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1,206 results on '"Foà R"'

205. WHO classification and WPSS predict posttransplantation outcome in patients with myelodysplastic syndrome: a study from the Gruppo Italiano Trapianto di Midollo Osseo (GITMO)

Author

Alessandrino, Ep, Della Porta MG, Bacigalupo, A, Van Lint MT, Falda, M, Onida, F, Bernardi, M, Iori, Ap, Rambaldi, A, Cerretti, R, Marenco, P, Pioltelli, P, Malcovati, L, Pascutto, C, Oneto, R, Fanin, R, Bosi, A, Gruppo Italiano Trapianto di Midollo Osseo, Levis, A, Bandini, G, Casini, M, Rossi, G, Angelucci, E, Baronciani, D, La Nasa, G, Milone, G, Mordini, N, Guidi, S, Corradini, P, Milani, R, Morra, E, Lambretenghi Deliliers, G, Ciceri, F, Castagna, L, Narni, F, Selleri, C, Scimè, R, Iannitto, E, Musso, M, Locatelli, F, Martelli, F, Visani, G, Di Bartolomeo, P, Cavanna, L, Papineschi, Federico, Messina, G, Gugliotta, L, Foà, R, Locasciulli, A, Majolino, I, Chiusolo, P, Leone, G, Arcese, W, Carella, Am, Cascavilla, N, Mazza, P, Bruno, B, Boccadoro, M, Cerno, M, and Raimondi, R.

Published
2008

206. Melphalan, prednisone, and lenalidomide treatment for newly diagnosed myeloma: a report from the GIMEMA--Italian Multiple Myeloma Network

Author

Palumbo, Antonio, Falco, P, Corradini, P, Falcone, A, DI RAIMONDO, F, Giuliani, N, Crippa, C, Ciccone, G, Omedè, P, Ambrosini, Mt, Gay, F, Bringhen, S, Musto, P, Foà, R, Knight, R, Zeldis, Jb, Boccadoro, Mario, Petrucci, Mt, and GIMEMA ITALIAN MULTIPLE MYELOMA NETWORK

Subjects
Male, Melphalan, Cancer Research, medicine.medical_specialty, Drug-Related Side Effects and Adverse Reactions, Maximum Tolerated Dose, medicine.drug_class, Administration, Oral, Gastroenterology, chemistry.chemical_compound, Maintenance therapy, Prednisone, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Lenalidomide, Multiple myeloma, Aged, Dose-Response Relationship, Drug, business.industry, Middle Aged, medicine.disease, Survival Analysis, Nitrogen mustard, Thalidomide, Surgery, Oncology, chemistry, Corticosteroid, Female, Multiple Myeloma, business, medicine.drug
Abstract

Purpose Lenalidomide has shown significant antimyeloma activity in clinical studies. Oral melphalan, prednisone, and thalidomide have been regarded as the standard of care in elderly multiple myeloma patients. We assessed dosing, efficacy, and safety of melphalan, prednisone, and lenalidomide (MPR) in newly diagnosed elderly myeloma patients. Patients and Methods Oral melphalan was administered in doses ranging from 0.18 to 0.25 mg/kg on days 1 to 4, prednisone at a 2-mg/kg dose on days 1 to 4, and lenalidomide at doses ranging from 5 to 10 mg on days 1 to 21, every 28 days for nine cycles, followed by maintenance therapy with lenalidomide alone. Aspirin was given as a prophylaxis for thrombosis. Results Fifty-four patients were enrolled and evaluated after completing the assigned treatment schedule. The maximum tolerated dose was defined as 0.18 mg/kg melphalan and 10 mg lenalidomide. With these doses, 81% of patients achieved at least a partial response, 47.6% achieved a very good partial response, and 23.8% achieved a complete immunofixation-negative response. In all patients, 1-year event-free and overall survival rates were 92% and 100%, respectively. At the maximum tolerated dose, grade 3 adverse events included neutropenia (38.1%), thrombocytopenia (14.2%), febrile neutropenia (9.5%), vasculitis (9.5%), and thromboembolism (4.8%); grade 4 adverse events were neutropenia (14.2%) and thrombocytopenia (9.5%). Conclusion Oral MPR therapy is a promising first-line treatment for elderly myeloma patients. Hematologic adverse events were frequent but manageable. A low incidence of nonhematologic adverse events was noted. Aspirin appears to provide adequate antithrombosis prophylaxis.

Published
2007

208. Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma

Author

Dimopoulos, M. Spencer, A. Attal, M. Prince, H.M. Harousseau, J.-L. Dmoszynska, A. San Miguel, J. Hellmann, A. Facon, T. Foà, R. Corso, A. Masliak, Z. Olesnyckyj, M. Yu, Z. Patin, J. Zeldis, J.B. Knight, R.D.

Abstract

Background: Lenalidomide is a structural analogue of thalidomide with similar but more potent biologic activity. This phase 3, placebo-controlled trial investigated the efficacy of lenalidomide plus dexamethasone in the treatment of relapsed or refractory multiple myeloma. Methods: Of 351 patients who had received at least one previous antimyeloma therapy, 176 were randomly assigned to receive 25 mg of oral lenalidomide and 175 to receive placebo on days 1 to 21 of a 28-day cycle. In addition, all patients received 40 mg of oral dexamethasone on days 1 to 4, 9 to 12, and 17 to 20 for the first four cycles and subsequently, after the fourth cycle, only on days 1 to 4. Patients continued in the study until the occurrence of disease progression or unacceptable toxic effects. The primary end point was time to progression. Results: The time to progression was significantly longer in the patients who received lenalidomide plus dexamethasone (lenalidomide group) than in those who received placebo plus dexamethasone (placebo group) (median, 11.3 months vs. 4.7 months; P

Published
2007

209. ERK1/2 phosphorylation is an independent predictor of complete remission in newly diagnosed adult acute lymphoblastic leukemia

Author

Gregorj, C, Ricciardi, Mr, Petrucci, Mt, Scerpa, Mc, De Cave, F, Fazi, P, Vignetti, M, Vitale, A, Mancini, M, Cimino, G, Palmieri, S, Di Raimondo, F, Specchia, G, Fabbianof, Cantore, N, Mosna, F, Camera, A, Luppi, Mario, Annino, L, Miraglia, E, Fioritoni, G, Ronco, F, Meloni, G, Mandelli, F, Andreeff, M, Milella, M, Foà, R, Tafuri, A, and GIMEMAAcute Leukemia Working Party

