[Evaluation study of the opinion on Di Bella's multimodal therapy of patients with tumors. 2].
Di Filippo F, Serraino D, Tirelli U
Divisione di Oncologia Medica A, Centro di Riferimento Oncologico, Aviano, Italia.
PURPOSE: To evaluate the opinion of patients with tumors who chose spontaneously to undergo the traditional anti-cancer treatment about Di Bella's therapy after the negative results of the experimental trial. MATERIALS AND METHODS: From November 23rd, 1998 to December 10th, 1998 a questionnaire was distributed among 50 patients with tumors. The questionnaire was anonymous, self-administered and included 9 questions. The data were compared, when possible, with those obtained in a previous study. RESULTS: Overall, 40 (70%) patients accepted favourably the conventional therapy; 27 (54%) patients did not believe in the experimental trial, as it was performed; 34 (68%) patients think the experimental trial should be repeated. CONCLUSIONS: The negative results of the experimental trial caused a distrustful feeling towards the Di Bella multi-therapy; but there is much confusion. There is a strong feeling that the conventional medicine is linked to powerful interests of the international pharmaceutical firms.
Immunological changes in peripheral blood and in lymphoid tissue after treatment of HIV-infected subjects with highly active anti-retroviral therapy (HAART) or HAART + IL-2.
Zanussi S, Simonelli C, Bortolin MT, D'Andrea M, Crepaldi C, Vaccher E, Nasti G, Politi D, Barzan L, Tirelli U, De Paoli P
Department of Microbiology, Immunology & Virology, Centro di Riferimento Oncologico IRCCS, Aviano, Ospedale di Pordenome, Italy.
This study presents the immunophenotypic and functional analysis of lymphocyte subsets obtained from peripheral blood and lymphoid tissue from HIV+ individuals treated with highly active anti-retroviral therapy (HAART) alone or in combination with 6 million units international (MUI) s.c. IL-2. Before treatment, the HIV+ patients had reduced CD4 and increased CD8 values in the peripheral blood and lymphoid tissue and impaired cytokine production by peripheral blood mononuclear cells (PBMC). After 24 weeks of treatment, all the HIV+ patients demonstrated increased CD4 values in peripheral blood and lymphoid tissue. The use of IL-2 did not promote an additional CD4 expansion compared with HAART alone; increased 'naive' and CD26+ CD4 cells and reduced CD8 cells were found in the peripheral blood and lymphoid tissue of the IL-2-treated, but not of the HAART-treated patients. Both types of treatment induced a significant reduction of the CD8/CD38+ cells. While HAART alone had negligible effects on cytokine production by PBMC, the combined use of HAART + IL-2 was unable to increase the endogenous production of IL-2, but caused an increase of IL-4, IL-13 and interferon-gamma (IFN-gamma) and a reduction of monocyte chemoattractant protein-1 (MCP-1) production. These data suggest that, although in this schedule IL-2 has minimal efficacy on CD4 recovery when compared with HAART alone, it produces an increase of 'naive' and CD26+ CD4 cells and a partial restoration of cytokine production. These data may be used to better define clinical trials aiming to improve the IL-2-dependent immunological reconstitution of HIV-infected subjects.
Published erratum appears in Drug Saf 1999 Jun;20(6):473
A risk and benefit assessment of treatment for AIDS-related Kaposi's sarcoma.
Nasti G, Errante D, Santarossa S, Vaccher E, Tirelli U
Division of Medical Oncology and AIDS, Centro di Riferimento Oncologico, Aviano, Pordenone, Italy.
