patients with WM. In this document, we present the results of the deliberations that took place to address these issues. We provide recommendations for history-taking and physical examination, laboratory studies, bone marrow aspiration and biopsy analysis and imaging studies. We also provide guidance on the initial evaluation of special situations, such as anaemia, hyperviscosity, neuropathy, Bing-Neel syndrome and amyloidosis. We hope these recommendations serve as a practical guidance to clinicians taking care of patients with a suspected or an established diagnosis of WM. [ABSTRACT FROM AUTHOR]
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- 2016
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5. Clonal architecture of CXCR4 WHIM-like mutations in Waldenström Macroglobulinaemia.
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Xu, Lian, Hunter, Zachary R., Tsakmaklis, Nicholas, Cao, Yang, Yang, Guang, Chen, Jie, Liu, Xia, Kanan, Sandra, Castillo, Jorge J., Tai, Yu‐Tzu, Zehnder, James L., Brown, Jennifer R., Carrasco, Ruben D., Advani, Ranjana, Sabile, Jean M., Argyropoulos, Kimon, Lia Palomba, M., Morra, Enrica, Trojani, Alessandra, and Greco, Antonino
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WALDENSTROM'S macroglobulinemia ,GENETIC mutation ,POLYMERASE chain reaction ,GENETICS ,IMMUNOGLOBULINS - Abstract
CXCR4
WHIM somatic mutations are distinctive to Waldenström Macroglobulinaemia ( WM), and impact disease presentation and treatment outcome. The clonal architecture of CXCR4WHIM mutations remains to be delineated. We developed highly sensitive allele-specific polymerase chain reaction ( AS- PCR) assays for detecting the most common CXCR4WHIM mutations ( CXCR4S338X C>A and C>G ) in WM. The AS- PCR assays detected CXCR4S338X mutations in WM and IgM monoclonal gammopathy of unknown significance ( MGUS) patients not revealed by Sanger sequencing. By combined AS- PCR and Sanger sequencing, CXCR4WHIM mutations were identified in 44/102 (43%), 21/62 (34%), 2/12 (17%) and 1/20 (5%) untreated WM, previously treated WM, IgM MGUS and marginal zone lymphoma patients, respectively, but no chronic lymphocytic leukaemia, multiple myeloma, non-IgM MGUS patients or healthy donors. Cancer cell fraction analysis in WM and IgM MGUS patients showed CXCR4S338X mutations were primarily subclonal, with highly variable clonal distribution (median 35·1%, range 1·2-97·5%). Combined AS- PCR and Sanger sequencing revealed multiple CXCR4WHIM mutations in many individual WM patients, including homozygous and compound heterozygous mutations validated by deep RNA sequencing. The findings show that CXCR4WHIM mutations are more common in WM than previously revealed, and are primarily subclonal, supporting their acquisition after MYD88L265P in WM oncogenesis. The presence of multiple CXCR4WHIM mutations within individual WM patients may be indicative of targeted CXCR4 genomic instability. [ABSTRACT FROM AUTHOR]- Published
- 2016
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6. Prognostic relevance of the flow cytometric count of medullar blasts in myelodysplastic syndromes.
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Molteni, Alfredo, Riva, Marta, Cesana, Clara, Speziale, Valentina, Nichelatti, Michele, Scarpati, Barbara, Greco, Rosa, Ravano, Emanuele, Cairoli, Roberto, Rossini, Silvano, and Morra, Enrica
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MYELODYSPLASTIC syndromes ,BONE marrow diseases ,DYSPLASIA ,FLOW cytometry ,PROGNOSIS ,HEMATOLOGY ,MICROSCOPY - Abstract
Objective The medullar blast count is a milestone in the prognostic assessment in myelodysplastic syndromes ( MDS). The optical microscopy ( OM) may sometimes be inaccurate in this disease. The aim of this work is to test the flow immunocytometric ( FCM) determinations of medullar immature cells ( CD45
± ) and the expression, among them, of CD33, CD34, and CD117 markers, for their prognostic relevance. Methods In a retrospective analysis of 98 patients affected by MDS, the IPSS was re-calculated by means of the FCM determination of blasts. Survival of patients at low or intermediate-1 IPSS risk was compared with the survival of patients at intermediate-2 or high IPSS risk. In the 64 cases with OM blast count lower than 5%, the survival of patients with the FCM count of medullar blasts ≤2% was compared with that of patients with FCM count >2%. Results Each single marker had a prognostic weight comparable to the optical blast count. The FCM blast count was particularly efficient in distinguishing the risk of having up to 2% or more than 2% of blasts in patients without OM excess of blasts. Conclusion This method is interesting as prognostic tool, especially in patients without excess of blast. [ABSTRACT FROM AUTHOR]- Published
- 2015
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7. Autologous stem cell transplantation with in vivo purged progenitor cells shows long-term efficacy in relapsed/refractory follicular lymphoma.
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Arcaini, Luca, Morello, Lucia, Tucci, Alessandra, Rusconi, Chiara, Ladetto, Marco, Rattotti, Sara, Bonfichi, Maurizio, Bottelli, Chiara, Gabutti, Cristina, Bernasconi, Paolo, Varettoni, Marzia, Gotti, Manuel, Troletti, Daniela, Guerrera, Maria Luisa, Fiaccadori, Valeria, Sciarra, Roberta, Ferretti, Virginia Valeria, Alessandrino, Emilio Paolo, Rossi, Giuseppe, and Morra, Enrica
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- 2015
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8. Feasibility of romiplostim discontinuation in adult thrombopoietin-receptor agonist responsive patients with primary immune thrombocytopenia: an observational retrospective report in real life clinical practice.
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Carpenedo, Monica, Cantoni, Silvia, Coccini, Veronica, Fedele, Marilena, Morra, Enrica, and Pogliani, Enrico Maria
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ROMIPLOSTIM ,DRUG efficacy ,T cells ,IMMUNE response - Abstract
Thrombopoietin mimetics are new treatment options for patients with immune thrombocytopenia (ITP). Because of their mechanism of action, long-term administration was envisioned in order to maintain effective thrombopoiesis. We report on 30 romiplostim treated patients: 13/27 responders (48%) achieved stable platelet counts on a mean romiplostim dose of 2.43 µg/kg and were able to stop romiplostim after a mean of 44.3 weeks (range 12-122) on therapy with sustained response maintained at a mean of 26 months (range 12-52). No bleeding events occurred during the observational period. No specific patient's features nor pattern of early response seemed to predict for sustained response. However, patients achieving safe platelet counts at lower dosages are probably worth a try of therapy tapering and discontinuation. Our observations support feasibility of romiplostim safe suspension in a relevant proportion of ITP patients. [ABSTRACT FROM AUTHOR]
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- 2015
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9. Invasive fungal infections in lymphoproliferative disorders: a monocentric retrospective experience.
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Nosari, Anna Maria, Pioltelli, Maria Luisa, Riva, Marta, Marbello, Laura, Nichelatti, Michele, Greco, Antonino, Molteni, Alfredo, Vismara, Eleonora, Gabutti, Cristina, Volonterio, Alberto, Lombardi, Pierluigi, and Morra, Enrica
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HEALTH outcome assessment ,COMORBIDITY ,COMMUNICABLE disease treatment ,MYCOSES ,LYMPHOPROLIFERATIVE disorders ,LYMPHOMA treatment ,CHRONIC lymphocytic leukemia treatment ,MORTALITY ,THERAPEUTICS - Abstract
Invasive fungal infections (IFIs) seem to be a relevant cause of morbidity and mortality in patients with chronic lymphoproliferative disorders. We studied retrospectively the epidemiology, clinical manifestations and outcome of invasive fungal infections in 42 patients with lymphoproliferative diseases, treated between January 2004 and February 2012 for probable or proven IFI. In our entire population (1355 patients) of chronic lymphoproliferative malignancies, the incidence of probable/proven IFI was 3% (molds 2.3%, yeasts 0.5%, mixed infections 0.2%). Eight patients developed a yeast infection documented by blood cultures in seven cases and by the microscopic observation of Candida spp. in the vitreum after vitrectomy in one case. Among molds we diagnosed three proven infections by histologic evidence of Aspergillus spp. ( n = 2) and Mucor ( n = 1) in the lung and 28 probable mycoses. Three mixed infections from both molds and yeasts were also observed. Twenty-two cases showed positivity of galactomannan antigen in the serum ( n = 16), in bronchoalveolar lavage (BAL) fluid ( n = 4) or in both ( n = 2). Cultures were positive in 11 cases. The overall rate of response to therapy was 64%. Fungal-attributable mortality rate was 17%, with a significant difference between molds and yeasts (16% vs. 25%, p = 0.03). At univariate analysis, the only risk factors related to mortality were severe and prolonged neutropenia ( p = 0.003) and age ( p = 0.03). Among molds, the rapid start of antifungals was probably partially responsible, together with new drugs, for the reduction of mortality, despite the severe immunosuppression of these patients. [ABSTRACT FROM AUTHOR]
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- 2014
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10. Associated cancers in waldenström macroglobulinemia: clues for common genetic predisposition.