Subjects
Oncology, Adult, Male, medicine.medical_specialty, Multivariate analysis, Adolescent, Immunology, acute lymphoblastic leukemia, prognostic assessment in acute leukemias, ERK signaling, Biochemistry, Flow cytometry, Predictive Value of Tests, Acute lymphocytic leukemia, Internal medicine, White blood cell, Leukocytes, Medicine, Humans, Phosphorylation, ERK1/2, adult acute lymphoblastic leukemia, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase 3, medicine.diagnostic_test, business.industry, Remission Induction, Complete remission, Cell Biology, Hematology, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma, medicine.disease, Flow Cytometry, Prognosis, Haematopoiesis, medicine.anatomical_structure, Predictive value of tests, Adult Acute Lymphoblastic Leukemia, Female, business
Abstract

Extracellular signal-regulated kinase-1/2 (ERK1/2) is frequently found constitutively activated (p-ERK1/2) in hematopoietic diseases, suggesting a role in leukemogenesis. The aim of this study was to assess the expression and clinical role of p-ERK1/2 in adult acute lymphoblastic leukemia (ALL). In 131 primary samples from adult de novo ALL patients enrolled in the Gruppo Italiano per le Malattie Ematologiche dell'Adulto (GIMEMA) Leucemia Acute Linfoide (LAL) 2000 protocol and evaluated by flow cytometry, constitutive ERK1/2 activation was found in 34.5% of cases; these results were significantly associated with higher white blood cell (WBC) values (P = .013). In a multivariate analysis, p-ERK1/2 expression was an independent predictor of complete remission achievement (P = .027). Effective approaches toward MEK inhibition need to be explored in order to evaluate whether this may represent a new therapeutic strategy for adult ALL patients.

Published
2007

211. A PROSPECTIVE PHASE II STUDY ON TANDEM AUTOGRAFTING-ONMYELOABLATIVE ALLOGRAFTING FOR NEWLY DIAGNOSED MULTIPLE MYELOMA: FINAL RESULTS OF A MULTICENTER GITMO (GRUPPO ITALIANO TRAPIANTO MIDOLLO OSSEO) PROTOCOL

Author

Sorasio, R., Patriarca, F., Giaccone, L., Mattei, D., Allione, B., Carnevale Schianca, F., Rambaldi, A., Casini, M., Montefusco, V., Parma, M., Bavaro, P., Onida, F., Busca, A., Castagna, L., Iori, A.P., Rotta, M., Fiore, F., Benedetti, E., Mordini, N., Massaia, M., Palumbo, A., Aglietta, M., Lewis, A., Foà, R., Di Bartolomeo, P., Pogliani, E., Lambertenghi-Deliliers, G., Falda, M., Petrini, M., Corradini, P., Fanin, R., Ricardi, U., Ciccone, G., Baldi, I., Bruno, B., and Boccadoro, M.

Subjects
Settore MED/15 - Malattie del Sangue
Published
2007

213. New therapies in onco-hematology and new infectious risk factors

Author

Ilaria DEL GIUDICE and Foà, R.

Subjects
Risk Factors, Hematologic Neoplasms, Hematopoietic Stem Cell Transplantation, Humans, Infections, Combined Modality Therapy
Abstract

The biologic, clinical and therapeutic setting is nowadays such that risk factors for infectious complications are constantly changing and progressively increasing in patients suffering from onco-hematologic conditions. In addition to situations that are well known or that are gradually being recognized related both to the underlying disease and to treatment, such as neutropenia, neutrophil dysfunction, mucosal damage, concomitant monocytopenia and lymphopenia, abnormalities within the host cellular and humoral compartments, impairments in cytokine networks, alterations in T lymphocytes/tumor interactions, crosstalks between neoplastic cells and accessory cells, etc, over the last few years we are witnessing important changes in the overall management of patients with hematologic malignancies. Historically, the categories at risk were represented by patients with acute leukemia and patients undergoing an allogeneic stem cell transplant. In both, the likelihood of eradicating the disease requires necessarily a myeloablative therapeutic strategy, complicated in the allografted patients by the risks of graft-versus-host disease (GvHD), the required immunosuppressive treatment and the recently documented role that cytokines may play in the development of acute GvHD. Considerable changes have occurred in recent years. From the identification of "new" diseases at risk (e.g. lymphomas occurring in HIV+ individuals), to the progressive and constant increase in allotransplant procedures, to the development of new transplant procedures (cord blood, matched-unrelated or mismatched donor transplant, mini-transplant, the administration of donor lymphocytes), to the development of new drugs that can induce immunosuppression, to the clinical use of certain monoclonal antibodies (MoAb), to the combined use of chemotherapy plus MoAb. These developments are associated with other general considerations. Within these: 1) the growing use of ablative therapies in diseases for which for many years the approach has been less aggressive or indeed conservative; 2) the progressive recognition of categories of patients with unfavorable prognosis for whom an aggressive approach is required; 3) the constant improvement in mean life expectancy and "biologic" age of patients; thus, the progressive changes in the definition of "old age". Taken together, this has led, on the one hand, to an increase in the categories of onco-hematologic patients at risk of infective complications and to a major focus on the immune compartment of the affected patients, and, on the other hand, to an overall broadening of the infective scenario.

Published
2006

215. ERK1/2 phosphorylation in adult acute lymphoblastic leukemia patients: prognostic role and in vitro effects of MEK inhibition

Author

Gregorj, C, Ricciardi, Maria Rosaria, Petrucci, Mt, Scerpa, Mc, De Cave, F, Fazi, P, Vitale, A, Mancini, M, Cimino, Giuseppe, Palmieri, S, Di Raimondo, F, Specchia, G, Fabbiano, F, Cantore, N, Mosna, F, Camera, A, Luppi, M, Annino, L, Miraglia, E, Fioritoni, G, Ronco, F, Meloni, G, Andreeff, M, Milella, M, Mandelli, Franco, Foà, R, and Tafuri, Agostino

Published
2006

220. BREAST CANCER RESISTANCE PROTEIN (BCRP) EXPRESSION AFFECT EVENT-FREE SURVIVAL IN ADULT ACUTE LYMPHOBLASTIC LEUKEMIA PATIENTS

Author

Gregorj, C, DE CAVE, Fabiana, Petrucci, Mt, Ricciardi, Maria Rosaria, Scerpa, Mc, Vignetti, M, Vitale, A, Meloni, G, Liso, V, Di Raimondo, F, Ferrara, F, Fabbiano, F, Camera, A, Fioritoni, G, Miraglia, E, Annino, L, Cascavilla, N, Marmont, F, Mazza, P, Perbellini, O, Cartore, N, Luppi, M, Nobile, F, Sica, S, Salvi, F, Mandelli, Franco, Foà, R., and Tafuri, Agostino

Published
2006

222. Is bone marrow trephine biopsy always mandatory in staging Hodgkin's disease?

Author

Cavalieri, E., Anselmo, A. P., Gianfelici, V., Frattarelli, N., Edoardo Pescarmona, Foà, R., and Pulsoni, A.

