263 results on '"Tura A"'
Search Results
2. Gene expression profiling of normal and malignant CD34-derived megakaryocytic cells
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Tenedini, Elena, Fagioli, Maria Elena, Vianelli, Nicola, Tazzari, Pier Luigi, Ricci, Francesca, Tagliafico, Enrico, Ricci, Paolo, Gugliotta, Luigi, Martinelli, Giovanni, Tura, Sante, Baccarani, Michele, Ferrari, Sergio, and Catani, Lucia
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- 2004
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3. Cyclin D1 overexpression is a favorable prognostic variable for newly diagnosed multiple myeloma patients treated with high-dose chemotherapy and single or double autologous transplantation
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Soverini, Simona, Cavo, Michele, Cellini, Claudia, Terragna, Carolina, Zamagni, Elena, Ruggeri, Deborah, Testoni, Nicoletta, Tosi, Patrizia, de Vivo, Antonio, Amabile, Marilina, Grafone, Tiziana, Ottaviani, Emanuela, Giannini, Barbara, Cangini, Delia, Bonifazi, Francesca, Neri, Antonino, Fabris, Sonia, Tura, Sante, Baccarani, Michele, and Martinelli, Giovanni
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- 2003
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4. Multidimensional Geriatric Assessment for Elderly Patients (≥60 years) Submitted for Allogeneic Stem Cell Transplantation. a French (Paris) - Italian (Brescia) 10-Years Experience on 228 Patients
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Polverelli, Nicola, primary, Tura, Paolo, primary, Battipaglia, Giorgia, primary, Lisa, Gandolfi, primary, Zollner, Tatiana, primary, Malagola, Michele, primary, Morello, Enrico, primary, Turra, Alessandro, primary, Bernardi, Simona, primary, Zanaglio, Camilla, primary, Re, Federica, primary, Mohty, Mohamad, primary, and Russo, Domenico, primary
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- 2019
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5. A phase 2 study of imatinib in patients with relapsed or refractory Philadelphia chromosome–positive acute lymphoid leukemias
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Ottmann, Oliver G., Druker, Brian J., Sawyers, Charles L., Goldman, John M., Reiffers, Jose, Silver, Richard T., Tura, Sante, Fischer, Thomas, Deininger, Michael W., Schiffer, Charles A., Baccarani, Michele, Gratwohl, Alois, Hochhaus, Andreas, Hoelzer, Dieter, Fernandes-Reese, Sofia, Gathmann, Insa, Capdeville, Renaud, and O'Brien, Stephen G.
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- 2002
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6. Dendritic cells are functionally defective in multiple myeloma: the role of interleukin-6
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Ratta, Marina, Fagnoni, Francesco, Curti, Antonio, Vescovini, Rosanna, Sansoni, Paolo, Oliviero, Barbara, Fogli, Miriam, Ferri, Elisa, Della Cuna, Gioacchino Robustelli, Tura, Sante, Baccarani, Michele, and Lemoli, Roberto M.
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- 2002
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7. Imatinib induces hematologic and cytogenetic responses in patients with chronic myelogenous leukemia in myeloid blast crisis: results of a phase II study: Presented in part at the 43rd Annual Meeting of The American Society of Hematology, Orlando, FL, December 11, 2001.
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Sawyers, Charles L., Hochhaus, Andreas, Feldman, Eric, Goldman, John M., Miller, Carole B., Ottmann, Oliver G., Schiffer, Charles A., Talpaz, Moshe, Guilhot, Francois, Deininger, Michael W.N., Fischer, Thomas, O'Brien, Steve G., Stone, Richard M., Gambacorti-Passerini, Carlo B., Russell, Nigel H., Reiffers, Jose J., Shea, Thomas C., Chapuis, Bernard, Coutre, Steven, Tura, Sante, Morra, Enrica, Larson, Richard A., Saven, Alan, Peschel, Christian, Gratwohl, Alois, Mandelli, Franco, Ben-Am, Monique, Gathmann, Insa, Capdeville, Renaud, Paquette, Ronald L., and Druker, Brian J.
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- 2002
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8. Imatinib induces durable hematologic and cytogenetic responses in patients with accelerated phase chronic myeloid leukemia: results of a phase 2 study
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Talpaz, Moshe, Silver, Richard T., Druker, Brian J., Goldman, John M., Gambacorti-Passerini, Carlo, Guilhot, Francois, Schiffer, Charles A., Fischer, Thomas, Deininger, Michael W.N., Lennard, Anne L., Hochhaus, Andreas, Ottmann, Oliver G., Gratwohl, Alois, Baccarani, Michele, Stone, Richard, Tura, Sante, Mahon, Francois-Xavier, Fernandes-Reese, Sofia, Gathmann, Insa, Capdeville, Renaud, Kantarjian, Hagop M., and Sawyers, Charles L.
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- 2002
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9. A randomized study of interferon-α versus interferon-α and low-dose arabinosyl cytosine in chronic myeloid leukemia
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Baccarani, Michele, Rosti, Gianantonio, de Vivo, Antonio, Bonifazi, Francesca, Russo, Domenico, Martinelli, Giovanni, Testoni, Nicoletta, Amabile, Marilina, Fiacchini, Mauro, Montefusco, Enrico, Saglio, Giuseppe, and Tura, Sante
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- 2002
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10. Monitoring of minimal residual disease after CHOP and rituximab in previously untreated patients with follicular lymphoma
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Rambaldi, Alessandro, Lazzari, Manuela, Manzoni, Cristina, Carlotti, Emanuela, Arcaini, Luca, Baccarani, Michele, Barbui, Tiziano, Bernasconi, Carlo, Dastoli, Giuseppe, Fuga, Giovanna, Gamba, Enrica, Gargantini, Livio, Gattei, Valter, Lauria, Francesco, Lazzarino, Mario, Mandelli, Franco, Morra, Enrica, Pulsoni, Alessandro, Ribersani, Michela, Rossi-Ferrini, Pier Luigi, Rupolo, Maurizio, Tura, Sante, Zagonel, Vittorina, Zaja, Francesco, Zinzani, PierLuigi, Reato, Gigliola, and Foa, Robin
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- 2002
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11. Real-time quantitation of minimal residual disease in inv(16)-positive acute myeloid leukemia may indicate risk for clinical relapse and may identify patients in a curable state
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Buonamici, Silvia, Ottaviani, Emanuela, Testoni, Nicoletta, Montefusco, Vittorio, Visani, Giuseppe, Bonifazi, Francesca, Amabile, Marilina, Terragna, Carolina, Ruggeri, Deborah, Piccaluga, Pier Paolo, Isidori, Alessandro, Malagola, Michele, Baccarani, Michele, Tura, Sante, and Martinelli, Giovanni
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- 2002
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12. Chronic myeloid leukemia and interferon-α: a study of complete cytogenetic responders
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Bonifazi, Francesca, de Vivo, Antonio, Rosti, Gianantonio, Guilhot, François, Guilhot, Joëlle, Trabacchi, Elena, Hehlmann, Rüdiger, Hochhaus, Andreas, Shepherd, Patricia C.A., Steegmann, Juan Luis, Kluin-Nelemans, Hanneke C., Thaler, Josef, Simonsson, Bengt, Louwagie, Andries, Reiffers, Josy, Mahon, François Xavier, Montefusco, Enrico, Alimena, Giuliana, Hasford, Joerg, Richards, Sue, Saglio, Giuseppe, Testoni, Nicoletta, Martinelli, Giovanni, Tura, Sante, Baccarani, Michele, and for the European Study Group on Interferon in Chronic Myeloid Leukemia
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- 2001
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13. Interleukin-11 induces Th2 polarization of human CD4+ T cells
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Curti, Antonio, Ratta, Marina, Corinti, Silvia, Girolomoni, Giampiero, Ricci, Francesca, Tazzari, Pierluigi, Siena, Michela, Grande, Alexis, Fogli, Miriam, Tura, Sante, and Lemoli, Roberto M.
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- 2001
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14. Molecular monitoring of minimal residual disease in patients in long-term complete remission after allogeneic stem cell transplantation for multiple myeloma
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Cavo, Michele, Terragna, Carolina, Martinelli, Giovanni, Ronconi, Sonia, Zamagni, Elena, Tosi, Patrizia, Lemoli, Roberto M., Benni, Monica, Pagliani, Giorgio, Bandini, Giuseppe, and Tura, Sante
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- 2000
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15. Gene expression profiling of normal and malignant CD34-derived megakaryocytic cells
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Sergio Ferrari, Maria Elena Fagioli, Pier Luigi Tazzari, Giovanni Martinelli, Francesca Ricci, Sante Tura, Elena Tenedini, Michele Baccarani, Luigi Gugliotta, Paolo Ricci, Enrico Tagliafico, Lucia Catani, Nicola Vianelli, TENEDINI E, FAGIOLI ME, VIANELLI N, TAZZARI PL, RICCI F, TAGLIAFICO E, RICCI P, GUGLIOTTA L, MARTINELLI G, TURA S, BACCARANI M., FERRARI S, and CATANI L.
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Adult ,Male ,Hematopoiesis leukemia gene expression profiling megakaryocytic cells ,Immunology ,Antigens, CD34 ,Apoptosis ,Biology ,Biochemistry ,CFLAR ,Megakaryocyte ,Gene expression ,ESSENTIAL THROMBOCYTHEMIA ,medicine ,Humans ,Cell Lineage ,Cells, Cultured ,Thrombopoietin ,Aged ,Megakaryocytopoiesis ,urogenital system ,Gene Expression Profiling ,Cell Biology ,Hematology ,Middle Aged ,Cell biology ,Gene expression profiling ,medicine.anatomical_structure ,Female ,Stem cell ,Megakaryocytes ,Thrombocythemia, Essential - Abstract
Gene expression profiles of bone marrow (BM) CD34-derived megakaryocytic cells (MKs) were compared in patients with essential thrombocythemia (ET) and healthy subjects using oligonucleotide microarray analysis to identify differentially expressed genes and disease-specific transcripts. We found that proapoptotic genes such as BAX, BNIP3, and BNIP3L were down-regulated in ET MKs together with genes that are components of the mitochondrial permeability transition pore complex, a system with a pivotal role in apoptosis. Conversely, antiapoptotic genes such as IGF1-R and CFLAR were up-regulated in the malignant cells, as was the SDF1 gene, which favors cell survival. On the basis of the array results, we characterized apoptosis of normal and ET MKs by time-course evaluation of annexin-V and sub-G1 peak DNA stainings of immature and mature MKs after culture in serum-free medium with an optimal thrombopoietin concentration, and annexin-V–positive MKs only, with decreasing thrombopoietin concentrations. ET MKs were more resistant to apoptosis than their normal counterparts. We conclude that imbalance between proliferation and apoptosis seems to be an important step in malignant ET megakaryocytopoiesis.
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- 2004
16. Rapid Induction of CD40 on a Subset of Granulocyte Colony-Stimulating Factor–Mobilized CD34+ Blood Cells Identifies Myeloid Committed Progenitors and Permits Selection of Nonimmunogenic CD40− Progenitor Cells
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Rondelli, Damiano, Lemoli, Roberto M., Ratta, Marina, Fogli, Miriam, Re, Francesca, Curti, Antonio, Arpinati, Mario, and Tura, Sante
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- 1999
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17. Treatment and Clinical Management of Primary Mediastinal Large B-Cell Lymphoma With Sclerosis: MACOP-B Regimen and Mediastinal Radiotherapy Monitored by 67Gallium Scan in 50 Patients
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Zinzani, Pier Luigi, Martelli, Maurizio, Magagnoli, Massimo, Pescarmona, Edoardo, Scaramucci, Laura, Palombi, Francesca, Bendandi, Maurizio, Martelli, Maria Paola, Ascani, Stefano, Orcioni, Giulio Fraternali, Pileri, Stefano A., Mandelli, Franco, and Tura, Sante
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- 1999
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18. An Evidence-Based Analysis of the Effect of Busulfan, Hydroxyurea, Interferon, and Allogeneic Bone Marrow Transplantation in Treating the Chronic Phase of Chronic Myeloid Leukemia: Developed for the American Society of Hematology: Presented in part at the Education Session of the American Society of Hematology, December 5, 1998, Miami Beach, FL.
