Search PubMed⌕ Search

Biomedical subjects

F Silvestri

Publications and source records attributed to F Silvestri.

At least 55 records · Page 3Linked to original sources

The therapy of primary adult systemic CD30-positive anaplastic large cell lymphoma: results of 40 cases treated in a single center.

The outcome of a series of adult patients, affected by primary systemic CD30-positive anaplastic large cell lymphoma (ALCL), treated with a sequential intensive therapeutic program, has been analyzed and all data available in the literature have been reviewed. Forty consecutive, unselected patients with ALCL were treated with the F-MACHOP regimen, followed by radiotherapy (RT) for residual mediastinal disease (15 cases) and by autologous stem cell transplantation (ASCT) conditioned with BAVC (29 cases). Eighty-nine percent (32/36) of the patients younger than 60 years were eligible for completing the sequential treatment. Since then, 3 patients in CR refused ASCT, 1 was excluded for cardiac toxicity and 3 progressed and died of disease. Thus, 29 have been so far submitted to the transplant procedure. CR and PR rates were 40% and 45% respectively after CHT; 52.5% and 35% after RT; 80% and 5% after ASCT, with 78% of patients transplanted in PR convertin to a CR. Actuarial overall survival is 85% at 48.5 months (93% at 66 months for the 29 transplanted patients) and disease free survival is 100% at 54 and 64 months respectively, with no relapses observed among patients who reached a CR. Considering our data and those of the literature, it can be concluded that although the role of ASCT in the therapy of ALCL must not be considered as definitive, its efficacy in converting PR into CR and in preventing relapses, suggests that a randomized trial comparing CHT alone vs CHT+ASCT should be undertaken.

Adolescent↗

Cardiac tamponade: an unusual, fatal complication of infective endocarditis.

Infective endocarditis still occurs in Western countries and so far, it has been an important medical problem. The spectrum of infective endocarditis complications may be extremely wide. We report two unusual cases of infective endocarditis complicated with heart rupture and pericardial effusion. In one case, the infective process spread from the aortic valve developing a sinus of Valsalva aneurysm with subsequent aortic perforation. The perforation reached the right auricular epicardial region with subsequent epicardial rupture and hemopericardium. In the other patient, an infective process of the aortic cusps induced the formation of multiple abscesses in the left ventricle and in the right atrium. An annular abscess of the tricuspid valve was found. From the right atrium, an infected fistula spread through the atrial wall and perforated the epicardial surface of the right auricle. Aside from the rare occurrence of these complications in patients affected with infective endocarditis, these cases are of clinical interest because they raise the problem of the need of greater sensitivity to the diagnosis of endocarditis and proper diagnostic approach.

Aged↗

Somatic hypermutation, clonal diversity, and preferential expression of the VH 51p1/VL kv325 immunoglobulin gene combination in hepatitis C virus-associated immunocytomas.

A high prevalence of chronic hepatitis C virus (HCV) infection has recently been shown in a subset of B-cell non-Hodgkin's lymphomas, most of which belong to the lymphoplasmacytoid lymphoma/immunocytoma subtype and are characterized by the production of a monoclonal IgM cryoglobulin with rheumatoid factor activity. To better define the stage of differentiation of the malignant B cell and to investigate the role of chronic antigen stimulation in the pathogenesis of the HCV-associated immunocytomas, we analyzed the variable (V) region gene repertoire in 16 cases with this type of tumor. The lymphoma-derived V gene sequences were successfully determined in 8 cases; 5 of them expressed the 51p1 VH gene in combination with the kv325 VL gene. Moreover, a monoclonal 51p1-expressing B-cell population was detected in 4 of the remaining immunocytomas by an allele-specific Ig gene fingerprinting assay, indicating that HCV-associated immunocytomas represent clonal proliferations of a highly selected B-cell population. Somatic mutations and intraclonal diversity were observed in all of the lymphoma V genes, and clonally related IgM and IgG VH transcripts indicative of isotype switching were present in one case. These findings are consistent with an antigen-driven process and support a role for chronic antigen stimulation in the growth and clonal evolution of HCV-associated immunocytomas.

Adult↗

Impact of hepatitis C virus infection on clinical features, quality of life and survival of patients with lymphoplasmacytoid lymphoma/immunocytoma.