Subjects
Adult, Male, Biopsy, Humans, Bone Marrow Cells, Female, Middle Aged, Unnecessary Procedures, Hodgkin Disease, Aged, Neoplasm Staging
Abstract

We reviewed data from 690 adult patients with Hodgkin's disease (HD) to determine whether bone marrow trephine biopsy (BMTB) is mandatory for all patients. The data suggest that it is not necessary in clinical stage I-IIA. However, bilateral BMTB is recommended in the presence of B symptoms also in patients with localized stage disease.

Published
2005

226. Expansion of natural killer cells with lytic activity against autologous blasts from adult and pediatric acute lymphoid leukemia patients in complete hematologic remission

Author

Torelli, G. F., Guarini, A., ROBERTA MAGGIO, Alfieri, C., Vitale, A., and Foà, R.

Subjects
Adult, Interleukin-15, all, autologous blasts, cytotoxicity, immunotherapy, nk, Receptors, IgG, Remission Induction, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Flow Cytometry, Coculture Techniques, Killer Cells, Natural, Cytokines, Humans, Interleukin-2, Child, Signal Transduction
Abstract

Natural killer (NK) cells constitute an important area of research for hematologic malignancies. The anti-leukemic activity of NK cells against acute myeloid leukemia (AML) blasts has been described, but very few data are available for acute lymphoid leukemia (ALL). The present study was designed to investigate whether: (i) NK effectors could be expanded from adult and pediatric ALL patients in complete remission; (ii) the signal transduction machinery of these cells was preserved; (iii) NK cells showed cytotoxic activity against autologous blasts; (iv) interleukin (IL)-2, IL-12 and IL-15 were able to increase lytic activity in our in vitro model; (v) any differences in cytotoxic activity could be found between expanded effectors from adult and pediatric patients.We co-cultured patients' peripheral blood mononuclear cells (PBMC) with the feeder cell line RPMI 8866 and analyzed the NK cells' expansion capacity by cell count and cytofluorimetric analyses. Signal transduction of expanded effector cells was evaluated by Western blot. 51Cr release assays, before and after stimulation with activating cytokines, were performed to analyze the cytotoxic potential of effector cells against tumor cell lines and autologous blast cells. Data were analyzed with t-tests for paired data.We obtained an average 40-fold increase in NK cells. Signal transduction through the CD16 receptor was preserved. Patients' expanded cells showed cytotoxic activity against target cell lines comparable to that of normal donors. More significantly, these cells also exerted a lytic effect against autologous blasts. In addition, incubating these effectors for 24 hours with IL-2 + IL-15 significantly increased this cytotoxic function. No differences in expansion and cytotoxic activity were found between pediatric and adult patients.These findings document for the first time the possibility of expanding ex vivo cytotoxic effectors with autologous killing capacity from ALL patients in remission, and suggest a new potential immunotherapeutic strategy for the management of early disease recurrence or of residual disease.

Published
2005

233. Tumor evolutionary directed graphs and the history of chronic lymphocytic leukemia

Author

Wang, J, Khiabanian, H, Rossi, D, Fabbri, G, Gattei, V, Forconi, F, Laurenti, Luca, Marasca, R, Del Poeta, G, Foà, R, Pasqualucci, L, Gaidano, G, Rabadan, R., Laurenti, Luca (ORCID:0000-0002-8327-1396), Wang, J, Khiabanian, H, Rossi, D, Fabbri, G, Gattei, V, Forconi, F, Laurenti, Luca, Marasca, R, Del Poeta, G, Foà, R, Pasqualucci, L, Gaidano, G, Rabadan, R., and Laurenti, Luca (ORCID:0000-0002-8327-1396)

Abstract

Cancer is a clonal evolutionary process, caused by successive accumulation of genetic alterations providing milestones of tumor initiation, progression, dissemination and/or resistance to certain therapeutic regimes. To unravel these milestones we propose a framework, tumor evolutionary directed graphs (TEDG), which is able to characterize the history of genetic alterations by integrating longitudinal and cross-sectional genomic data. We applied TEDG to a chronic lymphocytic leukemia (CLL) cohort of 70 patients spanning 12 years, and show that: (a) the evolution of CLL follows a time-ordered process represented as a global flow in TEDG that proceeds from initiating events to late events; (b) there are two distinct and mutually exclusive evolutionary paths of CLL evolution; (c) higher fitness clones are present in later stages of the disease, indicating a progressive clonal replacement with more aggressive clones. Our results suggest that TEDG may constitute an effective framework to recapitulate the evolutionary history of tumors.

Published
2014

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

Author

Mauro, Fr, Molica, S, Laurenti, Luca, Cortelezzi, A, Carella, Am, Zaja, F, Chiarenza, A, Angrilli, F, Nobile, F, Marasca, R, Musolino, C, Brugiatelli, M, Piciocchi, A, Vignetti, M, Fazi, P, Gentile, G, De Propris, M, Starza, Id, Marinelli, M, Chiaretti, S, Del Giudice, I, Nanni, M, Albano, F, Cuneo, A, Guarini, A, Foà, R., Laurenti, Luca (ORCID:0000-0002-8327-1396), Mauro, Fr, Molica, S, Laurenti, Luca, Cortelezzi, A, Carella, Am, Zaja, F, Chiarenza, A, Angrilli, F, Nobile, F, Marasca, R, Musolino, C, Brugiatelli, M, Piciocchi, A, Vignetti, M, Fazi, P, Gentile, G, De Propris, M, Starza, Id, Marinelli, M, Chiaretti, S, Del Giudice, I, Nanni, M, Albano, F, Cuneo, A, Guarini, A, Foà, R., and Laurenti, Luca (ORCID:0000-0002-8327-1396)

