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1. SARS-CoV-2 infection in patients with chronic lymphocytic leukemia: The Italian Hematology Alliance on COVID-19 cohort.

Author

Merli M, Ferrarini I, Merli F, Busca A, Mina R, Falini B, Bruna R, Cairoli R, Marchetti M, Romano A, Cavo M, Arcaini L, Trentin L, Cattaneo C, Derenzini E, Fracchiolla NS, Marchesi F, Scattolin A, Billio A, Bocchia M, Massaia M, Gambacorti-Passerini C, Mauro FR, Gentile M, Mohamed S, Della Porta MG, Coviello E, Cilloni D, Visani G, Federici AB, Tisi MC, Cudillo L, Galimberti S, Gherlinzoni F, Pagano L, Guidetti A, Bertù L, Corradini P, Passamonti F, and Visco C

Subjects
Adult, Aged, Aged, 80 and over, Humans, Male, Middle Aged, COVID-19 Testing, SARS-CoV-2, COVID-19 complications, Hematology, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy
Abstract

COVID-19, the disease caused by SARS-CoV-2, is still afflicting thousands of people across the globe. Few studies on COVID-19 in chronic lymphocytic leukemia (CLL) are available. Here, we analyzed data from the CLL cohort of the Italian Hematology Alliance on COVID-19 (NCT04352556), which included 256 CLL patients enrolled between 25 February 2020 and 1 February 2021. Median age was 70 years (range 38-94) with male preponderance (60.1%). Approximately half of patients (n = 127) had received at least one line of therapy for CLL, including 108 (83.7%) who were on active treatment at the time of COVID-19 or received their last therapy within 12 months. Most patients (230/256, 89.9%) were symptomatic at COVID-19 diagnosis and the majority required hospitalization (n = 176). Overall, after a median follow-up of 42 days (IQR 24-96), case fatality rate was 30.1%, and it was 37.5% and 24.4% in the first (25 February 2020-22 June 2020) and second wave (23 June 2020-1 February 2021), respectively (p = 0.03). At multivariate analysis, male sex (HR 1.82, 95% CI 1.03-3.24, p = 0.04), age over than 70 years (HR 2.23, 95% CI 1.23-4.05, p = 0.01), any treatment for CLL given in the last 12 months (HR 1.72, 95% CI 1.04-2.84, p = 0.04) and COVID-19 severity (severe: HR 5.66, 95% CI 2.62-12.33, p < 0.0001; critical: HR 15.99, 95% CI 6.93-36.90, p < 0.0001) were independently associated with poor survival. In summary, we report a dismal COVID-related outcome in a significant fraction of CLL patients, that can be nicely predicted by clinical parameters., (© 2022 John Wiley & Sons Ltd.)

Published
2023
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2. SIE, SIES, GITMO evidence-based guidelines on novel agents (thalidomide, bortezomib, and lenalidomide) in the treatment of multiple myeloma.

Author

Barosi G, Merlini G, Billio A, Boccadoro M, Corradini P, Marchetti M, Massaia M, Tosi P, Palumbo A, Cavo M, and Tura S

Subjects
Antineoplastic Combined Chemotherapy Protocols administration & dosage, Boronic Acids administration & dosage, Bortezomib, Hematology legislation & jurisprudence, Hematology organization & administration, Humans, Lenalidomide, Multiple Myeloma pathology, Neoplasm Grading methods, Pyrazines administration & dosage, Societies, Medical legislation & jurisprudence, Societies, Medical organization & administration, Thalidomide administration & dosage, Thalidomide analogs & derivatives, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Evidence-Based Practice, Hematology methods, Multiple Myeloma drug therapy, Practice Guidelines as Topic
Abstract

In this project, we produced drug-specific recommendations targeting the use of new agents for multiple myeloma (MM). We used the GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) system which separates the judgments on quality of evidence from the judgment about strength of recommendations. We recommended thalidomide and bortezomib in MM patients candidates to autologous stem cell transplantation (ASCT) (weak positive). We did not recommend novel agents as maintenance therapy after ASCT (weak negative). In patients not candidate to ASCT, thalidomide or bortezomib (strong positive) associated with melphalan and prednisone were recommended. In these patients, no specific course of action could be recommended as for maintenance therapy. In patients who are refractory or relapsing after first-line therapy, we recommended bortezomib and pegylated liposomal doxorubicin, or lenalidomide and dexamethasone combinations (weak positive).

Published
2012
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3. Secondary infections worsen the outcome of COVID-19 in patients with hematological malignancies: A report from the ITA-HEMA-COV

Author

Zappasodi P, Cattaneo C, Ferretti V, Mina R, Ferreri AJ, Merli F, Oberti M, Krampera M, Romano A, Zerbi C, Ferrari J, Cavo M, Marco Salvini M, Bertù L, Fracchiolla N, Marchesi F, Massaia M, Marasco V, Cairoli R, Scattolin AM, Vannucchi AM, Gambacorti-Passerini C, Musto P, Gherlinzoni F, Cuneo A, Pinto A, Trentin L, Bocchia M, Galimberti, Coviello E, Morotti A, Falini B, Turrin M, Tafuri A, Billio A, Gentile M, Lemoli M, Venditti A, Della Porta M, Lanza F, Rigacci L, Tosi P, Mohamed S, Corso A, Luppi M, Giuliani N, Busca A, Pagano L, Bruno R, Grossi P, Corradini P, Passamonti F, Arcaini L., Zappasodi, P, Cattaneo, C, Ferretti, V, Mina, R, Ferreri, A, Merli, F, Oberti, M, Krampera, M, Romano, A, Zerbi, C, Ferrari, J, Cavo, M, Marco Salvini, M, Bertù, L, Fracchiolla, N, Marchesi, F, Massaia, M, Marasco, V, Cairoli, R, Scattolin, A, Vannucchi, A, Gambacorti-Passerini, C, Musto, P, Gherlinzoni, F, Cuneo, A, Pinto, A, Trentin, L, Bocchia, M, Galimberti, Coviello, E, Mc, Morotti, A, Falini, B, Turrin, M, Tafuri, A, Billio, A, Gentile, M, Lemoli, M, Venditti, A, Della Porta, M, Lanza, F, Rigacci, L, Tosi, P, Mohamed, S, Corso, A, Luppi, M, Giuliani, N, Busca, A, Pagano, L, Bruno, R, Grossi, P, Corradini, P, Passamonti, F, Arcaini, L, Zappasodi, Patrizia, Cattaneo, Chiara, Ferretti, Virginia Valeria, Mina, Roberto, Ferreri, Andrés José María, Merli, Francesco, Oberti, Margherita, Krampera, Mauro, Romano, Alessandra, Zerbi, Caterina, Ferrari, Jacqueline, Cavo, Michele, Salvini, Marco, Bertù, Lorenza, Fracchiolla, Nicola Stefano, Marchesi, Francesco, Massaia, Massimo, Marasco, Vincenzo, Cairoli, Roberto, Scattolin, Anna Maria, Vannucchi, Alessandro Maria, Gambacorti-Passerini, Carlo, Musto, Pellegrino, Gherlinzoni, Filippo, Cuneo, Antonio, Pinto, Antonello, Trentin, Livio, Bocchia, Monica, Galimberti, Sara, Coviello, Elisa, Tisi, Maria Chiara, Morotti, Alessandro, Falini, Brunangelo, Turrini, Mauro, Tafuri, Agostino, Billio, Atto, Gentile, Massimo, Lemoli, Roberto Massimo, Venditti, Adriano, Della Porta, Matteo Giovanni, Lanza, Francesco, Rigacci, Luigi, Tosi, Patrizia, Mohamed, Sara, Corso, Alessandro, Luppi, Mario, Giuliani, Nicola, Busca, Alessandro, Pagano, Livio, Bruno, Raffaele, Grossi, Paolo Antonio, Corradini, Paolo, Passamonti, Francesco, and Arcaini, Luca

Subjects
Cancer Research, Lymphoma, Coinfection, COVID-19, Hematology, General Medicine, Settore MED/15, hematological malignancie, secondary infections, Settore MED/15 - MALATTIE DEL SANGUE, COVID-19 Testing, Oncology, Hematologic Neoplasms, secondary infection, outcome, Humans, hematological malignancies, Aged
Abstract

The impact of secondary infections (SI) on COVID-19 outcome in patients with hematological malignancies (HM) is scarcely documented. To evaluate incidence, clinical characteristics, and outcome of SI, we analyzed the microbiologically documented SI in a large multicenter cohort of adult HM patients with COVID-19. Among 1741 HM patients with COVID-19, 134 (7.7%) had 185 SI, with a 1-month cumulative incidence of 5%. Median time between COVID-19 diagnosis and SI was 16 days (IQR: 5-36). Acute myeloid leukemia (AML) and lymphoma/plasma cell neoplasms (PCN) were more frequent diagnoses in SI patients compared to patients without SI (AML: 14.9% vs. 7.1%; lymphoma/PCN 71.7% vs. 65.3%). Patients with SI were older (median age 70 vs. 66 years, p = 0.002), with more comorbidities (median Charlson Comorbidity Index 5 vs. 4, p < 0.001), higher frequency of critical COVID-19 (19.5% vs. 11.5%, p = 0.046), and more frequently not in complete remission (75% vs. 64.7% p = 0.024). Blood and bronchoalveolar lavage were the main sites of isolation for SI. Etiology of infections was bacterial in 80% (n = 148) of cases, mycotic in 9.7% (n = 18) and viral in 10.3% (n = 19); polymicrobial infections were observed in 24 patients (18%). Escherichia coli represented most of Gram-negative isolates (18.9%), while coagulase-negative Staphylococci were the most frequent among Gram-positive (14.2%). The 30-day mortality of patients with SI was higher when compared to patients without SI (69% vs. 15%, p < 0.001). The occurrence of SI worsened COVID-19 outcome in HM patients. Timely diagnosis and adequate management should be considered to improve their prognosis.

