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A Ambrosetti

Publications and source records attributed to A Ambrosetti.

At least 55 records · Page 3Linked to original sources

Mediastinal large-B-cell lymphoma with sclerosis: a clinical study of 21 patients.

We report the clinical findings of 21 consecutive patients affected by mediastinal large B-cell lymphoma with sclerosis. This type of lymphoma is a recently described histopathologic entity characterized on clinical grounds by distinctive features, which, according to our series, can be summarized as follows: young age (median, 30 years; range, 15 to 42 years), prevalence of females over males (15 v six), rare occurrence of superficial lymph node enlargement (three of 21 patients), and involvement of unusual extranodal sites (kidney six, adrenal cortex two patients). The clinical course appears to be closely related to treatment. In fact, complete remission (CR) was not obtained in the six patients submitted to conventional cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP plus bleomycin (CHOP-Bleo) regimens until 1985, as opposed to 13 CRs reached in the 15 patients subsequently treated with more aggressive regimens after 1985 (methotrexate with leucovorin, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin [MACOP-B], 12 patients; methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone [M-BACOD], two patients; and vincristine, cyclophosphamide, fluorouracil, cytarabine, doxorubicin, methotrexate, and prednisone [F-MACHOP], one patient; plus involved-field radiotherapy, 10 patients). Among the 13 patients who achieved a CR, only one relapse was observed at 10 months. The median overall survival of complete responders after an observation period of 11 to 69 months has not yet been reached, and the event-free survival curve indicates that 90% of patients who achieve CR may be potentially cured.

Adolescent↗

Serum levels of soluble interleukin-2 receptor in hairy cell leukaemia: a reliable marker of neoplastic bulk.

In hairy cell leukaemia (HCL), the strong membrane expression of the Tac antigen, corresponding to the p55 chain of the interleukin-2 receptor (IL-2R), is associated with the presence in the serum of high levels of a soluble form of the same molecule (sIL-2R). Previous observations that therapy-induced clinical and haematologic improvement in HCL is accompanied by a progressive decrease of sIL-2R suggest a possible correlation between sIL-2R levels and tumour burden. To verify this hypothesis, we monitored the variation of sIL-2R values in 13 non-splenectomized HCL patients admitted for treatment with recombinant interferon alpha-2. The data were correlated with the estimated weight of bone marrow (BM) and spleen infiltration, which in these patients almost entirely account for the tumour mass. The regression analysis test showed a direct correlation between sIL-2R values and both BM neoplastic involvement (r = 0.63) and spleen tumour mass (r = 0.76). In addition, the correlation was further improved (r = 0.86) when sIL-2R values were correlated with the total neoplastic mass, as calculated by the sum of spleen and BM neoplastic tissue weight. These data indicate that the detection of sIL-2R in HCL is a reliable non-invasive marker of tumour burden, which can be regarded as an additional useful tool for monitoring treatment response.

Adult↗

Bone marrow transplantation monitoring by DNA analysis.

Variable Number of Tandem Repeats (VNTR) DNA polymorphisms analysis was used in bone marrow transplantation (BMT) follow up. Three Acute Myeloid Leukemia (AML) transplants were investigated with YNH 24/MspI and with EFD 64.2/Rsa or HinfI highly polymorphic VNTRs. Absence of mosaicism and complete engraftment of donor cells was observed in two cases, while mixed hematopoietic chimerism was present in a case in which T cell depleted marrow was transplanted. VNTR systems represent accurate and sensitive individual specific markers for monitoring the clinical course of patients undergoing BMT, and for detecting the biological origin of relapses.

Bone Marrow Transplantation↗

Origin of the soluble interleukin-2 receptor in the serum of patients with hairy cell leukemia.