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

235. The Krüppel-like factor 2 transcription factor gene is recurrently mutated in splenic marginal zone lymphoma

Author

Piva, R, primary, Deaglio, S, additional, Famà, R, additional, Buonincontri, R, additional, Scarfò, I, additional, Bruscaggin, A, additional, Mereu, E, additional, Serra, S, additional, Spina, V, additional, Brusa, D, additional, Garaffo, G, additional, Monti, S, additional, Dal Bo, M, additional, Marasca, R, additional, Arcaini, L, additional, Neri, A, additional, Gattei, V, additional, Paulli, M, additional, Tiacci, E, additional, Bertoni, F, additional, Pileri, S A, additional, Foà, R, additional, Inghirami, G, additional, Gaidano, G, additional, and Rossi, D, additional

Published
2014
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242. MDR1/P-gp expression predicts achievement of remission in adult acute lymphoblastic leukemia patients treated according to the GIMEMA 0496 protocol

Author

Petrucci, Mt, Gregorj, C, Ricciardi, Maria Rosaria, Mancini, M, Cimino, Giuseppe, Mecucci, C, Tedeschi, A, Fioritoni, G, Ferrara, F, Di Raimondo, F, Gallo, E, Liso, V, Fabbiano, F, Cascavilla, N, Pizzolo, G, Camera, A, Pane, F, Lanza, F, Cilloni, D, Annino, L, Vitale, A, Vegna, Ml, Vignetti, M, Foà, R, and Tafuri, Agostino

Published
2002

244. Hematopoietic stem cell transplantation for children with high-risk acute lymphoblastic leukemia in first complete remission: A report from the AIEOP registry

Author

Fagioli, F, Quarello, P, Zecca, M, Lanino, E, Rognoni, C, Balduzzi, A, Messina, C, Favre, C, Foà, R, Ripaldi, M, Rutella, S, Basso, G, Prete, A, Locatelli, F, Fagioli, Franca, Quarello, Paola, Zecca, Marco, Lanino, Edoardo, Rognoni, Carla, Balduzzi, Adriana, Messina, Chiara, Favre, Claudio, Foà, Roberto, Ripaldi, Mimmo, Rutella, Sergio, Basso, Giuseppe, Prete, Arcangelo, Locatelli, Franco, Fagioli, F, Quarello, P, Zecca, M, Lanino, E, Rognoni, C, Balduzzi, A, Messina, C, Favre, C, Foà, R, Ripaldi, M, Rutella, S, Basso, G, Prete, A, Locatelli, F, Fagioli, Franca, Quarello, Paola, Zecca, Marco, Lanino, Edoardo, Rognoni, Carla, Balduzzi, Adriana, Messina, Chiara, Favre, Claudio, Foà, Roberto, Ripaldi, Mimmo, Rutella, Sergio, Basso, Giuseppe, Prete, Arcangelo, and Locatelli, Franco

Abstract

Children with high-risk acute lymphoblastic leukemia in first complete remission can benefit from allogeneic hematopoietic stem cell transplantation. We analyzed the outcome of 211 children with high-risk acute lymphoblastic leukemia in first complete remission who were given an allogeneic transplant between 1990 and 2008; the outcome of patients who, despite having an indication for transplantation and a suitable donor, did not receive the allograft for different reasons in the same time period was not analyzed. Sixty-nine patients (33%) were transplanted between 1990 and 1999, 58 (27%) between 2000 and 2005, and 84 (40%) between 2005 and 2008. A matched family donor was employed in 138 patients (65%) and an unrelated donor in 73 (35%). The 10-year probabilities of overall and disease-free survival were 63.4% and 61%, respectively. The 10-year cumulative incidences of transplantation-related mortality and relapse were 15% and 24%, respectively. After 1999, no differences in either disease-free survival or transplant-related mortality were observed in patients transplanted from unrelated or matched family donors. In multivariate analysis, grade IV acute graft-versus-host disease was an independent factor associated with worse disease-free survival. By contrast, grade I acute graft-versus-host disease and age at diagnosis between 1 and 9 years were favorable prognostic variables. Our study, not intended to evaluate whether transplantation is superior to chemotherapy for children with acute lymphoblastic leukemia in first complete remission and high-risk features, shows that the allograft cured more than 60% of these patients; in the most recent period, the outcome of recipients of grafts from matched family and unrelated donors was comparable. © 2013 Ferrata Storti Foundation.

