PubMed Health⌕ Search

Biomedical subjects

A Dattilo

Publications and source records attributed to A Dattilo.

At least 19 recordsLinked to original sources
PubMed1999

Surface CD14 positivity in B-cell chronic lymphocytic leukaemia is related to clinical outcome.

The aberrant expression of the myelomonocytic antigen CD14 was investigated in 128 untreated patients diagnosed with B-cell chronic lymphocytic leukaemia (B-CLL). A cut-off value of 5 x 10(9)/l CD14-positive cells was chosen for statistical analysis because it showed the best discriminating power among patients with different clinical features. 56 cases had a CD14+ cell count >5 x 10(9)/l. A significant correlation was found between Rai and Binet stages and total tumour mass (TTM) score on one hand, and the absolute CD14+ cell cut-off, on the other. This relationship was more evident in Rai 0-II and Binet A-B stages, where a CD14+ cell count >5 x 10(9)/l was preferentially distributed among patients with a higher tumoral mass. In univariate analysis the survival probability at 5 and 10 years showed a significant correlation with Rai and Binet stages, TTM score, CD14+ absolute cell count and median age. The median overall survival (OS) was 63 months for patients with a CD14+ cell count >5 x 10(9)/l and 136 months for those with a CD14+ cell count < 5 x 10(9)/l. In the multivariate Cox regression model, Rai stage, age and CD14+ cell count were independent significant factors for the prediction of OS. Finally, when the same analysis was restricted to Rai stages 0-II, CD14+ cell count was the only significant independent parameter influencing OS, with a relative death risk of 3.8. In conclusion, these data reveal that CD14+ represents an important marker for predicting OS in B-CLL patients and, therefore, we suggest that it should be included in the immunological characterization of B-CLL.

Female↗
PubMed1999

Clinico-biological implications of increased serum levels of interleukin-8 in B-cell chronic lymphocytic leukemia.

BACKGROUND AND OBJECTIVE: Constitutive cellular expression and serum release of biologically active interleukin-8 (IL-8) has been reported in B-cell chronic lymphocytic leukemia (CLL). Given the autocrine role played by IL-8 in the process of cell accumulation characteristic of this disease we tried to investigate clinico-biological implications of increased serum levels of this cytokine in an unselected series of B-cell CLL patients. DESIGN AND METHODS: Serum levels of IL-8 were determined at the time of diagnosis in 58 previously untreated B-CLL patients using an immunoenzyme assay. Results were correlated with main clinico-hematologic features as well as with the risk of disease progression. Finally, we looked for associations between IL-8 and molecules directly involved in apoptosis, such as intracellular bcl-2 and soluble APO-1/Fas. RESULTS: Increased serum levels of IL-8 were found in 15 out of 58 (25.8%) B-cell CLL patients. Serum levels of IL-8 did not reflect clinico-biological features representative of tumor mass such as clinical stage, histopathologic pattern of bone marrow (BM) involvement, b2-microglobulin, sCD23 and sCD27 titers. Interestingly, circulating levels of IL-8 paralleled those of intracellular bcl-2 (r = 0.522; p = 0.01), thus confirming that the antiapoptotic effect of IL-8 can be exerted through a bcl-2 dependent pathway. Levels of IL-8 did not match those of soluble Apo-1/Fas (r = -0.013; p = 0.943). Finally, stage A patients with levels of IL-8 above the median value (i.e. 4.5 pg/mL) were more likely to progress to a more advanced clinical stage than those with levels below the median value (p < 0.05). INTERPRETATION AND CONCLUSIONS: IL-8 is an interesting marker in B-cell CLL, closely involved in the pathogenesis of disease. Furthermore, it is useful for predicting the pace of disease progression in early clinical stages.

Apoptosis↗
PubMed1999

Natural history of early chronic lymphocytic leukemia. A single institution study with emphasis on the impact of disease-progression on overall survival.

