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F Cavalli

Publications and source records attributed to F Cavalli.

At least 37 records · Page 2Linked to original sources
PubMed2001

Intensification of salvage treatment with high-dose sequential chemotherapy improves the outcome of patients with refractory or relapsed aggressive non-Hodgkin's lymphoma.

The aim of the present study was to retrospectively evaluate whether a high-dose sequential chemotherapy programme (HDS: cyclophosphamide, methotrexate, etoposide) administered prior to autologous transplantation could optimize the salvage of patients with refractory or relapsed aggressive non-Hodgkin's lymphoma. Between 1985 and 1999, 103 patients (median age 43 years, range 16-65) from eight Italian centres and one Swiss centre, with refractory (n = 38) or relapsed (n = 65) diffuse large B-cell and T-cell lymphoma, were treated using HDS followed by high-dose regimens with autologous haematopoietic stem cell transplantation. Eighty-three patients responded to the HDS regimen (81%, 95% C.I., 73- 88%) and 79 eventually achieved a complete response (CR) after autotransplantation (90%, 95% C.I., 81- 96%). None of 20 cases resistant to HDS attained CR. Treatment-related mortality was 4%. After a median follow-up of 24 months (range 6-174 months), 3-year estimates of overall survival, event-free survival and disease-free survival were 47% (95% C.I., 36-59%), 44% (95% C.I., 34-54%) and 64% (95% C.I., 50-74%) respectively. Multivariate analysis showed that chemosensitivity to HDS represented the strongest predictor of both CR and survival. This retrospective study shows that salvage treatment using HDS had relatively low toxicity and was associated with remarkable response rates, allowing further effective therapy with high-dose autograft programmes.

Adolescent↗
PubMed2001

MALT Lymphomas.

This review addresses the biology and the treatment of lymphomas arising from mucosa-associated lymphoid tissue (MALT). This entity, first described in 1983, represents about 8% of all non-Hodgkin's lymphomas and was recently re-classified as "extranodal marginal zone lymphomas of MALT-type." The term marginal zone lymphoma (MZL) encompasses the three closely related lymphoma subtypes of nodal, primary splenic and extranodal lymphomas of MALT type: the latter represent the vast majority of MZL. These lymphomas arise at different anatomic sites, are composed of mature B-cells lacking expression of CD5 and CD10, often present with overlapping morphologic features, but typically quite distinct clinical behaviors. Only very recently cytogenetic/molecular genetic observations have underlined the distinctiveness of these three lymphoid neoplasms, which in both the R.E.A.L. and WHO-classifications are included in the general term of MZL. MALT lymphomas arise in numerous extranodal sites, but gastric MALT lymphoma is the most common and best studied and is, therefore, the paradigm for the group as a whole. Dr. Isaacson describes the principal histological features of these lymphomas, including criteria to distinguish this entity from other small B-cell lymphomas. Several lines of evidence suggest that gastric lymphoma arises from MALT acquired as the result of aH. pyloriinfection. However, at least 1/3 of cases do not respond to eradication ofH. pylori. Very recent data suggest that both t(11;18) (q21;q21) and bcl10 nuclear expression are associated with failure to respond to this treatment. Dr. Gascoyne discusses the biologic function of proteins deregulated through the different translocations, which play a role in pathogenesis of MALT lymphomas, emphasizing particularly their influence in disrupting the apoptotic pathway. Dr. Zucca reviews findings suggesting that MALT lymphoma is an antigen driven neoplasm. He also presents specific guidelines for treatment of gastric lymphomas trying to shed some light on the amazingly inconsistent and confusing data in the literature. Taking advantage on the more than 300 non-gastric MALT lymphomas collected by the International Extranodal Lymphoma Study Group (ILESG), Dr. Cavalli compares gastric lymphomas with those arising in many other sites. Overall, the data presented in this session will underline the fact, that MALT lymphomas are characterized by some unique biological properties.

Anti-Bacterial Agents↗
PubMed2000

Identifying breast cancer patients at high risk for bone metastases.