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Silver, Richard T., Woolf, Steven H., Hehlmann, Rüdiger, Appelbaum, Frederick R., Anderson, James, Bennett, Charles, Goldman, John M., Guilhot, Francois, Kantarjian, Hagop M., Lichtin, Alan E., Talpaz, Moshe, and Tura, Sante
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- 1999
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19. Elderly Aggressive-Histology Non-Hodgkin's Lymphoma: First-Line VNCOP-B Regimen Experience on 350 Patients
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Zinzani, Pier Luigi, Storti, Sergio, Zaccaria, Alfonso, Moretti, Luciano, Magagnoli, Massimo, Pavone, Enzo, Gentilini, Patrizia, Guardigni, Luciano, Gobbi, Marco, Fattori, Pier Paolo, Falini, Brunangelo, Lauta, Vito Michele, Bendandi, Maurizio, Gherlinzoni, Filippo, De Renzo, Amalia, Zaja, Francesco, Mazza, Patrizio, Volpe, Ettore, Bocchia, Monica, Aitini, Enrico, Tabanelli, Maurizio, Leone, Giuseppe, and Tura, Sante
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- 1999
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20. Cyclin D1 overexpression is a favorable prognostic variable for newly diagnosed multiple myeloma patients treated with high-dose chemotherapy and single or double autologous transplantation
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Marilina Amabile, Carolina Terragna, Antonio De Vivo, Tiziana Grafone, Michele Cavo, Barbara Giannini, Delia Cangini, Sante Tura, Sonia Fabris, Nicoletta Testoni, Antonino Neri, Michele Baccarani, Patrizia Tosi, Emanuela Ottaviani, Claudia Cellini, Simona Soverini, Giovanni Martinelli, Deborah Ruggeri, Elena Zamagni, and Francesca Bonifazi
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Adult ,Male ,medicine.medical_specialty ,Pathology ,medicine.medical_treatment ,Immunology ,Gene Expression ,Sensitivity and Specificity ,Biochemistry ,Gastroenterology ,Dexamethasone ,Disease-Free Survival ,Cyclin D1 ,Predictive Value of Tests ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Autologous transplantation ,Antineoplastic Agents, Alkylating ,Cyclophosphamide ,Melphalan ,Multiple myeloma ,Chromosome Aberrations ,Chemotherapy ,Chromosomes, Human, Pair 13 ,medicine.diagnostic_test ,Reverse Transcriptase Polymerase Chain Reaction ,business.industry ,Chromosomes, Human, Pair 11 ,Hematopoietic Stem Cell Transplantation ,Reproducibility of Results ,Cell Biology ,Hematology ,Middle Aged ,Prognosis ,medicine.disease ,Combined Modality Therapy ,Chemotherapy regimen ,medicine.anatomical_structure ,Doxorubicin ,Vincristine ,Female ,Bone marrow ,Multiple Myeloma ,Trisomy ,business ,Fluorescence in situ hybridization - Abstract
We used a sensitive real-time reverse transcription–polymerase chain reaction assay to quantify cyclin D1 mRNA levels in bone marrow samples collected at diagnosis from 74 newly diagnosed multiple myeloma (MM) patients who were randomized to undergo either single or double autologous peripheral blood stem cell transplantation as part of first-line therapy for their malignancy. In 46 cases, fluorescence in situ hybridization (FISH) analysis and/or conventional cytogenetics were performed to detect chromosome 11 abnormalities. Patients with the t(11;14) or trisomy 11 significantly overexpressed cyclin D1 (P < .0001) in comparison with patients without 11q abnormalities, who had cyclin D1 mRNA levels similar to healthy donors. Overall, 32 (43%) of 74 patients showed cyclin D1 overexpression. No difference was found between cyclin D1–positive (group A) and cyclin D1–negative (group B) patients with respect to presenting clinical and laboratory characteristics, including chromosome 13 abnormalities, as well as to response to therapy and overall survival, both of which were calculated on an intent-to-treat basis. Patients who overexpressed cyclin D1 had significantly longer duration of remission in comparison with patients who did not (41 vs 26 months, respectively; P = .02). As a result, median event-free survival (EFS) was longer in group A than in group B (33 vs 24 months, respectively; P = .055). We concluded that cyclin D1 overexpression is closely associated with 11q abnormalities and identifies a subset of MM patients who are more likely to have prolonged duration of remission and EFS following autologous transplantation.
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- 2003
21. Imatinib induces hematologic and cytogenetic responses in patients with chronic myelogenous leukemia in myeloid blast crisis: results of a phase II study
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Thomas C. Shea, Jose J. Reiffers, Richard Stone, Steven Coutre, Sante Tura, John M. Goldman, Franco Mandelli, Charles L. Sawyers, François Guilhot, Carole B. Miller, Michael W. Deininger, Insa Gathmann, Monique Ben-Am, Moshe Talpaz, Alan Saven, Andreas Hochhaus, Nigel H. Russell, Christian Peschel, Eric J. Feldman, Charles A. Schiffer, Alois Gratwohl, Enrica Morra, Carlo Gambacorti-Passerini, Renaud Capdeville, Thomas M. Fischer, Brian J. Druker, Richard A. Larson, S. O'Brien, Bernard Chapuis, Oliver G. Ottmann, and Ronald Paquette
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Adult ,Male ,Oncology ,medicine.medical_specialty ,Myeloid ,Immunology ,Fusion Proteins, bcr-abl ,Antineoplastic Agents ,Philadelphia chromosome ,Biochemistry ,Chronic phase chronic myelogenous leukemia ,Piperazines ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,Enzyme Inhibitors ,neoplasms ,Aged ,Cytopenia ,business.industry ,Imatinib ,Cell Biology ,Hematology ,Middle Aged ,Prognosis ,medicine.disease ,Blood Cell Count ,Survival Rate ,Kinetics ,Pyrimidines ,Treatment Outcome ,medicine.anatomical_structure ,Imatinib mesylate ,Benzamides ,Cytogenetic Analysis ,Imatinib Mesylate ,Female ,Blast Crisis ,business ,Tyrosine kinase ,Chronic myelogenous leukemia ,medicine.drug - Abstract
Blast crisis is the most advanced stage of chronic myelogenous leukemia (CML) and is highly refractory to therapy. CML is caused by expression of the chimeric BCR-ABL tyrosine kinase oncogene, the product of the t(9;22) Philadelphia translocation. Imatinib (Glivec, formerly STI571) is a rationally developed, orally administered inhibitor of the Bcr-Abl tyrosine kinase. A total of 260 patients with CML were enrolled in a phase II trial, of whom 229 had a confirmed diagnosis of CML in blast crisis. Patients were treated with imatinib in daily oral doses of 400 mg or 600 mg. Imatinib induced hematologic responses in 52% of patients and sustained hematologic responses lasting at least 4 weeks in 31% of patients, including complete hematologic responses in 8%. For patients with a sustained response, the estimated median response duration was 10 months. Imatinib induced major cytogenetic responses in 16% of patients, with 7% of the responses being complete. Median survival time was 6.9 months. Nonhematologic adverse reactions were frequent but generally mild or moderate. Episodes of severe cytopenia were also frequent and were attributable to the underlying condition and treatment with imatinib. Drug-related adverse events led to discontinuation of therapy in 5% of patients, most often because of cytopenia, skin disorders, or gastrointestinal reactions. These results demonstrate that imatinib has substantial activity and a favorable safety profile when used as a single agent in patients with CML in blast crisis. Additional clinical studies are warranted to explore the efficacy and feasibility of imatinib used in combination with other antileukemic drugs.
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- 2002
22. Imatinib induces durable hematologic and cytogenetic responses in patients with accelerated phase chronic myeloid leukemia: results of a phase 2 study
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Moshe Talpaz, Andreas Hochhaus, Anne L. Lennard, Richard T. Silver, Thomas M. Fischer, Sofia Fernandes-Reese, Insa Gathmann, Charles L. Sawyers, Michael W. Deininger, Hagop M. Kantarjian, Richard Stone, Charles A. Schiffer, John M. Goldman, François Xavier Mahon, Oliver G. Ottmann, S Tura, Francois Guilhot, Renaud Capdeville, Brian J. Druker, Michele Baccarani, A Gratwohl, and Carlo Gambacorti-Passerini
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Adult ,Male ,medicine.medical_specialty ,Immunology ,Leukemia, Myeloid, Accelerated Phase ,Biochemistry ,Gastroenterology ,Chronic phase chronic myelogenous leukemia ,Disease-Free Survival ,Piperazines ,Bone Marrow ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,Survival rate ,Aged ,Aged, 80 and over ,Blood Cells ,Dose-Response Relationship, Drug ,business.industry ,Imatinib ,Cell Biology ,Hematology ,Middle Aged ,Protein-Tyrosine Kinases ,Prognosis ,medicine.disease ,Hematologic Response ,Survival Rate ,Pyrimidines ,Treatment Outcome ,Imatinib mesylate ,Benzamides ,Cytogenetic Analysis ,Toxicity ,Imatinib Mesylate ,Female ,business ,Progressive disease ,Chronic myelogenous leukemia ,medicine.drug - Abstract
Chronic myelogenous leukemia (CML) is caused by expression of the BCR-ABL tyrosine kinase oncogene, the product of the t(9;22) Philadelphia translocation. Patients with CML in accelerated phase have rapidly progressive disease and are characteristically unresponsive to existing therapies. Imatinib (formerly STI571) is a rationally developed, orally administered inhibitor of the Bcr-Abl kinase. A total of 235 CML patients were enrolled in this study, of whom 181 had a confirmed diagnosis of accelerated phase. Patients were treated with imatinib at 400 or 600 mg/d and were evaluated for hematologic and cytogenetic response, time to progression, survival, and toxicity. Imatinib induced hematologic response in 82% of patients and sustained hematologic responses lasting at least 4 weeks in 69% (complete in 34%). The rate of major cytogenetic response was 24% (complete in 17%). Estimated 12-month progression-free and overall survival rates were 59% and 74%, respectively. Nonhematologic toxicity was usually mild or moderate, and hematologic toxicity was manageable. In comparison to 400 mg, imatinib doses of 600 mg/d led to more cytogenetic responses (28% compared to 16%), longer duration of response (79% compared to 57% at 12 months), time to disease progression (67% compared to 44% at 12 months), and overall survival (78% compared to 65% at 12 months), with no clinically relevant increase in toxicity. Orally administered imatinib is an effective and well-tolerated treatment for patients with CML in accelerated phase. A daily dose of 600 mg is more effective than 400 mg, with similar toxicity.
