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C Pascutto

Publications and source records attributed to C Pascutto.

16 recordsLinked to original sources
PubMed2006

Prevalence of HCV infection in nongastric marginal zone B-cell lymphoma of MALT.

BACKGROUND: Hepatitis C virus (HCV) infection is frequently associated with B-cell non-Hodgkin's lymphomas. We investigated the prevalence of HCV infection in nongastric marginal zone lymphomas of mucosa-associated lymphoid tissue (MALT) in order to define the relationship between the viral infection and the presenting features, treatment, and outcome. METHODS: We retrospectively studied 172 patients with a histological diagnosis of marginal zone B-cell lymphoma of MALT, except for stomach, and with available HCV serology, among a series of 208 patients. RESULTS: HCV infection was documented in 60 patients (35%). Most HCV-positive patients (97%) showed a single MALT organ involvement. HCV-positive patients showed a more frequent involvement of skin (35%), salivary glands (25%), and orbit (15%). The majority of stage IV HCV-positive patients (71%) had a single MALT site with bone marrow involvement. The overall response rate was similar in HCV-positive (93%) and HCV-negative patients (87%). Overall survival (OS) and event-free survival (EFS) did not differ according to HCV infection. In multivariate analysis, advanced disease (stage III-IV) was associated with a poorer OS (P = 0.0001), irrespective of HCV serostatus. CONCLUSIONS: This study shows that nongastric marginal zone lymphomas are characterized by a high prevalence of HCV infection. Patients with involvement of a single MALT site have the highest prevalence of HCV. HCV-positive nongastric lymphomas of MALT show an indolent course similar to HCV-negative patients and seem an ideal target for exploiting the antilymphoma activity of antiviral treatments.

Antibodies, Viral↗
PubMed2006

Flow cytometry evaluation of erythroid dysplasia in patients with myelodysplastic syndrome.

Erythroid dysplasia is the pathologic hallmark of myelodysplastic syndromes (MDS). To develop a quantitative flow-cytometry approach to its evaluation, we analyzed the expression of CD71, CD105, cytosolic H-ferritin (HF), cytosolic L-ferritin (LF) and mitochondrial ferritin (MtF) in erythroblasts from 104 MDS patients, 69 pathologic control patients and 19 healthy subjects. Six-parameter, 4-color flow cytometry was employed, and data were expressed as mean fluorescence intensity. Compared with pathologic and healthy controls, MDS patients had higher expression of HF (P < 0.001) and CD105 (P < 0.001), and lower expression of CD71 (P < 0.001). MtF was specifically detected in MDS with ringed sideroblasts, and there was a close relationship between its expression and Prussian blue staining (r = 0.89, P < 0.001). In vitro cultures of myelodysplastic hematopoietic progenitors showed that both HF and MtF were expressed at a very early stage of erythroid differentiation, and that MtF expression is specifically related to mitochondrial iron loading. A classification function based on expression levels of HF, CD71 and CD105 allowed us to correctly classify > 95% of MDS patients. This flow-cytometry approach provides an accurate quantitative evaluation of erythroid dysplasia and allows a reliable diagnosis of sideroblastic anemia, and may therefore be a useful tool in the work-up of patients with MDS.

Adult↗
PubMed2005

Efficacy, toxicity and feasibility of a shorter schedule of DCEP regimen for stem cell mobilization in multiple myeloma.

From 2000 to 2004, 152 patients with multiple myeloma aged or=4 x 10(6) cells/kg. The proportion of patients in whom mobilization failed was similar in the two groups. The incidence of WHO grade III neutropenia was higher in group II, although the difference was not statistically significant; the percentage of patients requiring hospitalization for severe infections was similar in the two groups. The incidence of WHO grade IV thrombocytopenia did not differ between the two groups. The response rate was 72% in group I and 80% in group II with similar percentages of patients achieving good responses. DCEP-short is a good mobilizing regimen, sharing the same characteristics as infusional-DCEP: high mobilizing efficacy, low toxicity and good antitumor activity. This new schedule of DCEP does, however, allow complete outpatient management and so could be advantageously included in any high-dose therapy program.

Antigens, CD34↗
PubMed2005

Flow cytometry evaluation of erythroid and myeloid dysplasia in patients with myelodysplastic syndrome.

