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Biomedical subjects

F Cavalli

Publications and source records attributed to F Cavalli.

At least 73 records · Page 4Linked to original sources
PubMed1999

Marginal zone B-cell lymphoma: A clinical comparison of nodal and mucosa-associated lymphoid tissue types. Non-Hodgkin's Lymphoma Classification Project.

PURPOSE: In the International Lymphoma Study Group classification of lymphoma, extranodal marginal zone B-cell lymphoma (MZL) of mucosa-associated lymphoid tissue (MALT) type is listed as a distinctive entity. However, nodal MZL is listed as a provisional entity because of questions as to whether it is truly a disease or just an advanced stage of MALT-type MZL. To resolve the issue of whether primary nodal MZL without involvement of mucosal sites exists and whether it is clinically different from extranodal MALT-type lymphoma, we compared the clinical features of these two lymphomas. PATIENTS AND METHODS: Five expert hematopathologists reached a consensus diagnosis of MZL in 93 patients. Seventy-three were classified as having MALT-type MZL because of involvement of a mucosal site at the time of diagnosis, and 20 were classified as having nodal MZL because of involvement of lymph nodes without involvement of a mucosal site. RESULTS: A comparison of the clinical features of nodal MZL and MALT-type MZL showed that more patients with nodal MZL presented with advanced-stage disease (71% v 34%; P =. 02), peripheral lymphadenopathy (100% v 8%; P <.001), and para-aortic lymphadenopathy (56% v 14%; P <.001) than those with MALT-type MZL. However, fewer patients with nodal MZL had a large mass (> or = 5 cm) than those with MALT-type MZL (31% v 68%; P =.03). The 5-year overall survival of patients with nodal MZL was lower than that for patients with MALT-type MZL (56% v 81%; P =.09), with a similar result for failure-free survival (28% v 65%; P =.01). Comparisons of patients with International Prognostic Index scores of 0 to 3 showed that those with nodal MZL had lower 5-year overall survival (52% v 88%; P =.025) and failure-free survival (30% v 75%; P =.007) rates than those with MALT-type MZL. CONCLUSION: Nodal MZL seems to be a distinctive disease entity rather than an advanced stage of MALT-type MZL because the clinical presentations and survival outcomes are different in these two types of MZL. Clinically, nodal MZL is similar to other low-grade, node-based B-cell lymphomas, such as follicular and small lymphocytic lymphomas.

Adult↗
PubMed1999

ChlVPP/ABV-VP16 hybrid regimen for advanced Hodgkin's disease: a study in 36 patients.

Prolonged remission can now be induced in the majority of patients with advanced Hodgkin's disease (HD) by the use of non-cross-resistant regimens. The aim of this retrospective analysis was to evaluate the efficacy and tolerability of a hybrid chemotherapy regimen (ChlVPP/ABV-VP16) in this unfavorable subset of patients. From 1982 to 1997 thirty-six previously untreated patients with advanced HD, Stages IIB to IV according to the Ann Arbor classification, were treated with the ChlVPP/ABV-VP16 regimen. The median age of the group was 29 years (range, 18 to 74), and 50% of them had bulky disease. Complete remission (CR) was induced in 31 patients (86%); 3 patients achieved partial responses and 2 had progressive disease. The median follow-up duration is 5.7 years, with a 5-year overall survival rate of 80%. At 5 years, the time to progression (TTP) and event-free survival (EFS) were 71% and 64%, respectively. Acute toxicity was quite acceptable, and there were no treatment-related deaths. A total of 3 second malignancies (8%) were documented. In conclusion, the ChlVPP/ABV-VP16 hybrid is an active regimen for use in advanced HD. Its overall survival, TTP and CR rates make this regimen an attractive alternative to MOPP/ABVD. However, the possibility of the development of second tumors is worrisome, although the relatively brief interval between the end of treatment and tumor detection may imply caution about the possible relationship.