PURPOSE: To identify patient populations at high risk for bone metastases at any time after diagnosis of operable breast cancer, because these patients are potential beneficiaries of treatment with bisphosphonates. PATIENTS AND METHODS: We evaluated data from 6,792 patients who were randomized in International Breast Cancer Study Group clinical trials between 1978 and 1993. Median follow-up was 10. 7 years. A total of 1,275 patients (18.7%) presented with node-negative disease, whereas 3,354 patients (49.4%) had one to three and 2,163 patients (31.9%) had four or more involved axillary lymph nodes. We also assessed the incidence of subsequent bone metastases in the cohort of 1,220 patients who had a first event in local or regional sites or soft tissue alone. Median follow-up for this cohort was 7.7 years from first recurrence. RESULTS: For the entire population with operable disease, the cumulative incidence of bone metastases at any time was 8.2% at 2 years from randomization and 27.3% at 10 years. The highest cumulative incidences of bone metastases at any time were among patients who had four or more involved axillary nodes at the time of diagnosis (14.9% at 2 years and 40.8% at 10 years) and among patients who had as their first event a local or regional recurrence or a recurrence in soft tissue, without any other overt metastases (21.1% at 2 years from first recurrence and 36.7% at 10 years). CONCLUSION: Treatments to prevent bone metastases may have a major impact on the course of breast cancer and may be most efficiently studied in populations with several involved axillary nodes at the time of presentation and in populations with local or regional recurrence or recurrence in soft tissue.

Aged↗
PubMed2000

Classical (HIV-negative) cutaneous Kaposi's sarcoma: a case report and a short review of the literature.

Classical Kaposi's sarcoma is a sporadic disease with a markedly higher incidence in the Mediterranean area. The two original forms of this disease, the Caucasian (classical) and the African, are now well-documented entities. The immunosuppression-related form is a new, recently described subset of the disease, arising from the human immune deficiency virus (HIV) infection and/or the widespread use of immunosuppressive treatments. Cutaneous lesions are the most common manifestation of classical Kaposi's sarcoma. The case described in the present report is characterised by a history of slowly evolving disease affecting the lower extremities without spread to thoracic or abdominal organs, a lengthy remission following initial radiation therapy, and local relapse with a further remission after a second course of radiation. Current treatments, in particular radiation therapy, achieve disease control or at least control of disease-related symptoms (mainly pain) in most cases, even when cure is not possible.

Aged↗
PubMed2000

Association of gastric and Waldeyer's ring lymphoma: a molecular study.

The coexistence of Waldeyer's ring and gastrointestinal non-Hodgkin's lymphomas at presentation is well known. Moreover, localized gastrointestinal relapses following successful treatment of lymphomas of Waldeyer's ring and thyroid lymphomas occurring after a prolonged disease-free interval have also been described. We report two cases of concomitant lymphoma in Waldeyer's ring and stomach. On the basis of the molecular analysis of the immunoglobulin heavy chain gene rearrangements, two different patterns of concomitant involvement by a lymphoma in Waldeyer's ring and in the gastrointestinal region seem to exist. One is represented by the preferential dissemination of the lymphoma from one site to the other, the second by the apparently independent growth of clonally unrelated lymphomas at each site.

Complementarity Determining Regions↗
PubMed2000

Prognostic models for diffuse large B-cell lymphoma.

Prognosis of DLCL patients is variable and associated with well-defined risk factors. In the past decade several pretreatment variables have been incorporated into prognostic models to predict the death risk of individual patients. The International Prognostic Index (IPI), developed in an international consensus study, has been one of the most widely accepted of these models. In our study we applied some of the major prognostic models proposed for DLCLs in a cohort of 111 patients uniformly treated with a CHOP-like regimen in order to compare their sensitivity and specificity. We also evaluated the possibility of improving the IPI with the inclusion, from among the variables analysed, of serum beta-2 microglobulin level (beta-2M). The sensitivity, reflecting the ability to predict all failures in the cohort of patients as a whole, has improved from 45 to 73 per cent when the beta-2M-IPI model is compared with IPI, without a significant loss of specificity. Based on these results, the beta-2M-IPI may be useful for identifying the subset of patients with very poor prognoses. Therefore, the use of the serum beta-2M value in addition to the IPI may help in selection of the patients with DLCL at higher risk for treatment failure, and identification of those who may require specifically tailored therapeutic approaches.

Adult↗
PubMed2000

Eradication of Borrelia burgdorferi infection in primary marginal zone B-cell lymphoma of the skin.

