0000000000267823

AUTHOR

Francesco Merli

Differentiation on Biological Basis of Monoclonal B-Cell Lymphocytosis (MBL) From Chronic Lymphocytic Leukemia (CLL): Results of a Prospective GISL (Gruppo Italiano Studio Linfomi) Trial

Abstract Abstract 1360 The arbitrary cut-off of 5000/μL chronic lymphocytic leukemia (CLL)-phenotype cells in peripheral blood is generally used to separate monoclonal B-cell lymphocytosis (MBL) from CLL. However, a major concern is the biological differentiation, if any, between MBL and CLL. We tried to address the issue therefore analyzing 261 Rai stage 0 patients enrolled in a Gruppo Italiano Studio Linfomi (GISL) prospective multicentre trial designed to validate biological parameters in early CLL as well as to assess the impact on clinical outcome of an early versus delayed policy of treatment with subcutaneous alemtuzumab in the high biological risk. In this cohort, biological charact…

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The combined role of biomarkers and interim PET scan in prediction of treatment outcome in classical Hodgkin's lymphoma: a retrospective, European, multicentre cohort study

BACKGROUND: Early-interim fluorodeoxyglucose (FDG)-PET scan after two ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapy courses (PET-2) represents the most effective predictor of treatment outcome in classical Hodgkin's lymphoma. We aimed to assess the predictive value of PET-2 combined with tissue biomarkers in neoplastic and microenvironmental cells for this disease.METHODS: We enrolled 208 patients with classical Hodgkin's lymphoma and treated with ABVD (training set), from Jan 1, 2002, to Dec 31, 2009, and validated the results in a fully matched independent cohort of 102 patients with classical Hodgkin's lymphoma (validation set), enrolled from Jan 1, 2008, to De…

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Differences among young adults, adults and elderly chronic myeloid leukemia patients

Abstract BACKGROUND: The incidence of chronic myeloid leukemia (CML) increases with age, but it is unclear how the characteristics of the disease vary with age. In children, where CML is very rare, it presents with more aggressive features, including huge splenomegaly, higher cell count and higher blast cell percentage. PATIENTS AND METHODS: To investigate if after childhood the disease maintains or loses these characteristics of aggressiveness, we analyzed 2784 adult patients, at least 18 years old, registered by GIMEMA CML WP over a 40-year period. RESULTS: Young adults (YAs: 18-29 years old) significantly differed from adults (30-59 years old) and elderly patients (at least 60 years old)…

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Resveratrol-mediated apoptosis of hodgkin lymphoma cells involves SIRT1 inhibition and FOXO3a hyperacetylation

Resveratrol (RSV), a plant-derived stilbene, induces cell death in Hodgkin lymphoma (HL)-derived L-428 cells in a dose-dependent manner (IC50 = 27 μM, trypan blue exclusion assay). At a lower range (25 μM), RSV treatment for 48 hr causes arrest in the S-phase of the cell cycle, while at a higher concentration range (50 μM), apoptosis can be detected, with activation of caspase-3. The histone/protein deacetylase SIRT1 has been described as a putative target of RSV action in other model systems, even though its role in cancer cells is still controversial. Here we show that RSV, at both concentration ranges, leads to a marked increase in p53, while a decrease of SIRT1 expression level, as well…

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Response-guided ABVD chemotherapy plus involved-field radiation therapy for intermediate-stage Hodgkin lymphoma in the pre-positron emission tomography era: a Gruppo Italiano Studio Linfomi (GISL) prospective trial.

Abstract Purpose In the pre—positron emission tomography era, the Gruppo Italiano Studio Linfomi (GISL) investigated the feasibility and efficacy of a treatment based on a response-tailored number of doxorubicin/bleomycin/vinblastine/dacarbazine (ABVD) courses in 218 intermediate-stage Hodgkin lymphoma patients. Patients and Methods Patients with stage I/II showing at least one adverse prognostic factor and stage IIIA without adverse prognostic factors were recruited. Treatment included a first step of 3 ABVD courses, followed by an early-restaging. Patients in CR/CRu received 1 additional ABVD cycle, patients in PR received 3 more ABVD, and nonresponder patients went off study. Involved-fi…

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The clinical value of tumor burden at diagnosis in Hodgkin lymphoma