BACKGROUND: The non-Hodgkin's lymphoma (NHL) subgroup most frequently associated with hepatitis C virus (HCV) infection is the lymphoplasmacytoid lymphoma/immunocytoma (Lp-Ic). We have assessed the impact of the infection on the clinical features, quality of life and survival of HCV+ve Lp-Ic patients as compared to its impact in HCV-ve patients. PATIENTS AND METHODS: Seventy patients with Lp-Ic consecutively observed over a six-year period were studied. Clinical, virological and histopathological features were recorded at diagnosis. Quality of life was assessed using a scoring system including disease-related symptoms, performance status, working ability, hospital admissions and therapies required. RESULTS: Eighteen patients (26%) with HCV infection were identified. Significant differences between those patients and the HCV-ve group included number of symptomatic patients, Hb levels, serum protein levels, entity of the IgM monoclonal component, number of patients with cryoglobulins and with organ (liver, kidney) involvement, and entity and pattern of bone marrow infiltration. Survival rates were similar (P = 0.8383), but the quality-of-life score was significantly worse for the HCV+ve patients (P = 0.002). All anti-HCV Ab+ve patients tested positive for HCV RNA; genotype 2ac was detected in a significant proportion of cases. CONCLUSIONS: This study confirms that HCV infection is present in about one-third of patients with Lp-Ic. HCV infection does not seem to affect the overall survival of patients with Lp-Ic, but it affects the clinical expression of the disease, so that the overall quality of life of HCV+ve patients is significantly worse.

Adult↗

Autologous stem cell transplantation for aggressive non-Hodgkin's lymphomas in first complete or partial remission: a retrospective analysis of the outcome of 52 patients according to the age-adjusted International Prognostic Index.

The aim of the study was to retrospectively evaluate the outcome of patients with aggressive non-Hodgkin's lymphoma (NHL), undergoing autologous stem cell transplantation (ASCT) in first complete (CR) or partial (PR) remission, according to the age-adjusted International Prognostic Index (IPI). Fifty-two consecutive patients, aged less than 60 years, with intermediate- or high-grade NHL, and at least one of the following adverse risk factors: bulky disease, B symptoms or Ann Arbor stage III-IV, and at least a PR after CHT (and radiotherapy (RT) on residual mediastinal mass when required), underwent ASCT conditioned with BAVC. Sixty-five percent (33/52) of the patients achieved CR after CHT; 69% (36/52) after CHT + RT; 90% (47/52) after CHT +/- RT + ASCT. One death during conditioning and three major toxic events after ASCT were recorded. Overall survival (OS) is 98% at 37 months (16-88); disease-free survival (DFS) is 100% at 27 months (7-82). Comparing the observed results with those expected if patients were treated only with CHT, the sequential treatment including ASCT conferred an advantage in terms of CR rate of 14, 23 and 54%, respectively, in the low-intermediate (LI), high-intermediate (HI) and high (H)-risk groups, respectively. The 2-year OS advantage is 10, 21, 31 and 63%, respectively, and the 2-year DFS advantage is 12, 26, 38 and 39%, respectively. Even more striking is the 5-year projected advantage in the number of patients alive without disease, even when considering only the low (L) (P < 0.0001) and the LI (P < 0.0001) risk groups. For patients in the higher (HI + H) risk groups, ASCT should be included in the initial plan of treatment as consolidation of first CR or PR, but the differences seen in this study suggest a formal comparison in a randomized study also for patients in the LI risk group.

Adolescent↗

Multiple myeloma: presenting features and survival according to hospital referral. Eastern Cooperative Study Group on Monoclonal Gammopathies.

Two-hundred and 31 patients with a newly diagnosed multiple myeloma first seen and admitted to 17 hospitals located in the North-East of Italy between 1987 and 1992, were registered for a prospective study on the course of the disease. Median age was 68 years (range 41-90). Fifty-one per cent were in stage I, 9% in stage II and 40% in stage III. The presenting features and the survival of the 61 (26%) patients who were first admitted to a division of Hematology of a University Hospital (group HEM) were compared with those of the 170 (74%) patients who were referred to 16 divisions of Internal Medicine at General and County Hospitals (group INT). In the latter group, the patients were older (p = 0.002), had a poorer performance status ( p = 0.0001 ), a higher frequency of renal failure (p = 0.006) and anemia (p = 0.02) and higher beta2 microglobulin levels (p = 0.01). Median survival of group HEM patients did not differ significantly from group INT patients, if all stages were considered, but stage II and III patients of group INT had a significantly shorter median survival than advanced stage patients of group HEM (12 vs. 35 months, p = 0.01). If those older than 65 years or with unfavourable prognostic factors at presentation were excluded, prolonged survival of group INT patients was observed and the curves of the two groups did not differ significantly anymore. These results show that the patients recruited by a specialized centre may represent a selected population with better prognostic factors and younger age and this may affect analysis of clinical trials. Participation of minor centres in clinical trials may considerably contribute in improving interpretation of results of therapy in myeloma and be more representative of the entire population.

Adult↗

BCL-2 immunohistochemical evaluation in B-cell chronic lymphocytic leukemia and hairy cell leukemia before treatment with fludarabine and 2-chloro-deoxy-adenosine.