Primary cutaneous B-cell lymphomas have been associated with Borrelia burgdorferi, the spirochete responsible for Lyme disease. Recently, cutaneous marginal zone B-cell lymphoma has been proposed as a distinct clinical-pathological entity. We report a case of primary cutaneous marginal zone lymphoma, associated with B burgdorferi infection. Polymerase chain reaction (PCR) amplification of the third complementarity determining region (CDR3) of the immunoglobulin heavy chain gene showed the presence of a monoclonal lymphoproliferation, therefore strengthening the histological diagnosis of a malignant process. B burgdorfer-specific hbb gene sequences were detected by PCR in the lymphoma tissue at diagnosis but not after antibiotic treatment. A nearly complete clinical and histological regression was observed after B burgdorferi eradication, with immunohistochemistry studies showing disappearance of plasma cell differentiation and a marked decline in the number of CD3+ T cells and Ki-67+ cells. Our case confirms the link between B burgdorferi and some cutaneous lymphomas. The disappearance of the microorganism accompanied by the unequivocal decrease of most indicators of active T- and B-cell immune response strongly supported a pathogenetic role for B burgdorferi in sustaining an antigen-driven development and growth of this cutaneous marginal zone lymphoma. Antibiotic therapy (analogous to Helicobacter pylori infection in gastric MALT lymphoma) might be helpful with the aim of averting or at least deferring the indication for more aggressive treatment.

Aged↗
PubMed2000

Molecular detection of circulating neoplastic cells in patients with clinically localised gastric and non-gastric mucosa-associated lymphoid tissue lymphoma.

BACKGROUND: Unlike other low-grade lymphomas, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type usually presents with localised disease. AIM: To detect peripheral blood lymphoma involvement to establish the incidence of occult lymphoma dissemination. PATIENTS AND METHODS: In a series of 18 cases, peripheral blood was analysed by polymerase chain reaction, with primers directed to the third-complementarity determining region of the immunoglobulin heavy chain gene. RESULTS AND CONCLUSION: The presence of circulating neoplastic cells was detected in 21% of clinically localised cases. Moreover lymphoma cells were detected in 2 out of 6 morphologically normal bone marrow specimens. The present data show that, combining morphological and molecular methods, occult dissemination can be found in a large proportion of cases thus stressing the need for careful staging procedures. However, it has still to be clarified whether the presence of polymerase chain reaction-detectable circulating lymphoma cells can influence the outcome of mucosa-associated lymphoid tissue lymphoma patients submitted to antibiotic treatment (for gastric localisation) or local therapy (surgery or radiation, for non-gastric tumours).

Adult↗
PubMed2000

Docetaxel (Taxotere)-cisplatin (TC): an effective drug combination in gastric carcinoma. Swiss Group for Clinical Cancer Research (SAKK), and the European Institute of Oncology (EIO).

PURPOSE: A multi-centric trial was performed to explore the clinical activity, in terms of response and toxicity (primary objectives), duration of response and survival (secondary objectives), of docetaxel with cisplatin in advanced gastric cancer (AGC). PATIENTS AND METHODS: Patients with measurable unresectable and/or metastatic gastric carcinoma, performance status < or = 1, normal hematological, hepatic and renal functions and not pretreated for advanced disease by chemotherapy received up to eight cycles of TC (docetaxel 85 mg/m2 dl, cisplatin 75 mg/m2 dl) q3w. Dose escalation to 100 mg/m2 was performed in five patients and was discontinued for excessive toxicity. RESULTS: Forty-eight patients were accrued. A median of 5 cycles/patient was given. We observed 2 complete and 25 partial responses for an overall intent to treat response rate of 56% (95% CI: 41%-71%). Twelve patients had stable disease for > or = 9 weeks (3 cycles). The median time to progression and overall survival were 6.6 and 9 months, respectively. Grade > or = 3 toxicities were neutropenia 81%, anemia 32%, thrombocytopenia 4%, alopecia 36%, fatigue 9%, mucositis 9%, diarrhea 6%, nausea/vomiting 4%, neurologic 2%, and one anaphylaxis precluding treatment administration. We recorded nine episodes of non-fatal febrile neutropenia in eight patients, two of them with docetaxel at 100 mg/m2. There were no direct treatment-related deaths. CONCLUSIONS: TC is active in AGC with a high response rate in a multicentric trial. Despite its hematotoxicity, this regimen is well tolerated and can be recycled as originally planned in 78% of the cases. These results may serve as basis for further developments of docetaxel containing regimens in this disease.