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- 2002
23. Interleukin-11 induces Th2 polarization of human CD4+ T cells
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Antonio Curti, Sante Tura, Silvia Corinti, Francesca Ricci, Miriam Fogli, M Siena, Giampiero Girolomoni, Marina Ratta, Alexis Grande, Pierluigi Tazzari, and Roberto M. Lemoli
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CD4-Positive T-Lymphocytes ,Cells ,medicine.medical_treatment ,Immunology ,Antigen presentation ,Biology ,Biochemistry ,Interleukin 21 ,Th2 Cells ,Adjuvants, Immunologic ,Immunologic ,medicine ,Humans ,Cytotoxic T cell ,Adjuvants ,IL-2 receptor ,Cells, Cultured ,Cultured ,Monocyte ,CD28 ,Cell Differentiation ,Cell Biology ,Hematology ,Dendritic cell ,Interleukin-11 ,Cell biology ,Cytokine ,medicine.anatomical_structure - Abstract
Exploration of the immunomodulatory activities of the multifunctional cytokine interleukin-11 (IL-11) has prompted several therapeutic applications. The immunomodulatory effects of IL-11 on human antigen-presenting cells and on T cells were investigated. IL-11 inhibited IL-12 production by activated CD14+ monocytes, but not by mature dendritic cells (DCs) stimulated via CD40 ligation. Moreover, IL-11 did not affect either DC maturation, as demonstrated by phenotypic analysis and evaluation of cytokine production, or DC generation from progenitor cells in the presence of specific growth factors. Molecular analysis demonstrated the expression of IL-11 receptor messenger RNA in highly purified CD14+ monocytes, CD19+ B cells, CD8+, and CD4+T cells, and CD4+CD45RA+ naive T lymphocytes. In keeping with this finding, IL-11 directly prevented Th1 polarization of highly purified CD4+CD45RA+naive T cells stimulated with anti-CD3/CD28 antibodies, as demonstrated by significant increases of IL-4 and IL-5, by significantly decreased interferon-γ production and by flow cytometry intracellular staining of cytokines. Coincubation of naive T cells with DCs, the most potent stimulators of Th1 differentiation, did not revert IL-11–mediated Th2 polarization. Furthermore, parallel experiments demonstrated that the activity of IL-11 was comparable with that induced by IL-4, the most effective Th2-polarizing cytokine. Taken together, these findings show that IL-11 inhibits Th1 polarization by exerting a direct effect on human T lymphocytes and by reducing IL-12 production by macrophages. Conversely, IL-11 does not exert any activity on DCs. This suggests that IL-11 could have therapeutic potential for diseases where Th1 responses play a dominant pathogenic role.
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- 2001
24. Use of Lenalidomide in DEL(5q) MDS. a National AIFA (Agenzia Italiana del Farmaco) Registry Study
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Arcioni, Francesco, primary, Roncadori, Andrea, additional, Di Battista, Valeria, additional, Alimena, Giuliana, additional, Pane, Fabrizio, additional, Rossi, Giuseppe, additional, Buccisano, Francesco, additional, D'Emilio, Anna, additional, Di Renzo, Nicola, additional, Leoni, Pietro, additional, Caocci, Giovanni, additional, Rambaldi, Alessandro, additional, Avanzini, Paolo, additional, Visani, Giuseppe, additional, Tura, Sante, additional, Covezzoli, Anna, additional, and Mecucci, Cristina, additional
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- 2015
- Full Text
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25. Cycling Status of CD34+ Cells Mobilized Into Peripheral Blood of Healthy Donors by Recombinant Human Granulocyte Colony-Stimulating Factor
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Agostino Tafuri, Roberto M. Lemoli, Alessandra Fortuna, Lucia Catani, Maria Rosaria Ricciardi, Maria Teresa Petrucci, Damiano Rondelli, Sante Tura, Giuliana Leopardi, Miriam Fogli, and Cristina Ariola
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Immunology ,CD34 ,Stem cell factor ,Cell Biology ,Hematology ,Biology ,Biochemistry ,Transplantation ,Andrology ,Haematopoiesis ,Granulocyte macrophage colony-stimulating factor ,medicine.anatomical_structure ,medicine ,Bone marrow ,Progenitor cell ,Stem cell ,medicine.drug - Abstract
In this study, we assessed the functional and kinetic characteristics of highly purified hematopoietic CD34+ cells from the apheresis products of 16 normal donors undergoing glycosylated granulocyte colony-stimulating factor (G-CSF ) treatment for peripheral blood stem cells (PBSC) mobilization and transplantation in allogeneic recipients. Mobilized CD34+ cells were evaluated for their colony-forming capacity and trilineage proliferative response to selected recombinant human (rh) CSF in vitro and the content of very primitive long-term culture initiating cells (LTC-IC). In addition, the cycling status of circulating CD34+ cells, including committed clonogenic progenitor cells and the more immature LTC-IC, was determined by the cytosine arabinoside (Ara-C) suicide test and the acridine orange flow cytometric technique. By comparison, bone marrow (BM) CD34+ cells from the same individuals were studied under steady-state conditions and during G-CSF administration. Clonogenic assays in methylcellulose showed the same frequency of colony-forming unit cells (CFU-C) when PB-primed CD34+ cells and BM cells were stimulated with phytohemagglutinin–lymphocyte-conditioned medium (PHA-LCM). However, mobilized CD34+ cells were significantly more responsive than their steady-state BM counterparts to interleukin-3 (IL-3) and stem cell factor (SCF ) combined with G-CSF or IL-3 in presence of erythropoietin (Epo). In cultures added with SCF, IL-3, and Epo, we found a mean increase of 1.5- ± 1-fold (standard error of the mean [SEM]) of PB CFU–granulocyte-macrophage and erythroid progenitors (burst-forming units-erythroid) as compared with BM CD34+ cells (P < .05). Conversely, circulating and BM megakaryocyte precursors (CFU-megakaryocyte) showed the same clonogenic efficiency in response to IL-3, granulocyte-macrophage–CSF and IL-3, IL-6, and Epo. After 5 weeks of liquid culture supported by the engineered murine stromal cell line M2-10B4 to produce G-CSF and IL-3, we reported 48.2 ± 35 (SEM) and 62.5 ± 54 (SEM) LTC-IC per 104 CD34+ cells in PB and steady-state BM, respectively (P = not significant). The Ara-C suicide assay showed that 4% ± 5% (standard deviation [SD]) of committed precursors and 1% ± 3% (SEM) of LTC-IC in PB are in S-phase as compared with 25.5% ± 12% (SD) and 21% ± 8% (SEM) of baseline BM, respectively (P < .001). However, longer incubation with Ara-C (16 to 18 hours), in the presence of SCF, IL-3 and G-CSF, or IL-6, showed that more than 60% of LTC-IC are actually cycling, with no difference being found with BM cells. Furthermore, studies of cell-cycle distribution on PB and BM CD34+ cells confirmed the low number of circulating progenitor cells in S- and G2M-phase, whereas simultaneous DNA/RNA analysis showed that the majority of PB CD34+ cells are not quiescent (ie, in G0-phase), being in G1-phase with a significant difference with baseline and G-CSF–treated BM (80% ± 5% [SEM] v 61.9% ± 6% [SEM] and 48% ± 4% [SEM], respectively; P < .05). Moreover, G-CSF administration prevented apoptosis in a small but significant proportion of mobilized CD34+ cells. Thus, our results indicate that mobilized and BM CD34+ cells can be considered equivalent for the frequency of both committed and more immature hematopoietic progenitor cells, although they show different kinetic and functional profiles. In contrast with previous reports, we found that PB CD34+ cells, including very primitive LTC-IC, are cycling and ready to progress into S-phase under CSF stimulation. This finding should be taken into account for a better understanding of PBSC transplantation.
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- 1997
26. 3′-Azido 3′-Deoxythymidine + Methotrexate as a Novel Antineoplastic Combination in the Treatment of Human Immunodeficiency Virus-Related Non-Hodgkin's Lymphomas
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Francesco Gritti, Sante Tura, Filippo Gherlinzoni, P. Costigliola, Giuseppe Visani, E. Raise, Patrizio Mazza, Magda Mazzetti, O. Coronado, Patrizia Tosi, and Francesco Chiodo
- Subjects
Adult ,Male ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Immunology ,Neutropenia ,Biochemistry ,Gastroenterology ,chemistry.chemical_compound ,Zidovudine ,immune system diseases ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Medicine ,Aged ,Lymphoma, AIDS-Related ,Chemotherapy ,business.industry ,Lymphoma, Non-Hodgkin ,Cell Biology ,Hematology ,Middle Aged ,medicine.disease ,Lymphoma ,Regimen ,Methotrexate ,chemistry ,Antifolate ,Female ,business ,Diffuse large B-cell lymphoma ,medicine.drug - Abstract
We have previously reported that 3′-azido 3′-deoxythymidine (AZT) can possess a significant antineoplastic activity when combined with drugs that disrupt de novo thymidylate synthesis, such as 5-fluorouracil and methotrexate (MTX). The aim of the present study was to evaluate the efficacy and the tolerance of the combination AZT + MTX in human immunodeficiency virus (HIV)-related non-Hodgkin's lymphoma (NHL). Twenty-nine patients (22 men and 7 women), either newly diagnosed or pretreated, have been enrolled in the trial; the median age was 34 years, 45% had acquired immunodeficiency syndrome before lymphoma and 19 patients had less than 100 CD4 lymphocytes/μL. Histologic diagnoses were mainly Burkitt (27%) and diffuse large B-cell lymphoma (45%); extranodal involvement was present in 20 patients. The treatment plan included three weekly courses of MTX at 1 g/m2 (days 1, 8, and 15) plus oral AZT at 2 g/m2 (days 1, 2, and 3), 4 g/m2 (days 8, 9, and 10), and 6 g/m2 (days 15, 16, and 17), plus leucovorin rescue. From the eleventh patient on, in case of complete or partial remission, the treatment was continued with three additional courses, using AZT at the maximum dose. In 26 evaluable patients, the total (complete + partial) response rate was 77% (95% confidence interval, 58% to 89%), with complete remission (CR) in 46% of the patients (95% confidence interval, 29% to 65%). The median CR duration was 12.8 months. Grade III-IV neutropenia and anemia were observed in 52% and 31% of the courses, respectively. There was one therapy-related death due to bacteremia followed by septic shock; the only other recorded infection was a herpes vaginalis. In conclusion, we suggest that AZT + MTX is an effective and well-tolerated regimen in HIV-related NHL.
- Published
- 1997
27. Interferon-alpha and hydroxyurea in early chronic myeloid leukemia: a comparative analysis of the Italian and German chronic myeloid leukemia trials with interferon-alpha [letter]
- Author
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Ruediger Hehlmann, Jörg Hasford, Michele Baccarani, Tura S, Eliana Zuffa, and H Anseri
- Subjects
medicine.medical_specialty ,Pediatrics ,Intention-to-treat analysis ,business.industry ,Immunology ,Myeloid leukemia ,Alpha interferon ,Cell Biology ,Hematology ,Biochemistry ,language.human_language ,German ,Internal medicine ,language ,medicine ,Conventional chemotherapy ,business ,Busulfan ,Survival analysis ,Median survival ,medicine.drug - Abstract
In 1994, the Italian and the German Chronic myeloid leukemia (CML) trials comparing interferon-alpha (IFN-alpha) with conventional chemotherapy were published. The survival advantage in favor of IFN- alpha compared with hydroxyurea (HU; 72 v 52 months) was significant in the Italian (P < .002), but not in the German trial (66 v 56 months, P < .44). We set up a collaborative study to identify the reasons for the different outcomes. There are major differences in the trial protocols concerning admission criteria, treatment strategy, and definitions. The German patients were older and more seriously sick. Fifty-two of the 327 patients in the German IFN and HU arms did not fulfil Italian admission criteria, and 41 of the 322 Italian patients did not fulfil German admission criteria. Using mutually uniform admission criteria, the median survival times of the IFN patients are 76 (Italian) and 72 (German) months (P = .56). The Italian group administered IFN combined with HU as needed, whereas the German group strictly used IFN as monotherapy with rerandomization to busulfan (BU) or HU after IFN resistance or intolerability. The differences seen between the Italian and the German trial results can be accounted for by objective differences in study design, especially the admission criteria, treatment strategy, and bias due to intention to treat analysis. The detailed analysis of the data suggests that the combination of IFN with HU as needed is more effective than either agent alone.
