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E Vaccher

Publications and source records attributed to E Vaccher.

At least 19 recordsLinked to original sources
PubMed2005

KSHV/HHV-8 associated lymph node based lymphomas in HIV seronegative subjects. Report of two cases with anaplastic large cell morphology and plasmablastic immunophenotype.

BACKGROUND: Kaposi sarcoma associated herpesvirus (KSHV)/human herpesvirus 8 (HHV-8) associated lymphomas, which often develop in human immunodeficiency virus (HIV) infected patients with advanced AIDS, present predominantly as primary effusion lymphoma (PEL) or, less frequently, as "solid" extracavitary based lymphomas, associated with serous effusions. These last lymphomas, also called "solid PEL", have been reported before the development of an effusion lymphoma and after resolution of PEL. Interestingly, KSHV/HHV-8 associated lymphomas that present as solid or extracavitary based lesions in HIV seropositive patients without serous effusions have been reported recently. METHODS/RESULTS: This paper provides evidence for the existence of a previously undescribed KSHV/HHV-8 associated lymphoma in HIV seronegative patients without serous effusions. These lymphomas exhibit a predilection for the lymph nodes and display anaplastic large cell morphology. These tumours were completely devoid of common cell type specific antigens, including epithelial and melanocytic cell markers. B and T cell associated antigens and other commonly used lymphoid markers were absent or weakly demonstrable in a fraction of the tumour cells. Conversely, immunohistochemical studies showed strong immunostaining with plasma cell reactive antibodies. CONCLUSIONS: Analysis of viral infection and immunohistological studies are of primary importance to define this lymph node based KSHV/HHV-8 associated lymphoma with anaplastic large cell morphology and plasmablastic immunophenotype occurring in HIV seronegative patients without serous effusions.

Aged↗
PubMed2004

Mitoxantrone, vinorelbine and prednisone (MVD) in the treatment of metastatic hormonoresistant prostate cancer--a phase II trial.

A total of 28 patients were treated with mitoxantrone, vinorelbine and prednisone every 3 weeks. In all, 11 patients (46%) had a significant prostate-specific antigen decline for a median duration of 11.4 months. Eight patients (33%) achieved a partial response on pain, while seven (29%) obtained a stabilisation of the symptom. Median duration of the response was 9.5 months. A confirmed partial response was obtained in three out of seven patients who had bidimensionally measurable disease. Toxicity was manageable. Our study provides further support to the concept of combined antimicrotubule therapy for metastatic harmonoresistant prostate cancer, promoting the exploration of new regimens containing antimicrotubule agents in addition to mitoxantrone-prednisone.

Administration, Oral↗
PubMed2004

Effect of highly active antiretroviral therapy (HAART) on pharmacokinetics and pharmacodynamics of doxorubicin in patients with HIV-associated non-Hodgkin's lymphoma.

BACKGROUND: We demonstrated that highly active antiretroviral therapy (HAART) increases the toxic effect of cyclophosphamide, vincristine, doxorubicin (DOX) and prednisone (CHOP) in HIV-patients with non-Hodgkin's lymphoma (NHL). To ascertain the cause of increased toxicity, we investigated the pharmacokinetics of DOX in HIV-patients with NHL treated with CHOP with and without HAART. METHODS: Complete pharmacokinetics and pharmacodynamic analysis was determined in 19 patients during 38 cycles of chemotherapy: 19 cycles with CHOP and 19 CHOP + HAART in a crossover-designed study. HAART included protease inhibitors indinavir (IDV) in nine patients, saquinavir (SQV) hard gel in six patients and nelfinavir (NFV) in four patients. RESULTS: No significant effects of HAART on pharmacokinetics parameters of DOX were observed. Similarly, no differential effect on DOX pharmacokinetics among IDV, SQV, and NFV was evidenced. Significant associations (P=0.012) were observed between DOX AUC0-infinity (area under the concentration curve) and G3-G4 WHO haematologic toxicity, in patients treated with CHOP alone, but not in those treated with CHOP + HAART (P = not significant). CONCLUSION: We demonstrated that HAART therapy has no significant effect on DOX pharmacokinetics. DOX AUC appears to be a predictor of toxicity only in patients treated with CHOP alone. Other factors beside DOX plasma levels are detrimental for toxicity after CHOP + HAART. Therefore, pharmacodynamic interactions between HAART and DOX should be considered.

