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Biomedical subjects

G Del Poeta

Publications and source records attributed to G Del Poeta.

63 records · Page 4Linked to original sources

All-trans retinoic acid plus low doses of cytarabine for the treatment of "poor-risk" acute myeloid leukemias.

Thirteen refractory/resistant AML patients no suitable for additional aggressive chemotherapy, were treated with a combination including all-trans retinoic acid (45 mg/m2 sine die) and low doses of Ara-C (20 mg/m2 subcutaneously, twice in a day, days 1-10, every 28 days). Ten patients were evaluable; 8 of them achieved a complete remission, two patients with an important tumor burden, failed to achieve a response. One complete remission patient relapsed after 7 months but is still receiving the same therapy and is now in partial remission. We believe this combination effective as inducer of complete remission in those AML patients which cannot tolerate additional heavy treatments. The role of tumor burden in affecting response to therapy remains to be still evaluated.

Aged↗

Incidence of chromosome abnormalities and clinical significance of karyotype in de novo acute myeloid leukemia.

Cytogenetic studies with high-resolution banding were performed on specimens from 132 consecutive patients with de novo acute myeloid leukemia (AML). All patients were treated according to therapeutic protocols in the same institution. Clonal abnormalities were detected in 97 of the 124 patients in whom an adequate number of mitoses was obtained (78.2%). Neither sex, FAB classification, WBC, or the extent of bone marrow infiltrate affected the rate of chromosomal aberrations, whereas patients younger than 40 years had a greater proportion of normal karyotypes (p = 0.047). Two different chromosomal classifications were evaluated: the presence of normal and abnormal metaphases (NN-AN-AA classification), and a classification in cytogenetic categories, the latter being based on the frequency of cytogenetic abnormalities. Both classifications were found to correlate significantly with the clinical outcome. They also showed independent prognostic significance when age, sex, and FAB morphology were considered in a multivariate analysis. Two abnormalities were closely associated with specific clinical-pathologic subsets of AML. All the 15 patients with t(15;17) had acute promyelocytic leukemia; this translocation was not found in any other subset of AML. Eight of the nine patients presenting rearrangements at 11q23 belonged to a FAB subset with monocytic differentiation (M4 and M5). Our data suggest that cytogenetic findings should influence the therapeutic approach to AML. In particular, young patients with karyotypes associated with poor responses may be considered for more eradicating treatments, including allogenic bone marrow transplantation.

Acute Disease↗

Molecular characterization of Ph' + hybrid acute leukemia.

The configuration of the immunoglobulin heavy chain (IgH), T-cell receptor (TcR) beta and gamma chain regions, and the major breakpoint cluster region (M-bcr) genes were analysed in four cases of Ph' + acute leukemia (AL). Monoclonal rearrangements of the IgH region were detected in three cases exhibiting two phenotypically distinct cell populations (i.e. one lymphoid and one myeloid. In one of these cases, identical genetic events were observed by molecular analysis of FACS separated blasts. Multi-lineage rearrangements involving also the TcR gamma gene were observed in a biphenotypic AL showing co-expression of markers. The lack of rearrangements within the M-bcr gene, together with demonstration in one case of the Ph' + AL specific p190 protein product, pointed against the occurrence of chronic myeloid leukemias presenting in blastic transformation. Our results imply that such cases are to be considered as true AL and should therefore be included in the definition of hybrid AL.

Acute Disease↗

Soluble factors levels in the initial staging of high-grade non-Hodgkin's lymphomas.

Plasma levels of several soluble factors were assayed in 31 untreated patients with high-grade non-Hodgkin's lymphomas (NHL). The results showed statistically significant higher average levels of interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-2 receptor (IL-2r) and transferrin receptor (TF-r) in NHL patients compared to controls (p = 0.045, p = 0.047, p = 0.020, p = 0.026 and p = 0.033 respectively). IL-2, IL-2r and TF-r levels were found more elevated in Stages III/IV than in Stages I/II (p = 0.031, p = 0.016 and p = 0.048 respectively), whereas IL-6 concentrations were higher in patients presenting B symptoms (p = 0.011). Significant correlations were found between the erythrocyte sedimentation rate (ESR) and IL-6 (r = 0.681), and between beta 2 microglobulin (B2-m) and IL-2r (r = 0.622).

Adult↗

Mitoxantrone in combination with etoposide and cytarabine for treatment of poor prognosis acute non lymphoid leukemia patients.

BACKGROUND: The proved effectiveness and relatively low extrahematological toxicity of Mitoxantrone, Ara-C and Etoposide as single agents and in combination in the treatment of acute non lymphoid leukemia (ANLL) are well established. In a phase II study the efficacy and toxicity of an induction combination regimen with Mitoxantrone, Ara-C and Etoposide were evaluated for treatment of poor risk ANLL patients. METHODS: Twenty-seven poor prognosis ANLL patients were treated with Mitoxantrone, 7 mg/sm days 1-3; VP16, 150 mg/sm days 1-3; Ara-C, 200 mg/sm continuous infusion days 1-5. Median age of treated patients was 63 (17-78): 10 de novo leukemias (4 greater than 65 yrs 3 with cardiomyopathy); 12 secondary leukemias (5 secondary to a myelodysplastic syndrome, 5 to myeloproliferative syndrome, 2 to other neoplasias); 3 relapses; 2 refractory. RESULTS: Fifteen patients (55.5%) achieved CR (8 de novo leukemias, 3 relapses, 4 secondary leukemias); 7 died in induction, 5 progressed. Median remission duration was 27 weeks (range 5-70 wks) and overall median survival 13 weeks (range 4-80). Extraematological toxicity was low, but five patients died from infections and two from hemorrhages. CONCLUSIONS: The combination tested in this trial proved effective in the treatment of "poor risk" ANLL, but the results need to be confirmed on greater numbers of patients, mainly in the group of de novo leukemias that can't be treated with more aggressive regimens.

