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Biomedical subjects

G Castoldi

Publications and source records attributed to G Castoldi.

At least 127 records · Page 7Linked to original sources
PubMedDate not supplied

Immunophenotypic, cytogenetic and molecular investigations in two cases of CALLA positive acute myeloid leukemia.

Clinicopathological and cytogenetic features of two patients with acute myelogenous leukemia (AML) whose blast cells coexpressed myeloid-associated antigens and CALLA are described. Leukemia cells revealed myelomonocytic (FAB-M4) and monocytic (FAB-M5) features, while the nonblast cell population exhibited trilineage myelodysplasia in both cases, a finding suggestive of multiple-cell-lineage involvement. Cytogenetically, a deletion of the long arm of chromosome 6 was found in one patient, and normal metaphases were detected in the other. Molecular studies disclosed a rearrangement of the IgH locus in one patient. Clinically, these patients were unresponsive to antimyeloid regimens including Daunorubicin and Cytarabine, two agents normally also effective on lymphoblastic leukemias, possibly indicating the need for alternative protocols for the treatment of CALLA positive AML.

Aged↗
PubMedDate not supplied

Chromosome studies of enriched blast cell fractions in myelodysplastic syndromes terminating in acute myeloid leukemia.

For a better understanding of the karyotype evolution of different marrow cell populations in the course of MDS, 6 patients who eventually developed overt leukemia, belonging to a series of 46 MDS referred to our Institution, were studied ad diagnosis and at leukemic progression. In each case the blast cells were separated from the maturing precursors of the erythroid and granulocytic lineage by centrifugation on a Percoll density gradient. Parallel chromosome investigations were performed in each cell fraction. Cytogenetic analysis performed at presentation did not reveal distinctive karyotype features in metaphases arising in the blast enriched cell fraction, as compared with those obtained from the fraction containing erythroblasts and promyelocytes--myelocytes. These findings suggest that in the initial phase of MDS blast cells may lack distinctive cytogenetic features and may thus represent part of a clonal preleukemic proliferation. At the time of leukemia onset, clonal aberrations [trisomy 21 and del(11)(q23)] showing a restricted pattern of distribution within the blast cell enriched fractions were detected in two patients, whereas one patient showed an increase in size of the abnormal clone carrying monosomy 7, an aberration detected in metaphases obtained from both cell fractions. Thus, some evolutive steps in the natural history of these disorders can be heralded by the acquisition of chromosome aberrations more readily detectable in blast enriched cell fractions. In some cases, partial loss of differentiative capability by the abnormal clone may account for the detection, at leukemia onset, of chromosome aberrations involving both the blast cell fraction and the erythroblast-promyelocyte enriched cell fraction.

Blast Crisis↗
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Hairy cell leukemia. A therapeutical update.

This is a review of current treatment for hairy cell leukemia (HCL). Data for this analysis were obtained from the Italian HCL Registry, as well as from other published series. We have given space to the impact of interferon and pentostatin on the management of this disease. Other issues are also discussed, such as the relevance of achieving a complete remission with respect to overall and relapse-free survival. We include a final section on recommendations which may prove useful in designing an appropriate therapeutic strategy.

Adrenal Cortex Hormones↗
PubMedDate not supplied

Frequency and distribution of megakaryoblasts in FAB subtypes of ANLL: an immunocytochemical ultrastructural study.

BACKGROUND: Identification of early megakaryocyte (MK) precursors is difficult and conflicting. The prevalence of leukemias with a megakaryocytic component may be underestimated when conventional techniques are utilized. The recent development of immuno-ultrastructural procedures for simultaneous detection of platelet peroxidase reaction and specific platelet membrane antigens has increased our capability of recognizing blast cells of the megakaryocytic lineage. METHODS: In this study the occurrence and distribution of megakaryoblastic in the FAB subtypes of adult "de novo" acute myeloid leukemias was employed to detect megakaryocytic precursors. RESULTS: A megakaryoblastic proliferation was demonstrated in 8/42 cases (19%), with a much higher percentage than previously reported and an unusual distribution in the M2 subtype. CONCLUSIONS: These findings indicate that megakaryocytic involvement may be found rather frequently when an immunocytochemical ultrastructural method is applied to the characterization of leukemias.

Adult↗
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Primary gastric lymphoma: distribution and clinical relevance of different epidemiological factors.