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Morra, Enrica, Varettoni, Marzia, Tedeschi, Alessandra, Arcaini, Luca, Ricci, Francesca, Pascutto, Cristiana, Rattotti, Sara, Vismara, Eleonora, Paris, Laura, and Cazzola, Mario
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- 2013
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11. Should a Positive Direct Antiglobulin Test Be Considered a Prognostic Predictor in Chronic Lymphocytic Leukemia?
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Ricci, Francesca, Tedeschi, Alessandra, Vismara, Eleonora, Colombo, Chiara, Veronese, Silvio, Nichelatti, Michele, Cairoli, Roberto, Morra, Enrica, and Montillo, Marco
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- 2013
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12. Old and new prognostic factors in acute myeloid leukemia with deranged core-binding factor beta.
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Cairoli, Roberto, Beghini, Alessandro, Turrini, Mauro, Bertani, Giambattista, Nadali, Gianpaolo, Rodeghiero, Francesco, Castagnola, Carlo, Lazzaroni, Francesca, Nichelatti, Michele, Ferrara, Felicetto, Pizzolo, Giovanni, Pogliani, Enrico, Rossi, Giuseppe, Martinelli, Giovanni, and Morra, Enrica
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- 2013
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13. Verifying Hellström-Lindberg score as predictive tool for response to erythropoietin therapy according to the 'International Working Group' criteria, in anemic patients affected by myelodysplastic syndrome: a monocentric experience.
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Molteni, Alfredo, Riva, Marta, Greco, Rosa, Nichelatti, Michele, Ravano, Emanuele, Marbello, Laura, Nosari, Annamaria, and Morra, Enrica
- Abstract
The Hellström-Lindberg score (HLS) (1997) is designed to predict erythroid response to erythropoietin treatment in myelodysplastic patients. In order to test the validity of this scoring system, 58 patients affected by myelodysplastic syndrome, treated with a 'standard dose' approach between 2001 and 2010, were analyzed. The response to erythropoietin treatment was evaluated in accordance with the 'international working group' (IWG) criteria. Among the patients only two were scored 'poor,' 12 'intermediate,' and 44 'good' (15 of whom were scored '3' and 29 '4'). Although the system was verified as a predictive tool for response to erythropoietin therapy, we noted that of patients scored as 'good,' those with a numerical score of '4' responded more frequently than did those scored '3', as evaluated under both the 2006- and 2000-IWG ('major response') criteria. The modest response rate in patients scoring '3' did not show a difference in response rate in comparison to the 'intermediate' group. The present data suggest that only patients scoring '4' on the scale may show an adequate response to the standard dose erythropoietin therapy, while frontline high-dose therapy should be offered to other patients. A further analysis considering endogenous erythropoietin as a possible determinant of response revealed the optimal cut-off value of 80 mIU/mL, instead of the value of 100 mIU/mL utilized by the HLS. [ABSTRACT FROM AUTHOR]
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- 2013
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14. Fludarabine, Cyclophosphamide, and Rituximab in Salvage Therapy of Waldenström's Macroglobulinemia.
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Tedeschi, Alessandra, Ricci, Francesca, Goldaniga, Maria Cecilia, Benevolo, Giulia, Varettoni, Marzia, Motta, Marina, Pioltelli, Pietro, Gini, Guido, Barate, Claudia, Luraschi, Annamaria, Vismara, Eleonora, Frustaci, Anna Maria, Nichelatti, Michele, Vitolo, Umberto, Baldini, Luca, and Morra, Enrica
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- 2013
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15. Response assessment in Waldenström macroglobulinaemia: update from the VIth International Workshop.
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Owen, Roger G., Kyle, Robert A., Stone, Marvin J., Rawstron, Andy C., Leblond, Veronique, Merlini, Giampaolo, Garcia‐Sanz, Ramon, Ocio, Enrique M., Morra, Enrica, Morel, Pierre, Anderson, Kenneth C., Patterson, Christopher J., Munshi, Nikhil C., Tedeschi, Alessandra, Joshua, Douglas E., Kastritis, Efstathios, Terpos, Evangelos, Ghobrial, Irene M., Leleu, Xavier, and Gertz, Morie A.
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IMMUNE response ,WALDENSTROM'S macroglobulinemia ,CLINICAL trials ,HEALTH outcome assessment ,BONE marrow diseases ,IMMUNOGLOBULIN M - Abstract
This report represents a further update of the consensus panel criteria for the assessment of clinical response in patients with Waldenström macroglobulinaemia ( WM). These criteria have been updated in light of further data demonstrating an improvement in categorical responses with new drug regimens as well as acknowledgement of the fact that such responses are predictive of overall outcome. A number of key changes are proposed but challenges do however remain and these include the variability in kinetics of immunoglobulin M ( IgM) reduction with different treatment modalities and the apparent discrepancy between IgM and bone marrow/tissue response noted with some regimens. Planned sequential bone marrow assessments are encouraged in clinical trials. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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16. Gene expression profiling identifies ARSD as a new marker of disease progression and the sphingolipid metabolism as a potential novel metabolism in chronic lymphocytic leukemia.
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Trojani, Alessandra, Di Camillo, Barbara, Tedeschi, Alessandra, Lodola, Milena, Montesano, Simona, Ricci, Francesca, Vismara, Eleonora, Greco, Antonino, Veronese, Silvio, Orlacchio, Aldo, Martino, Sabata, Colombo, Chiara, Mura, Mariangela, Nichelatti, Michele, Colosimo, Anna, Scarpati, Barbara, Montillo, Marco, and Morra, Enrica
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SPHINGOLIPIDS ,LEUKEMIA ,CANCER prognosis ,GENE expression ,PROTEIN microarrays - Abstract
Background: Several studies demonstrated IGVH mutational status and ZAP70 expression as the most relevant prognostic markers in Chronic Lymphocytic Leukemia (CLL), suggesting the separation of two patient subgroups: with good mutated ZAP70 negative (MTZAP70^-) and poor unmutated ZAP70 positive (UMZAP70^{+}) prognosis. Design and methods: We determined the gene expression of B cells in 112 CLL patients divided into three classes: class 1 with MTZAP70^-, class 2 with UMZAP70^{+}, and class 3 included both UMZAP70^- and MTZAP70^{+}. Results: We found LPL, AGPAT2, MBOAT1, CHPT1, AGPAT4, PLD1 genes encoding enzymes involved in lipid metabolism overexpressed in UMZAP70^{+}. In addition, this study identified ARSD, a gene belonging to the sphingolipid metabolism, as a new gene significantly overexpressed in UMZAP70^{+} compared to MTZAP70^-. Western blots confirmed that ARSD protein levels were significantly different between the 3 classes of patients and normal controls. Statistical analysis identified a significant correlation between ARSD and IGVH; however, both ARSD protein level and IGVH were independently associated with the need for therapy of CLL patients. Conclusions: ARSD is a novel prognostic factor as the time to start therapy is shorter in patients with high levels of ARSD protein and sphingolipid metabolism could represent a new biological mechanism in CLL. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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17. Intensive consolidation therapy compared with standard consolidation and maintenance therapy for adults with acute myeloid leukaemia aged between 46 and 60 years: final results of the randomized phase III study (AML 8B) of the European Organization for Research and Treatment of Cancer (EORTC) and the Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto (GIMEMA) Leukemia Cooperative Groups
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Hengeveld, Marysia, Suciu, Stefan, Karrasch, Matthias, Specchia, Giorgina, Marie, Jean-Pierre, Muus, Petra, Petti, Maria, Rotoli, Bruno, Amadori, Sergio, Fioritoni, Guiseppe, Leoni, Pietro, Morra, Enrica, Thaler, Joseph, Resegotti, Luigi, Fazi, Paola, Vignetti, Marco, Mandelli, Franco, Zittoun, Robert, and Witte, Theo
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DRUG therapy ,DEATH (Biology) ,CYTARABINE ,DAUNOMYCIN - Abstract
The most effective post-remission treatment to maintain complete remission (CR) in adults aged between 46 and 60 years with acute myeloid leukaemia (AML) is uncertain. Previously untreated patients with AML in CR after induction chemotherapy with daunorubicin and cytarabine were randomized between two intensive courses of consolidation therapy containing high-dose cytarabine, combined with amsacrine or daunorubicin and a standard consolidation and maintenance therapy containing standard dose cytarabine and daunorubicin. One hundred fifty-eight CR patients were assigned to the intensive group and 157 patients to the standard group. After a median follow-up of 7.5 years, the 4-year survival rate was 32 % in the intensive group versus 34 % in the standard group ( P = 0.29). In the intensive group, the 4-year relapse incidence was lower than in the standard group: 55 and 75 %, respectively ( P = 0.0003), whereas treatment-related mortality incidence was higher: 22 versus 3 % ( P < 0.0001). Two intensive consolidation courses containing high-dose cytarabine as post-remission treatment in patients with AML aged between 46 and 60 years old did not translate in better long-term outcome despite a 20 % lower relapse incidence. Better supportive care and prevention of treatment-related complications may improve the overall survival after intensified post-remission therapy in this age group. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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18. Quality of life in elderly patients with essential thrombocythaemia. An Italian multicentre study.