High levels of soluble IL-2 receptor (sIL-2R) are detectable in the serum of HCL patients. To determine the cell source of this molecule, we evaluated the presence of sIL-2R in the supernatants obtained from in vitro cultures of leukemic (hairy cell, HC) and non-leukemic lymphocytes from six untreated HCL patients and from an additional four patients under therapy with rIFN-alpha 2. We demonstrated that cultured HCs at resting conditions were able to spontaneously release the sIL-2R, whereas control enriched B cells did not. This phenomenon was present only when culturing HCs recovered from patients observed at the time of diagnosis but was not observed during treatment with rIFN-alpha 2. Following activation in vitro with a series of different stimulatory agents including BCGF, phorbol myristate acetate, and anti-human IgM antibody, cultured HCs increased their capability to shed the IL-2R molecules. On the other hand, the release of sIL-2R from enriched T cell populations from HCL patients did not significantly differ from the value obtained in controls. Taken together, these findings provide evidence that leukemic B cells represent the main source of sIL-2R in HCL patients and further emphasize the importance of evaluating this parameter as a relevant marker for monitoring the effectiveness of rIFN-alpha 2 therapy.

Adult↗

Alpha-interferon activated cytotoxic lymphocytes in hairy cell leukemia patients: evaluation of cytotoxic events.

To further define the mechanisms responsible for the alpha-interferon (alpha-IFN) efficacy in the treatment of hairy cell leukemia (HCL), experiments were carried out to specify the cytotoxic events taking place following this type of therapy. Although an increased natural killer (NK) activity was demonstrable after alpha-IFN treatment, evidence has been provided that hairy cells were not specifically lysed either by fresh autologous/allogenic NK lymphocytes or by lymphokine activated killer (LAK) cells. This property could not be induced in vitro by alpha-IFN or by interleukin-2 (IL-2). Our data favour the hypothesis that the increase of NK cell activity observed following alpha-IFN therapy has not a direct antineoplastic effect but is likely to be of relevance for a non-specific enhancement of the host immune system. In alpha-IFN treated HCL this latter property may account for the better resistance to infections which usually represents the major cause of mortality in these patients.

Adult↗

Soluble interleukin-2 receptors in the sera of patients with hairy cell leukemia: relationship with the effect of recombinant alpha-interferon therapy on clinical parameters and natural killer in vitro activity.

In this study we provide evidence that the sera of patients with hairy cell leukemia (HCL) contain a factor that can prevent the binding of a monoclonal antibody specific for interleukin-2 receptor (IL-2R) to its target. This factor corresponds to the soluble form of IL-2R (sIL-2R), as assessed by a specific enzyme-linked immunosorbent assay test, and appears to be released by neoplastic hairy cells. The serum sIL-2R levels were very high at diagnosis and significantly reduced during recombinant alpha-interferon (rIFN alpha 2) therapy. Values of sIL-2R appeared to be inversely related to the natural killer in vitro function displayed by peripheral blood mononuclear cells from the same patients. The presence of sIL-2R in the serum of patients with HCL might be involved in the impairment of cell-mediated immunity observed in these patients and could represent a valuable marker for monitoring different phases of the disease and for modulating IFN therapy.

Antibodies, Monoclonal↗

Mediastinal large-cell lymphoma of B-type, with sclerosis: histopathological and immunohistochemical study of eight cases.

Eight cases of mediastinal non-lymphoblastic large-cell lymphoma have been studied by histopathological and immunohistochemical methods. A common clinical, morphological and immunophenotypic pattern was identified. Six of eight cases proved to be of B-cell origin by the expression of B-associated antigens detected by specific monoclonal antibodies. Cells of large size with nuclei of varying morphology and a peculiar type of fine compartmentalizing fibrosis were observed in all specimens. Clinically the disease was characterized by the young age of the patients, primary mediastinal involvement, aggressive behaviour and spread to unusual sites (kidneys in four cases). This seems to be a hitherto unrecognized entity in the field of non-Hodgkin's lymphomas, often misdiagnosed because of location and a morphology uncommon for B-cell malignancies. Immunohistochemical analysis on frozen tissue sections appears to be mandatory for a correct diagnosis. Nevertheless, this type of lymphoma could be suspected also on the basis of its peculiar clinicopathological characteristics.

