Guido Parvis
University of Turin
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Journal of Clinical Oncology | 2011
Corrado Tarella; Roberto Passera; Michele Magni; Fabio Benedetti; Andrea Rossi; Angela Gueli; Caterina Patti; Guido Parvis; Fabio Ciceri; Andrea Gallamini; Sergio Cortelazzo; Valerio Zoli; Paolo Corradini; Alessandra Carobbio; Antonino Mulè; Marco Bosa; Anna Maria Barbui; Massimo Di Nicola; Marco Sorio; Daniele Caracciolo; Alessandro M. Gianni; Alessandro Rambaldi
PURPOSE High-dose chemotherapy with peripheral blood progenitor cell (PBPC) autograft is effective in high-risk lymphoma, particularly with the addition of rituximab; however, it is associated with risk of secondary malignancy. These issues have been addressed in a series of 1,347 patients with lymphoma treated with a high-dose sequential (HDS) program. PATIENTS AND METHODS A total of 1,024 patients with B-cell lymphoma, 234 patients with Hodgkins lymphoma, and 89 patients with T-cell lymphoma were treated with HDS between 1985 and 2005 at 11 Gruppo Italiano Terapie Innovative Linfomi centers. HDS was given as salvage treatment to 707 patients (52%); 655 patients (49%) received a modified HDS, with high-dose cytarabine and two consecutive PBPC harvests. Rituximab-supplemented HDS was given to 523 patients (39%). RESULTS At a median follow-up of 7 years, the median overall survival (OS) was 16.2 years; in B-cell lymphoma the OS was significantly superior with rituximab HDS compared to HDS alone. The cumulative incidence at 5 and 10 years of secondary myelodysplasia/acute leukemia (sMDS/AL) were 3.09% and 4.52%, respectively, that of solid tumors were 2.54% and 6.79%, respectively. Factors associated with sMDS/AL were male sex and use of the second harvest PBPC for the graft; factors found to be associated with solid tumor were advanced age, post-HDS radiotherapy, and rituximab addition to HDS. Despite the increased risk of solid tumors, rituximab addition to HDS was still associated with survival advantages. CONCLUSION This analysis has relevant implications for the design and use of intensive chemoimmunotherapy with autograft. In addition, it offers useful insights toward the understanding and prevention of tumor development.
Leukemia & Lymphoma | 1992
Federico Caligaris-Cappio; M. G. Gregoretti; Franca Merico; Daniela Gottardi; Paolo Ghia; Guido Parvis; Luciana Bergui
The BM microenvironment in MM, in terms of adhesive features, is well organized to entrap circulating precursors with BM-seeking properties and is able to produce cytokines that offer them the optimal conditions for local growth and final differentiation. Likewise, the malignant B cell clone is equipped with adhesion molecules which enable the cell to establish close contacts with BM stromal cells. Furthermore a number of cytokines are released including IL-1 beta and M-CSF activating BM stromal cells to produce other cytokines, such as IL-6, that stimulate the proliferation of plasma cells. Finally, most cytokines produced locally, including IL-1 beta, TNF-beta, M-CSF, IL-3 and IL-6, also have OAF properties, explaining why the expansion of the B cell clone parallels the activation and numerical increase of the osteoclast population.