- Published
- 1996
28. A new method of 'in-cell reverse transcriptase-polymerase chain reaction' for the detection of BCR/ABL transcript in chronic myeloid leukemia patients
- Author
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Nicoletta Testoni, P. Farabegoli, Giovanni Martinelli, Donatella Raspadori, Sante Tura, S. Pelliconi, Eliana Zuffa, Cristina Carboni, Marilina Amabile, and Alfonso Zaccaria
- Subjects
Neoplasm, Residual ,Proto-Oncogene Proteins c-bcr ,Molecular Sequence Data ,Immunology ,Biology ,Philadelphia chromosome ,Polymerase Chain Reaction ,Sensitivity and Specificity ,Biochemistry ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,Proto-Oncogene Proteins ,hemic and lymphatic diseases ,Complementary DNA ,Gene expression ,medicine ,Humans ,RNA, Messenger ,Proto-Oncogene Proteins c-abl ,Oncogene Proteins ,ABL ,Base Sequence ,breakpoint cluster region ,Cell Biology ,Hematology ,Protein-Tyrosine Kinases ,medicine.disease ,Minimal residual disease ,Molecular biology ,Reverse transcriptase ,Cancer research - Abstract
Methods of detecting minimal residual disease (MRD) in chronic myeloid leukemia (CML) include chromosome analysis, Southern blotting, polymerase chain reaction (PCR) and fluorescent in situ hybridization (FISH) techniques. We report a novel method to detect intracellular messenger RNA (mRNA) by combining the techniques of reverse transcription (RT) and PCR performed directly inside the cells, without extraction of the nucleic acid. We applied this method, which we call “in-cell RT-PCR”, to detect hybrid BCR/ABL transcript within single cells. After cellular permeabilization and fixation of single cells in suspension, the neoplastic mRNA was reverse transcribed into cDNA, and the cDNA was amplified by PCR with fluorescent primers, specific for bcr/abl. Flow cytometry was used to detect cells positive for the amplified DNA within the cell cytoplasm. After transferring the amplified cells onto slides by cytospin, the positive cells for BCR/ABL cDNA were observed by fluorescent microscopy. The technique was capable of detecting low abundancy signals and distinguishing different levels of gene expression. The amplification products were found in the cells and supernatants. The distribution was critically affected by the protease digestion condition. The specificity of amplification was confirmed by a nested RT-PCR of BCR/ABL performed on extracted mRNA from the same sample, and by reamplification of supernatants. We have used the technique to study 10 Ph+ CML patients and three normal subjects as controls. Four patients were 100% Ph+ at diagnosis time and RT-PCR+ at cytogenetic and molecular analysis, respectively. In-cell RT- PCR showed that the residual non-neoplastic cells could be observed in all cases. In two patients undergoing interferon-alpha (IFN-alpha) therapy and in four bone-marrow transplanted patients, the in-cell RT- PCR was used to compare the level of Ph+ positivity detected by cytogenetic analysis with the number of cells expressing BCR/ABL transcript. In this manner, we could estimate the MRD. Our preliminary application of the technique suggests that it is capable of accurately identifying cells transcribing bcr/abl, and that it may have significant clinical applications in the detection of MRD.
- Published
- 1996
29. Monitoring of minimal residual disease after CHOP and rituximab in previously untreated patients with follicular lymphoma
- Author
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Francesco Lauria, Francesco Zaja, Enrica Morra, Michela Ribersani, Vittorina Zagonel, Cristina Manzoni, Giuseppe Dastoli, Maurizio Rupolo, Emanuela Carlotti, Livio Gargantini, Pier Luigi Rossi-Ferrini, Tiziano Barbui, Sante Tura, Franco Mandelli, Pier Luigi Zinzani, Mario Lazzarino, Alessandro Pulsoni, Valter Gattei, Enrica Gamba, Carlo Bernasconi, Gigliola Reato, M. Baccarani, Alessandro Rambaldi, Manuela Lazzari, Luca Arcaini, Giovanna Fuga, Robin Foà, Rambaldi, A, Lazzari, M, Manzoni, C, Carlotti, E, Arcaini, L, Baccarani, M, Barbui, T, Bernasconi, C, Dastoli, G, Fuga, G, Gamba, E, Gargantini, L, Gattei, V, Lauria, F, Lazzarino, M, Mandelli, F, Morra, E, Pulsoni, A, Ribersani, M, Rossi Ferrini, Pl, Rupolo, M, Tura, S, Zagonel, V, Zaja, Francesco, Zinzani, P, Reato, G, and Foa, R.
- Subjects
Adult ,Male ,medicine.medical_specialty ,Neoplasm, Residual ,medicine.medical_treatment ,Immunology ,Follicular lymphoma ,CHOP ,Biochemistry ,Gastroenterology ,Polymerase Chain Reaction ,Antibodies, Monoclonal, Murine-Derived ,Bone Marrow ,hemic and lymphatic diseases ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Cyclophosphamide ,Lymphoma, Follicular ,Survival analysis ,Aged ,Chemotherapy ,Blood Cells ,Genes, Immunoglobulin ,business.industry ,Antibodies, Monoclonal ,Cell Biology ,Hematology ,Middle Aged ,medicine.disease ,Prognosis ,Minimal residual disease ,Survival Analysis ,Surgery ,Lymphoma ,Genes, bcl-2 ,medicine.anatomical_structure ,Doxorubicin ,Vincristine ,Prednisone ,Rituximab ,Female ,Bone marrow ,business ,medicine.drug - Abstract
Minimal residual disease (MRD) following sequential administration of CHOP and rituximab was studied in previously untreated patients with follicular lymphoma. At diagnosis, the presence of Bcl-2/IgH-positive cells in the peripheral blood (PB) and/or bone marrow (BM) was demonstrated in all patients (n = 128) by polymerase chain reaction (PCR) analysis. Patients who achieved a clinical response following CHOP but remained PCR-positive were eligible for rituximab (375 mg/m2 intravenously, weekly for 4 weeks). After CHOP, 57% achieved a complete response (CR), 37% a partial response (PR), and 6% were nonresponders (NR). At this stage, patients proving PCR-negative (n = 41) or failing to achieve a clinical response (n = 8) were excluded from rituximab treatment. Seventy-seven patients received rituximab and entered a scheduled MRD follow-up program. At the first molecular follow-up (+12 weeks), 59% had converted to PCR negativity in the BM and PB, with a further increase documented at the second control (+28 weeks) with 74% PCR negative. At the last molecular follow-up (+44 weeks), 63% of the patients remained PCR negative. At 3 years, the estimated overall survival of all patients is 95% (95% confidence interval [CI], 86-98). For patients achieving PCR-negative status following CHOP and therefore excluded from rituximab treatment, freedom from recurrence (FFR) was 52% (95% CI, 28-71). For patients treated with rituximab, a durable PCR-negative status was associated with a better clinical outcome since FFR was 57% (95% CI, 23-81) compared with 20% (95% CI, 4-46) in patients who never achieved or lost the molecular negativity ( P
- Published
- 2002
30. Alpha-interferon in the treatment of chronic myeloid leukemia. The Italian Cooperative Study Group on Chronic Myeloid Leukemia [letter; comment]
- Author
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M Baccarani and S Tura
- Subjects
Oncology ,medicine.medical_specialty ,business.industry ,Immunology ,Alpha interferon ,Myeloid leukemia ,Cell Biology ,Hematology ,Biochemistry ,Internal medicine ,medicine ,Prospective cohort study ,business ,Survival analysis - Published
- 1995
31. Use of Lenalidomide in DEL(5q) MDS. a National AIFA (Agenzia Italiana del Farmaco) Registry Study
- Author
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Giuliana Alimena, Nicola Di Renzo, Anna D'Emilio, Pietro Leoni, Andrea Roncadori, Francesco Arcioni, Paolo Avanzini, Alessandro Rambaldi, Francesco Buccisano, Giuseppe Visani, Fabrizio Pane, Giovanni Caocci, Giuseppe Rossi, Valeria Di Battista, Sante Tura, Cristina Mecucci, and Anna Covezzoli
- Subjects
Pediatrics ,medicine.medical_specialty ,business.industry ,Anemia ,Immunology ,Disease progression ,Context (language use) ,Retrospective cohort study ,Cell Biology ,Hematology ,Neutropenia ,medicine.disease ,Biochemistry ,Partial response ,Medicine ,business ,Prospective cohort study ,Lenalidomide ,medicine.drug - Abstract
In Italy the use of lenalidomide (LEN) in MDS with del(5q) is ruled by a national agency (AIFA, Agenzia Italiana del Farmaco) Registry since 2008. We conducted an observational, non-interventional, multi-centre, retrospective/prospective cohort study, registered as MORE (ClinicalTrials.gov NCT01347944), to investigate the use LEN in the context of a "real world setting". Registry eligibility: IPSS low or intermediate-1 risk MDS with transfusion-dependent anemia and 5q31 deletion. MORE integration: retrospective collection of clinical, hematological and cytogenetic data at pre-registry time, at enrollment, after 4-6 cycles and 8-12 cycles of LEN, and at the last available follow-up and/or end of treatment. Hematological and cytogenetic response was assessed according to Cheson et al (Blood 2006). Statistical analysis used PL / SQL Developer and R open source software. 190 patients (M:F 60: 130) were included in this study (Table 1). GROUP A, (149 patients, median age 75 years) with complete data sets, and GROUP B (41 patients, median age 71 years), investigated only by FISH were analyzed separately. By integration of Registry with MORE forms, including disease history and/or treatment preceding inclusion in the Registry, information was recruited over a median time of 44 months (range 0.5-237). The complete erythroid response rate was 74.6% in group A and 78.6% in group B after 4-6 cycles treatment, and 85.8% and 88.9%, respectively after 8-12 cycles. The partial response rate was 11.5% in group A and 10.7% in group B at 4-6 months cycles. The complete cytogenetic response rate (only group A ) after 4-6 cycles was 7.8%. The partial response rate was 2.3 %. After 8-12 cycles complete response increased to 13% , partial response to 9.6 %. Leukemic evolution was observed in 18 cases (9.5%). Disease progression to a higher risk MDS was found in 12 cases (6.3%). Neutropenia (grade 3-4; 59%) and thrombocytopenia (grade 3-4; 21%) were predominant in the first 6 months of treatment. Infections (21%) mostly affected the upper respiratory tract. As far as we know this is the first report on LEN administration within a national registry. Despite being a retrospective study solid information on real life management of del(5q)-MDS were obtained. The known efficacy on erythropoiesis was strongly confirmed (FIG.1A). Notably, we also found a good response in low/int-1 IPSS cases with non-isolated 5q- (70.6%), suggesting that IPSS score plays a role in the successful response. The low rate of cytogenetic response possibly reflected the high level of variations in timing and dosage of LEN as well as heterogeneity of analyses in a non-centralized study. Nevertheless, results after 8-12 cycles (22.6%; FIG.1B) were similar to the 25% found with 5mg LEN in the European cooperative MDS004 study (Fenaux P et al, Blood 2011). AML evolution was found in 18/190 cases (9.6%) after a median of 7.5 LEN cycles (range 1-30). Moreover twelve additional cases (6.3%) showed progression to RAEB1 or RAEB2 after a median of 19.5 LEN cycles (range 4-56). In the MDS004 study a similar analysis gave 25.4 % of leukemic evolution and 2.9% of disease progression. This large series of MDS with del(5q) allowed us to confirm the efficacy of LEN in a "real world setting". Biological and clinical features seem to be critical for the success of this personalized therapy. Table 1. Table 1. Figure 1. Clinical-hematological features of 190 cases (MORE Study). Figure 1. Clinical-hematological features of 190 cases (MORE Study). Disclosures Roncadori: Celgene: Research Funding. Rossi:Celgene: Research Funding. D'Emilio:Celgene: Research Funding. Di Renzo:Celgene: Research Funding. Leoni:Celgene: Research Funding. Rambaldi:Roche: Honoraria; Novartis: Honoraria; Amgen: Honoraria; Celgene: Research Funding; Pierre Fabre: Honoraria. Avanzini:Celgene: Research Funding. Visani:Celgene: Research Funding. Tura:Celgene: Research Funding. Covezzoli:Celgene: Research Funding. Mecucci:Celgene: Research Funding.
