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Biomedical subjects

G Leone

Publications and source records attributed to G Leone.

At least 37 records · Page 2Linked to original sources
PubMed2005

Secondary acute myeloid leukaemia: results of conventional treatments. Experience of GIMEMA trials.

BACKGROUND: The aim of the study was to evaluate the outcome of acute myeloid leukaemia (AML) in patients with a previous malignancy (sAML) treated with chemo- and/or radiotherapy, enrolled in conventional trials. PATIENTS AND METHODS: In a multicentre setting, a prospective non-concurrent analysis was performed on 2513 new AML patients, aged 12-78 years, consecutively enrolled in EORTC-GIMEMA trials between 1987 and 2001. Thirty-eight patients with sAML were identified and compared with a group of 114 de novo AML patients matched according to age, French-American-British criteria, white blood cell count at diagnosis, trial and time of diagnosis of AML. Induction treatment response, disease-free survival (DFS), duration and overall survival (OS) were evaluated in the two groups. RESULTS: Comparing the complete remission (CR) rate between 38 sAML patients and 114 de novo AML patients, selected according to the previously reported criteria, we observed no difference in the CR rates [25/38 (66%) versus 66/114 (58%); Pearson chi(2) 0.7393, P=0.390] as well as no differences while comparing the DFS and the OS between the two groups. CONCLUSION: The results of this study suggest that sAML patients are characterised by a good performance status permitting their recruitment in conventional trials without a previous myelodysplastic phase. Similar to de novo AML patients, sAML patients show good response to treatment and the possibility of cure.

Acute Disease↗
PubMed2005

The risk of thrombosis in patients with acute leukemia: occurrence of thrombosis at diagnosis and during treatment.

BACKGROUND: Thromboembolism can occur during acute leukemia, especially acute lymphoid leukemia (ALL) treated with L-asparaginase. Yet, most reports are anecdotical and scarce data are available on the risk of thrombosis in acute myeloid leukemia (AML). OBJECTIVES: To evaluate the risk of thrombosis in patients with acute leukemia. PATIENTS AND METHODS: Three-hundred and seventy-nine consecutive adult patients with newly diagnosed acute leukemia were recruited in an observational cohort study conducted from January 1994 to December 2003. Diagnosis was ALL in 69 patients, acute promyelocytic leukemia (APL; FAB subtype M3) in 31, and non-M3 AML in 279. All first or recurrent symptomatic thromboembolic events objectively diagnosed were recorded. RESULTS: Twenty-four patients of the overall 379 (6.3%; 95% CI 4.1%-9.2%) had a first thrombosis, venous in 80% of the cases and arterial in 20%. At diagnosis, thrombosis was a presenting manifestation in 13 cases (3.4% of the whole cohort): 1.4% in ALL, 9.6% in APL, and 3.2% in non-M3 AML patients. Follow-up was carried out on 343 patients without thrombosis at diagnosis and further 11 thrombotic events (3.2%) were recorded. At 6 months from diagnosis, the cumulative incidence of thrombosis was 10.6% in ALL, 8.4% in APL, and 1.7% in non-M3 AML patients. The patients who received L-asparaginase had a 4.9-fold increased risk of thrombosis in comparison with those who did not (95% CI 1.5-16.0). The fatality rate due to thrombosis was 0.8%. CONCLUSIONS: In patients with acute leukemia, the risk of thrombosis is not negligible. Thombosis can be a presenting symptom at diagnosis in a significant portion of cases with APL (9.6%) and non-M3 AML (3.2%); a similar rate of thrombosis can occur during the subsequent course of the disease. The incidence of symptomatic thrombosis at diagnosis is relatively low in ALL patients (1.4%), but is significantly increased by further treatment up to 10.6%. Strategies of antithrombotic prophylaxis should be investigated in this setting.

Acute Disease↗
PubMed2004

A human umbilical cord stem cell rescue therapy in a murine model of toxic liver injury.