Published
2013

245. Italian cancer figures, report 2012: Cancer in children and adolescents

Author

Pisani, P, Buzzoni, C, Crocetti, E, Maso, L, Rondelli, R, Alessi, D, Aricò, M, Bidoli, E, Ferrari, A, Fusco, M, Gatta, G, Guzzinati, S, Jankovic, M, Locatelli, F, Maule, M, Mosso, M, Pastore, G, Pession, A, Rashid, I, Sacerdote, C, Terracini, B, Tognazzo, S, Trama, A, Ferretti, S, Porta, F, Mazzoleni, G, Tschugguel, B, De Valiere, E, Facchinelli, G, Falk, M, Cappello, T, Giacomin, A, Vercellino, P, Andreone, S, Marzola, L, Migliari, E, Carletti, N, Nenci, I, Caldarella, A, Corbinelli, A, Intrieri, T, Manneschi, G, Nemcova, L, Ocello, C, Sacchettini, C, Zappa, M, Paci, E, Serraino, D, Angelin, T, Birri, S, De Dottori, M, De Santis, E, Forgiarini, O, Zucchetto, A, Zanier, L, Vercelli, M, Orengo, M, Casella, C, Marani, E, Puppo, A, Celesia, M, Cogno, R, Levrieri, I, Manenti, S, Garrone, E, Quaglia, A, Pannozzo, F, Busco, S, Ramazzotti, V, Cercato, M, Battisti, W, Sperduti, I, Macci, L, Bugliarello, E, Valerio, O, Bernazza, E, Tamburo, L, Rossi, M, Curatella, S, Tamburrino, S, Fattoruso, S, Bisanti, L, Autelitano, M, Cuccaro, F, Randi, G, Ghilardi, S, Leone, R, Filipazzi, L, Bonini, A, Giubelli, C, Federico, M, Artioli, M, Valla, K, Braghiroli, B, Cirilli, C, Luminari, S, Pirani, M, Ferrari, L, Bellatalla, C, Panico, M, Perrotta, C, Vassante, B, Vitale, M, Michiara, M, Bozzani, F, Sgargi, P, Tumino, R, Rosa, M, Cascone, G, Frasca, G, Giurdanella, M, Martorana, C, Morana, G, Nicita, C, Rollo, P, Ruggeri, M, Sigona, A, Spata, E, Vacirca, S, Mangone, L, Di Felice, E, Pezzarossi, A, Caroli, S, Pellegri, C, Vicentini, M, D'Angelo, S, Balottari, P, Romagna, R, Falcini, F, Colamartini, A, Bucchi, L, Balducci, C, Ravegnani, M, Vitali, B, Cordaro, C, Caprara, L, Giuliani, O, Giorgetti, S, Palumbo, M, Vattiato, R, Ravaioli, A, Mancini, S, Tonelli, C, Amadori, M, Cremone, L, Iannelli, A, Senatore, G, Zevola, A, Sechi, O, Budroni, M, Cesaraccio, R, Pirino, D, Carboni, D, Fiori, G, Soddu, M, Mameli, G, Mura, F, Contrino, M, Madeddu, A, Tisano, F, Sciacca, S, Muni, A, Mizzi, M, Russo, M, Sacco, G, Aletta, P, Ziino, A, Tessandori, R, Fanetti, A, Maspero, S, Cecconami, L, Annulli, M, Moroni, E, Gonzalez, M, Zanetti, R, Rosso, S, Patriarca, S, Prandi, R, Sobrato, I, Gilardi, F, Busso, P, Piffer, S, Rizzello, R, Gentilini, M, Cappelletti, M, Rosa, F, Stracci, F, D'Alò, D, Scheibel, M, Costarelli, D, Spano, F, Rossini, S, Santucci, C, Petrinelli, A, Solimene, C, Bianconi, F, Brunori, V, Crosignani, P, Tagliabue, G, Contiero, P, Preto, L, Tittarelli, A, Maghini, A, Codazzi, T, Frassoldi, E, Gada, D, Costa, E, Grazia, L, Zambon, P, Baracco, M, Bovo, E, Cin, A, Fiore, A, Greco, A, Monetti, D, Rosano, A, Stocco, C, Donato, F, Limina, R, Adorni, A, Andreis, P, Zani, G, Piovani, F, Salvi, O, Puleio, M, Vitarelli, S, Candela, G, Pappalardo, G, Scuderi, T, Lottero, B, Ribaudo, M, Ricci, P, Guarda, L, Gatti, L, Bozzeda, A, Dall'Acqua, M, Pironi, V, Sardo, A, Mazzei, A, Sirianni, N, Lavecchia, A, Mancuso, P, Vitale, F, Cusimano, R, Amodio, R, Guttadauro, A, Ravazzolo, B, Bucalo, G, Trapani, C, Sunseri, R, Cascio, M, Brucculeri, M, Adamo, M, Mannino, R, Mistretta, A, Costa, A, Rudisi, G, Gola, G, Corti, M, Prosperini, E, Grandi, L, Sciacchitano, S, Fidelbo, M, Benedetto, G, Vasquez, E, Torrisi, A, Pesce, P, Calabretta, L, Bella, F, Leone, A, Ieni, A, Varvarà, M, Castaing, M, Di Prima, A, Benedetto, A, Paderni, F, Usala, M, Pala, F, Sini, G, Pintori, N, Canu, L, Demurtas, G, Doa, N, Lazzarato, F, Magnani, C, Merletti, F, Sarcerdote, C, Macerata, V, de Leon, M, Domati, F, Rossi, G, Goldoni, C, Rossi, F, De Gaetani, C, Benatti, P, Roncucci, L, Di Gregorio, C, Pedroni, M, Pezzi, A, Maffei, S, Mariani, F, Borsi, E, Cocchioni, M, Pascucci, C, Gennaro, V, Lazzarotto, A, Benfatto, L, Mazzucco, G, Montanaro, F, Traina, A, Carruba, G, Dolcemascolo, C, Staiti, R, Zarcone, M, Bisogno, G, Cuttini, M, De Rosa, M, Haupt, R, Soresina, A, Valsecchi, M, Fagioli, F, Bona, G, Dini, G, Conter, V, Biondi, A, Zecca, M, Fedeli, F, Massimino, M, Nespoli, L, Roncarolo, M, Basso, G, Cesaro, S, Memo, L, Bellettato, M, Tamaro, P, Mascarin, M, Rosolen, A, Izzi, G, Paolucci, P, Borgna Pignatti, C, Vecchi, V, Abate, M, D'Ambrosio, A, Favre, C, Caniglia, M, Pierani, P, Felici, L, Visani, G, Fioritoni, G, Foà, R, Riccardi, R, Frega, G, Clerico, A, Casale, F, Poggi, V, Amendola, G, Filosa, A, Ladogana, S, Presta, G, Tornesello, A, De Mattia, D, Consarino, C, Nobile, F, Sperlì, D, D'Angelo, P, Marino, S, Cosmi, C, Mura, R, Battisti, L, Maso, LD, Mosso, ML, Cappello, TD, Vercellino, PC, Orengo, MA, Celesia, MV, Cercato, MC, Artioli, ME, Vitale, MF, Rosa, MG, Giurdanella, MC, Rollo, PC, Ruggeri, MG, Romagna, Rt, Contrino, ML, Ziino, AC, Fanetti, AC, Annulli, ML, Gonzalez, ME, Gentilini, MA, Rosa, FL, Petrinelli, AM, Grazia, Ld, Cin, AD, Fiore, AR, Limina, RM, Sardo, AS, Lavecchia, AM, Cascio, MA, Brucculeri, MA, Adamo, MS, Sini, GM, de Leon, MP, Goldoni, CA, VALSECCHI, MARIA