Adolescent↗

Alpha-interferon activates the natural killer system in patients with hairy cell leukemia.

To elucidate the mechanisms of alpha-interferon's (alpha-INF) therapeutic effect on clinical and laboratory findings in hairy cell leukemia, we sequentially monitored different immunologic parameters in three patients treated with recombinant alpha-INF. The most evident effect of this treatment on the immune system was the recovery of natural killer (NK) cell in vitro activity of peripheral blood lymphocytes, which was severely impaired before therapy. In particular, NK function began to improve after 3 months, and a complete recovery was obtained after 6 months in all cases. This increase parallels the improvement in clinical and laboratory findings.

Adult↗

Immunohistochemical demonstration of follicular dendritic cells in bone marrow involvement of B-cell chronic lymphocytic leukemia.

Using a sensitive immunohistochemical technique and a specific monoclonal antibody (RFD-3), follicular dendritic cells (FDC) have been demonstrated in a significant proportion (6/12) of bone marrow samples from patients with nodular marrow involvement of B-cell chronic lymphocytic leukemia (B-CLL). In all cases with "packed marrow" involvement and advanced stages of disease the FDC were absent. As these accessory cells are normally present only in the lymph nodes, their presence in the bone marrow is in accord with the view that B-CLL might be the malignancy of an immature subpopulation of lymph node lymphocytes that invade the bone marrow.

Adult↗

B cells in chronic lymphocytic leukaemia. Comparative analysis of blood and bone marrow.

A study was performed on cell suspension from peripheral blood and bone marrow aspirates and on cryostat sections from bone marrow biopsies in order to investigate the membrane phenotype of neoplastic B cells in chronic lymphocytic leukaemia (B-CLL). The immunological analyses, performed on 43 patients, included rosetting ability with sheep and mouse erythrocytes, evaluation of surface immunoglobulins and reactivity with anti-HLA-DR, UCHT 1 (OKT-3 like) and RFA-1 (OKT-1 like) monoclonal antibodies. The results demonstrate that neoplastic B lymphocytes in B-CLL display an identical phenotype in peripheral blood and bone marrow. Possible interpretations on the origin of proliferating cells in B-CLL are discussed.

Adult↗

Distribution and heterogeneity of cells detected by HNK-1 monoclonal antibody in blood and tissues in normal, reactive and neoplastic conditions.

When studied with double staining techniques HNK-1+ cells include subsets not expressing T cell antigens (A), expressing T8 antigens (B) and expressing T4 antigens (C). Cells with phenotype A are observed as the dominant HNK-1+ population (greater than 50% of all HNK-1+ cells) in the blood from controls and from patients with solid tumours, infectious mononucleosis and sarcoidosis. Cells with phenotype B are always a substantial subset (35% of HNK-1+ cells) in the peripheral blood but in patients with B chronic lymphocytic leukaemia and angioimmunoblastic lymphadenopathy these cells are present in an even higher percentage (greater than 50% of all HNK-1+ cells). This cell subset is the only HNK-1+ population found in the few tumour samples where HNK-1+ cells are identifiable. Apart from these few cases of malignancies, the type A and B subsets are rare in the tissues. In these samples Leu 11+ cells seem to be absent. In contrast, cells with phenotype C are a minor population in the blood but represent most HNK-1+ cells in the germinal centres of lymph nodes and their malignant counterparts in follicular centre cell lymphoma. These HNK-1+, T4+ cells are Leu 11-. These phenotypic characteristics indicate that the most efficient NK cells may represent a circulating and not a tissue seeking population.

Adult↗

Immunohistologic study of bone marrow involvement in B-chronic lymphocytic leukemia.

