Biomedical subjects

F Lauria

Publications and source records attributed to F Lauria.

At least 109 records · Page 6Linked to original sources

PubMed1986

Molecular and immunological evidence of B-cell commitment in "null" acute lymphoblastic leukaemia.

The DNA configuration of the immunoglobulin (Ig) heavy and light chain genes and the expression of B-cell-related markers were evaluated in 13 cases of non-T, non-B, non-common ("null") acute lymphoblastic leukaemia (ALL). A rearrangement of the Ig heavy-chain gene was found in all cases studied; in 5 of these a structural reorganization of the kappa or lambda light chain gene was also demonstrated. Leukaemic cells from 10 of the 13 cases analysed showed one or more B-cell antigens, the expression of which followed a sequential order of presentation (OKB2, B4, BA-1, B1). The B-cell commitment was confirmed by means of a sensitive immunoperoxidase assay which revealed a weak expression of the common ALL (cALL) antigen in 7/10 cases tested, which were all cALL-negative by conventional immunofluorescence techniques. These findings suggest that in "null" ALL the neoplastic cells show molecular and immunological evidence of B-cell differentiation and that most cases may indeed be characterized by "early" cALL with a very low density expression of the cALL antigen. This was further documented in one case in which the expression of the cALL antigen (and of other B-cell markers) could be induced after exposure to 12-O-tetradecanoylphorbol-13-acetate (TPA). The presence in a few cases of myeloid features, particularly when the cALL antigen could not be demonstrated by the immunoperoxidase assay, suggests that the leukaemic process may sometimes involve a very early progenitor cell capable of both lymphoid and myeloid phenotypic differentiation. The heterogeneity of "null" ALL documented by this study may help to explain the variable clinical course and prognosis of these patients.

Antigens, Neoplasm↗

PubMed1986

Normal T-lymphocyte function in patients with Hodgkin's disease in long-lasting remission.

In 18 patients with Hodgkin's disease (HD) in long-lasting remission (more than 5 years), the distribution of circulating T-lymphocytes was analyzed using a series of monoclonal antibodies (OKT3, T4, T8, Leu-7, Leu-11 and T10) and correlated with cell function (helper capacity in a pokeweed mitogen system and natural killer (NK) activity). A reduced proportion of OKT4 (helper/inducer)-positive cells associated with a normal absolute number was consistently accompanied by a significant increase (p less than 0.005) in the proportion and absolute number of OKT8 (suppressor/cytotoxic)-positive cells. The OKT4-positive cells, despite their moderate percentage reduction, showed normal helper activity. A more extensive characterization of the lymphoid population in these patients documented a preserved cytotoxic function in a 51Cr release assay and increased proportion of cells expressing NK-associated antigens (Leu-7, Leu-11, OKT10) with a high number of cells coexpressing OKT8 and Leu-7. It is suggested that in patients with Hodgkin's disease in long-lasting remission no laboratory (or clinical) evidence of cellular immunodeficiency can be documented.

Adult↗

PubMed1986

Lymphoblastic lymphoma in adolescents and adults. Clinical, pathological and prognostic evaluation.

Sixty-four adult patients with lymphoblasts lymphoma (LB) identified according to Kiel Classification were analyzed retrospectively. Three distinct clinical presentations were identified: prevalent abdominal disease (29 pts = 45.3%), prevalent mediastinal disease (14 pts = 21.9%) and prevalent superficial node involvement (21 pts = 32.8%). On histological grounds, the patients with abdominal disease were mainly associated to "Burkitt like" cell lymphoma (55%); patients with mediastinal disease to convoluted cell type (58%); and those with superficial node disease to unclassified cell type (48%). Immunological studies showed a significant correlation between mediastinal disease and T phenotype (P = 0.0011), abdominal disease and B phenotype (P = 0.00042), and between superficial node disease and non-B non-T phenotype (P = 0.00024). Survival was independent of the type of clinical presentation and protocol employed but was correlated with the stage (P less than 0.0005), symptoms (P less than 0.025), bulky disease (P less than 0.025) and bone marrow involvement (P less than 0.025). Furthermore the response to therapy was strongly correlated with prognosis (P less than 0.0001) with 34.5 months median survival for complete responders, 9 months for partial responders, and 3 months for non-responders. Four patients underwent bone marrow transplantation (three autologous and one allogeneic BMT in a patient in leukemic phase); three of them are still in CR (18, 22, and 27 months from the transplant) while one patient had an early relapse and died 3 months later.

