acyclovir and Burkitt-Lymphoma

Both oral and intravenous acyclovir administration for seven days in the early stages of infectious mononucleosis caused an inhibition of oropharyngeal Epstein-Barr virus (EBV) replication. Minimal effect on clinical symptoms was observed. Development of normal cellular and humoral EBV-specific immunity was seen in all patients. The combination of intravenous acyclovir and prednisolone treatment for 10 days in 11 patients with fulminant mononucleosis caused transient cessation of virus shedding in all patients. A dramatic clinical effect on pharyngeal symptoms and on fever was seen in nine of 11 patients within 72 hours. Treatment with chemotherapy or irradiation is recommended in EBV-associated B cell lymphomas seen in immunosuppressed, transplanted, and human immunodeficiency virus-I seropositive patients. No effect of acyclovir has been reported, but such therapy may be considered in the early stage when EBV induces a polyclonal B cell activation. Acyclovir treatment is effective in the EBV-genome positive hairy leukoplakia in human immunodeficiency virus-seropositive patients. No effect of antiviral therapy has been reported in the X-linked lymphoproliferative syndrome. Prophylactic use of immunoglobulin or acyclovir has been suggested in susceptible children.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Burkitt Lymphoma; Clinical Trials as Topic; Female; Herpesviridae Infections; Herpesvirus 4, Human; Humans; Immune Tolerance; Infectious Mononucleosis; Lymphoproliferative Disorders; Male; Prednisolone

Topics: Acute Disease; Acyclovir; Antiviral Agents; Burkitt Lymphoma; Chronic Disease; Herpesvirus 4, Human; Humans; Infectious Mononucleosis; Nasopharyngeal Neoplasms; Recurrence; Tumor Virus Infections

The group of the human-pathogenic herpesviruses comprises five subgroups: Herpes simplex virus type 1 (HSV-1), Herpes simplex virus type 2 (HSV-2), varicella zoster virus (VZV), cytomegalovirus (CMV), and Epstein-Barr virus (EBV). Primary infection with these ubiquitous herpesviruses usually occurs in childhood or during adolescence and frequently remains inapparent. However, it can also give rise to a variety of clinical pictures. Important clinical manifestations of herpesvirus infections are mucocutaneous lesions (HSV-1, HSV-2, VZV) self-limited, lymphoproliferative diseases (CMV, EBV) and congenital malformations (CMV). Primary infection with herpesviruses leads to a persistent infection of the host. This clinically silent condition of latency can be interrupted and may cause pathological symptoms to recur by reactivation of latent herpesviruses. A classical example of the clinical manifestation of herpesvirus reactivation is herpes zoster following an overcome varicella disease. The mechanism of herpesvirus reactivation has not yet been fully clarified. Reactivation of herpesviruses might be attributable to a weakening of the cellular immunodefence. For the control of viral infections mainly two cellular effector systems are responsible: unspecific, cytotoxic, natural killer (NK) cells and specific cytotoxic thymus-dependent (T) lymphocytes. The functional impairment of these cytotoxic active cells my cause herpesvirus reactivation in immunodeficient or immunosuppressed persons. Interference with the immunological control function may also contribute to the genesis of herpesvirus-associated tumours. Such an association between herpesviruses and human tumours is assumed to exist especially in the case of EBV. The frequently life-endangering severity of local or disseminated herpesvirus infections calls for suitable measures ensuring efficient prophylaxis and therapy. However, the possibilities of a specific immunoprophylaxis (vaccine, special immunoglobulins) against herpesvirus infections are still rather limited. The development of antiviral substances has greatly benefited from the introduction of new agents (Acyclovir) and the production of sufficient quantities of interferon (IFN) preparations during the last few years. Impressive results were obtained with the nucleoside-related substance Acyclovir in the prevention and therapy of primary or reactivated HSV-1 or HSV-2 infections. The use of Acyclovir as prophylactic agent produced the effect tha

