27 results on '"Michela Ansuinelli"'
Search Results
2. PB1711: DROPLET DIGITAL PCR DETECTION OF THE T315I BCR::ABL1 KD MUTATION IN ADULT PH-POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA
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Deborah Cardinali, Marco Beldinanzi, Michela Ansuinelli, Loredana Elia, Irene Della Starza, Vittorio Bellomarino, Mabel Matarazzo, Mariangela DI Trani, Mattia Cola, Anna Rita Guarini, Robin Foà, and Sabina Chiaretti
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2023
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- View/download PDF
3. A multicenter total therapy strategy for de novo adult Philadelphia chromosome positive acute lymphoblastic leukemia patients: final results of the GIMEMA LAL1509 protocol
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Sabina Chiaretti, Michela Ansuinelli, Antonella Vitale, Loredana Elia, Mabel Matarazzo, Alfonso Piciocchi, Paola Fazi, Francesco Di Raimondo, Lidia Santoro, Francesco Fabbiano, Catello Califano, Giovanni Martinelli, Francesca Ronco, Felicetto Ferrara, Nicola Cascavilla, Catia Bigazzi, Alessandra Tedeschi, Simona Sica, Nicola Di Renzo, Angela Melpignano, Germana Beltrami, Marco Vignetti, and Robin Foa
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
The GIMEMA LAL1509 protocol, designed for adult (≥18-60 years) de novo Ph+ acute lymphoblastic leukemia patients, was based on a dasatinib plus steroids induction - with central nervous system prophylaxis - followed by dasatinib alone in patients in complete molecular response or chemotherapy and/or allogeneic transplantation in patients not reaching a complete molecular response. Sixty patients (median age 41.9 years) were enrolled: 33 were p190+, 18 p210+ and 9 p190/p210+. At the end of induction (day +85), 58 patients (97%) achieved a complete hematologic remission. No deaths in induction were recorded. Eleven patients (18.3%) obtained a complete molecular response. Among non-complete molecular responders (n=47), 22 underwent an allogeneic transplant. Seventeen hematologic relapses occurred (median 7 months, range 3-40.1), 13 during consolidation and 4 post-transplant. ABL1 mutations (5 T315I, 3 V299L, 1 E281K and 1 G254E) were found in 10/13 relapsed cases. With a median follow-up of 57.4 months (range: 4.2-75.6), overall survival and disease-free survival are 56.3% and 47.2%. A better diseasefree survival was observed in patients who obtained a molecular response at day +85 compared to cases who did not. The presence of additional copy number aberrations - IKZF1 plus CDKN2A/B and/or PAX5 deletions - was the most important unfavorable prognostic factor on overall and disease-free survival (p=0.005 and p=0.0008). This study shows that in adult Ph+ ALL long-term survivals can be achieved with a total-therapy strategy based on a chemo-free induction and, in complete molecular responders, also without further systemic chemotherapy. Finally, the screening of additional copy number aberrations should be included in the diagnostic work-up. EudraCT 2010-019119-39
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- 2021
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4. Philadelphia-like acute lymphoblastic leukemia is associated with minimal residual disease persistence and poor outcome. First report of the minimal residual disease-oriented GIMEMA LAL1913
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Sabina Chiaretti, Monica Messina, Irene Della Starza, Alfonso Piciocchi, Luciana Cafforio, Marzia Cavalli, Akram Taherinasab, Michela Ansuinelli, Loredana Elia, Guglielmo Albertini Petroni, Roberta La Starza, Martina Canichella, Alessia Lauretti, Maria Cristina Puzzolo, Valentina Pierini, Alessandra Santoro, Orietta Spinelli, Valerio Apicella, Saveria Capria, Francesco Di Raimondo, Paolo De Fabritiis, Cristina Papayannidis, Anna Candoni, Roberto Cairoli, Marco Cerrano, Nicola Fracchiolla, Daniele Mattei, Chiara Cattaneo, Antonella Vitale, Enrico Crea, Paola Fazi, Cristina Mecucci, Alessandro Rambaldi, Anna Guarini, Renato Bassan, and Robin Foà
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Early recognition of Ph-like acute lymphoblastic leukemia cases could impact on the management and outcome of this subset of B-lineage ALL. To assess the prognostic value of the Ph-like status in a pediatric-inspired, minimal residual disease (MRD)-driven trial, we screened 88 B-lineage ALL cases negative for the major fusion genes (BCR-ABL1, ETV6-RUNX1, TCF3-PBX1 and KTM2Ar) enrolled in the GIMEMA LAL1913 front-line protocol for adult BCR/ABL1-negative ALL. The screening - performed using the BCR/ABL1-like predictor - identified 28 Ph-like cases (31.8%), characterized by CRLF2 overexpression (35.7%), JAK/STAT pathway mutations (33.3%), IKZF1 (63.6%), BTG1 (50%) and EBF1 (27.3%) deletions, and rearrangements targeting tyrosine kinases or CRLF2 (40%). The correlation with outcome highlighted that: i) the complete remission (CR) rate was significantly lower in Ph-like compared to non-Ph-like cases (74.1% vs 91.5%, p=0.044); ii) at time point 2 (TP2), decisional for transplant allocation, 52.9% of Ph-like cases vs 20% of non-Ph-like were MRD-positive (p=0.025); iii) the Ph-like profile was the only parameter associated with a higher risk of being MRD-positive at TP2 (p=0.014); iv) at 24 months, Ph-like patients had a significantly inferior event-free and disease-free survival compared to non-Ph-like patients (33.5% vs 66.2%, p=0.005 and 45.5% vs 72.3%, p=0.062, respectively). This study documents that Ph-like patients have a lower CR rate, EFS and DFS, as well as a greater MRD persistence also in a pediatric-oriented and MRD-driven adult ALL protocol, thus reinforcing that the early recognition of Ph-like ALL patients at diagnosis is crucial to refine risk-stratification and to optimize therapeutic strategies.
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- 2020
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5. ZNF384 rearrangement is the most frequent genetic lesion in adult PH-negative and Ph-like-negative B-other acute lymphoblastic leukemia. Biological and clinical findings
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Sabina Chiaretti, Akram Taherinasab, Irene Della Starza, Martina Canichella, Michela Ansuinelli, Maria Stefania De Propris, Monica Messina, Orietta Spinelli, Alessandra Santoro, Lucia Anna De Novi, Deborah Cardinali, Mattia Schipani, Valentina Arena, Renato Bassan, Anna Guarini, and Robin Foà
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Cancer Research ,Oncology ,Hematology - Published
- 2022
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6. Circulating cell‐free DNA for target quantification in hematologic malignancies: Validation of a protocol to overcome pre‐analytical biases
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Roberta Soscia, Irene Della Starza, Lucia Anna De Novi, Caterina Ilari, Michela Ansuinelli, Marzia Cavalli, Vittorio Bellomarino, Luciana Cafforio, Mariangela Di Trani, Giovanni Cazzaniga, Grazia Fazio, Alessandra Santoro, Domenico Salemi, Orietta Spinelli, Manuela Tosi, Carolina Terragna, Valentina Robustelli, Teresa Bellissimo, Gioia Colafigli, Massimo Breccia, Sabina Chiaretti, Alice Di Rocco, Maurizio Martelli, Anna Guarini, Ilaria Del Giudice, and Robin Foà
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Cancer Research ,Oncology ,Hematology ,General Medicine - Abstract
Circulating tumor DNA (ctDNA) has become the most investigated analyte in blood. It is shed from the tumor into the circulation and represents a subset of the total cell-free DNA (cfDNA) pool released into the peripheral blood. In order to define if ctDNA could represent a useful tool to monitor hematologic malignancies, we analyzed 81 plasma samples from patients affected by different diseases. The results showed that: (i) the comparison between two different extraction methods Qiagen (Hilden, Germany) and Promega (Madison, WI) showed no significant differences in cfDNA yield, though the first recovered higher amounts of larger DNA fragments; (ii) cfDNA concentrations showed a notable inter-patient variability and differed among diseases: acute lymphoblastic leukemia and chronic myeloid leukemia released higher amounts of cfDNA than chronic lymphocytic leukemia, and diffuse large B-cell lymphoma released higher cfDNA quantities than localized and advanced follicular lymphoma; (iii) focusing on the tumor fraction of cfDNA, the quantity of ctDNA released was insufficient for an adequate target quantification for minimal residual disease monitoring; (iv) an amplification system proved to be free of analytical biases and efficient in increasing ctDNA amounts at diagnosis and in follow-up samples as shown by droplet digital PCR target quantification. The protocol has been validated by quality control rounds involving external laboratories. To conclusively document the feasibility of a ctDNA-based monitoring of patients with hematologic malignancies, more post-treatment samples need to be evaluated. This will open new possibilities for ctDNA use in the clinical practice.