Published
2022

4. Clinical characteristics and risk factors associated with COVID-19 severity in patients with haematological malignancies in Italy: a retrospective, multicentre, cohort study

Author

Passamonti, F, Cattaneo, C, Arcaini, L, Bruna, R, Cavo, M, Merli, F, Angelucci, E, Krampera, M, Cairoli, R, Della Porta MG, Fracchiolla, N, Ladetto, M, Gambacorti Passerini, C, Salvini, M, Marchetti, M, Lemoli, R, Molteni, A, Busca, A, Cuneo, A, Romano, A, Giuliani, N, Galimberti, S, Corso, A, Morotti, A, Falini, B, Billio, A, Gherlinzoni, F, Visani, G, Tisi, Mc, Tafuri, A, Tosi, P, Lanza, F, Massaia, M, Turrini, M, Ferrara, F, Gurrieri, C, Vallisa, D, Martelli, M, Derenzini, E, Guarini, A, Conconi, A, Cuccaro, A, Cudillo, L, Russo, D, Ciambelli, F, Scattolin, Am, Luppi, M, Selleri, C, Ortu La Barbera, E, Ferrandina, C, Di Renzo, N, Olivieri, A, Bocchia, M, Gentile, M, Marchesi, F, Musto, P, Federici, Ab, Candoni, A, Venditti, A, Fava, C, Pinto, A, Galieni, P, Rigacci, L, Armiento, D, Pane, F, Oberti, M, Zappasodi, P, Visco, C, Franchi, M, Grossi, Pa, Bertù, L, Corrao, G, Pagano, L, Corradini, P, ITA-HEMA-COV, Investigators., Passamonti, F., Cattaneo, C., Arcaini, L., Bruna, R., Cavo, M., Merli, F., Angelucci, E., Krampera, M., Cairoli, R., Della Porta, M. G., Fracchiolla, N., Ladetto, M., Gambacorti Passerini, C., Salvini, M., Marchetti, M., Lemoli, R., Molteni, A., Busca, A., Cuneo, A., Romano, A., Giuliani, N., Galimberti, S., Corso, A., Morotti, A., Falini, B., Billio, A., Gherlinzoni, F., Visani, G., Tisi, M. C., Tafuri, A., Tosi, P., Lanza, F., Massaia, M., Turrini, M., Ferrara, F., Gurrieri, C., Vallisa, D., Martelli, M., Derenzini, E., Guarini, A., Conconi, A., Cuccaro, A., Cudillo, L., Russo, D., Ciambelli, F., Scattolin, A. M., Luppi, M., Selleri, C., Ortu La Barbera, E., Ferrandina, C., Di Renzo, N., Olivieri, A., Bocchia, M., Gentile, M., Marchesi, F., Musto, P., Federici, A. B., Candoni, A., Venditti, A., Fava, C., Pinto, A., Galieni, P., Rigacci, L., Armiento, D., Pane, F., Oberti, M., Zappasodi, P., Visco, C., Franchi, M., Grossi, P. A., Bertu, L., Corrao, G., Pagano, L., Corradini, P., Passamonti F., Cattaneo C., Arcaini L., Bruna R., Cavo M., Merli F., Angelucci E., Krampera M., Cairoli R., Della Porta M.G., Fracchiolla N., Ladetto M., Gambacorti Passerini C., Salvini M., Marchetti M., Lemoli R., Molteni A., Busca A., Cuneo A., Romano A., Giuliani N., Galimberti S., Corso A., Morotti A., Falini B., Billio A., Gherlinzoni F., Visani G., Tisi M.C., Tafuri A., Tosi P., Lanza F., Massaia M., Turrini M., Ferrara F., Gurrieri C., Vallisa D., Martelli M., Derenzini E., Guarini A., Conconi A., Cuccaro A., Cudillo L., Russo D., Ciambelli F., Scattolin A.M., Luppi M., Selleri C., Ortu La Barbera E., Ferrandina C., Di Renzo N., Olivieri A., Bocchia M., Gentile M., Marchesi F., Musto P., Federici A.B., Candoni A., Venditti A., Fava C., Pinto A., Galieni P., Rigacci L., Armiento D., Pane F., Oberti M., Zappasodi P., Visco C., Franchi M., Grossi P.A., Bertu L., Corrao G., Pagano L., Corradini P., Passamonti, F, Cattaneo, C, Arcaini, L, Bruna, R, Cavo, M, Merli, F, Angelucci, E, Krampera, M, Cairoli, R, Della Porta, M, Fracchiolla, N, Ladetto, M, Gambacorti Passerini, C, Salvini, M, Marchetti, M, Lemoli, R, Molteni, A, Busca, A, Cuneo, A, Romano, A, Giuliani, N, Galimberti, S, Corso, A, Morotti, A, Falini, B, Billio, A, Gherlinzoni, F, Visani, G, Tisi, M, Tafuri, A, Tosi, P, Lanza, F, Massaia, M, Turrini, M, Ferrara, F, Gurrieri, C, Vallisa, D, Martelli, M, Derenzini, E, Guarini, A, Conconi, A, Cuccaro, A, Cudillo, L, Russo, D, Ciambelli, F, Scattolin, A, Luppi, M, Selleri, C, Ortu La Barbera, E, Ferrandina, C, Di Renzo, N, Olivieri, A, Bocchia, M, Gentile, M, Marchesi, F, Musto, P, Federici, A, Candoni, A, Venditti, A, Fava, C, Pinto, A, Galieni, P, Rigacci, L, Armiento, D, Pane, F, Oberti, M, Zappasodi, P, Visco, C, Franchi, M, Grossi, P, Bertu, L, Corrao, G, Pagano, L, and Corradini, P

Subjects
Male, Lymphoma, Comorbidity, 0302 clinical medicine, COVID-19, risk factors, death's rates, haematological malignancies, Retrospective Studie, Risk Factors, Neoplasms, 80 and over, haematological malignancies, Viral, Aged, 80 and over, education.field_of_study, Leukemia, Mortality rate, Lymphoma, Non-Hodgkin, Hazard ratio, Hematology, Plasma cell neoplasm, Middle Aged, Italy, 030220 oncology & carcinogenesis, Hematologic Neoplasms, Cohort, Plasma Cell, Female, Inpatient, Coronavirus Infections, Cohort study, Human, Adult, medicine.medical_specialty, Population, Pneumonia, Viral, Non-Hodgkin, Article, NO, Follow-Up Studie, 03 medical and health sciences, Betacoronavirus, Young Adult, COVID-19 haematological malignancies, Internal medicine, COVID-19, haematological malignancies, multicentre, retrospective, cohort study, Multivariable Cox, medicine, Humans, education, Hematologic Neoplasm, Neoplasms, Plasma Cell, Pandemics, Myeloproliferative Disorder, Aged, Retrospective Studies, Inpatients, Follow-Up Studies, Myeloproliferative Disorders, death's rates, Betacoronaviru, business.industry, Coronavirus Infection, SARS-CoV-2, Risk Factor, COVID-19, haematological malignancies, risk factors, COVID-19, Retrospective cohort study, Pneumonia, Settore MED/15, COVID-19 Drug Treatment, Settore MED/15 - MALATTIE DEL SANGUE, Standardized mortality ratio, business, 030215 immunology
Abstract

Summary Background Several small studies on patients with COVID-19 and haematological malignancies are available showing a high mortality in this population. The Italian Hematology Alliance on COVID-19 aimed to collect data from adult patients with haematological malignancies who required hospitalisation for COVID-19. Methods This multicentre, retrospective, cohort study included adult patients (aged ≥18 years) with diagnosis of a WHO-defined haematological malignancy admitted to 66 Italian hospitals between Feb 25 and May 18, 2020, with laboratory-confirmed and symptomatic COVID-19. Data cutoff for this analysis was June 22, 2020. The primary outcome was mortality and evaluation of potential predictive parameters of mortality. We calculated standardised mortality ratios between observed death in the study cohort and expected death by applying stratum-specific mortality rates of the Italian population with COVID-19 and an Italian cohort of 31 993 patients with haematological malignancies without COVID-19 (data up to March 1, 2019). Multivariable Cox proportional hazards model was used to identify factors associated with overall survival. This study is registered with ClinicalTrials.gov , NCT04352556 , and the prospective part of the study is ongoing. Findings We enrolled 536 patients with a median follow-up of 20 days (IQR 10–34) at data cutoff, 85 (16%) of whom were managed as outpatients. 440 (98%) of 451 hospitalised patients completed their hospital course (were either discharged alive or died). 198 (37%) of 536 patients died. When compared with the general Italian population with COVID-19, the standardised mortality ratio was 2·04 (95% CI 1·77–2·34) in our whole study cohort and 3·72 (2·86–4·64) in individuals younger than 70 years. When compared with the non-COVID-19 cohort with haematological malignancies, the standardised mortality ratio was 41·3 (38·1–44·9). Older age (hazard ratio 1·03, 95% CI 1·01–1·05); progressive disease status (2·10, 1·41–3·12); diagnosis of acute myeloid leukaemia (3·49, 1·56–7·81), indolent non-Hodgin lymphoma (2·19, 1·07–4·48), aggressive non-Hodgkin lymphoma (2·56, 1·34–4·89), or plasma cell neoplasms (2·48, 1·31–4·69), and severe or critical COVID-19 (4·08, 2·73–6·09) were associated with worse overall survival. Interpretation This study adds to the evidence that patients with haematological malignancies have worse outcomes than both the general population with COVID-19 and patients with haematological malignancies without COVID-19. The high mortality among patients with haematological malignancies hospitalised with COVID-19 highlights the need for aggressive infection prevention strategies, at least until effective vaccination or treatment strategies are available. Funding Associazione italiana contro le leucemie, linfomi e mieloma–Varese Onlus.