The purpose of this study was to develop a flow cytometric approach to the evaluation of marrow dysplasia in myelodysplastic syndromes (MDS). We first studied a cohort of 103 MDS patients as well as 46 pathological and healthy controls. Flow cytometry data were expressed as percentage of positive cells. Analysis of erythroid cells showed higher proportions of immature cells (P < 0.001) and decreased levels of CD71 expression on nucleated red cells (P = 0.02) in MDS. Analysis of myeloid cells showed lower proportions of CD10+ and higher proportions of CD56+ granulocytes (P < 0.001), and increased ratios of immature to mature cells (P = 0.007). Since no single immunophenotype could accurately differentiate MDS from other conditions, we used discriminant analysis for generating erythroid and myeloid classification functions using combinations of immunophenotypic parameters. These functions were prospectively validated in a testing cohort of 69 MDS patients and 46 pathological controls. A diagnosis of MDS was obtained in 60/69 cases (87%). No false-positive results were noticed among controls. Significant correlations between values of these functions and both degree of morphological dysplasia and the International Prognostic Scoring System were found. These findings indicate that flow cytometry evaluation of marrow dysplasia is feasible and may be useful in the work-up of individual MDS patients.

Antigens, CD34↗
PubMed2004

A model of in vivo purging with Rituximab and high-dose AraC in follicular and mantle cell lymphoma.

We studied a model of in vivo purging with Rituximab and high-dose (HD) cytarabine in 14 patients with relapsed/refractory follicular lymphoma and two with refractory mantle cell lymphoma enrolled in a program of HD chemotherapy and autotransplant. After two courses of debulking immunochemotherapy with Rituximab, Vincristine and Cyclophosphamide, we used a combination of Rituximab, HD cytarabine and granulocyte colony-stimulating factor for peripheral blood stem cells (PBSC) mobilization. The median number of CD34+ cells collected was 14.69 x 10(6)/kg (range 5.74-73.2). Monitoring of peripheral CD19+ and CD20+ B cells prior to and throughout the purging period showed that a treatment with Rituximab, Vincristine and Cyclophosphamide results in a profound depletion of B cells in peripheral blood. B-cell depletion persists during mobilization with Rituximab and HD cytarabine allowing a collection of PBSC free of B cells (median CD19+ and CD20+ cells counts 0%). Of nine patients PCR positive for bcl-2 or bcl-1 in blood and marrow at the start of immunochemotherapy, all showed PCR-negative PBSC. In conclusion, in patients with indolent lymphoma, the concurrent administration of Rituximab and HD cytarabine is a safe and efficient method to obtain in vivo purged PBSC. Immunochemotherapy prior to mobilization produces B-cell depletion and seems to be a useful preparative step.

Adult↗
PubMed2003

Urinary proteins in multiple myeloma: correlation with clinical parameters and diagnostic implications.

Renal failure is one of the worst complications occurring in multiple myeloma (MM) patients. It does not affect survival if reverted by a prompt chemotherapy before the damage becomes irreversible; therefore, the early diagnosis of renal dysfunction is crucial. High and low molecular weight urinary proteins have proved to be helpful in diagnosing initial renal damage since they are more sensitive than urea and creatinine serum levels or creatinine clearance. We studied the renal function of 111 MM patients through serum creatinine, urea, urinary IgG, alpha(1)-microglobulin (alpha(1)-M), and albumin (Alb). Two successive controls were made in a subset of 30 patients, categorized in three groups (improved, stable, worsened) according to the behavior of tumor burden markers (bone marrow plasmacytosis, monoclonal component, and beta(2)-microglobulin). In every group, we evaluated the behavior of urinary proteins. Renal dysfunction evaluated with serum parameters was present in 19 patients (17%), while if studied with urinary proteins was revealed in 71 patients (64.5%). Urinary proteins statistically correlated with each other. They correlated with creatinine, IgG, and alpha(1)-M also with urea. By contrast, they showed a variable correlation with clinical parameters: alpha(1)-M correlated with bone marrow plasmacytosis (BMPC) ( p=0.02) and beta(2)-M ( p=0.000001), IgG with all three disease parameters (MC p=0.0005, BMPC p=0.009, beta(2)-M p=0.007), and Alb only with beta(2)-M ( p=0.0004). In the subset of 30 patients followed with two successive controls, urinary proteins showed a parallel behavior with the indices of tumor burden. In conclusion, IgG, alpha(1)-microglobulin, and albumin are reliable and sensitive to precociously reveal renal damage, and we recommend their routine use for the definition and monitoring of renal function in multiple myeloma patients, mainly those in early stage, to better identify initial signs of progression.

