Paolo Servida
Vita-Salute San Raffaele University
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Featured researches published by Paolo Servida.
Science | 1995
Claudio Bordignon; Luigi D. Notarangelo; Nadia Nobili; Giuliana Ferrari; Giulia Casorati; Paola Panina; Evelina Mazzolari; Daniela Maggioni; Claudia Rossi; Paolo Servida; Alberto G. Ugazio; Fulvio Mavilio
Adenosine deaminase (ADA) deficiency results in severe combined immunodeficiency, the first genetic disorder treated by gene therapy. Two different retroviral vectors were used to transfer ex vivo the human ADA minigene into bone marrow cells and peripheral blood lymphocytes from two patients undergoing exogenous enzyme replacement therapy. After 2 years of treatment, long-term survival of T and B lymphocytes, marrow cells, and granulocytes expressing the transferred ADA gene was demonstrated and resulted in normalization of the immune repertoire and restoration of cellular and humoral immunity. After discontinuation of treatment, T lymphocytes, derived from transduced peripheral blood lymphocytes, were progressively replaced by marrow-derived T cells in both patients. These results indicate successful gene transfer into long-lasting progenitor cells, producing a functional multilineage progeny.
Lancet Oncology | 2009
Fabio Ciceri; Chiara Bonini; Maria Teresa Lupo Stanghellini; Attilio Bondanza; Catia Traversari; Monica Salomoni; Lucia Turchetto; Scialini Colombi; Massimo Bernardi; Jacopo Peccatori; Alessandra Pescarollo; Paolo Servida; Zulma Magnani; Serena Kimi Perna; Veronica Valtolina; Fulvio Crippa; Luciano Callegaro; Elena Spoldi; Roberto Crocchiolo; Katharina Fleischhauer; Maurilio Ponzoni; Luca Vago; Silvano Rossini; Armando Santoro; Elisabetta Todisco; Jane F. Apperley; Eduardo Olavarria; Shimon Slavin; Eva M. Weissinger; Arnold Ganser
BACKGROUND Procedures to prevent severe graft-versus-host disease (GVHD) delay immune reconstitution secondary to transplants of haploidentical haemopoietic stem cells for the treatment of leukaemia, leading to high rates of late infectious mortality. We aimed to systematically add back genetically engineered donor lymphocytes to facilitate immune reconstitution and prevent late mortality. METHODS In a phase I-II, multicentre, non-randomised trial of haploidentical stem-cell transplantation, we infused donor lymphocytes expressing herpes-simplex thymidine kinase suicide gene (TK-cells) after transplantation. The primary study endpoint was immune reconstitution defined as circulating CD3+ count of 100 cells per muL or more for two consecutive observations. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00423124. FINDINGS From Aug 13, 2002, to March 26, 2008, 50 patients (median age 51 years, range 17-66) received haploidentical stem-cell transplants for high-risk leukaemia. Immune reconstitution was not recorded before infusion of TK-cells. 28 patients received TK-cells starting 28 days after transplantation; 22 patients obtained immune reconstitution at median 75 days (range 34-127) from transplantation and 23 days (13-42) from infusion. Ten patients developed acute GVHD (grade I-IV) and one developed chronic GVHD, which were controlled by induction of the suicide gene. Overall survival at 3 years was 49% (95% CI 25-73) for 19 patients who were in remission from primary leukaemia at the time of stem-cell transplantation. After TK-cell infusion, the last death due to infection was at 166 days, this was the only infectious death at more than 100 days. No acute or chronic adverse events were related to the gene-transfer procedure. INTERPRETATION Infusion of TK-cells might be effective in accelerating immune reconstitution, while controlling GVHD and protecting patients from late mortality in those who are candidates for haploidentical stem-cell transplantation. FUNDING MolMed SpA, Italian Association for Cancer Research.
Leukemia & Lymphoma | 2008
Roberto Crocchiolo; Carla Canevari; Andrea Assanelli; Francesca Lunghi; Michela Tassara; Maria Teresa Lupo Stanghellini; Daniela Clerici; Claudio Landoni; Paolo Servida; Massimo Bernardi; Jacopo Peccatori; Andrés J.M. Ferreri; Luigi Gianolli; Claudio Bordignon; Federico Caligaris-Cappio; Fabio Ciceri; Ferruccio Fazio
We evaluated the prognostic role of 18FDG-PET performed before ASCT in patients affected by lymphoma who underwent high-dose chemotherapy followed by ASCT as first-line treatment for high-risk disease or as second-line or more for relapsed or refractory disease. We retrospectively analyzed 53 consecutive patients, 14 with Hodgkin Lymphoma (HL) and 39 with non-Hodgkin Lymphoma (NHL), treated between February 1999 and October 2006 at our institution, who had a pre-ASCT FDG-PET (pPET) evaluation. Median age was 45 years (range: 18 – 69). After a median follow-up of 31 months (range: 8 – 91), 7 out of 16 pPET+ patients and 10 out of 37 pPET− patients experienced lymphoma relapse. The 5-year OS is 90% and 55% (p = 0.01) in patients with negative and positive pPET, respectively. In conclusion, a positive pPET indicates a poorer outcome after ASCT with respect to a negative pPET; this subset of patients should be considered candidate to more intensive or investigational approaches.