Kaposi's sarcoma is the most common malignancy observed in patients with HIV-1 infection, and causes considerable morbidity and, when the lungs are involved, mortality. Therapy should be based on an evaluation of prognostic factors, in particular the extent and rate of tumour growth, patient symptoms, immune system condition and concurrent complications of AIDS. Nevertheless, considering the palliative role of Kaposi's sarcoma therapy, the potential benefits of therapy must be weighed against the high risk of adverse effects. Therefore, quality of life assessment is an integral component of therapeutic decisions. Localised Kaposi's sarcoma cutaneous tumours have been successfully treated with surgical excision, laser therapy, liquid nitrogen cryotherapy and radiotherapy. In patients with moderately extensive cutaneous or mucosal disease and CD4+ cell counts of > or =200/ml, immunotherapy and antiretroviral drugs are indicated. Preliminary results indicate that antiretroviral therapy might be effective and well tolerated in the treatment of less advanced Kaposi's sarcoma. In patients with aggressive and extensive mucocutaneous disease or with visceral manifestations of Kaposi's sarcoma, systemic cytotoxic therapy is indicated. However, the optimal treatment has yet to be found. The combination of doxorubicin, bleomycin and vincristine (ABV) has produced high overall response rates and is indicated as first-line treatment for patients with life-threatening or visceral disease. In patients who are leucopenic and require chemotherapy, single or dual agents associated with lower myelotoxicity [i.e. bleomycin, vincristine/vinblastine or a combination of bleomycin and vincristine/vinblastine (BV)] are most widely used. Other effective cytotoxic regimens are liposomal anthracyclines, paclitaxel and vinorelbine. To date, 3 randomised trials have compared these drugs to ABV and BV. In a large phase III study, the efficacy of liposomal daunorubicin was comparable with that of ABV. In 2 phase III studies, liposomal doxorubicin was compared with ABV and BV regimens and was found to be significantly more effective in producing objective responses. Therefore, liposomal doxorubicin, although more myelosuppressive than the BV regimen, is now considered by many physicians as the first-line therapy in patients with advanced stage Kaposi's sarcoma. Paclitaxel and vinorelbine have potential in Kaposi's sarcoma, but additional studies are needed to evaluate different schedules and to compare their activity with that of the reference regimens. Institution or continuation of both effective antiretroviral therapy and prophylaxis of opportunistic infections should be recommended to all patients receiving systemic cytotoxic therapies. However, attention must be paid to the cross-toxicity and possible pharmacokinetic interactions between antiretrovirals and antineoplastics.
The effects of CD40 ligation on peripheral blood mononuclear cell interleukin-12 and interleukin-15 production and on monocyte CD14 surface antigen expression in human immunodeficiency virus-positive patients.
Zanussi S, D'Andrea M, Simonelli C, Trabattoni D, Bortolin MT, Caggiari L, Tirelli U, Clerici M, De Paoli P
Department of Microbiology/Immunology/Virology, Centro di Riferimento Oncologico, Aviano, Italy.
Human immunodeficiency virus (HIV) infection causes dysregulation of surface phenotype, of accessory function and of cytokine production from peripheral blood mononuclear cells (PBMCs). As CD40 ligation induces several functional activities in these cells, this stimulation may partially mimic the situation occurring in vivo during an antigen-driven immune response. The aim of this study was to measure cytokine production and immunophenotypic changes induced by CD40 stimulation of PBMCs from HIV-positive patients. Under these experimental conditions, total and heterodimeric interleukin (IL)-12 production from PBMCs was similar, while IL-10 production was increased in HIV-positive patients compared with controls. On the contrary, CD40 ligation did not induce IL-15 production by PBMCs. Surface CD14 was down-modulated, as a consequence of CD40 stimulation, on monocytes from healthy controls but not on monocytes from HIV-positive patients. These data demonstrate that some of the CD40-mediated signals are disturbed in HIV-positive patients. These disturbances may contribute to the immune dysfunction seen in HIV infection.
AIDS-associated Kaposi's sarcoma is more aggressive in women: a study of 54 patients.
Nasti G, Serraino D, Ridolfo A, Antinori A, Rizzardini G, Zeroli C, Nigro L, Tavio M, Vaccher E, Tirelli U
Division of Medical Oncology and AIDS, Centro di Riferimento Oncologico, Aviano, Italy.
