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P Galieni

Publications and source records attributed to P Galieni.

At least 19 recordsLinked to original sources
PubMed1995

Clinical implications of cytokine and soluble receptor measurements in patients with newly-diagnosed aggressive non-Hodgkin's lymphoma.

Serum levels of 13 different cytokines and receptors were measured serially in 78 patients with aggressive non-Hodgkin's lymphoma (NHL) treated by 4 cycles of an intensive multi-agent chemotherapy regimen. Recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) was administered subcutaneously in 36 of these patients from day + 5 to day + 18 after each chemotherapy. Statistically significantly higher pretreatment levels of interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), the soluble IL-2 receptor (sIL-2r), the soluble transferrin receptor (sTf-r), and neopterin, were observed in NHL patients as compared to controls (p < 0.001 for all molecules). sIL-2r and sTf-r levels correlated with tumor burden (p < 0.001 and p = 0.003, respectively) whereas IL-6 was higher in patients presenting B symptoms (p < 0.001). Cytokine levels progressively declined to normal ranges in responding patients, while they remained elevated in non-responders. Relapsed patients also presented increased concentrations of several molecules. During the administration of GM-CSF, we observed the drastic increase of sIL-2r, while lower elevations were recorded for a number of cytokines, including IL-8, tumor necrosis factor-alpha, interleukin-1 beta, IL-6, and IL-2. However, upon completion of the induction treatment, cytokine/receptor levels were comparable among individuals with the same type of response, whether or not they had received GM-CSF. No single parameter was found to be of prognostic significance, but the combination of elevated IL-10 and of sIL-2r greater than 3000 U/ml selected a subgroup of 7 patients who failed induction treatment (p = 0.002). These results demonstrate that cytokine and soluble receptor measurements can provide valuable informations for a better management of NHL, in terms both of markers to monitor disease activity and of prognostic indicators.

Adult↗
PubMed1994

Detection of soluble interleukin-2 receptor and interleukin-10 in the serum of patients with aggressive non-Hodgkin's lymphoma. Identification of a subset at high risk of treatment failure.

BACKGROUND: This study explores the ability of the combined detection of soluble IL-2 receptor (sIL-2r) and interleukin-10 (IL-10) to predict treatment failure in patients with aggressive non-Hodgkin's lymphoma (NHL) and to evaluate the modifications in cytokine measurements induced by the therapeutic administration of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF). METHODS: Serum levels of sIL-2r and IL-10 were measured serially in 93 patients with newly diagnosed aggressive NHL treated with four courses of a multiagent chemotherapy regimen. GM-CSF was administered subcutaneously in 39 of these patients from day +5 to day +18 after each chemotherapy course. RESULTS: Pretreatment levels of sIL-2r were greatly elevated in patients with NHL compared with control subjects (P < 0.001), significantly correlating with the Ann Arbor stage (P < 0.001) and beta 2-microglobulin (beta 2-m) concentrations (r = 0.552, P = 0.004). IL-10 was detected in 37 patients at diagnosis, with no correlation with clinicohematologic parameters, and was not detected in the control sample (P < 0.001). Cytokine and receptor levels progressively declined to normal ranges in responding patients, whereas they remained elevated in nonresponders. During administration of GM-CSF, the authors observed an increase of sIL-2r, whereas lower elevations were recorded for IL-10. However, on completion of the induction treatment, cytokine/receptor levels were comparable in patients with the same type of response, whether or not they had received GM-CSF. In the five patients who were investigated at relapse, the levels of sIL-2r, beta 2-m, and lactic dehydrogenase were found to be elevated. IL-10 concentrations were high in three of these patients: two already had detectable levels at presentation, whereas one tested positive only on recurrence. No single parameter was associated with response to therapy, but the combination of elevated IL-10 and sIL-2r concentrations greater than 3000 U/ml resulted in a subset of eight patients who failed induction chemotherapy (P < 0.001). In addition, six of eight patients with high IL-10 and beta 2-m concentrations greater than 3.3 mg/l had an unfavorable outcome (P = 0.003). A multivariate regression model was used to identify sIL-2r (P = 0.004) and beta 2-m (P = 0.043) as the covariates that amplified the prognostic ability of IL-10. CONCLUSIONS: sIL-2r and IL-10 measurements provide valuable information for better management of patients with NHL as markers to monitor disease activity and as prognostic indicators.

Adolescent↗
PubMed1994

Prognostic value of serum IL-10 and soluble IL-2 receptor levels in aggressive non-Hodgkin's lymphoma.