Journal of Clinical Oncology | 2013
Umberto Vitolo; Marco Ladetto; Carola Boccomini; Luca Baldini; Federico De Angelis; Alessandra Tucci; Barbara Botto; Annalisa Chiappella; Annalisa Chiarenza; Antonello Pinto; Amalia De Renzo; Francesco Zaja; Claudia Castellino; Alessia Bari; Isabel Alvarez De Celis; Andrea Evangelista; Guido Parvis; Enrica Gamba; Chiara Lobetti-Bodoni; Giovannino Ciccone; Giuseppe Rossi
PURPOSE To evaluate the efficacy of rituximab maintenance in 60- to 75-year-old patients with advanced follicular lymphoma responding to brief first-line chemoimmunotherapy followed by rituximab consolidation. PATIENTS AND METHODS A total of 234 treatment-naive 60- to 75-year-old patients began chemoimmunotherapy with four monthly courses of rituximab, fludarabine, mitoxantrone, and dexamethasone (R-FND) followed by four weekly cycles of rituximab consolidation. Of these, 210 patients completed the planned treatment, and 202 responders were randomly assigned to rituximab maintenance (arm A) for 8 months, once every 2 months for a total of four doses, or to observation (arm B). RESULTS Median ages in arms A and B were 66 and 65 years, respectively. After induction and consolidation therapy, the overall response rate was 86%, with 69% complete remissions (CR). After a 42-month median follow-up from diagnosis, 3-year progression-free survival (PFS; the primary end point) and overall survival (OS) were 66% (95% CI, 59% to 72%) and 89% (95% CI, 85% to 93%), respectively. After randomization, 2-year PFS was 81% for rituximab maintenance versus 69% for observation, with a hazard ratio of 0.74 (95% CI, 0.45 to 1.21; P = .226), although this was not statistically significant. No differences between the two arms were detected for OS. Overall, the regimen was well-tolerated. The most frequent grade 3 to 4 toxicity was neutropenia (25% of treatment courses), with 13 infections. Two toxic deaths (0.8%) occurred during induction treatment. CONCLUSION A brief R-FND induction plus rituximab consolidation achieved excellent results with high CR and PFS rates, supporting the feasibility of this regimen in patients older than 60 years. A short rituximab maintenance did not achieve a statistically significant PFS improvement over observation.
Annals of Hematology | 1996
Gisella Volpe; B. Gamberi; Cristina Pastore; A. Roetto; M. Pautasso; Guido Parvis; C. Camaschella; Umberto Mazza; G. Saglio; Gianluca Gaidano
Microsatellite instability (MSI) represents one specific pattern of genomic instability and is one of the genetic lesions most frequently detected in human neoplasia. Although MSI has been found to be associated with a wide variety of solid cancers, its involvement in lymphoid malignancies is virtually unexplored. In this study, we have investigated the presence of MSI in chronic lymphoproliferative disorders by comparing the pattern of nine microsatellite repeats (two tetranucleotides, two trinucleotides, and five dinucleotides) on autologous germline and tumor DNA of 23 patients, including 17 with B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (B-CLL/SLL), four with hairy cell leukemia, one with lymphoplasmacytoid lymphoma, and one with T-cell chronic lymphocytic leukemia. All samples at diagnosis displayed a germline pattern of the microsatellites examined, thus suggesting that MSI is not involved in the pathogenesis of these lymphoproliferations. Also, no microsatellite alterations were observed in consecutive samples of B-CLL/SLL obtained from the same patient at various stages of the disease both before and after chemotherapy. Conversely, alterations in 3/9 microsatellite repeats were detected in one case of Richters syndrome which had evolved from a pre-existent B-CLL/SLL phase. Overall, the low frequency of MSI among chronic lymphoproliferative disorders adds further weight to the common view that the mechanisms and patterns of genomic instability in lymphoid neoplasia differ markedly from those commonly observed in solid cancers.
Leukemia & Lymphoma | 2013
Andrea Riccardo Filippi; Angela Botticella; Marilena Bellò; Barbara Botto; Anna Castiglione; Paolo Gavarotti; Daniela Gottardi; Guido Parvis; Gianni Bisi; Alessandro Levis; Umberto Vitolo; Umberto Ricardi
Abstract The aim of the study was to investigate whether interim positron emission tomography (iPET) is prognostic in a cohort of patients with early stage Hodgkin lymphoma (HL) homogeneously treated with 3–4 cycles of ABVD (adriamycin, bleomycin, vinblastine and dacarbazine) followed by 30 Gy involved field radiotherapy. Eighty patients were selected (stage I–IIA HL, availability of iPET, minimum follow-up of 12 months), and after central review, 70 were judged negative (iPET−: 87.5%) and 10 positive (iPET+: 12.5%). The two groups were then analyzed for response, progression-free survival (PFS) and overall survival (OS). Only one out of 70 iPET− patients relapsed, with 69 in continuous complete remission (CCR). All 10 iPET + patients achieved a complete response and maintained persistent CCR at follow-up. The 3-year PFS and OS were, respectively, 97% and 98.4% for iPET− and 100% and 100% for iPET+ (p = 0.63). iPET positivity does not seem to be a significant prognostic factor, and change in therapeutic strategy on the basis of iPET does not appear currently advisable outside clinical trials.