Published
2020

5. Fludarabine plus alemtuzumab (FA) front-line treatment in young patients with chronic lymphocytic leukemia (CLL) and an adverse biologic profile

Author

Mauro Francesca, R, Molica, Stefano, Laurenti, Luca, Cortelezzi, Agostino, Carella Angelo, M., Zaja, Francesco, Chiarenza, Annalisa, Angrilli, Francesco, Nobile, Francesco, Marasca, Roberto, Musolino, Caterina, Brugiatelli, Maura, Piciocchi, Alfonso, Vignetti, Marco, Fazi, Paola, Gentile, Giuseppe, De Propris Maria, S., Starza Irene Della, Marinelli, Marilisa, Chiaretti, Sabina, Del Giudice Ilaria, Nanni, Mauro, Albano, Francesco, Cuneo, Antonio, Guarini, Anna, Foà, Robin, per il gruppo GIMEMA Working Party Chronic Lymph, Massaia, M., Mauro, Fr, Molica, S, Laurenti, L, Cortelezzi, A, Carella, Am, Zaja, Francesco, Chiarenza, A, Angrilli, F, Nobile, F, Marasca, R, Musolino, C, Brugiatelli, M, Piciocchi, A, Vignetti, M, Fazi, P, Gentile, G, De Propris, M, Della Starza, I, Marinelli, M, Chiaretti, S, Del Giudice, I, Nanni, M, Albano, F, Cuneo, A, Guarini, A, and Foà, R.

Subjects
Oncology, Male, Cancer Research, medicine.medical_treatment, Chronic lymphocytic leukemia, THERAPY, Fludarabine, Monoclonal, Antineoplastic Combined Chemotherapy Protocols, Medicine, Chronic, Alemtuzumab, Humanized, Vidarabine, Neoadjuvant therapy, Hematology, Leukemia, STEM CELL TRANSPLANTATION, Medicine (all), Middle Aged, Lymphocytic, Neoadjuvant Therapy, Treatment Outcome, Female, PHASE-II TRIAL, medicine.drug, EXPRESSION, Adult, medicine.medical_specialty, Young, Biology, CLL, Antibodies, Monoclonal, Humanized, Humans, Leukemia, Lymphocytic, Chronic, B-Cell, Survival Analysis, Antibodies, Chronic lymphocytic leukemia, CLL, Young, Biology, Fludarabine, Alemtuzumab, STEM CELL TRANSPLANTATION, PHASE-II TRIAL, TERM FOLLOW UP, SUBCUTANEOUS ALEMTUZUMAB, DISEASE PROGRESSION, POOR PROGNOSIS, FREE SURVIVAL, EXPRESSION, RITUXIMAB, THERAPY, Internal medicine, SUBCUTANEOUS ALEMTUZUMAB, RITUXIMAB, Survival analysis, business.industry, DISEASE PROGRESSION, B-Cell, medicine.disease, Transplantation, Settore MED/15 - MALATTIE DEL SANGUE, POOR PROGNOSIS, Immunology, TERM FOLLOW UP, FREE SURVIVAL, business
Abstract

In 45, ≤ 60 years old patients with CLL and an adverse biologic profile, a front-line treatment with Fludarabine and Campath (Alemtuzumab(®)) was given. The overall response rate was 75.5%, the complete response rate (CR) 24.4% with the lowest CR rates, 16.7% and 8.3%, in 11q and 17p deleted cases. The 3-year progression-free survival (PFS) and overall survival were 42.5% and 79.9%, respectively. PFS was significantly influenced by CLL duration, beta2-microglobulin, and improved by post-remissional stem cell transplantation. Front-line fludarabine and alemtuzumab showed a manageable safety profile and evidence of a benefit in a small series of CLL patients with adverse biologic features.

Published
2014

6. Chlorambucil plus rituximab with or without maintenance rituximab as first-line treatment for elderly chronic lymphocytic leukemia patients

Author

Foà, R, Del Giudice, I, Cuneo, Antonio, Del Poeta, G, Ciolli, S, Di Raimondo, F, Lauria, F, Cencini, E, Rigolin, Gian Matteo, Cortelezzi, A, Nobile, F, Callea, V, Brugiatelli, M, Massaia, M, Molica, S, Trentin, L, Rizzi, R, Specchia, G, Di Serio, F, Orsucci, L, Ambrosetti, A, Montillo, M, Luigi Zinzani, P, Ferrara, F, Morabito, F, Angela Mura, M, Soriani, S, Peragine, N, Tavolaro, S, Bonina, S, Marinelli, M, Stefania De Propris, M, Della Starza, I, Piciocchi, A, Alietti, A, Runggaldier, Ej, Gamba, E, Romana Mauro, F, Chiaretti, S, Guarini, A., R. Foà, I. D. Giudice, A. Cuneo, G. D. Poeta, S. Ciolli, F. D. Raimondo, F. Lauria, E. Cencini, G. M. Rigolin, A. Cortelezzi, F. Nobile, V. Callea, M. Brugiatelli, M. Massaia, S. Molica, L. Trentin, R. Rizzi, G. Specchia, F. D. Serio, L. Orsucci, A. Ambrosetti, M. Montillo, P. L. Zinzani, F. Ferrara, F. Morabito, M. A. Mura, S. Soriani, N. Peragine, S. Tavolaro, S. Bonina, M. Marinelli, M. S. De, I. D. Starza, A. Piciocchi, A. Alietti, E. J. Runggaldier, E. Gamba, F. R. Mauro, S. Chiaretti, and A. Guarini

Subjects
Male, Murine-Derived, drug therapy/pathology, Male, Survival Analysis, Treatment Outcome, Antibodies, Disease-Free Survival, Drug Administration Schedule, Antibodies, Monoclonal, Murine-Derived, Antineoplastic Combined Chemotherapy Protocols, Monoclonal, 80 and over, 80 and over, Antibodie, Humans, therapeutic use, Chlorambucil, Chronic, Aged, Aged, 80 and over, Aged, Aged, Leukemia, Chlorambucil, Female, Induction Chemotherapy, Leukemia, Lymphocytic, Chronic, B-Cell, Rituximab, Survival Analysis, Treatment Outcome, Hematology, B-Cell, Lymphocytic, CLL, chlorambucil, administration /&/ dosage, Antineoplastic Combined Chemotherapy Protocol, administration /&/ dosage, Disease-Free Survival, Drug Administration Schedule, Female, Humans, Induction Chemotherapy, Leukemia, Settore MED/15 - Malattie del Sangue
Abstract

In a phase II trial, we evaluated chlorambucil and rituximab (CLB-R) as first-line induction treatment with or without R as maintenance for elderly chronic lymphocytic leukemia (CLL) patients. Treatment consisted of eight 28-day cycles of CLB (8 mg/m(2) /day, days 1-7) and R (day 1 of cycle 3, 375 mg/m(2) ; cycles 4-8, 500 mg/m(2) ). Responders were randomized to 12 8-week doses of R (375 mg/m(2) ) or observation. As per intention-to-treat analysis, 82.4\% (95\% CI, 74.25-90.46\%) of 85 patients achieved an overall response (OR), 16.5\% a complete response (CR), 2.4\% a CR with incomplete bone marrow recovery. The OR was similar across Binet stages (A 86.4\%, B 81.6\%, and C 78.6\%) and age categories (60-64 years, 92.3\%; 65-69, 85.2\%; 70-74, 75.0\%; ≥75, 81.0\%). CLB-R was well tolerated. After a median follow-up of 34.2 months, the median progression-free survival (PFS) was 34.7 months (95\% CI, 33.1-39.5). TP53 abnormalities, complex karyotype, and low CD20 gene expression predicted lack of response; SF3B1 mutation and BIRC3 disruption low CR rates. IGHV mutations significantly predicted PFS. R maintenance tended towards a better PFS than observation and was safe and most beneficial for patients in partial response and for unmutated IGHV cases. CLB-R represents a promising option for elderly CLL patients.

Published
2014

7. COVID-19 elicits an impaired antibody response against SARS-CoV-2 in patients with haematological malignancies

Author

Francesco Zaja, Filippo Gherlinzoni, Anna Maria Scattolin, Luca Arcaini, Roberto Cairoli, Mario Luppi, Carmen Fava, Patrizia Zappasodi, Matteo G. Della Porta, Monica Bocchia, Valeria Cardinali, Nicola Stefano Fracchiolla, Francesco Passamonti, Giuseppe Visani, M. Ladetto, Enrico Derenzini, Lorenza Bertù, Roberto Mina, Daniele Armiento, B. Mora, Anna Candoni, Alessandro Corso, A. M. Vannucchi, Paolo Corradini, Francesco Lanza, Pellegrino Musto, Agostino Tafuri, Carlo Visco, E. Coviello, Francesco Marchesi, Roberto M. Lemoli, Chiara Cattaneo, Alessandro Busca, Marco Salvini, Sara Galimberti, I. Romano, M. Merli, Mauro Krampera, Alessandra Romano, Paolo Grossi, Michele Cavo, E. O. La Barbera, Mauro Turrini, Livio Pagano, Adriano Venditti, Antonio Pinto, Patrizia Tosi, F. Farina, Riccardo Bruna, L. Petrucci, Massimo Massaia, Monia Marchetti, Carlo Gambacorti Passerini, Francesco Merli, Passamonti, F, Romano, A, Salvini, M, Merli, F, Porta, M, Bruna, R, Coviello, E, Romano, I, Cairoli, R, Lemoli, R, Farina, F, Venditti, A, Busca, A, Ladetto, M, Massaia, M, Pinto, A, Arcaini, L, Tafuri, A, Marchesi, F, Fracchiolla, N, Bocchia, M, Armiento, D, Candoni, A, Krampera, M, Luppi, M, Cardinali, V, Galimberti, S, Cattaneo, C, La Barbera, E, Mina, R, Lanza, F, Visani, G, Musto, P, Petrucci, L, Zaja, F, Grossi, P, Bertu, L, Pagano, L, Corradini, P, Derenzini, E, Marchetti, M, Scattolin, A, Corso, A, Tosi, P, Gherlinzoni, F, Gambacorti Passerini, C, Cavo, M, Fava, C, Turrini, M, Visco, C, Zappasodi, P, Merli, M, Mora, B, Vannucchi, A, Passamonti F., Romano A., Salvini M., Merli F., Porta M.G.D., Bruna R., Coviello E., Romano I., Cairoli R., Lemoli R., Farina F., Venditti A., Busca A., Ladetto M., Massaia M., Pinto A., Arcaini L., Tafuri A., Marchesi F., Fracchiolla N., Bocchia M., Armiento D., Candoni A., Krampera M., Luppi M., Cardinali V., Galimberti S., Cattaneo C., La Barbera E.O., Mina R., Lanza F., Visani G., Musto P., Petrucci L., Zaja F., Grossi P.A., Bertu L., Pagano L., Corradini P., Derenzini E., Marchetti M., Scattolin A.M., Corso A., Tosi P., Gherlinzoni F., Passerini C.G., Cavo M., Fava C., Turrini M., Visco C., Zappasodi P., Merli M., Mora B., Vannucchi A.M., Passamonti, F., Romano, A., Salvini, M., Merli, F., Porta, M. G. D., Bruna, R., Coviello, E., Romano, I., Cairoli, R., Lemoli, R., Farina, F., Venditti, A., Busca, A., Ladetto, M., Massaia, M., Pinto, A., Arcaini, L., Tafuri, A., Marchesi, F., Fracchiolla, N., Bocchia, M., Armiento, D., Candoni, A., Krampera, M., Luppi, M., Cardinali, V., Galimberti, S., Cattaneo, C., La Barbera, E. O., Mina, R., Lanza, F., Visani, G., Musto, P., Petrucci, L., Zaja, F., Grossi, P. A., Bertu, L., Pagano, L., Corradini, P., Derenzini, E., Marchetti, M., Scattolin, A. M., Corso, A., Tosi, P., Gherlinzoni, F., Passerini, C. G., Cavo, M., Fava, C., Turrini, M., Visco, C., Zappasodi, P., Merli, M., Mora, B., and Vannucchi, A. M.

