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F Nobile

Publications and source records attributed to F Nobile.

32 records · Page 2Linked to original sources
PubMed1981

Ph1-negative T lymphocytic colonies in agar cultures of peripheral blood in chronic myeloid leukemia.

T lymphocytic colony formation by peripheral lymphocytes separated by discontinuous albumin gradient centrifugation was evaluated in 8 patients with Philadelphia (Ph1)-positive chronic myeloid leukemia (CML). Colonies were obtained using a liquid-on-agar culture system recently introduced (PHA overlayer-leukocyte feeder layer assay) which has been shown to be simple and reliable. The pattern of colony growth in CML and in normal controls was similar, the peak ranging from the 4th to the 6th day. Also the morphological aspects of colonies did not differ in the two groups. Cells recovered from CML lymphocytic colonies were shown to belong to T cell lineage, as they are able to form spontaneous E-rosettes and to respond to mitogenic stimulation in vitro. In contrast, cells recovered from all other cultured fractions failed to display these properties. Cytogenetic analysis showed that T colony cells were Ph1-negative whereas the chromosome anomaly was found in nonlymphoid colonies of the same patients, thus suggesting a nonclonal origin of T lymphocytes in CML.

Agar↗
PubMed1980

Multiple myeloma in husband and wife.

An instance of multiple myeloma (MM) in a married couple is discussed, since cases of MM in husband and wife have rarely been observed. The patients were aged 60 when the disease was discovered, and the interval between the diagnosis in the mates was 44 months. Genetic or environmental factors that could have explained the occurrence of myelomatosis were not found in these spouses. Therefore, on absence of a defined cause, our observation, like others previously reported in the literature, should be considered, although exceptional, a chance event.

Female↗
PubMed1977

Selective removal of plasma cryoglobulins in cryoglobulinaemia.

Cryoglobulins were removed from the plasma of two patients with mixed cryoglobulinaemia (IgM(k)-IgG type) associated with severe membrano-proliferative glomerulonephritis and angiitis. The removal of about half the circulating cryo-Igs ('cryo-Igpheresis') was followed by a brisk rebound in cryo-Igs due to the rapid synthesis rate of monoclonal IgM(k) with anti-IgG activity. 'Cryo-Igpheresis' + cyclophosphamide treatment suppressed the rebound of cryo-IgGs, but not that of the cryo-IgMs. This differential effect was due to decrease of the antibody activity of cryo-IgMs. The clinical implications of such changes need further evaluation.

Cryoglobulins↗
PubMedDate not supplied

In vitro proliferative response of chronic lymphocytic leukemia.

The peripheral blood lymphocytes of 13 previously untreated chronic lymphocytic leukemia (CLL) patients showed a decreased and delayed response in vitro to plant mitogens (PHA and PWM) and specific antigens (PPD and MLC). In addition, the serum of these patients inhibited the mitotic reactivity of both autologous and homologous normal lymphocytes. Since incubation with CLL serum did not affect the SRBC-rosetting capacity of normal lymphocytes, we believe that CLL serum interferes with some metabolic stage in blastogenesis rather than at the level of mitogen membrane interaction. The in vitro transformation of lymph node, bone marrow and peripheral blood lymphocytes in some of these patients was also investigated. Stimulation of peripheral blood cells with plant mitogens resulted in a more serious impairment of the response than that found with bone marrow and lymph node cells. This could be explained by the fact that, although CLL is a widespread lymphoproliferative disorder, some preferential homing of normally reactive cells in the bone marrow and lymph nodes cannot be excluded. Finally, since no stimulation was observed in mixed leukocyte cultures (MLC), our experiments provide evidence that no antigenic differences are detectable in CLL lymphoid populations.

Aged↗
PubMedDate not supplied

Functions of T cells and recruitment of cellular response after in vitro mitogenic stimulation of lymphocytes in chronic lymphocytic leukaemia.

