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G Castoldi

Publications and source records attributed to G Castoldi.

At least 91 records · Page 5Linked to original sources
PubMed1993

Chromosome aberrations in CD34-positive acute myeloid leukemia. Correlation with clinicopathologic features.

Morphologic, immunologic, and cytogenetic features were studied in 30 newly diagnosed patients with CD34-positive (CD34+) de novo acute myeloid leukemia (AML) in comparison with 30 patients with CD34-negative (CD34-) AML. Karyotype at diagnosis was abnormal in 25/30 CD34+ AML patients, of which nine had major karyotype aberrations (MAKA). Clonal chromosome changes were detected in 9/30 patients with CD34- AML. The most frequent chromosome aberration in CD34+ patients was -5/5q-, an aberration showing a strong association with the M2 FAB subtype of AML. Other recurring chromosome changes involved chromosome 16q (four cases) and chromosome 17p (three cases). Total or partial monosomy 7q was detected in three cases. Among CD34- AML, two patients had the classical t(15;17) and two had structural aberrations of 6q. Among patients with CD34+ AML, nine had MAKA in association with trilineage myelodysplasia (TMDS). TMDS was infrequent in CD34+ AML without MAKA and in CD34- AML. Complete remission (CR) was achieved in 8/30 CD34+ AML (26%), as compared with 22/30 CD34- AML (73%), and median survival was 2 months in the former group and 8 months in the latter. No patient with CD34+ AML and MAKA achieved CR, whereas 8/21 CD34+ AML without complex chromosome changes or with normal karyotype achieved CR. In conclusion, a distinct cytogenetic profile may be associated with CD34+ AML. Cytogenetic findings in CD34+ AML may be clinically relevant in that they may disclose a subset of patients with MAKA with a low CR rate.

Adult↗
PubMed1993

Clinical review on features and cytogenetic patterns in adult acute myeloid leukemia with lymphoid markers.

Cytogenetic patterns in correlation with cytologic, biomolecular and clinical findings were studied in 45 adult patients with AML expressing at least one of the following lymphoid associated markers (LM): CD2, CD7, CD10, CD19, CD22, TdT. Four cytogenetic groups were recognized: group I, including 8 patients with 11q23 rearrangements; group II including 5 patients with the Ph chromosome; group III, with 19 patients and aberrations of the "myeloid type" including 4 cases with aberrations of chromosome 13, 3 cases with 1q and 7q anomalies, 2 cases with trisomy 11q; group IV, including 13 patients with normal karyotype. Patients showing extensive lineage infidelity were encountered more frequently in cytogenetic groups I and II than in groups III and IV. Two of 4 cases with aberrations of chromosome 13 showed two or more lymphoid features either at immunophenotyping or at biomolecular analysis of the configuration of lg and TCR genes. Patients with 11q23 rearrangements and with the Ph chromosome were generally young, presented with high WBC count and had low complete remission rate. Survival in Ph chromosome positive patients was uniformly short. We conclude that, although there is no cytogenetic anomaly specific for AML with LM, chromosome findings may be clinically relevant in AML with LM. A morphologic, immunologic and cytogenetic classification of AML with LM may constitute a working basis for future studies aimed at a better definition of clinicopathological features and optimal treatment strategy for these leukemias.

Adolescent↗
PubMed1993

Abnormal expression of N-CAM (CD56) adhesion molecule on myeloid and progenitor cells from chronic myeloid leukemia.

Bone marrow and peripheral blood samples from 36 patients with Philadelphia chromosome positive chronic myelogenous leukemia (Ph+ CML) (30 in chronic phase, four in accelerated phase, and two in blastic crisis) were tested with two CD56 monoclonal antibodies (My31 and Eric 1) using the Facscan flow cytometer. Two- and three-color fluorescence experiments indicated that CD13+/CD33+ myeloid cells from 19 out of the 36 patients were positive for CD56 in 12-77% of the cells. In contrast, no CD56 positivity was documented in myeloid cells from bone marrow (BM) of healthy donors. Immunocytochemical staining (APAAP technique) of CML peripheral blood (PB) and BM slides showed that CD56 expression was detectable from the myelocyte stage with the strongest staining in the metamyelocyte stage. Neutrophils were negative both by flow cytometry and APAAP analysis. In individual CML patients, an increasing number of CD56+ cells were recovered with progressively higher density cuts (1.065-1.077 g/ml), supporting the concept that the antigen level tends to increase during myeloid differentiation. Furthermore, 19% of CML patients coexpressed CD56 and CD34 antigens in 10-45% of the CD34+ cells. The myeloid nature of CD56+/CD34+ CML cells has been ascertained by granulocyte-macrophage colony-forming unit (CFU-GM) assays on CD56+ cells sorted on FACS. Furthermore, in six out of eight CML patients in whom we performed a comparative BM and PB analysis, we found that the CD56 expression was brighter and the number of positive cells significantly higher in the peripheral blood myeloid cells as compared to their BM counterpart. In short-term liquid cultures, low doses (50 U/ml) of alpha interferon down-regulated the CD56 expression in CML cells, accompanied by a significant reduction of the Ph positivity. In conclusion, the expression of CD56 on CML myeloid elements seems to represent an aberrant phenomenon which could affect the cell homing mechanisms and, probably, the pattern of tumor cell dissemination. In patients with CD56+ CML, its detection could be further used as a means of monitoring patients undergoing bone marrow transplantation, since its reappearance is associated with early relapse of the disease.

