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Biomedical subjects

A Perrotti

Publications and source records attributed to A Perrotti.

7 recordsLinked to original sources

Prolonged survival and low incidence of late toxic sequelae in advanced follicular lymphoma treated with a TBI-free autografting program: updated results of the multicenter consecutive GITMO trial.

This study provides an updated report of the consecutive multicenter Gruppo Italiano Trapianto Midollo Osseo trial employing an intensified, purging-free, total body irradiation-free, high-dose sequential chemotherapy schedule with peripheral blood stem cell autograft (i-HDS) in advanced-stage follicular lymphoma (FL). Special interest has been devoted to late toxicities and outcome in terms of molecular status. Ninety-two untreated FL patients aged <or=60 were enrolled by 20 Italian centers and evaluated on an intention-to-treat basis. Main findings are as follows: (1) 5.5-years overall survival projection of 80% (median follow-up: 68 months), with no differences related to age-adjusted IPI score; (2) 46 (50%) of 92 patients presently in continuous complete remission; (3) projected long-term progression-free survival exceeding 80% for patients collecting PCR-negative stem cell harvests or achieving molecular remission within the first 2 years from the end of therapy; (4) actuarial 5-years risk of developing secondary myelodysplasia and acute myeloid leukemia of 3.7%, with most of these events occurring in patients re-treated for recurrent lymphoma. These results demonstrate that i-HDS is feasible, effective and safe even in terms of long-term outcome. As the HDS schedule can be easily supplemented with Rituximab, it is one of the best options for random comparison with Rituximab-supplemented conventional chemotherapy.

Adolescent↗

Phase III comparative trial using CHOP vs CIOP in the treatment of advanced intermediate-grade non-Hodgkin's lymphoma.

Until now, literature data support the fact that the CHOP regimen represents the standard first line treatment for patients with advanced intermediate-grade non-Hodgkin's lymphoma. Recently, idarubicin has been introduced in clinical trials because of its favourable preclinical profile: it is more active than daunorubicin and doxorubicin against a number of experimental tumour systems and is significantly less cardiotoxic in animal models. From March 1991 to June 1993, 115 previously untreated patients with stage II to IV intermediate-grade non-Hodgkin's lymphoma, according to the Kiel classification, were enrolled in a phase III comparative trial. The objectives of the study were to compare the efficacy and safety of using idarubicin instead of doxorubicin in the polychemotherapeutic regimen CHOP (cyclophosphamide, doxorubicin, vincristine, and dexamethasone). Of the 115 patients registered for the trial, 103 were evaluable: 52 received CH (doxorubicin)OP and 51 received CI(Idarubicin)OP. Known prognostic factors were equally distributed among the two groups. There were no significant differences between the 2 groups in the rates of partial and complete response. The overall response rate was 87%, with complete response in 62%: 63% in the CHOP group, and 59% in the CIOP group. At 30 months (median 20 months), 86% of all CR patients were alive without disease in the CHOP group and 85% in the CIOP group. Patients treated with CHOP experienced severe alopecia more frequently (P = .004). Only three patients in the CIOP group showed cardiac adverse events (1 moderate and 2 mild), while in the CHOP group 4 mild, 2 moderate and 1 severe were recorded. LVEF monitoring was carried out in 31 patients of the CHOP group and in 27 of the CIOP group. A median drop of 8.3% of the LVEF was observed in patients treated with CHOP regimen as compared to 4.8% in patients with CIOP regimen (P = .0001). In this trial, the "idarubicin arm" (CIOP regimen) was found to have an equivalent therapeutic efficacy and, slightly, reduced clinical toxicity in comparison to the standard doxorubicin-containing CHOP regimen in patients with intermediate-grade non-Hodgkin's lymphoma.

Adult↗

[Antiphospholipid antibodies: their prevalence, clinical significance and correlation with cytokine levels in acute myeloid leukemia and non-Hodgkin's lymphoma].

Forty-five patients with de novo acute myeloid leukemia (AML) and 22 patients with newly-diagnosed non-Hodgkin lymphoma (NHL) were investigated. Tests for antiphospholipid antibodies (APA) included the measurement of anticardiolipin antibodies (aCL) with a solid-phase immunoassay, and the detection of the lupus-like anticoagulant (LA) activity. Fifteen patients with AML (33.3%) and 9 patients with non-Hodgkin lymphoma (40.9%) presented elevated APA at diagnosis, as compared to 3 out of 174 persons of the control group (p < 0.0001). APA titles became normal in all patients responding to treatment, whereas non-responders retained elevated levels. In addition, 2 patients (1 with AML and 1 with NHL) who had normal APA at diagnosis and were either refractory to treatment or in relapse, subsequently developed LA and/or aCL positivity. At presentation, the mean levels of IgG- and IgM-aCL in patients were not significantly different from controls, and concordance between aCL and LA results reached just 12%. With regard to the clinical course, we were not able to detect any statistically significant difference between patients with normal and elevated APA. Pretreatment concentrations of IL-6 and TNF-alpha in AML, and soluble form of the receptor for interleukin-2 (sIL-2r) in NHL were found significantly elevated compared to controls (p < 0.001, p = 0.011 and p = 0.016 respectively). In addition, the levels of these cytokines correlated with IgG-aCL at the different times of laboratory investigations. These results demonstrate that APA may have a role as markers of disease activity and progression in some haematological malignancies.

Acute Disease↗

Prevalence and clinical significance of elevated antiphospholipid antibodies in patients with idiopathic thrombocytopenic purpura.