BACKGROUND: Over the last 10 years the incidence of primary gastric lymphomas (PGL), and in particular those of MALT origin, has significantly increased. Recent works correlated this epidemiological observation to Helicobacter pylori (HP) infection. On the other hand, new evidence demonstrating that occupational exposure to pesticides and solvents has played an important role in the pathogenesis of non-Hodgkin lymphomas (NHL) has emerged from studies involving large series of patients. METHODS: Thirty PGL patients, observed between 1986-1992, were subdivided according to HP infection, history of previous gastric disturbances (G) and exposure to pesticides and solvents (T). RESULTS: On the basis of these parameters we divided the patients into three groups: T+HP+ (8), T+HP- (7), T-HP+ (9). T+ patients had a positive history of gastric problems or a positive histological biopsy in 13.3% of cases, versus 66.7% in T- patients. The incidence of HP infection in the T+ group was 53%, which proved to be comparable to the statistics for northeastern Italy, while in the T- group the incidence of infection was 100%. CONCLUSIONS: On the whole these data suggest that HP infection could be considered a pathogenetic factor in 34% of patients, while occupational exposure to pesticides and solvents could have played a more important role in 66% of these cases.

Aged↗
PubMedDate not supplied

Study of prognosis in acute myeloid leukemias (AML) by cluster analysis.

BACKGROUND: Cluster analysis is particularly effective in detecting homogeneous subgroups among large series of observations. We applied this relatively uncommon approach to the study of prognosis in 137 patients affected by acute myeloid leukemia (AML). METHODS AND RESULTS: Employing simple presentation parameters (age, WBC, splenomegaly, hepatomegaly) we used cluster analysis to define 3 groups with different overall survival (p = 0.0019). This classification was obtained following a rescaling of the variables and principal component analysis. Validation was performed through random definition of a control group. With the same variables, univariate analysis demonstrated age was the only prognostic factor, while Cox's model was not significant. CONCLUSIONS: In our series cluster analysis allowed a better definition of prognosis than Cox's analysis. Since the 3 groups are well identifiable, each patient can be rapidly classified and his allocation confirmed by discriminant functions. For cluster 2 we were able to project a possible myelodysplastic evolution, while cluster 3 was more frequently associated with a monocytic blastic component. We think that cluster analysis deserves consideration as an alternative statistical approach in the analysis of large series of data; its usefulness lies in its power to define homogeneous prognostic or biologic subgroups and to elaborate further hypotheses for new studies.

Acute Disease↗
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Flow cytometric analysis of anti-platelet antibodies in idiopathic thrombocytopenic purpura.

Anti-platelet antibody measurement may be important in defining the pathogenesis of thrombocytopenic states. In this paper we compared three anti-human immunoglobulin reagents by using them to detect anti-platelet antibodies on the platelet surface and in the serum of 14 patients with chronic idiopathic thrombocytopenic purpura (ITP) and 22 thrombocytopenic disorders. Samples were analyzed by both flow cytometry and a fluorescence microscope. In ITP patients, the direct test was positive in 50% of the cases, while the indirect technique proved to be positive in a slightly higher number of those tested (56%). Furthermore, the number of positive cases was similar for the three reagents used in this study, although the mean percentage of positive platelets was higher for the kappa/lambda monoclonal reagent. These data further support the sensitivity and reproducibility of flow cytometry analysis, which was capable of detecting antiplatelet antibodies in all patients with transfused Cooley's disease (regarded as positive control), as well as in a significant number of patients with ITP or related diseases. On the basis of the data presented here, definitive proof regarding the presence of anti-platelet antibodies in patients with thrombocytopenia still has to be found, and further studies are needed in order to ascertain the autoimmune nature of these disorders.

Blood Platelets↗
PubMedDate not supplied

Immunophenotypic and genotypic characterization of B-cell chronic lymphocytic leukemia patients from northern Italy.