BACKGROUND AND OBJECTIVE: Criteria for identifying patients with early chronic lymphocytic leukemia (CLL) who are likely to progress to a more advanced clinical stage rely on results of prospective clinical trials. Is not clear whether these same criteria apply to patients followed-up in the setting of clinical practice. With the aim of addressing this issue we investigated the clinical outcome of a series of patients with Binet stage A CLL. DESIGN AND METHODS: Two hundred and four Binet stage A CLL patients observed at a single institution over an 18-year period form the basis of this study. Different proposals for subclassifying Binet stage A were validated by using our patients as test-set cases. RESULTS: The survival of patients with early CLL (i.e., Binet stage A and Rai stage 0) was significantly different from that of an age- and sex-matched population. Three of 4 different criteria for subclassifying stage A (Rai substaging, Montserrat criteria, French Group proposal), when applied to our patients, gave similar results in terms of sample size, death rate and disease progression (DP) risk. The French Group proposal, based exclusively on blood counts and hemoglobin levels, was not effective in predicting the risk of DP. Forty-nine (23.5%) patients progressed to a more advanced clinical stage (30 to stage B and 19 to stage C); the risk of DP was 32.8% at 5 years and 49.6% at 10 years. When analyzed as a time-dependent variable (Mantel-Byar method), DP had a clear cut-impact on overall survival (p < 0.0001). Finally, outlook for survival of patients who experienced a change of clinical stage was similar to that of patients in that stage at the time of diagnosis. INTERPRETATION AND CONCLUSIONS: As many patients are now being diagnosed while asymptomatic and at a younger age than previously, an accurate evaluation of prognosis is mandatory in early CLL. How prognostic information translates into a policy of early or delayed therapy is still unclear. Our results further support a conservative approach for CLL in early stage; patients who progress into a more advanced stage have similar survival to those in that stage at diagnosis.

Adult↗
PubMed1998

Clinico-prognostic relevance of quantitative immunophenotyping in B-cell chronic lymphocytic leukemia with emphasis on the expression of CD20 antigen and surface immunoglobulins.

Expression of CD20, evaluated as antibody binding capacity (ABC) (i.e. absolute number of molecules of antibody per cell), was analyzed using flow cytometry on leukemic cells of 93 previously untreated patients, all fulfilling strict criteria of "immunologically typical" (i.e. CD5+, CD23+) B-cell chronic lymphocytic leukemia (CLL). Although changes of CD20 antigen density did not correlate with clinical parameters representative of either tumor mass (i.e. clinical stage, histological pattern of bone marrow involvement, absolute peripheral blood lymphocytosis) or disease progression (i.e. lymphocyte doubling time), a trend toward a better life-expectancy was observed in the low CD20 expression group compared with the high CD20 expression group (p = 0.05; relative risk of death, 0.51, 95% confidence interval, 0.24-1.04). Given the correlation between CD20 ABC and mean fluorescence intensity (MFI) of light chain (LC) surface immunoglobulins (Sm Ig) (r = 0.481, p < 0.0001), as well as the impact of MFI of Sm Ig LC on overall survival (p = 0.01; relative risk of death 0.44; 95% confidence interval, 0.10 to 0.76), we tried to verify whether a combination of B-cell markers, evaluated in a quantitative manner, could have additive prognostic properties. To this purpose we gave a value of 1 or 0 to each B-cell marker according to whether it was expressed at a low (i.e. CD20 ABC < 17.9 x 10(3) molecules/cell, MFI of LC Sm Ig < 100) or high (i.e. CD20 ABC > or = 17.9 x 10(3) molecules/cell, MFI of LC Sm Ig > or = 100) level thus allowing patient stratification into two groups with scores of 2 and 0-1, respectively. Survival of patients who scored 2 was significantly longer respectively. Survival of patients who scored 2 was significantly longer than that of patients who scored 0-1 (p = 0.02; relative risk of death, 0.44; 95% confidence interval, 0.22-0.72). However, when quantitative changes of CD20 antigen and LC Sm Ig expression, either alone or in combination, were simultaneously analyzed in a Cox model which included usual clinico-hematological features, only absolute peripheral blood lymphocytosis (p = 0.0001) and Binet clinical stages (p = 0.0001) maintained their prognostic power unmodified. Although variability of CD20 and Sm Ig expression make it possible to appreciate biological heterogeneity of B-cell CLL better, however, they cannot substitute well-established clinico-hematological features in the prognostic assessment of B-CLL patients.

Adult↗
PubMed1998

CD27 in B-cell chronic lymphocytic leukemia. Cellular expression, serum release and correlation with other soluble molecules belonging to nerve growth factor receptors (NGFr) superfamily.

