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F Buccisano

Publications and source records attributed to F Buccisano.

29 records · Page 2Linked to original sources
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↗
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↗
PubMed1996

Minimally differentiated acute myeloid leukemia (AML-M0): a distinct clinico-biologic entity with poor prognosis.

FAB proposals for the diagnosis of AML-M0 represent the formal recognition of a distinct entity which has been described over the past few years by several authors and called minimally differentiated acute myeloid leukemia. By definition, AML-M0 includes acute leukemias which do not fit morphological and cytochemical criteria for the diagnosis of AML, and for which myeloid lineage assignment can be made by immunological assay showing positivity for MPO, CD13, and CD33 and negativity for lymphoid markers. Involvement of an early myeloid progenitor in the leukemic process is a possible theory hypothesized to explain the existence of such a form. Validity of this assumption has been based on the observation that AML-M0 frequently bears "stem cell" markers such as CD34, HLA-DR, Tdt, CD7, and promiscuous IgH/TCR gene rearrangements, which are thought to occur in uncommitted cells. Finally, AML-M0 very frequently carries cytogenetic abnormalities common to MDS or secondary AML, such as -5/5q- or -7/7q- deletions and or complex karyotype. In our experience, AML-M0 is also very often associated with the MDR phenotype, which in turn has been found strictly linked to "stem cell" features, especially in MDS. These biological aspects, altogether, translate into a very unfavorable prognosis, confirming even from a clinical point of view that AML-M0 is a distinct entity. In conclusion, "stem cell" markers, MDR phenotype, complex chromosome lesions, frequent occurrence in elderly patients, and intrinsic chemoresistance characterize AML-M0 and indicate the need for tailored treatments, possibly involving the use of MDR modulators and/or differentiating agents.

Humans↗
PubMed1995

Contribution of immunophenotypic and genotypic analyses to the diagnosis of acute leukemia.

Diagnostic accuracy in acute leukemia (AL) can be improved if traditional morphology and cytochemistry are supplemented with immunophenotypic and genotypic analyses. This multiparameter approach is of crucial importance for the management of patients, as it enables the identification of leukemic syndromes with distinct biological features and response to treatment. Immunophenotyping using monoclonal antibodies has been universally accepted as a useful adjunct to morphological criteria. This technique is particularly valuable in diagnosing and subclassifying acute lymphoblastic leukemia and is also essential in certain types of acute myeloid leukemia (AML), such as AML with minimal differentiation or acute megakaryoblastic leukemia. Cytogenetic findings can be quite helpful in establishing the correct diagnosis and can add information of prognostic significance. A number of specific chromosomal abnormalities have been recognized that are very closely, and sometimes uniquely, associated with morphologically and clinically distinct subsets of leukemia. An even more basic understanding of normal and malignant hematopoietic cells has begun to evolve as molecular biology begins to unravel gene misprogramming by Southern and Northern blot analysis, the polymerase chain reaction, and fluorescence in situ hybridization. With the extensive use of these techniques it has become apparent that a proportion of leukemias exhibit the biologically relevant molecular defect in the absence of a karyotypic equivalent. On the other hand, apparently uniform chromosomal abnormalities such as the t(1;19) (q23;p13), t(9;22) (q33;q11), t(8;14) (q24;q32), or t(15;17) (q21;q21) may differ at the molecular level. Data collected from these modern technologies have introduced a greater complexity, which needs to be taken into consideration to improve both the diagnostic precision and the reproducibility of current classifications.

Acute Disease↗
PubMed1995

Recombinant interferon alpha 2a, thymopentin and low doses of cytosine arabinoside for the treatment of myelodysplastic syndromes: a pilot study.

Eighteen patients (pts) with myelodysplastic syndrome (MDS) were treated with thymopentin (TP) (50 mg subcutaneously for 5 days) and recombinant interferon alpha 2a (rIFN alpha 2a) (3 MU/m2 subcutaneously on the sixth day); the courses were delivered every week. Moreover those pts with > or = 10% blasts in the bone marrow were additionally treated with low dose cytosine arabinoside (LDARAc) (20 mg standard dose, subcutaneously, twice a day for seven days every four weeks). Sixteen pts were finally assessable for response. Seven pts (44%) were classified as good responders, 5 (31%) had a PR; the overall response rate (GR+PR) was 75%. Two pts (12.5%) showed stable disease and the 2 remaining (12.5%) had progressive disease. Six pts with an initial moderate anemia never required supportive care before and during the therapy; in contrast to 10 pts who were transfusion-dependent. After six months of therapy 2 pts decreased their transfusional needs by 50% (1 of them did not receive any transfusion over the following six months of therapy); 2 pts needed no packed red cell infusions and 1 pt decreased his transfusional support by 75%. Five pts kept an unchanged supportive care load. The overall median survival was 12.5 months. Therapy was generally well tolerated with acceptable compliance; the most frequently recorded side effects were neutropenia and thrombocytopenia grade 2-3 among the group receiving LDARAc. However no life-threatening infectious episodes or bleeding were observed. TP, rIFN alpha 2a and LDARAc can be safely administered on an outpatient basis to MDS pts and appears to have significant activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

CD7 expression in acute myeloid leukemia.