BACKGROUND AND METHODS: Immunoglobulin (Ig) gene expression and rearrangements provide information about cell lineage, clonality and differentiation of neoplastic lymphoid cells. We performed flow cytometry and Southern blot analysis in 25 patients with chronic lymphocytic leukemia (CLL) from the Po River delta region (Northern Italy), in order to correlate surface immunological phenotype and heavy and light chain gene rearrangements with clinical stages. RESULTS: In these 25 CLL cases, as in the larger group of 165, k-positive (k+) patients were more frequent than lambda-positive (lambda +) ones by a ratio of 59:41, with a predominance of lambda + in stage II (46:54) and of K+ in stage IV (77:23). However, the survival behavior of lambda + and k+ patients was not statistically different. Ig gene rearrangements were found in all patients in accordance with the immunophenotype. When Ig gene analysis was performed on two different occasions in 7 of the 8 who received chemotherapy, there was an increase in the percentage of the germline band. This variation was inversely related to changes in WBC count. In the treated subject who showed a reduction of both WBC count and the germline, there was rapid disease progression and short survival. CONCLUSIONS: Analysis of Ig gene rearrangements in our CLL patients demonstrated: i) the monoclonality of neoplastic cells; ii) no correlation between rearrangements and clinical stages, and iii) that this analysis may be a useful tool in evaluating biological behavior in selected CLL cases showing a discrepancy between hematological data and clinical response to therapy.

Clone Cells↗
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Philadelphia chromosome-positive acute myeloid leukemia: cytoimmunologic and cytogenetic features.

BACKGROUND: Little is known about the morphological and clinical features of the minority of acute myeloid leukemias (AML) that carry the t(9;22)(q34;q11) translocation. MATERIALS AND METHODS: Cytologic, cytogenetic and clinical features were studied at diagnosis and during disease evolution in 11 patients presenting with de novo AML. Diagnoses according to the FAB criteria were AML-M2 (3 cases), AML-MO and AML-M4 (2 cases each), AML-M4eos, AML-M5, AML-M6, AML-M7 (1 case each). RESULTS: Immunophenotyping disclosed positivity for CD33 or CD13 and for the CD34 stem cell antigen in all cases tested. Lymphoid-associated markers (LM) were detected in 7/9 patients. In 5 cases the expression of at least 2 LM was seen. In addition, evidence of clonal rearrangement of the immunoglobulin (Ig) and/or T-cell receptor (TCR) genes was documented in 3/4 evaluable cases. The Ph chromosome was found as the sole change in 5/11 cases; the karyotype reverted to normal in 2/4 patients who achieved complete remission. Rearrangement in the M-bcr region was detected by Southern blotting in 2/7 cases. CONCLUSIONS: This infrequent cytogenetic subset of de novo AML appears to be characterized by heterogeneous cytologic features, with frequent expression of lymphoid markers, and by unfavorable prognosis. The combination of clinical, cytologic and cytogenetic studies is important in distinguishing de novo AML with the t(9;22) from chronic myelogenous leukemia blast crisis.

Acute Disease↗
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Myelodysplastic syndromes with monocytic component: hematologic and cytogenetic characterization.

BACKGROUND AND OBJECTIVE: Patients with myelodysplastic syndromes (MDS) showing high numbers of abnormally localized immature precursors (ALIP) also display myelomonocytic antigens on immature cells, and it has been suggested that the presence of monocytosis could define a distinct subset of MDS characterized by poorer survival. The objective of this study was to analysis the incidence and significance of monocytosis among our series of patients with MDS and correlate the distributions of these elements with other hematologic features. METHODS: We evaluated the monocytic component in myelodysplastic syndromes in order to clarify the significance of monocytosis in MDS and its relationship with CMMoL and other MDS. Monocytosis was defined as a percentage of blood monocytes greater than 10%. RESULTS: Among a series of 139 consecutive MDS patients, we describe a group of 29 (20.8%) patients with monocytosis and dysplastic features involving multiple cell lineages which do not fulfill the criteria for diagnosis of CMMoL or aCML. These patients, who do not differ from MDS without monocytosis in the main clinical parameters, are characterized by relatively higher leukocyte (WBC 6.6 x 10(9)/L) and granulocyte counts (PMN 2.5 x 10(9)/L), hypercellular bone marrow and relatively poor prognosis. Among these patients, we observed a particularly high incidence of evolution to CMMoL (34.5%) and AML (17.2%) with monocytic component (FAB M4 and M5). Cytogenetic data demonstrated clonal chromosome changes in 11/13 patients with MDS and monocytosis, while only 19/41 patients without monocytosis showed clonal abnormalities. CONCLUSIONS AND PERSPECTIVES: The combination of hematologic and cytogenetic features in our study suggests that it is reasonable to consider myelodysplasia with monocytosis as a distinct disease subset of MDS, characterized by multilineage dysplasia along with a higher incidence of karyotype aberrations. The multi-step pathogenetic process in these patients may have reached a more advanced stage at which the relative or absolute increase in the number of monocytes may represent the first event in the subsequent progression of the disease towards acute leukemia.

