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Biomedical subjects

L Cavanna

Publications and source records attributed to L Cavanna.

At least 37 records · Page 2Linked to original sources

Alfa-interferon in the treatment of essential thrombocythemia: clinical results and evaluation of its biological effects on the hematopoietic neoplastic clone. Italian Cooperative Group on ET.

The efficacy of alfa-interferon (alfa-IFN) in essential thrombocythemia (ET) patients has been reported by several authors. The aim of this study is to assess the magnitude of the effect of alfa-IFN on the neoplastic clone. As of December 1993, 11 ET patients received alfa-IFN at a dose of 3-6 MU/s.c./day for 6 months. Ten of 11 obtained complete hematological remission (CHR) and one achieved partial hematological remission. Megakaryocyte concentration was reduced in six cases. The spleen,which was enlarged in four patients, decreased in size in two patients. Seven of eight patients who were symptomatic at diagnosis obtained resolution of symptoms. In order to obtain indications about the structural modifications induced by alfa-IFN in ET megakaryocytes (Mks), Fourier-transform infra-red microspectroscopy analysis performed on 10 single Mks of each patient, was done in seven of 11 patients; the analysis showed a reduction of A1/A2 ratios (A1 integrated area of the band at 1080 cm(-1) due to the nucleic acids absorption; A2 integrated area of the band at 1540 cm(-1) due to proteic components absorption) in five cases, and in three of these five patients A1/A2 ratios achieved normal values. After alfa-IFN treatment we did not observe any change in the methylation pattern of DNA from the granulocyte fraction. Our results confirm the efficacy of alfa-IFN in ET patients, and the decrease of A1/A2 ratios in several patients is a demonstration of the depth of the effect of alfa-IFN on the neoplastic clone. The results of clonality studies showed the persistence of clonal hematopoiesis. Whether higher alfa-IFN dose and/or more prolonged alfa-IFN therapy may allow a restoration of polyclonal hematopoiesis remains to be determined and should be explored in future clinical trials.

Adolescent↗

High prevalence of anti-HGV/E2 antibodies in HCV-positive patients with non Hodgkin's lymphoma.

We evaluated in a series of 33 HCV positive (both RT-PCR and HCV RIBA 2 assays) B cell non-Hodgkin's lymphomas (NHL) patients the prevalence of active and inactive HGV infection by HGV RNA assays (RT-PCR) and anti HGV antibodies directed against E2 structural protein (immunoenzimatic method), a reliable serologic marker of past HGV infection followed by viral clearance. We found only one patient with HGV positivity at RT-PCR (3%). Twenty-six of 33 patients were positive for anti HGV/E2 antibodies (78.8%) suggesting past infection. If confirmed, our preliminary data seem to suggest a higher incidence of HGV past infection in our group of HCV positive patients with B cell NHL.

Antibodies, Viral↗

A pilot study on the use of the ProMACE-CytaBOM regimen as a first-line treatment of advanced follicular non-Hodgkin's lymphoma. Gruppo Italiano per lo Studio dei Linfomi.