Adult↗
PubMed1999

Primary mediastinal large B-cell lymphoma (PMLCL): the need for prospective controlled clinical trials.

Primary mediastinal large-B cell lymphomas (PMLCL) are considered to be a distinct clinicopathologic entity among the diffuse large B-cell lymphomas. This study evaluated the prognostic factors and therapeutic outcome of PMLCL in a single-institution series. Twenty seven patients were reviewed. Nineteen of the 27 had Stage I-II and 8 had Stage III-IV disease. B-symptoms were found in 11 (41%) patients and bulky disease in 10 (37%). All patients were initially given combination chemotherapy (CT): doxorubicin-containing regimens to 23 patients (11 patients had CHOP, 12 more intensive third-generation regimens) and 4 elderly (>70 years) patients received CVP. Eleven responders were consolidated with irradiation (RT) as part of their initial treatment, with a median total dose of 39 Gy. Nineteen patients (70%) achieved clinical remission (15 CR and 4 PR) with their initial therapy. Forty-four percent of patients remained progression-free and 59% are alive at 3 years. The actuarial 10-year TTP and OS were 44% and 50%, respectively. Age >60 years, performance status >1 and IPI intermediate-high to high risk were significantly associated with poorer OS and TTP by univariate analysis (log-rank test). A better outcome was associated with the use of more aggressive chemotherapy regimens or with the inclusion of RT in the first-line treatment. In conclusion our analyses suggest that the application of radiotherapy in combination regimens and the use of more aggressive chemotherapy in the treatment of this particular lymphoma entity should be evaluated in prospective randomized trials.

Adult↗
PubMed1999

Immunoglobulin light chain kappa deletion rearrangement as a marker of clonality in mantle cell lymphoma.

Mantle cell lymphoma (MCL) express immunoglobulin light chain lambda (IgL-lambda) more frequently than other non-Hodgkin's lymphomas, and IgL-lambda producing B-cells usually delete one or both alleles of their IgL-kappa genes. This inactivation is mediated by a rearrangement between the kappa deletion element (kappa de) and the Recombinant Signal Sequence (RSS) in the region between the Joining genes and the Constant region, or the RSS at the 3'-site of a Variable (Vkappa) segment. This deletion appears as a feasible tool for detecting monoclonality and minimal residual disease by polymerase chain reaction (PCR). Among twelve MCL patients studied, ten presented IgL-lambda expression, and all but one among these revealed a monoclonal kappa de rearrangement by PCR analysis. Six of the nine cases showed a fusion between the kappa de and the intron RSS, whilst three with a Vkappa segment. Since MCL has the worst prognosis of all B-cell lymphomas and high-dose chemotherapy regimens have been proposed, PCR for the kappa de rearrangement might be a useful molecular tool to evaluate the ability of the different treatment modalities to eradicate the malignant clones.

Biomarkers↗
PubMed1999

Clonality assessment in blood of patients with mantle cell lymphoma.

The presence of circulating neoplastic cells at diagnosis was assessed in the blood of patients presenting with mantle cell lymphoma (MCL) to determine the feasibility of a diagnostic molecular assay. Blood samples from 16 patients with pathologically reviewed MCL were analysed for the t(11;14)(q13;q32) translocation by the polymerase chain reaction (PCR): 7 (44%) were found positive. The remaining cases were examined by PCR for the presence of circulating neoplastic B-cells by amplifying the third complementarity region (CDR3) of immunoglobulin heavy chain genes and the immunoglobulin light kappa chain deletion rearrangements. A further 7 (44%) patients showed the presence of clonal lymphoma cells, leaving only 2 (12%) of cases negative for circulating lymphomatous cells. This study suggests that there is a high incidence of lymphoma cells in the blood of patients presenting with MCL. PCR for these clonal cells may be diagnostically useful.

Clone Cells↗
PubMed1998

North-South twinning in paediatric haemato-oncology: the La Mascota programme, Nicaragua.