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- 2022
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7. Cytokine release syndrome in haploidentical stem cell transplant may impact T-cell recovery and relapse
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Roman M Shapiro, Haesook T Kim, Michela Ansuinelli, Indira Guleria, Corey S. Cutler, John Koreth, Mahasweta Gooptu, Joseph H Antin, Amar H Kelkar, Jerome Ritz, Catherine J. Wu, Robert J. Soiffer, Vincent T. Ho, Sarah Nikiforow, and Rizwan Romee
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Hematology - Abstract
Cytokine release syndrome (CRS) following haploidentical hematopoietic cell transplantation (HCT) resembles the CRS after chimeric antigen receptor (CAR)-T therapy. We conducted this single-center retrospective study evaluating the association of post-haploidentical HCT CRS with clinical outcomes and immune reconstitution. One hundred sixty-nine patients who underwent haploidentical HCT between 2011 and 2020 were identified. Of these, 98 patients (58%) developed CRS after HCT. CRS was diagnosed based on the presence of fever within the first 5 days after HCT without evidence of infection or infusion reaction, and graded according to established criteria. The development of post-haploidentical HCT CRS was associated with a lower incidence of disease relapse (p=0.024) but with an increased risk of chronic GVHD (p=0.01). The association of CRS with a lower incidence of relapse was not confounded by graft source or disease diagnosis. Neither CD34 nor TNC dose was associated with CRS independently of graft type. In patients developing CRS, CD4+ Treg (p
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- 2023
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8. Maintenance Therapy with Venetoclax/Azacitidine Can be Safely Given after Venetoclax/FluBu2 RIC Allogeneic Transplantation for the Treatment of High Risk MDS/AML: Results of a Phase 1 Study
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Jacqueline S. Garcia, Haesook T Kim, Jennifer Brock, H. Moses Murdock, Corey S. Cutler, Daniel J. DeAngelo, Christopher J. Gibson, Mahasweta Gooptu, Vincent Ho, John Koreth, Marlise R. Luskin, Sarah Nikiforow, Rizwan Romee, Roman M Shapiro, Richard M. Stone, Martha Wadleigh, Eric S. Winer, Michela Ansuinelli, Eliza Elliot, Geoffrey Fell, Hannah Karp, Jeremy Ryan, Anthony G. Letai, Coleman Lindsley, Robert J Soiffer, Joseph H. Antin, Fiona Loschi, and Jerome Ritz
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
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9. Blast morphology in the diagnostic work-up of Ph-like acute lymphoblastic leukemia
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Francesca Fazio, Gabriella Cunsolo, Francesca Mancini, Maria Stefania De Propris, Alfonso Piciocchi, Valentina Arena, Monica Messina, Michela Ansuinelli, Akram Taherinasab Taherinasab, Valerio Apicella, Antonella Vitale, Sabina Chiaretti, Anna Guarini, Ilaria del Giudice, and Robin Foà
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Cancer Research ,Oncology ,Ph-like acute lymphoblastic leukemia ,Humans ,Philadelphia Chromosome ,Hematology ,blast morphology ,B-lineage ALL ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,Blast Crisis - Published
- 2022
10. Author response for 'Applicability of droplet digital polymerase chain reaction for minimal residual disease monitoring in Philadelphia‐positive acute lymphoblastic leukaemia'
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Lucia Anna De Novi, Martina Canichella, Loredana Elia, Veronica Siravo, Irene Della Starza, Alessia Lauretti, Sabina Chiaretti, Anna Guarini, Michela Ansuinelli, Robin Foà, Akram Taherinasab, and Monica Messina
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business.industry ,Cancer research ,Lymphoblastic leukaemia ,Medicine ,Philadelphia positive ,Digital polymerase chain reaction ,business ,Minimal residual disease - Published
- 2021
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11. Emerging tyrosine kinase inhibitors for the treatment of adult acute lymphoblastic leukemia
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Sabina Chiaretti, Robin Foà, Michela Ansuinelli, and Laura Cesini
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Oncology ,medicine.medical_specialty ,medicine.medical_treatment ,Disease ,acute lymphoblastic leukemia ,PH chromosome ,PH-like signature ,tyrosine kinase inhibitors ,Internal medicine ,Humans ,Medicine ,Philadelphia Chromosome ,Pharmacology (medical) ,Protein Kinase Inhibitors ,Pharmacology ,High prevalence ,Minimal Residual Disease Negative ,business.industry ,Hematopoietic Stem Cell Transplantation ,Immunotherapy ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,medicine.disease ,respiratory tract diseases ,Leukemia ,Adult Acute Lymphoblastic Leukemia ,business ,Complete Hematologic Response ,Tyrosine kinase - Abstract
Introduction: The broadening of targeted and immunotherapeutic strategies markedly impacted on the management of acute lymphoblastic leukemia (ALL). The advent of tyrosine kinase inhibitors (TKIs) changed the history of Philadelphia-chromosome positive (Ph+) ALL. Nowadays, almost all Ph+ ALL patients treated with TKIs achieve a complete hematologic response, and most become minimal residual disease negative. In Ph- ALL, genomic profiling studies have identified a subtype associated with a high relapse risk and a transcriptional profile similar to that of Ph+ ALL, the so-called Ph-like ALL. Given the high prevalence of kinase-activating lesions in this subset, there is compelling evidence from experimental models and clinical observations favoring TKI administration.Areas covered: We discuss the main findings exploring the efficacy of TKIs in ALL.Expert opinion: The use of more potent TKIs will further enhance the inhibitory activity on leukemia cells and increase the possibility of eradicating the disease at a molecular level. In the future, 'combined' approaches of different inhibitors may be considered to prevent/avoid resistance and/or mutations. A rapid identification of Ph-like ALL patients is needed to propose early TKI-based intervention. Several questions remain open, including the initial TKI choice in Ph+ ALL and whether Ph-like ALL patients might benefit from immunotherapy.