Adolescent↗

PubMed1986

Hodgkin's disease (HD): a historical perspective.

Five hundred and seven patients with Hodgkin's lymphoma (HL), forming the basis of our 18 years experience, are retrospectively analyzed. Four therapeutic periods are recognizable: The 1966-1970 period was characterized by the absence of treatment and management policy. The 55 patients entered in this period experienced 70 and 56% survival at 5 and 10 yr, respectively, from diagnosis. The 1971-1974 period was characterized by the increasing knowledge of staging relevance and therapeutic approaches. The 153 patients who were treated in this period experienced 72 and 60% survival at 5 and 10 yr, respectively. The 1975-1980 period was characterized by a large combination of MOPP and radiotherapy. The 216 patients who entered this period observed 80 and 72.5% survival at 5 and 10 yr, respectively. The last therapeutic period (1980 to present time) is characterized by the increasing relevance of prognostic factors and alternating use of MOPP and ABVD as non-cross resistant regimen. The 83 patients who entered this period showed 90% survival at 5 yr. Both survival and disease-free survival were positively influenced by the change of therapeutic strategies during the four periods (P less than 0.005). Although better results have been recorded moving from one to the next therapeutic period, the present policy has been also based on the recognition of a high number of late complications due to the therapy. Preliminary results about the present therapeutic experience seem to indicate both a good remission rate and low incidence of complications.

Adult↗

PubMed1986

Reduced natural killer T-cells in B-cell chronic lymphocytic leukaemia identified by three monoclonal antibodies: Leu-11, A10, AB8.28.

The proportion of E-rosette positive T-lymphocytes capable of reacting with three monoclonal antibodies (MoAbs)--Leu-11, A10, AB8.28--which appear to recognize specifically natural killer (NK) cells, was assessed in a series of untreated patients with B-cell chronic lymphocytic leukaemia (B-CLL). Irrespective of the clinical stage of the disease, the capacity of B-CLL T-lymphocytes to react with all three MoAbs was significantly reduced compared with that of normal circulating T-cells (Leu-11: 2.5% +/- 1.9 SD; A10: 2.3% +/- 1.3; AB8.28: 7% +/- 6.6 v Leu-11: 13.5% +/- 4.5; A10: 8.5% +/- 4.6; AB8.28: 12% +/- 5.5). Furthermore, a marked difference was demonstrated between the reactivity with the Leu-11, A10, AB8.28 MoAbs and the proportion of Leu-7 positive T-cells, which in B-CLL is significantly higher than in normal blood (23% +/- 12.1 v 11.9% +/- 5.9). These findings are in agreement with previous evidence of a discrepancy in B-CLL between the phenotypic expression, assessed by Leu-7 positivity, and the true functional activity of NK T-cells, and suggest that the Leu-11, A10 and AB8.28 MoAbs correlate well with the depressed NK function found in this disease.

Antibodies, Monoclonal↗

PubMed1986

High-dose therapy followed by autologous bone marrow transplantation (ABMT) in previously untreated non-Hodgkin's lymphoma.

13 previously untreated patients with poor prognosis non-Hodgkin's lymphoma (NHL) underwent high-dose therapy followed by autologous bone marrow transplantation (ABMT). All patients experienced a great cytoreductive effect and 9 of them reached a complete remission (mean duration 32 months). The best results were observed in patients with more limited disease and in those without symptoms. 7 patients still remain in complete unmantained remission 15-46 months from the transplant. The probability of survival is 74% at 46 months. No therapy-related deaths were recorded. In differentiating our preliminary approach, we propose high dose therapy followed by ABMT as induction phase in patients with stage II and as consolidation after first line therapy in patients with stages III-IV. Further studies are warranted to determine which type of lymphoma may benefit more and which conditioning regimens may improve the remission rate.