Bcl-2 overexpression has been shown to be associated with several malignancies, including B-cell chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphomas (NHL), mainly low-grade and follicular in type. It has as yet not been described in hairy cell leukemia (HCL). In 30 patients with CLL and 14 with HCL who were consecutively selected for treatment with purine analogues (Fludarabine in CLL and 2-chloro-deoxy-adenosine in HCL), we evaluated bcl-2 oncoprotein expression in leukemic cells on marrow sections that were taken before treatment and stained immunohistochemically with a monoclonal antibody (Dakopatts 124 clone), by the avidin-biotin-peroxidase method. All samples were found to be bcl-2 positive, with a staining intensity that was moderate to strong in CLL and weak to moderate in HCL. 83% of CLL and 100% of HCL patients were responsive to purine analogues. These findings show that bcl-2 is overexpressed in almost all cases CLL and HCL and that bcl-2 overexpression does not predict a poor response to purine analogues, which are believed to induce apoptosis.

2-Chloroadenosine↗

Autologous stem cell transplantation for multiple myeloma: a single centre experience.

Thirty-two patients with multiple myeloma (MM) were autografted in our Centre over a 3-year period. Twenty-three patients had a newly diagnosed MM submitted to one induction regimen and 9 had a refractory or relapsing disease treated with at least two different chemotherapy lines: 15 out of 32 patients were sensitive to conventional treatment. In 2 patients BM was harvested while in the majority PBSC were collected after administration of 7 g/m2 Cyclophosphamide plus G-CSF (in 25 patients) or G-CSF alone at the dose of 16 microg/Kg/daily for 5-7 days (in 5 patients). Conditioning regimen was busulfan 16 mg/Kg plus melphalan 120 mg/m2. One patient died of cerebral hemorrhage after reinfusion of PBSC. Out of 31 evaluable patients, 24 (77%) had a response which was complete in 6 patients (19%) and partial in 18 patients (58%), 5 cases (17%) had no response, and 2 (6%) showed myeloma progression. There was a statistical difference in the outcome between newly diagnosed and pretreated patients (p = 0.003). At a median follow-up of 9 months (range 5-37), two patients had died for progression and 3 out of the 29 alive, relapsed after 17, 18 and 36 months respectively. Although median overall survival was not reached, there was a significant survival benefit for autografted patients in comparison with a matched control group conventionally treated in our Centre before 1994 (p = 0.02).

Journal Article↗

DNA content, apoptosis and mitosis in transplanted human hearts.

Aim of the study: To analyze the changes in DNA content, the percentage of apoptosis and the nuclear mitotic frequency of myocytes in transplanted human hearts. Methods: Twenty-three transplanted hearts were obtained from 22 patients. The mean interval between transplantation and death was 649 days (ranging from 13 to 2558 days). Ten control hearts were selected from individuals whose death was not due to primary heart disease. Tissue samples were obtained from the mid section of the lateral wall of left and right ventricles. DNA content was evaluated on isolated myocardial cells using image cytometry. In situ detection of apoptosis was performed by the terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP nick-end labeling (TUNEL) technique. Mitotic figures were examined by staining the nuclear DNA with YOYO-1 iodide. Myocytes were distinguished from stromal cells by using antibodies reacting with a-sarcomeric actin. Results: Comparing with control hearts, the myocytic changes after cardiac transplantation are characterized by: 1) a decrease in mononucleated myocytes and an increase in binucleated and multinucleated myocytes; 2) a decrease in diploid myocytic nuclei and a distinct augmentation of intermediate ploidies; 3) an increase in myocytic nuclei in DNA ploidies higher than 4c; 4) a marked augmentation of percentage of apoptotic myocytes and 5) an increased frequency of nuclear mitosis of myocytes; this fact appears as a declining phenomenon after six months of cardiac transplantation. Conclusion: After cardiac transplantation the DNA content of myocytes shows two completely different aspects: 1) a distinct increase in subdiploidy and intermediate ploidies related to myocyte injury induced by apoptosis and necrosis; 2) an increase in multinucleation, polyploidization and mitotic proliferation. Both myocyte growth and myocyte injury alter the function of the allograft and contribute to adaptation or failure of the graft. Furthermore, a relevant difference of age between the recipient and the donor may lead to a more marked myocyte damage and a lower myocyte growth. This tendency provides an evidence that age matching could be an important aspect in selecting the donor for the recipient.

Journal Article↗

Autologous stem cell transplantation in multiple myeloma: a single center experience.

This study shows the feasibility and safety of autologous stem cell transplantation in 32 of 98 multiple myeloma patients referred to our institution over a 3-year period. Complete response rate was 19% and partial response rate 58%. A significantly better outcome was shown among newly diagnosed patients in comparison with pretreated patients.

Adult↗