BACKGROUND: The role of intensive conventional dose chemotherapy in advanced low grade non-Hodgkin's lymphomas is a matter of debate. The Gruppo Italiano per lo Studio dei Linfomi conducted a study to evaluate the efficacy and toxicity of a third-generation polychemotherapeutic regimen, ProMACE-CytaBOM, as a first-line therapy in a selected group of patients with advanced follicular non-Hodgkin's lymphoma (Fo-NHL) who were younger than 60 years. METHODS: Thirty-nine patients were included in the study (14 males, 25 females; median age, 44 years; age range, 22-60 years). Their WF histotypes were B (9 patients), C (23 patients), and D (7 patients). All of the patients had disease in an advanced clinical stage (Stage III, 15 patients; Stage IV, 24 patients), and 9 patients had B symptoms. According to the age-adjusted International Prognostic Index (IPI), 20 patients exhibited low-intermediate risk, 14 high-intermediate risk, and 5 high risk. Three of the patients were not considered evaluable because they withdrew their consent after three (one patient) and four (two patients) cycles of therapy (one of these patients was in complete remission [CR], and two were in partial remission [PR]). Of the 36 evaluable patients, 4 received IF-RT after the 6 planned cycles of therapy. RESULTS: CR was achieved in 20 patients (55.5%) and PR in 14 (38.8%). One patient (2.7%) experienced disease progression during the treatment program. Eight of the 20 patients with CR (40%) relapsed. Eight patients (22.2%) died: 6 died of disease progression, 1 died of therapy consequences, and 1 died of an unrelated cause. With a median follow-up of 49 months (range, 28-79 months), the disease free survival rate was 60%. The overall survival rate was 80% after a median follow-up of 44 months (range, 3-79 months). The IPI stratification of patients showed a borderline statistical difference in terms of time to treatment failure and overall survival. The main hematologic toxicity was neutropenia (Grade 3 in approximately 10% of patients). One patient died of sepsis. Cotrimoxazole prophylaxis was always given. Cardiac toxicity (Grade 3) was observed in 1 patient at the end of the planned therapy. The average relative dose intensity of the drugs was 89% of the projected dose, without the regular use of growth factors. CONCLUSIONS: This study indicates that ProMACE-CytaBOM could be a suitable regimen for adult patients with advanced Fo-NHL, allowing a good CR rate and very good disease free survival rate. However, the occurrence of severe, albeit limited, adverse effects suggests that this regimen should first be used in controlled therapeutic protocols to verify its efficacy with respect to less intensive approaches.

Adult↗

In vivo biological response following low-dose interleukin-2 in complete remission B-cell non-Hodgkin's lymphoma patients. Italian Lymphoma Study Group (GISL).

The aim of the present study is to verify whether recombinant interleukin-2 (rIL-2) at low doses is well tolerated in aggressive lymphoma in complete remission (CR), and if there may be a biological justification for its use as a remission-maintenance therapy able to reduce the percentage of relapses. We treated 6 patients with B-cell non-Hodgkin's lymphoma (B-NHL) in CR following PM-Cytabom with rIL-2 3 IMU s.c. x 5 d per wk, every other wk for 8 wk. Our results show that this treatment provokes statistically significant changes in the absolute number of lymphocytes, eosinophils, CD25+ and CD122+ cells and soluble IL-2 receptors; these doses, however, are not sufficient to modify CD3+, CD16+ and CD56+ cell values or natural killer and lymphokine activated killer cell activity. Thus these findings do not appear to constitute a biological rationale for the use of rIL-2 at this dose and schedule as a remission-maintenance therapy in B-cell NHL. Nevertheless, the results are a valid basis for further study of the use of the same rIL-2 doses for a longer period of time in combination with other cytokines, in the hope that the biological effects can be augmented without increasing the toxic side effects.

Cytokines↗

Effects of thymostimulin with combination chemotherapy in patients with aggressive non-Hodgkin's lymphoma. A report from the Italian Lymphoma Study Group (GISL).

The purpose of this study was to test the efficacy and safety of thymostimulin (TS) administered in addition to conventional chemotherapy in patients with intermediate- and high-grade non-Hodgkin's lymphoma (IG, HG-NHL). A total of 150 patients with newly diagnosed IG- or HG-NHL were entered in a multicenter trial to compare the effectiveness of two different third-generation regimens (MACOP-B versus ProMACE-CytaBOM) and were randomized to receive chemotherapy (CT) alone or CT + TS. In both regimens doxorubicin was replaced by a 20% higher dose of epidoxorubicin. TS was administered i.m. at a dose of 1 mg/kg daily on days 22-28 of each drug course to patients treated with ProMACE-CytaBOM, and on days 22-29, 50-57, and 77-85 to patients treated with MACOP-B. There were 134 fully evaluable patients: 68 treated with CT alone and 66 treated with CT + TS. Patients treated with CT + TS had a higher complete remission (CR) rate compared to patients given CT alone (59.1% vs 42.4%; P = .05). CR were significantly higher for patients treated with CT + TS in the groups with IG-NHL (P = .01), in those aged less than 60 years (P = .05), with good performance status (P = .05), and normal hemoglobin levels (P = .05). Four-year survival rates are 64.5% for patients treated with CT + TS and 43.0% for those treated with CT alone (P = .30). No difference between the two treatment arms have been observed as regards drug-related toxicity and the number and severity of infectious episodes. The use of TS during the 7 days before chemotherapy has been associated with a significantly superior CR rate. The advantage of CT + TS was mostly obtained in patients with IG-NHL, and those with good performance status or normal hemoglobin levels. In these patients TS may have potentiated the host reactions against the tumor, leading to an increase in NK activity and the production of cytokines. This postulated increase in the effectiveness of chemotherapy after TS might also explain the absence of the expected myeloprotective action.