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Oliva, Esther, Piccin, Andrea, Mazzucconi, Maria, Morra, Enrica, Recine, Umberto, Pogliani, Enrico, Pane, Fabrizio, Gobbi, Marco, Gugliotta, Luigi, Krampera, Mauro, Cascavilla, Nicola, Cacciola, Rossella, Cacciola, Emma, Fioritoni, Giuseppe, Fanin, Renato, Liberati, Anna, Angelucci, Emanuele, and Tura, Sante
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THROMBOCYTOPENIA ,MYELOPROLIFERATIVE neoplasms ,THROMBOSIS ,HEMORRHAGE ,QUALITY of life - Abstract
Essential thrombocythaemia (ET) is a myeloproliferative neoplasm characterized by elevated platelet counts and increased incidence of thrombosis and haemorrhage. Median age at diagnosis is 65-70 years. Life expectancy is similar to that of the healthy population. Symptoms and complications may affect quality of life (QoL); in particular, in elderly patients ET may represent an additional burden. We performed a survey in 494 elderly ET patients to evaluate patient-reported outcomes (PROs). Comorbidities were present in 305 (62%) patients. Factorial analysis based on survey items representing psychological aspects of daily life identified an 'attitude domain' with four clusters of patients: (A) very pessimistic ( n = 99), (B) pessimistic ( n = 101), (C) optimistic ( n = 90), and (D) very optimistic ( n = 107). Patients in cluster A had more comorbidities ( p = 0.003) while patients in cluster D required fewer medical visits and were less disturbed by medications ( p < 0.0001). Independent factors predicting Short-Form Health Survey, version 2 physical QoL were grade of optimism ( p < 0.0001), gender ( p = 0.007), and Charlson comorbidity index ( p < 0.0001)). Grade of optimism and disturbances related to medication predicted mental QOL ( p < 0.0001). In conclusion, physicians should take into consideration PROs, as 'attitude' is associated with physical and mental QoL. Treatment should be tailored to patients' needs according to comorbidities, lifestyle, and psychological conditions. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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19. Fludarabine plus cyclophosphamide and rituximab in Waldenstrom macroglobulinemia.
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Tedeschi, Alessandra, Benevolo, Giulia, Varettoni, Marzia, Battista, Marta L., Zinzani, Pier L., Visco, Carlo, Meneghini, Vittorio, Pioltelli, Pietro, Sacchi, Stefano, Ricci, Francesca, Nichelatti, Michele, Zaja, Francesco, Lazzarino, Mario, Vitolo, Umbero, and Morra, Enrica
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FLUDARABINE ,ANTINEOPLASTIC agents ,CYCLOPHOSPHAMIDE ,RITUXIMAB ,LYMPHOCYTIC leukemia ,CHRONIC lymphocytic leukemia - Abstract
BACKGROUND: The combination of fludarabine, cyclophosphamide, and rituximab (FCR) has produced promising results in chronic lymphocytic leukemia and other lymphoproliferative disorders. The authors report the final results from a multicenter, prospective study examining FCR in Waldenstrom macroglobulinemia (WM). METHODS: Forty-three patients with symptomatic WM that was untreated or pretreated with 1 line of chemotherapy received rituximab 375 mg/m
2 intravenously on day 1 and fludarabine 25 mg/m2 and cyclophosphamide 250 mg/m2 intravenously on days 2 through 4. FCR was repeated every 28 days for up to 6 courses. RESULTS: The overall response rate was 79%, and the major response rate of 74.4%, including 11.6% complete remissions (CRs) and 20.9% very good partial remissions. An amelioration of the quality of responses was observed during follow-up, leading to 18.6% of CRs. No differences in terms of responses were observed among previously treated or untreated patients. Among the clinical and laboratory features that were considered, only the β2-microglobulin level had a significant impact in terms of achieving a major response. The major toxicity reported was grade 3/4 neutropenia, which occurred in 45% of courses and was the main reason for treatment discontinuation. After the end of treatment, 19 patients (44%) had long-lasting episodes of neutropenia. Three patients developed myelodysplastic syndrome during follow-up. CONCLUSIONS: The FCR regimen was capable of neutralizing adverse prognostic factors and proved to be active in patients with WM, leading to rapid disease control and good-quality responses. Because myelosuppression was the main concern, further studies are warranted to optimize dosages and treatment duration. Cancer 2011;. © 2011 American Cancer Society. [ABSTRACT FROM AUTHOR]- Published
- 2012
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20. Therapy-Related Myeloid Neoplasms in Chronic Lymphocytic Leukemia and Waldenstrom's Macroglobulinemia.
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Ricci, Francesca, Tedeschi, Alessandra, Montillo, Marco, and Morra, Enrica
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CHRONIC lymphocytic leukemia treatment ,WALDENSTROM'S macroglobulinemia ,CHRONIC lymphocytic leukemia ,DNA damage ,DRUG therapy ,LEUKEMIA etiology - Abstract
Secondary myelodysplasia (MDS) and acute myeloid leukemia (AML) are frequent long term complications in Chronic Lymphocytic Leukemia (CLL) and Waldenström Macroglobulinemia (WM) patients. Although disease-related immune-suppression plays a crucial role in leukemogenesis there is great concern that therapy may further increase the risk of developing these devastating complications. Nucleoside analogs (NA) and alkylating agents are considered appropriate agents in the treatment of both CLL and WM patients. Prolonged immunosuppression related to NA therapy and the incorporation of these agents or their metabolites into DNA, with potentially mutagenic action, leads to speculation that their therapeutic use might be responsible for an increased incidence of second cancer especially when combined with other DNA damaging agents like alkylating agents. In this review the published studies considering the occurrence of secondary MDS and AML in CLL and WM patients are reported and the potential role of chemotherapeutic agents in leukemogenesis is discussed. [ABSTRACT FROM AUTHOR]
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- 2011
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21. Flow cytometry and cytomorphology evaluation of hematologic malignancy in cerebrospinal fluids: comparison with retrospective clinical outcome.
