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A Zaccaria

Publications and source records attributed to A Zaccaria.

At least 37 records · Page 2Linked to original sources
PubMed1999

3q21 and 3q26 cytogenetic abnormalities in acute myeloblastic leukemia: biological and clinical features.

BACKGROUND AND OBJECTIVE: Acute myeloblastic leukemia (AML) with features of myelodysplastic syndrome (MDS) and abnormalities of megakaryocytopoiesis is often characterized by cytogenetic aberrations of the 3q21 and 3q26 bands involving inv(3)(q21q26) and (3;3)(q21;q26). These aberrations have been described in all FAB subtypes with the exception of M3, and in MDS and in megakaryoblastic crisis of chronic myeloid leukemia. We reviewed the biological and clinical features of 10 cases of AML with inv(3)(q21q26) and t(3;3)(q21;q26). DESIGN AND METHODS: Four hundred and sixteen patients with AML were studied in our Institute by cytogenetic analysis and 10 (2.4%) showed inv(3)(q21q26) (7 patients) or t(3;3)(q21;q26) (3 patients): 7 males, 3 females; median age, 43.5 yrs. We also used RT-PCR to investigate the pattern of expression of the EVI-1 gene in 5 patients. RESULTS: Additional chromosomal changes were demonstrated in 6 patients. In 5/10 cases a preceding MDS had been observed. A possible occupational exposure was established in 2 patients (a farmer and an histologist employing organic solvents) and another patient had a therapy-related leukemia. AML subtype was M1 in 9 patients and M2 in 1. A variable excess of micromegakaryocytes was observed in all the patients. In 5 patients the platelet count was normal or increased (median number: 172. 5x10(9)/L; range 55-440). Expression of EVI-1 gene was present in all the 5 patients studied. The clinical course and outcome was extremely poor: 9/10 patients were resistant and 1 patient showed a partial remission after induction therapy. Of the 9 patients resistant to the first line chemotherapy, 7 were also resistant to the second line chemotherapy. Three patients obtained a morphologic complete remission after third line chemotherapy (duration 1, 3 and 6 months); 2 of them were submitted to autologous bone marrow transplantation, but relapsed after 1 and 3 months. The median overall survival was 5.5 months. INTERPRETATION AND CONCLUSIONS: Our findings evidence a strong correlation between 3q21q26 chromosomal aberrations, abnormalities of megakaryocytopoiesis and lack of response to conventional chemotherapy and support the diagnostic and prognostic relevance of chromosome characterization in the classification of AML.

Adult↗
PubMed1999

Fludarabine-based chemotherapy in untreated mantle cell lymphomas: an encouraging experience in 29 patients.

BACKGROUND AND OBJECTIVE: A prospective study to evaluate the role of fludarabine alone or in combination with idarubicin in untreated patients with mantle cell lymphoma (MCL). DESIGN AND METHODS: Twenty-nine untreated patients with mantle cell lymphoma were stochastically treated with intravenous fludarabine at a dose of 25 mg/m(2)/day for 5 days (11 patients) or with a combination of fludarabine and idarubicin (FLU-ID) (fludarabine 25 mg/m(2) i.v. on days 1 to 3 and idarubicin 12 mg/m(2) i.v. on day 1 (18 patients). For both regimens, cycles were given at three-week intervals for a total of six courses. According to the International Prognostic Index, the most part of high-intermediate and high risk factor patients were in the FLU-ID subset: 7 (39%) patients vs. 2 (18%) in the fludarabine alone subset. RESULTS: Of the 29 patients, 8 (28%) obtained a complete response and 10 (35%) a partial response, with an overall response rate of 63%. The remaining 11 (37%) patients did not respond to the therapy. The overall response rates were 64% (7 patients) in the fludarabine group and 61% (11 patients) in the FLU-ID group. The complete response rate was 27% (3 patients) for fludarabine and 28% (5 patients) for FLU-ID. The toxicity was mild in terms of neutropenia and infections, and no fatalities occurred due to drug-induced side effects. INTERPRETATION AND CONCLUSIONS: These results suggest the efficacy of fludarabine alone or in combination with idarubicin in MCL patients. It will be important to increase this experience and to assess other fludarabine-containing regimens, in particular with cyclophosphamide plus idarubicin and with mitoxantrone and or cyclophosphamide, to test the true role of this approach in MCL.

Adult↗
PubMed1998

Anaplastic large cell lymphoma Hodgkin's-like: a randomized trial of ABVD versus MACOP-B with and without radiation therapy.