GRAZIA, BIONDI, ANDREA, Roncarolo, MG, Abate, ME, Mura, RM, Battisti, L., Pisani, P, Buzzoni, C, Crocetti, E, Maso, L, Rondelli, R, Alessi, D, Aricò, M, Bidoli, E, Ferrari, A, Fusco, M, Gatta, G, Guzzinati, S, Jankovic, M, Locatelli, F, Maule, M, Mosso, M, Pastore, G, Pession, A, Rashid, I, Sacerdote, C, Terracini, B, Tognazzo, S, Trama, A, Ferretti, S, Porta, F, Mazzoleni, G, Tschugguel, B, De Valiere, E, Facchinelli, G, Falk, M, Cappello, T, Giacomin, A, Vercellino, P, Andreone, S, Marzola, L, Migliari, E, Carletti, N, Nenci, I, Caldarella, A, Corbinelli, A, Intrieri, T, Manneschi, G, Nemcova, L, Ocello, C, Sacchettini, C, Zappa, M, Paci, E, Serraino, D, Angelin, T, Birri, S, De Dottori, M, De Santis, E, Forgiarini, O, Zucchetto, A, Zanier, L, Vercelli, M, Orengo, M, Casella, C, Marani, E, Puppo, A, Celesia, M, Cogno, R, Levrieri, I, Manenti, S, Garrone, E, Quaglia, A, Pannozzo, F, Busco, S, Ramazzotti, V, Cercato, M, Battisti, W, Sperduti, I, Macci, L, Bugliarello, E, Valerio, O, Bernazza, E, Tamburo, L, Rossi, M, Curatella, S, Tamburrino, S, Fattoruso, S, Bisanti, L, Autelitano, M, Cuccaro, F, Randi, G, Ghilardi, S, Leone, R, Filipazzi, L, Bonini, A, Giubelli, C, Federico, M, Artioli, M, Valla, K, Braghiroli, B, Cirilli, C, Luminari, S, Pirani, M, Ferrari, L, Bellatalla, C, Panico, M, Perrotta, C, Vassante, B, Vitale, M, Michiara, M, Bozzani, F, Sgargi, P, Tumino, R, Rosa, M, Cascone, G, Frasca, G, Giurdanella, M, Martorana, C, Morana, G, Nicita, C, Rollo, P, Ruggeri, M, Sigona, A, Spata, E, Vacirca, S, Mangone, L, Di Felice, E, Pezzarossi, A, Caroli, S, Pellegri, C, Vicentini, M, D'Angelo, S, Balottari, P, Romagna, R, Falcini, F, Colamartini, A, Bucchi, L, Balducci, C, Ravegnani, M, Vitali, B, Cordaro, C, Caprara, L, Giuliani, O, Giorgetti, S, Palumbo, M, Vattiato, R, Ravaioli, A, Mancini, S, Tonelli, C, Amadori, M, Cremone, L, Iannelli, A, Senatore, G, Zevola, A, Sechi, O, Budroni, M, Cesaraccio, R, Pirino, D, Carboni, D, Fiori, G, Soddu, M, Mameli, G, Mura, F, Contrino, M, Madeddu, A, Tisano, F, Sciacca, S, Muni, A, Mizzi, M, Russo, M, Sacco, G, Aletta, P, Ziino, A, Tessandori, R, Fanetti, A, Maspero, S, Cecconami, L, Annulli, M, Moroni, E, Gonzalez, M, Zanetti, R, Rosso, S, Patriarca, S, Prandi, R, Sobrato, I, Gilardi, F, Busso, P, Piffer, S, Rizzello, R, Gentilini, M, Cappelletti, M, Rosa, F, Stracci, F, D'Alò, D, Scheibel, M, Costarelli, D, Spano, F, Rossini, S, Santucci, C, Petrinelli, A, Solimene, C, Bianconi, F, Brunori, V, Crosignani, P, Tagliabue, G, Contiero, P, Preto, L, Tittarelli, A, Maghini, A, Codazzi, T, Frassoldi, E, Gada, D, Costa, E, Grazia, L, Zambon, P, Baracco, M, Bovo, E, Cin, A, Fiore, A, Greco, A, Monetti, D, Rosano, A, Stocco, C, Donato, F, Limina, R, Adorni, A, Andreis, P, Zani, G, Piovani, F, Salvi, O, Puleio, M, Vitarelli, S, Candela, G, Pappalardo, G, Scuderi, T, Lottero, B, Ribaudo, M, Ricci, P, Guarda, L, Gatti, L, Bozzeda, A, Dall'Acqua, M, Pironi, V, Sardo, A, Mazzei, A, Sirianni, N, Lavecchia, A, Mancuso, P, Vitale, F, Cusimano, R, Amodio, R, Guttadauro, A, Ravazzolo, B, Bucalo, G, Trapani, C, Sunseri, R, Cascio, M, Brucculeri, M, Adamo, M, Mannino, R, Mistretta, A, Costa, A, Rudisi, G, Gola, G, Corti, M, Prosperini, E, Grandi, L, Sciacchitano, S, Fidelbo, M, Benedetto, G, Vasquez, E, Torrisi, A, Pesce, P, Calabretta, L, Bella, F, Leone, A, Ieni, A, Varvarà, M, Castaing, M, Di Prima, A, Benedetto, A, Paderni, F, Usala, M, Pala, F, Sini, G, Pintori, N, Canu, L, Demurtas, G, Doa, N, Lazzarato, F, Magnani, C, Merletti, F, Sarcerdote, C, Macerata, V, de Leon, M, Domati, F, Rossi, G, Goldoni, C, Rossi, F, De Gaetani, C, Benatti, P, Roncucci, L, Di Gregorio, C, Pedroni, M, Pezzi, A, Maffei, S, Mariani, F, Borsi, E, Cocchioni, M, Pascucci, C, Gennaro, V, Lazzarotto, A, Benfatto, L, Mazzucco, G, Montanaro, F, Traina, A, Carruba, G, Dolcemascolo, C, Staiti, R, Zarcone, M, Bisogno, G, Cuttini, M, De Rosa, M, Haupt, R, Soresina, A, Valsecchi, M, Fagioli, F, Bona, G, Dini, G, Conter, V, Biondi, A, Zecca, M, Fedeli, F, Massimino, M, Nespoli, L, Roncarolo, M, Basso, G, Cesaro, S, Memo, L, Bellettato, M, Tamaro, P, Mascarin, M, Rosolen, A, Izzi, G, Paolucci, P, Borgna Pignatti, C, Vecchi, V, Abate, M, D'Ambrosio, A, Favre, C, Caniglia, M, Pierani, P, Felici, L, Visani, G, Fioritoni, G, Foà, R, Riccardi, R, Frega, G, Clerico, A, Casale, F, Poggi, V, Amendola, G, Filosa, A, Ladogana, S, Presta, G, Tornesello, A, De Mattia, D, Consarino, C, Nobile, F, Sperlì, D, D'Angelo, P, Marino, S, Cosmi, C, Mura, R, Battisti, L, Maso, LD, Mosso, ML, Cappello, TD, Vercellino, PC, Orengo, MA, Celesia, MV, Cercato, MC, Artioli, ME, Vitale, MF, Rosa, MG, Giurdanella, MC, Rollo, PC, Ruggeri, MG, Romagna, Rt, Contrino, ML, Ziino, AC, Fanetti, AC, Annulli, ML, Gonzalez, ME, Gentilini, MA, Rosa, FL, Petrinelli, AM, Grazia, Ld, Cin, AD, Fiore, AR, Limina, RM, Sardo, AS, Lavecchia, AM, Cascio, MA, Brucculeri, MA, Adamo, MS, Sini, GM, de Leon, MP, Goldoni, CA, VALSECCHI, MARIA GRAZIA, BIONDI, ANDREA, Roncarolo, MG, Abate, ME, Mura, RM, and Battisti, L.