Adolescent↗

PubMed1986

Analysis of T-cell receptor beta chain (T beta) gene rearrangements demonstrates the monoclonal nature of T-cell chronic lymphoproliferative disorders.

We investigated the rearrangement patterns of the gene coding for the beta chain of the T cell receptor (T beta) in 11 patients with T-cell derived chronic lymphoproliferative disorders, including T-cell prolymphocytic leukemia (T-PLL) and T-cell chronic lymphocytic leukemia (T-CLL). We found that all five cases of T-PLL, and five of six cases of T-CLL, displayed T beta-gene rearrangements, clearly establishing their monoclonal nature. Clonality could not be determined in one case of T-CLL where the T beta gene was found unrearranged. Our results demonstrate that the majority of cases of both clinically aggressive T-PLL and clinically indolent T-CLL are monoclonal. These results suggest that the analysis of T beta gene rearrangements represents a valid tool for the differential diagnosis and clinical monitoring of T-cell derived chronic lymphoproliferative diseases.

Humans↗

PubMed1986

Phenotypic and functional characterization of the circulating NK compartment in hairy cell leukaemia.

A phenotypic and functional analysis of the circulating natural killer (NK) cell population was carried out in a series of patients with hairy cell leukaemia (HCL). The overall mean NK activity of both the mononuclear and T cell fractions was reduced compared to that of normal controls (466 lytic units (lu) v 573 lu and 226 lu v 381 lu, respectively), though this difference did not reach statistical significance (P less than 0.05). Individual analysis of the data showed that in five out of 15 and in seven out of 16 cases the K562 killing by the mononuclear and T cells respectively was below the lowest s.d. limit for normal subjects. This reduced NK function was associated with a decreased ability of the effector cells to bind the target. The NK response to exogenous human leucocyte interferon was also generally depressed in cases with a low basal NK activity. The functional studies were complemented with the evaluation of the membrane expression of NK associated antigens. The percentage of circulating T cells recognized by the monoclonal antibody (MoAb) Leu-7 was significantly higher (P less than 0.001) in HCL than in normal blood (25.2% +/- 10.2 v 11.9 +/- 5.9 s.d.). However, the reactivity with two other NK-related MoAb, Leu-11 and AB8.28, was significantly lower (7.1% +/- 6.9 and 9.8% +/- 8.5; P less than 0.002) than with Leu-7 and moderately reduced compared with that of normal circulating T cells (11.7% + 6.1 & 12% + 5.5). These findings suggest that in a proportion of patients with HCL there is an impairment of the NK compartment, which may contribute towards the occurrence of the infective complications which are the primary cause of death in this disease.

Antibodies, Monoclonal↗

PubMed1985

T-helper phenotype chronic lymphocytic leukaemia and "adult T-cell leukaemia" in Italy. Endemic HTLV-I-related T-cell leukaemias in southern Europe.

Sixteen Italian patients with chronic T-cell lymphocytic leukaemia (T-CLL) and leukaemic T-helper phenotype lymphocytes (Thp-CLL) were investigated for serum antibodies against human T-cell leukaemia virus I (HTLV-I) or its integrated DNA sequences. Common features of this series of patients were an aggressive clinical course with poor response to treatment, high white blood-cell count, bone-marrow infiltration, splenomegaly, and chromosome abnormalities. Three patients had skin infiltration and one had hypercalcaemia. Immunological analysis showed a Thp (OKT4+) in all cases, and a heterogeneity, within the OKT4 population, of phenotypes and functional activities. Three patients had either HTLV-I integrated DNA sequences or anti-HTLV-I serum antibodies, or both. These patients had not received any blood transfusions, denied intimate contact with foreigners, and had always lived in small towns of central or southern Italy. Clinical and immunological findings in this series of patients suggest that both HTLV-I related and unrelated cases of Thp-CLL should be regarded as one disease arising from the same subpopulation of mature T-lymphocytes.

Adult↗

PubMed1985

Multimarker phenotypic characterization of adult and childhood acute lymphoblastic leukaemia: an Italian multicentre study.