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- 2021
12. a multicenter total therapy strategy for de novo adult philadelphia chromosome positive acute lymphoblastic leukemia patients final results of the gimema lal1509 protocol
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Francesca Ronco, Simona Sica, Nicola Di Renzo, Felicetto Ferrara, Robin Foà, Angela Melpignano, Paola Fazi, Alfonso Piciocchi, Catia Bigazzi, Michela Ansuinelli, Alessandra Tedeschi, Nicola Cascavilla, Giovanni Martinelli, Mabel Matarazzo, Marco Vignetti, Francesco Di Raimondo, Francesco Fabbiano, Catello Califano, Sabina Chiaretti, Loredana Elia, Germana Beltrami, Antonella Vitale, and L. Santoro
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medicine.medical_specialty ,Chemotherapy ,a multicenter total therapy strategy for de novo adult philadelphia chromosome positive acute lymphoblastic leukemia patients final results of the gimema lal1509 protocol ,Allogeneic transplantation ,Philadelphia Chromosome Positive ,ABL ,business.industry ,medicine.medical_treatment ,Lymphoblastic Leukemia ,BCR/ABL1+ ALL ,adults ,dasatinib ,Hematology ,Gastroenterology ,Dasatinib ,03 medical and health sciences ,Settore MED/15 - MALATTIE DEL SANGUE ,0302 clinical medicine ,CDKN2A ,030220 oncology & carcinogenesis ,Internal medicine ,Molecular Response ,medicine ,business ,030215 immunology ,medicine.drug - Abstract
The GIMEMA LAL1509 protocol, designed for adult (≥18-60 years) de novo Ph+ acute lymphoblastic leukemia patients, was based on a dasatinib plus steroids induction - with central nervous system prophylaxis - followed by dasatinib alone in patients in complete molecular response or chemotherapy and/or allogeneic transplantation in patients not reaching a complete molecular response. Sixty patients (median age 41.9 years) were enrolled: 33 were p190+, 18 p210+ and 9 p190/p210+. At the end of induction (day +85), 58 patients (97%) achieved a complete hematologic remission. No deaths in induction were recorded. Eleven patients (18.3%) obtained a complete molecular response. Among non-complete molecular responders (n=47), 22 underwent an allogeneic transplant. Seventeen hematologic relapses occurred (median 7 months, range 3-40.1), 13 during consolidation and 4 post-transplant. ABL1 mutations (5 T315I, 3 V299L, 1 E281K and 1 G254E) were found in 10/13 relapsed cases. With a median follow-up of 57.4 months (range: 4.2-75.6), overall survival and disease-free survival are 56.3% and 47.2%. A better diseasefree survival was observed in patients who obtained a molecular response at day +85 compared to cases who did not. The presence of additional copy number aberrations - IKZF1 plus CDKN2A/B and/or PAX5 deletions - was the most important unfavorable prognostic factor on overall and disease-free survival (p=0.005 and p=0.0008). This study shows that in adult Ph+ ALL long-term survivals can be achieved with a total-therapy strategy based on a chemo-free induction and, in complete molecular responders, also without further systemic chemotherapy. Finally, the screening of additional copy number aberrations should be included in the diagnostic work-up. EudraCT 2010-019119-39
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- 2021
13. Applicability of droplet digital polymerase chain reaction for minimal residual disease monitoring in Philadelphia-positive acute lymphoblastic leukaemia
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Robin Foà, Sabina Chiaretti, Loredana Elia, Martina Canichella, Veronica Siravo, Irene Della Starza, Alessia Lauretti, Lucia Anna De Novi, Monica Messina, Anna Guarini, Michela Ansuinelli, and Akram Taherinasab
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Cancer Research ,medicine.medical_specialty ,Prognostic factor ,Neoplasm, Residual ,Ph+ acute lymphoblastic leukemia ,Fusion Proteins, bcr-abl ,Philadelphia positive ,ddPCR ,Real-Time Polymerase Chain Reaction ,Gastroenterology ,law.invention ,law ,Internal medicine ,Biomarkers, Tumor ,Humans ,Medicine ,Philadelphia Chromosome ,Digital polymerase chain reaction ,Polymerase chain reaction ,Digital droplet pcr ,MRD ,business.industry ,Reproducibility of Results ,Hematology ,General Medicine ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,Prognosis ,Minimal residual disease ,Oncology ,Disease Progression ,Lymphoblastic leukaemia ,Neoplasm Recurrence, Local ,business - Abstract
In Ph+ acute lymphoblastic leukaemia (Ph+ ALL), minimal residual disease (MRD) is the most relevant prognostic factor. Currently, its evaluation is based on quantitative real-time polymerase chain reaction (Q-RT-PCR). Digital droplet PCR (ddPCR) was successfully applied to several haematological malignancies. We analyzed 98 samples from 40 Ph+ ALL cases, the majority enrolled in the GIMEMA LAL2116 trial: 10 diagnostic samples and 88 follow-up samples, mostly focusing on positive non-quantifiable (PNQ) or negative samples by Q-RT-PCR to investigate the value of ddPCR for MRD monitoring. DdPCR BCR/ABL1 assay showed good sensitivity and accuracy to detect low levels of transcripts, with a high rate of reproducibility. The analysis of PNQ or negative cases by Q-RT-PCR revealed that ddPCR increased the proportion of quantifiable samples (p
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- 2021
14. New dead/H-box helicase gene (ddx41) mutation in an Italian family with recurrent leukemia
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Cristina Mecucci, Eleonora Miulli, Martina Quintini, Roberto Latagliata, Michela Ansuinelli, Massimo Breccia, Benedetta Lucani, Francesca Fazio, Caterina Matteucci, Fabrizia Pellanera, and Ida Carmosino
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Genetics ,Cancer Research ,Mutation ,Myeloid ,Familial clustering ,Hematology ,Biology ,medicine.disease ,medicine.disease_cause ,Helicase Gene ,03 medical and health sciences ,Leukemia ,0302 clinical medicine ,Germline mutation ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,DEAD-box RNA helicases ,humans ,Italy ,leukemia ,mutation ,mental disorders ,medicine ,030215 immunology - Abstract
Familial clustering of myeloid malignancies with autosomal dominant (AD) inheritance was firstly recognized in 1999 by the identification of germline mutations associated with familial platelet dis...
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- 2021
15. Is now the time for molecular driven therapy for diffuse large B-cell lymphoma?
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Robin Foà, Federico De Angelis, Maurizio Martelli, Alice Di Rocco, and Michela Ansuinelli
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Oncology ,medicine.medical_specialty ,Cell of origin ,Antineoplastic Agents ,Bioinformatics ,03 medical and health sciences ,Therapeutic approach ,0302 clinical medicine ,immune system diseases ,hemic and lymphatic diseases ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Drug Discovery ,Biomarkers, Tumor ,medicine ,Humans ,Molecular Targeted Therapy ,neoplasms ,activated B cell (ABC) ,cell of origin (COO) ,CHOP regimen ,Diffuse large B cell lymphoma (DLBCL) ,gene expression profiling (GEP) ,germinal centre-B cell like (GCB) ,immunohistochemistry (IHC) ,rituximab ,Hematology ,Clinical Trials as Topic ,business.industry ,High grade B-cell lymphoma ,Prognosis ,medicine.disease ,Lymphoma ,Treatment Outcome ,Research Design ,030220 oncology & carcinogenesis ,Rituximab ,Lymphoma, Large B-Cell, Diffuse ,business ,Diffuse large B-cell lymphoma ,030215 immunology ,medicine.drug - Abstract
Recent genetic and molecular discoveries regarding alterations in diffuse large B-cell lymphoma (DLBCL) deeply changed the approach to this lymphoproliferative disorder. Novel additional predictors of outcomes and new therapeutic strategies are being introduced to improve outcomes. Areas covered: This review aims to analyse the recent molecular discoveries in DLBCL, the rationale of novel molecular driven treatments and their impact on DLBCL prognosis, especially in ABC-DLBCL and High Grade B Cell Lymphoma. Pre-clinical and clinical evidences are reviewed to critically evaluate the novel DLBCL management strategies. Expert commentary: New insights in DLBCL molecular characteristics should guide the therapeutic approach; the results of the current studies which are investigating safety and efficacy of novel 'X-RCHOP' will probably lead, in future, to a cell of origin (COO) based upfront therapy. Moreover, it is necessary to identify early patients with DLBCL who carried MYC, BCL2 and/or BCL6 rearrangements double hit lymphomas (DHL) because they should not receive standard R-CHOP but high intensity treatment as reported in many retrospective studies. New prospective trials are needed to investigate the more appropriate treatment of DHL.