- Published
- 2015
32. A phase 2 study of imatinib in patients with relapsed or refractory Philadelphia chromosome-positive acute lymphoid leukemias
- Author
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Thomas Fischer, Michele Baccarani, S Tura, Charles A. Schiffer, Jose J. Reiffers, Dieter Hoelzer, Stephen G. O'Brien, Insa Gathmann, A Gratwohl, Michael W. Deininger, Brian J. Druker, Oliver G. Ottmann, Renaud Capdeville, John M. Goldman, Sofia Fernandes-Reese, Andreas Hochhaus, Richard T. Silver, and Charles L. Sawyers
- Subjects
Adult ,Male ,medicine.medical_specialty ,Immunology ,Salvage therapy ,Antineoplastic Agents ,Neutropenia ,Philadelphia chromosome ,Biochemistry ,Gastroenterology ,Piperazines ,hemic and lymphatic diseases ,Internal medicine ,Acute lymphocytic leukemia ,medicine ,Humans ,Aged ,Salvage Therapy ,Acute leukemia ,business.industry ,Remission Induction ,Imatinib ,Cell Biology ,Hematology ,Middle Aged ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,medicine.disease ,Survival Analysis ,Imatinib mesylate ,Pyrimidines ,Benzamides ,Imatinib Mesylate ,Female ,business ,Blast Crisis ,medicine.drug ,Chronic myelogenous leukemia ,Follow-Up Studies - Abstract
The translocation (9;22) gives rise to the p190(Bcr-Abl) and p210(Bcr-Abl) tyrosine kinase proteins, considered sufficient for leukemic transformation. Philadelphia-positive (Ph(+)) acute leukemia patients failing to respond to initial induction therapy have a poor prognosis with few effective treatment options. Imatinib is an orally administered, potent inhibitor of the Bcr-Abl tyrosine kinase. We conducted a clinical trial in 56 patients with relapsed or refractory Ph(+) acute lymphoblastic leukemia (ALL; 48 patients) or chronic myelogenous leukemia in lymphoid blast crisis (LyBC; 8 patients). Imatinib was given once daily at 400 mg or 600 mg. Imatinib induced complete hematologic responses (CHRs) and complete marrow responses (marrow-CRs) in 29% of ALL patients (CHR, 19%; marrow-CR, 10%), which were sustained for at least 4 weeks in 6% of patients. Median estimated time to progression and overall survival for ALL patients were 2.2 and 4.9 months, respectively. CHRs were reported for 3 (38%) of the patients with LyBC (one sustained CHR). Grade 3 or 4 treatment-related nonhematologic toxicity was reported for 9% of patients; none of the patients discontinued therapy because of nonhematologic adverse reactions. Grade 4 neutropenia and thrombocytopenia occurred in 54% and 27% of patients, respectively. Imatinib therapy resulted in a clinically relevant hematologic response rate in relapsed or refractory Ph(+) acute lymphoid leukemia patients, but development of resistance and subsequent disease progression were rapid. Further studies are warranted to test the effects of imatinib in combination with other agents and to define the mechanisms of resistance to imatinib.
- Published
- 2002
33. Real-time quantitation of minimal residual disease in inv(16)-positive acute myeloid leukemia may indicate risk for clinical relapse and may identify patients in a curable state
- Author
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Francesca Bonifazi, Silvia Buonamici, Michele Malagola, Carolina Terragna, Nicoletta Testoni, Alessandro Isidori, Emanuela Ottaviani, Giuseppe Visani, Sante Tura, Vittorio Montefusco, Deborah Ruggeri, Giovanni Martinelli, Pier Paolo Piccaluga, Michele Baccarani, and Marilina Amabile
- Subjects
Oncology ,Male ,Neoplasm, Residual ,Oncogene Proteins, Fusion ,medicine.medical_treatment ,Salvage therapy ,Biochemistry ,Antineoplastic Combined Chemotherapy Protocols ,Bone Marrow Transplantation ,medicine.diagnostic_test ,Reverse Transcriptase Polymerase Chain Reaction ,Remission Induction ,Myeloid leukemia ,Bone Marrow Examination ,Hematology ,Middle Aged ,Prognosis ,Combined Modality Therapy ,Leukemia ,Treatment Outcome ,Female ,Adult ,Risk ,medicine.medical_specialty ,Adolescent ,Immunology ,Genes, abl ,Sensitivity and Specificity ,Disease-Free Survival ,Leukemia, Myelomonocytic, Acute ,Computer Systems ,Internal medicine ,medicine ,Biomarkers, Tumor ,Humans ,Risk factor ,Survival analysis ,Aged ,Retrospective Studies ,Salvage Therapy ,Chemotherapy ,business.industry ,Cell Biology ,medicine.disease ,Minimal residual disease ,Survival Analysis ,Surgery ,Bone marrow examination ,Karyotyping ,Chromosome Inversion ,business ,Chromosomes, Human, Pair 16 ,Follow-Up Studies - Abstract
The inv(16) cytogenetic subtype of acute myeloid leukemia (AML) has a relatively good prognosis. Many patients achieve complete remission (CR). The prognostic uncertainty of negative qualitative reverse transcription–polymerase chain reaction (RT-PCR) assays suggests the need to identify prognostically significant critical thresholds by real-time RT-PCR. A reliable and sensitive (10−5) real-time RT-PCR assay was set up for the evaluation of relevant CBFβ-MYH11/ABL transcript ratios and was applied to the 21 patients with inv(16) AML routinely referred for cytogenetic and molecular monitoring in Seràgnoli Institute (Bologna, Italy) since 1990. Among the 18 patients who underwent ablative chemotherapy, all achieved CR with a 3-year disease-free survival probability of 63% (95% CI, 40%-87%) and no recorded events after 26 months. Five patients had relapses; 2 died of disease and 3 entered second CR. Analysis of the 125 bone marrow (or peripheral blood) samples studied by real-time RT-PCR showed that transcript ratios of samples taken during CR at any time before a relapse were always greater than 0.12%, whereas those of samples taken during first or second CR from patients who did not subsequently have relapses were always less than 0.25%. This suggests that transcript ratios greater than 0.25% may correspond to high risk for relapse, whereas ratios below 0.12% might indicate the patient is in a curable state. If confirmed, such thresholds could open the way to a new phase in post-CR therapeutic decision making for patients with inv(16) AML.
- Published
- 2002
34. The long term outcome of the patients with chronic myeloid leukemia (CML) who have achieved complete cytogenetic response (CCgR) to interferon-alpha (IFN alpha). A collaborative European study of 317 cases
- Author
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Bonifazi, F, De Vivo, A, Rosti, G, Guilhot, F, Guilhot, J, Trabacchi, E, Hehlmann, R, Hochhaus, A, Shepherd, P, Steegmann, JL, Kluin-Nelemans, HC, Thaler, J, Simonsson, B, Louwagie, A, Reiffers, J, Mahon, FX, Montefusco, E, Alimena, G, Hasford, J, Richards, S, Saglio, G, Testoni, N, Martinelli, G, Tura, S, Baccarani, M, and CML, ESGI
- Published
- 2001
35. Molecular monitoring of minimal residual disease in patients in long-term complete remission after allogeneic stem cell transplantation for multiple myeloma
- Author
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Patrizia Tosi, Carolina Terragna, Monica Benni, Roberto M. Lemoli, Michele Cavo, Sante Tura, Giuseppe Bandini, Elena Zamagni, Giorgio Pagliani, Sonia Ronconi, and Giovanni Martinelli
- Subjects
Adult ,Male ,medicine.medical_specialty ,Neoplasm, Residual ,medicine.medical_treatment ,Immunology ,Graft vs Host Disease ,Hematopoietic stem cell transplantation ,Biochemistry ,Gastroenterology ,Polymerase Chain Reaction ,Lymphocyte Depletion ,Nuclear Family ,Bone Marrow ,Internal medicine ,medicine ,Humans ,Transplantation, Homologous ,Survival rate ,Multiple myeloma ,Monitoring, Physiologic ,Beta-2 microglobulin ,business.industry ,Histocompatibility Testing ,Hematopoietic Stem Cell Transplantation ,Cell Biology ,Hematology ,Middle Aged ,medicine.disease ,Minimal residual disease ,Transplantation ,Survival Rate ,medicine.anatomical_structure ,Female ,Bone marrow ,Stem cell ,business ,Multiple Myeloma ,beta 2-Microglobulin ,Immunosuppressive Agents - Abstract
In the present study, we used a polymerase chain reaction–based (PCR-based) strategy to retrospectively analyze the presence of residual myeloma cells in serial posttransplant bone marrow samples obtained from 13 patients in remission after allogeneic hemopoietic stem cell transplantation (allo SCT). For this purpose, patient-specific primers were generated from complementarity determining regions 2 and 3 of the rearranged IgH gene. The level of sensitivity of the PCR-based assay ranged from 1 in 105 to 1 in 106 normal marrow cells. Following transplantation, 9 of 12 patients who attained stringently defined complete remission (CR) remained persistently PCR− for a median of 36 months, and 4 of the patients remained PCR− up to the latest analysis, which was performed at 48, 72, 72, and 120 months, respectively, after allo SCT. None of the patients in the PCR− subgroup experienced a disease relapse, and only 1 of 4 PCR+ patients experienced a relapse. It is concluded that allo SCT has the potential ability to induce sustained serological and molecular CR in selected patients with multiple myeloma.