Adult↗
PubMed2002

Nasopharyngeal cancer WHO type II-III: monoinstitutional retrospective analysis with standard and accelerated hyperfractionated radiation therapy.

The aim of this study is to assess the impact of prognostic factors in patients with locoregionally advanced nasopharyngeal cancer (NPC), WHO type II-III, treated with two different radiation therapy (RT) schedules: standard radiation therapy (SRT), and accelerated hyperfractionated radiation therapy (HART), with or without sequential chemotherapy. Between January 1986 and December 1999, 78 consecutive NPC patients were treated either with SRT (until August 1993) or with HART (from September 1993). Of the 78 patients, 60 were males and 18 females, the median age was 56 years (range 14-83). Nine patients had a non-keratinizing carcinoma (WHO type II) and 69 an undifferentiated carcinoma (WHO type III). Five-year overall survival rate (OS) was 62%. Two months after RT, 73 patients were in complete remission. Disease-free survival (DFS) rates at 5 years were: 85% for the HART and 59% for the SRT group, respectively. A multivariate analysis, age (hazard ratio, HR=4.17 for > or = 60 vs. <50 years) and N-stage (HR=3.56 for N3a-N3b vs. N0-N1) were significant for survival, whereas N-stage (HR=8.23 for N3a-N3b vs. N0-N1) and RT schedule (HR=0.30 for HART vs. SRT) were significant for DFS. In our experience, HART achieved higher DFS rates than SRT; however, HART did not favourably affect OS. Toxicity was comparable in the two RT schedules.

Adolescent↗
PubMed2001

Human immunodeficiency virus-related non-Hodgkin lymphoma: activity of infusional cyclophosphamide, doxorubicin, and etoposide as second-line chemotherapy in 40 patients.

BACKGROUND: The prognosis of patients with human immunodeficiency virus (HIV)-related non-Hodgkin lymphoma (NHL) is poor. In fact, despite a high complete response (CR) rate, approximately 50% of these patients die from progressive lymphoma. METHODS: From November 1994 to April 2000, the authors treated 40 patients with resistant or recurrent HIV-related NHL with a 96-hour continuous intravenous infusion of cyclophosphamide (187.5 mg/m(2) per day), doxorubicin (12.5 mg/m(2) per day), and etoposide (60 mg/m(2) per day). RESULTS: The median number of cycles administered was two (range, one to six cycles). A CR was documented in 4 of 40 patients (10%), and a partial remission (PR) was documented in 7 of 40 patients (18%). The CR median duration was 6 months (range, 4--30+ months), whereas PRs lasted for 5 months (range, 2--8 months). The overall median survival was 4 months (range, < 1--33 months), and the median survival for responding patients was 10 months. CONCLUSIONS: The current data confirm that infusional cyclophosphamide, doxorubicin, and etoposide is active in patients with refractory or recurrent HIV-related NHL. However, the median survival of these patients remains poor, and the other innovative approaches should be used.

Adolescent↗
PubMed2001

Concomitant cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy plus highly active antiretroviral therapy in patients with human immunodeficiency virus-related, non-Hodgkin lymphoma.

