Publications by authors named "Valerio Zoli"

13 Publications

  • Page 1 of 1

The neutrophil to lymphocyte ratio (NLR) and the presence of large nodal mass are independent predictors of early response: A subanalysis of the prospective phase II PET-2-adapted HD0607 trial.

Cancer Med 2020 Dec 6;9(23):8735-8746. Epub 2020 Nov 6.

Ematologia, Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy.

Background: The neutrophil to lymphocyte ratio (NLR) and the lymphocyte to monocyte ratio (LMR) can reflect both the myeloid dysfunction and T-cell immune suppression and have prognostic significance.

Methods: In 771 newly diagnosed advanced-stage Hodgkin Lymphoma (HL) patients we evaluated the baseline values of NLR and LMR as predictors of clinical outcome. According to the multicenter prospective phase II GITIL-HD0607 trial, all patients received two ABVD courses and if PET-2 negative received four additional ABVD cycles while if PET-2-positive patients were randomized to either BEACOPP escalated (Be) plus BEACOPP baseline (Bb) (4 + 4 courses) or Be + Bb (4 + 4) and Rituximab. PET scans were centrally reviewed by an expert panel by Blinded Independent Central Review.

Results: Higher NLR and lower LMR were associated with a PET-2 positivity and failure to achieve long-term disease control, respectively. By univariate and multivariate analysis, large nodal mass (>7 cm), IPS ≥ 3, NLR > 6 were strong independent predictors of early PET-2 response after ABVD. Only NLR > 6 and IPS ≥ 3 were strong independent predictors of outcome at diagnosis; however, when PET-2 status was added, only PET-2-positive status and IPS ≥ 3 were independent predictors of PFS. Focusing on PET-2-negative patients, those with NLR > 6 had an inferior 3-year PFS compared to patients with NLR ≤ 6 (84% vs 89% months, P = .03).

Conclusion: In advanced-stage HL patients treated with a PET-2-driven strategy, IPS ≥ 3 and NLR > 6 are independent predictors of outcome at diagnosis while the presence of large nodal mass, IPS ≥ 3, and NLR > 6 at diagnosis are independent predictors of early ABVD response.
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http://dx.doi.org/10.1002/cam4.3396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724487PMC
December 2020

Treatment and prognosis of primary pulmonary lymphoma: A long-term follow-up study.

Eur J Haematol 2021 Jan 2;106(1):49-57. Epub 2020 Nov 2.

Haematology and Haematopoietic Stem Cells Transplant Unit, AO San Camillo-Forlanini, Rome, Italy.

Primary pulmonary lymphoma (PPL) is a rare disease with not well-defined optimal treatment. Outcomes and follow-up are variable in published data.

Objectives: To define the outcome and optimal treatment strategies in PPL.

Methods: We reviewed the medical records of 49 patients with PPL treated in three Italian Hematological Institutions between 2002 and 2018.

Results: Thirty-eight (77.5%) cases were indolent PPL, and 11 (22.5%) cases were aggressive PPL. The majority of patients were asymptomatic at diagnosis, early stages (stages IE-IIE), normal serum LDH, no bone marrow involvement, and low or low-intermediate risks of IPI. Local therapy ± immunotherapy or immuno-chemotherapy was possible in 18/49 (37%) patients. Twenty-eight (57%) patients were treated with immuno-chemotherapy after biopsy. Waiting and watching were reported in 3 (6%) patients. Overall, the CR and ORR were 83.7% and 95.9%. With a median follow-up of 62.5 months (range 0.8-199 months), the estimated 5- and 10-year OS rates were 85% and 72.3% for all patients, 89.2% and 80.3% for indolent PPL, and 70.7% and 47.1% for aggressive PPL. Aggressive PPL tended to have a high risk of progression in the first months (P = .056). No advantages were found for indolent PPL who received immuno-chemotherapy or more conservative approaches.