- Published
- 2000
36. Treatment and clinical management of primary mediastinal large B-cell lymphoma with sclerosis: MACOP-B regimen and mediastinal radiotherapy monitored by (67)Gallium scan in 50 patients
- Author
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Sante Tura, Maurizio Martelli, Pier Luigi Zinzani, Massimo Magagnoli, Stefano Ascani, Maurizio Bendandi, Franco Mandelli, Maria Paola Martelli, Edoardo Pescarmona, Giulio Fraternali Orcioni, Laura Scaramucci, Stefano Pileri, and Francesca Palombi
- Subjects
Male ,medicine.medical_treatment ,Gallium ,Biochemistry ,Prednisone ,Antineoplastic Combined Chemotherapy Protocols ,Citrates ,Prospective Studies ,Stage (cooking) ,Hematology ,Middle Aged ,Combined Modality Therapy ,classification ,Vincristine ,Female ,medicine.drug ,Adult ,tumor ,Lymphoma, B-Cell ,Prednisolone ,Immunology ,HIGH-DOSE CHEMOTHERAPY ,NON-HODGKINS-LYMPHOMA ,THERAPY ,FEATURES ,DISEASE ,TUMOR ,GA-67 ,CLASSIFICATION ,Mediastinal Neoplasms ,Bleomycin ,medicine ,features ,Humans ,Survival rate ,Cyclophosphamide ,Tomography, Emission-Computed, Single-Photon ,Chemotherapy ,disease ,therapy ,Sclerosis ,business.industry ,Cell Biology ,medicine.disease ,ga-67 ,Survival Analysis ,high-dose chemotherapy ,non-hodgkins-lymphoma ,Radiation therapy ,Regimen ,Methotrexate ,Doxorubicin ,Primary mediastinal B-cell lymphoma ,business ,Nuclear medicine - Abstract
To evaluate the efficacy of a combined modality treatment (MACOP-B plus mediastinal radiotherapy) and the advantages of Gallium-67-citrate single-photon emission (67GaSPECT) over computed tomography (CT) for restaging in patients with primary mediastinal large B-cell lymphoma (PMLBCL) with sclerosis. Between 1989 and 1998, 50 previously untreated patients with PMLBCL with sclerosis (70% with bulky mass) were treated with MACOP-B regimen plus mediastinal radiotherapy. The radiologic clinical stage with evaluation of tumor size included CT and 67GaSPECT at diagnosis, after chemotherapy, and after radiotherapy. Forty-three patients (86%) achieved a complete response and 7 were nonresponders to treatment. For the imaging evaluation, only 47 patients were evaluable because 3 had disease progression during chemotherapy. After treatment, 3/5 (60%) patients with positive 67GaSPECT and negative CT scan relapsed, as against 0/21 (0%) with negative 67GaSPECT and CT scan. Twenty-one patients had a positive CT scan: of these, the 4 with positive 67GaSPECT all progressed, whereas there were no relapses among the 17 with negative 67GaSPECT. After radiotherapy, there was a decrease of positive CT (from 33 to 21 cases) and of positive 67GaSPECT (from 31 to 9 cases). Relapse-free survival rate was 93% at 96 months (median 39 months). In patients with PMLBCL with sclerosis, MACOP-B plus radiation therapy is a very useful first-line treatment and radiation therapy may play an important role. As regards restaging, 67GaSPECT should be considered the imaging technique of choice at least in patients who show CT positivity.
- Published
- 1999
37. An evidence-based analysis of the effect of busulfan, hydroxyurea, interferon, and allogeneic bone marrow transplantation in treating the chronic phase of chronic myeloid leukemia: developed for the American Society of Hematology
- Author
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Rt, Silver, Sh, Woolf, Hehlmann R, Fr, Appelbaum, Anderson J, Bennett C, Jm, Goldman, François Guilhot, Hm, Kantarjian, Ae, Lichtin, Talpaz M, and Tura S
- Subjects
Evidence-Based Medicine ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Hydroxyurea ,Interferon-alpha ,Transplantation, Homologous ,Busulfan ,Combined Modality Therapy ,Bone Marrow Transplantation - Abstract
Because there are differing opinions regarding treatment of patients in the chronic phase of chronic myeloid leukemia (CML), the American Society of Hematology convened an expert panel to review and document evidence-based benefits and harms of treatment of CML with busulfan (BUS), hydroxyurea (HU), recombinant interferon-alpha (rIFN-alpha), and bone marrow transplantation (BMT). The primary measure for defining efficacy was survival. Analysis indicated a survival advantage for HU over BUS. Observational studies of rIFN-alpha suffer from numerous biases including sample size, variations in study populations, definitions of hematologic and cytogenetic remissions, and dose. That rIFN-alpha is more efficacious than chemotherapy is demonstrated by 6 prospective randomized trials. For patients with favorable clinical features in chronic phase, compared to HU and BUS, rIFN-alpha improves survival by a median of about 20 months. Most evidence suggests that rIFN-alpha is most effective when combined with other drugs and when given during the earliest stage of the chronic phase. Adding cytarabine to rIFN-alpha adds further survival benefit but increases toxicity. Limitations for evaluating the long-term benefits of allogeneic BMT include the retrospective nature of most studies, incomplete documentation of the clinical characteristics of the patients, paucity of the details on patient selection, lack of control groups, and limitations of survival calculations. Survival curves for BMT show that at least half of the patients transplanted remain alive 5 to 10 years after treatment, whereas similar curves for rIFN-alpha show a continuous relapse rate over time with the curves crossing at about 7 to 8 years. Estimates of long-term survival may be confounded by the selection biases mentioned and the analytic methods used. The magnitude of the incremental increase in benefit with BMT must be weighed against the potential serious harm and death that may accompany the procedure in the short term. The best results with BMT have been obtained when it is performed within 1 to 2 years from diagnosis. Since each treatment option involves tradeoffs between benefit and harm, patient choice must be based on the examination of facts presented in an unbiased fashion. Newly diagnosed younger patients and older patients who are candidates for BMT should also be offered information about IFN-based regimens, the tradeoffs involved, and, if possible, share in the treatment decision. Hopefully this analysis will provide the stimulus for evaluation of other important aspects of CML.
- Published
- 1999
38. Alternative BCR/ABL transcripts in chronic myeloid leukemia [letter; comment]
- Author
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Francesco Lauria, C. Rosso, Alfonso Zaccaria, Angelo Guerrasio, N Testoni, Algeri R, Angela Tassinari, G. Saglio, and Tura S
- Subjects
business.industry ,Immunology ,Cancer research ,Medicine ,Myeloid leukemia ,Cell Biology ,Hematology ,business ,Biochemistry - Published
- 1990
39. Randomized trial with or without granulocyte colony-stimulating factor as adjunct to induction VNCOP-B treatment of elderly high-grade non-Hodgkin's lymphoma
- Author
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P L, Zinzani, E, Pavone, S, Storti, L, Moretti, P P, Fattori, L, Guardigni, B, Falini, M, Gobbi, P, Gentilini, V M, Lauta, M, Bendandi, F, Gherlinzoni, M, Magagnoli, S, Venturi, E, Aitini, M, Tabanelli, G, Leone, V, Liso, and S, Tura
- Subjects
Lymphoma, Non-Hodgkin ,Age Factors ,Middle Aged ,Bleomycin ,Treatment Outcome ,Vincristine ,Antineoplastic Combined Chemotherapy Protocols ,Granulocyte Colony-Stimulating Factor ,Humans ,Prednisone ,Mitoxantrone ,Cyclophosphamide ,Aged ,Etoposide - Abstract
Age is an important prognostic parameter, especially in patients with advanced high-grade non-Hodgkin's lymphoma (HG-NHL) who require more intensive and extensive therapy for any possible chance of cure. We investigated the potential of granulocyte colony-stimulating factor (G-CSF) for reducing myelotoxicity, which is the most important dose-limiting factor for chemotherapy. Between March 1993 and June 1995, 158 previously untreated patients 60 years and older with HG-NHL were included in a cooperative randomized comparative trial and treated with a combination therapy including VNCOP-B (cyclophosphamide, mitoxantrone, vincristine, etoposide, bleomycin, and prednisone) with or without G-CSF. G-CSF was administered at 5 microg/kg/d throughout the treatment starting on day 3 of every week for 5 consecutive days. Of the 158 patients registered for the trial, 149 patients were evaluable: 77 received VNCOP-B plus G-CSF and 72 received VNCOP-B alone. The overall response rate was 81.5%, with complete response in 59%: 60% in the VNCOP-B plus G-CSF group, and 58% in the VNCOP-B group. At 30 months (median 24 months), 68% of all complete responders were alive without disease in the G-CSF group and 65% in the control group. Neutropenia occurred in 18 out of 77 (23%) of the G-CSF treated patients and in 40 out of 72 (55.5%) of the controls (P = .00005). Clinically relevant infections occurred in 4 out of 77 (5%) of the G-CSF group and in 15 out of 72 (21%) of the controls (P = .004). The delivered dose intensity was higher in patients receiving G-CSF (95% v 85%), but the difference was not statistically significant. Our data show that VNCOP-B is a feasible and effective regimen in elderly HG-NHL patients, and that the use of G-CSF reduces infection and neutropenia rates without producing any significant modifications to the dose intensity, CR rate, and relapse-free survival curve.
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- 1997
40. Interleukin-9 stimulates the proliferation of human myeloid leukemic cells
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Alessandra Fortuna, Miriam Fogli, Bagnara Gp, Marilina Amabile, Giuseppe Visani, Agostino Tafuri, Sante Tura, Giovanni Martinelli, Sergio Ferrari, Roberto M. Lemoli, Alexis Grande, Maria Rosaria Ricciardi, Maria Teresa Petrucci, and Laura Bonsi
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Adult ,Male ,medicine.medical_specialty ,acute myeloblastic-leukemia ,acute myelogenous leukemia ,cloning ,combination ,differentiation ,expression ,gm-csf ,growth-factor ,line ,marrow ,Adolescent ,Immunology ,Stem cell factor ,Biology ,Biochemistry ,Internal medicine ,medicine ,Tumor Cells, Cultured ,Humans ,Interleukin 9 ,Progenitor cell ,Clonogenic assay ,Interleukin 3 ,Aged ,Stem Cell Factor ,Cell growth ,Interleukin-9 ,Granulocyte-Macrophage Colony-Stimulating Factor ,Cell Biology ,Hematology ,Middle Aged ,Molecular biology ,Recombinant Proteins ,Haematopoiesis ,Leukemia, Myeloid, Acute ,Granulocyte macrophage colony-stimulating factor ,Endocrinology ,Female ,Cell Division ,medicine.drug - Abstract
Human interleukin-9 (IL-9) stimulates the proliferation of primitive hematopoietic erythroid and pluripotent progenitor cells, as well as the growth of selected colony-stimulating factor (CSF)-dependent myeloid cell lines. To further address the role of IL-9 in the development of acute leukemia, we evaluated the proliferative response of three leukemic cell lines and 32 primary samples from acute myeloblastic leukemia (AML) patients to recombinant human (rh)-IL-9 alone and combined with rh-IL-3, granulocyte-macrophage CSF (GM-CSF), and stem cell factor ([SCF] c-kit ligand). The colony-forming ability of HL60, K562, and KG1 cells and fresh AML cell populations upon IL-9 stimulation was assessed by a clonogenic assay in methylcellulose, whereas the cell-cycle characteristics of leukemic samples were determined by the acridine-orange flow cytometric technique and the bromodeoxyuridine (BRDU) incorporation assay. In addition, the terminal deoxynucleotidyl transferase assay (TDTA) and standard analysis of DNA cleavage by gel electrophoresis were used to evaluate induction of prevention of apoptosis by IL-9. Il-9, as a single cytokine, at various concentrations stimulated the colony formation of the three myeloid cell lines under serum-containing and serum-free conditions, and this effect was completely abrogated by anti-IL-9 monoclonal antibodies (MoAbs). When tested on fresh AML samples, optimal concentrations of IL- 9 resulted in an increase of blast colony formation in all the cases studied (mean +/- SEM: 19 +/- 10 colony-forming unit-leukemic [CFU- L]/10(5) cells plated in control cultures v 107 +/- 32 in IL-9- supplemented dishes, P < .02). IL-9 stimulated 36.8% of CFU-L induced by phytohemagglutinin-lymphocyte-conditioned medium (PHA-LCM), and it was the most effective CSF for promoting leukemic cell growth among those tested in this study (i.e., SCF, IL-3, and GM-CSF). The proliferative activity of IL-9 was also observed when T-cell-depleted AML specimens were incubated with increasing concentrations of the cytokine. Addition of SCF to IL-9 had an additive or synergistic effect of the two cytokines in five of eight AML cases tested for CFU-L growth (187 +/- 79 colonies v 107 +/- 32 CFU-L, P = .05). Positive interaction was also observed when IL-9 was combined with IL-3 and GM-CSF. Studies of cell-cycle distribution of AML samples demonstrated that IL-9 alone significantly augmented the number of leukemic cells in S-phase in the majority of cases evaluated. IL-9 and SCF in combination resulted in a remarkable decrease of the G0 cell fraction (38.2% +/- 24% v 58.6% +/- 22% of control cultures, P < .05) and induced an increase of G1- and S- phase cells. Conversely, neither IL-9 alone nor the combination of IL-9 and SCF had any effect on induction or prevention of apoptosis of leukemic cells. In summary, our results indicate that IL-9 may play a role in the development of AML by stimulating leukemic cells to enter the S-phase rather than preventing cell death. Moreover, IL-9 acts synergistically with SCF for recruiting quiescent leukemic cells in cell cycle.