During the last few years, morphological, immunohistochemical, and genetic findings have placed anaplastic large cell lymphoma (ALCL) as a distinct clinicopathologic entity, and several reports have focused on the existence of different subtypes of the tumor. Particular attention has been paid to the ALCL-Hodgkin's-like (HL) subtype, which seems to be on the border between Hodgkin's disease (HD) and high-grade non-Hodgkin's lymphoma (HG-NHL). From September 1994 to July 1997, during the course of an Italian multicentric trial, 40 ALCL-HLs were randomized to receive as front-line chemotherapy MACOP-B (methotrexate with leucovorin, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin-a third-generation HG-NHL regimen) or ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine-a scheme specific for HD). All patients with bulky disease in the mediastinum at diagnosis underwent local radiotherapy after the chemotherapeutic program. Complete response (CR) was achieved in 17 of the 19 (90%) patients who were treated with MACOP-B, and in 19 of the 21 (91%) patients who were administered ABVD. The probability of relapse-free survival, projected at 32 months, was 94% for the MACOP-B subset and 91% for the ABVD subset. The majority of patients with mediastinal bulky disease obtained CR (evaluated with 67Ga single photon emission computed tomography [SPECT]) after their radiotherapy. The present study suggests that ALCL-HL, in line with its borderline status, responds in an equivalent way to third-generation chemotherapy for HG-NHL and to conventional HD treatment in terms of both CR and relapse-free survival rates. However, as to the latter, a longer follow-up period may be needed before stating the absolute equivalence of the two regimens used.

Adolescent↗
PubMed1998

Internal carotid artery dissection in a patient with Behçet's syndrome.

The authors report a case of internal carotid artery dissection in a young woman with Behçet's syndrome. The authors postulate that a vasculitis of the vasa vasorum already suspected as the basis of aneurysm formation in course of Behçet's syndrome can account for occurrence of arterial dissection in this inflammatory condition.

Aortic Dissection↗
PubMed1998

Alloantigen presenting capacity, T cell alloreactivity and NK function of G-CSF-mobilized peripheral blood cells.

In this study we addressed whether the proportion and the function of antigen presenting cells (APC), T and NK lymphocytes are modified in the apheresis product of six healthy donors who received a stem cell mobilizing treatment with glycosylated G-CSF at 10 microg/kg/day x 5 days s.c. Flow cytometry analysis showed comparable percentages of HLA-DR+, CD19+, CD86+, CD80+ and CD1a+ cells in preG-CSF-peripheral blood mononuclear cells (preG-PBMC) and after mobilization in G-PBMC, whereas the proportion of CD14+ monocytes significantly increased in G-PBMC (3+/-1% vs 17+/-8%, P = 0.003). Analysis of lymphocyte subsets in preG-PBMC and G-PBMC showed similar proportions of CD3+, CD4+, CD8+ and CD28+ T cells, but a significantly lower percentage of CD16+ (11+/-7% vs 4+/-1%, P=0.01), CD56+ (15+/-6% vs 5+/-2%, P= 0.008), CD57+ (16+/-9% vs 5+/-2%, P=0.04), CD25+ (19+/-2% vs 9+/-6%, p=0.009) and CD122+ (5+/-2% vs 2+/-1%, P = 0.05) cells in G-PBMC. Unfractionated preG-PBMC and G-PBMC were irradiated and tested in primary mixed leukocyte culture (MLC) with two HLA-incompatible responders and induced efficient alloresponses in four of six cases, whereas G-PBMC stimulated poorly in the remaining two cases. Also, in allo-MLC with irradiated G-PBMC we detected lower amounts of IFN-gamma (P = 0.04) and of IL-2 (P = 0.06) than in allo-MLC with preG-PBMC. Furthermore, freshly isolated preG-PBMC and G-PBMC from each donor exerted comparable allogeneic responses to HLA-incompatible irradiated mononuclear cells in all cases. However, G-PBMC showed no NK activity against K562 target cells at any effector:target ratio tested. These data suggest that normal G-PBMC may prevent Thl alloresponses, maintain efficient alloreactivity to HLA mismatched antigens and have impaired NK activity.

Antigen Presentation↗
PubMed1998

Detection and monitoring of trisomy 8 by fluorescence in situ hybridization in acute myeloid leukemia: a multicentric study.

