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A Venditti

Publications and source records attributed to A Venditti.

At least 37 records · Page 2Linked to original sources
PubMed1998

Prognostic relevance of the expression of Tdt and CD7 in 335 cases of acute myeloid leukemia.

We have analyzed the expression of Tdt and CD7 in 335 cases of unequivocal acute myeloid leukemia (AML). Tdt was expressed in 80 (25%) of 321 evaluable cases. Twenty-six of 77 (34%) Tdt+ patients assessable for response, entered complete remission (CR) vs 121 of 209 (58%) Tdt- cases (P < 0.001). CD7 was expressed in 102 of 332 (30%) evaluable cases; 37 of 93 assessable (40%) CD7+ patients attained a CR as compared to 114/204 (56%) CD7- (P = 0.013). Duration of survival was significantly shorter for patients with CD7+ or Tdt+ AML (P = 0.006 and 0.001, respectively). In a multivariate analysis, Tdt was found to significantly adverse achievement of CR (P = 0.018), while CD7 affected duration of CR (P = 0.037). Overall the expression of either Tdt or CD7 correlated with a relatively high expression of CD34 (P < 0.001), GP-170 (P = 0.003), lymphoid antigens (LyAg) (P < 0.001), t(9;22) or anomalies of chromosome 5/7 (P < 0.001). Finally, we pooled the patients into four phenotypic classes, according to the presence of Tdt, CD7 or both: [Tdt-CD7-], [Tdt+CD7-], [Tdt-CD7+] and [Tdt+CD7+]. The category [Tdt+CD7+] was characterized by a more unfavorable outcome as suggested by a lower rate of CR (P < 0.001) and a shorter duration of survival as compared to cases [Tdt-CD7-], [Tdt+CD7-] and [Tdt-CD7+] (P = 0.002). This figure is consistent with the frequent convergence in the subset [Tdt+CD7+] of GP-170 positivity (P = 0.003), translocation t(9;22), anomalies of chromosome 5 and/or 7 (P < 0.001) and signs of lineage infidelity (deviant expression of lymphoid antigens) (P < 0.001). We conclude that the expression of Tdt or CD7 is associated with an unfavorable outcome and that the combination of both defines a clinical subset with a poorer prognosis due to the significantly higher association with MDR phenotype, and 'poor prognostic' chromosomal abnormalities.

Acute Disease↗
PubMed1998

Red blood cell depletion of cord blood using hydroxyethylstarch double sedimentation: analysis of 40 cases.

Cord blood has been shown to successfully reconstitute haematopoiesis following allogeneic transplantation in a variety of disorders. A major drawback of cord blood has been the risk of transfusion reaction secondary to ABO incompatibility and reduction in the stem cell pool if cord blood is manipulated to remove red cells. We report our experience on red blood cell depletion of cord blood (CB) with hydroxyethylstarch (HES) double sedimentation. The nucleated and mononucleated cell recovery passed from 78.4% at 90 min to 92.9% at 180 min and from 85% at 90 min to 96% at 180 min, respectively. The overall recovery of CCD34+ cells and of haemopoietic progenitors (CFU-GM) was 90.5% and 83.8%, respectively. The data indicate that HES double sedimentation is a simple and effective technique for cord blood manipulation, but further studies are necessary to evaluate the clonogenic progenitor recovery after thawing.

Cell Separation↗
PubMed1998

A comparative analysis of FISH, RT-PCR, and cytogenetics for the diagnosis of bcr-abl-positive leukemias.

Philadelphia (Ph) chromosome-positive leukemias, with the bcr-abl gene translocation, have a dismal prognosis. The identification of Ph-positive patients is vitally important because only aggressive therapeutic approaches, such as allogeneic bone marrow transplantation, may result in long-term disease-free survival. Routine diagnostic methods, such as Southern blot analysis and cytogenetics, may lead to false-negative results. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis is considered the most sensitive tool for the detection of the bcr-abl translocation, and it is widely used alone or in combination with karyotyping or Southern blot analysis to identify Ph-positive cases. In this study, we used fluorescence in situ hybridization (FISH) with BCR and ABL double-color probes for detecting Ph-positive leukemias. The FISH results were compared with the results of cytogenetic and RT-PCR analyses in 75 patients with leukemia or other myeloproliferative syndromes (chronic myeloid leukemia, 30; acute lymphoblastic leukemia, 24; acute myelogenous leukemia, 6; essential (hemorrhagic) thrombocythemia, 12; chronic myelomonocytic leukemia, 2; and polycythemia vera, 1). FISH analysis proved to be simple, extremely reliable and sensitive; bcr-abl fusion detection was successful in the presence of all types of molecular junctions i.e., (b2a2, b3a2, and e1a2). Furthermore, a Ph-positive case that proved fusion negative by RT-PCR was identified as positive by FISH. The sensitivity of RT-PCR and FISH related to Ph-positive cases were 97% and 100%, respectively. Regarding specificity, in 4 (5%) of 75 patients, RT-PCR provided false-positive results. Cross-contamination was identified because a new specimen was harvested and reanalyzed when FISH, cytogenetics, and RT-PCR results were contradictory. We believe FISH is an optimal diagnostic method to detect bcr-abl translocation that can be used alone or to validate the results of RT-PCR analysis.