- Published
- 1996
41. Lenalidomide Is Effective in Heavily Pretreated Non Hodgkin Lymphoma (NHL): Analysis of a Retrospective Data Collection
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Rigacci, Luigi, primary, Vitolo, Umberto, additional, Cox, M. Christina, additional, Devizzi, Liliana, additional, Fabbri, Alberto, additional, Zaccaria, Alfonso, additional, Zaja, Francesco, additional, Paesano, Paolo, additional, Rossi, Giuseppe, additional, Storti, Sergio, additional, Tura, Sante, additional, and Zinzani, Pier Luigi, additional
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- 2012
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42. Deferasirox Chelation Therapy in Transfusion Dependent MDS Patients. Final Report From the Gimema MDS0306 Prospective Trial
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Angelucci, Emanuele, primary, Santini, Valeria, additional, Tucci, Anna Angela Di, additional, Finelli, Carlo, additional, Cantore, Nicola, additional, Quarta, Giovanni, additional, D'Arco, Alfonso Maria, additional, Cascavilla, Nicola, additional, Saglio, Giuseppe, additional, Levis, Alessandro, additional, Pettinau, Martina, additional, Caocci, Giovanni, additional, Morra, Enrica, additional, Vallisa, Daniele, additional, Latte, Giancarlo, additional, Piciocchi, Alfonso, additional, Bontempi, Katia, additional, Vignetti, Marco, additional, and Tura, Sante, additional
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- 2012
- Full Text
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43. Lenalidomide in Myelodysplastic Syndromes with 5q Deletion. Results From the Italian National Cancer Registry
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Mecucci, Cristina, primary, Roncadori, Andrea, additional, La Starza, Roberta, additional, Arcioni, Francesco, additional, Levis, Alessandro, additional, Santini, Valeria, additional, Alimena, Giuliana, additional, Pane, Fabrizio, additional, Rossi, Giuseppe, additional, Cantonetti, Maria, additional, D'Emilio, Anna, additional, Di Renzo, Nicola, additional, Leoni, Pietro, additional, Caocci, Giovanni, additional, Rambaldi, Alessandro, additional, Avanzini, Paolo, additional, Visani, Giuseppe, additional, Tura, Sante, additional, and Covezzoli, Anna, additional
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- 2012
- Full Text
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44. Lenalidomide Administration in Heavily Pretreated Patients with Non Hodgkin Lymphoma – First Report of the REVEAL Study (REVlimid® Effectiveness of Administration in patients with Lymphoma)
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Rigacci, Luigi, primary, Zaja, Francesco, additional, Fabbri, Alberto, additional, Di Rocco, Alice, additional, Carella, Angelo Michele, additional, Devizzi, Liliana, additional, Vitolo, Umberto, additional, Zinzani, Pier Luigi, additional, and Tura, Sante, additional
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- 2011
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45. Deferasirox Chelation Therapy in Transfusion Dependent MDS Patients. Final Report From the Gimema MDS0306 Prospective Trial
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Katia Bontempi, Giancarlo Latte, Nicola Cascavilla, Giovanni Quarta, Giovanni Caocci, Anna Angela Di Tucci, Enrica Morra, Alfonso Maria D'Arco, Emanuele Angelucci, Alessandro Levis, Marco Vignetti, Sante Tura, Nicola Cantore, Valeria Santini, Giuseppe Saglio, Carlo Finelli, Alfonso Piciocchi, Daniele Vallisa, and Martina Pettinau
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Pediatrics ,medicine.medical_specialty ,Acute leukemia ,education.field_of_study ,Univariate analysis ,Blood transfusion ,business.industry ,medicine.medical_treatment ,Immunology ,Population ,Deferasirox ,Transfusion History ,Cell Biology ,Hematology ,Drug holiday ,Biochemistry ,medicine ,Adverse effect ,education ,business ,medicine.drug - Abstract
Abstract 425 Introduction. FDA and EMA have approved Deferasirox for iron chelation therapy for transfusion dependent MDS patients after a limited experience in selected MDS patients. Therefore we felt the need of a large, prospective, trial to verify Deferasirox safety, compliance, efficacy and effect on erythroid function in a large, “real world,” MDS population. Patients and Methods. One hundred fifty-two consecutive MDS IPSS lower risks (62 low and 90 intermediate1) transfusion dependent (minimum transfusion history 20 units received) patients were enrolled in 37 Italian centres. Patients received Deferasirox at the starting dose of 20 mg/kg. Characteristics of patients have been summarized by means of cross-tabulations for categorical variables and by means of median and range for continuous data. Adverse events (AEs) were defined according to CTCAE.3 (2003) definition. Disease progression was defined as advance to higher IPPS score group, development of acute leukemia or death. Efficacy of the treatment was measured by monitoring monthly serum ferritin levels. Transfusion independence was defined as three consecutive months without PRBC requirement with a minimum stable Hb level of 9 g/dl. The probability of drop out and transfusion independence were estimated using the appropriate non-parametric method, considering death and progression disease as a competing risk. Differences in univariate analysis were evaluated by Gray test. Fine and Gray model was used to evaluated prognostic factors in multivariate analysis. FriedmanÕs test was performed to evaluate differences in serum ferritin levels, hemoglobin level and transfusions input over time. Results. Ninety-six males and 56 females were enrolled. Median age was 72 years (66–77). Median interval diagnosis-enrolment was 32 months (17–54). Patients have been receiving regular blood transfusions for a median of 21 months (10–36) with a median number of units received of 37 (22–63). At baseline median CIRS co-morbidity score was 0 (0–1), CIRS severity score 0 (0–1), and Charlson co-morbidity score 0(0–1). Eighty-four patients (55%) prematurely interrupted the study while 68 (45%) completed the planned year of treatment. Risk of drop out was 18.8% and 28% at 6 and 12 months, respectively. Risk of disease progression or death was 12.7% and 25% at 6 and 12 months, respectively. In multivariate analyses significant risk factors for treatment interruption were shorter diagnosis-enrolment interval (P=0.0008), lower Deferasirox dose (p=0.008) and higher serum ferritin level (P=0.004). During the study 304 AEs were reported in 107 distinct patients. Of these events 93 (66 patients = 43%) were defined as possible-probably-certain drug related. Of these 93 related events fourteen in 11 distinct patients (7%) were superior to grade 2. Features of AEs were similar to those already reported. Serum ferritin significantly decreased during the study from a median starting value of 1966 ng/ml (1416–2998) to a median final value of 1475 ng/ml (915–2010), (P Conclusion. Less than 50% of the enrolled population was able to complete the planned year of treatment because of drop out (risk 28%) and progression (risk 25%) despite a limited number of >2 grade AEs. Noteworthy >69% of the AEs was not drug related indicating a basic vulnerability of this population. Deferasirox was effective in reducing serum ferritin levels. Clinical benefit was also related to erythroid improvement that was clinically significant reducing transfusion need in a relevant percentage of patients. ClinicalTrials.gov Identifier: NCT00469560 Disclosures: Angelucci: Novartis : Chair of Steering Committee of the Telesto trial Other. Vallisa:CELGENE CORPORATION: Research Funding.
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- 2012
46. Lenalidomide in Myelodysplastic Syndromes with 5q Deletion. Results From the Italian National Cancer Registry
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Sante Tura, Giuliana Alimena, Pietro Leoni, Cristina Mecucci, Anna Covezzoli, Fabrizio Pane, Alessandro Levis, Nicola Di Renzo, Giovanni Caocci, Anna D'Emilio, Giuseppe Rossi, Valeria Santini, Francesco Arcioni, Giuseppe Visani, Roberta La Starza, Paolo Avanzini, Maria Cantonetti, Andrea Roncadori, and Alessandro Rambaldi
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Pediatrics ,medicine.medical_specialty ,business.industry ,Myelodysplastic syndromes ,Immunology ,Cytogenetics ,Cell Biology ,Hematology ,Macrocytosis ,Neutropenia ,medicine.disease ,Biochemistry ,Cancer registry ,medicine.anatomical_structure ,White blood cell ,medicine ,Population study ,business ,Lenalidomide ,medicine.drug - Abstract
Abstract 3850 Background: Lenalidomide (LEN) is available in Italy for patients with intermediate-1- and low-risk myelodysplastic syndromes (MDS) associated with 5q deletion (5q-) since October 2008, based on a local disposition of the Italian Drug Agency (AIFA) issued according to a national law (Law 648/96). LEN is an oncological drug subject to intensive monitoring and, when it is prescribed in MDS, physicians are requested to enter the patient into a registry, which is entirely web-based. Methods: This observational, retrospective, multicenter study (registered at www.clinicaltrials.govasNCT01347944) has enrolled patients at 40 centres of 43 authorized in Italy. The study was approved by the ethic committee of each participating institution. The purpose was to analyse data available in the Registry and to integrate them with additional clinical and laboratory findings by filling up new e-forms in all cases with MDS and 5q- receiving LEN from October 31st, 2008 until the present. Diagnosis, treatment, follow-up and re-evaluation of patients were considered. Results: Study population included patients pre-treated and not pre-treated, with or without the integration form at the end of treatment. Pre-treated were defined as patients who were given LEN (from 1 to 12 cycles, median 3) before entering the AIFA registry. 158 patients (42 pre-treated and 116 not pre-treated) were eligible for this preliminary analysis. Median age was 75 (range, 38–89 years); 6 patients were younger than 50. There were 108 females (68.35%) and 50 males (31.6%) (table). Hematological findings evaluated at diagnosis were: hemoglobin (8.5g/dL, 57%), macrocytosis (MCV >98 fL, 54.4%), platelet count (400×109/L, 19%). Median white blood cell count was 4× 103/L with 54% neutrophils. Bone marrow blasts ≤5% were found in 75.9% of cases. The 5q- was detected by conventional cytogenetics in 131/158 cases (82.9%): it was isolated in 110 cases, associated with one additional in 15, and in complex karyotypes in 6. In 2 cases with normal karyotype and in 25 cases with failed cytogenetics the 5q- was demonstrated by fluorescence in situ hybridization (FISH). These cases could not be grouped as isolated or non-isolated. Patients received LEN at a daily dose of 10mg or 5 mg for 21 of 28 days as the starting dose. The dose and schedule was adjusted mainly based on blood count and hematological toxicity. Median time on treatment was 15.5 months (range, 1–45). Major and minor criteria for hematological and cytogenetic response are under evaluation. Transfusion independence at 6 months was reached in 77/103 cases (74.75%). Hematological toxicity could be evaluated in 148 cases. A total of 555 neutropenia events (36% grade 3 and 12.9% grade 4) and 422 thrombocytopenia events (10.9% grade 3 and 6.16% grade 4) were seen. Among 69 evaluable cases, 11 (15.9%) developed acute myeloid leukemia. In this group the median age was 72 (range, 62–85) and there were 4 males and 7 females. The median number of LEN cycles was 6 (range, 2–31). The median time from diagnosis of MDS was 34 months (range, 4–68). Chromosome 5q- at diagnosis was demonstrated by conventional cytogenetics in 8 cases (6 isolated and 2 with one additional change) and by FISH in 3. Comments: The Italian Drug Agency (AIFA) Registry provided us with a large series of MDS cases with 5q- to investigate appropriatness of LEN prescription and management. As expected LEN was successful to obtain transfusion independence in this patient population. Hematological toxicity was manageable. The number of cases with leukemic evolution is in line with data reported in the literature. These cases will be further investigated. Disclosures: Mecucci: CELGENE: Research Funding.