OBJECTIVE: To describe the epidemiologic and clinical features of AIDS-associated Kaposi's sarcoma (KS) in women compared with men. METHODS: In a retrospective study, within the Italian Cooperative Group on AIDS and Tumors (GICAT), we compared selected characteristics of 54 women and 108 men with AIDS-associated KS, matched by date of KS diagnosis and referral hospital. The chi2 test was used to test differences among proportions; the Kaplan-Meier method to estimate the survival time, and the Cox proportional hazard model was used to assess the role of gender, age, and CD4 cell count on death's risk. RESULTS: KS occurred at an earlier age (p = .001), was associated with a more severe immunodeficiency (p = .03), more advanced stages of HIV disease (p = .05), and had more aggressive presentation and course in women than in men. At KS diagnosis, women had a significantly increased proportion of visceral disease (p = .009), in particular pulmonary involvement (p = .002) and atypical sites of involvement (p = .008). The number of deaths due to KS was significantly higher (p = .01) in female patients. Both the higher proportion of visceral disease and of KS-related deaths observed in women did not change after adjusting for CD4 cell count and age. Women showed a decreased overall survival compared with men (8.9 and 14.4 months, respectively; p = .07), and the CD4 cell count at diagnosis significantly influenced survival. CONCLUSIONS: This study suggests that KS is more aggressive and life threatening in female than in male patients. This peculiar clinical behavior may reflect an inherently more aggressive biology of KS in women, possibly mediated by the level of immunodeficiency.
Hodgkin's disease in 35 patients with HIV infection: an experience with epirubicin, bleomycin, vinblastine and prednisone chemotherapy in combination with antiretroviral therapy and primary use of G-CSF.
Errante D, Gabarre J, Ridolfo AL, Rossi G, Nosari AM, Gisselbrecht C, Kerneis Y, Mazzetti F, Vaccher E, Talamini R, Carbone A, Tirelli U
Division of Medical Oncology, Aviano Cancer Center, Italy.
BACKGROUND: The optimal therapeutic approach for patients with Hodgkin's disease and human immunodeficiency virus infection (HD-HIV) is unknown. In an attempt to improve the results previously obtained with EBV (epirubicin, bleomycin and vinblastine) without G-CSF (Cancer 1994; 73: 437-44), in January 1993 we started a trial using chemotherapy (CT) consisting of EBV plus prednisone (EBVP), concomitant antiretroviral therapy (zidovudine, AZT or dideoxinosyne, DDI), and G-CSF. PATIENTS AND METHODS: Up to August, 1997, 35 (30 M/5 F) consecutive previously untreated patients (median age 34, range 21-53 years) with HD-HIV were enrolled in the European Intergroup Study HD-HIV. Their median performance status was 1 (range 1-3). At diagnosis of HD, 26% of the patients had AIDS, 90% had B symptoms at HD presentation and 83% had advanced-stage HD. Patients received E 70 mg/m2 i.v. on day 1, B 10 mg/m2 i.v. on day 1, V 6 mg/m2 i.v. on day 1 and P 40 mg/m2 p.o. from day 1 to day 5 (EBVP). Courses were repeated every 21 days for six cycles. AZT (250 mg x 2/day), or DDI (200 or 300 mg x 2/day) if AZT had been previously used, were given orally from the beginning of CT. G-CSF was given at the dose of 5 mcg/kg/day s.c. from day 6 to day 20 in all cycles. RESULTS: An overall response rate of 91% was observed. There were 74% complete responses (CR) and 17% partial responses (PR). Toxicity was moderate, with grade 3-4 leukopenia and thrombocytopenia in 10 (32%) and three (10%) patients, respectively. The median number of administered cycles was 6 (range 3-6). Twenty-three of 35 patients received AZT and nine patients received DDI. Three (8%) patients had opportunistic infections (OI) during or immediately after CT. The median CD4+ cell count was 219/mm3 (6-812) at HD diagnosis and 220/mm3 (2-619) after the end of combined therapy, and these numbers remained unchanged. Ten of 26 (38%) patients who achieved CR relapsed. Twenty-three patients died of HD progression alone or in association with OI, being the cause of death in 48% and 9% of patients respectively. The median survival was 16 months, with a survival rate of 32% and a disease-free survival of 53% at 36 months. CONCLUSIONS: The combined antineoplastic and antiretroviral treatment is feasible, but HD in HIV setting is associated with a more adverse prognosis than in the general population. Although the CR rate obtained was satisfactory, the relapse rate was high. Furthermore, comparison of the results of our two consecutive prospective studies demonstrated no overall improvement in the current trial with respect to the CR rate and survival.
Human immunodeficiency virus-associated Hodgkin's disease derives from post-germinal center B cells.