Conclusion: Our studies confirm the epidemiological and favorable survival of patients with PPL, suggesting a very conservative approach, particularly in indolent subtypes.
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http://dx.doi.org/10.1111/ejh.13507DOI Listing
January 2021

Prolonged survival in the absence of disease-recurrence in advanced-stage follicular lymphoma following chemo-immunotherapy: 13-year update of the prospective, multicenter randomized GITMO-IIL trial.

Haematologica 2019 11 11;104(11):2241-2248. Epub 2019 Apr 11.

Onco-Hematology Division, IEO, European Institute of Oncology IRCCS, Milano

A prospective trial conducted in the period 2000-2005 showed no survival advantage for high-dose chemotherapy with rituximab and autograft (R-HDS) conventional chemotherapy with rituximab (CHOP-R) as first-line therapy in 134 high-risk follicular lymphoma patients aged <60 years. The study has been updated at the 13-year median follow up. As of February 2017, 88 (66%) patients were alive, with overall survival of 66.4% at 13 years, without a significant difference between R-HDS (64.5%) and CHOP-R (68.5%). To date, 46 patients have died, mainly because of disease progression (47.8% of all deaths), secondary malignancies (3 solid tumor, 9 myelodysplasia/acute leukemia; 26.1% of all deaths), and other toxicities (21.7% of all deaths). Complete remission was documented in 98 (73.1%) patients and associated with overall survival, with 13-year estimates of 77.0% and 36.8% for complete remission no-complete remission, respectively. Molecular remission was documented in 39 (65%) out of 60 evaluable patients and associated with improved survival. In multivariate analysis, complete remission achievement had the strongest effect on survival (<0.001), along with younger age (=0.002) and female sex (=0.013). Overall, 50 patients (37.3%) survived with no disease recurrence (18 CHOP-R, 32 R-HDS). This follow up is the longest reported on follicular lymphoma treated upfront with rituximab-chemotherapy and demonstrates an unprecedented improvement in survival compared to the pre-rituximab era, regardless of the use of intensified or conventional treatment. Complete remission was the most important factor for prolonged survival and a high proportion of patients had prolonged survival in their first remission, raising the issue of curability in follicular lymphoma. (Registered at clinicaltrials.gov identifier: 00435955).
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http://dx.doi.org/10.3324/haematol.2018.209932DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6821615PMC
November 2019

Antiviral therapy in hepatitis C-infected patients prevents relapse of diffuse large B cell lymphoma.

Clin Exp Hepatol 2018 Sep 10;4(3):197-200. Epub 2018 May 10.

MASVE Center University of Florence, Italy.

Introduction: Hepatitis C infection (HCV) is highly prevalent worldwide and has a well-known association with B-cell lymphoid malignancies. While several studies have demonstrated that antiviral therapy (AT) is effective to induce a complete hematological response in HCV-related low-grade B cell lymphoma, in HCV-related high-grade B cell non-Hodgkin lymphomas such as diffuse large B cell lymphoma (DLBCL) chemotherapy is the only possible choice. However, the role of AT to reduce relapse of DLBCL after an effective chemotherapy containing rituximab (CT-R) has not been analyzed in previous studies. Therefore we analyzed whether patients with a sustained virological response (SVR) to AT had over time a reduction of lymphoma relapse compared to no-SVR patients.

Material And Methods: The study included 21 consecutive HCV-infected patients affected by DLBCL. The patients were treated with AT (direct-acting antivirals or pegylated interferon alfa plus ribavirin) concomitantly or after CT-R. Over time, we evaluated relapse of DLBCL in patients treated with CT-R according to response to AT.

Results: An SVR was achieved in 16 of 21 patients. Five patients relapsed on AT with PegIFN/R (pegylated interferon plus ribavirin). Over time lymphoma relapse was more frequent in patients without a virological response compared with patients with an SVR (RR = 12.0, 95% CI: 1.66-86, < 0.01 Fisher's exact test).

