Hepatic manifestations of tuberous sclerosis complex: a genotypic and phenotypic analysis. A retrospective review of the clinical records and radiological images of 205 patients with tuberous sclerosis complex (TSC) was performed to evaluate the prevalence and progression of hepatic lesions; examine the association of hepatic phenotype with genotype, age, and gender; and investigate the relationships between hepatic, renal, and pulmonary involvement. Hepatic angiomyolipomas (AML), cysts, and other benign lesions were identified in 30% of the cohort, and some lesions grew significantly over time. However, no patient had clinical symptoms or complications from hepatic lesions. TSC2 patients exhibited a higher frequency of AML compared to TSC1 patients (p = 0.037), and patients with no mutation identified exhibited a higher frequency of cysts compared to TSC2 patients (p = 0.023). Age was positively correlated with frequency of hepatic involvement (p < 0.001), whereas hepatic phenotype was independent of gender. Presence of hepatic AML was associated with presence of renal AML (p = 0.001). These findings confirm a high rate of asymptomatic hepatic lesions in TSC and further characterize the TSC phenotype.

Retroviral transfer of Herpes simplex virus thymidine kinase to T cells has been used to confer sensitivity to the antiviral agent ganciclovir. This has allowed therapeutic approaches to be developed in which T cells mediating graft-versus-hostGraft-versus-host disease (GVHD) is a T cell-mediated complication of allogeneic hematopoietic stem cell transplantation (HSCT), and despite advances in immunosuppression, remains a major cause of transplantationrelated morbidity and mortality. 1-3 Donor T cells are known to mediate a potent anti-leukemic effect in patients with hematological malignancies and this has been demonstrated by the successful use of donor lymphocyte infusions (DLI) for the treatment of patients with chronic myeloid leukemia (CML). 4 The depletion of T cells from HSC grafts is associated with a reduction in GVHD, but increases the risk of graft failure and leukemic relapse. 5 Furthermore, as a consequence of the prolonged period of immunodeficiency following T cell depletion, life-threatening viral and fungal infections are of serious concern. 6 In order to harness the beneficial effects of donor lymphocytes whilst limiting adverse effects, several groups have initiated clinical trials exploring the possibility of using genetically modified T cells fitted with the Herpes Simplex thymidine kinase (HSVTK) 'suicide' gene to direct selective elimination of actively dividing cells through activation of the prodrug ganciclovir (GCV) in the event of serious GVHD. 7,8 GCV and aciclovir (ACV) are anti-viral prodrugs that are widely used for the treatment of cytomegalovirus (CMV) and Herpes simplex virus (HSV) infections. They are poor substrates for mammalian nucleoside kinases, but are efficiently phosphorylated to the monophosphate form by HSV-TK. Cellular kinases mediate subsequent metabolism to produce toxic triphosphate derivatives that become incorporated into host cell DNA, leading to the death of actively dividing cells. 9 Bonini et al 7 reported the results from the first clinical trials using the HSV-TK/ganciclovir system for the management of GVHD following bone marrow transplantation (BMT). Twelve patients who had relapsed following allogeneic BMT or developed Epstein-Barr virus induced lymphoproliferative disease after T cell-depleted bone marrow transplantation were treated with infusions of donor T cells carrying HSV-TK. The transduced cells mediated anti-tumor effects in five patients and were detectable in some patients for up to 12 months. GVHD was effectively controlled in three of these five patients by the selective elimination of active T cells using ganciclovir. One case of chronic GVHD was only partially responsive to ganciclovir, and vector-related limitations included evidence of an immune response against the transgenes in two patients. 10 The group has now treated over 40 patients using this strategy, but results have yet to be fully evaluated. 11 Tiberghien et al 8 used HSV-TK transduced T cell infusions to prevent leukemic relapse in 14 patients undergoing BMT for haematolo...