Carbone A, Gloghini A, Larocca LM, Antinori A, Falini B, Tirelli U, Dalla-Favera R, Gaidano G
Division of Pathology and the AIDS Program, Centro di Riferimento Oncologico,
Istituto Nazionale Tumori, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Aviano, Italy. acarbone@ets.it
Human immunodeficiency virus-associated Hodgkin's disease (HIV-HD) displays several peculiarities when compared with HD of the general population. These include overrepresentation of clinically aggressive histologic types and frequent infection of Reed-Sternberg (RS) cells by Epstein-Barr virus (EBV). Recently, we have reported that the histogenesis of HD of the general population may be assessed by monitoring the expression pattern of BCL-6, a transcription factor expressed in germinal center (GC) B cells, and of CD138/syndecan-1 (syn-1), a proteoglycan associated with post-GC, terminal B-cell differentiation. In this study, we have applied these two markers to the study of HIV-HD histogenesis and correlated their expression status to the virologic features of this disease. We have found that RS cells of all histologic categories of HIV-HD consistently display the BCL-6(-)/syn-1(+) phenotype and thus reflect post-GC B cells. Although BCL-6(-)/syn-1(+) RS cells of HIV-HD express CD40, they are not surrounded by CD40 ligand-positive (CD40L+) reactive T lymphocytes, which, in HD of the general population, are thought to regulate the disease phenotype through CD40/CD40L interactions. Conversely, RS cells of virtually all HIV-HD express the EBV-encoded latent membrane protein 1 (LMP1), which, being functionally homologous to CD40, may contribute, at least in part, to the modulation of the HIV-HD phenotype.
Dynamics of provirus load and lymphocyte subsets after interleukin 2 treatment in HIV-infected patients.
Zanussi S, Simonelli C, Bortolin MT, D'Andrea M, Comar M, Tirelli U, Giacca M, De Paoli P
Department of Microbiology-Immunology and Virology, Centro di Riferimento Oncologico, IRCCS, Aviano, Italy.
The association of antiretroviral agents plus interleukin 2 (IL-2) represents an efficient approach to the treatment of HIV+ subjects. While the effects of IL-2 on the immune system have been investigated, little is known concerning its impact on HIV dynamics. Two antiretroviral drugs control HIV viremia, but have minimal effects on the proviral load, a predictor of disease progression and response to therapy. The aim of this study was to define the effect of rIL-2 on HIV proviral copy numbers and its relationship to changes in CD4+ and CD8+ subsets. Twelve HIV+ patients with CD4 cell counts between 200 and 500 cells/mm3 were treated with six cycles of subcutaneous rIL-2, in combination with zidovudine and didanosine. This regimen resulted in a rapid and durable decrease in proviral load in the peripheral blood, in an increase in CD8+ lymphocytes, and in the emergence of a CD4+CD45RA+ T subset. These results demonstrate that the rationale for IL-2 administration to HIV+ patients may depend not only on its effects on the immune system, but also on the reduction of the number of infected cells, reinforcing the notion that IL-2 can have a favorable impact on the natural history of HIV infection.
Condom use in female sex workers in Italy.
Spina M, Tirelli U
Publication Types:
Comment
Letter
Comments:
Comment on: Am J Public Health 1998 Apr;88(4):643-6
Concomitant therapy with subcutaneous interleukin-2 and zidovudine plus didanosine in patients with early stage HIV infection.
Simonelli C, Zanussi S, Sandri S, Comar M, Lucenti A, Talamini R, Bortolin MT, Giacca M, De Paoli P, Tirelli U
Division of Medical Oncology and AIDS, Aviano Cancer Center, Italy.
A phase II study was performed to evaluate the feasibility and activity of subcutaneous (SC) interleukin-2 (IL-2) administration plus zidovudine (ZDV) and didanosine (ddI) in patients with early stage HIV infection. Between October 1995 and October 1996, 12 patients completed 6 cycles of the following scheduled therapy: ZDV plus ddI and SC self-administration of 6 mIU of IL-2 at days 1 to 5 and 8 to 12 of a 28-day cycle for a total of 6 cycles (24 weeks). After 6 cycles, patients received only ZDV plus ddI and they were observed up for an additional 24 weeks. Our schedule was well tolerated as an outpatient regimen and led to a significant elevation in CD4 count, which lasted for 24 weeks after the end of IL-2 therapy. Moreover, CD4/CD25, as well as CD4/CD45RO and CD4/CD45RA, cell levels were significantly increased at the end of the therapy and remained significantly elevated after 24 weeks. During the 6 cycles, HIV-associated viremia was significantly decreased and, accordingly, we observed a significant decline of proviral DNA in peripheral blood mononuclear cells (PBMCs). During follow-up, 10 of 12 treated patients continued to show levels of HIV-related viremia <500 copies/ml. Our results demonstrated that IL-2 and ZDV plus ddI is a well tolerated and effective therapy for patients with HIV in early stages of the disease.