Subjects
Male, Myeloid, Antibodies, Viral, Gastroenterology, SARS‐CoV‐2, 80 and over, Covid-19, SARS-CoV-2, leukemia, lymphoma, myeloma, Viral, Covid‐19, Aged, 80 and over, biology, Hematology, Plasma cell neoplasm, Middle Aged, Adult, Aged, COVID-19, Female, Hematologic Neoplasms, Humans, Immunoglobulin G, Seroconversion, Young Adult, Antibody Formation, Leukemia, medicine.anatomical_structure, Antibody, Human, medicine.medical_specialty, Short Report, Antibodies, NO, Chemoimmunotherapy, Internal medicine, medicine, Hematologic Neoplasm, business.industry, Odds ratio, Settore MED/15, medicine.disease, Covid-19, SARS-CoV-2, leukemia, lymphoma, myeloma, Lymphoma, Settore MED/15 - MALATTIE DEL SANGUE, biology.protein, business
Abstract

COVID-19 is associated with high mortality in patients with haematological malignancies (HM) and rate of seroconversion is unknown. The ITA-HEMA-COV project (NCT04352556) investigated patterns of seroconversion for SARS-CoV-2 IgG in patients with HMs. A total of 237 patients, SARS-CoV-2 PCR-positive with at least one SARS-CoV-2 IgG test performed during their care, entered the analysis. Among these, 62 (26·2%) had myeloid, 121 (51·1%) lymphoid and 54 (22·8%) plasma cell neoplasms. Overall, 69% of patients (164 of 237) had detectable IgG SARS-CoV-2 serum antibodies. Serologically negative patients (31%, 73 of 237) were evenly distributed across patients with myeloid, lymphoid and plasma cell neoplasms. In the multivariable logistic regression, chemoimmunotherapy [odds ratio (OR), 3·42; 95% confidence interval (CI), 1·04–11·21; P=0·04] was associated with a lower rate of seroconversion. This effect did not decline after 180days from treatment withdrawal (OR, 0·35; 95% CI: 0·11–1·13; P=0·08). This study demonstrates a low rate of seroconversion in HM patients and indicates that treatment-mediated immune dysfunction is the main driver. As a consequence, we expect a low rate of seroconversion after vaccination and thus we suggest testing the efficacy of seroconversion in HM patients.

Published
2021

8. A prognostic model for patients with lymphoma and COVID-19: a multicentre cohort study

Author

Francesco Merli, Carlo Visco, Annarita Conconi, Daniele Vallisa, Elettra Ortu La Barbera, Sara Galimberti, Roberto Mina, Marianna Sassone, Anna Guidetti, Adriano Venditti, Alessandro Corso, Francesco Marchesi, Pellegrino Musto, Agostino Tafuri, Valentina Bonuomo, Filippo Gherlinzoni, Francesco Lanza, Monia Marchetti, Safaa M. Ramadan, Marco Salvini, Massimo Massaia, Elisa Coviello, Alessandro Busca, Luigi Petrucci, Daniele Armiento, Mauro Turrini, Alessandra Romano, Chiara Cattaneo, Francesco Passamonti, Matteo G. Della Porta, Anna Candoni, Luigi Rigacci, Luca Arcaini, Livio Trentin, Valeria Cardinali, Maria Chiara Tisi, Carmine Selleri, Carlo Gambacorti-Passerini, Andrés J.M. Ferreri, Patrizia Tosi, Riccardo Bruna, Mauro Krampera, Antonio Cuneo, Nicola Stefano Fracchiolla, Daniela Cilloni, Lorenza Bertù, Paolo Corradini, Annamaria Scattolin, Roberto Cairoli, Giuseppe Visani, Domenico Penna, Marco Ladetto, Antonello Pinto, Michele Cavo, Monica Bocchia, Sofia Pilerci, Luigi Marcheselli, Visco, C, Marcheselli, L, Mina, R, Sassone, M, Guidetti, A, Penna, D, Cattaneo, C, Bonuomo, V, Busca, A, Ferreri, A, Bruna, R, Petrucci, L, Cairoli, R, Salvini, M, Bertu, L, Ladetto, M, Pilerci, S, Pinto, A, Ramadan, S, Marchesi, F, Cavo, M, Arcaini, L, Coviello, E, Romano, A, Musto, P, Massaia, M, Fracchiolla, N, Marchetti, M, Scattolin, A, Tisi, M, Cuneo, A, Porta, M, Trentin, L, Turrini, M, Gherlinzoni, F, Tafuri, A, Galimberti, S, Bocchia, M, Cardinali, V, Cilloni, D, Corso, A, Armiento, D, Rigacci, L, La Barbera, E, Gambacorti Passerini, C, Visani, G, Vallisa, D, Venditti, A, Selleri, C, Conconi, A, Tosi, P, Lanza, F, Candoni, A, Krampera, M, Corradini, P, Passamonti, F, and Merli, F

Subjects
Adult, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Aged, Aged, 80 and over, Cohort Studies, Humans, Middle Aged, Prognosis, SARS-CoV-2, Young Adult, COVID-19, Lymphoma, Lymphocyte, medicine.medical_treatment, Disease, NO, lymphoma, COVID-19, multicentre cohort study, SARS-CoV-2, Internal medicine, medicine, 80 and over, lymphoma, covid-19, anti-cd20, business.industry, Regular Article, Immunosuppression, Hematology, Settore MED/15, medicine.disease, medicine.anatomical_structure, Cohort, Prognostic model, business, Cohort study
Abstract

Lymphoma represents a heterogeneous hematological malignancy (HM), which is characterized by severe immunosuppression. Patients diagnosed of coronavirus disease 2019 (COVID-19) during the course of HM have been described to have poor outcome, with only few reports specifically addressing lymphoma patients. Here, we investigated the clinical behavior and clinical parameters of a large multicenter cohort of adult patients with different lymphoma subtypes, with the aim of identifying predictors of death. The study included 856 patients, of whom 619 were enrolled prospectively in a 1-year frame and were followed-up for a median of 66 days (range 1-395). Patients were managed as outpatient (not-admitted cohort, n = 388) or required hospitalization (n = 468), and median age was 63 years (range 19-94). Overall, the 30- and 100-days mortality was 13% (95% confidence interval (CI), 11% to 15%) and 23% (95% CI, 20% to 27%), respectively. Antilymphoma treatment, including anti-CD20 containing regimens, did not impact survival. Patients with Hodgkin’s lymphoma had the more favorable survival, but this was partly related to significantly younger age. The time interval between lymphoma diagnosis and COVID-19 was inversely related to mortality. Multivariable analysis recognized 4 easy-to-use factors (age, gender, lymphocyte, and platelet count) that were associated with risk of death, both in the admitted and in the not-admitted cohort (HR 3.79 and 8.85 for the intermediate- and high-risk group, respectively). Overall, our study shows that patients should not be deprived of the best available treatment of their underlying disease and indicates which patients are at higher risk of death. This study was registered with ClinicalTrials.gov, NCT04352556.

Published
2022

9. SARS-CoV-2 infection in patients with chronic lymphocytic leukemia: The Italian Hematology Alliance on COVID-19 cohort

Author

Michele Merli, Isacco Ferrarini, Francesco Merli, Alessandro Busca, Roberto Mina, Brunangelo Falini, Riccardo Bruna, Roberto Cairoli, Monia Marchetti, Alessandra Romano, Michele Cavo, Luca Arcaini, Livio Trentin, Chiara Cattaneo, Enrico Derenzini, Nicola Stefano Fracchiolla, Francesco Marchesi, Annamaria Scattolin, Atto Billio, Monica Bocchia, Massimo Massaia, Carlo Gambacorti‐Passerini, Francesca Romana Mauro, Massimo Gentile, Sara Mohamed, Matteo Giovanni Della Porta, Elisa Coviello, Daniela Cilloni, Giuseppe Visani, Augusto Bramante Federici, Maria Chiara Tisi, Laura Cudillo, Sara Galimberti, Filippo Gherlinzoni, Livio Pagano, Anna Guidetti, Lorenza Bertù, Paolo Corradini, Francesco Passamonti, Carlo Visco, Merli, M, Ferrarini, I, Merli, F, Busca, A, Mina, R, Falini, B, Bruna, R, Cairoli, R, Marchetti, M, Romano, A, Cavo, M, Arcaini, L, Trentin, L, Cattaneo, C, Derenzini, E, Fracchiolla, N, Marchesi, F, Scattolin, A, Billio, A, Bocchia, M, Massaia, M, Gambacorti-Passerini, C, Mauro, F, Gentile, M, Mohamed, S, Della Porta, M, Coviello, E, Cilloni, D, Visani, G, Federici, A, Tisi, M, Cudillo, L, Galimberti, S, Gherlinzoni, F, Pagano, L, Guidetti, A, Bertu, L, Corradini, P, Passamonti, F, and Visco, C