BACKGROUND: Several studies have demonstrated that bone marrow contains a subpopulation of stem cells capable of participating in the hepatic regenerative process, even if some reports indicate quite a low level of liver repopulation by human stem cells in the normal and transiently injured liver. AIMS: In order to overcome the low engraftment levels seen in previous models, we tried the direct intraperitoneal administration of human cord blood stem cells, using a model of hepatic damage induced by allyl alcohol in NOD/SCID mice. METHODS: We designed a protocol based on stem cell infusion following liver damage in the absence of irradiation. Flow cytometry, histology, immunohistochemistry and RT-PCR for human hepatic markers were performed to monitor human cell engraftment. RESULTS: Human stem cells were able to transdifferentiate into hepatocytes, to improve liver regeneration after damage and to reduce the mortality rate both in both protocols, even if with qualitative and quantitative differences in the transdifferentiation process. CONCLUSIONS: We demonstrated for the first time that the intraperitoneal administration of stem cells can guarantee a rapid liver engraftment. Moreover, the new protocol based on stem cell infusion following liver damage in the absence of irradiation may represent a step forward for the clinical application of stem cell transplantation.

Animals↗
PubMed2004

G20210A prothrombin gene polymorphism and coronary ischaemic syndromes: a phenotype-specific meta-analysis of 12 034 subjects.

OBJECTIVE: To investigate the possible link between the G20210A prothrombin gene variant and different forms of ischaemic heart disease. DESIGN: Phenotype-specific meta-analysis of 19 studies published within March 2002, globally including 4944 patients and 7090 controls. Sample size, inclusion criteria, geographical location, clinical presentation, age, cardiovascular risk factors, and angiographic extent of disease were extracted from each study. Analyses were done according to Mantel-Haenszel. RESULTS: Overall, the odds ratio (OR) for unspecified ischaemic heart disease associated with the 20210A allele was 1.21 (95% confidence interval (CI) 0.99 to 1.59, n = 12 034). Similar findings were seen for acute coronary syndromes (unstable angina and myocardial infarction) and for myocardial infarction without age limits (OR 1.24, 95% CI 0.98 to 1.63, n = 10 240; and OR 1.19, 95% CI 0.93 to 1.58, n = 9765). The effects were similar in male and female subjects. In the 1931 subjects < 55 years of age, the OR for myocardial infarction increased to 1.77 (95% CI 1.16 to 3.42) and in the 1359 subjects < 45 years to 2.30 (95% CI 1.27 to 4.59). No significant association was found between the 20210A allele and the presence of angiographically documented coronary disease (OR 1.08, 95% CI 0.70 to 1.64, n = 3444). However, patients with 0/1 vessel disease at angiography showed a greater prevalence of the A allele than those with multivessel disease (relative risk 2.0, 95% CI 1.2 to 3.1, n = 2376). CONCLUSIONS: G20210A prothrombin gene polymorphism may represent a modest but significant risk factor for myocardial infarction at young ages and favour the expression of ischaemic heart disease among individuals who have a limited extent of coronary atherosclerosis at angiography.

Adult↗
PubMed2004

Novel carboxymethylcellulose-based microporous hydrogels suitable for drug delivery.

Several materials capable of acting as structures for controlled release were analysed for the fabrication of matrices. Among those used, hydrophilic polysaccharides appeared to be the most suitable materials. Carboxymethylcellulose (a semi-synthetic polysaccharide) was chemically cross-linked with a 60% and 90% cross-linking degree in order to obtain hydrogels and utilised as matrix for the realisation of controlled drug release systems. The morphology of the gels was changed in order to obtain a microporous structure with different porosity (14, 30 and 40 microm). The obtained porous matrices were characterised in terms of pore density, dimension and swelling behaviour. The influence of both the pore dimension and technique of loading on the release kinetics was analysed. By increasing the pore dimension the release of ibuprofen-lysin was slower. Inducing the microporous structure after the loading of the hydrogel with the drug resulted in a slower release.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2003

Hypermethylation of GpG islands in the promoter region of p15(INK4b) in acute promyelocytic leukemia represses p15(INK4b) expression and correlates with poor prognosis.

We evaluated the methylation status of p15 gene in a series of 65 patients with newly diagnosed acute promyelocytic leukemia (APL) receiving homogeneous treatment. Moreover, in 32 of them, the methylation status of p15 gene was correlated to the p15 m-RNA expression. In total, 31 patients had no p15 methylation (U group). An abnormal methylation pattern was found in 34 patients: in seven of these patients only methylated DNA was detected (M group), while in the remaining 27 patients (M/U group), both methylated and unmethylated DNA were amplified. Patients from M group showed a higher incidence of relapses and a lower disease-free survival (DSF) with respect to patients from U and M/U groups (29, 64 and 79% at 5 years for M, U/M and U patients, respectively, P=0.03), while p15 methylation had no impact on overall survival. The p15 expression was detectable in all patients with unmethylated DNA, in none of patients with fully methylated DNA and in 60% of patients with partially methylated DNA. The DFS estimate at 5 years for p15-negative patients was significantly lower than that of p15-positive patients (P=0.03). These data confirm that the presence of p15 methylation negatively influences the prognosis of APL, mainly when it represses the p15 gene transcription.