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Cesana, Clara, Klersy, Catherine, Scarpati, Barbara, Brando, Bruno, Faleri, Maurizio, Bertani, Giambattista, Gatti, Arianna, Volpato, Elisabetta, Barba, Claudia, Ferri, Ursula, Scampini, Linda, Grillo, Giovanni, Lando, Giuliana, Nosari, Annamaria, Morra, Enrica, and Cairoli, Roberto
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DIAGNOSTIC use of flow cytometry ,HEMATOLOGY ,CEREBROSPINAL fluid ,COMPARATIVE studies ,RETROSPECTIVE studies - Abstract
n independent clinical assessment was compared with flow cytometry (FCM) and cytomorphology results obtained on 227 cerebrospinal fluids investigated for hematologic malignancy, in a retrospective longitudinal study with a median observation time of 11 months. A combined method assessment (CMA), defining 'positive' a sample if at least one method gave 'positive' results, was also tested. Eleven out of 55 screening samples and 53 out of 166 follow-up samples resulted positive at clinical evaluation. FCM and CM were concordant with positive clinical assessment in 68.5% and 51.5% of cases, respectively. According to CMA, 10.5% of samples (resulting false negative by either FCM or cytomorphology) were rescued as true positive. FCM retained significantly higher accuracy than cytomorphology ( p = 0.0065) and 100% sensitivity when at least 220 leukocytes were acquired. CMA accuracy was higher than FCM accuracy and significantly higher than cytomorphology accuracy in the analysis of all samples ( p < 0.0001), samples from mature B/T cell neoplasms ( p = 0.0021), and samples drawn after intrathecal treatment ( p = 0.0001). When acquiring ≤220 leukocytes, FCM accuracy was poor, and combining cytomorphology added statistically significant diagnostic advantage ( p = 0.0043). Although FCM is the best diagnostic tool for evaluating CSF, morphology seems helpful especially when clinically positive follow-up samples are nearly acellular. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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22. Multicenter Independent Assessment of Outcomes in Chronic Myeloid Leukemia Patients Treated With Imatinib.
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Gambacorti-Passerini, Carlo, Antolini, Laura, Mahon, François-Xavier, Guilhot, Francois, Deininger, Michael, Fava, Carmen, Nagler, Arnon, Della Casa, Chiara Maria, Morra, Enrica, Abruzzese, Elisabetta, D'Emilio, Anna, Stagno, Fabio, le Coutre, Philipp, Hurtado-Monroy, Rafael, Santini, Valeria, Martino, Bruno, Pane, Fabrizio, Piccin, Andrea, Giraldo, Pilar, and Assouline, Sarit
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CANCER research ,CHRONIC myeloid leukemia ,IMATINIB ,MORTALITY ,DRUG side effects - Abstract
Background Imatinib slows development of chronic myeloid leukemia (CML). However, available information on morbidity and mortality is largely based on sponsored trials, whereas independent long-term field studies are lacking. Patients and Methods Consecutive CML patients who started imatinib treatment before 2005 and who were in complete cytogenetic remission (CCyR) after 2 years (±3 months) were eligible for enrollment in the independent multicenter Imatinib Long-Term (Side) Effects (ILTE) study. Incidence of the first serious and nonserious adverse events and loss of CCyR were estimated according to the Kaplan–Meier method and compared with the standard log-rank test. Attainment of negative Philadelphia chromosome hematopoiesis was assessed with cytogenetics and quantitative polymerase chain reaction. Cumulative incidence of death related or unrelated to CML progression was estimated, accounting for competing risks, according to the Kalbleisch–Prentice method. Standardized incidence ratios were calculated based on population rates specific for sex and age classes. Confidence intervals were calculated by the exact method based on the χ2 distribution. All statistical tests were two-sided. Results A total of 832 patients who were treated for a median of 5.8 years were enrolled. There were 139 recorded serious adverse events, of which 19.4% were imatinib-related. A total of 830 nonserious adverse events were observed in 53% of patients; 560 (68%) were imatinib-related. The most frequent were muscle cramps, asthenia, edema, skin fragility, diarrhea, tendon, or ligament lesions. Nineteen patients (2.3%) discontinued imatinib because of drug-related toxic effects. Forty-five patients lost CCyR, at a rate of 1.4 per 100 person-years. Durable (>1 year) negative Philadelphia chromosome hematopoiesis was attained by 179 patients. Twenty deaths were observed, with a 4.8% mortality incidence rate (standardized incidence ratio = 0.7; 95% confidence interval = 0.40 to 1.10, P = .08), with only six (30%) associated with CML progression. Conclusions In this study, CML-related deaths were uncommon in CML patients who were in CCyR 2 years after starting imatinib, and survival was not statistically significantly different from that of the general population. [ABSTRACT FROM PUBLISHER]
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- 2011
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23. Mutations of CD79A, CD79B and EZH2 genes in immunodeficiency-related non-Hodgkin lymphomas.
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Capello, Daniela, Gloghini, Annunziata, Martini, Maurizio, Spina, Michele, Tirelli, Umberto, Bertoni, Francesco, Rinaldi, Andrea, Morra, Enrica, Rambaldi, Alessandro, Sinigaglia, Fabiola, Larocca, Luigi Maria, and Carbone, Antonino
- Subjects
GENETIC mutation ,LYMPHOMAS ,HODGKIN'S disease ,IMMUNODEFICIENCY ,POLYMERASE chain reaction - Abstract
The article discusses a study which investigated the involvement of CD79A, EZH2, and CD79B gene mutations in immunodeficiency-related non-Hodgkin lymphomas (ID-NHL). Using polymerase chain reaction amplification and direct sequencing, the study identified only EZH2 mutations in 3/116 ID-NHL primary samples. It notes that among the immunocompetent hosts' aggressive NHL, EZH2 mutations are selectively confined to cases of diffuse large B-cell lymphoma (DLBCL) with a germinal centre (GC) phenotype.
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- 2011
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24. Report From the Sixth International Workshop on Waldenström's Macroglobulinemia.
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Treon, Steven P., Merlini, Giampaolo, Morra, Enrica, Patterson, Christopher J., and Stone, Marvin J.
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- 2011
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25. Dasatinib, even at low doses, is an effective second-line therapy for chronic myeloid leukemia patients resistant or intolerant to imatinib. Results from a real life-based Italian multicenter retrospective study on 114 patients.
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Visani, Giuseppe, Breccia, Massimo, Gozzini, Antonella, Specchia, Giorgina, Montefusco, Enrico, Morra, Enrica, Annunziata, Mario, Camera, Andrea, Cavazzini, Francesco, Stagno, Fabio, Pregno, Patrizia, Usala, Emilio, Santini, Valeria, Piccaluga, Pier Paolo, and Isidori, Alessandro
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- 2010
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26. Single nucleotide polymorphism-arrays provide new insights in the pathogenesis of post-transplant diffuse large B-cell lymphoma.
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Rinaldi, Andrea, Capello, Daniela, Scandurra, Marta, Greiner, Timothy C., Chan, Wing C., Bhagat, Govind, Rossi, Davide, Morra, Enrica, Paulli, Marco, Rambaldi, Alessandro, Rancoita, Paola M. V., Inghirami, Giorgio, Ponzoni, Maurilio, Moreno, Santiago M., Piris, Miguel A., Mian, Michael, Chigrinova, Ekaterina, Zucca, Emanuele, Favera, Riccardo D., and Gaidano, Gianluca
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LYMPHOMA treatment ,GENETIC polymorphisms ,CARCINOGENESIS ,TRANSPLANTATION immunology ,HLA histocompatibility antigens ,B cell lymphoma - Abstract
Post-transplant lymphoproliferative disorders (PTLD) are complications of solid organ transplantation associated with severe morbidity and mortality. Diffuse large B-cell lymphoma (DLBCL) represents the most common form of monomorphic PTLD. We studied 44 cases of post-transplant DLBCL (PT-DLBCL) with high-density genome wide single nucleotide polymorphism-based arrays, and compared them with 105 cases of immunocompetent DLBCL (IC-DLBCL) and 28 cases of Human Immunodeficiency Virus-associated DLBCL (HIV-DLBCL). PT-DLBCL showed a genomic profile with specific features, although their genomic complexity was overall similar to that observed in IC- and HIV-DLBCL. Among the loci more frequently deleted in PT-DLBCL there were small interstitial deletions targeting known fragile sites, such as FRA1B, FRA2E and FRA3B. Deletions at 2p16.1 (FRA2E) were the most common lesions in PT-DLBCL, occurring at a frequency that was significantly higher than in IC-DLBCL. Genetic lesions that characterized post-germinal center IC-DLBCL were under-represented in our series of PT-DLBCL. Two other differences between IC-DLBCL and PT-DLBCL were the lack of del(13q14.3) ( MIR15/MIR16) and of copy neutral LOH affecting 6p [major histocompatibility complex (MHC) locus] in the latter group. In conclusion, PT-DLBCL presented unique features when compared with IC-DLBCL. Changes in PT-DLBCL were partially different to those in HIV-DLBCL, suggesting different pathogenetic mechanisms in the two conditions linked to immunodeficiency. [ABSTRACT FROM AUTHOR]
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- 2010
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27. Bortezomib plus dexamethasone can improve stem cell collection and overcome the need for additional chemotherapy before autologous transplant in patients with myeloma.