Topics: Acyclovir; Antiviral Agents; Burkitt Lymphoma; Chickenpox; Cytomegalovirus; Cytomegalovirus Infections; Female; Herpes Genitalis; Herpes Simplex; Herpes Zoster; Herpesviridae; Herpesviridae Infections; Herpesvirus 3, Human; Herpesvirus 4, Human; Humans; Immunity, Cellular; Immunization, Passive; Infectious Mononucleosis; Male; Nasopharyngeal Neoplasms; Simplexvirus; Smallpox Vaccine; T-Lymphocytes; Vidarabine

Topics: Acyclovir; Adult; Antiviral Agents; Burkitt Lymphoma; Chickenpox; Child; Cytomegalovirus Infections; Disease Susceptibility; Enterovirus Infections; Herpes Simplex; Herpes Zoster; Humans; Immunologic Deficiency Syndromes; Immunosuppression Therapy; Infectious Mononucleosis; Orthomyxoviridae Infections; Respirovirus Infections; Vidarabine; Virus Diseases

Treatment options for Epstein-Barr virus (EBV)-associated Burkitt lymphoma in Africa are limited because of chemotherapy-associated toxicity. Since other EBV-associated diseases respond to antiviral agents, we investigated adding an antiviral agent, valacyclovir, to the current chemotherapy regimen in Malawi. In this phase I safety study, we showed that cyclophosphamide combined with valacyclovir was safe. Phase II efficacy trials should now be undertaken.. Nucleoside analogues, including acyclovir, ganciclovir, and their precursors, have shown some efficacy against several Epstein-Barr virus (EBV)-associated diseases, including active EBV infection and posttransplantation lymphoproliferative disorder (PTLD). They have also been proposed as a possible treatment for EBV-associated malignancies, including endemic Burkitt lymphoma. The safety of nucleoside analogues in combination with chemotherapy in the developing world has not been studied and is necessary before any large scale efficacy trials are conducted.. Children 3-15 years old meeting inclusion criteria were assigned to a 3+3 dose escalation trial of combination valacyclovir (15 and 30 mg/kg, 3 times daily for 40 days) and cyclophosphamide (CPM) (40 mg/kg day 1, 60 mg/kg on days 8, 18, and 28) or CPM monotherapy. Subjects were monitored for clinical and laboratory toxicity and had EBV levels measured regularly. Dose-limiting toxicity (DLT) was our primary outcome.. We found that the combination of valacyclovir and CPM was safe and did not lead to any DLT compared with CPM monotherapy. The most common side effects were vomiting, abdominal pain, and tumor site pain, which were similar in both arms. Patients with measurable serum EBV showed decreased loads over their treatment course.. We recommend a phase II valacyclovir dose of 30 mg/kg 3 times daily for 40 days. We also observed that 6 of our 12 patients with presumed Burkitt lymphoma had measurable EBV viral loads that decreased over the course of their treatment, suggesting that phase II studies should investigate this correlation further. This study paves the way for a phase II efficacy trial of combined valacyclovir and CPM in the treatment of endemic Burkitt lymphoma.

Topics: Acyclovir; Adolescent; Antineoplastic Agents, Alkylating; Antiviral Agents; Burkitt Lymphoma; Child; Child, Preschool; Cyclophosphamide; Drug Therapy, Combination; Female; Herpesvirus 4, Human; Humans; Malawi; Male; Standard of Care; Treatment Outcome; Valacyclovir; Valine; Viral Load