Adult↗
PubMed2002

An immunogenetic map of Lombardy (Northern Italy).

For this study we consulted the Bone Marrow Donors' Registry of Lombardy (Italy) and analyzed 43937 HLA-A,B phenotypes and 13922 HLA-A,B,DR phenotypes. We estimated the HLA-A,B and HLA-A,B,DR haplotype frequencies via the maximum-likelihood method. We analyzed the genetic structure of the 11 provinces of Lombardy by means of Principal Component Analysis and Correspondence Analysis, and estimated the variety of the different haplotypes at provincial level and the percentage of unique phenotypes at village level. We found 11189 different HLA-A,B phenotypes, 661 different HLA-A,B haplotypes and more than 4000 different HLA-A,B,DR haplotypes. We identified 20 villages, in Western Lombardy, very rich in unique/rare phenotypes. Here we report a formula which allows the identification of a putative donor matched for two haplotypes with a recipient. This result may be of great importance for the genetic study of the population of Lombardy and, even more, for bone marrow transplantation programs.

Alleles↗
PubMed2001

Biochemical markers of bone disease in asymptomatic early stage multiple myeloma. A study on their role in identifying high risk patients.

BACKGROUND AND OBJECTIVES: Skeletal involvement is typical of multiple myeloma (MM) and its occurrence increases with the progression of the disease. We performed a study to evaluate the clinical importance of osteocalcin (bone gla-protein, BGP) and bone alkaline phosphatase (b-AP) as indices of osteoblastic activity, and deoxypyridoline (DPD) as a marker of bone resorption. DESIGN AND METHODS: Fifty-two MM patients, 39 patients with monoclonal gammopathy of undetermined significance (MGUS), and 30 normal controls entered the study. Of the 52 MM patients, 10 showed lytic lesions at standard X-rays and 42 did not; 21 were untreated and 31 had been treated with chemotherapy (combined with bisphophonates in 15). Of these last, 12 had progressive disease and 19 were in plateau phase. RESULTS: DPD levels were higher in MM patients than in patients with MGUS or healthy controls (p = 0.0001 and p = 0.0008, respectively). No statistical differences were seen between patients with MGUS and healthy controls. BGP serum levels were significantly lower in MM patients than in MGUS patients (p = 0.001) or healthy controls (p = 0.001). b-AP was significantly higher in MGUS patients than in MM patients (p = 0.04). Biochemical parameters were analyzed in a continuous fashion and after dichotomization into low and high values with respect to normal ones. Abnormal high values of DPD showed statistically significant correlations with presence of osteolysis (p = 0.008), advanced stage (p = 0.03) and abnormal beta2-microglobulin (beta2M) values (p = 0.03), while DPD as a continuous variable correlated significantly only with the presence of osteolysis (p = 0.02). In contrast, neither BGP nor b-AP showed statistical correlations with the presence of lytic lesions, or with other clinical or laboratory parameters. In 15 patients followed with serial controls, modifications of DPD levels reflected bone disease status well. Of the 42 patients without radiologic evidence of skeletal lesions, 15 had abnormal DPD values. Spinal magnetic resonance imaging (MRI) showed initial lytic lesions in 10 of them. INTERPRETATION AND CONCLUSIONS: Biochemical markers of bone metabolism are useful in evaluating and monitoring skeletal involvement in MM patients. They may help clinicians to identify: 1) from among patients without radiologic evidence of lytic lesions, those who deserve more accurate radiologic examinations (namely MRI); 2) from among asymptomatic patients, and in association with spinal MRI, those patients at higher risk of progression who might benefit from early treatment.

Adult↗
PubMed1998

The Sardinian IDDM study: 1. Epidemiology and geographical distribution of IDDM in Sardinia during 1989 to 1994.