Adenocarcinoma↗
PubMed2000

Proposing phase I studies: patients', relatives', nurses' and specialists' perceptions.

PURPOSE: As of now the primary objective of studies on informed consent in phase I trials has been to assess patients' expectations and reasons for participation. We have previously shown that the quantity of information provided through a procedure of subsequent oral interviews with patients was adequate while the attention paid by the physician to the emotional needs and concerns of patients was not. We wanted therefore to assess and compare the perceptions of the information provided about the investigational study of patients, relatives, the research nurse and the investigator responsible for the phase I trial and the impact this information had on the patients' level of anxiety and depression. PATIENTS AND METHODS: The participation to a phase I study was proposed to patients through two subsequent interviews, the latter attended also by patients' relatives, the research nurse and the investigator coordinating the phase I trial. After the second interview, attendees were requested to complete a questionnaire assessing the principal reason for participating in the study and the informative, emotional and interactive dimension of the information. Patients were also requested to complete the Hospital Anxiety and Depression (HAD) scale before and after the second interview. RESULTS: The completed questionnaires of 31 of 42 patients were retrieved and analysed. The possibility to benefit from the study was indicated as the main reason for participating by 59% of the patients while it was judged to be the case in 78% and 86% of the patients by the nurse and the investigator, respectively. The information was judged to be clear and sufficient in almost all cases by all attendees, while the investigator judged that a lower percentage of patients felt at ease and could express their main worries during the interview, had been helped and were less worried after it than it was judged by the nurse and the relatives. Patients' state of anxiety and depression was not adversely affected by the information provided. CONCLUSIONS: Informing patients on the option of receiving an investigational treatment within a phase I study is feasible and can be done in a way felt appropriate by patients and relatives, nursing and medical professionals. Providing information in an appropriate manner does not increase patients' anxiety and depression. Divergence between the aims and interests of the investigators and patients might explain the difference in the evaluation of physician, a problem which could perhaps be partially overcome by the application of innovative phase I designs.

Adult↗
PubMed2000

Lack of CD95/FAS gene somatic mutations in extranodal, nodal and splenic marginal zone B cell lymphomas.

Germline CD95 (also known as FAS, APT1 and APO1) gene mutations have been associated with benign lymphoproliferative diseases and autoimmune processes. Somatic mutations have been reported in human tumours, including lymphomas. Since marginal zone B cell lymphomas usually arise in a background of chronic inflammation, often of autoimmune origin, we searched for CD95 gene mutations in an unselected series of marginal zone B cell lymphomas. The CD95/FAS full coding region, comprising exon-intron junctions, was amplified from genomic DNA by polymerase chain reaction (PCR) in 10 separate reactions. PCR products were analysed by single-strand conformation polymorphism (SSCP) and visualised by silver staining. Bands exhibiting an altered electrophoretic mobility were sequenced. Twenty-seven cases of marginal zone B cell lymphomas of whom fresh or frozen tumour material was available (18 extranodal, five splenic and four nodal) were studied. Previously described silent polymorphisms in exons 7 (C836T) and 3 (T416C) were detected in 42% and in 19% of the cases, respectively. One silent T-to-A substitution at bp 431, within exon 3, was found in one case. Our results did not reveal the presence of CD95 somatic mutations in unselected cases of marginal zone B cell lymphomas. On the basis of our data, we cannot rule out that other genes coding for proteins involved in the CD95-induced apoptotic pathway might be altered. However, this pathway does not seem to play an important role in the pathogenesis of these lymphoma subtypes.

Antigens, Neoplasm↗
PubMed2000

BCL10 gene mutations rarely occur in lymphoid malignancies.