Abstract

This study describes up-to-date cancer incidence and survival in Italian paediatric and adolescent patients, based on data collected by the network of Italian cancer registries (AIRTUM). It updates the monograph published on the same topic in 2008. The main objective of this monograph is to present the statistics according to standard rigorous epidemiological methods and disseminate them to a wide range of readers, including the lay public. Given the deep impact of the 2008 monograph on the general public, in this update we complement descriptive statistics with additional data and commentaries on issues of importance for public health, in order to provide unambiguous criteria on how to interpret the statistics. The study is the result of the collaboration between AIRTUM and AIEOP (Italian Association of Paediatric Haematology and Oncology) with contributions from interested parties, including representatives of parent associations. The monograph is divided into three parts. The first part presents incidence rates, survival probabilities, and time trends, by sex, age, geographical area, and cancer site or type, by means of tables and graphs as in the previous monograph, to facilitate direct comparisons. Four articles summarize and comment the results. The second part uses data from AIRTUM and AIEOP to outline patient management and health care issues; it includes estimates of the number of new cases in the next decade and of young adults living after a paediatric cancer diagnosis. Health organizational aspects of treatment services for paediatric patients, based on the AIEOP database, are also discussed, along with long-term complications in cured patients. The third section describes the changes in mortality trends due to improving therapies and healthcare services, and discusses risk factors and prevention of childhood cancer, late adverse events in cured patients, and other related issues.

Published
2013

246. B-cell receptor configuration and adverse cytogenetics are associated with autoimmune hemolytic anemia in chronic lymphocytic leukemia

Author

Maura, F, Visco, C, Falisi, E, Reda, G, Fabris, S, Agnelli, L, Tuana, G, Lionetti, M, Guercini, N, Novella, E, Nichele, I, Montaldi, A, Autore, F, Gregorini, A, Barcellini, W, Callea, V, Mauro, Fr, Laurenti, Luca, Foà, R, Neri, A, Rodeghiero, F, Cortelezzi, A., Laurenti, Luca (ORCID:0000-0002-8327-1396), Maura, F, Visco, C, Falisi, E, Reda, G, Fabris, S, Agnelli, L, Tuana, G, Lionetti, M, Guercini, N, Novella, E, Nichele, I, Montaldi, A, Autore, F, Gregorini, A, Barcellini, W, Callea, V, Mauro, Fr, Laurenti, Luca, Foà, R, Neri, A, Rodeghiero, F, Cortelezzi, A., and Laurenti, Luca (ORCID:0000-0002-8327-1396)

Abstract

The development of autoimmune hemolytic anemia (AIHA) in patients with chronic lymphocytic leukemia (CLL) is associated with specific biological features. The occurrence of AIHA was hereby investigated in a retrospective series of 585 CLL patients with available immunoglobulin heavy chain variable (IGHV) gene status. AIHA occurred in 73 patients and was significantly associated with an IGHV unmutated (UM) status (P < 0.0001) and unfavorable [del(17)(p13) and del(11)(q23)] cytogenetic lesions (P < 0.0001). Stereotyped HCDR3 sequences were identified in 29.6% of cases and were similarly represented among patients developing or not AIHA; notably, subset #3 was associated with a significantly higher risk of AIHA than the other patients (P = 0.004). Multivariate analysis showed that UM IGHV, del(17)(p13) and del(11)(q23), but not stereotyped subset #3, were the strongest independent variables associated with AIHA. Based on these findings, we generated a biological risk score for AIHA development according to the presence of none (low risk), one (intermediated risk), or two (high risk) of the independent risk factors. Overall, our data indicate that UM IGHV status and/or unfavorable cytogenetic lesions are associated with the risk of developing secondary AIHA in CLL patients and suggest a possible role of specific stereotyped B-cell receptor subsets in a proportion of cases.

Published
2013

247. Integrated mutational and cytogenetic analysis identifies new prognostic subgroups in chronic lymphocytic leukemia

Author

Rossi, D, Rasi, S, Spina, V, Bruscaggin, A, Monti, S, Ciardullo, C, Deambrogi, C, Khiabanian, H, Serra, R, Bertoni, F, Forconi, F, Laurenti, Luca, Marasca, R, Dal Bo, M, Rossi, Fm, Bulian, P, Nomdedeu, J, Del Poeta, G, Gattei, V, Pasqualucci, L, Rabadan, R, Foà, R, Dalla Favera, R, Gaidano, G., Laurenti, Luca (ORCID:0000-0002-8327-1396), Rossi, D, Rasi, S, Spina, V, Bruscaggin, A, Monti, S, Ciardullo, C, Deambrogi, C, Khiabanian, H, Serra, R, Bertoni, F, Forconi, F, Laurenti, Luca, Marasca, R, Dal Bo, M, Rossi, Fm, Bulian, P, Nomdedeu, J, Del Poeta, G, Gattei, V, Pasqualucci, L, Rabadan, R, Foà, R, Dalla Favera, R, Gaidano, G., and Laurenti, Luca (ORCID:0000-0002-8327-1396)

Abstract

The identification of new genetic lesions in chronic lymphocytic leukemia (CLL) prompts a comprehensive and dynamic prognostic algorithm including gene mutations and chromosomal abnormalities and their changes during clonal evolution. By integrating mutational and cytogenetic analysis in 1274 CLL samples and using both a training-validation and a time-dependent design, 4 CLL subgroups were hierarchically classified: (1) high-risk, harboring TP53 and/or BIRC3 abnormalities (10-year survival: 29%); (2) intermediate-risk, harboring NOTCH1 and/or SF3B1 mutations and/or del11q22-q23 (10-year survival: 37%); (3) low-risk, harboring +12 or a normal genetics (10-year survival: 57%); and (4) very low-risk, harboring del13q14 only, whose 10-year survival (69.3%) did not significantly differ from a matched general population. This integrated mutational and cytogenetic model independently predicted survival, improved CLL prognostication accuracy compared with FISH karyotype (P < .0001), and was externally validated in an independent CLL cohort. Clonal evolution from lower to higher risk implicated the emergence of NOTCH1, SF3B1, and BIRC3 abnormalities in addition to TP53 and 11q22-q23 lesions. By taking into account clonal evolution through time-dependent analysis, the genetic model maintained its prognostic relevance at any time from diagnosis. These findings may have relevant implications for the design of clinical trials aimed at assessing the use of mutational profiling to inform therapeutic decisions.