Analysis of the geographical variation of risk for a disease is a key issue in descriptive epidemiology and may provide useful suggestions for planning further studies to identify the underlying causes. We adopted a Bayesian approach to investigate the geographical distribution of insulin-dependent diabetes mellitus (IDDM) incidence rate across Sardinia. Data on incidence of IDDM in children aged under 15 years (619 IDDM cases) in Sardinia was obtained by the Sardinian Eurodiab ACE register. The overall completeness of ascertainment was: 91.3%. The average yearly standardized incidence rate for the years 1989-1994 was 33.24 per 100000 (95% C.I. 30.60, 35.88), which is the second highest in Europe after Finland. Sex and age-specific risks were higher in males than in females. Considering the variation of IDDM risk according to the age at diagnosis, the risk profile increased up to the 13th year of age for both sexes, being steeper in males. The degree of geographical variation in IDDM risk was small with a slight difference between the highest and the lowest standardized rate across the map. Indeed, even the municipalities at lowest risk in Sardinia showed a risk higher than most European countries. The Sardinian population is genetically atypical, characterized by genetic homogeneity and marked susceptibility to autoimmune diseases. Our finding of a small geographical variation within the island coupled with a marked temporal trend previously observed in data on military conscripts could be interpreted as evidence of a relatively recent environmental aetiological factor that was uniformly distributed across the island and had its effect in a genetically predisposed population.

Age Factors↗
PubMed1997

Disease mapping with errors in covariates.

We describe Bayesian hierarchical-spatial models for disease mapping with imprecisely observed ecological covariates. We posit smoothing priors for both the disease submodel and the covariate submodel. We apply the models to an analysis of insulin Dependent Diabetes Mellitus incidence in Sardinia, with malaria prevalence as a covariate.

Bayes Theorem↗
PubMed1995

[Bayesian analysis of ecological studies].

Studying the space-time variation of risk for a given disease may give etiological clues and suggestions for planning further studies to investigate the underlying causes. When the observed events are rare, approaches based on maximum likelihood may lead to unstable and largely uninformative estimates of risk and of its time trend due to Poisson sampling variation. In this paper we propose a general Bayesian model for analyzing the variation of risk in space and time. We applied the Bayesian model to the analysis of the geographical variation of breast cancer mortality, to an ecological study on the correlation between lung cancer mortality and degree of urbanization and industrialization and to the analysis of the space-time variation of cumulative prevalence of Insulin Dependent Diabetes Mellitus (IDDM) as observed in military examinations between 1954 and 1989.

Bayes Theorem↗
PubMedDate not supplied

Statistical issues in the analysis of disease mapping data.

In this paper we discuss a number of issues that are pertinent to the analysis of disease mapping data. As an illustrative example we consider the mapping of larynx cancer across electoral wards in the North West Thames region of the U.K. Bayesian hierarchical models are now frequently employed to carry out such mapping. In a typical situation, a three-stage hierarchical model is specified in which the data are modelled as a function of area-specific relative risks at stage one; the collection of relative risks across the study region are modelled at stage two; and at stage three prior distributions are assigned to parameters of the stage two distribution. Such models allow area-specific disease relative risks to be 'smoothed' towards global and/or local mean levels across the study region. However, these models contain many structural and functional assumptions at different levels of the hierarchy; we aim to discuss some of these assumptions and illustrate their sensitivity. When relative risks are the endpoint of interest, it is common practice to assume that, for each of the age-sex strata of a particular area, there is a common multiplier (the relative risk) acting upon each of the stratum-specific risks in that area; we will examine this proportionality assumption. We also consider the choices of models and priors at stages two and three of the hierarchy, the effect of outlying areas, and an assessment of the level of smoothing that is being carried out. For inference, we concentrate on the description of the spatial variability in relative risks and on the association between the relative risks of larynx cancer and an area-level measure of socio-economic status.

Age Factors↗
PubMedDate not supplied

Bayesian analysis of space-time variation in disease risk.

The analysis of variation of risk for a given disease in space and time is a key issue in descriptive epidemiology. When the data are scarce, maximum likelihood estimates of the area-specific risk and of its linear time-trend can be seriously affected by random variation. In this paper, we propose a Bayesian model in which both area-specific intercept and trend are modelled as random effects and correlation between them is allowed for. This model is an extension of that originally proposed for disease mapping. It is illustrated by the analysis of the cumulative prevalence of insulin dependent diabetes mellitus as observed at the military examination of 18-year-old conscripts born in Sardinia during the period 1936-1971. Data concerning the genetic differentiation of the Sardinian population are used to interpret the results.

Adolescent↗