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- 2012
47. Lenalidomide Is Effective in Heavily Pretreated Non Hodgkin Lymphoma (NHL): Analysis of a Retrospective Data Collection
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Sante Tura, Alfonso Zaccaria, Umberto Vitolo, Pier Luigi Zinzani, Giuseppe Rossi, Luigi Rigacci, Sergio Storti, Francesco Zaja, Alberto Fabbri, Paolo Paesano, Liliana Devizzi, and M. Christina Cox
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Oncology ,medicine.medical_specialty ,business.industry ,Immunology ,Follicular lymphoma ,Phases of clinical research ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Surgery ,Refractory Non-Hodgkin Lymphoma ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Rituximab ,Mantle cell lymphoma ,business ,Diffuse large B-cell lymphoma ,Multiple myeloma ,medicine.drug ,Lenalidomide - Abstract
Abstract 3694 Based on published favorable Phase 2 data in patients with relapsed/refractory non Hodgkin Lymphoma (NHL)(Wiernik, 2008), the Italian Drug Agency (AIFA) granted the nulla osta to patients with NHL who were ineligible to receive more intensive curative treatments, which allowed off-label treatment with lenalidomide on a case by case basis. From April 2008 to December 2010, 180 NHL patients, most of them diagnosed with Diffuse Large B Cell Lymphoma (DLBCL) and Mantle Cell Lymphoma (MCL), were treated with lenalidomide. All patients were tracked in an ad hoc database, in order to ensure compliance with the Risk Management Plan (RMP) already in place for the authorized use of lenalidomide in the multiple myeloma indication. Data collected from this cohort of NHL patients were retrospectively analyzed, with the aim to assess the safety and efficacy of lenalidomide administered to a heavily pretreated patient population in the context of routine clinical practice. To our knowledge, this is the largest NHL patient cohort treated with lenalidomide outside of a clinical trial. Data on 157 patients from 44 Italian sites have been collected and analyzed to date. Patient demographics and disease characteristics were as follows: median age 70 years (range 19–92); median number of prior treatments 3 (range 1–17); 94% of patients previously treated with rituximab. The lymphoma subtypes included DLBCL in 44%, MCL in 35%, Follicular Lymphoma (FL) in 9% and Transformed Lymphoma (TL) in 6% of cases. As expected, 62% of patients had Stage IV disease, in keeping with the highly unfavorable characteristics of a heavily pretreated patient population. In the majority of treatment cycles, lenalidomide was administered at a dose of 25 mg (61%) and in combination (58%). Analyzing all cycles, dexametasone was the preferred drug combined with lenalidomide (35%), while rituximab was added in 10%. Median number of administered lenalidomide cycles was 3 (range 1–27). According to the International Workshop on Lymphoma Response Criteria 42 % of patients responded, with 18% CR + CRu and 24 % PR. The breakdown of overall responses according to the different lymphoma subtypes shows: a rate of 45%, 39%, 54%, and 33% in DLBCL, MCL, FL, and TL patients, respectively. Median duration of response was 7.8 months overall, 14.2 months specifically for patients who achieved CR/CRu. Median TTP and PFS are 7.8 and 5.7 months (Figure 1) respectively, and median OS 21.8 months (Figure 2). The safety and tolerability profile of lenalidomide appears to be comparable to what was already known from published clinical trial results in NHL (Wiernik et al., JCO 2008, Habermann et al., BJH 2009, Witzig et al., Ann of Onc 2011, Zaja et al., Haematol 2011, Zinzani et al., Clin Lymph Myel Leuk 2011, Wang et al., Lancet Onc 2012). No secondary neoplasms have been reported to date. In conclusion, with the limitations of a retrospective data collection, this analysis provides intriguing results on the use of an immunomodulatory drug such as lenalidomide in a large cohort of heavily pretreated NHL patients, who have limited therapeutic options or who are ineligible for more intensive curative treatments. In this very unfavorable patient setting, lenalidomide has shown incouraging response rates as well as PFS and OS values, suggesting anti-lymphoma activity. Figure 1 Figure 1. Figure 2. Figure 2. Disclosures: Off Label Use: Lenalidomide (Revlimid) has indication in the treatment of multiple myeloma. Based on several published phase II study we have used this drug, granted by the nulla osta of the Italian Drug Agency (AIFA), as off-label therapy of non Hodgkin lymphomas regardless of histology. The aim of this retrospective study was to assess the safety and efficay of this drug in a cohort of patients heavily pretreated.
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- 2012
48. High plasma levels of tumor necrosis factor-alpha may be predictive of veno-occlusive disease in bone marrow transplantation
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L, Gugliotta, L, Catani, N, Vianelli, F, Gherlinzoni, M C, Miggiano, G, Bandini, and S, Tura
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Tumor Necrosis Factor-alpha ,Hepatic Veno-Occlusive Disease ,Humans ,Bone Marrow Transplantation - Published
- 1994
49. Iron Chelation Therapy with Deferasirox In Transfusion Dependent Myelodysplastic Syndrome Patients. Preliminary Report From the Prospective MDS0306 GIMEMA Trial
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Angelucci, Emanuele, primary, Santini, Valeria, additional, Di Tucci, Anna Angela, additional, Casa, Chiara Della, additional, Finelli, Carlo, additional, Volpe, Antonio, additional, Pogliani, Enrico Maria, additional, Quarta, Giovanni, additional, Levis, Alessandro, additional, D'Arco, Alfonso Maria, additional, Saglio, Giuseppe, additional, Cascavilla, Nicola, additional, Morra, Enrica, additional, Vallisa, Daniele, additional, Foà, Robin, additional, Leone, Giuseppe, additional, Storti, Sergio, additional, Gabbas, Attilio, additional, Annino, Luciana, additional, Magro, Domenico, additional, Tosi, Patrizia, additional, Caocci, Giovanni, additional, Musto, Pellegrino, additional, Amadori, Sergio, additional, Leoni, Pietro, additional, Gobbi, Marco, additional, Piciocchi, Alfonso, additional, Vignetti, Marco, additional, Porcedda, Serenella, additional, and Tura, Sante, additional
- Published
- 2010
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50. Lenalidomide Administration in Heavily Pretreated Patients with Non Hodgkin Lymphoma – First Report of the REVEAL Study (REVlimid® Effectiveness of Administration in patients with Lymphoma)
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Pier Luigi Zinzani, Angelo Michele Carella, Luigi Rigacci, Francesco Zaja, Sante Tura, Liliana Devizzi, Umberto Vitolo, Alice Di Rocco, and Alberto Fabbri
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medicine.medical_specialty ,business.industry ,Immunology ,Retrospective cohort study ,Context (language use) ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Lymphoma ,Surgery ,Internal medicine ,medicine ,Rituximab ,Mantle cell lymphoma ,business ,Diffuse large B-cell lymphoma ,Multiple myeloma ,medicine.drug ,Lenalidomide - Abstract
Abstract 4979 Lenalidomide (Revlimid®) is an oral treatment authorized in the US and EU for use in relapse/refractory multiple myeloma. Since March 2008, lenalidomide, in combination with Dexamethasone, is marketed in Italy in the aforementioned indication. The Italian Drug Agency (AIFA) has also granted authorization for the off-label use of lenalidomide in patients with Non Hodgkin Lymphoma (NHL) who have no residual therapeutic option, provided these patients are tracked in a registry, in order to ensure their compliance with the Risk Management Plan (RMP) already in place for the multiple myeloma indication. The authorization was granted based on preliminary published favorable phase 2 data (Wiernik, 2008; Habermann, 2009). April 2008 to November 2010 lenalidomide was prescribed (following the 94/98 Italian law) to over 200 NHL patients, mainly diagnosed as Diffuse Large B Cell Lymphoma (DLBCL) and Mantle Cell Lymphoma (MCL). This retrospective observational study was undertaken to gather clinic-pathological and laboratory data about this cohort of NHL patients, with the objective to evaluate the safety and the efficacy of lenalidomide administered, in the context of routine clinical practice, to a heavily pretreated patient population with no remaining therapeutic alternative. Also, efforts will be done in order to identify prognostic factors which can affect response to lenalidomide treatment. As of today, data on 30 patients treated at 6 sites have been collected and analyzed. Patient demographics and disease characteristics are summarized in Table 1. Patient median age was 70.5 years (range 36.0 – 90.0); median number of previous treatments was 5 (range 1 – 17). Over ninety three per cent (93.3%.) of the patients were previously treated with Rituximab. Forty per cent (40%) had DLBC histology, 16.7% MCL, 13.3% follicular histology and 16.7% were transformed lymphomas. As expected, 60% of the patients had stage IV disease, in keeping with the highly unfavorable characteristics of a heavily pretreated patient population. Responses were assessed according to the International Workshop on Lymphoma Response Criteria (IWRC). The number of lenalidomide cycles administered varied between 1 and 15 in this small patient group; 69.2% of the patients, evaluated at cycle 3, showed an objective response (OR). Table 1 TABLE T3 DEMOGRAPHIC CHARACTERISTICS (EVALUABLE POPULATION) Demographic and Disease Characteristics on evaluable population (N=30) Gender Male 20 (66.7%) Female 10 (33.3%) Age (years) N 30 Mean (SD) 69.8 (11.2) Median 70.5 Range 36.0- 90.0 Time since diagnosis (years) N 22 Mean (SD) 8.82 (8.3) Median 3.30 Range 0.45- 9.0 Histology DLBCL 40% Follicular 13.3% MCL 16.7% Transformed 16.7% Stage Stage III 20% Stage IV 60% Data on approximately 180 patients treated at 46 sites throughout Italy will be analysed and presented. Only subjects who refuse to make their data available for review and analysis, or are currently participating in an interventional clinical study (from the date of enrollment into the interventional study) will be excluded. Although very preliminary, this experience indicates that lenalidomide has interesting anti- lymphoma efficacy, even in patients who have exhausted all available therapeutic options. Disclosures: Off Label Use: The Italian Drug Agency (AIFA) has also granted authorization for the off-label use of lenalidomide in patients with Non Hodgkin Lymphoma (NHL) who have no residual therapeutic option, provided these patients are tracked in a registry, in order to ensure their compliance with the Risk Management Plan (RMP) already in place for the multiple myeloma indication.
- Published
- 2011
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