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- 2017
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16. Relapsed/refractory diffuse large B-cell lymphoma patients. A multicenter retrospective analysis of eligibility criteria for car-T cell therapy
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Robin Foà, Francesco Merli, Francesco Rotondo, Domenico Penna, Francesca Re, Mariateresa Giaimo, Alessio Farcomeni, Maurizio Martelli, Arianna Di Rocco, Giulia De Luca, Luigi Petrucci, Alice Di Rocco, Antonio Cuneo, Michela Ansuinelli, and Gian Matteo Rigolin
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Oncology ,Cancer Research ,medicine.medical_specialty ,CAR-T cells ,Lymphoma ,car-t cell eligibility ,car-t cells ,Diffuse large B-cell lymphoma ,relapse-refractory disease ,Antigens, CD19 ,Adoptive ,CAR-T cell eligibility ,Cell- and Tissue-Based Therapy ,Immunotherapy, Adoptive ,Humans ,Lymphoma, Large B-Cell, Diffuse ,Receptors, Chimeric Antigen ,NO ,03 medical and health sciences ,0302 clinical medicine ,Refractory ,Internal medicine ,Receptors ,Large B-Cell ,Retrospective analysis ,Medicine ,In patient ,Antigens ,CD19 ,business.industry ,Chimeric Antigen ,Hematology ,medicine.disease ,Diffuse ,Chimeric antigen receptor ,030220 oncology & carcinogenesis ,Relapsed refractory ,CAR T-cell therapy ,Immunotherapy ,Car t cells ,Settore SECS-S/01 ,business ,030215 immunology - Abstract
Anti-CD19 chimeric antigen receptor (CAR) T cells represent the first approved third-line therapy associated with long-term remissions in patients with refractory/relapsed (R/R) diffuse large B-cell lymphoma (DLBCL). Eligibility criteria to identify patients who can successfully receive CAR-T are still debated. For this reason, the aim of this study was to identify factors influencing eligibility and define a realistic patient estimate. Of 1100 DLBCL patients, 137 were included. Based on the Juliet trial inclusion criteria, only 64 patients (46.7%) would be eligible. Median overall survival (OS) was 8.04 months in eligible
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- 2020
17. Philadelphia-like acute lymphoblastic leukemia is associated with minimal residual disease persistence and poor outcome. First report of the minimale residual disease-oriented GIMEMA LAL1913
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Roberto Cairoli, Robin Foà, Orietta Spinelli, Enrico Crea, Antonella Vitale, Alessandra Santoro, Loredana Elia, Monica Messina, Maria Ctristina Puzzolo, Sabina Chiaretti, Michela Ansuinelli, Chiara Cattaneo, Nicola Stefano Fracchiolla, Marzia Cavalli, Valerio Apicella, Valentina Pierini, Paolo de Fabritiis, Guglielmo Albertini Petroni, Alfonso Piciocchi, Cristina Mecucci, Irene Della Starza, Cristina Papayannidis, Anna Guarini, Luciana Cafforio, Alessia Lauretti, Daniele Mattei, Akram Taherinasab, Renato Bassan, Francesco Di Raimondo, Martina Canichella, Saveria Capria, Roberta La Starza, Alessandro Rambaldi, Marco Cerrano, Anna Candoni, Paola Fazi, Chiaretti, S, Messina, M, Della Starza, I, Piciocchi, A, Cafforio, L, Cavalli, M, Taherinasab, A, Ansuinelli, M, Elia, L, Petroni, G, La Starza, R, Canichella, M, Lauretti, A, Puzzolo, M, Pierini, V, Santoro, A, Spinelli, O, Apicella, V, Capria, S, Di Raimondo, F, De Fabritiis, P, Papayannidis, C, Candoni, A, Cairoli, R, Cerrano, M, Fracchiolla, N, Mattei, D, Cattaneo, C, Vitale, A, Crea, E, Fazi, P, Mecucci, C, Rambaldi, A, Guarini, A, Bassan, R, and Foa, R
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Adult ,medicine.medical_specialty ,Minimal Residual Disease Persistence ,Neoplasm, Residual ,Philadelphia-Like Acute Lymphoblastic Leukemia ,Gastroenterology ,Disease-Free Survival ,Article ,03 medical and health sciences ,0302 clinical medicine ,MED/15 - MALATTIE DEL SANGUE ,Internal medicine ,hemic and lymphatic diseases ,medicine ,Adults ,Neoplasm ,Humans ,Philadelphia Chromosome ,Child ,Adult all ,business.industry ,Minimal residual disease ,Editorials ,Complete remission ,breakpoint cluster region ,Ph-like ,Hematology ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,Settore MED/15 ,Prognosis ,medicine.disease ,Ph-like ALL ,GIMEMA LAL ,minimal residual disease-oriented ,Adult Acute Lymphoblastic Leukemia ,030220 oncology & carcinogenesis ,Acute Disease ,business ,Human ,030215 immunology - Abstract
Early recognition of Philadelphia-like (Ph-like) acute lymphoblastic leukemia (ALL) cases could impact on the management and outcome of this subset of B-lineage ALL. In order to assess the prognostic value of the Ph-like status in a pediatric-inspired, minimal residual disease (MRD)- driven trial, we screened 88 B-lineage ALL cases negative for major fusion genes (BCR-ABL1, ETV6-RUNX1, TCF3-PBX1 and KTM2Ar) enrolled in the GIMEMA LAL1913 front-line protocol for adult BCR/ABL1-negative ALL. The screening - performed using the “BCR/ABL1-like predictor” - identified 28 Ph-like cases (31.8%), characterized by CRLF2 overexpression (35.7%), JAK/STAT pathway mutations (33.3%), IKZF1 (63.6%), BTG1 (50%) and EBF1 (27.3%) deletions, and rearrangements targeting tyrosine kinases or CRLF2 (40%). The correlation with outcome highlighted that: i) the complete remission rate was significantly lower in Ph-like compared to non-Phlike cases (74.1% vs. 91.5%, P=0.044); ii) at time point 2, decisional for transplant allocation, 52.9% of Ph-like cases versus 20% of non-Ph-like were MRD-positive (P=0.025); iii) the Ph-like profile was the only parameter associated with a higher risk of being MRD-positive at time point 2 (P=0.014); iv) at 24 months, Ph-like patients had a significantly inferior event-free and disease-free survival compared to non-Ph-like patients (33.5% vs. 66.2%, P=0.005 and 45.5% vs. 72.3%, P=0.062, respectively). This study documents that Ph-like patients have a lower complete remission rate, event-free survival and disease-free survival, as well as a greater MRD persistence also in a pediatric-oriented and MRD-driven adult ALL protocol, thus reinforcing that the early recognition of Ph-like ALL patients at diagnosis is crucial to refine risk-stratification and to optimize therapeutic strategies. Clinicaltrials gov. Identifier: 02067143.