BACKGROUND AND OBJECTIVE: The role of fluorescence in situ hybridization (FISH) in the detection and monitoring of trisomy 8 (+8) in acute myelogenous leukemia (AML) has not been defined exactly. This multicentric study was performed in order to: i) analyze the sensitivity of interphase FISH with respect to conventional chromosome analysis (CCA) in detecting +8; ii) compare the results of FISH and CCA in the quantitation of the frequency of +8-positive cells; iii) analyze the possible role of FISH in the cytogenetic follow-up of patients with +8. DESIGN AND METHODS: One hundred and ninety-eight nonconsecutive patients with a diagnosis of AML seen at five centers over a 3-year period were studied by CCA and FISH with a chromosome 8-specific centromeric probe. Two hundred interphase cells were scored in each test and the cut-off for the recognition of +8 was set at 3%. An irrelevant pericentromeric probe was used as negative control in those cases with an apparently normal karyotype and trisomy 8 in interphase cells. FISH studies were conducted at diagnosis and, in 14 cases with +8, on 1.5 occasions during follow-up. RESULTS: Karyotype aberrations were seen in 121 cases (61.1%), with +8 being present in 38 of them (16 as the sole aberration). Interphase FISH detected +8 in 37/38 cases; in a patient with 1/10 metaphases with +8, 2.3% interphase cells with 3 signals were seen. Fourteen additional cases with occult +8 were detected by FISH, which showed 4-22% interphase cells with three signals; 6 patients had an abnormal karyotype without +8, 3 had a normal karyotype, 5 had no analyzable mitoses. In 24 cases with > 15 analyzable metaphases, percent variations between CCA and FISH in the estimation of the size of the trisomic clone ranged between 0.4% and 51%, median value 22%. Underestimation of the percent of trisomy 8 by FISH occurred in all 10 cases with > 90% +8 metaphases. In 7/14 cases investigated sequentially, FISH detected 5-35% trisomic cells in the BM after induction therapy (4 CR, 3 PR); 4 cases relapsed with +8 at 8-15 months. The absence of +8 in remission marrows was documented in the remaining 7 cases, 4 of which relapsed at 20-32 months. INTERPRETATION AND CONCLUSIONS: It is concluded that FISH was a valuable method in this multicentric study since it showed greater sensitivity than CCA in detecting minor clones with +8, in patients with both normal and abnormal karyotypes. The role of FISH in the cytogenetic follow-up of trisomies in AML patients may be promising.

Acute Disease↗
PubMed1998

Prior treatment with alpha-interferon does not adversely affect the outcome of allogeneic BMT in chronic phase chronic myeloid leukemia.

BACKGROUND AND OBJECTIVE: Controlled clinical trials have shown that Interferon-alpha (IFN-alpha) is able to control myeloid proliferation and to suppress the Ph+ clonal hemopoiesis in early chronic phase chronic myeloid leukemia (CML): a growing number of patients are treated with this agent from diagnosis. However, if a CML patient has an HLA-identical sibling, bone marrow transplant (BMT) represents the best choice of treatment. Since IFN-alpha is known to modify the immunologic response and to increase marrow fibrosis, information is needed on the outcome of patients transplanted after IFN-alpha treatment. DESIGN AND METHODS: We analyzed retrospectively 32 Ph+ CML patients submitted to BMT in the last 6 years in Institute "Serágnoli". All the patients were in 1st chronic phase, their median age was 37 years, the donors were HLA-identical (27/32) or 1 Ag-mismatched (5/32) siblings. Big BuCy was the conditioning regimen employed for all and GVHD prophylaxis was based on CsA in 4 patients and Csa+MTX in 28 patients; all patients received homogeneous pre and post-transplant supportive care, antimicrobial and antiviral prophylaxis. These patients were divided into 2 groups according to the treatment before BMT: 16 received IFN from diagnosis to BMT (mean dose 6.9 MU/daily) for at least 6 mos (mean 23 mos, range 8-75) and 16 received chemotherapy alone (hydroxyurea [HU]). RESULTS: Hematological recovery was comparable in the two groups: time to 0.5 x 10(9)/L PMN was 20.5 days (range 11-32) in the IFN group and 20 days (range 10-32) in the HU group; time to 50 x 10(9)/L platelets was 28 days (range 20-117) in the IFN group and 27 days (range 20-112) in the HU group. The incidence of acute GVHD was not different in the two groups for any grade of the disease; in patients who survived more than 100 days, chronic GVHD occurred in the two groups with the same frequency. Seven patients died of transplant related mortality (TRM), 4 in the IFN group and 3 in the HU group. Hematological relapse was observed in only one case in the HU group; no cytogenetic relapse occurred. Disease free survivals at 7 years are 61% and 72%, respectively; the difference is not significant. INTERPRETATIONS AND CONCLUSIONS: Notwithstanding the low number of patients included in this study, the data reported here confirm that prior treatment with alpha-IFN does not adversely affect transplant outcome.