Bone Marrow↗
PubMed1998

Role of human leukocyte interferon-alpha in the treatment of patients with polycythemia vera.

Eighteen patients with polycythemia vera who were less than 60 years old received human leukocyte interferon-alpha subcutaneously at a starting dose of 3 MU three times a week. The interferon dose was escalated to 6 MU three times a week if it was well tolerated and disease was not controlled after 3 months of treatment at the lower dose. Hematologic response was defined as complete if the hematocrit was maintained at less than 45% in the absence of phlebotomy and partial if the hematocrit was kept at 45% to 50%, associated with a 50% or greater reduction of phlebotomy requirements; no response was defined as a response less than a partial response. Complete disease control was achieved in 11 patients, with partial control in a further six cases. One patient failed to respond. Median duration of response was 16 months (range 5 to 43 months), with 15 patients still under treatment. Therapy with human leukocyte interferon-alpha significantly improved (p <.01) phlebotomy requirements, the degree of splenomegaly, pruritus scores, iron stores and mean red cell volume values, and platelet and leukocyte counts. Interferon treatment did not produce remarkable side effects and no patient withdrew from the study because of intolerance. We conclude that subcutaneous human leukocyte interferon-alpha is an effective and well-tolerated therapy in the management of polycythemia vera-associated myeloproliferation and pruritus in patients less than 60 years old.

Adult↗
PubMed1998

Multiparametric analysis for the enumeration of CD34+ cells from bone marrow and stimulated peripheral blood.

Determination of CD34+ cells was performed in bone marrow and G-CSF mobilised peripheral blood samples. We adopted three different protocols of analysis: the Milan/Mulhouse protocol, the ISHAGE guidelines for CD34+ cell determination and our own protocol based upon the use of PAINT-A-GATEPRO software analysis program. An excellent correlation was demonstrated between the three methods (r2 0.98); however the analysis of variance showed a statistically significant difference between the results generated with the three methods (P=0.001). The differences between the three procedures are discussed with a special focus on the value of CD34+dim cells and the role of CD45 in the setting of a double staining. We have in fact identified a minor subset (CD34+CD38+CD45-) which would go unrecognised based upon its CD45 negativity.

Antigens, CD34↗
PubMed1997

Minimally differentiated acute myeloid leukemia (AML-M0): comparison of 25 cases with other French-American-British subtypes.

We compared the immunophenotypic and karyotypic features of 25 cases of minimally differentiated acute myeloid leukemia (AML-M0) with those of 247 cases comprising all AML French-American-British (FAB) classification. Myeloperoxidase (MPO) was detectable with a specific monoclonal antibody in all cases of AML-M0, whereas CD13 and CD33 were both negative in 4 of the 25 cases. Thus, anti-MPO reliably detects minimal myeloid differentiation in AML-M0. CD34 and terminal deoxynucleotidyl transferase (TdT) were more frequently expressed in AML-M0 (96% and 68% of the cases, respectively) than in the other FAB subsets (P < .001 for both). By contrast, GP-170 and CD7 were less frequently expressed in AML-M0 than in FAB classes such as M1, M4, and M5 (P = .02 and .003, respectively). A total of 80% of AML-M0 cases carried lymphoid markers (including TdT), and 48% showed a coordinate positivity for two or more of them. CD2, CD5, CD10, and CD19 were expressed in a similar fashion among the different FAB groups, whereas CD4 expression was significantly more frequent in AML-M0, AML-M4, and AML-M5 (P = .014). AML-M0 was characterized by a more frequent occurrence of complex karyotypes. In addition, approximately 20% of cases had TdT positivity, complex karyotypes, and anomalies of chromosome 5 and/or 7, a pattern not observed in the other FAB subsets. Finally, 80% of anomalies of chromosome 5 and/or 7 in AML-M0 were comprised within complex karyotypes, whereas only 13% of the remaining FAB cases carried this feature. In summary, AML-M0 frequently expresses immunophenotypic and karyotypic aspects that are likely to identify a "stem cell" pattern.