Conclusions: AT during or after CT-R is an important strategy to prevent relapse of DLBCL in HCV patients when the patients have achieved an SVR. Our results suggest that eradication of HCV infection may result in long-term prevention of B-cell non-Hodgkin's lymphoma relapse.
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http://dx.doi.org/10.5114/ceh.2018.78124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6185930PMC
September 2018

Randomized Trial Comparing R-CHOP Versus High-Dose Sequential Chemotherapy in High-Risk Patients With Diffuse Large B-Cell Lymphomas.

J Clin Oncol 2016 11 31;34(33):4015-4022. Epub 2016 Oct 31.

Sergio Cortelazzo, Atto Billio, Andrea Piccin, and Giovanni Negri, Ospedale Centrale di Bolzano, Bolzano; Corrado Tarella and Riccardo Bruna, Azienda Ospedaliera Ordine Mauriziano and University of Turin; Marco Ladetto and Manuela Zanni, Azienda Ospedaliera Universitaria (AOU) Città della Salute e della Scienza, Turin; Alessandro Massimo Gianni, Paolo Corradini, and Massimo Di Nicola, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Nazionale dei Tumori, University of Milano; Andrés J.M. Ferreri, IRCCS San Raffaele Scientific Institute; Valentina Tabanelli and Stefano Pileri, Istituto Europeo di Oncologia; Alessandro Rambaldi, University of Milano, Milan; Anna Maria Barbui, Andrea Rossi, Giuseppe Gritti, Arianna Masciulli, Federica Delaini, Cristina Boschini, and Alessandro Rambaldi, Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo; Caterina Patti and Antonino Mulé, Azienda Ospedali Riuniti Villa Sofia-Cervello, Palermo; Valerio Zoli, Ospedale San Camillo Forlanini, Rome; Claudia Castellino, Ospedale S. Croce e Carle, Cuneo; Francesco Di Raimondo, AOU Policlinico Vittorio Emanuele University of Catania, Catania; Fabio Benedetti, University of Verona; Marco Chilosi, Azienda Ospedaliera Universitaria Integrata Verona, Verona; Giorgio La Nasa, Ospedale Binaghi, Cagliari; Guido Gini, Ospedali Riuniti, Ancona; Livio Trentin, Azienda Ospedaliera-Università di Padova, Padua; Maurizio Frezzato, Ospedale San Bortolo, Vicenza; Leonardo Flenghi, Azienda Ospedaliera di Perugia, Perugia; and Simona Falorio, Ospedale Civile Spirito Santo, Pescara, Italy.

Purpose The benefit of high-dose chemotherapy with autologous stem-cell transplantation (ASCT) as first-line treatment in patients with diffuse large B-cell lymphomas is still a matter of debate. To address this point, we designed a randomized phase III trial to compare rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP)-14 (eight cycles) with rituximab plus high-dose sequential chemotherapy (R-HDS) with ASCT. Patients and Methods From June 2005 to June 2011, 246 high-risk patients with a high-intermediate (56%) or high (44%) International Prognostic Index score were randomly assigned to the R-CHOP or R-HDS arm, and 235 were analyzed by intent to treat. The primary efficacy end point of the study was 3-year event-free survival, and results were analyzed on an intent-to-treat basis. Results Clinical response (complete response, 78% v 76%; partial response, 5% v 9%) and failures (no response, 15% v 11%; and early treatment-related mortality, 2% v 3%) were similar after R-CHOP versus R-HDS, respectively. After a median follow-up of 5 years, the 3-year event-free survival was 62% versus 65% ( P = .83). At 3 years, compared with the R-CHOP arm, the R-HDS arm had better disease-free survival (79% v 91%, respectively; P = .034), but this subsequently vanished because of late-occurring treatment-related deaths. No difference was detected in terms of progression-free survival (65% v 75%, respectively; P = .12), or overall survival (74% v 77%, respectively; P = .64). Significantly higher hematologic toxicity ( P < .001) and more infectious complications ( P < .001) were observed in the R-HDS arm. Conclusion In this study, front-line intensive R-HDS chemotherapy with ASCT did not improve the outcome of high-risk patients with diffuse large B-cell lymphomas.
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http://dx.doi.org/10.1200/JCO.2016.67.2980DOI Listing
November 2016

Hepatitis C virus-related B cell subtypes in non Hodgkin's lymphoma.