- 26. Molecular biology of hematopoiesis 6/ Abraham, N.G. and other eds. New York: Kluwer Academic/Plenum Publisher, 1999 (25): 191-202 pagg
Carbone A., Tirelli U., Gloghini A., Falini B., Dalla-Favera R., Gaidano G.
The pathologic spectrum of AIDS-related non-Hodgkin’s lymphomas.
Macor F., Meneguzzo N., Antonini-Canterin F., Viel E., Pavan D., Barzan L., Franchin G., Tirelli U., Nicolosi G.L.
Major cardiovascular events following infusional 5-fluorouracil and cisplatin antineoplastic therapy.
Tirelli U., Vaccher E
Neoplastic disease.
The role and activity of an Italian volunteer organization providing information and emotional support for patients with cancer.
De Lorenzo F, Paglia C, Duce I, Tirelli U, Thomas R, Vecchio G.
Associazione Italiana Malati di Cancro, parenti e amici (AIMaC), Rome, Italy; Divisione di Oncologia Medica A, Centro di Riferimento Oncologico, Aviano, Italy; Consultant Clinical Oncologist; Department of Oncology, Addenbroke's Hospital University Trust, Cambridge, UK; Dipartimento di Biologia e Patologia Cellulare e Molecolare L. Califano, Universita Federico II, Naples, Italy.
Discordant hhv8 detection in a young hiv-negative patient with kaposi's sarcoma and sarcoidosis.
di Gennaro G, Canzonieri V, Schioppa O, Nasti G, Carbone A, Tirelli U.
Division of Medical Oncology A, National Cancer Institute, Aviano, Italy.
Human herpesvirus 8 (HHV8), which has been suggested as the causal agent of Kaposi's sarcoma (KS), has also been implicated in the pathogenesis of sarcoidosis. We describe a patient affected concomitantly by sarcoidosis and KS. HHV8 sequences were detected with PCR only on KS lesions, whereas sarcoid tissues did not harbor HHV8 DNA. Immune dysfunction related to sarcoidosis may have facilitated the oncogenic role of HHV8 and the development of KS.
Chronic hepatitis C in HIV-coinfected patients: feasibility and efficacy of interferon-alpha2b and ribavirin combination therapy.
Nasti G, di Gennaro G, Rizzardini G, Cadorin L, Tirelli U.
Publication Types:
Letter
Hodgkin's disease: clinical presentation and treatment.
Tirelli U, Vaccher E, Spina M, Carbone A.
Aviano Cancer Center.
Publication Types:
Review
Review, tutorial
A 20-year experience on malignant lymphomas in patients aged 70 and older at a single institute.
Tirelli U, Carbone A, Monfardini S, Zagonel V.
Division of Medical Oncology A, National Cancer Institute, Via Pedemontana Occ.le 12, 33081, Aviano, PN, Italy. oma@cro.it
We have evaluated the clinico-pathological and therepeutical outcome of patients aged 70 and older with malignant lymphomas treated at a single institute over a 20-year period of time. Among the several studies evaluated, the most important is a prospective randomized study comparing a new regimen, VMP (VP 16, Mitoxantrone and Prednimustine) vs the goal standard CHOP in unfavorable non-Hodgkin's lymphoma (NHL), showing that CHOP is significantly better than VMP in terms of objective response rate, progression free and overall survival. Therefore CHOP remains the standard regimen also for patients of over 70 years of age and stage II--IV intermediate and high grade NHL.
A 20-year experience on malignant lymphomas in patients aged 70 and older at a single institute.
Tirelli U, Carbone A, Monfardini S, Zagonel V.