Antineoplastic Combined Chemotherapy Protocols↗

Autoimmune thyroid dysfunctions in hematologic malignancies treated with alpha-interferon.

The widespread use of alpha-interferon (IFN-alpha) therapy in different diseases draws attention to its side effects, such as autoimmune-related diseases, especially thyroid autoimmune dysfunctions. Data about hepatitis and nonhematologic neoplasia are available, while data about hematologic malignancies are fragmentary. We studied the incidence of autoimmune-related disturbances and thyroid dysfunctions in 54 consecutive patients suffering from hematologic malignancies, treated with recombinant human IFN-alpha for a mean time of 15.9 +/- 8.9 months. Our results minimize the incidence of autoimmune dysfunctions in hematologic malignancies as side effects of IFN-alpha therapy. We registered the appearance of autoantibodies in only 3 females (5% of total): 2 patients (1 affected with essential thrombocythemia and one with multiple myeloma) presented antithyroglobulin antibodies with no clinical symptoms; 1 patient, affected with essential thrombocythemia, developed antinuclear antibodies with arthralgia and myalgia. ARA criteria for systemic lupus erythematosus were not fulfilled but the therapy had to be interrupted. No patient developed thyroid dysfunction. In patients with hematologic malignancies, the dosage and the duration of IFN-alpha treatment do not seem to influence the appearance of autoantibodies, while female sex appears to be a risk factor.

Adult↗

ProMECE-CytaBOM vs MACOP-B in advanced aggressive non-Hodgkin's lymphoma: long term results of a multicenter study of the Italian Lymphoma Study Group (GISL).

A randomized trial was designed in order to compare the efficacy and feasibility of ProMECE-CytaBOM (P-C) and MACOP-B (M-B) in patients with advanced, aggressive non Hodgkin's lymphoma (NHL). P-C and M-B were chosen due to their association with a very high complete remission rate when compared to other published protocols. The study was conducted on 210 patients with intermediate or high-grade NHL in stage I bulky, or stages II-IV, randomized to receive either 6 courses of P-C delivered every 28 days (106 patients), or 12 weeks of M-B chemotherapy (104 patients). In both regimens doxorubicin was replaced by a 20% higher dose of epidoxorubicin (i.e. 30 mg/m2 of the analog). At the end of induction therapy patients could receive additional radiotherapy to residual masses or to sites of previous bulky disease. The two groups of patients were compared for response rates, number and severity of therapy related side effects, overall survival, disease-free survival, and time to treatment failure. Sixty-five patients (62%) treated with P-C and 69 patients (67%) treated with M-B achieved a complete remission, with no significant differences between the two treatment arms (P = 0.13). The overall objective response rate (complete + partial remission) was 74% for patients treated with P-C, and 81% for patients treated with M-B, respectively. The 4-year relapse-free survival rate was 59% for P-C and 69% for M-B, respectively (P = 0.11).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Study of prognosis in Waldenström's macroglobulinemia: a proposal for a simple binary classification with clinical and investigational utility.