Adult↗
PubMed2003

Monochromatic excimer light 308 nm in the treatment of vitiligo: a pilot study.

OBJECTIVE: To study the efficacy and safety of monochromatic excimer light (MEL) on 37 vitiligo patients referred to our clinic. METHODS: In a pilot study, 37 patients (17 males, 20 females) with acrofacial (n=21), focal (n=11), segmental (n=1), and generalized (n=4) vitiligo were treated twice weekly with MEL for a maximum period of 6 months. RESULTS: Thirty-five patients (95%) showed signs of repigmentation within the first eight treatments. The treatment resulted in good repigmentation in 16 patients, and excellent repigmentation in 18 patients. Adverse events were limited to transient erythema. In addition, some patients (n=3) not responding to prior narrow-band UVB (NB UVB) phototherapy showed good results with MEL in our series. CONCLUSIONS: Treatment with 308 nm MEL for vitiligo may be more effective in obtaining rapid repigmentation than phototherapy with NB UVB. The results in this study are similar to those recently reported with a 308 nm excimer laser, but 308 MEL could present some advantages: the possibility of treating larger areas compared to the 308 nm excimer laser, with shorter treatment times and better patient compliance. The overall good results and the early appearance of repigmentation contribute to reducing the cumulative exposure to UV radiation.

Adolescent↗
PubMed2003

Efficacy of granulocyte transfusions for neutropenia-related infections: retrospective analysis of predictive factors.

BACKGROUND: The transfusion of G-CSf-primed granulocytes (GTX) might represent an important treatment option for neutropenia-related infections unresponsive to conventional antimicrobial therapies and to recombinant hematopoietic growth factors. However, few studies to date have identified the factors that can predict clinical outcome and the patient populations who are likely to benefit most from GTX. The primary endpoint of the present retrospective study was to evaluate the efficacy of GTX in 22 patients with hematological malignancies who developed neutropenia-related bacterial and fungal infections that were unresponsive to appropriate antimicrobial therapies. METHODS: Peripheral blood granulocytes were collected by continuous-flow leukapheresis from HLA-identical siblings after priming with G-CSF. The response to GTX was classified as 'favorable' if clinical symptoms and signs of infection resolved or 'unfavorable' if clinical symptoms and signs of infection were unchanged or worsened. Control of infection at Day 30 after the enrollment in the GTX program was considered as the outcome variable in multiple regression analysis. RESULTS: Two patients died of infection before receiving the granulocyte concentrates. Bacterial infections (monomicrobial or mixed bacteremias) were documented in 11 patients, whereas fungal infections (fungemia or focal fungal infections) were diagnosed in seven patients. In two patients, no infecting agent could be isolated (clinical infection). Control of infection at Day 30 after the first GTX was achieved in 10 of 20 assemble patients. Overall, 54% of patients with bacterial infections had a favorable response, compared with 57% of patients with fungal infections. No differences in terms of survival were found when comparing patients with bacterial and those with fungal infections at a median follow-up 90 days from the first GTX. In univariate analysis, disease status before GTX, e.g., complete or partial remission, and spontaneous recovery of the neutrophil count were significantly associated with control of infection. when multivariate regression models were formed, the recovery 0.5 x 10 (9)/L PMN was the only parameter that significantly and independently correlated with a favorable response to GTX. DISCUSSION: GTX can be used to successfully treat bacterial as well as fungal infections in severely neutropenic patients when administered early after the onset of febrile neutropenia in patients with remission of the underlying disease and who are likely to recover marrow function.

Adult↗
PubMed2002

Phosphatidylserine exposure in platelet concentrates during the storage period: differences between the platelets collected with different cell separators.