Division of Medical Oncology A, National Cancer Institute, Via Pedemontana Occ.le 12, 33081, Aviano, PN, Italy. oma@cro.it
We have evaluated the clinico-pathological and therepeutical outcome of patients aged 70 and older with malignant lymphomas treated at a single institute over a 20-year period of time. Among the several studies evaluated, the most important is a prospective randomized study comparing a new regimen, VMP (VP 16, Mitoxantrone and Prednimustine) vs the goal standard CHOP in unfavorable non-Hodgkin's lymphoma (NHL), showing that CHOP is significantly better than VMP in terms of objective response rate, progression free and overall survival. Therefore CHOP remains the standard regimen also for patients of over 70 years of age and stage II--IV intermediate and high grade NHL.
Primary effusion lymphoma cell lines harbouring human herpesvirus type-8.
Carbone A, Cilia AM, Gloghini A, Capello D, Perin T, Bontempo D, Canzonieri V, Tirelli U, Volpe R, Gaidano G.
Division of Pathology, Centro di Riferimento Oncologico, IRCCS, Istituto Nazionale Tumori, Aviano, Italy. acarbone@ets.it
Primary effusion lymphoma (PEL) is a novel lymphoma entity consistently infected by HHV-8 that occurs predominantly in immunodeficient patients and is characterized by liquid growth in the serous body cavities. In order to facilitate the understanding of PEL pathogenesis and histogenesis, we have established three PEL cell lines termed CRO-AP/2, CRO-AP/3 and CRO-AP/5. All cell lines have been derived from HIV positive homosexual men affected by PEL with (in the case of CRO-AP/2 and CRO-AP/5) or without (in the case of CRO-AP/3) a previous history of Kaposi's sarcoma. The cell lines are representative of both virologic variants of PEL, i.e. HHV-8+ EBV+ PEL (CRO-AP/2 and CRO-AP/5) and HHV-8+ EBV- PEL (CRO-AP/3). Morphologic and phenotypic features of CRO-AP/2, CRO-AP/3 and CRO-AP/5 are typical of PEL, and include morphology bridging immunoblastic and anaplastic features as well as an indeterminate (non B- non T-cell) phenotype. The B-cell nature of the cell lines is documented by the presence of rearranged immunoglobulin genes. The detailed analysis of the molecular and phenotypic features of CRO-AP/2, CRO-AP/3 and CRO-AP/5 has allowed the identification of recurrent chromosomal abnormalities of PEL and has contributed to the definition of PEL as a lymphoma of post-germinal center, pre-terminally differentiated B-cells.
Characterization of a novel HHV-8-positive cell line reveals implications for the pathogenesis and cell cycle control of primary effusion lymphoma.
Carbone A, Cilia AM, Gloghini A, Capello D, Fassone L, Perin T, Rossi D, Canzonieri V, De Paoli P, Vaccher E, Tirelli U, Volpe R, Gaidano G.
Divisions of Pathology, Centro di Riferimento Oncologico, IRCCS, Istituto Nazionale Tumori, Aviano, Italy.
Primary effusion lymphoma (PEL) represents a peculiar type of B cell lymphoma which associates with HHV-8 infection and preferentially grows in liquid phase in the serous body cavities. In this report, we provide the detailed characterization of a newly established PEL cell line, termed CRO-AP/6. The cell line was obtained from the pleural effusion of a HIV-positive patient with PEL. Its derivation from the tumor clone was established by immunogenotypic analysis. Detailed phenotypic investigations defined that CRO-AP/6 reflects pre-terminally differentiated B cells expressing the CD138/syndecan-1 antigen. Karyotypic studies of CRO-AP/6 identified several chromosomal abnormalities, whereas genotypic studies ruled out the involvement of molecular lesions associated with other types of B cell lymphoma. Both CRO-AP/6 and the parental tumor sample harbored infection by HHV-8. Conversely, EBV infection was present in the parental tumor sample although not in CROAP/6, indicating that CRO-AP/6 originated from the selection of an EBV-negative tumor subclone. The pattern of viral (HHV-8 v-cyclin) and cellular (p27Kip1) regulators of cell cycle expressed by CRO-AP/6, together with the results of growth fraction analysis, point to abrogation of the physiological inverse relationship between proliferation and p27Kip1 expression. Also, both CRO-AP/6 and the parental tumor sample display biallelic inactivation of the DNA repair enzyme gene O6-methylguanine-DNA methyltransferase (MGMT) by promoter methylation. Overall, the CRO-AP/6 cell line may help understand cell cycle control of PEL cells, may clarify the relative contribution of HHV-8 and EBV to the disease growth and development and may facilitate the identification of recurrent cytogenetic abnormalities highlighting putative novel cancer related loci relevant to PEL.