Both oral and intravenous acyclovir administration for seven days in the early stages of infectious mononucleosis caused an inhibition of oropharyngeal Epstein-Barr virus (EBV) replication. Minimal effect on clinical symptoms was observed. Development of normal cellular and humoral EBV-specific immunity was seen in all patients. The combination of intravenous acyclovir and prednisolone treatment for 10 days in 11 patients with fulminant mononucleosis caused transient cessation of virus shedding in all patients. A dramatic clinical effect on pharyngeal symptoms and on fever was seen in nine of 11 patients within 72 hours. Treatment with chemotherapy or irradiation is recommended in EBV-associated B cell lymphomas seen in immunosuppressed, transplanted, and human immunodeficiency virus-I seropositive patients. No effect of acyclovir has been reported, but such therapy may be considered in the early stage when EBV induces a polyclonal B cell activation. Acyclovir treatment is effective in the EBV-genome positive hairy leukoplakia in human immunodeficiency virus-seropositive patients. No effect of antiviral therapy has been reported in the X-linked lymphoproliferative syndrome. Prophylactic use of immunoglobulin or acyclovir has been suggested in susceptible children.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Burkitt Lymphoma; Clinical Trials as Topic; Female; Herpesviridae Infections; Herpesvirus 4, Human; Humans; Immune Tolerance; Infectious Mononucleosis; Lymphoproliferative Disorders; Male; Prednisolone

This study aimed to assess the inhibitory activities of methanol extracts from the microalgae Ankistrodesmus convolutus, Synechococcus elongatus, and Spirulina platensis against Epstein-Barr virus (EBV) in three Burkitt's lymphoma (BL) cell lines, namely Akata, B95-8, and P3HR-1. The antiviral activity was assessed by quantifying the cell-free EBV DNA using real-time polymerase chain reaction (PCR) technique. The methanol extracts from Ankistrodesmus convolutus and Synechococcus elongatus displayed low cytotoxicity and potent effect in reducing cell-free EBV DNA (EC(50)<0.01 µg/ml) with a high therapeutic index (>28000). After fractionation by column chromatography, the fraction from Synechococcus elongatus (SEF1) reduced the cell-free EBV DNA most effectively (EC(50)=2.9 µg/ml, therapeutic index>69). Upon further fractionation by high performance liquid chromatography (HPLC), the sub-fraction SEF1'a was most active in reducing the cell-free EBV DNA (EC(50)=1.38 µg/ml, therapeutic index>14.5). This study suggests that microalgae could be a potential source of antiviral compounds that can be used against EBV.

Topics: Acyclovir; Antiviral Agents; Base Sequence; Burkitt Lymphoma; Cell Line, Tumor; Chlorophyta; DNA, Viral; Foscarnet; Herpesvirus 4, Human; Humans; Lymphoid Progenitor Cells; Microalgae; Polymerase Chain Reaction; Spirulina; Synechococcus; Viral Load

This brief communication focuses on aspects of a recent case report (Yonsei Med J 2005;46:425-30) on a full and sustained remission of Hodgkin's lymphoma (HL) after a single day of chemotherapy. A septic episode required stopping chemotherapy and starting amphotericin B and acyclovir. Remission evidence was seen within days of starting these. A review of research supporting the notion that amphotericin B can reactivate latent Epstein-Barr virus and thus allow acyclovir to kill infected HL cells is given. Experimental work is required to confirm or refute this possibility. If successful, amphotericin B and acyclovir treatment could be extended to other EBV-driven cancers such as Burkitt's lymphoma, nasopharyngeal carcinoma and the occasional EBV-related epithelial cancer of the breast, colon, prostate, and others.

Topics: Acyclovir; Amphotericin B; Anti-Bacterial Agents; Burkitt Lymphoma; Drug Synergism; Ganciclovir; Herpesvirus 4, Human; Hodgkin Disease; Humans; Remission Induction; Tumor Necrosis Factor-alpha; Virus Activation