Antibodies, Monoclonal↗
PubMed1993

Immunoblastic malignant lymphoma in adult onset Still's disease.

Lymphadenopathy commonly occurs in patients with adult onset Still's disease (AOSD). Besides the more common reactive hyperplasia, the histological pattern may occasionally be confused with that of malignant lymphoma. A case of AOSD that developed an immunoblastic malignant lymphoma is described. Immunohistochemistry showed the B cell nature of the proliferating cells. As a result, AOSD should be added to the list of systemic rheumatic diseases, the course of which may be complicated by lymphoproliferative malignancies. Our case underlines the need for a careful examination and of close followup to detect this eventuality earlier.

Female↗
PubMed1992

Distinct cytogenetic and clinicopathologic features in acute myeloid leukemia after occupational exposure to pesticides and organic solvents.

BACKGROUND: To study the correlation of environmental exposure to potentially mutagenic agents and the clinicopathologic picture in acute myeloid leukemia (AML), clinical features, morphologic characteristics, immunophenotype, and cytogenetics were studied in 59 patients with newly diagnosed AML. METHODS: Based on interviews on occupational hazards and hobbies showing prolonged contact with pesticides (18 patients) and organic solvents (7 patients), 25 patients were categorized as "exposed". Thirty-four patients were categorized as "unexposed,", based on anamnestic findings. RESULTS: Light microscopic studies showed myelodysplasia involving multiple cell lineages in all assessable patients with professional exposure to pesticides and organic solvents, whereas morphologic aberrations of the non-blast cell population were confined to a minority of cells in unexposed patients. These findings were confirmed by electron microscopic studies in 31 patients. Immunologic analysis showed the presence of a minor megakaryoblastic component in six exposed patients and showed positive findings for the CD34 stem cell marker in 85% of exposed patients, a figure significantly higher as compared with that for unexposed subjects. Cytogenetic studies confirmed the frequent occurrence of 5q and/or 7q aberrations in patients occupationally exposed (10 of 25 cases). Other recurring chromosome aberrations in the exposed group were 17p-, trisomy 11q, and translocation of 16q, 6p, 7p, and 11p, whereas the classic AML-specific translocations (i.e., t[15;17]; t[8;21]) were detected only in unexposed subjects. Conventional chemotherapy achieved complete remission in 1 of 19 exposed patients, as opposed to 14 of 29 unexposed patients, with a median survival of 2 months in the former group and 8 months in the latter. CONCLUSIONS: Taken together, these findings document that AML in patients professionally exposed to toxic substances may represent a distinct cytogenetic and clinicopathologic entity. The clinicobiologic characteristics in these exposed patients are similar to the features of AML arising in patients with prior chemotherapy for another tumor, thus suggesting that similar transformation pathways may underlie leukemogenesis induced by cytotoxic drugs and by environmental exposure to some pesticides or organic solvents.

Acute Disease↗
PubMed1992

Morphologic, immunologic and cytogenetic studies in acute myeloid leukemia following occupational exposure to pesticides and organic solvents.