Subjects
Settore MED/15 - MALATTIE DEL SANGUE, Cancer Research, BTK inhibitors, Oncology, chronic lymphocytic leukemia, COVID-19, outcome, SARS-CoV-2, BTK inhibitor, Hematology, General Medicine
Abstract

COVID-19, the disease caused by SARS-CoV-2, is still afflicting thousands of people across the globe. Few studies on COVID-19 in chronic lymphocytic leukemia (CLL) are available. Here, we analyzed data from the CLL cohort of the Italian Hematology Alliance on COVID-19 (NCT04352556), which included 256 CLL patients enrolled between 25 February 2020 and 1 February 2021. Median age was 70 years (range 38–94) with male preponderance (60.1%). Approximately half of patients (n = 127) had received at least one line of therapy for CLL, including 108 (83.7%) who were on active treatment at the time of COVID-19 or received their last therapy within 12 months. Most patients (230/256, 89.9%) were symptomatic at COVID-19 diagnosis and the majority required hospitalization (n = 176). Overall, after a median follow-up of 42 days (IQR 24–96), case fatality rate was 30.1%, and it was 37.5% and 24.4% in the first (25 February 2020–22 June 2020) and second wave (23 June 2020–1 February 2021), respectively (p = 0.03). At multivariate analysis, male sex (HR 1.82, 95% CI 1.03–3.24, p = 0.04), age over than 70 years (HR 2.23, 95% CI 1.23–4.05, p = 0.01), any treatment for CLL given in the last 12 months (HR 1.72, 95% CI 1.04–2.84, p = 0.04) and COVID-19 severity (severe: HR 5.66, 95% CI 2.62–12.33, p < 0.0001; critical: HR 15.99, 95% CI 6.93–36.90, p < 0.0001) were independently associated with poor survival. In summary, we report a dismal COVID-related outcome in a significant fraction of CLL patients, that can be nicely predicted by clinical parameters.

Published
2022

10. Practical management of ibrutinib in the real life: Focus on atrial fibrillation and bleeding

Author

Marco Montillo, Paolo Corradini, Roberto Marasca, Pier Luigi Zinzani, Maurizio Martelli, Giuseppe Boriani, Francesca Romana Mauro, Giorgio Minotti, Antonio Cuneo, Stefano Molica, Gianluca Gaidano, Alessandra Tedeschi, Robin Foà, Anna Falanga, Antonio Pinto, Massimo Massaia, Umberto Vitolo, Paolo Ghia, Boriani, Giuseppe, Corradini, Paolo, Cuneo, Antonio, Falanga, Anna, Foà, Robin, Gaidano, Gianluca, Ghia, Paolo Prospero, Martelli, Maurizio, Marasca, Roberto, Massaia, Massimo, Mauro, Francesca Romana, Minotti, Giorgio, Molica, Stefano, Montillo, Marco, Pinto, Antonio, Tedeschi, Alessandra, Vitolo, Umberto, Zinzani, Pier Luigi, Boriani, G, Corradini, P, Cuneo, A, Falanga, A, Foà, R, Gaidano, G, Ghia, P, Martelli, M, Marasca, R, Massaia, M, Mauro, F, Minotti, G, Molica, S, Montillo, M, Pinto, A, Tedeschi, A, Vitolo, U, and Zinzani, P

Subjects
Chronic lymphocytic leukaemia, Cancer Research, 030204 cardiovascular system & hematology, Atrial fibrillation, Bleeding, Ibrutinib, Hematology, Oncology, chemistry.chemical_compound, 0302 clinical medicine, Piperidines, Risk Factors, Atrial Fibrillation, Medicine, Randomized Controlled Trials as Topic, Clinical Trials as Topic, Anticoagulant, Waldenstrom macroglobulinemia, atrial fibrillation, bleeding, chronic lymphocytic leukaemia, ibrutinib, General Medicine, Anti-Arrhythmia Agents, Anticoagulants, Hematologic Neoplasms, Hemorrhage, Humans, Platelet Aggregation Inhibitors, Pyrazoles, Pyrimidines, Anti-Arrhythmia Agent, 030220 oncology & carcinogenesis, Platelet aggregation inhibitor, Risk assessment, Human, medicine.medical_specialty, medicine.drug_class, NO, 03 medical and health sciences, Internal medicine, Hematologic Neoplasm, Contraindication, business.industry, Risk Factor, Platelet Aggregation Inhibitor, Adenine, medicine.disease, Pyrimidine, chemistry, Pyrazole, Mantle cell lymphoma, business
Abstract

The Bruton tyrosine kinase inhibitor ibrutinib (IB) has attained an important role in the treatment of patients with chronic lymphocytic leukaemia, mantle cell lymphoma, and Waldenström macroglobulinemia, significantly improving clinical outcomes. However, IB therapy has been associated with an increased risk of atrial fibrillation (AF) and bleeding. We report on the expert opinion that a group of Italian haematologists, cardiologists, and pharmacologists jointly released to improve the practical management of patients at risk for AF and bleeding during treatment with IB. A proper pretreatment assessment to identify patients who are at a higher risk, careful choice of concomitant drugs, regular monitoring, and multispecialist approach were characterized as the main principles of clinical management of these patients. For patients developing AF, anticoagulant and antiarrhythmic therapy must be guided by considerations about efficacy, safety, and risk of pharmacokinetic interactions with IB. For patients experiencing bleeding or requiring procedures that increase the risk of bleeding, considerations about platelet turnover, IB-related platelet dysfunctions, and bleeding worsening by concomitant anticoagulants or antiplatelet agents provide clues to manage bleeding. Overall, AF and bleeding are manageable clinical events in patients receiving IB, not requiring drug interruption in most cases. Preexisting AF should not represent an absolute contraindication to IB therapy. For each patient candidate for IB, strategies of risk assessment and mitigation may allow to exploit the life-saving effects of in chronic lymphocytic leukaemia and mantle cell lymphoma.

Published
2018

11. Chlorambucil plus rituximab as front-line therapy for elderly and/or unfit chronic lymphocytic leukemia patients: Correlation with biologically-based risk stratification

Author

Barbara Vannata, Antonio Cuneo, Roberto Marasca, Idanna Innocenti, Giovanni D'Arena, Marta Coscia, Alfonso Piciocchi, P. Galieni, Luca Laurenti, Giovanni Del Poeta, Anna Marina Liberati, Sonia Maria Orlando, Donato Mannina, Gabriele Pozzato, Riccardo Boncompagni, Stefano Molica, Francesca Romana Mauro, Massimo Massaia, Filomena Russo, Dimitar G. Efremov, Robin Foà, Stefania Ciolli, Donatella Vincelli, Francesco Autore, Laurenti, L., Innocenti, I., Autore, F., Ciolli, S., Mauro, F. R., Mannina, D., Del Poeta, G., D'Arena, G., Massaia, M., Coscia, M., Molica, S., Pozzato, G., Efremov, D. G., Vannata, B., Marasca, R., Galieni, P., Cuneo, A., Orlando, S., Piciocchi, A., Boncompagni, R., Vincelli, D., Liberati, A. M., Russo, F., and Foa, R.

Subjects
Oncology, medicine.medical_specialty, Chronic lymphocytic leukemia, MEDLINE, Risk Assessment, NO, 03 medical and health sciences, 0302 clinical medicine, Chlorambucil, Chronic Lymphocytic Leukemia, Rituximab, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, 80 and over, Humans, Chronic, Online Only Articles, Aged, Aged, 80 and over, Hematology, Leukemia, Antineoplastic Combined Chemotherapy Protocol, business.industry, Leukemia, Lymphocytic, Chronic, B-Cell, Middle Aged, B-Cell, Front line, Settore MED/15, medicine.disease, Lymphocytic, Settore MED/15 - MALATTIE DEL SANGUE, 030220 oncology & carcinogenesis, business, Risk assessment, CLL, 030215 immunology, medicine.drug, Human
Abstract

First-line treatment for young/fit patients with chronic lymphocytic leukemia (CLL) is the combination of fludarabine, cyclophosphamide and rituximab (FCR), which has improved these patients’ progression-free survival and overall survival,1 but is poorly tolerated by elderly patients or patients with comorbidities.2 Such patients have been historically treated with chlorambucil, which is well tolerated but does not improve survival.3 To improve outcomes, chlorambucil has been combined with anti-CD20 monoclonal antibodies. Three prospective studies4–6 and one retrospective7 one investigated the combination of chlorambucil with rituximab (Chl-R) as front-line treatment for elderly CLL patients or for younger patients unsuitable for fludarabine-based therapies. Overall response rates ranging from 66% to 84% have been reported, with complete response rates of 8–26% and progression-free survival from 16.3 to 34.7 months.

Published
2017

12. A phase II multi-center trial of pentostatin plus cyclophosphamide with ofatumumab in older previously untreated chronic lymphocytic leukemia patients

Author

Ester Orlandi, Marco Montillo, Marianna Rossi, Lydia Scarfò, Giulia Quaresmini, Gianluca Gaidano, Agostino Cortelezzi, Guido Nador, Antonella Anastasia, Lorenzo De Paoli, Davide Rossi, Marina Motta, Daniela Dalceggio, Anna Maria Frustaci, Fausto Rossini, Marta Coscia, Massimo Massaia, Alessandro Rambaldi, Alessandra Tedeschi, Roberto Cairoli, Paola Picardi, Tedeschi, A, Rossi, D, Motta, M, Quaresmini, G, Rossi, M, Coscia, M, Anastasia, A, Rossini, F, Cortelezzi, A, Nador, G, Scarfo, L, Cairoli, R, Frustaci, A, Dalceggio, D, Picardi, P, de Paoli, L, Orlandi, E, Rambaldi, A, Massaia, M, Gaidano, G, and Montillo, M

Subjects
Oncology, medicine.medical_specialty, Chronic lymphocytic leukemia, Cyclophosphamide, Elderly, Ofatumumab, Pentostatin, Hematology, Cyclophosphamide, Chronic lymphocytic leukemia, Ofatumumab, chemistry.chemical_compound, Elderly, immune system diseases, hemic and lymphatic diseases, Internal medicine, medicine, Pentostatin, Online Only Articles, business.industry, Hematology, medicine.disease, Fludarabine, Leukemia, chemistry, Immunology, Rituximab, business, Untreated Chronic Lymphocytic Leukemia, medicine.drug
Abstract