We describe the La Mascota twinning programme between La Mascota paediatric hospital in Managua, Nicaragua, and hospitals in Monza and Milan, Italy, and Bellinzona, Switzerland. The programme was based on the belief that an attempt to reduce the gap in mortality from cancer in childhood between developed and less developed countries should become an integral part of the care and research activity of a haemato-oncological department of a developed country and not simply an exercise in solidarity. This programme for acute lymphoblastic leukaemia shows that intellectual, organisational, and financial resources can be generated by a twinning programme. What is vital for such programmes is a long-term commitment to a comprehensive and holistic strategy that incorporates supply of drugs, training and supervision of health professionals, and the care of the children and of their parents.

Child↗
PubMed1998

High-dose sequential chemotherapy with autologous blood stem cell rescue for relapsed or resistant lymphoma.

The high-dose sequential regimen developed by Gianni et al. in Milan is a novel concept in which five active drugs are administered sequentially at their maximum tolerated dosages. In previous studies this treatment was efficacious in relapsed Hodgkin's disease and in "de novo" high-risk high-grade NHL. We tested the feasibility, toxicity and efficacy of this approach, administered with simplified supportive measures, as salvage regimen for patients with relapsed (n = 17) or resistant (n = 3) lymphoma (9 high-grade NHL, 4 low-grade NHL and 7 Hodgkin's disease). The regimen included sequential administration of cyclophosphamide (7 g/m2), methotrexate (8 g/m2), etoposide (2 g/m2), mitoxantrone (60 mg/m2) and melphalan (180 mg/m2) over a period of 8 weeks in an effort to reduce hospitalisation to a minimum. Of the 20 initial patients, 15 completed the planned programme. The regimen was subjectively well tolerated despite frequent hospital stays (median 44 days). Recovery of absolute neutrophil and platelet counts after transplantation occurred on the average on days 13 and 11 respectively. A second neutrophil and platelet nadir was seen 7-8 weeks after transplantation. Long-term side effects were a severe stenosing postactinic oesophagitis and a secondary subacute monoblastic leukaemia. At a median follow-up of 24 months, the 2 years disease-free and overall survival are 27% and 60% respectively. Of the 15 patients actually transplanted, 7 (47%) are alive disease-free. Although as feasible and effective as other high-dose regimens, this regimen requires longer hospital stays and its costs may be higher than those of other high-dose programmes.

Adult↗
PubMed1998

A novel flow cytometric method for the quantification of p53 gene expression.

We describe a rapid and simple flow cytometry technique for the detection and quantification of p53 in several human cell lines, including an adenocarcinoma cell line (SW 626) having a mutant (m) p53, and a pre-B leukemia cell line (NALM-6) having wild-type (wt) p53. By introducing a second antibody coupled to RPE-fluorescence, the discrimination between control and specific peaks was improved over that achieved with methods used previously. To quantify the content of p53 molecules in the cells, we used a series of beads with the capability to bind mouse monoclonal IgG antibodies. p53 cell content, expressed as antibody binding capacity (ABC), was directly quantified from logarithmic scattergrams; the results were reproducible in all cell lines tested. Flow cytometric results were compared with those of a standard immunocytochemistry method routinely used for the detection of p53 in cells, and found to be in correlation. Furthermore, cytometric data also reflect ELISA determinations. In summary, we showed for the first time that (i) p53 can be clearly detected by flow cytometry in various cell lines, (ii) p53 can be quantitated in terms of number of molecules per cell, and (iii) it can be easily monitored as a function of time after stimulation.

Adenocarcinoma↗
PubMed1998

Hematotoxicity on human bone marrow- and umbilical cord blood-derived progenitor cells and in vitro therapeutic index of methoxymorpholinyldoxorubicin and its metabolites.