In vitro stimulation of peripheral blood lymphocytes from ten patients with chronic lymphocytic leukaemia (CLL) was investigated under various culture conditions. It was confirmed that the mitogenic reactivity of whole cell populations (PBL) was delayed and depressed. When CLL rosette-forming cells (RFC) were stimulated, their 3H-thymidine uptake was increased, but the pattern of the response was similar to that of whole PBL, thus suggesting some impairment of these cells. Furthermore, in order to evaluate the possible recruitment of B cells, generally thought to be unresponsive, some co-culture experiments were performed in which 10(4) normal lymphocytes and 10(5) CLL whole PBL or RFC-depleted cell populations were stimulated with mitogens. An amplified response of the CLL lymphocytes was obtained in all co-cultures, and this effect was more evident when specific T cell stimulants were used; autologous CLL T lymphocytes, on the contrary, failed to display such a 'synergic' effect. These results indicate that normal lymphocytes are able to recruit a large number of CLL lymphocytes in the mitogenic response; furthermore, the fact that in co-cultures of CLL T-depleted fractions a better response was obtained with T cell mitogens suggests that the definition of CLL as a clonal expansion of unresponsive 'B' lymphocytes may be inadequate.

Aged↗
PubMedDate not supplied

Thrombotic thrombocytopenic purpura: a rare late complication of allogeneic bone marrow transplantation.

Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) usually occurs in a setting of systemic infection or graft-versus-host reaction during the first weeks following transplant. We report a case of fatal TTP that developed eight months after allogeneic bone marrow transplantation (BMT) without any evident association with other transplantation-related complications. Conditioning chemotherapy could have induced the disorder by causing damage to the vascular endothelium. The removal of immunosuppression, including cessation of cyclosporin A (CyA), may have precipitated the disease.

Adult↗
PubMedDate not supplied

In vitro chemosensitivity of chronic lymphocytic leukemia B-cells to multidrug regimen (CEOP) compounds using the MTT colorimetric assay.

BACKGROUND: Anthracycline-containing regimens have given controversial clinical results in CLL. Therefore, we explored the in vitro behavior of CLL B-cells after exposure to the compounds included in the most frequently used combination therapy regimen (CEOP). METHODS: A 4-day MTT colorimetric assay was used in vitro to test the effect of CEOP regimen drugs, either alone or in combination, on CLL B-cells. All drugs but mafosfamide, tested in place of cyclophosphamide, were used at concentrations corresponding to the in vivo dosage employed in the CEOP regimen. Chlorambucil was also studied since it represents the standard treatment for this disease. RESULTS: Epirubicin, prednisone and vincristine displayed a cytotoxic effect in 15, 13 and 4 out of 30 samples, respectively. Combinations of the same drugs showed a synergistic effect in 6 out of 13 assays. A cytotoxic effect of chlorambucil was detected in 2 out of 5 responders to the combination of CEOP regimen drugs, and in 3 out of 7 non responders. Mafosfamide induced a reduction in cell survival in 60-80% of the samples, depending on its concentration. CONCLUSIONS: The MTT assay is suitable for evaluating the in vitro chemosensitivity of CLL B-cells to multidrug regimen compounds. In the present study 40% of samples were resistant to CEOP regimen components in vitro. The possible role of MTT in predicting the clinical response to the CEOP regimen should still be established by prospective in vitro and in vivo studies.

Adult↗
PubMedDate not supplied

Prophylaxis against infections with low-dose intravenous immunoglobulins (IVIG) in chronic lymphocytic leukemia. Results of a crossover study.

BACKGROUND: In a recently reported study, low doses of intravenous immunoglobulins (IVIG) were shown to be as effective as high doses in protecting chronic lymphocytic leukemia (CLL) patients against infections, although a control group was not included. With this background we started a crossover study of low-dose IVIG prophylaxis aimed at investigating its superiority over empirical treatment of infections. MATERIALS AND METHODS: Forty-two CLL patients with hypogammaglobulinemia (IgG < 600 mg/dL) and/or a history of at least one episode of severe infection in the 6 months preceding inclusion in the study were randomly allocated to receive either an infusion of 300 mg/kg IVIG every 4 weeks for 6 months or no treatment. Then they were switched to observation or IVIG for another 12 months; finally, they received IVIG or no therapy for 6 more months. RESULTS: A significantly lower incidence of infectious episodes was observed during IVIG prophylaxis in 30 patients who completed the 6-month period of either observation or IVIG therapy. The same applied to the 17 patients who completed 12 months of either observation or IVIG prophylaxis. Interestingly, the restoration of serum IgG levels obtained in 17 out of 25 patients (mean percent value of IgG increase, 41.8%) did not parallel a decrease in the number of infectious episodes. CONCLUSIONS: A protective effect against infections is demonstrated for low-dose IVIG in the present study. A benefit was shown in patients who completed either 12 or 6 months of IVIG prophylaxis; however, even this low-dose treatment is not a cost effective way to prevent infection in CLL patients.