There is a significant need to develop an efficient treatment, without sacrificing efficacy, for older fit patients with chronic lymphocytic leukemia (CLL) as fludarabine, cyclophosphamide and rituximab (FCR) have very often led to treatment-related toxicities, causing delay or therapy

Published
2015

13. Intermediate-dose melphalan improves survival of myeloma patients aged 50 to 70: results of a randomized controlled trial

Author

Patrizia Falco, Cecilia Rus, Mariella Grasso, Vito Michele Lauta, Maria Teresa Petrucci, Angelo Michele Carella, Martina Nunzi, Antonio Capaldi, Tommaso Caravita, Anna Maria Barbui, Federica Cavallo, Fausto Rossini, Pellegrino Musto, Vincenzo Callea, Alessandra Bertola, Franco Mandelli, Massimo Massaia, Giovannino Ciccone, Mario Boccadoro, Sara Bringhen, Antonio Palumbo, Tommasina Guglielmelli, Franco Dammacco, Anna Marina Liberati, Patrizia Pregno, Cesare Bergonzi, Enrico Pogliani, Palumbo, A, Bringhen, S, Petrucci, M, Musto, P, Rossini, F, Nunzi, M, Lauta, V, Bergonzi, C, Barbui, A, Caravita, T, Capaldi, A, Pregno, P, Guglielmelli, T, Grasso, M, Callea, V, Bertola, A, Cavallo, F, Falco, P, Rus, C, Massaia, M, Mandelli, F, Carella, A, Pogliani, E, Liberati, A, Dammacco, F, Ciccone, G, and Boccadoro, M

Subjects
Male, Melphalan, medicine.medical_treatment, DIAGNOSED MULTIPLE-MYELOMA, COMBINATION CHEMOTHERAPY, Salvage therapy, THERAPY, Biochemistry, Gastroenterology, MED/15 - MALATTIE DEL SANGUE, Prednisone, FINAL ANALYSIS, Medicine, Multiple myeloma, Standard treatment, Hematology, Middle Aged, Chemotherapy regimen, Treatment Outcome, STEM-CELL TRANSPLANTATION, AUTOLOGOUS TRANSPLANTATION, INTENSIVE MELPHALAN, TANDEM TRANSPLANTS, STAGING SYSTEM, 200 MG/M(2), Female, Survival Analysi, Multiple Myeloma, Human, medicine.drug, medicine.medical_specialty, Immunology, Disease-Free Survival, Follow-Up Studie, Internal medicine, Humans, Antineoplastic Agents, Alkylating, Aged, Salvage Therapy, Chemotherapy, business.industry, Cell Biology, medicine.disease, Survival Analysis, Surgery, Regimen, business, Follow-Up Studies
Abstract

High-dose therapy is an effective standard treatment for multiple myeloma patients. Evidence that intermediate-dose therapy improves survival is limited. At diagnosis, about 70% of patients are older than 65. Intermediate-dose regimen is very well tolerated in older patients. In a multicenter study, 194 patients were randomized to receive at diagnosis either conventional chemotherapy (6 courses of oral melphalan and prednisone [MP]) or intermediate-dose therapy (2 courses of melphalan at 100 mg/m(2) [MEL100]) with stem cell support. Response rate was higher after MEL100. Near-complete remission (nCR) was 6% after MP and 25% after MEL100 (P = .0002). At 3 years, MEL100 increased event-free survival (EFS) from 16% to 37% and overall survival (OS) from 62% to 77% (P < .001). Similar results were observed in patients aged 65 to 70: nCR was 8% after MP and 25% after MEL100 (P = .05); at 3 years, MEL100 improved EFS from 18% to 31% (P = .01) and OS from 58% to 73% (P = .01). Patients aged 65 to 70 had a median OS of 37.2 months (MP) versus 58 months (MEL100). Intermediate-dose melphalan improves response rate, EFS, and OS in myeloma patients, specifically in those aged 65 to 70. It constitutes a more effective first-line regimen than standard treatment for elderly patients.

Published
2004
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14. Bendamustine and subcutaneous Alemtuzumab combination is an effective treatment in relapsed/refractory chronic lymphocytic leukemia patients

Author

Lorenzo De Paoli, Ester Orlandi, Marina Motta, Nicola Cascavilla, Andrea Gallamini, Anna Maria Frustaci, Davide Rossi, Enrica Morra, Alessandra Tedeschi, Paolo Ghia, Massimo Massaia, Marta Coscia, Marco Montillo, Gianluca Gaidano, Valeria Belsito Petrizzi, Michele Nichelatti, Montillo, M, Tedeschi, A, Gaidano, G, Coscia, M, Petrizzi, Vb, Orlandi, E, Cascavilla, N, Ghia, PAOLO PROSPERO, Motta, M, Gallamini, A, Frustaci, Am, Rossi, D, De Paoli, L, Nichelatti, M, Morra, E, and Massaia, M.

Subjects
Adult, Male, Oncology, Bendamustine, medicine.medical_specialty, Bendamustine, alemtuzumab, chronic lymphocytic leukemia, Adolescent, Cyclophosphamide, Injections, Subcutaneous, Chronic lymphocytic leukemia, Pharmacology, Antibodies, Monoclonal, Humanized, Drug Administration Schedule, Recurrence, hemic and lymphatic diseases, Internal medicine, medicine, alemtuzumab, Bendamustine Hydrochloride, Humans, Effective treatment, Online Only Articles, Antineoplastic Agents, Alkylating, Survival analysis, Aged, business.industry, Hematology, Middle Aged, medicine.disease, Leukemia, Lymphocytic, Chronic, B-Cell, Survival Analysis, Fludarabine, Drug Combinations, Regimen, Treatment Outcome, Injections, Intravenous, Nitrogen Mustard Compounds, Alemtuzumab, chronic lymphocytic leukemia, Female, business, medicine.drug
Abstract

Alemtuzumab has been extensively used in the salvage setting of chronic lymphocytic leukemia (CLL) resulting less effective on bulky lymphadenopathy.[1][1] Higher response rates have been achieved when combined with fludarabine and cyclophosphamide (FC), but this regimen has led to some safety

Published
2014

15. A PHASE II MULTI-CENTER TRIAL OF PENTOSTATIN PLUS CYCLOPHOSPHAMIDE WITH OFATUMUMAB (PCO) IN OLDER PREVIOUSLY UNTREATED CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) PATIENTS

Author

Montillo, M, Rossi, D, Motta, M, Quaresmini, G, Rossi, M, Coscia, Marta, Anastasia, A, Rossini, F, Cortellezzi, A, Nador, G, Scarfo, L, Cairoli, R, Frustaci, Am, Dal Ceggio, D, Picardi, P, De Paoli, L, Orlandi, E, Rambaldi, A, Morra, E, Massaia, Massimo, Tedeschi, A., Montillo, M, Rossi, D, Motta, M, Quaresmini, G, Rossi, M, Coscia, M, Anastasia, A, Rossini, F, Cortellezzi, A, Nador, N, Scarfo, L, Cairoli, R, Frustaci, A, Dal Ceggio, D, Picardi, P, De Paoli, L, Orlandi, E, Rambaldi, A, Morra, M, Massaia, M, and Tedeschi, A

Subjects
hematology
Published
2014

16. A randomized, open-label, multicentre, phase 2/3 study to evaluate the safety and efficacy of lumiliximab in combination with fludarabine, cyclophosphamide and rituximab versus fludarabine, cyclophosphamide and rituximab alone in subjects with relapsed chronic lymphocytic leukaemia