Published
2013

248. TP53 mutations are frequent in adult acute lymphoblastic leukemia cases negative for recurrent fusion genes and correlate with poor response to induction therapy

Author

Chiaretti, S, Brugnoletti, F, Tavolaro, S, Bonina, S, Paoloni, F, Marinelli, M, Patten, N, Bonifacio, M, Kropp, Mg, Sica, Simona, Guarini, A, Foà, R., Sica, Simona (ORCID:0000-0003-2426-3465), Chiaretti, S, Brugnoletti, F, Tavolaro, S, Bonina, S, Paoloni, F, Marinelli, M, Patten, N, Bonifacio, M, Kropp, Mg, Sica, Simona, Guarini, A, Foà, R., and Sica, Simona (ORCID:0000-0003-2426-3465)

Abstract

Acute lymphoblastic leukemia (ALL) is a disease of either B-cell (80–85%) or T-cell (20–25%) derivation. Several molecular aberrations (i.e. BCR-ABL1, MLL/AFF1, SIL/TAL1 and E2A/PBX1) confer an overall poor outcome.1,2 However, a proportion of patients do not carry known genetic abnormalities and have a heterogeneous clinical course. P53 plays a crucial role in cell cycle regulation and apoptosis after DNA damage, and its role in tumorigenesis is well-recognized in solid and hematologic malignancies, particularly acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL), in which its deregulation represents an important predictor of poor outcome.3–10

Published
2013

249. Complete remission obtained with azacitidine in a patient with concomitant therapy related myeloid neoplasm and pulmonary mucormycosis

Author

Capria, S, De Angelis, F, Gentile, G, Trisolini, Sm, Brocchieri, S, Canichella, M, Chiusolo, Patrizia, Micozzi, A, Foà, R, Meloni, G., Chiusolo, Patrizia (ORCID:0000-0002-1355-1587), Capria, S, De Angelis, F, Gentile, G, Trisolini, Sm, Brocchieri, S, Canichella, M, Chiusolo, Patrizia, Micozzi, A, Foà, R, Meloni, G., and Chiusolo, Patrizia (ORCID:0000-0002-1355-1587)

Abstract

Mucormycosis is the third cause of invasive mycosis after candidiasis and aspergillosis in AML patients, representing a poor prognostic factor associated with a high rate of fatal outcome. We report a case of a patient with AML and a concomitant pulmonary mucormycosis at diagnosis, who obtained a complete remission both of her AML and of the fungal infection. The incidence of the infection at the onset of leukemia is extremely unusual, and, to our knowledge, the sporadic cases reported in the literature are included in heterogeneous series retrospectively examined. In our case, Liposomal Amphotericin B as single agent appeared incapable of controlling the infection, so anti-infective therapy was intensified with posaconazole and simultaneously antileukemic treatment with 5-azacitidine was started, with the understanding that the only antifungal treatment would not have been able to keep the infection under control for a long time if not associated with a reversal of neutropenia related to the disease. We observed a progressive improvement of the general conditions, a healing of pneumonia and a complete remission of the leukemic disease, suggesting that a careful utilization of the new compounds available today, in terms of both antifungal and antileukemic treatment, may offer a curative chance a patient who would have otherwise been considered unfit for a potentially curative therapeutic strategy.

Published
2013

250. Reduced susceptibility to apoptosis correlates with kinetic quiescence in disease progression of chronic lymphocytic leukaemia

Author

Ricciardi, Mr, Petrucci, Mt, Gregorj, C, Ariola, C, Lemoli, ROBERTO MASSIMO, Fogli, M, Mauro, Fr, Cerretti, R, Foà, R, Mandelli, F, and Tafuri, A.

Subjects
Adult, Aged, 80 and over, B-Lymphocytes, p27(kip1), T-Lymphocytes, Tumor Suppressor Proteins, Blotting, Western, Cell Cycle, Apoptosis, Cell Cycle Proteins, apoptosis, cell cycle, chronic lymphocytic leukaemia, disease progression, p27 kip1, Middle Aged, Flow Cytometry, Leukemia, Lymphocytic, Chronic, B-Cell, Culture Media, Case-Control Studies, Disease Progression, Humans, Lymphocytes, Microtubule-Associated Proteins, Cells, Cultured, Cyclin-Dependent Kinase Inhibitor p27, Aged
Abstract

The role of apoptosis and cell kinetics in the mechanisms of disease progression of chronic lymphocytic leukaemia (CLL) is still unclear. In the present study, we investigated the susceptibility of leukaemic cells taken from 75 CLL patients with either stable (STD) or progressive disease (PRD) to enter apoptosis. Particular attention was paid to the relationship between cell cycle status and autologous serum (AS). The susceptibility to enter apoptosis was significantly greater in STD than in PRD, both in standard medium (mean = 23.62% +/- 14.7 versus 14.23% +/- 7.2; P = 0.02) and in the presence of AS (mean = 23.03% +/- 17.9 versus 11.27% +/- 7.6; P = 0.01). Furthermore, cell kinetics studies revealed a higher quiescence in PRD than in STD cases, both in terms of a lower RNA content (P = 0.04) and of higher expression of the negative cell cycle regulator p27kip1 (P = 0.03). These kinetic differences were confirmed by short-term in vitro culture both in fetal calf serum and in AS. The results of this study indicate that CLL cells from PRD cases are characterized by a higher degree quiescence and much lower susceptibility to apoptosis when compared with STD ones. In this context, AS does not appear to play a specific role. The association between these kinetic characteristics and disease progression in CLL prompts further studies to establish whether higher quiescence may be responsible for the decreased susceptibility of PRD cells to enter apoptosis.

Published
2001

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