Prognostic evaluation of Waldenström's macroglobulinemia (WM) is unreliable, few studies considered prognostic factors in WM and only one was derived from a multivariate analysis. One hundred forty-four retrospective, previously untreated patients with clinically overt WM were studied to learn whether overall survival was related to any of the various clinical features presented at diagnosis. Patients were homogeneously treated with intermittent doses of chlorambucil for as long as this showed an effect on the monoclonal component. The population was randomly subdivided into a 90-patient exploratory sample, on whom investigation would be conducted, and in a 54-patient test sample, on whom the results would be validated. In the exploratory sample univariate analysis identified the following parameters as the most important for prognosis: age (< or > or = 70 years), platelet count (< or > or = 120 x 10(9)/L), presence or absence of an abnormal number of red blood cells in the urine, hemoglobin concentration (< or > or = 9 g/dL), erythrocyte sedimentation rate (< or > or = 110 mm at first hour), presence or absence of cryoglobulinemia and of weight loss. Cox multivariate analysis showed that only hemoglobin, age, weight loss, and cryoglobulinemia independently affected survival. These four clinical variables were also shown to be able to discriminate survival significantly in the test sample. Moreover, it was possible to demonstrate (both in the exploratory and the test sample) that clear-cut, albeit dichotomic, survival discrimination can be reached with the presence at diagnosis of either no more than one, or any two or more, of these four prognosticators. These simple clinical criteria could be the basis of an initial binary, prognostic classification of WM, which could help in differentiating therapy according to the severity of the disease, and in properly designing future clinical trials.

Adult↗

Lytic bone lesions suspected for metastasis: ultrasonically guided fine-needle aspiration biopsy.

Ultrasonically guided fine-needle aspiration biopsy (US-FNAB) was performed in 30 patients with a lytic bone lesions suspected for metastasis detected by conventional radiological examinations. The patients were selected for US-FNAB on the basis of the ability of the ultrasound examination to clearly visualize the lesion. The cytological diagnosis was confirmed at surgery in 3 cases, and at clinical and radiological follow-up after more than 6 months in the remaining cases. The lesions were located mostly in the thoracic skeleton (ribs and sternum) and pelvic bone. We diagnosed malignancy in 26 cases and benign lesions in 2 cases. An inadequate sample was obtained in 1 case, and 1 case yielded a false-negative result. According to these results, we obtained a sensitivity of 93%. We conclude that ultrasonically guided fine-needle aspiration biopsy is a useful technique to obtain a pathological diagnosis in cases of lytic bone lesions that can be visualized with this imaging technique.

Adenocarcinoma↗

Small (< or = 3 cm) hepatic lesions. Results of sonographically guided fine-needle biopsy in 385 patients.

Three hundred ninety-five consecutive patients with sonographically detected hepatic lesions < or = 3 cm in diameter were submitted to ultrasonically guided fine-needle biopsy: 24 (6.1%) were < or = 1 cm in diameter; 142 (36%) were between 1.1 and 2 cm, and 229 (57.9%) were between 2.1 and 3 cm in diameter. In the 385 controlled cases, we obtained a cytohistological diagnosis of malignancy in 243 (63.1%): 135 hepatocellular carcinomas, 97 metastases, and 11 hepatic lymphomas. There were 104 true negatives (27%) and 38 false negatives (9.9%). The sensitivity of ultrasonically guided fine needle biopsy in the total series was 86.5%, the specificity 100%, with an overall accuracy of 90.1%. The overall accuracy was higher for lesions between 2.1 and 3 cm in diameter (90%) and was lower for lesions located in the sixth segment (84.6%). The correct diagnosis was obtained in the 83.3% (135/162) of small hepatocellular carcinomas versus 89.8% (97/108) in cases of small metastatic lesions.

Biopsy, Needle↗

Incidence of gallstones in a population of patients with cirrhosis.

One hundred and sixty-five patients with cirrhosis were prospectively investigated, by regular ultrasonographic follow up, to assess the incidence of gallstones. The mean length of follow up was 33 months (range 12 to 108). Cholelithiasis was diagnosed in 31 patients (18.8%), with a cumulative incidence over 84 months of 38.3% (4.7% yearly incidence). The risk of gallstones was similar in males (38%) and females (38.3%), although the final cumulative incidence was reached at 72 months in males. The percentage of patients with new stones was higher in alcoholic cirrhosis (28.9%) (with a cumulative incidence of 48.8% at 84 months) and lower in hepatitis-related cirrhosis (1.9%) (only one new case at 96 months of follow up) (p < 0.001). The cumulative incidence of gallstones in the Child's C group reached 49.3% at 48 months versus 24% in Child's B and 6.4% in Child's A (p < 0.0001). At multivariate analysis, Child's C and alcoholic cirrhosis were shown to be the independent variables significantly associated with a high risk of development of cholelithiasis. This study confirms that cirrhosis represents a high risk factor for gallstones. The risk is greater for alcoholic cirrhosis and increases with the severity of the disease.