PURPOSE: MMDX [3'-deamino-3'-[2(S)-methoxy-4-morpholinyl] doxorubicin], an anthracycline derivative active in vitro and in vivo against multidrug-resistant tumors, is currently under investigation in phase I clinical trials. In vivo it is metabolically activated, resulting in more cytotoxic compounds. We determined in vitro the toxic concentration of a 1-h period of exposure to doxorubicin (DX), MMDX, and bioactivated MMDX on hematopoietic progenitors and tumor cell lines. METHODS: DX and MMDX were tested on both bone marrow- (BM) and cord blood (hCB)-derived clonogenic cells, whereas the metabolites were tested on hCB only. All substances were tested on seven tumor cell lines. RESULTS: BM cells proved to be twice as sensitive as hCB cells to cytotoxics, and MMDX was twice as toxic as DX against hCB cells; MMDX activated with normal rat-liver microsomes and with dexamethasone-induced rat microsomes were, respectively, 70 and 230 times more toxic than MMDX. A comparison of the cytotoxic concentrations on hematopoietic progenitors and tumor cells, revealed that DX and MMDX had 5-fold stronger activity on tumor cell lines than on granulocyte/macrophage colony-forming cells (GM-CFCs), whereas bioactivated MMDX showed comparable cytotoxicity against tumor cells and hematopoietic progenitors. CONCLUSIONS: MMDX metabolites are very potent but display a lower degree of tumor selectivity than MMDX. Strategies to reduce MMDX metabolization should be developed to optimize the therapeutic index of this new anthracycline.

Antibiotics, Antineoplastic↗
PubMed1998

Palliative care of cancer patients: audit of current hospital procedures.

The palliative care of cancer patients admitted for tumour-related symptoms to three different departments (medical oncology, radiotherapy, internal medicine) of a general hospital was prospectively audited. The physicians directly responsible for the patients provided prospective data by reporting both the diagnostic and therapeutic interventions performed and the degree of control achieved for each symptom. A patient form for evaluation of the control achieved in the case of each symptom by means of linear analogue scales was also provided. The appropriateness of all procedures was evaluated by two external auditors. Over 6 months, 125 such admissions were recorded: 24 patients entered the study and the management of 56 symptoms, the most common of which were pain and dyspnoea, was reviewed. A total of 72 diagnostic procedures were performed, deemed necessary for only 50% of symptoms, optional for 15%, and performed as part of a logical sequence for 38%. A total of 130 therapeutic interventions were undertaken, deemed necessary for 55% of symptoms, optional for 15% and carried out as part of a logical sequence for 44%. Re-evaluations of symptoms and physician and patient evaluations of the degree of control achieved could not be assessed because of lack of information. The audit could not be repeated owing to the low accrual of patients and incompleteness of the data collection. Reasons for failure of the study and proposals for feasible methods of auditing the management of symptoms in cancer patients are discussed.

Adult↗
PubMed1998

Prognostic impact of amenorrhoea after adjuvant chemotherapy in premenopausal breast cancer patients with axillary node involvement: results of the International Breast Cancer Study Group (IBCSG) Trial VI.

Adjuvant chemotherapy-induced amenorrhoea has been shown to be associated with reduced relapses and improved survival for premenopausal breast cancer patients. Amenorrhoea was, therefore, studied to define features of chemotherapy (i.e. duration and timing) and disease-related factors which are associated with its treatment effects. We reviewed data from IBCSG Trial VI, in which accrual was between July 1986 and April 1993. 1196 of the 1475 eligible patients (81%) were evaluable for this analysis. The median follow-up was 60 months. Women who experienced amenorrhoea had a significantly better disease-free survival (DFS) than those who did not (P = 0.0004), although the magnitude of the effect was reduced when adjusted for other prognostic factors (P = 0.09). The largest treatment effect associated with amenorrhoea was seen in patients assigned to receive only three initial CMF courses (5-yr DFS: 67% versus 49%, no amenorrhoea; hazard ratio, 0.55; 95% confidence interval, 0.38 to 0.81; P = 0.002). DFS differences between amenorrhoea categories were larger for patients with ER/PR positive tumours (hazard ratio, 0.65; 95% confidence interval, 0.53 to 0.80; P = 0.0001). Furthermore, patients whose menses returned after brief amenorrhoea had a DFS similar to those whose menses ceased and did not recover (hazard ratio, 1.10; 95% confidence interval, 0.75 to 1.62; P = 0.63). The effects associated with a permanent or temporary chemotherapy-induced amenorrhoea are especially significant for node-positive breast cancer patients who receive a suboptimal duration of CMF chemotherapy. Cessation of menses, even for a limited time period after diagnosis of breast cancer, might be beneficial and should be prospectively investigated, especially in patients with oestrogen receptor-positive primaries.