Author

Awan, Farrukh T, Hillmen, Peter, Hellmann, Andrzej, Robak, Tadeusz, Hughes, Steven G., Trone, Denise, Shannon, Megan, Flinn, Ian W., Byrd, John C., Riveros, Dardo, Pavlovsky, Santiago, Iastrebner, Claudio M., Carney, Dennis A., Deveridge, Sandra, Durrant, Simon, Hahn, Uwe H., Hertzberg, Mark, Leahy, Michael F., David, Ma, Marlton, Paula, Mulligan, Stephen, Opat, Stephen S., Tiley, Campbell, Wickham, Nicholas W., Cannell, Paul, Gatalano, John, Catalano, John, Cull, Gavin, Luen B., To, Hopfinger, Georg, Jager, Ulrich, Linkesch, Werner, Petzer, Andreas, Schwarzmeier, Josef, Steurer, Michael, Greil, Richard, Bememan, Zwi, Bosly, Andre, Bron, Dominique, Janssens, Ann, Offner, Fritz, Van Den Neste, Eric W., Ka Lung, Wu, Van Hoof, Achiel, Maiolino, Angelo, Pinczowski, Helio, Zanichelli, Maria A., Pereira, Juliana, Larratt, Loree, Spaner, David, Howson Jan, Kang, Chen, Christine I., Cantin, Guy, Fernandez, Louis A., Fraser, Graeme, Mayer, Jiri, Trneny, Marek, Jebavy, Ladislav, Bordessoule, Dominique, Lamy, Thierry, Milpied, Noel, Truchan Graczyk, Malgorzata, Eghbali, Houchingue, Karsenti, Jean Michel, Celigny, Philippe Solal, Mans, Le, Cazin, Bruno, Gyan, Emmanuel, Lepretre, Stephane, Bergmann, Lothar, Tsionos, Konstantinos, Lokeshwar, Nilesh M., Agarwal, Mohan B., Ross, Cecil R., Deshmukh, Chetan D., Narayanan, Geetha, Raina, Vinod, Bondarde, Shailesh A., Shah, Bhavin A., Bairey, Osnat, Tikva, Petach, Shvidel, Lev, Ambrosetti, Achille, Rossi, Policlinico G. B., Angelucci, Emanuele, Carella, Angelo M., Massaia, Massimo, Zinzani, Pier L., Caligaris Cappio, Federico, Foa, Roberto, Gaidano, Gianluca, della Caritá, A. O. Maggiore, Leone, Giuseppe, Santoro, Armando, Griskevicius, Laimonas, Jurgutis, Romualdas, Baker, Bartrum W., Hawkins, Timothy, Corbett, Gillian M., Ganly, Peter, D'Souza, Alvyn B., Deptala, Andrzej, Holowiecki, Jerzy, Kloczko, Janusz, Skotnicki, Aleksander, Zdziarska, Barbara, Kyrcz Krzemien, Slawomira, Dmoszynska, Anna, Moreira, Anna, Pereira, Ana P., Colita, Andrei, Moicean, Andreea D., Vasilica, Mariana, Danaila, Catalin, Gheorghita, Emanuil, Pavlov, Vyacheslav V., Rossiev, Viktor A., Konstantinova, Tatiana, Samoilova, Olga S., Novgorod, Nizhniy, Shelekhova, Tatyana, Zaritsky, Andrey Y., Abdulkadyrov, Kudrat M., Zyuzgin, Ilya S., Pristupa, Alexander S., Loscertales, Javier, Vidal, Joan Besalduch, de Mallorca, Palma, Gonzalez, Marcos, Ortuno, Francisco, Giraldo, Pilar, Nathwani, Amit, Agrawal, Samir G., Rule, Simon, Dearden, Claire E., Bloor, Adrian J., Haynes, Andrew, Singer, Charles, Boclek, Robert G., Bosserman, Linda D., Chan, David, Davidson, Sheldon J., Dichmann, Robert A., Farber, Charles, Hart, Lowell, Hermann, Robert, Eddie, Hu, Janakiraman, Nalini, Jonas, William, Liem, Kiem D., Mcintyre, Rosemary E., O'Brien, Susan, Patel, Giribala, Rado, Thomas, Schilder, Russell, Smith, Scott E., Stock, Wendy, Turturro, Francesco, Venugopal, Parameswaran, Anderson, Thomas C., Berry, William, Boyd, Thomas E., Byrd, John, Cooper, Maureen, Flinn, Ian, Gersh, Robert, Gordon, David, Guzley, Gregory J., Wilks, Sharon T., Klein, Andreas, Krauss, John C., Lister, John, Mandell, Lance, Molina, Arthur, Cooper, Barry, Pendergrass, Kelly B., Reeder, Craig, Savin, Michael A., Spitzer, Gary, Tuscano, Joseph M., Vandeventer, Hendrik, Eradat, Herbert A., Masood, Aisha, Mena, Raul, F. T. Awan, P. Hillmen, A. Hellmann, T. Robak, S. G. Hughe, D. Trone, M. Shannon, I. W. Flinn, J. C. Byrd, L. U. C., and Riveros D, Iastrebner CM, Carney DA, Deveridge S, Durrant S, Hahn UH, Hertzberg M, Leahy MF, Ma D, Marlton P, Mulligan S, Opat SS, Tiley C, Wickham NW, Cannell P, Gatalano J, Cull G, B To L, Catalano J, Wickham NW, Hopfinger G, Jager U, Linkesch W, Petzer A, Schwarzmeier J, Steurer M, Greil R, Bememan Z, Bosly A, Bron D, Janssens A, Offner F, Van Den Neste EW, Wu KL, Van Hoof A, Maiolino A, Pinczowski H, Zanichelli MA, Pereira J, Larratt L, Spaner D, Howson-Jan K, Chen CI, Fernandez LA, Fraser G, Mayer J, Trneny M, Jebavy L, Bordessoule D, Lamy T, Milpied N, Eghbali H, Karsenti JM, Celigny PS, Cazin B, Gyan E, Lepretre S, Bergmann L, Tsionos K, Lokeshwar NM, Agarwal MB, Ross CR, Deshmukh CD, Narayanan G, Raina V, Bondarde SA, Shah BA, Bairey O, Ben-Yehuda D, Shvidel L, Ambrosetti A, Angelucci E, Carella AM, Massaia M, Zinzani PL, Caligaris-Cappio F, Foa R, Gaidano G, Leone G, Santoro A, Griskevicius L, Jurgutis R, Baker BW, Hawkins T, Corbett GM, Ganly P, D'Souza AB, Deptala A, Hellmann A, Holowiecki J, Kloczko J, Skotnicki A, Zdziarska B, Robak T, Dmoszynska A, Moreira I, Pereira AP, Colita A, Moicean AD, Gheorghita E, Vasilica M, Pavlov VV, Rossiev VA, Konstantinova T, Samoilova OS, Novgorod N, Shelekhova T, Zaritsky AY, Abdulkadyrov KM, Zyuzgin IS, Pristupa AS, Loscertales J, Casado LF, Gonzalez M, Ortuno F, Giraldo P, Servet M, Nathwani A, Howson-Jan K, Agrawal SG, Hillmen P, Rule S, Dearden CE, Bloor AJ, Haynes A, Singer C, Boclek RG, Bosserman LD, Chan D, Davidson SJ, Dichmann RA, Farber C, Guzley GJ, Hermann R, Hu E, Janakiraman N, Jonas W, Liem KD, Mcintyre RE, O'Brien S, Patel G, Rado T, Schilder R, Smith SE, Stock W, Turturro F, Venugopal P, Berry W, Boyd TE, Byrd J, Cooper M, Flinn I, Gersh R, Gordon D, Wilks ST, Klein A, Krauss JC, Lister J, Mandell L, Molina A, Pendergrass KB, Reeder C, Savin MA, Spitzer G, Tuscano JM, van Deventer H, Eradat HA, Cooper B, Masood A, Mena R.

Subjects
Oncology, Male, Chronic lymphocytic leukaemia, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], Pharmacology, Antibodies, Monoclonal, Murine-Derived, Recurrence, hemic and lymphatic diseases, Monoclonal, Antineoplastic Combined Chemotherapy Protocols, 80 and over, Medicine, drug therapy, Male, Middle Aged, Recurrence, Vidarabine, Chronic, Aged, 80 and over, Leukemia, Medicine (all), Antibodies, Monoclonal, Hematology, Middle Aged, Adult, Aged, Aged, Lymphocytic, Fludarabine, Tolerability, Small lymphocytic lymphoma, administration /&/ dosage/adverse effects, Female, Humans, Leukemia, Rituximab, Female, Vidarabine, medicine.drug, Adult, Murine-Derived, medicine.medical_specialty, Cyclophosphamide, chemical and pharmacologic phenomena, CD23, Lumiliximab, Aged, Humans, Leukemia, Lymphocytic, Chronic, B-Cell, Antibodies, chronic lymphocytic leukaemia, lumiliximab, small lymphocytic lymphoma, Internal medicine, administration /&/ dosage/adverse effects/analogs /&/ derivatives, 80 and over, Antibodie, Adverse effect, Lymphocytic leukaemia, business.industry, administration /&/ dosage/adverse effects, Antibodie, B-Cell, administration /&/ dosage/adverse effects, Cyclophosphamide, Interim analysis, administration /&/ dosage/adverse effects, Antineoplastic Combined Chemotherapy Protocol, business
Abstract

Item does not contain fulltext Lumiliximab is a chimeric monoclonal antibody that targets CD23 on the surface of chronic lymphocytic leukaemia (CLL) B-cells. Early phase clinical studies with lumiliximab alone and in combination with fludarabine, cyclophosphamide and rituximab (FCR) established its potential efficacy and tolerability. The 152CL201 trial [Lumiliximab with fludarabine, cyclophosphamide and rituximab (FCR) versus FCR alone in subjects with relapsed CLL; LUCID] was a phase 2/3, randomized (1:1), open-label, multicentre study of lumiliximab in combination with FCR versus FCR alone in patients with relapsed CLL. Six hundred and twenty-seven patients were randomized to either arm. Overall the combination of lumiliximab with FCR was not significantly better than FCR alone (overall response rate 71% vs. 72%, complete response rate 16% vs. 15%, median progression-free survival 24.6 vs. 23.9 months respectively, for FCR with and without lumiliximab). There was a slightly increased incidence of adverse events with lumiliximab but these increases did not appear to lead to differences in eventual outcomes. An interim analysis failed to show sufficient efficacy of the combination of lumiliximab with FCR. The study was therefore stopped early for lack of efficacy. Despite the eventual outcome, the LUCID trial is one of the largest studies that provides valuable insight into the efficacy and tolerability of FCR as a therapeutic option for patients with relapsed CLL.

Published
2014

17. SIE, SIES, GITMO evidence-based guidelines on novel agents (thalidomide, bortezomib, and lenalidomide) in the treatment of multiple myeloma

Author

Mario Boccadoro, Monia Marchetti, Sante Tura, Paolo Corradini, Giovanni Barosi, Antonio Palumbo, Giampaolo Merlini, Patrizia Tosi, Michele Cavo, Atto Billio, Massimo Massaia, Barosi G, Merlini G, Billio A, Boccadoro M, Corradini P, Marchetti M, Massaia M, Tosi P, Palumbo A, Cavo M, and Tura S.

Subjects
Oncology, Melphalan, medicine.medical_specialty, Pharmacology, Guideline, Recommendations, Bortezomib, Autologous stem-cell transplantation, Maintenance therapy, Multiple myeloma, Internal medicine, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Lenalidomide, Dexamethasone, Societies, Medical, business.industry, General Medicine, Hematology, medicine.disease, Boronic Acids, Thalidomide, GRADE, Evidence-Based Practice, Pyrazines, Practice Guidelines as Topic, Neoplasm Grading, business, medicine.drug
Abstract

In this project, we produced drug-specific recommendations targeting the use of new agents for multiple myeloma (MM). We used the GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) system which separates the judgments on quality of evidence from the judgment about strength of recommendations. We recommended thalidomide and bortezomib in MM patients candidates to autologous stem cell transplantation (ASCT) (weak positive). We did not recommend novel agents as maintenance therapy after ASCT (weak negative). In patients not candidate to ASCT, thalidomide or bortezomib (strong positive) associated with melphalan and prednisone were recommended. In these patients, no specific course of action could be recommended as for maintenance therapy. In patients who are refractory or relapsing after first-line therapy, we recommended bortezomib and pegylated liposomal doxorubicin, or lenalidomide and dexamethasone combinations (weak positive).

