acyclovir and Retinoblastoma

Epstein-Barr virus-associated lymphoproliferative disease (EBV-LPD) is a serious disorder seen in various states of immunodeficiency, often with a fatal outcome. In this article, a patient with EBV-lymphoma after autologous stem cell rescue for treatment of a nonhematologic solid tumor is described. The child, a 4-year-old boy, had unilateral retinoblastoma with metastatic spread to the central nervous system. He had previously received both local tumor bed and craniospinal radiation therapy together with intensive myeloablative alkylator chemotherapy before autologous stem cell rescue. Histologically confirmed lymphoma with evidence of active EBV proliferation developed within cervical lymph nodes 3 weeks after his first autologous stem cell rescue. A complete clinical remission of the lymphadenopathy was obtained after infusions of rituximab (an anti-CD20 monoclonal antibody), acyclovir, and high-titer anticytomegalovirus immunoglobulin. The patient died approximately 6 months later of persistent and progressive retinoblastoma without any clinical evidence of lymphoma. It is concluded that EBV-LPD should be included in the differential diagnosis in patients in whom lymphadenopathy develops after autologous stem cell rescue.

Topics: Acyclovir; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Antiviral Agents; Carboplatin; Central Nervous System Neoplasms; Child, Preschool; Combined Modality Therapy; Cyclophosphamide; Disease Progression; Epstein-Barr Virus Infections; Etoposide; Eye Enucleation; Eye Neoplasms; Fatal Outcome; Hematopoietic Stem Cell Transplantation; Herpesvirus 4, Human; Humans; Immunocompromised Host; Immunoglobulins, Intravenous; Immunosuppressive Agents; Immunotherapy; Lymphoma, Large B-Cell, Diffuse; Male; Meningeal Neoplasms; Methylprednisolone; Neoplasm Recurrence, Local; Neoplasms, Second Primary; Optic Nerve Neoplasms; Radiotherapy, Adjuvant; Retinoblastoma; Rituximab; Thiotepa; Vincristine

The purpose was to determine the potential of gene therapy for retinoblastoma using transfer of the herpes simplex virus thymidine kinase (HSV-TK) gene into retinoblastoma cells (Y79 cell line).. A retrovirus-packaging cell line PA317 was electroporated with a retroviral vector plasmid bearing HSV-TK and neomycin-resistance genes to produce a PA317-TK cell line releasing a replication-defective vector bearing both genes. Y79 was transduced by exposure to transmissible virus-containing medium from PA317-TK, and new clones of Y79 containing the HSV-TK gene (Y79-TK) were established. Sensitivity to ganciclovir (GCV) and acyclovir (ACV) was investigated in Y79 and Y79-TK and the effect of HSV-TK-positive cells on negative cells ("bystander effect") was determined in vitro. The effect of antitumorigenesis in a nude mouse system was also investigated.. There were no differences in the growth pattern or the morphology between Y79 and Y79-TK. Y79-TK was more sensitive to GCV and ACV than was Y79. The cytotoxicity of Y79-TK was dose dependent. An obvious "bystander effect" was present with the addition of GCV. In vivo studies confirmed the ability of GCV to kill Y79-TK.. In this study a model is proposed for the introduction of a drug-sensitivity gene into Y79 and the possibility is raised of treating retinoblastoma with gene therapy. The results suggest that the transfer of the HSV-TK gene into Y79 followed by the administration of GCV could serve as a model for gene therapy for retinoblastoma.

Topics: Acyclovir; Animals; Defective Viruses; Dose-Response Relationship, Drug; Electroporation; Ganciclovir; Gene Transfer Techniques; Genetic Therapy; Genetic Vectors; Herpesvirus 1, Human; Humans; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Retinal Neoplasms; Retinoblastoma; Retroviridae; Thymidine Kinase; Tumor Cells, Cultured