Adult↗
PubMed1998

[The role of vena cava filters in the prevention of pulmonary embolism and hemodynamic changes in the venous system of the lower limbs].

BACKGROUND: On the basis of recent investigations, pulmonary embolism represents the third cause of death. If only hospitalized population over 65 years of age is considered, this pathology is quite the first cause of mortality. As deep venous thrombosis of the lower limbs represents the main cause of pulmonary embolism (90%), it should be right to suggest interruption of venous flow at caval level. The aim of this prospective report is to evaluate the efficacy of vena cava filter in pulmonary embolism prevention and the hemodynamic variations it can cause in the venous district of lower limbs. METHODS: 137 definitive caval filters were positionated from 1989 to 1996. Average follow-up was 12.6 months. Patients were controlled at 2-7 days, 1 month and than every 6 months. RESULTS: Filter perviousness was observed with Kaplan and Meyer's curve and it was 94.7%. There was pulmonary embolism in just 2 cases (1.4%). Filter perviousness was not depending on anticoagulant treatment. CONCLUSIONS: In conclusion, this prospective experience underlines that: caval filter is effective in pulmonary embolism prophylaxis; there are not important hemodynamic alterations of inferior vena cava, below filter; anticoagulating treatment does not influence filter perviousness; there are not hemodynamic alterations after slight dislocations of caval filter; finally there is a direct relation between level of deep venous thrombosis and post-phlebitic manifestations.

Hemodynamics↗
PubMed1997

Amplification of third-complementary-determining-region (CDR-III) of heavy chain immunoglobulin gene (IgH) in one hundred adult acute leukemias.

We applied a simple polymerase chain reaction (PCR) based method for detecting immunoglobulin heavy-chain (IgH) gene rearrangement, using its CDR-III region to assess B-cell clonality in a series of 100 acute lymphoblastic leukemias (ALL) (84 B-cell lineage, 4 null-ALL and 12 T-ALL). The amplified CDR-III regions can be generated in all the B-lineage ALL and separated by size by polyacrylamide gel electrophoresis (PAGE), thereby providing a specific diagnostic marker for each B cell clone. Size heterogeneity resulting from independent IgH rearrangement events and the high resolution power after electrophoresis and silver staining of the PAGE gels can be used to generate a "fingerprint" of the PCR fragments representing either the spectrum of B-cell clonality in complex populations of B lymphocytes or the partially genomic configuration of the VH-N-DH-N-JH region. At diagnosis, we found the presence of one clonal IgH heavy-chain gene rearrangement in 80 B-cell lineage and null ALL and a biclonal rearrangement in 8 cases. The CDR-III bands were of sizes ranging from 80 to 130 bp. The PCR analysis of the IgH gene enabled us to obtain a CDR-III leukemia specific product in all cases, thereby providing a specific and diagnostic marker for each B-cell clone.

Adult↗
PubMed1996

A new method of "in-cell reverse transcriptase-polymerase chain reaction" for the detection of BCR/ABL transcript in chronic myeloid leukemia patients.

Methods of detecting minimal residual disease (MRD) in chronic myeloid leukemia (CML) include chromosome analysis, Southern blotting, polymerase chain reaction (PCR) and fluorescent in situ hybridization (FISH) techniques. We report a novel method to detect intracellular messenger RNA (mRNA) by combining the techniques of reverse transcription (RT) and PCR performed directly inside the cells, without extraction of the nucleic acid. We applied this method, which we call "in-cell RT-PCR", to detect hybrid BCR/ABL transcript within single cells. After cellular permeabilization and fixation of single cells in suspension, the neoplastic mRNA was reverse transcribed into cDNA, and the cDNA was amplified by PCR with fluorescent primers, specific for bcr/abl. Flow cytometry was used to detect cells positive for the amplified DNA within the cell cytoplasm. After transferring the amplified cells onto slides by cytospin, the positive cells for BCR/ABL cDNA were observed by fluorescent microscopy. The technique was capable of detecting low abundancy signals and distinguishing different levels of gene expression. The amplification products were found in the cells and supernatants. The distribution was critically affected by the protease digestion condition. The specificity of amplification was confirmed by a nested RT-PCR of BCR/ABL performed on extracted mRNA from the same sample, and by reamplification of supernatants. We have used the technique to study 10 Ph+ CML patients and three normal subjects as controls. Four patients were 100% Ph+ at diagnosis time and RT-PCR+ at cytogenetic and molecular analysis, respectively. In-cell RT-PCR showed that the residual non-neoplastic cells could be observed in all cases. In two patients undergoing interferon-alpha (IFN-alpha) therapy and in four bone-marrow transplanted patients, the in-cell RT-PCR was used to compare the level of Ph+ positivity detected by cytogenetic analysis with the number of cells expressing BCR/ABL transcript. In this manner, we could estimate the MRD. Our preliminary application of the technique suggests that it is capable of accurately identifying cells transcribing bcr/abl, and that it may have significant clinical applications in the detection of MRD.