BACKGROUND The authors investigated the clinical role of tumor burden (TB) in patients with Hodgkin lymphoma, relating this parameter to most of the current clinical and prognostic factors and to the best predictive multifactorial models. METHODS The volume of TB at diagnosis was measured directly from the initial staging computed tomography scans in 351 patients who were treated on standard protocols. The mean patient age was 34.0 years ± 16.4 years. Forty-six patients had clinical Stage I disease, 201 patients had Stage II disease, 64 patients had Stage III disease, and 40 patients had Stage IV disease. There were 146 symptomatic patients. Overall survival (OS), disease-free survival (DFS…

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R-CVP versus R-CHOP versus R-FM for the initial treatment of patients with advanced-stage follicular lymphoma: results of the FOLL05 trial conducted by the Fondazione Italiana Linfomi.

Purpose Although rituximab (R) is commonly used for patients with advanced follicular lymphoma (FL) requiring treatment, the optimal associated chemotherapy regimen has yet to be clarified. Patients and Methods We conducted an open-label, multicenter, randomized trial among adult patients with previously untreated stages II to IV FL to compare efficacy of eight doses of R associated with eight cycles of cyclophosphamide, vincristine, and prednisone (CVP) or six cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or six cycles of fludarabine and mitoxantrone (FM). The principal end point of the study was time to treatment failure (TTF). Results There were 534 patients…

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Comparison of prognostic models in patients with advanced Hodgkin disease

Several prognostic systems have been elaborated for patients with Hodgkin disease (HD) over the last 12 years, but early identification of a reasonably large group of both low and high risk, advanced stage patients remains unsatisfactory.Seven well known models were applied to 516 patients with advanced HD, with 315 patients used for the study sample and 201 patients used for the test sample. Individual performances as well as joint performances were analyzed univariately and multivariately in relation to overall survival, recurrence free survival, and time to treatment failure by means of a proportional hazards model.None of the models identified a group containing10% of patients from the …

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Rituximab with cyclophosphamide, vincristine, non-pegylated liposomal doxorubicin and prednisone as first-line treatment for splenic marginal zone lymphoma: a Fondazione Italiana Linfomi phase II study

Rituximab ® provides high response rates and effective disease palliation in patients with splenic marginal zone lymphoma (SMZL). We conducted a phase II trial in patients with SMZL who were either untreated or were splenectomized but had shown disease progression within 1 year after splenectomy. Treatment consisted of six courses of Rituximab with cyclophosphamide, vincristine, non-pegylated liposomal doxorubicin and prednisone (R-COMP). Fifty-one patients were eligible for the analysis. The overall response rate was 84%. The 6-year progression-free survival and overall survival were 54% and 72%, respectively. Toxicity was substantial (grade ≥ 3 neutropenia: 26%; grade ≥ 3 infections: 8%).…

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Vinblastine, bleomycin, and methotrexate chemotherapy plus irradiation for patients with early-stage, favorable Hodgkin lymphoma

BACKGROUND. The acknowledged effectiveness of vinblastine, bleomycin, and methotrexate (VBM) chemotherapy in patients with early-stage Hodgkin lymphoma has been associated with conflicting toxicity reports. METHODS. One hundred forty-three patients were evaluated clinically and had favorable Stage IA or IIA Hodgkin lymphoma. Ninety-three patients were treated with the standard VBM schedule combined with extended-field radiotherapy (EFRT), leaving the choice of the therapeutic sequence free. Fifty subsequent patients were treated with a slightly modified VBM schedule (VbMp) combined with RT limited to involved fields (IF-RT) and delivered only after the end of chemotherapy. In the VbMp sched…

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Response-based chemotherapy and involved field radiation for intermediate stage Hodgkin disease. A GISL/NHLSG trial.

Abstract Background. Most of the patients with advanced stage Hodgkin lymphoma can be cured with a standard course of six cycle of ABVD chemotherapy plus involved field (IF)radiotherapy. Patients with less advanced stage or with a more responsive disease could possibly achieve a cure with a shorter course of chemotherapy. In 1992, in the pre-PET era, the GISL addressed the issue of the proper number of chemotherapy cycles planning a response-oriented, ABVD-based study for intermediate-stage Hodgkin’s lymphoma patients. Patients and Methods. From January 1992 to December 2002, 218 patients younger than 70 were enrolled. Eligible patients had histologically confirmed and clinically staged Hod…

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