BCL10, a gene involved in apoptosis signalling, has recently been identified through the cloning of chromosomal breakpoints in extranodal (MALT-type) marginal zone lymphomas carrying the t(1;14)(p22;q32) translocation. BCL10 was also found mutated in these cases as well as in other types of lymphoid and solid tumors, suggesting that its inactivation may play an important pathogenetic role; however, this has been questioned by recent studies showing a lack of somatic mutations in human cancers. We report the mutation analysis of exons 1-3 of the BCL10 gene in DNAs from 228 cases of lymphoid malignancies (30 B cell chronic lymphocytic leukemias, 123 B and 45 T non-Hodgkin's lymphomas and 30 multiple myelomas). Somatic mutations were detected in four cases (approximately 2%): one small lymphocytic, one follicular and two diffuse large cell lymphomas. The mutations were all within exon 3 and have not been previously reported. Our data suggest that BCL10 mutations may play only a limited role in the pathogenesis of lymphoid neoplasms.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Extranodal lymphomas.

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Central Nervous System Neoplasms↗
PubMed2000

Burdens and benefits of adjuvant cyclophosphamide, methotrexate, and fluorouracil and tamoxifen for elderly patients with breast cancer: the International Breast Cancer Study Group Trial VII.

PURPOSE: Information on the tolerability and efficacy of adjuvant chemoendocrine therapy for older women is limited. We studied these issues using the data collected as part of the International Breast Cancer Study Group Trial VII. PATIENTS AND METHODS: Postmenopausal women with operable, node-positive breast cancer were randomized to receive either tamoxifen alone for 5 years (306 patients) or tamoxifen plus three consecutive cycles of classical cyclophosphamide (100 mg/m(2) orally days 1 to 14), methotrexate (40 mg/m(2) intravenous days 1 and 8), and fluorouracil (600 mg/m(2) intravenous days 1 and 8) every 28 days (CMF; 302 patients). The median follow-up was 8.0 years. RESULTS: Among the 299 patients who received at least one dose of CMF, women 65 years of age or older (n = 76) had higher grades of toxicity compared with women less than 65 years old (n = 223) (P =.004). More women in the older age group compared with the younger women experienced grade 3 toxicity of any type (17% v 7%, respectively), grade 3 hematologic toxicity (9% v 5%, respectively), and grade 3 mucosal toxicity (4% v 1%, respectively). Older patients also received less than their expected CMF dose compared with younger postmenopausal women (P =.0008). The subjective burdens of treatment, however, were similar for younger and older patients based on quality-of-life measures (performance status, coping, physical well-being, mood, and appetite). For older patients, the 5-year disease-free survival (DFS) rates were 63% for CMF plus tamoxifen and 61% for tamoxifen alone (hazards ratio [HR], 1.00; 95% confidence interval [CI], 0.65 to 1.52; P =.99). For younger patients, the corresponding 5-year DFS rates were 61% and 53% (HR, 0.70; 95% CI, 0.53 to 0.91; P =.008), but the test for heterogeneity of CMF effect according to age group was not statistically significant. The reduced effectiveness of CMF among older women could not be attributed to dose reductions according to dose received. CONCLUSION: CMF tolerability and effectiveness were both reduced for older patients compared with younger postmenopausal node-positive breast cancer patients who received tamoxifen for 5 years. The development and evaluation of less toxic and more effective chemotherapy regimens are required for high-risk elderly patients.

Age Factors↗
PubMed2000

Extranodal marginal zone B-cell lymphoma genotyping by Alu-polymerase chain reaction.

DNA amplification by polymerase chain reaction (PCR) with primers designed on the widely distributed Alu sequences allows the production of specific inter-Alu DNA-fingerprints. Amplification of tumour and matched normal DNA can show differences due to genetic alterations within the tumour genome. We applied this approach to study low-grade extranodal marginal zone B-cell lymphoma (of MALT type). After digestion with restriction enzymes, DNA samples were separately amplified by PCR with three different Alu-primers. A comparison between the fingerprint pattern from lymphoma and normal samples was made. Inter-Alu bands differing between the two samples were excised from the gel, cloned and sequenced. Nine cases of low-grade MALT-lymphomas have been analysed, giving seventeen different bands between tumour and normal. DNA sequence analysis showed identities for three of them with sequences available at the GenBank. The methodology of Alu-PCR to detect DNA-based abnormalities, in addition or combination with RNA-based methods, is a powerful tool to identify candidate regions frequently altered in tumours. With the increased available genomic sequences through the Human Genome Project, there will be an increasing probability of picking up perfect homologies with these sequences using cloned differential Alu-PCR bands in BLAST searches through genome databases.

Alu Elements↗