Detection of Epstein-Barr virus (EBV) DNA in the cerebrospinal fluid (CSF) is associated with acquired immunodeficiency syndrome (AIDS)-related brain lymphoma. Real-time polymerase chain reaction (PCR) was performed to quantify EBV DNA in CSF and plasma from 42 patients with AIDS-related non-Hodgkin's lymphoma (NHL). Twenty patients had primary central nervous system lymphoma (PCNSL) and 22 systemic NHL, including 12 with central nervous system involvement (CNS-NHL). As controls, 16 HIV-infected patients with other CNS disorders were examined. EBV DNA was detected in the CSF from 16/20 (80%) patients with PCNSL, 7/22 (32%) with systemic NHL, 8/12 (67%) with CNS-NHL, and 2/16 (13%) of the controls. The viral EBV DNA levels were significantly higher in the CSF from patients with PCNSL or CNS-NHL compared to patients with systemic NHL or controls. EBV DNA was detected in plasma from 5/16 (31%) patients with PCNSL, 9/16 (56%) with systemic NHL, 4/9 (44%) with CNS-NHL, and 4/15 (27%) controls. No difference in plasma viral load was found between patient groups. From the patients with CNS-NHL, plasma samples drawn prior to CNS involvement contained significantly higher EBV DNA levels than those from systemic NHL patients without subsequent CNS involvement. EBV DNA levels in the CSF, but not in plasma, from patients treated with antiherpes drugs were significantly lower than in untreated patients. High CSF EBV DNA levels were found in HIV-associated brain lymphomas and the viral load can be clinically useful. High plasma EBV DNA levels might predict CNS involvement in systemic NHL.

Topics: Acyclovir; Antiviral Agents; Biomarkers, Tumor; Burkitt Lymphoma; Central Nervous System Neoplasms; DNA, Viral; Epstein-Barr Virus Infections; Ganciclovir; Herpesvirus 4, Human; Humans; Lymphoma, AIDS-Related; Lymphoma, Large B-Cell, Diffuse; Polymerase Chain Reaction; Retrospective Studies; Viral Load

The aim of this study was to determine the incidence and outcome of herpes zoster hospitalised children with cancer in Kota Baru. It was a retrospective review from January 1994 to December 1998. The diagnosis of herpes zoster was a clinical one. Herpes zoster was diagnosed in 10 of 188 (5%) children with malignancy. The most common malignancy was leukaemia. Nine children were treated with acyclovir. No child developed visceral dissemination and there were no deaths.

Topics: Acyclovir; Antiviral Agents; Burkitt Lymphoma; Child; Child, Preschool; Female; Herpes Zoster; Humans; Immunocompromised Host; Leukemia, Myeloid, Acute; Malaysia; Male; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Retrospective Studies; Treatment Outcome

Two HIV patients with Epstein-Barr virus (EBV)-associated B cell lymphoma of high grade malignancy enjoyed prolonged remission after therapy with COPBLAM and the antiviral agent Acyclovir. After 3, respectively 5 cycles of treatment, the patients (stage C3 according to CDC) responded to the administered drugs by achieving complete remission. Under maintenance therapy with Acyclovir for 32, respectively 31 months, both patients still remain free of lymphoma as of today.

Topics: Acyclovir; Adult; Antineoplastic Combined Chemotherapy Protocols; Antiviral Agents; Bleomycin; Burkitt Lymphoma; Cyclophosphamide; Doxorubicin; Humans; Lymphoma, AIDS-Related; Lymphoma, Non-Hodgkin; Male; Middle Aged; Prednisone; Procarbazine; Remission Induction; Vincristine

To assess whether oral acyclovir can eliminate persistent Epstein-Barr virus (EBV) infection and thereby prevent EBV-associated lymphoma development in HIV-seropositive homosexual men.. Persistent EBV infection was examined in a group of 21 HIV-seropositive homosexual men before, during and after treatment with oral acyclovir at a dose of 800 mg every 6 h (10 individuals) or with a placebo (11 individuals).. In 13 individuals, EBV was isolated from the oropharynx before and after treatment (seven cases from the acyclovir-treated group and six from the placebo-treated group). A significant reduction in virus isolation occurred during treatment in the acyclovir-treated group, but not in the placebo-treated group. In seven cases in whom EBV shedding was detected before and after treatment, the EBV strain isolated was identical throughout the study, even when acyclovir had abolished detectable shedding for the duration of the treatment. In two other cases more than one strain was detected. On examination of the EBV type present, 89% of a group of 18 patients consistently shed type A virus, 5.5% type B virus and 5.5% showed evidence of co-infection with both virus types. This compares with figures of 100, 0 and 0%, respectively, in a control group of HIV-seronegative individuals.. High-dose acyclovir therapy does not eliminate persistent EBV infection from the oropharynx of healthy HIV-seropositive individuals and therefore would not necessarily prevent lymphoma development. Our results suggest that infection by type B EBV, and co-infections of both A and B type, are more common in HIV-seropositives than HIV-seronegatives.