Modern Pathology | 2004
Maurilio Ponzoni; David G. Savage; Andrés J.M. Ferreri; Giancarlo Pruneri; Giuseppe Viale; Paolo Servida; Francesco Bertolini; Attilio Orazi
Microvascular density (MVD) is substantially increased in bone marrow biopsies of patients with chronic idiopathic myelofibrosis (CIMF). CD105, a useful molecule for assessing MVD in various malignancies, is preferentially expressed by recently formed microvessels. Increased serum-soluble CD105 in patients with chronic myeloproliferative disorders, including CIMF, was documented. CD105 MVD has not so far been investigated in CIMF: to this end, the results in 55 patients with CIMF and 21 controls were compared with the conventional CD34 immunostaining as well as traditional histological and clinical disease features. The MVD mean values estimated by both CD105 and CD34 were significantly higher in CIMF patients than in controls (P<0.00001). In addition, the proportion of CD105-positive megakaryocytes was significantly higher in CIMF than in controls (P<0.0001). A degree of reticulin fibrosis >2 correlated with increased CD105 MVD (P=0.05). A multivariate analysis confirmed that CD105-positive MVD was an independent adverse prognosticator. This study demonstrates that while MVD, as assessed by both CD34 and CD105 immunostaining, is significantly increased in CIMF, only CD105-determined MVD correlates with the degree of fibrosis and is prognostically relevant. These findings provide a rationale for the investigational use of anti-CD105-targeted drugs in CIMF.
Hematology-oncology Clinics of North America | 1998
Effie W. Petersdorf; Claudio Anasetti; Paolo Servida; Paul Martin; John A. Hansen
This article examines the diversity and biologic role of human lymphocyte antigen (HLA) genes as related to marrow transplantation for chronic myelogenous leukemia (CML). A better understanding of the nature and function of HLA variation is necessary as unrelated marrow transplantation evolves into a safe and effective treatment for CML. HLA matching is an important aspect of donor selection criteria and has a role in engraftment as well as the development of graft-versus-host disease and tolerance after transplant.
Bone Marrow Transplantation | 2006
Macro Bregni; Katharina Fleischhauer; Massimo Bernardi; Alessandra Pescarollo; E. Guggiari; F. Lunghi; S. Deola; S. Scaramuzza; F. Re; E. Setola; M. Monari; B. Mazzi; Paolo Servida; Paolo Corradini; Jacopo Peccatori
We assessed mammaglobin (MMG) gene expression in bone marrow (BM) aspirates from patients with advanced breast cancer who had received a reduced-intensity conditioning and stem cell allografting, in order to detect a graft-versus-tumor effect on micrometastatic disease. Nine patients received a reduced-intensity conditioning with fludarabine, cyclophosphamide, and thiotepa, followed by peripheral blood allografting from HLA-identical sibling donors. Nested RT-PCR analysis with sequence-specific primers for MMG was carried out on a monthly basis on BM samples. Three patients had MMG-positive BM, four patients had MMG-negative BM before allografting, and two were undetermined. In two patients, a clinical response after allografting (partial remission) occurred concurrently with the clearance of MMG expression, at a median of 6 months after allografting, following immune manipulation. In two patients, a prolonged stable disease and negative MMG expression occurred after day +360 from allografting. In two patients, progression of the disease was associated with MMG RT-PCR changing from negative to positive. In one case, a disease response occurring after donor lymphocyte infusion and grade II acute GVHD was heralded by negativization of MMG expression. Although preliminary, these data suggest that a graft-versus-breast cancer effect is detectable on micrometastatic BM disease.
Science | 1997
Chiara Bonini; Giuliana Ferrari; Simona Verzeletti; Paolo Servida; Elisabetta Zappone; Luciano Ruggieri; Maurilio Ponzoni; Silvano Rossini; Fulvio Mavilio; Catia Traversari; Claudio Bordignon
Science | 2002
Alessandro Aiuti; Shimon Slavin; Memet Aker; Francesca Ficara; Sara Deola; Alessandra Mortellaro; Shoshana Morecki; Grazia Andolfi; Antonella Tabucchi; Filippo Carlucci; Enrico Marinello; Federica Cattaneo; Sergio Vai; Paolo Servida; Miniero R; Maria Grazia Roncarolo; Claudio Bordignon
Human Gene Therapy | 1995
Principal Investigators: Claudio Bordignon; Chiara Bonini; Investigators: Simona Verzeletti; Nadia Nobili; Daniela Maggioni; Catia Traversari; Raffaella Giavazzi; Paolo Servida; Elisabetta Zappone; Elena Benazzi; Massimo Bernardi; Fulvio Porta; Fulvio Mavilio; Silvano Rossini; R. Michael Blaese; Fabio Candotti
Blood | 2007
Fabio Ciceri; Chiara Bonini; Sarah Marktel; Elisabetta Zappone; Paolo Servida; Massimo Bernardi; Alessandra Pescarollo; Attilio Bondanza; Jacopo Peccatori; Silvano Rossini; Zulma Magnani; Monica Salomoni; Claudia Benati; Maurilio Ponzoni; Luciano Callegaro; Paolo Corradini; Marco Bregni; Catia Traversari; Claudio Bordignon