World J Hepatol 2011 Nov;3(11):278-84

Adriano M Pellicelli, Cecilia D'Ambrosio, Roberto Villani, Arnaldo Andreoli, Liver Unit, Azienda Ospedaliera San Camillo Forlanini, Circonvallazione Gianicolense 87, 00149 Rome, Italy.

Aim: To evaluate if indolent B cell-non Hodgkin's lymphoma (B-NHL) and diffuse large B-cell lymphoma (DLBCL) in hepatitis C virus (HCV) positive patients could have different biological and clinical characteristics requiring different management strategies.

Methods: A group of 24 HCV related B-NHL patients (11 indolent, 13 DLBCL) in whom the biological and clinical characteristics were described and confronted. Patients with DLBCL were managed with the standard of care of treatment. Patients with indolent HCV-related B-NHL were managed with antiviral treatment pegylated interferon plus ribavirin and their course observed. The outcomes of the different approaches were compared.

Results: Patients with DLBCL had a shorter duration of HCV infection and a higher prevalence of HCV genotype 1 compared to patients with indolent B-NHL in which HCV genotype 2 was the more frequent genotype. Five of the 9 patients with indolent HCV-related B-NHL treated with only antiviral therapy, achieved a complete response of their onco-haematological disease (55%). Seven of the 13 DLBCL patients treated with immunochemotheraphy obtained a complete response (54%).

Conclusion: HCV genotypes and duration of HCV infection differed between B-NHL subtypes. Indolent lymphomas can be managed with antiviral treatment, while DLBCL is not affected by the HCV infection.
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http://dx.doi.org/10.4254/wjh.v3.i11.278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3225032PMC
November 2011

Risk factors for the development of secondary malignancy after high-dose chemotherapy and autograft, with or without rituximab: a 20-year retrospective follow-up study in patients with lymphoma.

J Clin Oncol 2011 Mar 28;29(7):814-24. Epub 2010 Dec 28.

Hematology and Cell Therapy, A.O. Mauriziano, Nuclear Medicine and Hematology, A.O.U.S. Giovanni B., Clinica Medica, A.O.U.S. Luigi-Orbassano, University of TorinoTorino, Italy.

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 Hodgkin's 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.
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http://dx.doi.org/10.1200/JCO.2010.28.9777DOI Listing
March 2011

Alemtuzumab (Campath-1H) and CHOP chemotherapy as first-line treatment of peripheral T-cell lymphoma: results of a GITIL (Gruppo Italiano Terapie Innovative nei Linfomi) prospective multicenter trial.

Blood 2007 Oct 20;110(7):2316-23. Epub 2007 Jun 20.

Hematology Department, Ospedale Santa Croce, Cuneo, Italy.

To evaluate in a prospective multicenter trial the feasibility and clinical efficacy of the combination of alemtuzumab (Campath-1H) with the cyclophosphamide/doxorubicin/vincristine/prednisone (CHOP) regimen (CHOP-C) as the primary treatment for patients with peripheral T-cell lymphoma (PTCL), between January 2003 and December 2005, 24 consecutive patients with PTCL entered the study and received 8 CHOP courses. Alemtuzumab was added at 30 mg subcutaneously at day -1 initially to the first 4 courses (4 patients), and then to all 8 courses (20 patients). Complete remission (CR) was achieved in 17 (71%) patients, 1 had partial remission, and 6 had stable/progressive disease. At a median follow-up of 16 months (range, 5-42 months), 14 patients were alive, 9 had died from progressive disease, and 1 had died from pneumonia at day +198 while in CR. So far, 13 are disease-free, with an overall median duration of response of 11 months. The most frequent side effects were grade 4 neutropenia and cytomegalovirus (CMV) reactivation. Major infections were Jacob-Creutzfeldt (J-C) virus reactivation, pulmonary invasive aspergillosis, Staphylococcus sepsis, and pneumonia. This study shows that CHOP-C: (1) is a feasible chemoimmunotherapy regimen; (2) is effective in PTCL with a high rate of CR achievement; and (3) is associated with mostly manageable infectious complications. This clinical trial was registered with the Osservatorio Nazionale sulla Sperimentazione cinica as ID no. 141202.
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http://dx.doi.org/10.1182/blood-2007-02-074641DOI Listing
October 2007

Fludarabine, cyclophosphamide and mitoxantrone for untreated follicular lymphoma: a report from the non-Hodgkin's lymphoma co-operative study group.