A multicentre phenotypic study was carried out in Italy combining conventional immunological techniques with monoclonal antibody (MoAb) analysis in 190 cases of adult and childhood acute lymphoblastic leukaemia (ALL), in an attempt to define better the lineage relationship of the neoplastic cells. Of the 140 children evaluated, 79.3% expressed the common ALL (cALL) antigen (all analyses performed by MoAb), 11.4% were T-ALL and 9.3% were non-T, non-B, non-common ('null') ALL. The proportion of adult cALL cases was slightly lower (64% of the 50 cases studied) than that of childhood ALL, whilst the incidence of T-ALL was significantly higher in adults than in children (26% v. 11.4%, P less than 0.05). Because of the high proportion of cALL cases, the incidence of 'null' ALL in adult patients was similar (10%) to that of children, and lower than previously reported. The recognition of early pre-T-ALL cases (T1+, RFT2+, T10+, T6-, T11-, E-) contributed to the overall low proportion of 'null' ALL; prior to the use of MoAb, such cases would probably have been classified as undifferentiated acute leukaemia or 'null' ALL. The search for B-cell-related markers showed that the incidence of pre-B-ALL cases (cytoplasmic immunoglobulin positive cases) was similar in adults and in children (25.6% and 32%, respectively). Furthermore, the great majority of cases studied expressed the BA-1 antigen (92.8% of adults and 79% of children), whilst the BA-2 antigen was found in 53% of cases (tested only in children), confirming a hierarchy in the expression of B-cell related markers in cALL: BA-1, BA-2, CyIg. Several of the 'null' cases also expressed the BA-1 antigen on a variable proportion of cells, pointing to a possible B-cell origin of the blasts. This multicentre study shows that both in adult and in childhood ALL the combined use of conventional immunological markers and of a panel of MoAb allows identification of the cell lineage of the great majority of cases, thus reducing the number of 'null' ALL. Furthermore, these findings suggest that practically all cases of ALL belong either to the T or to the B cell compartment and that the neoplastic cells appear blocked at different levels along the lymphoid differentiation pathway.

Acute Disease↗

PubMed1985

Malignant histiocytosis (true histiocytic lymphoma) clinicopathological study of 25 cases.

Twenty-five cases originally diagnosed as malignant histiocytosis/true histiocytic lymphoma were reviewed according to both pathological and clinical criteria. Microscopically, they were characterized by large, pleomorphic tumour cells showing variable degrees of atypia and phagocytic activity. The growth more often appeared as diffuse, being limited to the sinuses in only two cases. Cytochemistry on touch imprints showed tumour cells strongly positive for acid phosphatase and alpha-naphthyl-acetate esterase in all the samples tested. Immunohistochemistry on paraffin embedded sections using specific antisera showed tumour cell positivity for lysozyme in 12 of 25 cases, for alpha 1-antitrypsin in 24 of 25 cases and for alpha 1-antichymotrypsin in all 25 cases. Immunophenotyping on frozen-sections in three cases displayed a clear-cut reactivity of the neoplastic cells with the monoclonal antibody OKM1. Clinically, the disease more often presented with B-symptoms, lymphadenopathy and mediastinal involvement. In the majority of the patients (18/25) it had a fatal and rapid course, despite therapy (median survival: 9 months; mean survival: 12 months). The presence of B-symptoms and bulky disease appeared as the only factors influencing the prognosis, both suggesting a more aggressive course of the tumour.

Adolescent↗

PubMed1985

Non-Hodgkin's lymphomas in leukaemic phase: incidence, prognosis and therapeutic implications.

248 patients with non-Hodgkin lymphomas (NHL) were retrospectively analysed in an attempt to elucidate the risk factors, the prognostic importance and the therapeutic implications of blood involvement. Bone marrow involvement and large spleen were significantly correlated to leukaemic manifestations (P less than 0.0001 and P less than 0.0005, respectively); conversely no correlations were seen with bulky disease and symptoms. Among low-grade malignant lymphomas (LGML) centroblastic-centrocytic follicular and diffuse or diffuse and "CLL" subtypes were mostly associated with blood involvement (31% and 55%, respectively). Among high-grade malignant lymphomas (HGML) lymphoblastic type is more frequently associated with blood involvement (42%) than the other subtypes. Blood involvement was not clearly correlated with the prognosis either in LGML (median survival 39 and 36 months for leukaemic and non-leukaemic patients, respectively) or HGML (median survival 12 and 18 months, respectively), although a shorter survival of leukaemic than non-leukaemic lymphoblastic lymphoma was observed (median survival 8 months versus 14 months, respectively). The poorer response rate to therapy of leukaemic patients (median duration of CR22 and 5 months in LGML and HGML, respectively) as opposed to non-leukaemic patients (median duration of CR 29 and 23 months, respectively) led us to consider an alternative treatment in such patients.