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Corso, Alessandro, Barbarano, Luciana, Mangiacavalli, Silvia, Spriano, Mauro, Alessandrino, Emilio P., Cafro, Anna Maria, Pascutto, Cristiana, Varettoni, Marzia, Bernasconi, Paolo, Grillo, Giovanni, Carella, Angelo M., Montalbetti, Luigi, Lazzarino, Mario, and Morra, Enrica
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DEXAMETHASONE ,PREGNANE ,MULTIPLE myeloma ,B cell lymphoma ,MONOCLONAL gammopathies ,ETOPOSIDE ,ANTINEOPLASTIC agents - Abstract
The aim of this phase II trial was to investigate the efficacy of bortezomib plus dexamethasone (Vel-Dex) as induction therapy in patients with multiple myeloma (MM) and to define the role of intensification before transplantation. Fifty-seven patients were treated with four courses of Vel-Dex, two cycles of dexamethasone, cyclophosphamide, etoposide and cisplatin (DCEP), and a single autologous transplant. Fourteen patients (25%) went off-study: seven after Vel-Dex, seven after DCEP. All patients yielded high numbers of stem cells (median CD34+ cells 7.5 × 106/kg); 54 of the 57 patients (94%) collected ≥4 × 106/kg CD34+ cells, 60% with a single leukapheresis. The overall response rate (ORR) after Vel-Dex was 86% (70% had a very good partial response [VGPR] or better) regardless of cytogenetic abnormalities and International Staging System stage (ISS). The response at the end of the two DCEP cycles remained unchanged in 35 patients (70%), worsened in 15 (20%), and improved in 5 (10%). Because of the consistent drop-out, the ORR in intention-to-treat analysis decreased significantly from 86% after Vel-Dex to 76% after DCEP, and 73% after transplantation. However, when considering the subset of 43 patients who completed the program, the ORR was 96% (complete response 39%, VGPR 41%, partial response 16%). In conclusion, Vel-Dex produces high response rates, improves stem cell collection, and overcomes the need for intensification before autologous transplantation. [ABSTRACT FROM AUTHOR]
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- 2010
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28. ZAP-70, IgVh, and cytogenetics for assessing prognosis in chronic lymphocytic leukemia.
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Trojani, Alessandra, Montillo, Marco, Nichelatti, Michele, Tedeschi, Alessandra, Colombo, Chiara, Veronese, Silvio, Mura, Maria Angela, Ricci, Francesca, Scarpati, Barbara, Colosimo, Anna, Lodola, Milena, and Morra, Enrica
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BIOMARKERS ,CYTOGENETICS ,PROTEINS ,CHRONIC lymphocytic leukemia ,B cells ,BONE marrow ,PATIENTS - Abstract
Background: New prognostic factors such as IgVh mutational status, ZAP-70 protein expression and cytogenetic abnormalities have shown to offer important prognostic information for patients with chronic lymphocytic leukemia (CLL). Our aim was to evaluate the optimal cut-off for IgVh mutational status, ZAP-70 expression and cytogenetic abnormalities in association with disease progression defined as the need for treatment within 3~years from diagnosis in 170 patients with B-CLL. Design and methods: Receiver operating characteristics (ROC) analysis and multivariate general linear models (GLMs) were used to investigate the most significant cut-off values of these biomarkers and their prognostic impact. Results: Our findings estimated that the optimal cut-off for IgVh mutation status and for ZAP-70 protein expression was 97% and 16.5% respectively and a high concordance between the two was demonstrated. We identified 30% as being the best-cut-off for 17p-, 11q- and 6q-. In univariate analysis 17p- was found to be a significant predictor of the event only for the whole population. Multivariate analysis including all biological parameters, identified 11q deletion as the only significant regressor. Conclusions: We assessed that IgVh mutational status, ZAP-70 protein and 6q- are powerful prognostic markers. Analyses of all these factors revealed that 11q deletion was the strongest predictor of disease progression in B-CLL. [ABSTRACT FROM AUTHOR]
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- 2010
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29. The spectrum of use of rituximab in chronic lymphocytic leukemia.
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Tedeschi, Alessandra, Vismara, Eleonora, Ricci, Francesca, Morra, Enrica, and Montillo, Marco
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- 2010
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30. Current Therapeutic Options for Chronic Lymphocytic Leukemia.
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Tedeschi, Alessandra, Vismara, Eleonora, Ricci, Francesca, Morra, Enrica, and Montillo, Marco
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CHRONIC lymphocytic leukemia treatment ,LYMPHOCYTIC leukemia ,CANCER chemotherapy ,LEUKEMIA ,ALKYLATING agents ,PURINES ,PATIENTS ,THERAPEUTICS - Abstract
The article discusses the options for the current therapeutic treatment of chronic lymphocytic leukemia (CLL). Subjects for the initial therapy in the treatment of (CLL) include those who have Rai stage 0 or Binet stage A until the disease progresses and not including patients with asymptomatic CLL. Also presented is the overview of first-line therapy for the treatment of CLL from the alkylating agents to purine analogues. Chlorambucil is considered the first-line treatment accepted while alemtuzumab and bendamustine are frontline therapies.
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- 2009
31. Molecular characterization of post-transplant lymphoproliferative disorders of donor origin occurring in liver transplant recipients.
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Capello, Daniela, Rasi, Silvia, Oreste, Pierluigi, Veronese, Silvio, Cerri, Michaela, Ravelli, Erika, Rossi, Davide, Minola, Ernesto, Colosimo, Anna, Gambacorta, Marcello, Muti, Giuliana, Morra, Enrica, and Gaidano, Gianluca
- Abstract
Post-transplant lymphoproliferative disorders (PTLDs) represent a frequent complication of solid organ transplantation. Although most PTLDs arise from recipient lymphoid cells, a considerable fraction of cases may arise from donor B-cells. In an attempt to clarify the histogenesis and pathogenesis of PTLDs derived from donor B-cells, monoclonal PTLDs occurring in liver transplant recipients were chosen as a model to compare donor (D-PTLDs) versus recipient PTLDs (R-PTLDs). The tumour panel included nine D-PTLDs and six R-PTLDs. D-PTLDs were early-onset, EBV-infected lymphoproliferations classified as polymorphic PTLD (P-PTLD; n = 7) or diffuse large B-cell lymphoma (DLBCL; n = 2) with tumour localization confined to the hepatic hilum. All R-PTLDs were late-onset DLBCLs and showed extrahepatic localization. A BCL-6
− /MUM1+ /CD138+/− phenotype, consistent with a post-germinal centre (GC) stage of pre-terminal B-cell differentiation, was observed in all D-PTLDs and in 2/6 R-PTLDs, whereas a BCL6+ /MUM1− /CD138− profile, reminiscent of GC B-cells, was detected in 4/6 R-PTLDs. The presence of somatic IGHV hypermutation was observed in 6/9 D-PTLDs and in 4/6 R-PTLDs, suggesting derivation from antigen-experienced B-cells. IGHV4-39 was the IGHV gene most frequently encountered, being rearranged in 3/9 D-PTLDs. Among IGHV-mutated PTLDs, a mutational profile suggesting antigen stimulation and/or selection was observed in 4/6 D-s and in 2/4 R-PTLDs. The presence of ongoing IGHV mutations was detected in 2/4 D-PTLDs. Aberrant SHM was detected in 10/15 (66.7%) PTLDs, including 6/9 D-PTLDs and 4/6 R-PTLDs. Our findings suggest that (i) D-PTLDs show a clinical presentation distinct from R-PTLDs; (ii) immunophenotypic and genetic features of D-PTLDs are consistent with mature, GC-experienced B-cells; (iii) transformed donor-derived B-cells may experience antigen-driven stimulation and selection, and may acquire genetic lesions during neoplastic expansion in the recipient environment; and (iv) EBV infection and expression of viral oncoproteins may be relevant in the pathogenesis of D-PTLDs. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]- Published
- 2009
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32. Fludarabine-Based Combination Therapies for Waldenström's Macroglobulinemia.