Bone marrow trephine biopsies from 17 patients with B-chronic lymphocytic leukemia (B-CLL) were studied by immunohistologic techniques in order to investigate the cellular phenotypes of both neoplastic (B-lymphoid) and reactive (T-lymphoid) infiltrates. For this purpose, several heteroantisera and monoclonal antibodies against human Ig isotypes, HLA-DR antigens, and T-cell subpopulations were used in immunofluorescence. The findings were analyzed in relationship to the histologic pattern of involvement, as well as to the immunologic data of cell suspensions from peripheral blood. In all cases, the dominant lymphoid population within the bone marrow infiltrates showed identical phenotypic characteristics of B-CLL cells from the blood (HLA-DR+, mu +, most frequently delta +, kappa +, or lambda +, and weakly RFA-1+). The infiltration by these malignant B cells was diffuse in 5 cases and nodular plus interstitial in 12. The number of T cells (UCHT1+, RFA-1+, mu) was variable (5%-25%) in the different samples, but the values were high when compared to the proportion of T cells in normal bone marrow and in the blood of most patients studied. Furthermore, a clear predominance of T cells exhibiting the inducer phenotype (Leu-3+) was observed in all bone marrow samples, which is in contrast with the findings from peripheral blood, where T cells with the suppressor/cytotoxic phenotype (Leu-2+) were dominant. These data suggest a different blood and tissue distribution of inducer and suppressor/cytotoxic cells in B-CLL, which may have important pathophysiologic significance.

Adult↗

Detection of normal and malignant megakaryocytes by anti beta-thromboglobulin serum. An immunofluorescence study.

An antiserum to beta-thromboglobulin was used in immunofluorescence to detect normal and malignant megakaryocytes. In normal peripheral blood and bone marrow smears, only platelets and megakaryocytes were specifically stained by this antiserum. Among 25 cases of acute lymphoid and non-lymphoid leukaemia, only 2 exhibited a clear positivity in a % of blasts, thus proving their megakaryocytic origin. This method is proposed as a simple and useful tool to detect normal and malignant megakaryocytes on smears.

Adult↗

Terminal transferase expression in relapsed acute myeloid leukaemia.

In three cases of acute myeloid leukaemia marked increases in expression of the nuclear enzyme, terminal deoxynucleotidyl transferase (TdT), were observed during disease relapse. The first case was heterogeneous at diagnosis, consisting of subpopulations of large TdT- myeloblasts and small TDT+ blasts; however, at relapse there was complete replacement by TdT+ lymphoblasts. The other cases at diagnosis were both typical acute myeloid leukaemia, TdT-; at relapse, one showed a mixture of TdT- myeloblasts and TdT+ lymphoblasts, while in the other, TdT was demonstrated on a subpopulation of myeloblasts. No chromosomal abnormalities were found. It is suggested that in the first two cases these phenomena may have been due to leukaemic involvement of a pluripotential stem cell, or that sub-clones with different properties may have coexisted. In the third case at relapse, TdT was expressed aberrantly by malignant myeloid cells.

Aged↗

[The use of betamethasone in polychemotherapy of lymphoproliferative diseases].

In recent years very encouraging results have been obtained in the treatment of lymphoproliferative disorders with the use of combination chemotherapy regimens. We have treated with protocols including betamethasone 29 patients with Hodgkin's disease, 33 affected by non-Hodgkin's lymphomas, 29 with chronic lymphocytic leukemia, 7 with acute lymphoblastic leukemia and 9 patients affected by multiple myeloma. Results have been very satisfactory in patients with advanced stage Hodgkin's disease (67% complete remission), in high malignancy non Hodgkin's lymphomas (47% complete remission) and in acute lymphoblastic leukemia (100% of patients in complete remission). Our results suggest that the use of betamethasone as a part of combination chemotherapy regimens may be very useful in the treatment of lymphoproliferative disorders.

Adolescent↗