Adolescent↗

PubMed1985

T-cell prolymphocytic leukaemia: a clinical and immunological study.

2 cases of T-cell prolymphocytic leukaemia (T-PLL) were investigated for their reactivity with a series of monoclonal antibodies (MoAbs) as well as for the cytochemical expression and functional activity of the pathological cells. Both patients showed morphological (large cells with abundant cytoplasm and eccentric and irregularly shaped nucleus with large and prominent nucleoli) and clinical (high leucocyte count and splenomegaly) features typical of T-PLL. The cells from 1 patient expressed a helper/inducer phenotype (T4+, T8-) and were reactive with the anti-Tac (interleukin-2 receptor) MoAb, while the other case co-expressed both the T4 and the T8 antigens. The response to phytohaemagglutinin and the natural killer activity (assessed by 51chromium release) were significantly reduced in both cases, while the helper capacity, tested in a pokeweed mitogen-driven system, was maintained only in the 1st case. This latter case which expressed a more mature phenotype (T4+, T8-) responded well to chemotherapy.

Acid Phosphatase↗

PubMed1985

Interleukin 2 (IL 2) and interferon-gamma production by T lymphocytes from patients with B-chronic lymphocytic leukemia: evidence that normally released IL 2 is absorbed by the neoplastic B cell population.

The capacity of T lymphocytes from patients with B cell chronic lymphocytic leukemia (B-CLL) to release interleukin 2 (IL 2) and interferon (IFN)-gamma was assessed following various stimuli. The spontaneous release of IL 2 and IFN-gamma was practically absent both with B-CLL and normal T lymphocytes. By contrast, after stimulation with phytohemagglutinin (PHA) or with PHA plus 12-O-tetradecanoylphorbol-13-acetate, the production of IL 2 and IFN-gamma by B-CLL T lymphocytes was similar to that of normal T lymphocytes, irrespective of the reversed T lymphocyte subset distribution (OKT4/OKT8 ratio) observed in B-CLL. However, the titer of IL 2 was greatly reduced when autologous leukemic B cells were added to the culture system. Unlike IL 2, the presence of leukemic B cells did not affect the titer of IFN-gamma in the culture supernatants. The indication that IL 2 may be adsorbed in vivo by the neoplastic B cells was further confirmed by the demonstration of the IL 2 receptor (revealed by anti-Tac monoclonal antibody) on the leukemic B cells, particularly following mitogenic stimulation, and by the evidence that exogenous IL 2 can be directly absorbed by untreated B-CLL T lymphocytes to release IFN-gamma and IL 2 is preserved, but that IL 2 may be rapidly removed by the neoplastic B-CLL cells, thus contributing to the well-documented T lymphocyte abnormalities present in this disease.

Absorption↗

PubMed1984

Impaired distribution of T-lymphocyte subsets in patients with haemophilia.

The distribution of T-lymphocyte subsets was assessed using monoclonal antibodies in 20 symptom-free patients with haemophilia. In 15 patients, the T-cell subsets appear substantially balanced with only a moderate reduction in the proportion and absolute number of OKT4 positive cells. In the remaining 5, all with a reversed OKT4/OKT8 ratio, the proportion and absolute number of OKT4 positive cells was significantly reduced (p less than 0.0002) while the absolute number of OKT8 positive cells was normal or reduced although the proportion of these cells appeared increased. Functional studies, testing the proliferative response to PHA and PWM, were normal in all cases including those with immunological abnormalities. These results suggest that a proportion of patients with classic haemophilia show some immunological abnormalities similar to those observed in patients with acquired immunodeficiency syndrome and that regular evaluation of several immunological parameters is warranted in these patients.

Adolescent↗

PubMed1984

Prognostic significance of lymphography in stage IIIs Hodgkin's disease (HD).