The clinical significance of the expression of CD7 antigen on the blasts of 207 consecutive patients with de novo acute myeloid leukemia (AML) was evaluated. For this purpose, fifty-three CD7+ patients (23 females and 30 males; mean age 52 years) were analyzed and classified into the following subtypes according to French-American-British (FAB) classification: 7 M0, 13 M1, 9 M2, 1 M3, 9 M4, 14 M5. Immunophenotypic studies were carried out by flow cytometry and blast cells were selected on the basis of forward light scatter gating and pan-myeloid marker, either CD13 or CD33. All the CD7+ patients were negative for surface CD3 and T-cell-receptor (TCR) molecules. We found no correlation between CD7 expression and sex, age, hepatosplenomegaly and/or central nervous system involvement. The immaturity of CD7+ leukemic cells was supported by the high expression of CD34 (P = 0.001). CD7 positivity was significantly associated with a white blood cell count (WBC) greater than 100 x 10(9)/L (P = 0.003). P-Glycoprotein (P-170) expression was also evaluated in 135 patients by a flow-cytometric assay: there was a close relationship between CD7 and P-170 positivity (P < 0.001). For remission induction, all patients received therapeutic regimens routinely used for AML. The complete remission (CR) rate was significantly lower in CD7+ cases (32% vs 74%, P = 0.001). The overall survival and disease free survival rate of CD7+ AML was lower than those of CD7- patients (P < 0.001 and = 0.002, respectively). CD7+ AML with coexpression of CD14 had a particularly unfavourable response and prognosis in comparison with CD7+ patients without CD14.(ABSTRACT TRUNCATED AT 250 WORDS)

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

All-trans retinoic acid and low-dose cytosine arabinoside for the treatment of 'poor prognosis' acute myeloid leukemia.

Thirty-three patients with 'poor prognosis' acute myeloid leukemia, no longer suitable for aggressive chemotherapy, were treated with daily oral all-trans retinoic acid (45 mg/m2) daily and subcutaneous cytosine arabinoside (20 mg standard dose twice a day, day 1 to 10, every 4 weeks). Seventeen patients were males and 16 females, the median age was 67 (range 39-82 years). Eleven patients were at onset of disease, 15 were refractory to previous conventional therapies, three were in first relapse and three in second relapse and one patient had a secondary AML. Seventeen patients had a bone marrow blast infiltration < 50% and 16 > or = 50%. A total of 16 (48%) patients entered complete remission; the rate of complete remission increased to 88% in those patients (n = 17) with < 50% blast infiltration at the time of entering the study. Seventeen patients (52%) were resistant. The difference in response to therapy, according to bone marrow blast percentage (< or > or = 50%), was statistically significant (P < 0.001). Median duration of complete remission was 34.4 weeks (range 6.4-62.8). Mild to moderate hematologic toxicity was the most common side-effect. In conclusion all-trans retinoic acid and low-dose cytosine arabinoside appears to be an effective regimen for inducing complete remission in 'poor prognosis' acute myeloid leukemia and patients with < 50% bone marrow infiltration are likely to represent the ideal target to receive this combination therapy.

Adult↗
PubMed1994

Minimally differentiated acute myeloid leukaemia (AML-M0): cytochemical, immunophenotypic and cytogenetic analysis of 19 cases.

We describe our experience in the identification of 19 cases of AML-M0 categorized among 200 consecutive AML cases. Leukaemic cells from our cases were morphologically marked by agranular basophilic cytoplasm, finely dispersed chromatin and prominent nucleoli. In two cases heavily vacuolated and monocytoid-shaped blasts were also observed. Cytochemistry (MPO, SBB, alpha ANAE, alpha NBE, NASDCAE, AP, PAS) was negative in 14 cases, five cases expressing a very faint cytoplasmic positivity for alpha NBE (not exceeding 30% of the blasts) and alpha ANAE (not exceeding 41%) which was sodium fluoride resistant. In these five cases other monocytic markers (e.g. CD14) were not in favour of myelomonocytic differentiation. All the cases were anti-MPO positive at frequency > 10%. Phenotypic analysis also revealed myeloid features with all the patients having at least one myeloid antigen (CD13, CD33, CD15), Tdt was expressed in nine cases and CD7 in six cases. All cases but one were positive for CD34. Cytogenetic analysis, performed in 16 cases, showed no adequate growth in two cases and no consistent abnormality in four; among the remaining 10 cases no consistent abnormality was observed, the most common finding was trisomy 8 (two cases) and 4 (two cases) and aberrations of chromosomes 2, 3, 5, 7, 9, 12 and 21. No cases of (t9;22), Ph chromosome were observed. Interestingly three out of five patients with faint alpha NBE/alpha ANAE positivity relapsed as typical M4 (one case) or M5a (two cases).

Acute Disease↗