Cell Lineage↗
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Detection of numerical aberrations in hematologic neoplasias by fluorescence in situ hybridization.

BACKGROUND AND OBJECTIVE: Over the last 5 years, fluorescence in situ hybridization (FISH) techniques have had an important impact on molecular cytogenetic diagnosis, providing a better understanding of the role of numerical aberrations in hemopoietic neoplasms. The objective of this article is to analyze the clinical applications of FISH in the management of hemopoietic malignancies. EVIDENCE AND INFORMATION SOURCES: The material examined in the present review includes articles and abstracts published in journals covered by the Science Citation Index and Medline, and personal published and unpublished data. STATE OF ART: FISH technology has the advantage of being relatively simple, fast and flexible. Published data and ongoing prospective studies show that, under well-controlled experimental conditions, interphase FISH is more sensitive than conventional metaphase analysis in the detection of numerical abnormalities. Due to the relatively high rate of false positive results, FISH cannot be used for the study of minimal residual disease. However, since molecular strategies for the detection of small-sized aneuploid clones have not been developed yet, FISH represents a useful adjunct to conventional cytogenetics, especially for the quantitation of the size of abnormal clones during the course of the disease and to monitor XX/XY chimerism following sex mis-matched bone marrow transplantation. Different approaches to the study of multiple cell-lineage involvement by chromosome changes have been developed that take advantage of FISH techniques by: a) simultaneous FISH and membrane immunophenotyping of cytologic and histologic preparations; b) two-step analysis based on assessment of the morphology of cells on panoptical stains, with subsequent hybridization and relocation of previously identified cells; c) FISH analysis of enriched cell fractions obtained by cell sorting or by separation of bone marrow cells on a density gradient, and d) study of single hemopoietic colonies grown in semisolid media. PERSPECTIVES: New molecular cytogenetic techniques, such as dual color FISH comparative genomic hybridization, are at hand that will greatly improve the diagnostic power of cytogenetics and make FISH increasingly useful in research laboratories as well as in clinical practice.

Aneuploidy↗
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Potential clinical applications of rhGM-CSF in acute myeloid leukemia based on its biologic activity and receptor interaction.

BACKGROUND AND OBJECTIVE: Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a multilineage hemopoietic growth factor that stimulates proliferation, differentiation, and survival of progenitor cells, enhances the functional activities of mature myeloid effector cells, and plays a key role in host defense and the inflammatory process. Although the clinical use of rhGM-CSF in patients affected by lymphoid malignancies is widely accepted, its utility and safety in the management of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) is still controversial. The three main schedules adopted for clinical application of GM-CSF in AML are as follows: A) post-chemotherapy, in order to shorten the duration of neutropenia and/or monocytopenia; B) prechemotherapy to recruit blast cells into active cell cycle phases, and to increase their sensitivity to cell cycle-dependent cytotoxic drugs; C) as a mobilizing agent to induce the release of progenitor cells from bone marrow into circulation (peripheral blood progenitor cell transplantation-PBPC). The objective of this paper is to analyze the potential clinical applications of rhGM-CSF in AML. EVIDENCE AND INFORMATION SOURCES: The material examined in the present review includes several personal papers in this field and articles and abstracts published in journals covered by the Science Citation Index. STATE OF THE ART: Based on current knowledge, it may be argued that rhGM-CSF should be used only in a subset of AML patients at high risk of infection mortality, including elderly subjects, and/or in those AML patients who relapse or are resistant to induction treatment. However, the risk of stimulating the leukemic clone following GM-CSF therapy should be kept in mind when using this growth factor in the clinical setting, even though the great majority of the reported papers on this subject have shown that GM-CSF therapy does not affect relapse rates, frequency of remissions or patient life expectancy. PERSPECTIVES: It is likely that new data from controlled clinical trials will clarify the therapeutic role of GM-CSF in myeloid-derived malignancies, allowing the establishment of consensus guidelines for its use.

Acute Disease↗