Bone Marrow Transplantation | 2009
Michele Magni; M. Di Nicola; Carmelo Carlo-Stella; Paola Matteucci; L Devizzi; Corrado Tarella; Fabio Benedetti; Maurizio Martelli; Caterina Patti; Guido Parvis; Alessandro Rambaldi; Tiziano Barbui; A. M. Gianni
High-dose sequential chemotherapy and in vivo rituximab-purged stem cell autografting in mantle cell lymphoma: a 10-year update of the R-HDS regimen
British Journal of Haematology | 2006
Davide Rossi; Clara Deambrogi; Daniela Capello; Michaela Cerri; Monia Lunghi; Guido Parvis; Giuseppe Saglio; Gianluca Gaidano; Daniela Cilloni
The natural history of Philadelphia-negative chronic myeloproliferative disorders (Ph-CMPD) is characterised by a chronic phase that, in a fraction of cases, may progress to acute leukaemia (Jaffe et al, 2001). The risk of leukaemic transformation is time-, ageand treatment-dependent, and is approximately 1–5% for essential thrombocythaemia (ET), 5–10% for polycythaemia vera (PV) and 10–30% for idiopathic myelofibrosis (IMF) (Jaffe et al, 2001). The JAK2 mutation occurs in 70–90% of PV and 30–50% ET and IMF (Baxter et al, 2005; Kralovics et al, 2005) in chronic phase. The aim of this study was to verify the prevalence of the JAK2 mutation in acute myeloid leukaemia (AML) evolved from Ph-CMPD. Samples were derived from five PV, ten ET and five IMF patients at the time of transformation to AML. In four cases (cases 12A/12B, 13A/13B, 14A/14B, 15A/15B), the corresponding chronic phase was also available. Bone marrow (BM) samples were collected at diagnosis of chronic and/or leukaemic phase. Chronic phases of PV, ET and IMF and AML were diagnosed according to the World Health Organization criteria (Jaffe et al, 2001). In all cases, the presence of BCR/ABL rearrangement was ruled out. For each patient, BM samples were simultaneously investigated for the JAK2 mutation by cDNA sequencing and mutation-specific polymerase chain reaction (Baxter et al, 2005; Kralovics et al, 2005). All patients provided informed consent. The JAK2 mutation was identified in 5/20 (25Æ0%) AML secondary to Ph-CMPD (Table I). In all mutated cases, the normal JAK2 sequence could be detected in addition to the mutated allele. JAK2 mutation occurred in 3/5 (60Æ0%) cases of AML transformed from PV, 2/5 (40Æ0%) AML transformed from IMF and 0/11 AML transformed from ET (Table I). In four AML transformed from ET (cases 12B, 13B, 14B, 15B), the corresponding chronic phase sample was also
Journal of Clinical Oncology | 2018
Andrea Gallamini; Corrado Tarella; Simonetta Viviani; Andrea Rossi; Caterina Patti; Antonino Mulè; Marco Picardi; Alessandra Romano; Maria Cantonetti; Giorgio La Nasa; Livio Trentin; Silvia Bolis; Davide Rapezzi; Roberta Battistini; Daniela Gottardi; Paolo Gavarotti; Paolo Corradini; Michele Cimminiello; Corrado Schiavotto; Guido Parvis; Roberta Zanotti; Guido Gini; Andrés J.M. Ferreri; Piera Viero; Maurizio Miglino; Atto Billio; Abraham Avigdor; Alberto Biggi; Federico Fallanca; Umberto Ficola
Purpose To investigate the progression-free survival (PFS) of patients with advanced Hodgkin lymphoma (HL) after a risk-adapted treatment strategy that was based on a positive positron emission tomography scan performed after two doxorubicin, vinblastine, vincristine, and dacarbazine (ABVD) cycles (PET2). Patients and Methods Patients with advanced-stage (IIB to IVB) HL were consecutively enrolled. After two ABVD cycles, PET2 was performed and centrally reviewed according to the Deauville five-point scale. Patients with a positive PET2 were randomly assigned to four cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) followed by four cycles of standard BEACOPP with or without rituximab. Patients with a negative PET2 continued ABVD, and those with a large nodal mass at diagnosis (≥ 5 cm) in complete remission with a negative PET at the end of chemotherapy were randomly assigned to radiotherapy or no further treatment. The primary end point was 3-year PFS. Results Of 782 enrolled patients, 150 (19%) had a positive and 630 (81%) a negative PET2. The 3-year PFS of all patients was 82%. The 3-year PFS of those with a positive and negative PET2 was 60% and 87%, respectively ( P < .001). The 3-year PFS of patients with a positive PET2 assigned to BEACOPP with or without rituximab was 63% versus 57% ( P = .53). In 296 patients with both interim and post-ABVD-negative PET who had a large nodal mass at diagnosis, radiotherapy was randomly added after chemotherapy without a significant PFS improvement (97% v 93%, respectively; P = .29). The 3-year overall survival of all 782 patients was 97% (99% and 89% for PET2 negative and positive, respectively). Conclusion The PET-driven switch from ABVD to escalated BEACOPP is feasible and effective in high-risk patients with advanced-stage HL.