Aged↗
PubMedDate not supplied

In vitro sensitivity of chronic lymphocytic leukemia B-cells to fludarabine, 2-chlorodeoxyadenosine and chlorambucil: correlation with clinico-hematological and immunophenotypic features.

BACKGROUND: Chlorambucil (CLB), 2-chlorodeoxyadenosine (2-CDA) and fludarabine (FAMP) are among the most widely used drugs in chronic lymphocytic leukemia (CLL). Therefore we evaluated in vitro sensitivity to these drugs and cross-resistance of purine analogs. In addition, we correlated the in vitro data with the main clinico-hematological variables and surface markers. PATIENTS AND METHODS: Eighty CLL samples obtained from 63 untreated and 17 treated CLL patients were tested in vitro with the MTT assay. Lethal dose (LD)50 values were calculated to determine sensitivity to CLB, 2-CDA and FAMP. RESULTS: Samples were clustered either for a one-log increase of LD50 values or for LD50 threshold values of 3 microM for FAMP, 0.3 microM for 2-CDA and 7 microM for CLB, which correspond to the therapeutically achievable plasmatic levels of these drugs. A higher number of samples sensitive to 2-CDA were identified by the first approach; with the second method the relative order of sensitivity was FAMP > 2-CDA > CLB. Concerning 2-CDA and FAMP cross-resistance, out of 61 samples resistant to 2-CDA, 29.5% were sensitive to FAMP. Conversely, 13.9% out of 43 samples resistant to FAMP were sensitive to 2-CDA. No correlation was found between the main clinico-hematological features and the LD50 values of each drug either considering the whole series or only the untreated cases. In vitro drug sensitivity was also evaluated during the steady-state of the disease and at disease progression in six untreated cases. We observed a mean increase in the LD50 values of about 13, 38 and 22 times for CLB, FAMP and 2-CDA, respectively. Among the treated cases, the LD50 values of both purine analogs and CLB correlated with bone marrow histology. CLL cells expressing CD14, CD11c, CD11b, and FMC7 were more resistant in vitro to purine analogs but not to CLB. CONCLUSIONS: This study suggests that i) the purine analogs exert a greater cytotoxic effect on CLL cells; ii) 2-CDA and FAMP are not cross-resistant in vitro in a percentage of CLL samples, iii) a possible change in LD50 values may be related to modification of the disease status, and iv) the expression of certain surface markers, which are CLL-unrestricted, identifies samples with higher in vitro resistance to purine analogs.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Clinical significance of sIL2R, sCD23, sICAM-1, IL6 and sCD 14 serum levels in B-cell chronic lymphocytic leukemia.

BACKGROUND: The aim of the study was to establish the role exerted by some soluble factors in B-CLL disease mechanisms. MATERIALS AND METHODS: Serum levels of sIL2R, sCD23, sICAM-1, IL6 and sCD14 were detected in 47 B-CLL patients. Thirty-seven out of the 47 cases were in advanced/progressive stage, while the remaining 10 patients were defined as smouldering B-CLL. Twenty normal controls provided the reference values. Serum samples of 24 out 37 advanced/progressive cases were measured before and six months after the start of chemotherapy. RESULTS: The advanced/progressive patients showed significantly higher levels of sIL2R, sICAM-1 and sCD23 as compared to normal subjects. Furthermore, sIL2R, sICAM-1 and IL6 values were significantly higher in advanced/progressive B-CLL than in smouldering B-CLL patients. A statistically significant difference was found between smouldering B-CLL and controls for sCD14 only. sIL2R and sICAM-1 levels directly correlated with total tumor mass (TTM) score, sCD23 with both TTM score and lymphocytosis, and sCD14 with IgG serum values. sIL2R and sCD23 levels lowered significantly after chemotherapy, but only sCD23 and TTM variations after chemotherapy were closely correlated. CONCLUSIONS: sCD23 may be considered the only indicator of tumor mass, while the other soluble factors can be released through different mechanisms. In particular, sICAM-1 seems to correlate with the ability of the tumor to spread, while the sCD14 increase could indicate a role for this soluble factor in preventing infections in B-CLL patients.

Aged↗