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Tedeschi, Alessandra, Alamos, Sara Miqueleiz, Ricci, Francesca, Greco, Antonino, and Morra, Enrica
- Published
- 2009
33. Fludarabine in the treatment of chronic lymphocytic leukemia: a review.
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Ricci, Francesca, Tedeschi, Alessandra, Morra, Enrica, and Montillo, Marco
- Published
- 2009
34. Radiofrequency ablation of hepatic Hodgkin lymphoma.
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Rusconi, Chiara, Rampoldi, Antonio Gaetano, Ravelli, Erika, Nosari, Anna Maria, Zilioli, Vittorio Ruggero, Vanzulli, Angelo, and Morra, Enrica
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LETTERS to the editor ,RADIO frequency - Abstract
A letter to the editor is presented in response to the article about the study of Radio-frequency ablation (RFA) of a residual hepatic localization in the previous issue.
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- 2009
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35. Prospective monocentric study of non-tunnelled central venous catheter-related complications in hematological patients.
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Nosari, Anna Maria, Nador, Guido, Gasperi, Andrea De, Ortisi, Giuseppe, Volonterio, Alberto, Cantoni, Silvia, Nichelatti, Michele, Marbello, Laura, Mazza, Ernestina, Mancini, Valentina, Ravelli, Erica, Ricci, Francesca, Ciapanna, Denis, Garrone, Federica, Gesu, Giovanni, and Morra, Enrica
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CATHETERIZATION complications ,RESEARCH methodology evaluation ,EXPERIMENTAL design ,MYELOID leukemia ,THROMBOCYTOPENIA ,NEUTROPENIA - Abstract
Indwelling central venous catheters (CVCs) are used in the management of hematologic patients. However, insertion and maintenance of CVCs are susceptible to complications. Study design and methods data concerning 388 consecutive catheterisations, performed in oncohematologic patients between April 2003 and December 2004, were prospectively collected. At insertion thrombocytopenia was present in 109 cases (28.1%) and neutropenia in 67 (17.3%). Hemorrhage after CVC insertion occurred in five thrombocytopenic patients (1.3%). The median duration of catheterisation was 18.8 days (range 1-89), longer in the 7-French CVCs utilised in leukemic patients (24.3 days) and shorter in 12-French CVCs (11 days), used for PBSC harvesting. Deep venous thrombosis was diagnosed in 13 cases (3.3%). Ninety-two catheterisations (12.6/1000 days-catheter) were complicated by infections: 19 local infections (4.8%) and 73 (18.8%) bacteraemias of which 45 (11.6%) were catheter-related, mainly due to Gram positive germs (32/45, 71.1%). The frequency of catheter-related bacteraemia was 7.2 events/1000 days-catheter. Thirteen CVCs were removed due to thrombosis, 15 due to infections, 20 due to malfunction, the remaining 333 at patients discharge. At univariate analysis high-dose chemotherapy (p = 0.013), 7-Fr lumen (p = 0.023), acute myeloid leukemia (AML) (p = 0.001), duration of neutropenia >10 days and length of catheterisation were significantly correlated to infection. Multivariate analysis confirmed the duration of catheterisation, AML and high-dose chemotherapy as risk factors. Even though hematological in-patients are at increased risk for bleeding and infections, non-tunnelled CVCs offer a safe venous access also in patients affected by severe thrombocytopenia and prolonged neutropenia. [ABSTRACT FROM AUTHOR]
- Published
- 2008
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36. DCEP chemotherapy followed by a single, fixed dose of pegylated filgrastim allows adequate stem cell mobilization in multiple myeloma patients.
- Author
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Zappasodi, Patrizia, Nosari, Anna Maria, Astori, Cesare, Ciapanna, Dennis, Bonfichi, Maurizio, Varettoni, Marzia, Mangiacavalli, Silvia, Morra, Enrica, Lazzarino, Mario, and Corso, Alessandro
- Subjects
DRUG therapy ,ANTHROPOMETRY ,CELLS ,LEUCOCYTES ,CELL separation - Abstract
BACKGROUND: Pegylated filgrastim (PEG-f), a long-lasting granulocyte–colony-stimulating factor, has been used in different hematologic conditions to shorten chemotherapy-induced neutropenia and to mobilize peripheral blood stem cells. Data on mobilization efficacy in patients with multiple myeloma are, however, still limited. STUDY DESIGN AND METHODS: The feasibility and mobilizing capacity of DCEP chemotherapy followed by a single subcutaneous dose of 6 mg of PEG-f in 23 myeloma patients (11 females and 12 males) whose median age was 55 years (range, 31-67 years) were investigated. RESULTS: The median number of CD34+ cells collected was 5.72 × 10
6 per kg body weight with a range between 0 × 106 and 29.4 × 106 per kg body weight. Twenty patients (87%) yielded more than 2 × 106 per kg body weight CD34+ cells. Among the 22 patients who mobilized some CD34+ cells, 27 leukapheresis procedures were carried out (a single leukapheresis procedure in 17 patients and 2 leukapheresis procedures in 5). The median interval between the start of chemotherapy and the first leukapheresis procedure was 12 days (range, 11-16 days). With regard to tolerability, 7 patients complained of mild to moderate back pain, controlled with oral analgesics. No patient was hospitalized, and no fever or infections occurred. CONCLUSION: These results, compared with those previously reported for the DCEP-filgrastim combination, suggest that DCEP chemotherapy followed by PEG-f is a promising combination to mobilize peripheral blood stem cells in myeloma patients. [ABSTRACT FROM AUTHOR]- Published
- 2008
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37. Alemtuzumab in the treatment of fludarabine refractory B-cell chronic lymphocytic leukemia (CLL).
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Montillo, Marco, Ricci, Francesca, Miqueleiz, Sara, Tedeschi, Alessandra, and Morra, Enrica
- Published
- 2008
38. Limited Feasibility of Double Transplant in Multiple Myeloma.
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Corso, Alessandro, Mangiacavalli, Silvia, Barbarano, Luciana, Alessandrino, Emilio Paolo, Cairoli, Roberto, Morra, Enrica, and Lazzarino, Mario
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MEDICAL research ,TRANSPLANTATION of organs, tissues, etc. in children ,MULTIPLE myeloma ,TUMORS in children ,CHILDHOOD cancer - Abstract
The article discusses a study which aimed to evaluate the efficacy and the feasibility of a front-line double transplant program in young multiple myeloma patients. Study subjects were enrolled in a multicenter, nonrandomized, high-dose program including 2 transplants. The study concluded that single transplant programs is favored for the treatment of younger MM patients.
- Published
- 2007
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39. High-dose idarubicin in combination with Ara-C in patients with relapsed or refractory acute lymphoblastic leukemia: a pharmacokinetic and clinical study.