Bone Marrow Transplantation | 2014
Michele Magni; M. Di Nicola; Caterina Patti; Rosanna Scimè; Antonio Mulè; Alessandro Rambaldi; T Intermesoli; P Viero; Corrado Tarella; Angela Gueli; L Bergui; Livio Trentin; A Barzan; Fabio Benedetti; Achille Ambrosetti; F. Di Raimondo; Annalisa Chiarenza; Guido Parvis; Atto Billio; I Attolico; Attilio Olivieri; Mauro Montanari; Carmelo Carlo-Stella; Paola Matteucci; L Devizzi; Anna Guidetti; Simonetta Viviani; Pinuccia Valagussa; A. M. Gianni
The importance of early therapy intensification in B-cell CLL (B-CLL) patients remains to be defined. Even though several studies have been published, no randomized trials comparing directly autologous stem cell transplant (ASCT) and the accepted conventional therapy (that is, rituximab, fludarabine and CY; R-FC) have been reported so far. To assess the benefit of a first-line aggressive therapy, we designed a multicenter, randomized, phase 3 trial comparing R-FC and high-dose chemotherapy supported by ASCT in patients under 65 years of age, with stage B(II) or C B-CLL. Primary end point was CR: 96 patients were enrolled (48 in each arm). On an intent-to-treat basis, the CR rates in the ASCT and R-FC arms were 62.5% and 58%, respectively. After 5 years of follow-up, PFS was 60.4% in the ASCT arm and 65.1% in the R-FC arm, time to progression 65.8 and 70.5%, and overall survival 88% vs 88.1%, respectively. Our trial demonstrates, for the first time in a randomized manner, that frontline ASCT does not translate into a survival advantage when compared with benchmark chemoimmunotherapy in B-CLL patients; the possibility of its clinical benefit in certain subgroups remains uncertain.
Oncotarget | 2017
Giovanna Carrà; Cristina Panuzzo; Davide Torti; Guido Parvis; Sabrina Crivellaro; Ubaldo Familiari; Marco Volante; Deborah Morena; Marcello Francesco Lingua; Mara Brancaccio; Angelo Guerrasio; Pier Paolo Pandolfi; Giuseppe Saglio; Riccardo Taulli; Alessandro Morotti
Chronic Lymphocytic Leukemia (CLL) is a lymphoproliferative disorder with either indolent or aggressive clinical course. Current treatment regiments have significantly improved the overall outcomes even if higher risk subgroups - those harboring TP53 mutations or deletions of the short arm of chromosome 17 (del17p) - remain highly challenging. In the present work, we identified USP7, a known de-ubiquitinase with multiple roles in cellular homeostasis, as a potential therapeutic target in CLL. We demonstrated that in primary CLL samples and in CLL cell lines USP7 is: i) over-expressed through a mechanism involving miR-338-3p and miR-181b deregulation; ii) functionally activated by Casein Kinase 2 (CK2), an upstream interactor known to be deregulated in CLL; iii) effectively targeted by the USP7 inhibitor P5091. Treatment of primary CLL samples and cell lines with P5091 induces cell growth arrest and apoptosis, through the restoration of PTEN nuclear pool, both in TP53-wild type and -null environment. Importantly, PTEN acts as the main tumor suppressive mediator along the USP7-PTEN axis in a p53 dispensable manner. In conclusion, we propose USP7 as a new druggable target in CLL.