Topics: Acyclovir; Administration, Oral; Adult; Blotting, Southern; Burkitt Lymphoma; Herpesviridae Infections; Herpesvirus 4, Human; HIV Seropositivity; Homosexuality; Humans; Male; Oropharynx; Tumor Virus Infections

Epstein-Barr virus (EBV) is associated with lymphomas and lymphoproliferative diseases that occur mainly in immunocompromised patients, but the role EBV plays in their pathogenesis is unclear. The evidence linking EBV etiologically to these disorders includes the presence of EBV DNA and nuclear antigens in the lesions and serologic evidence that some patients with these lesions are experiencing primary or reactivated EBV infections. These syndromes may represent proliferation of cells latently infected with EBV, but the possibility of viral replication has not been rigorously studied. DNA extracted from biopsies of 35 lymphoproliferative diseases was probed with regions of the EBV genome capable of distinguishing circular, episomal DNA found in latency from linear, replicating EBV DNA. All samples contained restriction fragments characteristic of fused termini, indicative of circular, latent genomes. Thirteen samples contained additional restriction fragments diagnostic of linear EBV DNA. Therefore, replicating EBV DNA is found in approximately 40% of EBV-associated lymphoproliferative disorders.

Topics: Acyclovir; Adolescent; Adult; Blotting, Southern; Burkitt Lymphoma; Cell Line; Child; Child, Preschool; Deoxyribonuclease BamHI; DNA Probes; DNA Replication; DNA, Viral; Female; Herpesvirus 4, Human; Humans; Immune Tolerance; Lymphoma; Lymphoproliferative Disorders; Male; Middle Aged; Nucleic Acid Hybridization; Restriction Mapping; Tumor Cells, Cultured; Virus Replication

The selective and potent anti-herpesvirus drug, (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVdU), has been examined for its inhibitory effects on several parameters of Epstein-Barr virus (EBV) infection in the lymphoblastoid cell lines Raji, P3HR-1, B-95-8 and P3 hybrid cells (a human embryo oropharyngeal cell line fused with a nasopharyngeal carcinoma cell line). At a dosage of 0.03 to 0.1 mM, BVdU caused a marked inhibition of (i) spontaneous viral capsid antigen (VCA) expression in B-95-8 and P3 hybrid cells, (ii) VCA expression and DNA synthesis in B-95-8 cells induced with croton oil and n-butyrate, (iii) early antigen (EA) expression and DNA synthesis in Raji cells superinfected with EBV, and (iv) VCA expression and DNA synthesis in B-95-8 cells superinfected with EBV. In its inhibitory effects on these various parameters of EBV infection, BVdU appears to be comparable to acyclovir [9-(2-hydroxyethoxymethyl)guanine], another selective anti-herpesvirus drug which has been previously recognized as an effective inhibitor of EBV replication.

Topics: Acyclovir; Animals; Antiviral Agents; Arabinonucleosides; Bromodeoxyuridine; Burkitt Lymphoma; Callitrichinae; Cell Line; Drug Evaluation, Preclinical; Herpesviridae Infections; Herpesvirus 4, Human; Humans; Hybrid Cells; In Vitro Techniques; Thymidine; Virus Cultivation; Virus Replication

A monoclonal diffuse histiocytic lymphoma developed during the course of a serologically documented primary Epstein-Barr virus infection in a 22-year-old cardiac transplant recipient taking cyclosporine and prednisone. Throat washings revealed the virus at tumor presentation, and the tumor was shown to contain Epstein-Barr nuclear antigen-positive cells and the viral genome. Prolonged inversion of the T cell helper/suppressor ratio was demonstrated. A brief course of acyclovir appeared to halt viral shedding in the throat but had no apparent effect on the tumor.