Antineoplastic Combined Chemotherapy Protocols↗

Triple immunofluorescence evaluation of CD15, CD34 and class II expression by flow cytometry in normal and leukemic bone marrows.

BACKGROUND: The CD15/CD34 phenotype has been reported as aberrant and exploited for monitoring minimal residual disease in acute myeloid leukemia (AML) patients. Moreover, CD15/CD34 has been described as a rare phenotype in normal bone marrow (NBM) (< 0.10%). We used a triple immunofluorescence assay to investigate the expression of CD15, CD34 and class II antigens in normal (NMB) and leukemic (LBM) bone marrows. METHODS: A FACScan for quantitative fluorescence and the PAINT-A-GATE program for multiparametric analysis were utilized. Fifteen normal bone marrow and fifteen leukemic bone marrow samples were studied with a triple immunofluorescence assay. A FACSorter was used for sorting. RESULTS: Eleven out of 15 normal marrows contained less than 0.67% (range 0.01-0.66) cells which coexpressed CD15, CD34 and class II antigens. Three normal marrows contained more than 0.67% but less than 1.84% (range 1.05-1.83) triple stained cells. The entire group of leukemic marrows coexpressed triple stained cells with a frequency higher than 1% (range 1.1-48.6); furthermore, 10 samples contained the same population at frequencies higher than 10%. The difference between normal and leukemic marrows was statistically significant (p = < 0.001). Triple positive cells (TPc) from NBM were sorted for morphology, which proved to be consistent with myeloid progenitor features (early myeloblasts). This confirms that CD15+ CD34+ Class II+ precursors are commonly expressed in NMB, although at low frequency. Interestingly, 12 (80%) AMLs out of 15 were diagnosed as M1 (5) or M2 (7), while the remaining were M4 (2) and M5a (1). Additionally, all M2 cases were positive at percentages higher than 10%. Apparently CD15, CD34, class II expression correlates mainly with granulocyte differentiation. Two complete remission (CR) LBM, positive at onset for the triple combination, were regularly monitored. In one case the TPc percentage always remained near the normal values found in NBM (0.72%), and this patient is still in CR. In the other, overt relapse was preceded by a progressive increase in the TPc percentage. CONCLUSIONS: Although the presence in NBM of CD15+ CD34+ and class II+ precursors hinders minimal residual disease detection, we conclude that this unusual combination may distinguish a leukemic population and may allow monitoring of "early relapse".

Acute Disease↗

Diagnosis of acute myeloid leukemia and system Coulter VCS.

BACKGROUND: The aim of this study was to evaluate the possible contribution VCS could make in a hematological laboratory for the diagnosis of acute myeloid leukemia (AML). MATERIALS AND METHODS: Peripheral blood samples from 42 AML patients and 58 normal donors were analyzed by flow cytometry with the VCS. Normal and leukemic peripheral blood samples were tested to establish a correlation between VCS data and the reference manual method. We evaluated the sensitivity threshold of the VCS for blast cell detection in progressively diluted samples. We looked at a correlation between different scatterplots and flags and the FAB classification of acute myeloid leukemia in order to identify a characteristic VCS image for each subtype. Thirty-four bone marrow samples (18 normal donors and 16 leukemic patients) were analyzed by the VCS system to demonstrate a characteristic scattergram distribution. Further, we tried to compare scatterplots to the flags of leukemic bone marrow samples and, finally, we compared VCS scatterplots with aberrant antigen expression in AML cases. RESULTS AND CONCLUSIONS: Overall VCS specificity was 93.1% (54/58) in peripheral blood samples; sensitivity was 100% (42/42) and VCS efficiency was 96%. In AML the characteristic X6 flag was observed in 95.23% of the cases (40/42). In peripheral samples discrimination was made between AML M1 with agranular blasts > 50% of the non erythroid cells (NEC), M4, M5 on the one hand, and AML M1 with granular blasts > 50% of NEC, M2, M3 on the other: the X5 flag was often present in the second group because of the different localization of the cells (p = 0.001). In all normal bone marrow samples we observed granuloblasts in different maturation stages in the neutrophil region of the DF1 VCS scatterplot corresponding to the X5X6 flags or, rarely, to the X5X6X1, because of the presence of immature erythroid cells. This association X5X6 was never observed alone in patients affected by AML. In our study, it was difficult to identify peculiar scatterplots and alarms for each FAB class of AML. Nevertheless, we observed that in all M4 and M5 FAB cases the blastic cells both in the peripheral blood and in the bone marrow samples were located in the monocyte region, with the frequent presence of the X3 flag often associated with the X6 flag. Eight out of the 16 AML bone marrow samples (1 FAB M0, 1 M2, 1 M3, 2 M4, 3 M5) showed the X2 flag and partial localization of blasts in the lymphoid region. In all these cases the presence of some small blastic cells with agranular cytoplasm was confirmed by morphological observation and cytochemical stainings.

Acute Disease↗