Antibodies against phospholipid antigens (APA) have been demonstrated in idiopathic thrombocytopenic purpura (ITP), but their clinical and pathogenetic significance has remained elusive. In this study we analyzed the prevalence and clinical features of ITP patients with elevated APA. In addition, we prospectively evaluated APA levels after treatment with corticosteroids and compared them with platelet-associated immunoglobulin (PAIgG) titers. We studied 149 patients with newly diagnosed ITP. Of these, 78 had a platelet count less than 50 x 10(9)/L and received an initial treatment with oral prednisone (PDN). In 71 asymptomatic cases with platelet counts between 50 x 10(9)/L and 120 x 10(9)/L, no therapy was scheduled. However, in five of them, the platelet count fell below 50 x 10(9)/L after more than 12 months; these patients were treated with PDN. Tests for APA included the measurement of anticardiolipin antibodies (ACA) with a solid-phase immunoassay and the detection of the lupus-like anticoagulant (LA) activity with coagulation tests that included kaolin-clotting time, dilute Russel's Viper venom time, activated partial thromboplastin time (aPTT), and dilute aPTT. Controls consisted of 174 apparently healthy subjects. Either LA or elevated ACA was seen in 69 patients (46.3%) at diagnosis. LA and ACA were both elevated in 24 cases (16.1% of the overall patient population and 34.8% of patients with high APA concentrations). No correlation was found between LA ratio values and ACA-IgG or -IgM titers, or between ACA-IgG and ACA-IgM levels. The presence of these antibodies was not associated with sex, age, platelet count, or the severity of hemorrhages. PAIgG was detected in 106 of 127 cases (83%). Again, no relationship was observed with clinical parameters or with APA levels. However, all cases with elevated APA also had increased PAIgG. With regard to the clinical course, we were not able to detect any significant difference between patients with normal and elevated APA. An initial complete response to prednisone treatment was observed in 43 of 83 cases (51.8%), with 13 (15.7%) achieving a prolonged complete remission. APA levels were not significantly modified after PDN therapy and on relapse. We conclude that APA positivity is a common finding in patients with ITP and does not select a category with different clinical features. APA levels are not influenced by immunosuppressive therapy with steroids and are not related to the activity of the disease. Therefore, we do not support a role for APA in the pathogenesis of ITP.

Adolescent↗

Erythema multiforme during GM-CSF therapy.

A 52-year-old Caucasian man treated with granulocyte-macrophage colonystimulating factor (GM-CSF) developed a cutaneous eruption on legs and ankles with clinical and histologic features of erythema multiforme. Laboratory studies indicated that the eruption occurred at the time of peripheral blood lymphocyte recovery and that it was coincidental with serum peaks of interleukin-1 (IL-1), interleukin-2 (IL-2), interleukin-6 (IL-6) and tumour necrosis factor-alpha. We postulate that GM-CSF provoked erythema multiforme in a predisposed individual as a consequence of either an inappropriate cytokine secretion or of an abnormal amplification mechanism following lymphocyte recovery.

Erythema Multiforme↗

Antiphospholipid antibodies: prevalence, clinical significance and correlation to cytokine levels in acute myeloid leukemia and non-Hodgkin's lymphoma.

This study was designed to explore the prevalence and clinical significance of elevated antiphospholipid antibodies (APA) titres in patients affected by acute myeloid leukemia (AML) and high-grade non-Hodgkin's lymphoma (NHL). We also analyzed possible correlations with circulating levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and the soluble form of the receptor for interleukin-2 (sIL-2r). Nineteen patients with de novo AML and 14 patients with newly-diagnosed NHL were investigated. Tests for APA included the measurement of anticardiolipin antibodies (ACA) with a solid-phase immunoassay, and the detection of the lupus-like anticoagulant (LA) activity. Five patients with AML (26.3%) and 5 patients with NHL (35.7%) presented elevated APA at diagnosis, as compared to 3 of 174 persons of the control group (p < 0.0001). APA titres became normal in all patients responding to treatment, whereas non-responders retained elevated levels. In addition, 6 patients (4 with AML and 2 with NHL), who had normal APA at diagnosis and were either refractory to treatment or in relapse, subsequently developed LA and/or ACA positivity. At presentation, the mean levels of IgG- and IgM-ACA in patients were not significantly different from controls, and concordance between ACA and LA results reached just 30%. With regard to the clinical course, we were not able to detect any statistically significant difference between patients with normal and elevated APA. Pretreatment concentrations of IL-6 and TNF-alpha in AML, and sIL-2r in NHL were found significantly elevated compared to controls (p = 0.003, p = 0.009 and p = 0.024 respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Soluble factors levels in the initial staging of high-grade non-Hodgkin's lymphomas.

Plasma levels of several soluble factors were assayed in 31 untreated patients with high-grade non-Hodgkin's lymphomas (NHL). The results showed statistically significant higher average levels of interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-2 receptor (IL-2r) and transferrin receptor (TF-r) in NHL patients compared to controls (p = 0.045, p = 0.047, p = 0.020, p = 0.026 and p = 0.033 respectively). IL-2, IL-2r and TF-r levels were found more elevated in Stages III/IV than in Stages I/II (p = 0.031, p = 0.016 and p = 0.048 respectively), whereas IL-6 concentrations were higher in patients presenting B symptoms (p = 0.011). Significant correlations were found between the erythrocyte sedimentation rate (ESR) and IL-6 (r = 0.681), and between beta 2 microglobulin (B2-m) and IL-2r (r = 0.622).

Adult↗