Adult↗
PubMed1998

Distribution of mobilized progenitor cells in the buffy coat of the haemonetics MCS3p cell separator: a study to optimize the collection of progenitors by leukapheresis.

Hematopoietic progenitor and stem cells for transplantation can be mobilized into the circulation and collected by leukapheresis. In this procedure, the leukocytes are distributed in the buffy coat along a density gradient, and the composition of the final product depends on which layer was collected. For the Haemonetics MCS3p Cell Separator, the manufacturer recommended starting the progenitor cell collection at a light transmission of 30%-40% (compared with plasma) and continue it for 40-50 ml. To optimize the use of this machine, the buffy coat it produces was studied in 12 patients by collecting it in fractions of increasing specific weight. Each fraction was analyzed by morphology, immunocytometry, and cell culture. We found that the buffy coat uniformly contains 8 times more leukocytes than blood, but the proportion of each white cell type varies along a gradient. The lymphocyte-predominant lighter layers are richer in CD34+ cells when compared with the granulocyte-predominant denser layers (6-14 times versus 2-4 times more than blood). The majority of CD34+ cells are found at a light transmission of 10%-70% (hematocrit 6-9). We conclude that cells for transplantation should be collected in a lighter fraction of the buffy coat than originally suggested by the manufacturer.

Antigens, CD↗
PubMed1998

Rare syndromes in Hodgkin's disease.

The presentation of Hodgkin's disease is in the vast majority of cases rather classical. However, there are some rare syndromes which might be very puzzling. In this contribution, we will discuss some of these rare syndromes. We will concentrate on following topics: (1) pruritus (itching), (2) cutaneous manifestations of HD, (3) alcohol-related pain, (4) nephrotic syndrome, (5) hemolytic anemia, (6) idiopathic thrombocytopenia purpura (UTP), (7) ivory vertebrae, and (8) CNS involvement.

Alcohol Drinking↗
PubMed1998

Management of rare forms of lymphoma.

The recent Revised European-American Classification of Lymphoma (REAL) classification system has been shown to allow easy, accurate, and reproducible identification of several clinically distinctive lymphoma subtypes. Many of these well-recognized lymphoma entities are relatively rare, as shown by a recent large survey of more than 1400 non-Hodgkin's lymphoma (NHL) cases from eight different countries. The purpose of this article is to summarize the present information known about these less common entities. Particular attention will be paid to the management problems of the following subtypes: the marginal-zone B-cell lymphomas of nodal type (or monocytoid lymphoma, comprising 1.8% of total cases in the above-mentioned series), the extranodal marginal-zone B-cell lymphomas (or mucosa-associated lymphoma tissue [MALT] lymphomas, representing 7.6% of the cases), the splenic marginal-zone B-cell lymphomas (< 1% of cases), the mantle cell lymphomas (6% of cases), and the primary mediastinal large B-cell lymphomas (2.4% of cases). Also, the main non-cutaneous peripheral T-cell lymphoma types, which including the natural killer (NK) disorders comprise less than 12% of all lymphoma cases, are discussed.

Humans↗