BACKGROUND: The feasibility and efficacy of concomitant chemotherapy and highly active antiretroviral therapy (HAART) is still unknown in patients with human immunodeficiency virus (HIV)-related malignancies. To evaluate the impact of chemotherapy plus HAART on the clinical course of patients with HIV-related, systemic, non-Hodgkin lymphoma (HIV-NHL), the authors compared retrospectively a group of 24 patients with HIV-NHL who were treated with the cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy regimen plus HAART with a group of 80 patients who were treated with CHOP chemotherapy or a CHOP-like regimen (i.e., cyclophosphamide, doxorubicin, teniposide, and prednisone with vincristine plus bleomycin) without receiving antiretroviral therapy. METHODS: All patients were enrolled in two sequential trials performed at the Aviano Cancer Center, Italy, from April 1988 to December 1998. HAART was included with combination therapy from January 1997. Antiretroviral regimens consisted of two reverse transcriptase inhibitors and one protease inhibitor. RESULTS: The two treatment groups were well matched with regard to patient demographics, NHL characteristics, HIV status, and treatment, i.e., the number of cycles and chemotherapy dose. The response rates were similar between the two groups. Severe anemia (Grade 3-4 according to the World Health Organization criteria) was significantly greater in the patients who received CHOP-HAART compared with the patients who received CHOP alone (33% vs. 7%, respectively; P = 0.001). Leukopenia was similar between the two groups, but colony stimulating factor support was significantly greater in the CHOP-HAART group than in the control group (92% vs. 66%, respectively; P = 0.03). Seventeen percent of CHOP-HAART patients developed severe autonomic neurotoxicity, whereas none of the CHOP patients developed neurotoxicity (P = 0.002). At similar median follow-up, opportunistic infection (OI) rates and mortality were significantly lower in the CHOP-HAART patients than in the CHOP patients (18% vs. 52%, respectively; P = 0.05; and 38% vs. 85%, respectively; P = 0.001). The median survival for CHOP-HAART patients was not reached, whereas the medial survival of CHOP patients was 7 months (P = 0.03). CONCLUSIONS: The combination of CHOP plus HAART is feasible and may reduce the morbidity from OIs in HIV-NHL patients. However, careful attention must be directed to cross toxicity and possible pharmacokinetic interactions between antiretroviral and antineoplastic drugs. The impact of the combined chemotherapy plus HAART treatment on patient survival needs urgently to be evaluated in prospective studies.

AIDS-Related Opportunistic Infections↗
PubMed2001

Lymphocyte subsets and viral load in patients with HIV-associated non-Hodgkin's lymphoma treated with anti-CD20 monoclonal antibody and chemotherapy.

The anti-CD20 monoclonal antibody Rituximab is a novel antitumor agent used in association with chemotherapy (CT) for the treatment of high-grade/intermediate non-Hodgkin's lymphomas (NHL) in HIV-negative populations. This therapeutic combination is currently also being explored in HIV-positive patients with NHL (HIV-NHL). The objective of our study was to determine CD4 and CD8T cell counts, HIV plasma viremia and proviral load in patients with CD20-positive HIV-NHL treated with Rituximab plus CT and highly active antiretroviral therapy (HAART). We studied eight patients with HIV-NHL treated by anti-CD20 and CT before, after three, and after six cycles of therapy; CD4, CD8 and CD19 lymphocyte subsets were measured by monoclonal antibodies and flow cytometry. HIV plasma viremia was determined by the b-DNA assay, and proviral load by a quantitative competitive PCR. CD4T cell counts remained stable after three cycles of therapy, while a significant reduction of this subset was present at the end of therapy. HIV plasma viremia was significantly reduced after the third cycle, but returned to pretreatment levels at the end of therapy; we also observed individual fluctuations of proviral load during therapy, this marker being increased in two out of three patients at the end of therapy. These observations suggest that Rituximab plus CT accelerated the rate of CD4 depletion and of HIV replication in the peripheral blood of HIV-NHL patients and that HAART may be able to delay these effects.

Adult↗
PubMed2001

Clinical aspects and management of Hodgkin's disease and other tumours in HIV-infected individuals.