BACKGROUND AND OBJECTIVE: CD27, a transmembrane homodimer belonging to the nerve growth factor (NGF) receptor superfamily, is typically expressed on leukemic CD5+ cells in B-cell chronic lymphocytic leukemia (CLL) and found in soluble form in the serum of CLL patients. Therefore, we investigated clinico-biological implications of increased serum levels of sCD27 in an unselected series of B-CLL patients. DESIGN AND METHODS: Serum CD27 (sCD27) levels were determined at the time of diagnosis in 82 previously untreated B-CLL patients using a sandwich enzyme-linked immunoassay (ELISA). Results were correlated with either clinico-hematological or biological features. Finally, quantitative flow cytometric analyses of membrane CD27 (mCD27) expression were carried out on peripheral blood (PB) cells of 22 B-CLL patients and 5 healthy controls, respectively. RESULTS: CD27 was found to be expressed on the surface of both resting normal and leukemic B cells. sCD27 levels were significantly higher in B-CLL patients (median value 2150 U/mL) than in healthy controls (median value 220 U/mL) (p < 0.0001). There was a close relationship between sCD27 and soluble TNF-alpha, another molecule belonging to the NGF receptor superfamily. Changes in sCD27 level correlated with clinical stage, beta 2 microglobulin and LDH. INTERPRETATION AND CONCLUSIONS: These findings indicate that sCD27 is a reliable marker of tumor mass in B-CLL. Its potential prognostic value should be tested in prospective studies.

Aged↗
PubMed1998

Increased bcl-2/bax ratio in B-cell chronic lymphocytic leukemia is associated with a progressive pattern of disease.

In order to evaluate clinical implications of altered expression of bcl-2 and bax proteins in B-cell chronic lymphocytic leukemia (CLL) we studied 27 patients with this disease. Cytofluorometric levels of bcl-2 did not reflect the status of disease. In contrast bax expression was lower in progressive than in non-progressive disease, therefore leading to a higher bcl-2/bax ratio in patients of the former group. If confirmed in longitudinal studies, quantitative cytofluorometric evaluation of bcl-2 and bax protein might help to identify patients with progressive disease who could possibly benefit from early therapy.

Biomarkers, Tumor↗
PubMed1996

Intercellular adhesion molecules (ICAMs) 2 and 3 are frequently expressed in B cell chronic lymphocytic leukemia.

Using different monoclonal antibodies (moAbs) from the 5th International Workshop on Leukocyte Differentiation Antigens we studied the expression of intercellular adhesion molecules (ICAMs) 2 and 3 on a homogeneous group of 23 B cell chronic lymphocytic leukemia (CLL) patients. Our results show that either ICAM-2 or ICAM-3 are constitutively expressed on CD5+ B-CLL cells. Owing to the role of ICAM molecules in governing the migration and traffic of lymphocytes to lymph nodes, our findings need to be validated in a more consistent patient series to understand clinico-prognostic implications of such an expression.

Antibodies, Monoclonal↗
PubMed1995

Expression on leukemic cells and serum circulating levels of intercellular adhesion molecule-1 (ICAM-1) in B-cell chronic lymphocytic leukemia: implications for prognosis.

Expression of intercellular adhesion molecule-1 (ICAM-1) has been correlated clinical and laboratory characteristics of 62 patients with untreated CD5+ chronic lymphocytic leukemia (CLL). ICAM-1 was detected on B-CLL cells from 19 out of 62 patients (30.6%) and its expression did not correlate with the majority of immunological markers. An important finding of this study was the association between ICAM-1 expression and mean fluorescence intensity (MFI) of Slg (r = 0.507; P < 0.001). As far as correlation with clinical parameters is concerned, a statistically significant association between Binet clinical stages and ICAM-1 expression was found (P < 0.05). Furthermore, an atypical CLL morphology was more frequently encountered among patients who expressed ICAM-1 (P < 0.005). To obtain more information on the role of ICAM-1 in CLL we measured serum levels with a sandwich enzyme immunoassay. In 47 B-cell CLL patients studied, the mean value of circulating ICAM-1 levels was significantly higher (561 +/- 201 ng/ml) than that observed in 25 normal controls (353 +/- 162 ng/ml; P < 0.005); a clear correlation being found with Binet clinical stages (P = 0.026) and bone marrow (BM) histology (P < 0.005). We conclude that circulating ICAM-1 is elevated in CLL and such an increase reflects tumor mass as defined by clinical stages and BM histology, rather than peripheral blood lymphocytosis (r = 0.240). Even if soluble ICAM-1 appears to be less specifically increased that soluble CD23 serum levels, these circulating molecules were not completely independent of each other (r = 0.512; P < 0.001).

Female↗
PubMedDate not supplied

CD11c expression in B-cell chronic lymphocytic leukemia. A comparison of results obtained with different monoclonal antibodies.