We investigated the prognostic significance of interleukin-10 (IL-10) and soluble interleukin-2 receptor (sIL-2r) levels in the pretreatment serum of 105 individuals with newly-diagnosed aggressive non-Hodgkin's lymphoma (NHL). Commercially available enzyme-linked immunoassay kits were used for cytokine and receptor measurements. Detectable levels of IL-10 were found in 42 (40%) patients at diagnosis, with no correlation with clinico-haematological parameters, but in no control samples (P < 0.001). Pretreatment concentrations of sIL-2r were markedly increased in individuals with NHL when compared to controls (2614 +/- 893 U/ml v 219 +/- 65 U/ml, P < 0.001), patients with stage III/IV presenting higher values than those with stage II disease (3885 +/- 1196 U/ml v 1732 +/- 646 U/ml, P < 0.001). No single parameter was associated with the achievement of complete remission, but the combination of elevated IL-10 and of sIL-2r greater than 3000 U/ml selected a subset of patients with a high probability of failing induction therapy (P < 0.001). Life-table analysis also indicated that patients with these characteristics have a significantly shorter event-free survival. In a multivariate analysis the combination of IL-10 with sIL-2r was found to have greater predictive strength than the combination of IL-10 with beta 2-microglobulin. We conclude that IL-10 and sIL-2r measurements can be expected to improve existing methods of risk assignment in aggressive NHL.

Adult↗
PubMed1993

Correlations between apoptotic and proliferative indices in malignant non-Hodgkin's lymphomas.

Cell production versus cell loss rates were estimated, across the boundaries of histological classification, in 50 cases of malignant non-Hodgkin's lymphomas by use of mitotic indices, percentage of Ki-67+ cells and percentage of PC10+ cells as proliferative indices, and the relative number of apoptotic bodies (apoptotic indices, AIs) as parameters. Regression analysis revealed significant (P < 0.01) positive correlations between the AIs and the proliferative indices; among the immunohistochemically assessed proliferative indices; and between these, the mitotic indices and the AIs on the one hand and histological malignancy grades on the other hand. The cellular protein BCL-2, which counteracts apoptosis, was significantly (P < 0.01) more often expressed in lymphomas with low than in those with high AIs. Multivariate analysis of data showed that of all parameters tested in this series, only the AIs correlated significantly (P < 0.05) with overall lethality. The correlation between BCL-2 positivity of lymphoma cells and overall survival did not quite attain significance (P = 0.08). Results of the present study suggest that high AIs and lack of BCL-2 expression may be adverse prognostic factors, independent of histological grade.

Apoptosis↗
PubMed1989

Phase II study of a new alkylating agent (PTT-119) in resistant-relapsed non-Hodgkin's lymphomas.

In a phase II study we evaluated the effect and toxicity of a new alkylating agent, PTT-119, in 26 patients with non-Hodgkin's lymphomas (NHL) resistant to or relapsed after other chemotherapy. PTT was scheduled by escalating the dose from 2.0 to 3.3 mg/kg every 3 weeks. Among 21 evaluable patients with NHL, 12 (57%) showed a good response (CR + PR) to PTT-119. Tolerance was acceptably good; no major side effects related to liver, cardiac, or renal toxicity were recorded. The most commonly recorded side effects were nausea and vomiting, alopecia, and phlebitis; diarrhea and drug-related fever were rarely seen. This report indicates a potential usefulness for PTT-119, a non-cross-resistant alkylating agent, in the treatment of NHL.

Adult↗
PubMed1989

Evidence that long-term bone marrow culture of patients with multiple myeloma favors normal hemopoietic proliferation.

Long-term bone marrow cultures (LTBMC) were initiated with marrow aspirate cells from 12 patients with multiple myeloma (MM) using the Dexter system. The myeloid and the neoplastic myeloma cell growths were evaluated for up to 6-9 weeks. Our results demonstrate the development of an adherent layer capable of supporting normal granulopoiesis with a concomitant drop in the growth of myeloma cells. The B lymphocyte monoclonal proliferative compartment was also studied with bromodeoxyuridine (Brdurd), an analog of thymidine incorporated during the S-phase, and the labeling index was calculated. The ability to form myeloma stem cell colonies in a modified plasma clot short-term assay was also evaluated. The results confirmed that the neoplastic B lineage compartment was not able to grow in Dexter's system for more than 4 weeks in 11 of 12 cases studied, with the disappearance of Brdurd-positive cells after two weeks, whereas LTBMC were able to sustain the growth of myeloid progenitors. These data indicate the potential applicability of this culture method in selecting normal hematopoietic progenitors from patients with multiple myeloma. This approach can have significant implications for aggressive treatment of patients with multiple myeloma, especially in trials involving autologous bone marrow transplantation (ABMT).

Adult↗
PubMed1989

Histology and immunohistology of bone marrow biopsy in multiple myeloma.