Human immunodeficiency virus-associated Hodgkin's disease.
Spina M, Vaccher E, Nasti G, Tirelli U.
Division of Medical Oncology A, National Cancer Institute, Aviano, Italy.
Hodgkin's disease represents the most common type of non-acquired immunodeficiency virus (AIDS)-defining tumor that occurs in the human immunodeficiency virus (HIV)-positive population. More than 300 cases of Hodgkin's disease in HIV-infected individuals have been reported, mainly from the European countries (ie, Italy, Spain, and France) and to a lesser extent from the United States. All series have documented unusually aggressive tumor behavior, including a higher frequency of unfavorable histologic subtypes, advanced stages, and poorer therapeutic outcome, as compared with the behavior of Hodgkin's disease outside of the HIV setting.
Epidemiological, biological and clinical features of HIV-related lymphomas in the era of highly active antiretroviral therapy.
Tirelli U, Spina M, Gaidano G, Vaccher E, Franceschi S, Carbone A.
Publication Types:
- Editorial
- Review
- Review, Tutorial
Insights into the reasons for discontinuation of the first highly active antiretroviral therapy (HAART) regimen in a cohort of antiretroviral naive patients. I.CO.N.A. Study Group. Italian Cohort of Antiretroviral-Naive Patients.
d'Arminio Monforte A, Lepri AC, Rezza G, Pezzotti P, Antinori A, Phillips AN, Angarano G, Colangeli V, De Luca A, Ippolito G, Caggese L, Soscia F, Filice G, Gritti F, Narciso P, Tirelli U, Moroni M.
Institute of Infectious and Tropical Diseases, University of Milan, Italy. adarmin@tin.it
OBJECTIVE: To evaluate the frequency of discontinuation of the first highly active antiretroviral regimen (HAART) and the factors predictive of discontinuing for toxicity and failure in a population-based cohort of HIV-positive individuals in Italy, naive from antiretrovirals at enrolment. METHODS: The study population consisted of individuals who initiated HAART and had at least one follow-up visit. The primary end-points were discontinuation of any component of HAART for drug toxicity and discontinuation for failure. Survival analyses were performed to identify predictive factors for reaching the two end-points. RESULTS: Eight hundred and sixty-two individuals initiated HAART; in 727 of them (84.3%) this consisted of two nucleoside reverse transcriptase inhibitors (NRTI) and one protease inhibitor (PI). Over a median follow-up of 45 weeks, 312 patients (36.2%) discontinued therapy: 182 (21.1%) discontinued due to toxicity, 44 (5.1%) due to failure. The probability of discontinuing HAART at 1 year was 25.5% [95% confidence interval (CI), 21.9-28.9] due to toxicity and 7.6% (95% CI, 4.9-1 0.3) due to failure. Independent factors associated with discontinuation for toxicity were: gender [relative hazard (RH) = 0.51; 95% CI, 0.32-0.80 for men versus women], type of treatment (indinavir-containing regimens, RH = 1.94; 95% CI, 1.10-3.41 and ritonavir-containing regimens, RH = 3.83; 95% CI, 2.09-7.03 versus hard-gell saquinavir) and time spent on treatment (RH = 0.89; 95% CI, 0.80-0.98 for each additional month). Discontinuation due to failure was independently associated with the most recent HIV-RNA (RH = 3.20; 95% CI, 1.74-5.88 for log10 copies/ml higher), and with type of treatment (indinavir-containing regimens, RH = 0.21; 95% CI, 0.06-0.78 and ritonavir-containing regimens, RH = 0.23; 95% CI, 0.04-1.26 versus hard-gell saquinavir). CONCLUSIONS: If the current HAART regimen caused no toxicity, less than 10% of naive patients discontinue their first HAART regimen because of failure after 1 year from starting therapy.