In order to analyze the correlation between environmental exposure and the clinicopathological picture in acute myeloid leukemia (AML), cytogenetic, cyto-immunologic and clinical studies were performed in 70 newly diagnosed AML patients, 30 of which were anamnestically exposed to pesticides (21 cases) or to organic solvents (9 cases). Clonal chromosome aberrations, with involvement of chromosome 5 and/or 7 were more frequently encountered among exposed patients. While the classical t(15;17), t(8;21) and t(9;11) were detected more frequently among non-exposed patients, other recurring chromosome changes in the exposed group were: rearrangements leading to total or partial monosomy 17p (5 cases), structural aberrations involving the band 16q22 (4 cases), trisomy 11q (2 cases), breaks involving bands 6p23, 7p14, 11q13 (2 cases each). Cytologically, trilineage myelodysplasia was observed in 21 exposed patients, whereas morphologic aberrations of the non-blast cell population were confined to a minority of cells in most patients non-exposed. Immunologic studies revealed positivity for the CD34 stem cell marker in 80% exposed patients vs 22% in the non-exposed group. Conventional chemotherapy achieved complete remission in 3/21 patients exposed and in 16/32 patients non-exposed. Median survival was 2 months in the former group and 9 months in the latter group. These findings show that AML following occupational exposure to pesticides and organic solvents may represent a distinct cytogenetic and clinicopathological entity.

Adolescent↗
PubMed1992

Complement receptor 1 (CR1) expression in chronic myeloid leukemia.

The complement receptor 1 (CR1), also called CD35, is a polymorphic glycoprotein which mediates a variety of neutrophil functions, including phagocytosis and, probably, tumor cell cytotoxicity. The role played by this molecule in chronic myeloid leukemia (CML) is not yet well understood. CML frequently shows a marked decrease of CR1 antigens on both the neutrophil population and myeloid precursors. This reduced expression appears to be related to disease activity, since patients at more advanced clinical stages, as well as those who develop blastic crisis, have been found to express the lowest levels of CR1 antigens. At the onset of the disease low CR1 expression on CML neutrophils seems to be associated with a higher risk of blastic transformation. Furthermore, CML neutrophils deficient in CR1 lack the ability to respond to PMA stimulation, suggesting a failure in CR1 granular storage. In patients lacking CR1, the number of receptors increased to normal levels following exposure of CML cells to therapeutic concentrations of recombinant alpha interferon. The role played by the CR1 molecule in sustaining neutrophil-mediated tumor cell cytotoxicity has yet to be definitively proved; studies performed by our group are relevant here, since complete suppression of tumor lysis following receptor neutralization by anti CR1 monoclonal antibodies was demonstrated in a large number of normal and CML individuals. In CML patients, the evidence of a direct relationship between lytic activity and antigen receptor levels seems to further support the involvement of CR1 molecules in tumor cell lysis, function.(ABSTRACT TRUNCATED AT 250 WORDS)

Blast Crisis↗
PubMed1992

[Current view on non-Hodgkin lymphomas. Origin and evolution in relation to cytogenetic-histologic correlations].

Recent advances in immunology, cytogenetics and molecular genetics has allowed for a better understanding of the origin and evolution of non Hodgkin lymphoma (NHL). Over the last decade a number of recurrent chromosome aberrations has been disclosed and some correlations with well defined histologic subsets of B-cell NHL has been established. Five important cytogenetic-histologic associations has been documented, well defined by combined cytologic, immunologic and genetic investigations: t(14;18) (q32;q21) and NHL of follicle centre cell origin, frequently with follicular histologic pattern; t(8;14) (q24;q32) and Burkitt's lymphoma, Burkitt-like lymphoma or the equivalent small non-cleaved cell category of the "working formulation system"; t(3;22) (q27;q11) and diffuse large cell lymphoma; t(11;14) (q13;q32) and mantle zone lymphoma; trisomy 12 and chronic lymphocytic leukemia and well-differentiated small lymphocytic lymphoma. Molecular genetic studies elucidated some mechanisms operating during the normal lymphocyte differentiation which may be held responsible for the illegitimate recombination between the immunoglobulin genes and some oncogenes normally located on other chromosome regions. It has thus been demonstrated that the early events leading to neoplastic transformation in B-cell neoplasias occur in immature lymphocyte precursors in the bone marrow during the assembly of the immunoglobulin heavy chain gene. According to some recent studies chromosome changes may have prognostic value in B-cell NHL and chronic lymphocytic leukemia and may be employed in clinical practice in the construction of proportional hazard models in several histologic subsets of NHL.

Humans↗
PubMed1991

Lymphoblastic lymphoma with primary splenic involvement and the classic 14;18 translocation.