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- 2020
18. BEAM vs FEAM high-dose chemotherapy: retrospective study in lymphoma patients undergoing autologous stem cell transplant
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Svitlana Gumenyuk, Francesco Marchesi, Atelda Romano, Livio Pupo, Francesco Pisani, A. Di Rocco, M. D. Caputo, Francesca Palombi, Elena Papa, Daniela Renzi, Diana Giannarelli, Silvia Maria Trisolini, Marco Canfora, Andrea Mengarelli, Ida Provenzano, Michela Ansuinelli, Saveria Capria, Alessandra Serrao, Maria Cantonetti, and Antonio Spadea
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Oncology ,Adult ,Male ,medicine.medical_specialty ,Transplantation Conditioning ,Adolescent ,MEDLINE ,Transplantation, Autologous ,03 medical and health sciences ,High dose chemotherapy ,Young Adult ,0302 clinical medicine ,Text mining ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Young adult ,Melphalan ,Aged ,Etoposide ,Retrospective Studies ,Transplantation ,Carmustine ,Cytarabine ,Female ,Hematopoietic Stem Cell Transplantation ,Middle Aged ,business.industry ,Retrospective cohort study ,Hematology ,Settore MED/15 ,medicine.disease ,Lymphoma ,030220 oncology & carcinogenesis ,Stem cell ,business ,Autologous ,030215 immunology - Published
- 2017
19. Role of Blinatumomab in Minimal Residual Disease and Hematologic Relapsed/Refractory Adult Acute Lymphoblastic Leukemia Patients Treated over 5 Years. a Single Center Experience
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Maria Stefania De Propris, Robin Foà, Anna Maria Testi, Irene Della Starza, Anna Guarini, Antonella Vitale, Maria Luisa Moleti, Sabina Chiaretti, Clara Minotti, Claudio Cartoni, Giovanna Pecoraro, Walter Barberi, Anna Paola Iori, Michela Ansuinelli, Francesca Mancini, Loredana Elia, Silvia Maria Trisolini, and Saveria Capria
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medicine.medical_specialty ,business.industry ,education ,Immunology ,Context (language use) ,Cell Biology ,Hematology ,Single Center ,medicine.disease ,Biochemistry ,Minimal residual disease ,Transplantation ,Clinical trial ,Internal medicine ,Acute lymphocytic leukemia ,Cohort ,medicine ,Blinatumomab ,business ,health care economics and organizations ,medicine.drug - Abstract
Background. Hematologic and, to a lesser extent, molecular relapsed/refractory in adult acute lymphoblastic leukemia (R/R ALL) is associated with a poor outcome, with low rates of subsequent complete remission (CR) and short survival. Blinatumomab has shown to be effective in both settings. Aims and methods. In this retrospective, single center study we aimed at: 1) evaluating the efficacy of blinatumomab in both hematologic and molecular R/R patients enrolled in clinical trials and in a real life setting; 2) identifying predictive factors impacting on overall and disease free-survival (OS and DFS), and 3) establishing the feasibility and the role of a subsequent allogenic stem cell transplantation (HSCT). Thirty-six adult patients (≥18 years) in hematologic or molecular R/R ALL were treated with blinatumomab between January 2012 and March 2017. Blinatumomab was administered either in the context of a clinical trial (Blast, MT103-211, Tower, Alcantara), in a compassionate use program or according to AIFA (Agenzia Italiana del Farmaco) guidelines. Blinatumomab was administered as continuous infusion for 4 weeks, followed by a 2-week wash out. A stepwise dose of 9 µg/day during the first week of cycle 1 followed by 28 µg/day thereafter, was administered for hematologic R/R cases and a flat dose of 15 µg /m2/day for molecular R/R patients. Patients who witnessed a response received up to 4 additional cycles or underwent a HSCT; patients showing after 1 cycle an increase in the blast count or of minimal residual disease levels, discontinued treatment. Results. Thirty-six patients were analyzed: 21 (58.4%) were in hematologic R/R and 15 (41.6%) in molecular R/R. Four patients had high-risk genetic features (2 BCR/ABL1 and 2 MLL/AF4). Thirteen patient were treated in the context of a clinical trial. All patients received at least one cycle of blinatumomab. At the end of the first cycle, among the 21 hematologic R/R pts, 14 (67%) achieved a CR and 10/14 (71%) also a CMR, while in the molecular R/R group 12/15 (80%) achieved a CMR. As expected, the rate of CMR was significantly higher in the molecular R/R cases as opposed to hematologic R/R (80% vs 52%, p=0.05). Notably, all 4 patients treated for a primary refractory disease, achieved a CR and CMR after the first cycle as opposed to hematologic relapsed cases (p=0.08). With a median follow-up of 33.9 months (range 1-89), the overall OS and DFS at 3 years are 34% and 42.5%, respectively. OS was significantly better for molecular R/R cases than for hematologic R/R cases (54.2% vs 26.1%, p=0.05), while no significant differences were observed in DFS. OS and DFS are 100%, respectively, for refractory cases. Median OS is 6.75 months for hematological R/R, while it is not reached for molecular R/R. Median DFS is 26 months for both groups. Predictive factors for non-response were the status of disease prior to blinatumomab (hematologic vs molecular R/R) and primary refractoriness. A better, though not significant, outcome was observed for patients treated in first rather than in subsequent relapse, and in cases without molecular aberrations (p=0.07, p=0.09). Overall, 14 patients - 9 with molecular and 5 with hematologic R/R at enrollment - underwent a HSCT: 8 are in continuous CR (median follow-up: 17 months, range 5-73). Among the 22 patients who did not receive a HSCT, including 16 molecular and 6 hematologic R/R at enrollment), 7 are in continuous CR (median follow-up: 51 months, range 10-89). Due to the small sample size, we cannot define the role of transplant; transplant-related mortality (TRM) was observed in 3/14 (21.4%). Treatment was well tolerated: the most common adverse events were pyrexia (55%), infectious events (33.3%) and neurotoxicity (19.4%); hematologic toxicity was rare and more frequent in hematologic R/R. Conclusions. Treatment with blinatumomab was safe and effective. As expected, patients treated in molecular R/R had better survival rates than hematologic R/R patients. Despite the small number, all primary refractory patients responded to blinatumomab, suggesting that in these cases immunotherapeutic strategies can be extremely effective, irrespective of a chemo-insensitive disease. HSCT did not impact on OS and DFS, possibly due to the small number of the cohort. Finally, no differences in terms of adverse events, DFS or OS were observed between patients treated in the context of a clinical trial or in a real-life setting. Disclosures Chiaretti: Incyte: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Shire: Membership on an entity's Board of Directors or advisory committees. Foà:Abbvie: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Shire: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Shire: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Membership on an entity's Board of Directors or advisory committees.
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- 2019
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20. Concomitant Treatment with Ruxolitinib and Deferasirox in the Management of Iron Overload in Patients with Myelofibrosis: A Multicenter Italian Experience
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Ambra Di Veroli, Rossella Renso, Giuseppe A. Palumbo, Massimiliano Bonifacio, Luigi Scaffidi, Elena Maria Elli, Raffaele Porrini, Giovanni Caocci, Daniele Cattaneo, Carlo Gambacorti-Passerini, Mario Tiribelli, Michela Ansuinelli, Ida Carmosino, Emanuele Sutto, Marianna Caramella, Nicola Polverelli, Roberto Latagliata, Giulia Benevolo, Alessandra Iurlo, Elisabetta Abruzzese, Massimo Breccia, Uros Markovic, Elena Crisà, Malgorzata Monika Trawinska, Lucia Biale, and Daniela Cilloni
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medicine.medical_specialty ,Ruxolitinib ,Thrombocytosis ,Anemia ,business.industry ,Surrogate endpoint ,Immunology ,Deferasirox ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Internal medicine ,Concomitant ,medicine ,In patient ,business ,Myelofibrosis ,medicine.drug - Abstract
Introduction: Deferasirox (DFX) is the currently available iron-chelation therapy (ICT) for the management of iron overload (IOL), mainly in myelodysplastic syndromes; recently, two retrospective independent studies (Di Veroli, 2018; Elli, 2019) demonstrated that a treatment with DFX is feasible and effective also in the setting of myelofibrosis (MF). However, no data are still available regarding the concomitant use of DFX in patients (pts) treated with Ruxolitinib (Rux). Aims and Methods: We retrospectively collected in 16 Italian Centers 59 pts (M: 37; F: 22) with primary MF (n=41) or post-Polycythemia Vera (n=9) and post-Essential Thrombocythemia (n=9) MF, treated with Rux and DFX for the management of IOL secondary to transfusion-dependent anemia. Primary endpoint of the study was to evaluate the efficacy of DFX in terms of reduction of ferritin levels and hematological improvement (HI). Additional endpoints were the safety of DFX associated to Rux treatment and the impact on survival and leukemic evolution. Results: The main features of pts at diagnosis and at baseline of DFX treatment are reported in Table 1 (column A). Pts started DFX after a median time from MF diagnosis of 26.7 months [Interquartile range (IR) 2.6-240.9] and from transfusion dependency of 13.5 months (IR 1.5 - 145.3). Forty-eight pts started DFX when already under Rux treatment, while 11 pts before Rux treatment. The median ferritin level (FL) at baseline was 1675 ng/mL (IR 646-6447). The median starting dose of DFX was 1000 mg/day (12.5 mg/kg/day). All pts were evaluable for DFX response (> 3 months of DFX), with a median time of DFX and Rux exposure of 14.5 months (IR 3.2-73.3) and 40 months (2.1-88.6), respectively; the median period of concomitant DFX-Rux treatment was 11.1 months (3.7-58.4). As to ICT efficacy, 24 pts (40.7%) obtained an iron chelation response (ICR), defined as a stable reduction of FL < 1.000 ng/mL or a reduction ≥ 50% of FL respect to baseline. The main variables analyzed in pts with ICR or no ICR were reported in Table 1 (Column B and C, respectively). At univariate analysis, pts who obtained ICR did not presented significant differences compared to pts without ICR, except for a significantly lower median FL at diagnosis (251 vs 496 mcg/l, p=0.008). As expected, ICR pts showed a progressive significant reduction of FL at 3, 6, 12 and 18 months, respect to baseline, in contrast to pts without ICR (p < 0.0001). The median time of exposure to DFX was higher in ICR vs no ICR group (22.0 vs 12.9 months, p=0.03), as well as the median time of concomitant DFX-Rux treatment (14.2 vs 9.7 months, p=0.019). The International Working Group criteria (Cheson, 2006) were applied to assess HI during ICT. Erythroid response (ER) was defined as complete (CR: achievement of transfusion independency), partial (PR: reduction in the transfusion requirement ≥ 50% and/or increase of haemoglobin levels) or no response (NR). ER was observed in 25 pts (42.4%) with ten (17%) obtaining CR, 15 (25.4%) PR and 34 (57.6%) NR. Obtainment of ICR predicted for the achievement of ER: 17 (70.8%) pts with ICR achieved CR or PR compared to 8 (22.8%) without ICR (p =0.0007). DFX-related toxicities occurred in 30 pts (50.8%) and consisted mainly in renal impairment (32.2%), liver enzymes alterations (6.7%) or epigastric pain (8.4%): however, only in one case was observed a grade 3 toxicity. Overall, a dose reduction/temporary discontinuation related to DFX-toxicity was reported in 14 (23.7%) pts; however only 5 (8.4%) pts completely discontinued ICT because of grade ≥ 2 toxicity. After a median follow-up from diagnosis of 58.6 months (IR 7.1-282.9), 19 pts (32.2%) died [13 of them (22%) for leukemic evolution or disease progression]. The 3-year cumulative overall survival (Figure 1) and the 3-year cumulative incidence of leukemic evolution (Figure 2) from DFX initiation were 75.1% (95%CI 55.6 - 94.6) and 20.2% (95%CI 2.1 - 38.3) in pts who obtained ICR compared to 54.5% (95%CI 31.9 - 77.1) and 36.1% (95%CI 13.1 - 59.1) in pts without ICR, respectively (p=0.13 and p=0.153). Conclusions: The present multicenter study showed that ICT with DFX is effective and safe also in this setting of pts receiving concomitant Rux treatment. HI with ER seems occur in a significant proportion of pts and correlates with the achievement of ICR. Further larger and prospective investigations are required in order to evaluate the impact on survival and leukemic evolution of this combination. Disclosures Elli: Novartis: Membership on an entity's Board of Directors or advisory committees. Iurlo:Novartis: Other: Speaker Honoraria; Incyte: Other: Speaker Honoraria; Pfizer: Other: Speaker Honoraria. Benevolo:Novartis Pharmaceuticals: Consultancy. Abruzzese:BMS: Consultancy; Incyte: Consultancy; Novartis: Consultancy; Pfizer: Consultancy. Bonifacio:Novartis: Honoraria; Amgen: Honoraria; BMS: Honoraria; Pfizer: Honoraria; Incyte: Honoraria. Cilloni:Janssen: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Tiribelli:Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees. Trawinska:Novartis: Consultancy, Honoraria. Breccia:BMS: Honoraria; Pfizer: Honoraria; Incyte: Honoraria; Novartis: Honoraria; Celgene: Honoraria. Gambacorti-Passerini:Bristol-Meyers Squibb: Consultancy; Pfizer: Honoraria, Research Funding. Palumbo:Janssen: Honoraria; Celgene: Honoraria; Teva: Honoraria; Novartis: Honoraria; Amgen: Honoraria; Hospira: Honoraria. Latagliata:Celgene: Honoraria; Novartis: Honoraria; Janssen: Honoraria; Pfizer: Honoraria.
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- 2019
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21. PS935 APPLICABILITY OF DROPLET DIGITAL PCR (DDPCR) FOR MINIMAL RESIDUAL DISEASE MONITORING (MRD) IN PHILADELPHIA-POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA
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Robert Foa, Veronica Siravo, Martina Canichella, Monica Messina, Michela Ansuinelli, Sabina Chiaretti, Alessia Lauretti, Loredana Elia, L.A. De Novi, I. Della Starza, Marzia Cavalli, and A. Guarini
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Oncology ,medicine.medical_specialty ,business.industry ,Lymphoblastic Leukemia ,Internal medicine ,medicine ,Philadelphia positive ,Digital polymerase chain reaction ,Hematology ,business ,Minimal residual disease - Published
- 2019
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22. Primary mediastinal large B-cell lymphoma
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Maurizio Martelli, Andrés Ferreri, Alice Di Rocco, Michela Ansuinelli, and Peter W.M. Johnson
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0301 basic medicine ,Pathology ,medicine.medical_specialty ,PET-CT scan ,CD30 ,Primary mediastinal large B-cell lymphoma ,Histopathology ,CHOP ,Prognostic factors ,Mediastinal Neoplasms ,Chemotherapy ,Consolidation radiotherapy ,Immunotherapy ,Hematology ,Oncology ,Geriatrics and Gerontology ,03 medical and health sciences ,0302 clinical medicine ,International Prognostic Index ,immune system diseases ,Positron Emission Tomography Computed Tomography ,hemic and lymphatic diseases ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Neoplasm Staging ,Thymic Lymphoma ,business.industry ,Prognosis ,medicine.disease ,Lymphoma ,030104 developmental biology ,030220 oncology & carcinogenesis ,Rituximab ,Lymphoma, Large B-Cell, Diffuse ,Primary mediastinal B-cell lymphoma ,business ,Diffuse large B-cell lymphoma ,medicine.drug - Abstract
Primary mediastinal large B-cell lymphoma (PMBCL) is a unique type of B-cell lymphoma probably arising from a putative thymic medullary B cell. It constitutes 6–10 % of all diffuse large B-cell lymphomas (DLBCL), occurring more often in young females. It is characterised by a diffuse proliferation of medium to large B cells associated with sclerosis and a degree of compartmentalisation. CD30 staining is observed in the vast majority of cases (~80 %), although it is weaker and less homogeneous than in cHL and anaplastic large-cell lymphoma. Molecular analysis shows it to be distinct from other types of DLBCL. PMBCL is characterised by an invasive anterior mediastinal mass, often producing local compressive symptoms. Some retrospective analyses suggested that it might respond better to third-generation chemotherapy regimens than to the more commonly used CHOP. However, the addition of rituximab reduced these differences and R-CHOP is now the most widely used treatment, as it is for other types of DLBCL. The role of consolidation with local radiotherapy, which is often used to treat residual mediastinal masses, still remains unclear. Treatment with R-CHOP followed by radiation therapy has excellent results, with a 5-year survival of 70–85 %. The role of FDG-PET scanning is the subject of prospective studies, and it is hoped that in the future, this will allow the de-escalation of radiation therapy based upon more accurate prognostic information as treatment proceeds.
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- 2017
23. Second cancer incidence in primary mediastinal B-cell lymphoma treated with methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin regimen with or without rituximab and mediastinal radiotherapy: Results from a monoinstitutional cohort analysis of long-term survivors
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Maurizio Valeriani, Vincenzo Tombolini, Marco Alfò, Maurizio Martelli, Giuseppe Minniti, Daniela Musio, Alice Di Rocco, Maria Luisa Moleti, Michela Ansuinelli, Vitaliana De Sanctis, Mattia Falchetto Osti, Lavinia Grapulin, Stefano Bracci, Alessandra Spagnoli, and Eleonora Russo
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Oncology ,Male ,Cancer Research ,medicine.medical_treatment ,Leucovorin ,Kaplan-Meier Estimate ,chemistry.chemical_compound ,0302 clinical medicine ,Cancer Survivors ,Antineoplastic Combined Chemotherapy Protocols ,Cumulative incidence ,Thyroid cancer ,lymphoma ,myeloid leukemias ,radiotherapy ,hematology ,oncology ,cancer research ,Incidence ,Neoplasms, Second Primary ,Hematology ,General Medicine ,Middle Aged ,Combined Modality Therapy ,Treatment Outcome ,Vincristine ,030220 oncology & carcinogenesis ,Rituximab ,Female ,medicine.drug ,Adult ,Risk ,medicine.medical_specialty ,Lymphoma, B-Cell ,Cyclophosphamide ,Adolescent ,Bleomycin ,Mediastinal Neoplasms ,03 medical and health sciences ,Young Adult ,Internal medicine ,medicine ,Humans ,Radiotherapy ,business.industry ,medicine.disease ,Radiation therapy ,Methotrexate ,chemistry ,Doxorubicin ,Prednisone ,Primary mediastinal B-cell lymphoma ,business ,030215 immunology - Abstract
Our aim is to assess the incidence of second cancer in long-time surviving primary mediastinal B-cell lymphoma (PMBCL) patients treated with combined radiochemoimmunotherapy (standard methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin with rituximab and mediastinal radiation therapy at a dose of 30 to 36 Gy). For this purpose, 92 points were evaluated. After a median overall survival of 137 months (range 76-212), we recorded second cancer in 3 of 80 long-surviving patients (3.75%) with cumulative incidence of 3.47% at 15 years and 11% at 17 years, with a 17-year second cancer-free survival of 82%. We observed 2 papillary thyroid cancers with a standardized incidence ratio (SIR) of 7.97 and an absolute excess risk (AER) of 17. 84 and 1 acute myeloid leukemia (AML) with an SIR of 66.53 and an AER of 10.05. No breast cancer occurred. Although we should take into account the limits of the proposed statistical analysis, combined modality treatment was related to a significant SIR and AER for thyroid cancer and acute myeloid leukemia.