Base Sequence↗
PubMed1996

'Fingerprinting' of HLA-DQA by polymerase chain reaction and heteroduplex analysis.

We have developed a rapid, non-radioisotopic PCR fingerprinting technique for analysis of the HLA-Class II DQA gene second exon polymorphism, and have applied it to DNA samples from 210 healthy individuals. The technique is based on the formation of specific patterns (fingerprints) of homoduplexes or heteroduplexes between in vitro amplified DNA sequences. After electrophoresis on non-denaturing polyacrylamide gels and ethidium bromide fluorescence or silver staining, different HLA-DQA types give allele-specific banding patterns. HLA DQA typing is done by visual comparison between the sample's fingerprint patterns and appropriate controls. Similar fingerprints can be resolved by mixing the sample with a standard DNA in an amplified 'DNA crossmatch'. This application of PCR fingerprinting is useful to confirm the HLA-DQA serological typing and to improve the molecular characterization of this polymorphic region.

Alleles↗
PubMed1996

All-trans retinoic acid and in vitro cytokine production by acute promyelocytic leukemia cells.

Leukemic cells spontaneously secrete cytokines involved in the proliferation of the clone; in this study we evaluated the effects of all-trans retinoic acid (ATRA) on the in vitro autocrine production of cytokines by acute myeloid leukemia cells. Thirty acute nonlymphoid leukemia cases (ANLL) (10 APL and 20 ANLL of other cytotypes than APL) were studied; the in vitro secretions of IL-1 alpha, IL-3, IL-4, IL-6, IL-10, G-CSF, GM-CSF, TNF-alpha were tested with and without ATRA addition. After 5 d exposure to ATRA 10(-6) M APL-treated samples showed a significant reduction of IL-6 (p = 0.008) and GM-CSF (p = 0.03) and a significant increase of IL-1 alpha (p = 0.01) production, if compared to untreated APL samples. No difference was seen in IL-3, IL-10 and IL-4 productions; G-CSF production resulted absent in all but 3 APL cases, in which addition of ATRA determined increase in the production. Interestingly, the 3 G-CSF-producing cases did not obtain clinical remission with ATRA; GM-CSF and IL-6 were spontaneously produced by all the cases, and 7 of 10 APL patients subsequently obtained complete remission after induction. TNF-alpha was produced only in 1 case. No statistical difference was seen in all the productions obtained from other than promyelocytic acute leukemic cells, both with and without ATRA addition. However, it is noteworthy that the production of IL-6 was more than twice as high in ANLL non-APL than in APL cases. In conclusion, these data could thus suggest possible complementary mechanisms of the exhaustion of the leukemic clone upon treatment with ATRA.

Bone Marrow↗
PubMed1996

Clinical implications of serum levels of soluble CD23 and tumor necrosis factor alpha in low-grade non-Hodgkin's lymphoma.

In the last few years the research for new biological features in low-grade non-Hodgkin's lymphoma has provided important results. Several biological parameters are under evaluation and, in particular, cytokines and soluble receptors levels are showing their importance as prognostic parameters. In the present study, serum levels of tumor necrosis factor alpha (TNF-alpha) and soluble CD23 (sCD23) were measured at the time of diagnosis and after induction polychemotherapy in 40 patients with newly diagnosed low-grade non-Hodgkin's lymphoma (LG-NHL). The treatments were CIOP (cyclophosphamide, idarubicin, vincristine, prednisone) regimen for 28 patients and FMP (fludarabine, mitoxantrone, prednisone) scheme for 12 patients. Pretreatment levels of TNF-alpha were highly elevated in patiets with LG-NHL compared with healthy controls (p = 0.005) and were significantly correlated with the Ann Arbor stage (p = 0.001). sCD23 was detected in 35 patients at diagnosis and were markedly increased in LG-NHL patients when compared to healthy controls (p = 0.005); patients with advanced stage presented higher values than those with early stage disease (p = 0.002). All the complete responders (20/40, 50%) showed a decrease of TNF-alpha and sCD23 levels. By contrast, the combination of high levels of TNF-alpha and sCD23 correspond to a group of non-responders. Our results suggest that TNF-alpha and sCD23 are specific prognostic parameters for LG-NHL, and that they could be used as tumor markers within a potential biological prognostic index.

Adolescent↗