B5-fixed/paraffin-embedded Jamshidi needle biopsies from 125 multiple myeloma patients were reviewed according to both morphological and immunohistological criteria. At microscopic examination, the following parameters were evaluated: i) grade of malignancy (low = 56; intermediate = 50; high = 19); ii) growth pattern (interstitial +/- sheets/nodules = 90; nodular = 13; packed marrow = 18; sarcomatous = 4); III) histological stage (I = 64; II = 35; III = 26). Comparison of the findings in trephine biopsies and aspirates showed that in 30% of the cases the latter led to an underestimation of the tumor burden. Immunohistochemical determination of Ig easily allowed: i) differential diagnosis from exuberant reactive plasmacytosis; ii) recognition and counting of neoplastic plasma cells; iii) detection of minimal residual disease after treatment. Immunohistochemistry also confirmed phenotypic aberration of neoplastic plasma cells, showing positivity for CD45, EMA, and cytokeratins in 14%, 59%, and 25% of the cases, respectively. Furthermore, it displayed expression of the P-glycoprotein in 4/8 resistant cases. These findings underline that routinely processed Jamshidi needle biopsies can be of great value in the study of patients with multiple myeloma.

Acute Disease↗
PubMed1989

Improvement of Durie & Salmon staging for multiple myeloma by adding platelet count as a stratifying variable: a multivariate regression analysis of 163 untreated patients.

The presenting clinical features of 163 previously untreated patients with multiple myeloma were correlated with survival duration using univariate and multivariate regression analyses. The univariate proportional hazard analysis ranked the parameters in the following order of importance: platelet count, haemoglobin level (Hb), tumour cell mass stage, lytic bone lesions, creatinine and age. When the individual contribution of each variable was assessed by multivariate regression analysis, platelet count was confirmed to be the dominant feature for prognosis, while clinical stage provided additional information. The introduction of platelet count could then be used to improve the discriminating power of Durie & Salmon staging, by allowing separation of the high-risk group (stages II and III) into a smaller subgroup (22%) of thrombocytopenic patients (less than 150 x 10(9) platelets/l) whose risk of death was actually very high (median survival: 9 months) and a larger subgroup (46%) of patients with normal platelet count and intermediate or standard risk (median survival: 48 months).

Humans↗
PubMed1989

Normal myeloid progenitors (CFU-GM) in multiple myeloma: a preliminary study in view of autologous BMT.

Normal granulocyte-macrophage precursors (CFU-GM) were studied in 65 multiple myeloma patients by means of culture assays. The patients were divided into separate groups on the basis of previous therapy (i.e. analysis performed at diagnosis or after chemotherapy), time elapsed from the last therapy (i.e. more or less than 1 month) and clinical features of the disease (i.e. tumor stage, immunoglobulin type, bone marrow plasma cell infiltration). The results were evaluated by Wilcoxon rank sum test and linear regression analysis. There was no statistical difference in CFU-GM cloning efficiency or in the number of CFU-GM/ml of bone marrow, even though a larger CFU-GM recovery was found in patients evaluated at diagnosis or at least 1 month or more from previous chemotherapy. In addition, no correlation was demonstrated between bone marrow plasma cell percentage and CFU-GM cloning efficiency. This finding was confirmed by the number of myeloid bone marrow cells in S-phase, assessed by the bromodeoxyuridine labeling index, which showed similar results in patients with different degrees of plasma cell infiltration. In conclusion our data indicate that the granular-monocytic lineage keeps its cell-line potentiality regardless of the degree of marrow plasma cell infiltration and the type of therapeutic approach. These data suggest that autologous bone marrow transplantation might be feasible even in patients with a large neoplastic infiltration.

Adult↗
PubMed1989

Prognostic variables and clinical staging in multiple myeloma.

To evaluate the most important factors in the prognosis and staging of multiple myeloma (MM), the presenting clinical features of 163 previously untreated patients with MM were correlated with survival duration using univariate and multivariate regression analyses. The univariate proportional hazard analysis ranked the parameters in the following order of importance: platelet count, hemoglobin level (Hb), tumor cell mass stage, lytic bone lesions, creatinine, and age. When the individual contribution of each variable was assessed by multivariate regression analysis, platelet count was confirmed to be the dominant feature for prognosis and clinical stage provided additional information. The introduction of platelet count could then be used to improve the reliability of the Durie and Salmon staging, by allowing to separate the high-risk group (stages II and III) into a smaller subgroup (22%) of thrombocytopenic patients (less than 150 x 10(9) platelets/L) whose risk of death was actually very high (median survival, 9 months) and a larger subgroup (46%) of patients with normal platelet count and intermediate or standard risk (median survival, 48 months). This simple change in the prognostic system gave rise to markedly different survival curves also after the exclusion of patients with renal failure and applied successfully to both old and young patients (greater than and less than 50 years, respectively). Finally, platelet count, Hb, and lytic bone lesions could be combined simply to stratify patients with normal renal function into three risk groups: (1) low (39% of cases; median survival, 79 months), (2) intermediate (53% of cases; median survival, 48 months), and (3) high (8% of cases; median survival, 19 months).

Bone Marrow↗