Aged↗

MOPP/EBV/CAD hybrid chemotherapy with or without limited radiotherapy in advanced or unfavorably presenting Hodgkin's disease: a report from the Italian Lymphoma Study Group.

PURPOSE: We explored the feasibility, toxicity, and preliminary results of a chemotherapy (CT) regimen, mechlorethamine, vincristine, procarbazine, and prednisone (MOPP)/epidoxirubicin, bleomycin, and vinblastine (EBV)/lomustine (CCNU), doxorubicin, and vindesine (CAD), derived through hybridization, shortening, and intensification of a corresponding 10-drug alternating combination CAD/MOPP/doxorubicin, bleomycin, and vinblastine (ABV), effective in treatment of advanced Hodgkin's disease (HD). PATIENTS AND METHODS: Hybridization involved all drugs except CCNU and mechlorethamine, which were administered in alternating cycles; the length of therapy was reduced from nine to six cycles. The average projected drug doses during the six cycles were increased by 42%, with an overall 1.54 dose-intensification; epidoxorubicin was substituted for doxorubicin at equivalent tumoricidal doses. Radiotherapy (RT) was optional and its indications were limited. RESULTS: Eighty assessable patients with previously untreated, advanced or unfavorably presenting HD were treated in nine cooperating institutions between 1988 and 1991. RT was delivered to 22 patients. Remissions were complete (CR) in 75 patients (93%), partial in three (4%), and null in two (3%). The median relative dose-intensity was 0.71 for the overall regimen. Three of five patients who failed to achieve CR, and two of the four who relapsed, received lower relative dose-intensive cycles. Nonhematologic toxicity was acceptable, but there was considerable hematologic toxicity. Fatal gastrointestinal bleeding was seen in one patient. CONCLUSION: Caution is advised due to the short median follow-up period. Nevertheless, in addition to the excellent response rate, (1) the results were reached through abbreviation, intensification, and hybridization of an existing alternating regimen; (2) RT had limited use in this program, which may have contributed to lowering the risk of second tumors; and (3) the results were obtained in a multicenter study (a condition that often impairs results from clinical trials).

Adolescent↗

Acute myelocytic leukemia and chronic myelomonocytic leukemia simultaneously with resectable breast cancer: a report of two cases.

This report describes 2 patients who developed acute myelocytic leukemia (AML) type M2 and chronic myelomonocytic leukemia (CMML) of the FAB classification, respectively 2 months and 2 weeks after diagnosis of operable breast cancer. The patient with AML showed pancytopenia 2 months before the diagnosis of AML, had a normal karyotype, and showed a good response to chemotherapy. The patient with CMML had a normal karyotype, and she was treated with hydroxyurea and supportive therapy. The 2 patients had no previous exposure to irradiation or cytotoxic therapy. These cases show that breast cancer and either leukemia or myelodysplastic syndrome may be associated even without previous irradiation or combination chemotherapy.

Aged↗

Ultrasonically guided percutaneous splenic tissue core biopsy in patients with malignant lymphomas.

Ultrasonically (US) guided percutaneous tissue core biopsy of the spleen was done on 46 patients with malignant lymphomas. The biopsies were undertaken as a staging procedure in 32 patients, as a restaging procedure in 7, during follow-up in 2, and as a diagnostic step in 5 (previously undiagnosed cases with clinically and ultrasonographically suspected lymphoma). In 45 patients, the tissue core specimens obtained by US-guided biopsies were sufficient for a correct histologic examination; in one patient, the specimen was considered inadequate. The tissue core specimens showed splenic involvement in 12 patients and normal splenic tissue in the other 33. These latter cases were confirmed by splenectomy, by laparoscopy with larger splenic biopsy needles, and by clinical and US follow-up over a period of 6 to 30 months. In all previously undiagnosed patients (five), splenic biopsies allowed histologic subtyping. Additional immunologic subclassification into B-cell and T-cell types of lymphomas was done in two instances. There were no complications in this series. These results suggest that percutaneous US-guided splenic tissue core biopsy is a useful and safe technique for the diagnosis, staging, and follow-up of malignant lymphoma.

Adolescent↗