Adolescent↗
PubMed1997

In vitro down-regulation of bcl-2 expression by all-trans retinoic acid in AML blasts.

Using flow cytometry, we have investigated the effects of 0.5 microM all-trans-retinoic acid (ATRA) on bcl-2 expression in the blast cells of 25 acute myeloblastic leukemia (AML) patients and the HL-60 cell line after incubation for 6 days. We observed a significant decrease of bcl-2 expression after treatment with ATRA in 12 of 25 AML samples and the HL-60 cells. The mean fluorescence intensity (MFI) ratio for the bcl-2 levels of the ATRA responders (n = 12) was reduced to 7.9 +/- 4.8 following incubation with ATRA compared with 10.9 +/- 6.5 (mean +/- SD) for control samples incubated without ATRA (p = 0.011). There was no significant difference between the baseline bcl-2 MFI ratio in the ATRA responders (11.14 +/- 7, n = 12) and the non responders (14.18 +/- 11.3, n = 13; p = 0.432). The down-regulation of bcl-2 expression by ATRA was not significantly associated with CD34-negative or -positive AML. There was no correlation between AML subtypes and regulation of bcl-2 expression by ATRA. Complete remission and overall survival were not significantly improved in bcl-2 down-regulated cases. Our data confirm that ATRA can down-regulate the bcl-2 expression in AML blasts. Because many chemotherapeutic agents also operate through the activation of programmed cell death and bcl-2 levels are positively associated with resistance to apoptosis, ATRA can be used in combination chemotherapy to increase the chemosensitivity of some patients with AML.

Antineoplastic Agents↗
PubMed1997

A microgranular variant of acute promyelocytic leukemia with atypical morpho-cytochemical features and an early myeloid immunophenotype.

This report describes a unique case of acute promyelocytic leukemia (APL) showing elusive morphologic features, an atypical pattern of cytochemical reactions, and a previously unreported immunophenotype consistent with a very early myeloid form: CD13 (+), CD33 (+), CD9 (+), CD2 (+), HLA-DR (-), CD34 (+), CD117 (+), and TdT (+). The diagnosis of AML M3 variant was made only after genotypic analyses revealed the PML/RAR alpha rearrangement associated with the typical (15;17) (q22;q21) translocation. This example of 'asynchronous differentiation' emphasizes the need for a multiparameter approach to the diagnosis of acute leukemia.

Adult↗
PubMed1997

Efficacy and safety of human leucocyte interferon-alpha treatment in patients younger than 60 years of age with polycythaemia vera.

OBJECTIVES: To evaluate the therapeutic activity and toxicity of human leucocyte interferon-alpha (lIFN-alpha) in patients with polycythaemia vera (PV) aged less than 60 years. DESIGN: An open clinical study. SETTING: Department of Medical Sciences, Regina Apostolorum Hospital, Albano Laziale, and Chair of Haematology, University of Rome 'Tor Vergata', S. Eugenio Hospital, Rome, Italy. SUBJECTS: Fourteen patients with PV and aged < 60 years who had active disease as indicated by the need for phlebotomy and/or cytoreductive therapy. INTERVENTIONS: lIFN-alpha administered subcutaneously at the starting dose of 3 MU thrice weekly. The interferon dose could be escalated to six MU thrice weekly if it was well tolerated and disease was not controlled after three months of treatment at the lower dose. MAIN OUTCOME MEASURES: Change in phlebotomy requirements, spleen size, pruritus score and haematological parameters after 6 months of treatment. Evaluation of lIFN-alpha side effects. RESULTS: Complete or partial disease control was achieved in 13 patients. Six patients achieved a complete response (CR) and four a partial response (PR) after 3 months of therapy. Dose escalation in partial or nonresponders resulted in two patients switching from a status of PR to CR, and three other patients achieving a partial response after being unresponsive to the lower dosage. Human leucocyte interferon-alpha therapy significantly improved (P < 01) phlebotomy requirements, the degree of splenomegaly, pruritus scores, iron stores and MCV values, and platelet and leucocyte counts. A mild flu-like syndrome (low-grade fever, nausea and myalgias) appeared during the early phase of therapy in the majority of patients, but no patient had to discontinue lIFN-alpha because of intolerance. CONCLUSIONS: Subcutaneous human leucocyte interferon-alpha appears an effective and well tolerated therapy in the management of PV-associated myeloproliferation and pruritus in patients aged less than 60 years.