In order to obtain more information on the pattern of CD11c-positivity in otherwise typical B-cell chronic lymphocytic leukemia (CLL), we analyzed immunological and clinico-pathological features of 99 such patients studied with two different monoclonal antibodies (MoAbs). Fifty-two out of 70 (74.2%) patients stained with IOM-11C MoAb and 3 out of 29 (10.3%) patients stained with Leu-M5 MoAb had more than 30% CD11c positive cells (P < 0.0002). The two groups were similar with regard to the expression of B-cell CLL-related antigens (CD5, CD20, CD23), as well as clinico-pathological features (i.e. Binet clinical stage and pattern of bone marrow involvement), thus suggesting that differences in CD11c expression were due to different reactivity patterns of the MoAbs utilized. In our experience, the use of different reagents may affect immunophenotyping results, thus providing conflicting data at times.

Aged↗
PubMedDate not supplied

Differential expression of BCL-2 oncoprotein and Fas antigen on normal peripheral blood and leukemic bone marrow cells. A flow cytometric analysis.

BACKGROUND: Fas antigen (Ag) has recently been identified as the putative surface molecule capable of transducing apoptotic signals into cells. Alterations in the expression of proto-oncogene bcl-2 have been implicated in the regulation of apoptosis. MATERIALS AND METHODS: By employing a monoclonal antibody to bcl-2 protein (124 clone) and to Fas Ag (UB2 clone) the expression of these molecules was analyzed at flow cytometry on bone marrow (BM) and peripheral blood (PB) samples from patients suffering from different lymphoid and myeloid leukemic diseases (27 acute non-lymphocytic leukemia [ANLL]; 14 acute lymphocytic leukemia [ALL]; 19 B-cell chronic lymphocytic leukemia [CLL]; 2 Ph1+ chronic myeloid leukemia [CML]; one CD8+ T-cell chronic lymphoproliferative disorders). Results were compared with those observed on normal PB leukocytes and BM B-cell precursors from patients with non-neoplastic hematological disorders. RESULTS: Fas Ag was constitutively expressed by both monocytes and neutrophils, while lymphocytes expressed bcl-2 with no difference between B and T cell subsets. Interestingly, bcl-2 expression was always absent on neutrophils. When dealing with ANLL patients, a relatively low bcl-2 and high Fas Ag phenotype characterized subtypes with granulocytic (M2) or promyelocytic (M3) differentiation. This observation was confirmed in a small number of patients for whom bcl-2 levels were quantified as antibody binding capacity (ABC) in molecules/cell. Leukemic cells from patients with ALL constitutively expressed bcl-2, the pattern of this expression being quantitatively lower than that of immature B-cell precursors. Finally, high bcl-2 and low Fas Ag expression represented a crucial part of the B-cell CLL immunophenotype. CONCLUSIONS: Although based on a small number of patient and control samples, our results suggest that bcl-2 and Fas Ag are coordinately expressed on normal PB leukocytes. Fas Ag is expressed at low levels on B-CLL cells, generally considered long-surviving cells. The relatively lower bcl-2-expression detected in both M2 and M3 subtypes may explain, at least in part, the higher remission rates obtained in these forms of ANLL than in other less differentiated morphological variants.

B-Lymphocytes↗
PubMedDate not supplied

Cellular expression and serum circulating levels of CD23 in B-cell chronic lymphocytic leukemia. Implications for prognosis.

BACKGROUND: CD23 is a functionally relevant molecule in B-cell chronic lymphocytic leukemia (CLL) which mediates growth and differentiation signals in B-cells. An intriguing feature of CD23 is its ability to be cleaved from the cell surface and released into the serum. MATERIALS AND METHODS: Serum levels of soluble CD23 (sCD23) were determined with a sandwich enzyme immunoassay at the time of diagnosis in 90 previously untreated CLL patients, in order to evaluate whether they reflected disease activity and tumor load. Results were correlated with those dealing with CD23 expression on leukemic cells to verify whether the cellular counterpart determines serum levels. RESULTS: CD23 was detected on peripheral blood mononuclear cells (PBMC) from 78 out of 90 (86.6%) B-CLL patients, without correlation with clinical stage. Circulating levels of sCD23 in the serum of patients with CLL were highly elevated in comparison to 15 normal controls (p < 0.0005); this increase reflected tumor mass as defined by either clinical stage (p < 0.0005) or bone marrow (BM) histology (p < 0.0005). Neither percentage nor absolute number of CD23+ cells correlated with circulating levels. Interestingly, life expectancy was significantly shorter in patients with higher serum levels of sCD23 (p < 0.0005). When integrated into the Binet clinical staging system, sCD23 led to isolation of two subgroups with different prognosis among intermediate-risk patients. Furthermore, longitudinal studies support the idea that sCD23 can be utilized as an indicator of disease progression. CONCLUSIONS: sCD23 is a highly sensitive and suitable marker with prognostic potential in B-CLL.

Aged↗