Topics: Acyclovir; Adult; Burkitt Lymphoma; Cyclosporins; Heart Transplantation; Herpesvirus 4, Human; Humans; Immunosuppression Therapy; Male; Postoperative Complications; Prednisone

The diterpene ester promoter of mouse skin tumors, 12-O-tetradecanoylphorbol-13-acetate (TPA), efficiently induces Epstein-Barr virus (EBV)-associated DNA polymerase (DNA nucleotidyltransferase) activity in the EBV-producing lymphoblastoid cell line, P3HR-1. With the use of intervent dilution chromatography followed by sequential DEAE-cellulose and phosphocellulose column chromatography, the virus-associated enzyme has been isolated and purified 300-fold. The partially purified EBV DNA polymerase activity could be distinguished from cellular polymerases by its activation with salt and its degree of sensitivity to N-ethylmaleimide and phosphonoacetic acid. The enzyme showed maximum activity for copying activated calf thymus DNA in the presence of 100 mM ammonium sulfate. In the absence of salt, the enzyme utilized with high efficiency deoxyoligomer-homopolymer templates, but failed to copy poly(rA) . oligo(dT)10 and oligo(dT)10, showing that the enzyme had properties distinct from DNA polymerase gamma, reverse transcriptase, and terminal deoxynucleotidyltransferase. The partially purified enzyme is strongly inhibited by acyclovir triphosphate and thus has properties similar to herpes simplex virus DNA polymerase.

Topics: Acyclovir; Antiviral Agents; Burkitt Lymphoma; Cell Line; DNA Polymerase I; DNA Polymerase II; DNA-Directed DNA Polymerase; Enzyme Induction; Ethylmaleimide; Guanine; Herpesvirus 4, Human; Humans; Kinetics; Phorbols; Phosphonoacetic Acid; Tetradecanoylphorbol Acetate

Acyclovir [9-(2-hydroxyethoxymethyl)guanine] triphosphate inhibits Epstein-Barr virus (EBV)-associated DNA polymerase (DNA nucleotidyltransferase; EC 2.7.7.7) to a greater extent than it inhibits host alpha and beta DNA polymerases. The affinity of the compound for viral polymerase is 100-fold higher than for alpha-polymerase. The extent of inhibition is dependent upon the base composition of the template-primer. The inhibition is prevented by increasing concentrations of deoxyguanosine triphosphate. The EBV-associated DNA polymerase reaction in the presence of the inhibitor, although depressed, proceeds at a linear rate over a long period of time. In contrast, the reaction of Escherichia coli DNA polymerase I in the presence of 2',3'-dideoxythymidine 5'-triphosphate, a DNA chain terminator, levels off after initial linearity. Preincubation of acyclovir triphosphate with DNA and enzyme does not increase its inhibitory activity. The virus-producing cell line P3HRF-1 consistently shows reduced viral genome numbers and viral capsid antigen on prolonged exposure to acyclovir. The number of EBV genomes returns to the control level when the cells are grown in drug-free medium. The results suggest that a competitive mechanism is the major mode of acyclovir inhibition of EBV replication.

Topics: Acyclovir; Burkitt Lymphoma; Cells, Cultured; DNA, Viral; Guanine; Herpesvirus 4, Human; Humans; Kinetics; Nucleic Acid Synthesis Inhibitors; Substrate Specificity; Templates, Genetic; Viral Proteins; Virus Replication

Topics: Acyclovir; Ammonium Sulfate; Burkitt Lymphoma; Cell Line; Chromatography; DNA-Directed DNA Polymerase; Gene Expression Regulation; Guanine; Herpesvirus 4, Human; Humans; Hydrogen-Ion Concentration; Nucleic Acid Synthesis Inhibitors; Phosphonoacetic Acid; Viral Proteins