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Tedeschi, Alessandra, Montillo, Marco, Strocchi, Elena, Cafro, Anna, Tresoldi, Elisabetta, Intropido, Liliana, Nichelatti, Michele, Marbello, Laura, Baratè, Claudia, Camaggi, Carlo, and Morra, Enrica
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PHARMACOKINETICS ,INTRAVENOUS therapy ,LYMPHOBLASTIC leukemia ,CEREBROSPINAL fluid ,METABOLITES - Abstract
High dose (HD) Ara-C combined with a single HD idarubicin dose (IDA) is an efficient and safe salvage regimen for patients with refractory or relapsed acute lymphoblastic leukemia as indicated by phase II studies. No data are available on the pharmacokinetics of IDA after a rapid HD intravenous infusion. An open phase II pharmacokinetic and clinical study was performed to evaluate antileukemic efficacy, IDA pharmacokinetics and to investigate the presence of IDA and its reduced metabolite idarubicinol (IDAol) in cerebrospinal fluid (CSF) of patients treated with HD-IDA. Twenty-five patients with refractory or relapsed acute lymphoblastic leukemia received Ara-C 3 g/m
2 from days 1–5, idarubicin (HD-IDA) 40 mg/m2 as rapid intravenous (i.v.) infusion on day 3 and subcutaneous G-CSF 5 μg/kg from day 7 until PMN recovery. Pharmacokinetics of IDA was evaluated after HD idarubicin administration in nine of these patients. CSF samples were collected in 15 patients at different times. IDA and IDAol concentrations were quantified by a validated HPLC assay described in detail elsewhere. Eleven patients (44%, 95% CI: 23–65%) achieved complete remission with median disease free survival for 6 months. After administration of HD-IDA i.v. bolus of 40 mg/m2 , plasma level profiles of unchanged drug and IDAol were similar to those previously described after standard dose and measured with the same analytical method. The mean terminal half-life measured for IDA in this group of patients (14.9 h) was not significantly different from the mean value observed after standard dose (13.9 h, P = 0.72). IDAol t1/2 was also similar after HD-IDA (46.2 h) and standard dose (39.4 h, P = 0.79). Pharmacokinetic data reveal that in our series of patients IDA and IDAol clearances are significantly higher than those observed in patients treated with 12 mg/m2 of IDA but, although the administered dose (mg/m2 ) of the drug is 3.3 times higher, IDA exposure (measured in terms of AUC) is only 2.3 times and IDAol exposition 2.1 times greater. Furthermore, HD infusion resulted in a ratio between the AUC of parent drug and idarubicinol not different from the value observed with the standard-dose. IDA and IDAol were measurable only in 3 of the 15 cerebrospinal fluid samples collected. Responses observed in our series are comparable to those reported with other salvage regimens. The IDA exposure lower than expected may explain the safety of the single i.v. administration of 40 mg/m2 of IDA, combined with HD Ara-C, with a degree of myelosuppression equivalent to that reported with this agent administered in standard doses. Our data do not allow us to clearly attribute this behavior to a pharmacokinetic non-linearity since the baseline creatinine clearance, even within normal values, and patient age are significantly different in the two groups. Cerebrospinal fluid penetration was poor, reaching levels not considered as cytotoxic. [ABSTRACT FROM AUTHOR]- Published
- 2007
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40. Primary nodal marginal zone B-cell lymphoma: clinical features and prognostic assessment of a rare disease.
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Arcaini, Luca, Paulli, Marco, Burcheri, Sara, Rossi, Andrea, Spina, Michele, Passamonti, Francesco, Lucioni, Marco, Motta, Teresio, Canzonieri, Vincenzo, Montanari, Mauro, Bonoldi, Emanuela, Gallamini, Andrea, Uziel, Lilj, Crugnola, Monica, Ramponi, Antonio, Montanari, Francesca, Pascutto, Cristiana, Morra, Enrica, and Lazzarino, Mario
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LYMPHOMAS ,B cell lymphoma ,HEPATITIS C virus ,PROGNOSIS ,DIAGNOSTIC microbiology - Abstract
This study defined the clinical features and assessed the prognosis of 47 patients (17 males, 30 females, median age 63 years) with primary nodal marginal zone B-cell lymphoma. Forty-five per cent had stage IV disease. Hepatitis C virus serology was positive in 24%. According to the Follicular Lymphoma International Prognostic Index (FLIPI), 33% were classified as low-risk, 34% as intermediate-risk, and 33% as high-risk. The 5-year overall survival (OS) was 69%. In univariate analysis worse OS was associated with: FLIPI ( P = 0·02), age > 60 years ( P = 0·05) and raised lactate dehydrogenase ( P = 0·05). In multivariate analysis, only FLIPI predicted a worse OS ( P = 0·02). [ABSTRACT FROM AUTHOR]
- Published
- 2007
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41. Analysis of immunoglobulin heavy and light chain variable genes in post-transplant lymphoproliferative disorders.
- Author
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Capello, Daniela, Cerri, Michaela, Muti, Giuliana, Lucioni, Marco, Oreste, Pierluigi, Gloghini, Annunziata, Berra, Eva, Deambrogi, Clara, Franceschetti, Silvia, Rossi, Davide, Alabiso, Oscar, Morra, Enrica, Rambaldi, Alessandro, Carbone, Antonino, Paulli, Marco, and Gaidano, Gianluca
- Abstract
Post-transplant lymphoproliferative disorders (PTLD) derive from antigen-experienced B-cells and represent a major complication of solid organ transplantation. We characterized usage, mutation frequency and mutation pattern of immunoglobulin variable (IGV) gene rearrangements in 50 PTLD (polymorphic PTLD, n=10; diffuse large B-cell lymphoma, n=35; and Burkitt/Burkitt-like lymphoma, n=5). Among PTLD yielding clonal IGV amplimers, a functional IGV heavy chain (IGHV) rearrangement was found in 40/50 (80.0%) cases, whereas a potentially functional IGV light chain rearrangement was identified in 36/46 (78.3%) PTLD. By combining IGHV and IGV light chain rearrangements, 10/50 (20.0%) PTLD carried crippling mutations, precluding expression of a functional B-cell receptor (BCR). Immunohistochemistry showed detectable expression of IG light chains in only 18/43 (41.9%) PTLD. Failure to detect a functional IGV rearrangement associated with lack of IGV expression. Our data suggest that a large fraction of PTLD arise from germinal centre (GC)-experienced B-cells that display impaired BCR. Since a functional BCR is required for normal B-cell survival during GC transit, PTLD development may implicate rescue from apoptosis and expansion of B-cells that have failed the GC reaction. The high frequency of IGV loci inactivation appears to be a peculiar feature of PTLD among immunodeficiency-associated lymphoproliferations. Copyright © 2006 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]
- Published
- 2006
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42. Update on Recommendations for Assessing Response from the Third International Workshop on Waldenström's Macroglobulinemia.
- Author
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Kimby, Eva, Treon, Steven P., Anagnostopoulos, Athanasios, Dimopoulos, Meletios, Garcia-Sanz, Ramon, Gertz, Morie A., Johnson, Stephen, LeBlond, Veronique, Fermand, Jean-Paul, Maloney, David G., Merlini, Giampaolo, Morel, Pierre, Morra, Enrica, Nichols, Gwen, Ocio, Enrique M., Owen, Roger, Stone, Marvin, and Bladé, Joan
- Published
- 2006
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43. Aberrant somatic hypermutation in post-transplant lymphoproliferative disorders.
- Author
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Cerri, Michaela, Capello, Daniela, Muti, Giuliana, Rambaldi, Alessandro, Paulli, Marco, Gloghini, Annunziata, Berra, Eva, Deambrogi, Clara, Rossi, Davide, Franceschetti, Silvia, Conconi, Annarita, Morra, Enrica, Pasqualucci, Laura, Carbone, Antonino, and Gaidano, Gianluca
- Subjects
LYMPHOPROLIFERATIVE disorders ,GENETIC mutation ,B cell lymphoma ,BURKITT'S lymphoma ,IMMUNOGLOBULINS ,GENES ,AIDS - Abstract
The article focuses on somatic hypermutation (SHM) in post-transplant lymphoproliferative disorders (PTLD). Monoclonal PTLD include polymorphic PTLD, diffuse large B-cell lymphoma (DLBCL) and Burkitt/Burkitt-like lymphoma. Most PTLD originate from germinal centre experienced B cells that have undergone the physiological SHM process targeting immunoglobulin variable genes. Aberrant SHM is a pathogenetic mechanism implicated in DLBCL of immunocompetent hosts and acquired immuno-deficiency syndrome related lymphomas that target the 5' region, including coding sequences, of multiple proto-oncogenes relevant to lymphomagenesis.
- Published
- 2004
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44. research paper Incidence of novel N-glycosylation sites in the B-cell receptor of lymphomas associated with immunodeficiency.