Ninety-six patients with pathological stage IIIs Hodgkin's disease, uniformly treated with six cycles of MOPP and TNI, were retrospectively analysed in an effort to determine whether the lymphographic aspect of lymph nodes influence the prognosis. Case material was grouped according to the presence of lymph nodes less than 3 cm in diameter or larger at lymphography. Five-year survival and disease-free survival were 85 and 78% for patients with small lymph node involvement, compared to 48 and 30% for patients with larger lymph nodes. The comparative analysis between the lymphographic aspect and other prognostic factors shows that large lymphographic involvement is strongly correlated with the presence of large spleen involvement (P less than 0.0000029), followed by stage III2 (P less than 0.000612), followed by greater than or equal to 5 involved sites (P less than 0.012), followed by age greater than 40 yr (P less than 0.047). Conversely, no significant correlation was found with symptoms, histology and mediastinal involvement. Modifications of current treatment for both large and small lymph node involvement are discussed.

Adult↗

PubMed1984

B-chronic lymphocytic leukaemia patients with stable benign disease show a distinctive membrane phenotype.

The circulating B cells of 98 patients with B-CLL were analysed with a panel of conventional markers and monoclonal antibodies including RFA-1 and RFA-4. A subgroup of patients was defined with a distinctive double membrane marker phenotype (RFA-1+, RFA-4+). These patients showed features of clinical stability. Their physical signs, haematological features and lymphocyte counts remained unchanged for 5-10 years: therefore, the RFA-1+, RFA-4+ membrane phenotype appears to identify a subgroup of B-CLL patients with a particularly non-progressive disease.

Aged↗

PubMed1984

Discrepancy between phenotypic and functional features of natural killer T-lymphocytes in B-cell chronic lymphocytic leukaemia.

The phenotypic expression and functional capacity of natural killer (NK) T-lymphocytes (E+, OKT3+) were analysed in a series of untreated patients with B-cell chronic lymphocytic leukaemia (B-CLL). The mean value of NK activity of B-CLL T-lymphocytes, tested against the K562 cell line, was significantly depressed (P less than 0.01) in the 20 cases studied, compared with that of normal T-cells. Incubation with human leucocyte interferon produced an increase (P less than 0.05) in NK activity, although the mean value was still significantly lower (P less than 0.05) than that obtained with normal T-cells. Furthermore, the formation of effector-target conjugates was significantly lower (P less than 0.01) among B-CLL T-cells compared with normal T-lymphocytes. Despite the reduced NK functions observed in the majority of B-CLL patients, the capacity of T-cells to react with the monoclonal antibody (MoAb) Leu-7 (HNK-1 clone), assessed in 60 patients, was significantly higher (P less than 0.001) in B-CLL than in normal blood (mean 24% +/- 10.6 SD v 9% +/- 4.2), irrespective of the clinical stage of the disease. These findings suggest that the reduced cytotoxic ability of B-CLL T-lymphocytes may be due either to an expanded population of immature T-cells which already express a cytotoxic-like phenotype (E+, OKT3+, HNK-1+) but which lack adequate cytotoxic functions, or, alternatively, to an intrinsic defect of the natural effectors present within the T-cell population of B-CLL. The T-cell functional abnormalities documented in this study, together with other defective functions previously described, may be implicated in some of the complications frequently associated with B-CLL, particularly the high incidence of secondary neoplasms. There is growing evidence that natural cytotoxicity may play a major role in the immune surveillance system, both against tumour cells and virus-infected cells (Herberman & Ortaldo, 1981). Natural killer (NK) cells are a morphologically homogeneous population of large granular lymphocytes with azurophilic granules in the cytoplasm (Timonen et al, 1981), which are non-adherent and express receptors for the Fc portion of IgG. About 50% of these cells form rosettes with sheep red blood cells (E-rosettes) (West et al, 1977). A monoclonal antibody (MoAb) which appears to react with practically all human NK cells (HNK-1 clone, Leu-7; Becton Dickinson) has been recently produced (Abo & Balch, 1981).(ABSTRACT TRUNCATED AT 400 WORDS)

Antibodies, Monoclonal↗