Published
2012

18. Acute myeloid leukemia cells constitutively express the immunoregulatory enzyme indoleamine 2,3-dioxygenase

Author

Valentina Salvestrini, Simona Pandolfi, Michela Aluigi, Milena Piccioli, Antonio Curti, Stefano Pileri, Ilaria Durelli, F. Fiore, Alessandro Isidori, Elena Zavatto, Elisa Ferri, Massimo Massaia, Roberto M. Lemoli, Michele Baccarani, Alberto L Horenstein, Alessandra D'Addio, Curti A, Aluigi M, Pandolfi S, Ferri E, Isidori A, Salvestrini V, Durelli I, Horenstein AL, Fiore F, Massaia M, Piccioli M, Pileri SA, Zavatto E, D'Addio A, Baccarani M, and Lemoli RM.

Subjects
Regulation of gene expression, chemistry.chemical_classification, Cancer Research, Myeloid leukemia, RNA, Hematology, Biology, medicine.disease, Gene Expression Regulation, Enzymologic, Gene Expression Regulation, Neoplastic, Leukemia, Enzyme, Oncology, chemistry, Leukemia, Myeloid, Reference Values, hemic and lymphatic diseases, Reference values, Acute Disease, Immunology, medicine, Humans, Indoleamine-Pyrrole 2,3,-Dioxygenase, RNA, Messenger, Indoleamine 2,3-dioxygenase
Abstract

Acute myeloid leukemia cells constitutively express the immunoregulatory enzyme indoleamine 2,3-dioxygenase

Published
2007

19. Modulation of tryptophan catabolism by human leukemic cells results in the conversion of CD25- into CD25+ T regulatory cells

Author

Simona Pandolfi, Ilaria Durelli, Mario P. Colombo, Elisa Ferri, Giuseppina Bonanno, Alessandro Isidori, Sergio Rutella, Michele Baccarani, Antonio Curti, Valentina Salvestrini, Massimo Massaia, Barbara Valzasina, Roberto M. Lemoli, Alberto L. Horenstein, Michela Aluigi, F. Fiore, Curti A, Pandolfi S, Valzasina B, Aluigi M, Isidori A, Ferri E, Salvestrini V, Bonanno G, Rutella S, Durelli I, Horenstein AL, Fiore F, Massaia M, Colombo MP, Baccarani M, and Lemoli RM.

Subjects
Adult, CD4-Positive T-Lymphocytes, Immunology, Gene Expression, chemical and pharmacologic phenomena, Biology, Biochemistry, T-Lymphocytes, Regulatory, Interleukin 21, Mice, hemic and lymphatic diseases, Cell Line, Tumor, Cytotoxic T cell, Animals, Humans, Indoleamine-Pyrrole 2,3,-Dioxygenase, IL-2 receptor, Antigen-presenting cell, Interleukin 3, DNA Primers, CD40, Base Sequence, Interleukin-2 Receptor alpha Subunit, Tryptophan, hemic and immune systems, Forkhead Transcription Factors, Cell Biology, Hematology, Natural killer T cell, Coculture Techniques, Leukemia, Myeloid, Acute, biology.protein, Interleukin 12, Cancer research
Abstract

Indoleamine 2,3-dioxygenase (IDO) is a novel immunosuppressive agent expressed in some subsets of normal and neoplastic cells, including acute myeloid leukemia (AML) cells. Here, we show that IDO expression correlates with increased circulating CD4+CD25+FOXP3+ T cells in patients with AML at diagnosis. In vitro, IDO+ AML cells increase the number of CD4+ CD25+ T cells expressing surface CTLA-4 and FOXP3 mRNA, and this effect is completely abrogated by the IDO inhibitor, 1-methyl tryptophan (1-MT). Purified CD4+CD25+ T cells obtained from coculture with IDO+ AML cells act as T regulatory (Treg) cells because they do not proliferate, do not produce interleukin (IL)–2, and inhibit naive T-cell proliferation. Coculture with IDO+AML cells results in the conversion of CD4+CD25− into CD4+CD25+ T cells, which is completely abrogated by 1-MT. Moreover, in mice, intrasplenic injection of IDO+ leukemia/lymphoma A20 cells induces the expansion of bona fide Treg cells by conversion of CD4+CD25− T cells; this effect is counteracted by 1-MT treatment. These data indicate that AML cells induce T-cell tolerance by directly converting CD4+CD25− T cells into CD4+CD25+ Treg cells through an IDO-dependent mechanism.

Published
2007

20. Phase I/II clinical trial of sequential subcutaneous and intravenous delivery of dendritic cell vaccination for refractory multiple myeloma using patient-specific tumour idiotype protein or idiotype (VDJ)-derived class I-restricted peptides

Author

Antonio Curti, Elisa Ferri, Claudia Cellini, Alessandra D'Addio, Cristiana Di Bello, Massimo Massaia, Patrizia Comoli, Valeria Giudice, Carolina Terragna, Roberto M. Lemoli, Michele Baccarani, Gabriele Gugliotta, Michele Cavo, Patrizia Tosi, Roberto Conte, Curti A, Tosi P, Comoli P, Terragna C, Ferri E, Cellini C, Massaia M, D'Addio A, Giudice V, Di Bello C, Cavo M, Conte R, Gugliotta G, Baccarani M, and Lemoli RM.

Subjects
Idiotype, Adult, Male, Antibodies, Neoplasm, medicine.medical_treatment, Injections, Subcutaneous, Immunoglobulin Variable Region, Cancer Vaccines, Autologous stem-cell transplantation, Immunoglobulin Idiotypes, Antigens, Neoplasm, medicine, Cytotoxic T cell, Humans, Antigen-presenting cell, Multiple myeloma, Aged, Immunity, Cellular, biology, business.industry, Vaccination, Hematology, Immunotherapy, Dendritic Cells, Middle Aged, medicine.disease, Peptide Fragments, Treatment Outcome, Immunology, Hemocyanins, Injections, Intravenous, biology.protein, Immunoglobulin Joining Region, Female, Immunocompetence, business, CD14, Multiple Myeloma, Keyhole limpet hemocyanin
Abstract

Summary Fifteen multiple myeloma (MM) patients who had failed maintenance therapy after tandem autologous stem cell transplantation underwent anti-idiotype (Id) vaccination with dendritic cells (DCs). CD14+-derived DCs were loaded with the autologous Id as whole protein (=6) or Id-derived class I-restricted peptides (=9) and keyhole limpet hemocyanin (KLH). Vaccination consisted of three subcutaneous (sc) and two intravenous injections of increasing DC doses at 2 weeks interval. DC therapy was well tolerated. Most patients developed both humoral and T-cell responses to KLH, suggesting immunocompetence. Eight of 15 patients developed an Id-specific T-cell proliferative response, 8/15 increased interferon-γ-secreting T cells and 4/15 showed an Id-positive delayed-type hypersensitivity test. Anti-Id cytotoxic T-lymphocyte precursors increased after DC vaccination in 2/2 evaluable patients. A more robust T-cell response was observed after sc DC injections and increased Id-specific T-cell proliferation was found up to 1 year after vaccination. VDJ-derived peptides were as effective as the whole protein in stimulating T-cell responses. Clinically, 7/15 patients have stable disease after a median follow-up of 26 months, one patient achieved durable partial remission after 40 months, and seven patients progressed. In conclusion, sc injections of cryopreserved Id-pulsed DCs were safe and, in contrast with intravenous administrations, induced anti-MM T-cell responses.

Published
2007

21. A VEGF-dependent autocrine loop mediates proliferation and capillarogenesis in bone marrow endothelial cells of patients with multiple myeloma

Author

Franco Dammacco, Diego Guidolin, Domenico Ribatti, Michele Cavo, Teresa Cirulli, Patrizia Tosi, Roberto Ria, Massimo Massaia, Francesca Russo, Angelo Vacca, RIA R, VACCA A, RUSSO F, CIRULLI T, MASSAIA M, TOSI P, CAVO M., GUIDOLIN D, RIBATTI D, and DAMMACCO F.

Subjects
Adult, Male, Vascular Endothelial Growth Factor A, Umbilical Veins, Pathology, medicine.medical_specialty, Time Factors, Angiogenesis, Blotting, Western, Bone Marrow Cells, Culture Media, Serum-Free, Neovascularization, chemistry.chemical_compound, medicine, Humans, RNA, Messenger, Phosphorylation, Autocrine signalling, Aged, Cell Proliferation, Aged, 80 and over, Mitogen-Activated Protein Kinase 1, Matrigel, Neovascularization, Pathologic, Reverse Transcriptase Polymerase Chain Reaction, business.industry, Autophosphorylation, Hematology, Middle Aged, Vascular Endothelial Growth Factor Receptor-2, Capillaries, Endothelial stem cell, Vascular endothelial growth factor, Drug Combinations, medicine.anatomical_structure, chemistry, Culture Media, Conditioned, Cancer research, Female, Proteoglycans, Collagen, Endothelium, Vascular, Laminin, Bone marrow, medicine.symptom, Multiple Myeloma, business
Abstract

SummaryThe expression/function of vascular endothelial growth factor (VEGF) and its receptor 2 (VEGFR-2/KDR) in multiple myeloma (MM)-associated angiogenesis is under scrutiny. We show here that bone marrow endothelial cells (EC) from 16 patients with MM (MMEC) highly expressed VEGF-A (the main VEGF isoform) and VEGFR-2 at both mRNA and protein level, whereas EC from 14 patients with monoclonal gammopathy unassociated/unattributable (MG[u]) (MG[u]EC) and 12 human umbilical veins (HUVEC) expressed very low mRNAs and/or proteins. MMEC showed constitutive autophosphorylation in both VEGFR-2 and the associated extracellular signal-regulated kinase-2 (ERK-2), whereas this was marginal in MG[u]EC and HUVEC. MMEC proliferated rapidly and formed a closely-knit capillary meshwork on Matrigel. These cell functions were reduced in the other EC. Autophosphorylation, proliferation and capillarogenesis were prevented by a neutralizing antiVEGF-A antibody, and more efficaciously by an anti-VEGFR-2 antibody. Both antibodies had no effect or were poorly effective on the other EC. These findings as a whole suggest the existence of an autocrine loop of VEGF in MMEC. Since this is very likely a mechanism for the amplification of VEGF activity in neovascularization, it would constitute an appropriate target for antiangiogenic management in MM.

Published
2004

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