Clinicopathologic features of a case of lymphoblastic lymphoma (LyL) with the classic 14;18 translocation are described in this article. The patient had prominent splenomegaly with numerous splenic nodules, exhibiting a homogeneous blast cell infiltrate and occasional cells with cleft nuclei, a picture suggestive of high-grade non-Hodgkin lymphoma (NHL) possibly lymphoblastic. Early B-cell features were detected immunologically, thus confirming the diagnosis of LyL. The presence of primary splenic involvement and of the t(14;18)(q32;q21) are unusual in this histologic subset of B-cell NHL, these cytogenetic and clinicopathologic characteristics being typically associated with low- or intermediate-grade NHL of follicle center origin. These features, along with the presence of some centrocytelike cells in the biopsy sections, suggest that an unusual pattern of histologic evolution from a follicle center cell NHL may have occurred in this case of LyL.

Aged↗
PubMed1990

Phase II cooperative study with a new alkylating drug, PTT-119, in the treatment of non-Hodgkin's lymphomas.

In a phase II cooperative study involving eleven Italian haematological units, the efficacy and toxicity of a new alkylating compound, PTT-119, was evaluated in 53 patients with non-Hodgkin's lymphoma (NHL). Forty-five of the patients had been previously treated with various regimens of chemotherapy, the remaining eight were at the onset of the disease. PTT-119 was scheduled at 3.0 mg/kg every three weeks for a minimum of three administrations. Seven patients achieved a complete remission (CR), 19 a partial remission (PR); the overall response rate was 49%. The median duration of response was 6 months. Most frequent adverse effects were alopecia, nausea and vomiting and phlebitis due to the drug infusion. Myelosuppression was severe only in patients with bone marrow involvement or who were heavily pretreated. No liver, cardiac or renal toxicity was recorded. These data indicate that PTT-119 is an effective drug in the treatment of NHL; the matter of its non-cross-resistance with other alkylating compounds warrants further studies.

Adult↗
PubMed1990

Morphologic, immunologic and cytogenetic studies in erythroleukaemia: evidence for multilineage involvement and identification of two distinct cytogenetic-clinicopathological types.

Clinical features, as well as morphology, immunophenotype and cytogenetics were retrospectively studied in 20 patients with an original diagnosis of erythroleukaemia (EL) reclassified according to the FAB criteria. Fifteen patients had de novo EL, five patients had therapy-related EL. Myelodysplasia preceded the onset of EL in eight cases and myelodysplastic features involving multiple haemopoietic lineages were observed at leukaemia presentation in all cases. Immunologic findings confirmed multilineage involvement, showing sub-population of cells expressing platelet-associated markers in more than 50% of cases tested and the presence of a myelomonocytic component, besides glycophorin A-positive cells. Cytogenetically, major karyotype aberrations (MAKA), defined by the presence of three or more aberrant events in the same clone, were observed in 14 cases, minor karyotype aberrations (MIKA) were observed in four cases and normal karyotype in two cases. No differences in the cytological-cytogenetic picture of our patients with de novo EL, and with therapy-related EL were found suggesting that aetiological factors and/or pathogenetic mechanisms common to EL and secondary leukaemia may exist. All patients with MAKA had leftward shift of erythropoiesis with proerythroblasts and basophilic erythroblasts usually representing more than 50% of all erythroid cells. In patients with MIKA or normal karyotype, maturatio of erythroid cells, though morphologically abnormal, was quantitatively preserved and early erythroblasts never exceeded 25% of erythroid cells. Clinically, the haemoglobin level at presentation, as well as in the proportion of patients achieving complete remission after chemotherapy, appeared to be lower in the maturation arrest-MAKA group as compared to the preserved maturation-MIKA/normal karyotype group. Median survival was shorter in the former group (3.5 months) than in the latter (median 13 months). Morphologic-immunologic-cytogenetic studies thus allow for the identification of two distinct cytogenetic-clinicopathological types of EL.

Adult↗
PubMed1989

Cytogenetic analysis of different cellular populations in chronic myelomonocytic leukemia.

Karyotypes of different cellular populations made after separation of bone marrow cells on a gradient of Percoll were evaluated in seven patients affected by chronic myelomonocytic leukemia diagnosed according to FAB criteria. Megakaryocytes, monocytic cells, and granulocytic and erythroid precursors were preferentially collected after centrifugation between density layers of 1045-1050 mg/ml, 1050-1060 mg/ml, and 1065-1070 mg/ml, respectively. The enriched cell fractions were cultured separately and submitted to cytogenetic investigation after short-term culture. Some chromosome aberrations (5q-,+8) were observed in all cellular fractions in three patients, thus providing cytogenetic evidence of the involvement of a common progenitor stem cell in this myelodysplastic disorder. On the other hand, chromosome abnormalities such as del(3)(q21) and del(11)(q23) appeared to be confined to the megakaryocytic and the monocytic fractions, respectively, in two patients. It is conceivable that lineage-restricted aberrations may develop as a consequence of a multistep clonal evolution and may show a close relationship with the hemopoietic differentiative processes.