Leuk Lymphoma 2004 Jun;45(6):1141-7

Division of Haematology I, S. Martino Hospital, Genoa, Italy.

The aim of the study was to determine the safety and efficacy of the combination of fludarabine (FLU), cyclophosphamide (CY) and mitoxantrone (FLU/CY/MITO) in untreated follicular lymphomas (FL), Sixty patients with newly diagnosed stage II bulky to IV FL, median age 59 years (range 36-70), received FLU/CY/MITO regimen (FLU 25 mg/m2 days 1-3, CY 300 mg/m2 days 1-3, Mito 10 mg/m2 day 1). Patients received antibiotic oral prophylaxis during all treatments, and growth factors (G-CSF) when grade III granulocytopenia (WHO) occurred. The overall response rate was 87%: 46 patients achieved complete response (CR) (77%), 6 a partial response (10%) and 8 were non-responders. Fifty patients are surviving with a median observation time of 31 months. The 4-year estimated probability of overall survival and failure-free survival were 78.2% and 45% respectively. Thirty-five patients (58%) are still in CR. Sixty percent of patients experienced grade III-IV granulocytopenia. Two patients suffered grade III pulmonary infection and one grade III liver toxicity. In a subset of 46 patients, bcl-2 translocation was positive in bone marrow (BM) and/or peripheral blood (PB) of 36 patients. At the end of treatment, 25 of these patients had CR and 19 (76%) converted to polymerase chain reaction (PCR) negativity. FLU/CY/MITO regimen showed a high level of activity in follicular lymphoma. Toxicity, mainly hematological, was acceptable and the treatment was made feasible by the use of antibiotic prophylaxis and G-CSF. Significant non-hematological toxicities were seen, but no patients died. The conversion of bcl-2 from positive to negative by PCR in BM and/or PB suggests a possible role for this treatment in clearing minimal residual disease and improving patients' outcome.
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http://dx.doi.org/10.1080/10428190310001623874DOI Listing
June 2004

Primary cardiac lymphoma: report of two cases occurring in immunocompetent subjects.

Leuk Lymphoma 2004 Apr;45(4):781-8

Hematology and Bone Marrow Transplantation Unit, Ospedale "S. Camillo-Forlanini", Rome, Italy.

Primary cardiac lymphomas (PCLs), involving solely heart and/or pericardium at presentation, are rare events. They are frequently recognized at autopsy and generally carry a poor prognosis due either to a delay in the diagnosis or to infiltration of heart structures. We report here on two patients with large B-cell PCL. One is a 52-year-old man who presented with multiple cardiac tumors infiltrating mainly the right atrium and the inter-atrial septum. Diagnosis was established by ultrasound-assisted transesophageal biopsy of the intra-atrial multilobated tumor mass. He was treated with Rituximab-implemented high-dose sequential (R-HDS) chemotherapy followed by autologous peripheral blood stem cell transplantation, attaining complete response. He had no evidence of disease 24 months from onset. The second patient was a 70-year-old woman who presented with pericardial tamponade and low-output cardiac failure. Despite prompt pericadiocentesis and chemotherapy with cyclophosphamide and vincristine, she died 2 weeks later. Postmortem examination revealed large B-cell lymphoma proliferation confined to the heart. Whether primitive heart localizations represent an independent prognostic factor, and what specific measures should be adopted in patients with this rare presentation is the subject of the present report and review of the literature.
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http://dx.doi.org/10.1080/10428190310001617259DOI Listing
April 2004