Stanford V regimen and concomitant highly active antiretroviral therapy is feasible and active in patients with Hodgkin's disease and HIV infection.
Spina M, Gabarre J, Fasan M, Vaccher E, Tirelli U.
Publication Types:
- Clinical Trial
- Clinical Trial, Phase II
- Letter
- Multicenter Study
Effects of 2-year antiretroviral combination therapies on HIV-1 DNA levels.
Zanussi S, Bortolin MT, Tirelli U, Nasti G, Vaccher E, Giacca M, De Paoli P.
Publication Types:
- Clinical Trial
- Letter
- Randomized Controlled Trial
Effects of therapy with highly active anti-retroviral therapy (HAART) and IL-2 on CD4+ and CD8+ lymphocyte apoptosis in HIV+ patients.
Caggiari L, Zanussi S, Bortolin MT, D'andrea M, Nasti G, Simonelli C, Tirelli U, De Paoli P.
Department of Microbiology, Immunology and Virology and Division of Medical Oncology and AIDS,Centro di Riferimento Oncologico, IRCCS, Aviano, Italy.
The kinetics and effects of in vivo spontaneous apoptosis and activation-induced cell death (AICD) upon CD4+ and CD8+ lymphocyte subsets and CD4 naive cell numbers were studied in HIV+ subjects with CD4 pretreatment values > 200/mm3, who were subsequently treated for 48 weeks with HAART alone or in combination with six cycles of subcutaneous IL-2. Irrespective of the type of treatment, patients showed a statistically significant increase in CD4 cell counts after 4 weeks, although the CD4 naive subset only increased significantly in the IL-2-treated subjects at the end of treatment. The percentage of CD4 cells undergoing spontaneous apoptosis and AICD was significantly reduced in all patients after 4 weeks and this reduction was maintained until the end of therapy; however, the level always remained significantly higher in comparison with healthy subjects. A statistically significant reduction in CD8 apoptosis levels required at least 24 weeks of therapy. Together these data suggest that a reduction in the level of apoptosis may contribute to the early rise in CD4 numbers measured after HAART, but that later on HAART is unable to improve further this biological parameter. Although the use of IL-2 had no additional effects on spontaneous apoptosis and AICD, it may be beneficial by stimulating a late increase in the numbers of CD4 naive cells in HIV-treated subjects.
Plasma viral load concentrations in women and men from different exposure categories and with known duration of HIV infection. I.CO.N.A. Study Group.
Rezza G, Lepri AC, d'Arminio Monforte A, Pezzotti P, Castelli F, Dianzani F, Lazzarin A, De Luca A, Arlotti M, Leoncini F, Manconi PE, Rizzardini G, Minoli L, Poggio A, Ippolito G, Phillips AN, Moroni M.
Centro Operativo AIDS, Istituto Superiore di Sanita, Rome, Italy. g.rezza@iss.it
CONTEXT: According to recent studies, women have lower plasma HIV RNA concentrations than men. However, these studies did not take into account the duration of HIV infection. OBJECTIVES: To analyze the relationship between viral load and gender among individuals with known date of seroconversion. SETTING: Sixty infectious disease clinics in Italy. DESIGN: Cross-sectional analysis of data collected at enrollment in a cohort study. PARTICIPANTS: Injecting drug users and heterosexual contacts naive to antiretroviral therapy at enrollment (245 men; 170 women). MAIN OUTCOME MEASURES: Plasma HIV RNA concentrations, measured using quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) or signal amplification b-DNA assays before antiretroviral therapy. RESULTS: Plasma HIV RNA concentrations were similar by age and exposure category (p =.80 and p =.39, respectively). Median viral load among women was roughly half that of men (p =.002). The association between viral load and gender remained significant after fitting a two-way analysis of variance (p =.03) and after adjusting for CD4 count, modality of HIV transmission, and age at enrollment in a regression model. Viral load was 0.27 log10 copies/ml (95% confidence interval, 0.05-0.40; p =.01) lower in women (i.e., 50% lower in the raw scale). CONCLUSIONS: Plasma HIV RNA concentrations were found to be lower among women, even when considering the duration of HIV infection. Compared with men, it is possible women should be given highly aggressive antiretroviral therapy at lower HIV-RNA concentrations.