Adult↗
PubMed1997

P-glycoprotein expression in de novo acute myeloid leukemia.

Detection of the multidrug resistance P-glycoprotein (PGP) phenotype was performed at the time of diagnosis in 223 patients with acute myeloid leukemia (AML) by flow cytometry using C219 Monoclonal Antibody (MoAb). On the other hand, JSB1 MoAb was tested in 173 of these samples. At onset, PGP was detected in 57.4% of cases with C219 and 75.9% of cases with JSB1. There was no correlation between PGP expression and sex, age, marrow blast percentage or extramedullary disease. On the contrary, strict correlations were noted either between C219 negativity and FAB M3 subtype or between C219 positivity and FAB M5 group (P = 0.003). Significant correlation was found between PGP phenotype and CD7, as 143 of 223 samples had similar patterns of staining with C219 (P < 0.0001). Finally, there was a close relationship between C219 and JSB1 positivity: all the C219+ cases were positive for JSB1 (P < 0.0001). Concerning the karyotype, most patients with monosomy or del (7) were MDR positive; on the other hand, most patients with t(8;21) or t(15;17) were MDR negative. Rh123 accumulation studies showed a significant decrease of mean fluorescence intensities both in C219 and in JSB1 positive cases in comparison with PGP negative ones (P < 0.001). A significant decrease of remission induction rates (CR) was highlighted both between C219+ and C219- and between JSB1+ and JSB1- cases (32.1% v 62.1% and 32.6% v 73.8%, respectively, with P < 0.0001). The overall survival and the remission duration (CCR) were significantly shorter both in C219+ and in JSB1+ patients with no relationship to age. Furthermore, a higher rate of early relapses was noted among MDR+ when compared with MDR- patients both for C219+ and JSB1+ cases. The combination (C219- JSB1+) identified a subset of patients with an intermediate prognosis. On multivariate analysis, C219 and JSB1 were confirmed to be independent prognostic factors for achievement of CR, overall survival and CCR. In conclusion, the assessment of MDR phenotype by flow cytometry is a crucial prognostic factor of treatment outcome in AML.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

[Clinical significance of Hürthle cell in the cytology of thyroid disease].

The natural history of Hürthle cell (HC) lesions has been the focus of a considerable debate. The difficulties in defining the malignant potential of HC has led to the current designation of HC tumor, with the implication that it may behave as either a benign or a malignant lesion. The objective of our study was to verify the clinical and prognostic relevance of the cytological diagnosis of HC in the thyroid lesion, 10,950 consecutive patients (F/M = 5.6/1) with thyroid nodules were evaluated by means of fine needle aspiration biopsy (FNAB). Cytological diagnosis showed the presence of HC in 285 cases (2.6%), with a F/M ratio of 8.2/1. In 123 cases (43.2%) cytologic diagnosis resulted benign. A suspicious pattern of follicular neoplasm was observed in 159 cases (55.8%). Only in 3 cases (1%) thyroid carcinomas were preoperatively identified. No false positive or negative cases were observed. Among the HC lesions, 85 patients (29.8%) underwent thyroid surgery because of a malignant or suspicious cytologic diagnosis, continuous nodular growth despite LT4 therapy, mechanical compression or clinical judgement. The other two hundred patients were clinically evaluated and, one year later, repeated FNAB confirmed the cytologic diagnosis of benignity. Among the follicular neoplasm nodules, 80 cases (55.3%) were surgically explored, and thyroid carcinoma diagnosed in 30 of them (37.5%), this percentage being greater than that observed in the group of non-HC follicular neoplasm (17%). Pathologic criteria for malignancy (vascular invasion, transcapsular penetration, destructive capsular invasion) were described in 25 out of all carcinomas.

Adenocarcinoma, Follicular↗
PubMed1996

Intensive treatment of patients age 60 years and older with de novo acute myeloid leukemia: analysis of prognostic factors.

