Search PubMed⌕ Search

Biomedical subjects

F Mandelli

Publications and source records attributed to F Mandelli.

At least 361 records · Page 20Linked to original sources

Evaluation of factor VII antigen in factor VII congenital deficiencies with a new ELISA assay.

An evaluation of a new Enzyme Linked Immunosorbent Assay (ELISA) factor VII:Ag assay in factor VII congenital deficiencies was carried out. This assay was compared to factor VII:C assay and the Inhibitor Neutralization Assay (INA) for factor VII:Ag, both in normals and F VII-deficient patients. The correlations between ELISA F VII:Ag and VII:C, as well as the one between INA F VII:Ag and VII:C, were good (r = .86 and .81, respectively). The correlation between the two immunologic methods of assay in normals was fairly good (r = 0.73, P less than 0.001); whereas in mild F VII deficiencies (heterozygotes for F VII deficiencies), the two methods correlated very well (r = .96). In the severe deficiencies, ELISA F VII:Ag assay allowed the evaluation of F VII protein levels below 1 u/dl. The sensitivities of the INA and ELISA assays were evaluated by creating artificially prepared plasmas containing serial amounts of purified F VII: INA was unable to pick up F VII protein levels lower than 75 ng/ml, whereas the ELISA assay could detect up to 5 ng of F VII.

Adult↗

Risk of iron overload and 'hemochromatosis allele(s)' in patients on maintenance hemodialysis.

In the present study, we have evaluated the relationship between serum ferritin (SF) levels, 'hemochromatosis allele(s)', blood transfusions and iron parenteral administration in 69 hemodialysis patients. We demonstrated significantly higher SF levels in patients with hemochromatosis allele(s) (HA+) than in patients without hemochromatosis alleles (HA-). In addition, HA+ patients who had received blood transfusions up to 15 months prior to the study had SF levels even higher than those without blood transfusions. On the other hand, HA- patients had normal levels of SF, independent of blood transfusions. After intravenous administration of 1 g iron saccharate, SF levels were significantly higher only in HA+ transfused patients. In conclusion, our study demonstrated that HA+ patients are at a higher risk of iron overload and therefore the use of transfusional and/or parenteral iron should be strictly limited.

Adolescent↗

Glucocorticoid receptors predict response to combination chemotherapy in patients with acute lymphoblastic leukemia.

Glucocorticoid receptor levels were quantified in leukemic blasts from peripheral blood of 86 patients with acute lymphoblastic leukemia. Subsequent achievement of complete remission correlated with high receptor levels. Forty-seven of 50 patients with leukemic cells containing more than 6,000 receptor sites and 22 of 36 patients with cells containing less than 6,000 receptor sites achieved remission. The study of glucocorticoid receptors in leukemic cells may predict response to combination chemotherapy in acute lymphoblastic leukemia patients.

Acute Disease↗

Prognosis in chronic lymphocytic leukemia: a retrospective multicentric study from the GIMEMA group.

Clinical and biological data were evaluated using Desu univariate analyses or Cox multivariate analyses in a series of 1,777 chronic lymphocytic leukemia (CLL) patients from an Italian Cooperative Group. In univariate analyses, age and sex of patients, presence of bone marrow (BM; greater than or equal to 50%), and peripheral blood (PB; greater than or equal to 60,000/microL) lymphocytosis, anemia (hemoglobin [Hb] less than 11 g/dL), thrombocytopenia (less than 100,000/microL), direct Coombs' test positivity, hepatomegaly, splenomegaly, and extent of lymph node involvement were shown to be of significant prognostic value. Multivariate analyses, through a stepwise procedure, showed that the most important prognostic variables are Hb, hepatomegaly, lymph node involvement, PB lymphocytosis, and age and sex of patients. Further covariates would produce an improvement having a nonsignificant P value. Based on the results of multivariate analyses, a four-step staging using the significant variables of the Cox model is proposed.