BACKGROUND AND OBJECTIVES: Platelet alterations occur during the production and storage of platelet concentrates, the so called "storage lesion". We studied the platelet alterations during the storage period in apheresis concentrates, employing flow cytometry for phosphatidylserine (PS) detection on platelets during the five days of storage. MATERIAL AND METHODS: Twenty-seven single donor platelet concentrates harvested with the Cobe Trima, Baxter Amicus, or Haemonetics MCS+ were analyzed for PS exposure by flow cytometry on the day of production (day 1) and on days 3 and 5 of storage. Furthermore PS expression was analyzed in platelet donors' blood samples withdrawn before plateletpheresis. RESULTS: PS expression on platelets gave the following median values: in blood donors before apheresis it was 1.12% (0.13-1.78) in platelets concentrates on the first day (2 h after apheresis) 2.06% (0.66-15.2), the third day 6.57% (1.98-51.13) and the fifth day 23.04% (3.86-80.23). All differences between median values of PS expression in blood samples before apheresis, and platelets concentrates on days 1, 3 and 5 of storage, are statistically significant. The expression of PS in platelet concentrates was analyzed in relation to the blood cell separator used for the collection procedure and showed the following results: on day 1 the median values of PS in platelet concentrates collected with the three different blood cell separators, Trima, Cobe and MCS, did not show statistically significant differences. On day 3, the platelets concentrates collected with the Trima and with the MCS showed differences that were statistically significant. Those were respectively 10.59% (4.56-51.13) and 3.53% (1.98-12.61), p = 0.005. The PS expression in platelet concentrates collected with the Trima and MCS showed differences that are also statistically significant on day 5 at respectively 32.4% (9.61-80.23) and 8.57% (3.86-48.42), p = 0.005. CONCLUSIONS: PS exposure in platelet concentrates on days 3 and 5 rise to levels that could compromise the quality of the platelet units. Improvements in standardized platelet quality controls, and in platelet collection systems are required to reduce the storage lesions in platelets concentrates.

Adult↗
PubMed2002

Administration of low-dose interleukin-2 plus G-CSF/EPO early after autologous PBSC transplantation: effects on immune recovery and NK activity in a prospective study in women with breast and ovarian cancer.

This study evaluated the effects of low-dose IL-2 plus G-CSF/EPO on post-PBSC transplantation (PBSCT) immune-hematopoietic reconstitution and NK activity in patients with breast (BrCa) and ovarian cancer (OvCa). To this end, two consecutive series of patients were prospectively assigned to distinct post-PBSCT cytokine regimens (from day +1 to day +12) which consisted of G-CSF (5 microg/kg/day) plus EPO (150 IU/kg/every other day) in 17 patients (13 BrCa and 4 OvCa) or G-CSF/EPO plus IL-2 (2 x 10(5) IU/m(2)/day) in 15 patients (10 BrCa and 5 OvCa). Hematopoietic recovery and post-transplantation clinical courses were comparable in G-CSF/EPO- and in G-CSF/EPO plus IL-2-treated patients, without significant side-effects attributable to IL-2 administration. In the early and late post-transplant period a significantly higher PMN count was observed in G-CSF/EPO plus IL-2-treated patients (P = 0.034 and P = 0.040 on day +20 and +100, respectively). No significant differences were found between the two groups of patients in the kinetics of most lymphocyte subsets except naive CD45RA(+) T cells which had a delayed recovery in G-CSF/EPO plus IL-2 patients (P = 0.021 on day +100). No significant difference was observed between NK activity in the two different groups, albeit a significantly higher NK count was observed in G-CSF/EPO plus IL-2 series on day +20 (P = 0.020). These results demonstrate that low-dose IL-2 can be safely administered in combination with G-CSF/EPO early after PBSCT and that it exerts favorable effects on post-PBSCT myeloid reconstitution, but not on immune recovery.

Adult↗
PubMed2002

Transforming growth factor-beta1 transcriptionally activates CD34 and prevents induced differentiation of TF-1 cells in the absence of any cell-cycle effects.