BACKGROUND: This study aimed to define pre-treatment parameters with prognostic significance in elderly patients with de novo acute myeloid leukemia (AML) who were treated with aggressive regimens. METHODS: We analyzed, retrospectively, the clinical and laboratory features of 159 consecutive patients age >60 years with AML. Ninety-two patients presenting as de novo AML were considered suitable for aggressive chemotherapy according to inclusion criteria not different from those commonly used for younger adults. They belonged to all of the French-American-British classification types except M3, and their median age was 67 years (range: 60-79). Antileukemic treatment consisted of 1 of 3 sequential protocols adopted at the S. Eugenio University Hospital of Rome between 1987 and 1993. The three therapeutic groups were similar in number and presenting characteristics. In addition to arabinosylcytosine, induction schedules included mitoxantrone (Groups I and II) or daunorubicin (Group III), and etoposide (Groups I and III). Once in complete remission (CR), patients were consolidated with two other courses of chemotherapy using reduced dosages of the same drugs given during induction. RESULTS: Induction treatment achieved a 52.2% CR rate, with median remission duration and event free survival (EFS) of 35 and 27 weeks, respectively. Because no significant differences between the results of the three therapeutic groups were observed, all cases were pooled to evaluate the prognostic factors. In univariate analysis, the only presenting characteristic significantly associated with failure of induction treatment was age >67 years (P=0.007). Factors associated with an increased likelihood of shorter remission duration were CD7 expression on leukemic cells (P=0.007) and an abnormal karyotype (P=0.010; those predicting shorter EFS were a chromosomal status other than normal (P=0.002) and detection of CD14 antigen (P=0.008). Logistic regression results identified age and CD14 expression as the variables with independent prognostic impact on CR achievement. In a stepwise proportional hazards general linear model, CD7 and karyotype retained their predictive value regarding remission duration, whereas the karyotypic pattern at diagnosis and CD14 antigen expression were the most important determinants of EFS, with age showing a borderline statistical value. A simple "risk factor score" was developed that would allow for stratification of patients into prognostic groups. CONCLUSIONS: Cytogenetic analysis and immunophenotyping might help to select elderly patients with AML who have little benefit from current therapeutic strategies and with whom new approaches might be experimented.

Acute Disease↗
PubMed1996

Clinical relevance of P-glycoprotein expression in de novo acute myeloid leukemia.

Cytofluorimetric detection of the multidrug resistance (MDR)-associated membrane protein (P-170) was performed at the time of diagnosis in 158 patients with acute myeloid leukemia using the C219 monoclonal antibody (MoAb). In 108 of these cases the JSB1 MoAb was also tested. An improved histogram subtraction analysis, based on curve fitting and statistical test was applied to distinguish antigen-positive from antigen-negative cells. A marker was considered positive when more than 20% of the cells were stained. At onset, P-170 was detected in 43% of cases with C219 and in 73% of cases with JSB1. There was a strict correlation between C219 and JSB1 positivity, as all C219+ cases were also positive for JSB1 MoAb (P < .001). No relationship was found between sex, age, organomegaly, and MDR phenotype. Significant correlation was found between CD7 and both C219 and JSB1 expression (P < .001 and .001, respectively). C219-negative phenotype was more often associated with a normal karyotype (24 of 55 with P = .030). Rhodamine 123 (Rh123) staining and flow cytometry analysis showed a significantly decreased mean fluorescence in 51 C219+ and 38 JSB1+ patients compared to 42 MDR negative ones (P < .001). The rate of first complete remission (CR) differed both between C219+ and C219- cases and between JSB+ and JSB- ones (30.9% v 71.1% and 35.4% v 93.1%, respectively, P < .001). Of the 21 C219+ patients who had yielded a first CR, 19 (90.4%) relapsed, compared with 28 of 64 (43.7%) C219- patients (P < .001). Of the 28 JSB1+ patients in first CR, 17 (60.7%) relapsed relative to 8 (29.6%) of 27 JSBI- ones (P = .021). A higher rate of relapses among MDR+ compared with MDR- patients was observed both for C219 and JSB1 MoAbs taken separately (C219 80% v 44%; JSB1 52% v 27%), with no relationship to age. The survival rates (Kaplan-Meyer method) were significantly shorter both in C219+ patients and in JSB1+ cases (P < .001). Disease-free survival curves followed this same trend. The combination (C219- JSB1+) identified a subset of patients with an intermediate outcome compared to C219 positive cases. The prognostic value of both markers (C219 and JSB1) was confirmed in multivariate analysis. These results suggest that the assessment of MDR phenotype by flow cytometry may be an important predictor of treatment outcome.

ATP Binding Cassette Transporter, Subfamily B, Mem↗