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- 2016
24. Peripheral T-Cell Lymphomas (PTCL) Treated With Or Without Upfront Autologous Stem Cell Transplantation: Results Of a Retrospective Single Center Analysis
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Robin Foà, Paolo Paesano, Michela Ansuinelli, Saveria Capria, Alice Di Rocco, Maurizio Martelli, Angelo Fama, Eleonora Russo, Laura Cesini, and Giovanna Meloni
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medicine.medical_specialty ,Chemotherapy ,business.industry ,medicine.medical_treatment ,Immunology ,Induction chemotherapy ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Gastroenterology ,Chemotherapy regimen ,Surgery ,Lymphoma ,Regimen ,International Prognostic Index ,Autologous stem-cell transplantation ,B symptoms ,Internal medicine ,medicine ,medicine.symptom ,business - Abstract
Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of rare diseases, characterized by an aggressive behavior and a poor clinical outcome. High-dose therapy followed by autologous stem cell transplantation (ASCT) has been used as salvage and upfront treatment with conflicting results. However, no standard therapy has so far been established due to the lack of randomized studies. The records of 54 untreated patients with a confirmed diagnosis of PTCL managed at our Institute between 2001 and 2011 were reviewed. The histologic subtypes were: 37 (68%) peripheral T-cell lymphomas unspecified (PTCL-U), 13 (24%) anaplastic large cell lymphomas (ALCL), of which 4 (30%) ALK-positive, 2 (4%) angio-immunoblastic lymphomas (AITL) and 2 (4%) enteropathy-associated T-cell lymphomas (EATL). The clinical characteristics were: median age 56 years (range 18-79); 40 men and 14 women; 13 (24%) and 41 (76%) patients were, respectively, in Ann Arbor stages I-II and III-IV. An elevated serum LDH was present in 33% of patients, 48% had B symptoms and 24% had a bone marrow involvement. The ECOG performance status was 2-3 in 28% of patients. According to the International Prognostic Index (IPI) and the prognostic index for T-cell lymphomas (PIT), 11% and 22% were classified as low risk, 30% and 33% as low-intermediate risk, 12% and 33% as high-intermediate risk and 29% and 12% as high risk, respectively. CHOP-like regimens were given to 32 (59%) patients, 14 of whom received the CHOEP regimen. The remaining 22 (41%) patients were treated with more intensive third generation regimens (MACOP-B like). ASCT was planned as upfront consolidation therapy for 16/54 (30%) patients. A complete response (CR) was obtained in 30/54 (55.5%) patients, a partial response in 7 (13%), while 17 (31.5%) patients showed a lymphoma progression during induction therapy. No difference in terms of CR rate was observed between the CHOP-like and MACOP-B-like regimens. At a median follow-up of 19 months (range 3-138), the 5-years OS and 5-years PFS were 32% (95% CI 25.3-38.5) and 27% (95% CI 20.2-34.5), respectively. At univariate analysis, bone marrow involvement (p=0.003), PIT high risk group (p The prognosis of PTCLs remains poor despite the use of intensive chemotherapy regimen including upfront ASCT. More active induction chemotherapy regimens, including novel agents, should be designed in an attempt to increase the quality of response before ASCT consolidation therapy. Disclosures: No relevant conflicts of interest to declare.
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- 2013
25. The Neutrophil/Lymphocyte Ratio (N/L) Is a Prognostic Marker in Patients with Diffuse Large B Cell Lymphoma: A Prospective Study from the Lazio Lymphoma Registry
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Elena Maiolo, Cristiano Tesei, Marco Montanaro, Eleonora Alma, Livio Pupo, Roberta Battistini, Giuseppe Cimino, Virginia Naso, Anna Marina Liberati, Valerio Zoli, Federico De Angelis, Maria Paola Bianchi, Giuliana Rizzuto, Valeria Tomarchio, Maria Cantonetti, Francesca Palombi, Maria Chiara Tisi, Michela Ansuinelli, Elisabetta Abruzzese, Ombretta Annibali, Paola Anticoli Borza, Stefan Hohaus, and Maria Christina Cox
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Vincristine ,medicine.medical_specialty ,Pathology ,business.industry ,Immunology ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Gastroenterology ,Lymphoma ,International Prognostic Index ,B symptoms ,Median follow-up ,Internal medicine ,medicine ,Absolute neutrophil count ,Rituximab ,medicine.symptom ,business ,Diffuse large B-cell lymphoma ,medicine.drug - Abstract
The neutrophil/lymphocyte ratio (N/L) at diagnosis has been shown to be a prognostic factor for survival in solid tumors. An increase in the neutrophil count is a marker of inflammation which is an essential part of the neoplastic process. Conversely, a decrease of the peripheral lymphocyte count might reflect an impairment of the host defense mechanism associated with advanced and aggressive cancers. Since There are only few reports on the N/L ratio in non-Hodgkin lymphomas. We studied the prognostic role of the N/L ratio at diagnosis in 286 patients with diffuse-large-B-cell lymphoma (DLBCL) enrolled in a multicenter prospective registry of the Lazio region in Italy The median age at diagnosis was 69 years (27-91) and the female/male ratio was:141/145.First, we analyzed for associations between N/L ratio and patient characteristics. The optimal cut-off value for the N/L was obtained using the Receiver Operating Curve (ROC) and according to the published data in solid tumor. N/L ≥ 4 was significantly associated with presence of B-symptoms (p=0.01) and elevated LDH levels (p=0.007) at diagnosis. Most patients were treated with R-CHOP (rituximab, cyclophosphamide, Adriamycin, vincristine, and prednisone) or R-CHOP-like (90%). Complete Remission (CR) + Partial Remission (PR) were obtained in 210/286 (73%). The median follow up period was 15 months (range: 1-33 months): 27 patients died for lymphoma relapse/progression and 16 for other causes. Patients with N/L ≥ 4 experienced a higher rate of relapse, while N/L< 4 was associated to a significantly better Overall (OS, P < 0.05) and Event Free Survival (EFS, P< 0.01). (Figure 1, panel a and b).Furthermore, considering only patients with IPI score ≤ 3, those with N/L Conclusion: The N/L ratio may be a useful and unexpensive prognostic marker in patients with DLBCL. The inferior outcome observed in patients with N/L ≥ 4 might reflect an immune and inflammatory imbalance induced by a more aggressive tumor, releasing directly or indirectly inflammatory cytokines and/or inducing immune suppression or exhaustion. A link with inflammation is suggested by the correlation of N/L ratio ≥ 4 with high LDH levels and the presence of B symptoms. Figure 1. Panel A. Overall Survival (OS) and Panel B. Event Free Survival (EFS) by N/L ratio. Panel C. Overall Survival (OS) by N/L in patients with IPI score ≤ 3. Table 1.Baseline patients characteristics (N = 268) and compared by N/L < 4 or ≥ 4 by using Chi-Square Test for categorical variables. Abbreviations not included in the text: IPI = International Prognostic Index; LDH = lactate dehydrogenase, PD: Progression Disease, NA: Not Applicable. Disclosures Cimino: Celgene: Honoraria; Bristol-Mayer: Honoraria.