A number of cytokines modulate self-renewal and differentiation of hematopoietic elements. Among these is transforming growth factor beta1 (TGF-beta1), which regulates cell cycle and differentiation of hematopoietic cells, but has pleiotropic activities depending on the state of responsiveness of the target cells. It has been previously shown by us and other authors that TGF-beta1 maintains human CD34(+) hematopoietic progenitors in an undifferentiated state, independently of any cell cycle effects, and that depletion of TGF-beta1 triggers differentiation accompanied by a decrease in CD34 antigen expression. In the present work, we show that exogenous TGF-beta1 upregulates the human CD34 antigen in the CD34(+) cell lines TF-1 and KG-1a, but not in the more differentiated CD34(-) cell lines HL-60 and K-562. We further studied this effect in the pluripotent erythroleukemia cell line TF-1. Here, TGF-beta1 did not effect cell growth, but induced transcriptional activation of full-length CD34 and prevented differentiation induced by differentiating agents. This effect was associated with nuclear translocation of Smad-2, activation of TAK-1, and with a dramatic decrease in p38 phosphorylation. In other systems TGF-beta1 has been shown to activate a TGF-beta-activated kinase 1 (TAK1), which in turn, activates p38. The specific inhibitor of p38 phosphorylation, SB202190, also increased CD34 RNA expression, indicating the existence of a link between p-38 inhibition by TGF-beta1 and CD34 overexpression. Our data demonstrate that TGF-beta1 transcriptionally activates CD34 and prevents differentiation of TF-1 cells by acting independently through the Smad, TAK1 and p38 pathways, and thus provide important clues for the understanding of hematopoietic development and a potential tool to modify response of hematopoietic cells to mitogens or differentiating agents.

Antigens, CD34↗
PubMed2002

Acute megakaryoblastic leukemia: experience of GIMEMA trials.

The objective of the study was to evaluate the incidence, characteristics, treatment and outcome of acute megakaryoblastic leukemia (AMeL) in patients enrolled in GIMEMA trials. Between 1982 and 1999, 3603 new consecutive cases of AML aged over 15 years were admitted to GIMEMA trials. Of them, 24 were AMeL. The incidence of AMeL among AML patients enrolled in GIMEMA trials was 0.6% (24/3603). Diagnosis was based on morphological criteria. Out of 11 cytogenetic studies performed two presented chromosome 3 abnormalities. Twelve patients (50%) reached a CR, five (21%) died in induction and seven (27%) were unresponsive. The median duration of CR was 35 weeks (range 10-441). Seven patients underwent transplantation procedures (1 BMT, 4 aBMT, 2 aPBSCT). Four patients died in CR due to chemotherapy-related complications. Comparing the CR rate between AMeL and the other cases of AML enrolled in GIMEMA trials, no differences were observed. These results were mirrored for different age groups. The median survival was 40 weeks. At present, after a follow-up of a minimum of 2 years, only two patients are alive in CR, all the others having died. A 5-year Kaplan-Meier curve shows a disease-free survival of 17% and an actuarial overall survival of 10%. AMeL is a rare form of AML. The CR duration and the overall survival in this group of patients are very poor, even if similar to those observed in other AML. Furthermore, a high number of deaths in CR were observed. On the basis of these data, a specific therapeutic approach, possibly with innovative treatments, should be evaluated.

Adolescent↗
PubMed2002

Increased prevalence of the G20210A prothrombin gene variant in acute coronary syndromes without metabolic or acquired risk factors or with limited extent of disease.

AIMS: To investigate the prevalence of the G20210A prothrombin and G1691A factor V gene variants in patients with acute coronary syndrome stratified according to risk factor profile and to extent of coronary disease, in comparison with matched healthy controls. METHODS AND RESULTS: The 20210 prothrombin and the 1691 factor V loci were genotyped in 247 patients < or =65 years of age (190 myocardial infarction and 57 unstable angina as first presentation of disease) and in 247 healthy age- and sex-matched controls. The prevalence of the 1691A factor V allele was similar in cases and controls. The frequency of heterozygotes for the 20210A prothrombin allele was 6.5% among patients and 2.8% among controls (OR 2.4, 95% CI 1.0-5.9), increasing to 8.7% in patients with a family history of myocardial infarction (OR 3.3, 95% CI 1.2-9.1), to 9.9% in patients (n=81) with < or =1 vessel disease (OR 3.8, 95% CI 1.3-10.8), and to 13.0% in patients who were normocholesterolaemic, non-diabetic, normotensive and non-smokers (OR 5.1, 95% CI 1.2-21.4). CONCLUSIONS: These findings suggest that the 20210A prothrombin allele represents an inherited risk factor for acute coronary syndrome among patients who have limited extent of coronary disease at angiography or who lack major metabolic and acquired risk factors.

Acute Disease↗