As the AIDS epidemic advances, the spectrum of malignancies encountered is expanding. Several non-AIDS defining cancers, i.e. Hodgkin's disease (HD), anal and testicular cancer, are increasing in incidence in HIV-infected patients. The widespread use of highly active antiretroviral therapy (HAART) in industrialised countries has resulted in substantial improvement in the survival of HIV-infected patients. It is likely that in the future, cancers associated with long-term mild immune suppression will occur at an increased rate in long-term survivors of HIV infection. The natural history of the majority of non-AIDS defining tumours differs from that of the general population. Unusual aspects of tumour localisation, growth behaviour and therapeutical responses distinguish tumours in patients with HIV infection from those without. This paper reviews the most relevant data on the epidemiology, pathology, clinical features and treatment of the most frequently reported non-AIDS defining tumours, i.e. HD, lung, testicular and skin cancers.

Adult↗
PubMed2001

[Systemic HIV-non-Hodgkin lymphoma in the era of HAART. Natural history].

In the era of highly active antiretroviral therapy (HAART), systemic non-Hodgkin lymphoma (NHL) represented the most frequent cancer associated to HIV infection. In contrast to Kaposi's sarcoma and primary central nervous system lymphoma (PCNSL) which incidence have been declining after introduction of HAART, systemic NHL-HIV has relatively stable remained. Systemic HIV related NHL are markedly heterogeneous both histologically and clinically and this clinicophatological heterogenity reflects variability in the molecular lesions associated to these lymphomas and immunological status of these patients. The introduction of HAART has substantially modified the approach to HIV related lymphomas. The results of recent monoinstitutional study of Aviano Cancer's Institute on 235 patients have suggested that HAART would otherwise allow a long life expectancy with longer disease free survival and overall survival. In fact the reduced of morbidity of AIDS patients bought by HAART justified the use of aggressive antineoplastic therapies.

Adult↗
PubMed2000

Analysis and significance of anti-latent membrane protein-1 antibodies in the sera of patients with EBV-associated diseases.

Anti-latent membrane protein-1 (LMP-1) is an EBV-encoded type III integral membrane protein with oncogenic potential that is expressed most consistently in various EBV-associated malignancies. Unlike many other EBV proteins, LMP-1 Abs have rarely been demonstrated in EBV-associated disease conditions. We established a high level LMP-1-expressing cell clone and used it for the detection, quantitation, and characterization of these Abs in various human sera in immunoblots and ELISA. Our results demonstrate that, in contrast to the commonly held notion, LMP-1 induces significant humoral immune responses in EBV-associated malignant conditions especially in nasopharyngeal carcinoma (NPC) patients in whom >70% sera are positive for these Abs, and their titers correlate with the clinical condition of the tumors. Interestingly, anti-LMP-1 Abs of IgA isotype were found only in NPC patients. These Abs were absent from the sera of infectious mononucleosis and chronic EBV infection patients, whereas a small fraction ( approximately 5%) of the healthy, EBV-seropositive individuals were positive for them; however, their OD values were much lower than those of NPC patients. These studies demonstrate, for the first time, the potential significance of LMP-1-specific Abs for the diagnosis and prognosis of EBV-associated malignancies, especially of NPC.

Antibodies, Viral↗
PubMed2000

Role of brain biopsy in the management of focal brain lesions in HIV-infected patients. Gruppo Italiano Cooperativo AIDS & Tumori.

In this multicenter, retrospective study of 160 brain biopsies in the assessment of HIV-related focal brain lesions, diagnostic sensitivity was acceptable (87%), but the procedure carried considerable morbidity (7.5%) and mortality (3.1%). Moreover, it is not always possible to initiate the changes in therapy indicated by the results, and overall survival remains poor, with a median of 2 months. Criteria for brain biopsy for the diagnosis of focal brain lesions should be redefined to include selected patients for whom a less invasive approach does not yield a definitive diagnosis.

Adult↗