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Forconi, Francesco, Capello, Daniela, Berra, Eva, Rossi, Davide, Gloghini, Annunziata, Cerri, Michaela, Muti, Giuliana, Morra, Enrica, Paulli, Marco, Magrini, Umberto, Lucioni, Marco, Rambaldi, Alessandro, Lauria, Francesco, Carbone, Antonio, Stevenson, Freda K., and Gaidano, Gianluca
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GLYCOSYLATION ,B cells ,LYMPHOMAS ,IMMUNODEFICIENCY ,ANTIBODY diversity ,HEMATOLOGY - Abstract
Novel N-glycosylation sites are introduced by somatic mutation into the V genes of the majority of follicular lymphomas. Sites are positively selected and rare in normal memory B cells, indicating a potential role in tumour survival in the germinal centre (GC). The incidence of c. 40% in diffuse large B-cell lymphomas (DLBCL) parallels the known heterogenity of the disease. Immunodeficiency-related non-Hodgkin's lymphomas (NHL) include post-transplant lymphoproliferative disorders (PTLD) and acquired immunodeficiency syndrome-related NHL (AIDS-NHL). Most PTLD derive from B cells that carry mutated V
H genes and that have completed the GC reaction. All AIDS-NHL carry mutated VH genes and variable features of GC or post-GC cells. To determine if N-glycosylation is a feature of immunodeficiency-related lymphomas, we analysed the VH genes of 19 PTLD and 36 AIDS-NHL. Novel sites were rare in PTLD (4/19), similar to memory B cells ( P = 0·15). AIDS-NHL, including DLBCL and Burkitt's lymphomas (BL), showed heterogeneity with 16 of 36 (44%) having novel sites. The findings indicate no selection of N-glycosylation sites in PTLD, consistent with post-GC features. The variable incidence of N-glycosylation sites in AIDS-NHL mirrors that in DLBCL and sporadic BL of immunocompetent hosts, supporting the known heterogeneity of these disorders, and possibly pointing to distinct routes of tumour development. [ABSTRACT FROM AUTHOR]- Published
- 2004
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45. Short Report Frequent aberrant promoter hypermethylation of O6-methylguanine-DNA methyltransferase and death-associated protein kinase genes in immunodeficiency-related lymphomas.
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Rossi, Davide, Gaidano, Gianluca, Gloghini, Annunziata, Deambrogi, Clara, Franceschetti, Silvia, Berra, Eva, Cerri, Michaela, Vendramin, Chiara, Conconi, Annarita, Viglio, Alessandra, Muti, Giuliana, Oreste, Pierluigi, Morra, Enrica, Paulli, Marco, Capello, Daniela, and Carbone, Antonino
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HEMATOLOGY ,BLOOD diseases - Abstract
Aberrant promoter hypermethylation is a mechanism of tumour suppressor gene inactivation. We explored aberrant promoter hypermethylation of multiple genes in 88 human immunodeficiency virus (HIV)-non Hodgkin lymphomas (NHL), 25 post-transplant lymphoproliferative disorders (PTLD) and five common variable immunodeficiency (CVI)-related NHL. Twenty-six of 79 (32·9%) HIV-NHL, eight of 14 (57·1%) PTLD and two of five (40·0%) CVI–NHL showed aberrant hypermethylation of O
6 -methylguanine-DNA methyltransferase ( MGMT). Aberrant hypermethylation of death-associated protein-kinase ( DAP-K) occurred in 70 of 84 (83·3%) HIV–NHL, 19 of 25 (72·0%) PTLD and three of five (60·0%) CVI–NHL. These data implicate MGMT and DAP-K hypermethylation in lymphomagenesis of immunodeficient hosts. In particular, promoter hypermethylation of DAP-K represents the most frequent molecular alteration yet identified in immunodeficiency-related lymphomas. [ABSTRACT FROM AUTHOR]- Published
- 2003
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46. Epstein–Barr virus (EBV) load and interleukin-10 in EBV-positive and EBV-negative post-transplant lymphoproliferative disorders.
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Muti, Giuliana, Klersy, Catherine, Baldanti, Fausto, Granata, Simonetta, Oreste, Pierluigi, Pezzetti, Laura, Gatti, Marta, Gargantini, Livio, Carmela, Marianna, Mancini, Valentina, Gerna, Giuseppe, and Morra, Enrica
- Subjects
LYMPHOPROLIFERATIVE disorders ,EPSTEIN-Barr virus ,INTERLEUKIN-10 ,DIAGNOSIS - Abstract
Summary. Post-transplant lymphoproliferative disorders (PTLDs) are heterogeneous severe complications occurring in 1–10% of transplanted patients. In most cases, PTLDs are associated with Epstein–Barr virus (EBV) infection but, recently, some clinical studies have reported an increasing number of EBV-negative PTLDs. Several studies have emphasized the critical role of the early identification of patients at risk for PTLD, in prompting the adoption of either pre-emptive strategies or timely treatment. To this purpose, monitoring of EBV DNA load in peripheral blood mononuclear cells is considered to be a useful test. Moreover, recently, the role of interleukin (IL)-10 in EBV-related diseases has been remarked, and high levels of IL-10 have been detected in PTLD patients. In this study, both EBV load and IL-10 were monitored in 38 PTLD patients at diagnosis and during follow-up, as well as in a control group, in order to establish the diagnostic role of the two tests, their relationship with the different PTLD subsets (EBV-positive and EBV-negative) and their behaviour during treatment. Results of our study suggest that the usefulness of IL-10 assay for early diagnosis of PTLD is similar to that of EBV load quantification, and its clinical diagnostic value is lower in EBV-negative than in EBV-positive PTLDs. [ABSTRACT FROM AUTHOR]
- Published
- 2003
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47. E2A–PBX1 fusion in adult acute lymphoblastic leukaemia: biological and clinical features.
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Foa, Robin, Vitale, Antonella, Mancini, Marco, Cuneo, Antonio, Mecucci, Cristina, Elia, Loredana, Lombardo, Romina, Saglio, Giuseppe, Torelli, Giuseppe, Annino, Luciana, Specchia, Giorgina, Damasio, Eugenio, Recchia, Anna, Di Raimondo, Francesco, Morra, Enrica, Volpe, Ettore, Tafuri, Agostino, Fazi, Paola, Hunger, Stephen P., and Mandelli, Franco
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LYMPHOBLASTIC leukemia ,HEMATOLOGY - Abstract
Summary. Molecular and cytogenetic studies performed in 305 adult acute lymphoblastic leukaemia (ALL) patients enrolled in the gimema (Gruppo Italiano Malattie EMatologiche dell'Adulto) multicentric protocols identified an E2A–PBX1 fusion and/or t(1;19) in 10 patients (3·3%). All had common ALL, were mostly CyIg
+ and were CD34/CD13/CD33– . Nine patients achieved a complete remission (CR); five patients showed a haematological relapse after 7 months (median). Four patients are alive in first CR with a median follow-up of 29 months; three patients are molecularly negative. This abnormality is frequently associated with early treatment failure. E2A–PBX1+ adult ALL should be considered for intensified treatment strategies and monitoring of minimal residual disease. [ABSTRACT FROM AUTHOR]- Published
- 2003
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48. Phase II study of cladribine and cyclophosphamide in patients with chronic lymphocytic leukemia and prolymphocytic leukemia.
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Montillo, Marco, Tedeschi, Alessandra, O'Brien, Susan, Raimondo, Francesco Di, Lerner, Susan, Ferrajoli, Alessandra, Morra, Enrica, and Keating, Michael J.
- Published
- 2003
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49. Invasive aspergillosis in haematological malignancies: Clinical findings and management for intensive chemotherapy completion.
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Nosari, Annamaria, Oreste, Pierluigi, Cairoli, Roberto, Montillo, Marco, Carrafiello, Gianpaolo, Astolfi, Alberto, Muti, Giuliana, Marbello, Laura, Tedeschi, Alessandra, Magliano, Enrico, and Morra, Enrica
- Published
- 2001
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50. Rituximab (IDEC-C2B8): Validation of a Sensitive Enzyme-Linked Immunoassay Applied to a Clinical Pharmacokinetic Study.
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Iacona, Isabella, Lazzarino, Mario, Avanzini, Maria Antonietta, Rupolo, Maurizio, Arcaini, Luca, Astori, Cesare, Lunghi, Francesca, Orlandi, Ester, Morra, Enrica, Zagonel, Vittorina, and Regazzi, Mario B.
- Published
- 2000
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