Aged↗
PubMed1989

Human lymphoblastoid interferon as initial therapy in hairy cell leukaemia: a multicentre study in non-splenectomized patients. Italian Cooperative Group for Hairy Cell Leukemia.

The Italian Cooperative Group for Hairy Cell Leukaemia (ICGHCL), between April 1985 and June 1987, conducted a multicentre study using human lymphoblastoid alpha-interferon as primary therapy as an alternative to splenectomy. Forty-eight evaluable patients with HCL entered the study, 38 of them had splenomegaly, in five patients the spleen was not palpable and five were unfit for surgery because of age and general condition. Daily dose of 3 MU s.c. alpha-IFN was given for 12 weeks, or until a satisfactory and stable response was obtained. Among these 48 patients the response rate after 3 months of therapy was 63%, with seven patients (15%) achieving complete remission and 23 (48%) partial remission; 13 (27%) patients had a minor response. In five patients no response was observed and they died within 2 months of treatment. Five other patients, after an initial response, presented a re-expansion of the disease. Actuarial survival at 30 months was 88.8% for the entire group of 48 patients and 92% for the 38 patients who would normally be treated by splenectomy. Thus, alpha-IFN as primary treatment in HCL offered a reasonable therapy for splenomegalic patients. The timing and validity of splenectomy still remains an open question.

Adult↗
PubMed1988

Significance and limits of cerebrospinal fluid beta-2-microglobulin measurement in course of acute lymphoblastic leukemia.

Cerebrospinal fluid beta-2-microglobulin (CSF-beta 2m) was measured longitudinally in 48 patients affected by acute lymphoblastic leukemia (ALL). Thirteen developed a central nervous system (CNS) involvement during the course of the disease; although moderately higher mean CSF-beta 2m levels were found in these subjects, no significant statistical differences were observed in comparison with patients without this complication and compared with the control group. No correlations were found between beta 2m and other biochemical parameters in CSF. Furthermore, CSF-beta 2m levels appeared to be influenced by previous combined chemoradiotherapeutic treatment for CNS prophylaxis, presence of meningeal non-neoplastic infiltrates, patients' ages, amount of CSF blasts, and their immunological phenotype. In particular, only clearly B-committed leukemic cells, when tested, showed a strong surface expression of beta 2m, as demonstrated by immunocytochemical detection of this protein on cell membrane. However, in specific cases, CSF beta 2m measurement and CSF/serum beta 2m ratio were helpful in diagnosing and monitoring isolated CNS disease. Such findings suggest that CSF-beta 2m assay may be a useful tool in the management of CNS involvement in the course of ALL in only selected patients, as several factors can modify the outcome.

Adult↗
PubMed1987

Monoclonal origin of B cells producing k, lambda and k lambda immunoglobulin light chains in a patient with chronic lymphocytic leukemia.

Immunoglobulin gene rearrangements can be used as genetic markers of clonality in the study of B-cell populations [4]. We have therefore analysed the structure and expression of heavy and light chain immunoglobulin genes in lymphocytes of a patient with chronic lymphocytic leukemia, where we found both k and lambda producing B cells, but in most of the cells both k and lambda chains were co-expressed on the same surface membrane. Single rearrangements were observed in mu, JH, k and lambda DNA sequences, thus providing strong evidence for the monoclonal origin of the cells bearing different light chains. Moreover, the analysis of Ig sequence RNA showed, in addition to normal mu, k and lambda mRNA molecules, high levels of a small lambda related RNA sequence. These findings are discussed in relation to a model of B-lymphocyte differentiation which could be either an additional or an alternative hypothesis to the current one of isotypic exclusion.

Aged↗
PubMed1987

Chromosome abnormalities in myelofibrosis.

Cytogenetic analysis was performed on megakaryocyte-enriched cell fractions obtained by separation on discontinuous Percoll gradients from blood, bone marrow, and ascitic fluid of 12 patients with myelofibrosis with myeloid metaplasia (MMM). The most common abnormalities appeared to involve chromosomes 1, 3, 7, 8, 11, 13, 21 and 22. Although no specific chromosome rearrangements were observed in megakaryocytic fractions from different tissues of the patients with MMM, the presence in one case of a 3q-abnormality restricted to polyploid metaphases only, and of a 3q paracentric inversion in another patient, seems to confirm a close relationship between the involvement of chromosome 3 and dysplastic thrombopoiesis.

Chromosome Aberrations↗