Adult↗

Treatment of acute myelogenous leukemia in children: results of the Italian Cooperative Study AIEOP/LAM 8204.

One hundred thirty-three children with acute myelogenous leukemia (AML) entered the multicenter Pediatric Branch of the Italian Association Against Leukemia trial AIEOP/LAM 8204 between July 1982 and May 1986. Induction therapy consisted of two courses of daunomycin (DNM) plus cytosine arabinoside (Ara-C). Those patients who achieved remission were given four courses of consolidation with DNM, 6-thioguanine (6-TG) and escalated doses of Ara-C followed by six courses of sequential continuation therapy using monthly pairs: etoposide (VP-16)/Ara-C, Ara-C/6-TG, and DNM/Ara-C. Periodic intrathecal Ara-C was used for CNS prophylaxis. One hundred seven (80%) children achieved complete remission (CR). Kaplan-Meier estimates of 3-year disease-free survival (DFS) and event-free survival (EFS) are 41% and 33%, respectively. Relapses occurred in 34 patients after 5 to 97 weeks (32 marrow; 2 marrow plus CNS). Overall, 14 patients died of complications during treatment (nine during induction; five during the postremission phase), mostly from infection. Risk factor analysis showed that induction failures occurred predominantly in children with French-American-British (FAB) M5 and in those with elevated leukocyte counts; by step-up Cox analysis, only FAB subtype was predictive of remission success. None of the variables examined was significant for predicting the duration of remission. Hyperleukocytosis was predictive of a significantly worse EFS rate. These results are encouraging and further support the use of intensive chemotherapy programs for childhood AML.

Adolescent↗

Sequential combination chemotherapy of high-grade non-Hodgkin's lymphoma with 5-fluorouracil, methotrexate, cytosine-arabinoside, cyclophosphamide, doxorubicin, vincristine, and prednisone (F-MACHOP).

An intensive treatment program was developed to achieve durable remissions in a high proportion of previously untreated patients with advanced stages of diffuse high-grade non-Hodgkin's lymphoma (NHL). Fifty-six patients (15-68 years) received a course of F-MACHOP (5-fluorouracil, methotrexate, cytosine-arabinoside, cyclophosphamide, doxorubicin, vincristine, and prednisone) every 3-4 weeks for 6 courses. Cycle active drugs were sequentially administered to expose rapidly proliferating tumor cells to the synergistic effects of these agents throughout the cell cycle. Forty-three patients achieved complete remission (77%) and 80% of the complete responders are projected to be alive and disease-free at 4 1/2 years (median follow-up 33 months). Up to 70% of all patients are predicted to be alive at 5 years. Bulky tumor, "B"-symptoms and lymphoblastic histology were poor prognostic factors, particularly when associated with clinically detectable disease after three courses. Toxicity included transitory myelodepression in most patients (2 septic deaths). This protocol provides effective and tolerable therapy for the majority of patients with advanced stages of diffuse aggressive NHL.

Adolescent↗

Increased susceptibility of peripheral mononuclear cells of leukemic patients to HTLV-I infection in vitro.

Peripheral mononuclear cells (MNC) collected from 12 healthy donors and 44 leukemic patients at various stages of the disease were tested for natural killer (NK) activity and for their susceptibility to HTLV-I infection in vitro, measured in terms of percentage of p19 positive cells. MNC from leukemic donors at any stage of leukemia (ie, onset or relapse, ON/REL; complete remission or off-therapy, CR/OT donors) were highly susceptible to HTLV-I infection. This was true for acute leukemias of lymphoblastic (ALL) or nonlymphoblastic (ANLL) type. MNC of ON/REL patients were more susceptible to HTLV-I than those of CR/OT donors. In addition, leukemic blasts were more rapidly infected (ie, within five to seven days) than the HTLV-I-susceptible normal cord-blood lymphocytes. However, the presence of circulating blasts was not essential to virus susceptibility, since CR/OT MNC, presumably free of leukemic blasts, were still more susceptible to HTLV-I than normal cells. Basal NK function of MNC from leukemic patients was significantly lower than that detectable in healthy controls. However, no correlation was found between susceptibility to HTLV-I infection and NK activity.