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- 2016
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26. Peripheral T-Cell Lymphomas Not Otherwise Specified: Potential Novel Molecular Entities Based on Both Tumor and Microenvironment Cellular Components
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Wing C. Chang, Cristiana Carniti, Tayla Heavican, Paolo Corradini, Javeed Iqbal, Umberto Vitolo, Alessio Pellegrinelli, Antonino Neri, Anna Dodero, Luca Agnelli, Annalisa Chiappella, Michela Ansuinelli, Roberto Piva, Jiayu Yu, Francesco Zaja, Alice Di Rocco, Elisabetta Mereu, Francesco Maura, Niccolo Bolli, Antonello Cabras, and Elisa Pellegrino
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0301 basic medicine ,TBX21 ,T cell ,Immunology ,Cell ,Not Otherwise Specified ,GATA3 ,Double negative ,Cell Biology ,Hematology ,Biology ,Biochemistry ,Gene expression profiling ,03 medical and health sciences ,030104 developmental biology ,medicine.anatomical_structure ,Gene expression ,medicine ,Cancer research - Abstract
INTRODUCTION: The diagnosis of Peripheral T-cell lymphomas not otherwise specified (PTCL-NOS) is currentlybased on an "exclusion criteria" model, since PTCL-NOS lack pathognomonic features. Nevertheless, based on gene expression data, Iqbal et al(Blood 2014) have recently identified two different PTCL-NOS subgroups with different biological and prognostic features that accounts for approximately 80% of the cases and have different biological and prognostic features: one characterized by TBX21 overexpression and T-CD8+ molecular profile; the other by GATA3 overexpression and T-CD4+ profile. Herein, we used a wide comprehensive gene expression profiling (GEP) data set in order to further investigate the molecular features of different PTCL-NOS molecular entities. MATHERIAL AND METHODS: A data set were created including samples from 8 main published series (GSE6338, GSE14879, GSE19067, GSE19069, GSE58445 and GSE65823 at http://www.ncbi.nlm.nih.gov/geo/; E-TABM-702 and E-TABM-783 at https://www.ebi.ac.uk/arrayexpress) for a total of 541 patients. R/Bioconductor was used to generate and analyze the gene expression data. We applied the CIBERSORT algorithm (Gentles et al, Nat Gen 2015), which connects specific global expression profiles to the relative prevalence of tissue components (tumour and microenvironment cells). RESULTS: We first re-classified each sample included in the investigated data set based on previously published signatures (Iqbal et al. Blood 2014, Agnelli et al. Blood 2012). This approach led to a final data set of 144 PTCL-NOS (28%), 127 AITL (23%), 69 ALCL Alk neg (12%), 56 ALCL Alk pos (10%), 59 NK (11%) %), together with 86 healthy T-cell tissues. To our knowledge, this is the largest GEP data set ever described in PTCL so far. In the 144 PTCL-NOS cases, two main molecular clusters were extracted based on published signature, replicating previous findings: the first was characterized by both GATA3 expression (GATA3+) and T-CD4+ cell origin; the second by TBX21 expression (TBX21+) and T-CD8+ cell origin. Approximately 30% of all PTCL-NOS were characterized by neither GATA3 (GATA-) nor TBX21 expression (TBX21-), and for this reason they were classified as "double negative" PTCL-NOS. Based on data obtained by the CIBERSORT algorithm we found that the contribution of cellular microenvironment components was extremely heterogeneous and variable through the entire PTCL-NOS series. A significant T-CD4+ and T-CD8+ cell enrichment was reported among GATA3+ and TBX21+ groups, respectively. Interestingly, a fraction of GATA3+ PTCL-NOS (n=11, 7.6%) was characterized by a significant γδ T-cell component. Conversely, PTCL-NOS GATA3+ patients without γδ T-cell component signature were characterized by a low non-T-cell microenvironment component. This may reflect the major tumour infiltration due to higher proliferation rate as suggested by the strong GATA3 correlation with MIB1 and MYC expression (p Based on the clinical data available for 105/144 PTCL-NOS, poor overall survival (OS) was associated with GATA3 expression (p=0.03) [3-y OS 26.4% (range 20-32.8%) vs 47.3% (range 40-54.5%)]. However, such a poor outcome was less evident when we limited the clinical evaluation to patients younger than 60 years (40/105). Among low GATA3 expressors, TBX21 expression was associated with better OS compared to other "double negative" PTCL-NOS (p=0.07) [3-y OS 66.7% (range 51-82.4%) vs 36.4% (range 22-51%)]. Higher CIBERSORT-predicted T-CD8+ contribution was associated with better OS among patients younger than 60 years (p=0.03) [3-y OS 70% (range 55.6-84.5%) vs 30% (range 21.7-38.3%)]. No other variables or clusters were associated with significant impact on OS. CONCLUSION: Our study based on an innovative computational approach and a large and comprehensive gene expression data set, confirmed the great molecular heterogeneity of PTCL-NOS, suggesting that the current molecular classification of PTCL-NOS may be further improved in the future. Disclosures No relevant conflicts of interest to declare.
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- 2016
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27. Short-course R-CHOP followed by 90Y-Ibritumomab tiuxetan in previously untreated high-risk elderly diffuse large B-cell lymphoma patients: 7-year long-term results
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Vittorio Stefoni, Letizia Gandolfi, Pier Luigi Zinzani, Gianluca Gaidano, Lisa Argnani, Chiara Bottelli, Beatrice Casadei, Alessandro Broccoli, Chiara Ciochetto, Cinzia Pellegrini, Maria Giuseppina Cabras, Michela Ansuinelli, Stefoni, Vittorio, Casadei, Beatrice, Bottelli, C, Gaidano, G, Ciochetto, C, Cabras, M. G, Ansuinelli, M, Argnani, Lisa, Broccoli, Alessandro, Gandolfi, Letizia, Pellegrini, Cinzia, and Zinzani, PIER LUIGI
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Male ,medicine.medical_specialty ,Vincristine ,Cyclophosphamide ,medicine.medical_treatment ,Ibritumomab tiuxetan ,Gastroenterology ,Antibodies, Monoclonal, Murine-Derived ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,R-CHOP, (90)Y-Ibritumomab tiuxetan, high-risk elderly diffuse large B-cell lymphoma ,medicine ,Humans ,Yttrium Radioisotopes ,Aged ,Aged, 80 and over ,business.industry ,lymphoma ,90Y-Ibritumomab tiuxetan ,first line ,Antibodies, Monoclonal ,Hematology ,Middle Aged ,Radioimmunotherapy ,medicine.disease ,Combined Modality Therapy ,Survival Analysis ,Surgery ,Regimen ,Treatment Outcome ,Oncology ,Doxorubicin ,030220 oncology & carcinogenesis ,Prednisolone ,Prednisone ,Original Article ,Female ,Rituximab ,Lymphoma, Large B-Cell, Diffuse ,business ,Diffuse large B-cell lymphoma ,Follow-Up Studies ,030215 immunology ,medicine.drug - Abstract
An update at 7 years was conceived for our multicenter phase II study in which 55 elderly high-risk untreated diffuse large B-cell lymphoma patients were treated with 90Y-ibritumomab tiuxetan after a short course of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) as long-term follow-up analyses of this combined therapeutic modality are lacking. The overall response rate to the entire regimen was 80%, including 73% (40/55) of complete response (CR) rate and 7% (4/55) of partial response rate. At the time of writing, 24/55 (43.6%) patients experienced a progression disease and 20 of 40 (50%) patients who obtained a CR are still alive in continuous CR. With a median follow-up of 7 years, the disease-free survival was 43.3% and the progression-free survival was 36.1%. The overall survival at 7.9 years was 38.9% (27 deaths mainly because of lymphoma). Two patients developed secondary hematological malignancies, an acute myeloid leukemia and a myelodysplastic syndrome, at 4 and 3 years from radioimmunotherapy, respectively. Our data confirm the feasibility, efficacy and safety of four cycles of R-CHOP followed by radioimmunotherapy consolidation even in the long term: this combination allows dispensing less chemotherapy in a frail group of patients without invalidating response quality and duration.
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- 2016
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