Adolescent↗

CALLA-negative, TdT- and CD7-positive acute lymphoblastic leukemia: a phenotype associated with poor prognosis.

Eight ALL patients displaying a CD7+, Tdt+, CD10-, T MoAbs-, myeloid MoAbs-, AP+ phenotype are described. Some patients showed well-known risk factors such as cytogenetic abnormalities, high WBC count, mediastinal mass, and/or organomegalies. The clinical behaviour was very poor and only one patient is in CR and off therapy. Therefore such a pre-T phenotype, although sometimes associated with the other risk factors, could be considered a poor prognosis phenotype.

Adolescent↗

Efficacy of a combined treatment with ASTA-Z 7654 and VP16-213 in vitro in eradicating clonogenic tumor cells from human bone marrow.

The efficacy of autologous bone marrow transplantation in leukemia and lymphoma may depend upon the selective elimination of malignant cells from human bone marrow in vivo and in vitro. A cyclophosphamide derivative (ASTA-Z 7654) and etoposide (VP16-213) have been tested on lymphoma and leukemia cell lines in a model that may represent a bone marrow situation in complete remission. The influence of different concentrations of normal mononuclear cells and tumor cells in this model and the activity of the two chemotherapeutic agents in the presence of bone marrow cells or peripheral blood cells were evaluated. A major inhibitory effect was observed using the two agents in combination; low doses of ASTA-Z and VP16 consecutively added to the mixture of malignant cells and normal mononuclear cells resulted in a greater elimination of tumor line cells than with ASTA-Z alone at the current 100 micrograms/ml dose. In contrast, no major toxicity on normal human bone marrow precursors was observed; the effect of treatment on hemopoietic recovery with the two agents either alone or in combination was evaluated on CFU-GM growth after long-term bone marrow cultures. Despite a profound growth inhibition at day 0, a recovery was observed in all cases after 7 or 14 days. The use of multiple chemotherapeutic agents in the treatment of bone marrow in vitro could decrease the possibility of malignant cells surviving while sparing normal bone marrow precursors.

Bone Marrow↗

Selective expression of fos proto-oncogene in human acute myelomonocytic and monocytic leukemias: a molecular marker of terminal differentiation.

Expression of human fos proto-oncogene (c-fos) was analyzed in primary cells from 50 untreated acute lymphocytic (ALL) and myeloblastic (AML) leukemias. c-fos RNA, analyzed by blot hybridization, was detected virtually only in myelomonocytic (M4) and monocytic (M5) AML. Both M4 and M5 samples show a strong positive correlation between the amount of c-fos transcripts and the percentage of leukemic cells expressing surface antigens specific for mature monocytes and macrophages. Normal mature monocytes exhibit a detectable level of c-fos RNA, which is virtually unaltered on activation to macrophage differentiation, but is always below that observed in M4 through M5 monocyticlike cells. These data provide evidence that c-fos expression is linked to terminal monocyte and macrophage differentiation in normal and leukemic hemopoiesis.

Antigens, Neoplasm↗

Unusual dermatologic toxicity of long-term therapy with hydroxyurea in chronic myelogenous leukemia.

The unusual appearance of extensive skin ulcerations was observed in 17 patients with chronic myelogenous leukemia on continuous chemotherapy with hydroxyurea. The strict relationship between ulcers and therapy was proved by the complete (14 cases) or almost complete (3 cases) healing of lesions after therapy was discontinued. The possible pathogenetic mechanisms responsible for skin alterations are considered. The particular importance of the continuous hydroxyurea administration modality clearly emerges, suggesting the use of different administration modalities to reduce such serious side effects.

Adult↗