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The genetic modification of T cells with a suicide gene grants a mechanism of control of adverse reactions, allowing safe infusion after partially incompatible hematopoietic stem cell transplantation (HSCT). In the TK007 clinical trial, 22 adults with hematologic malignancies experienced a rapid and sustained immune recovery after T cell-depleted HSCT and serial infusions of purified donor T cells expressing the HSV thymidine kinase suicide gene (TK+ cells). After a first wave of circulating TK+ cells, the majority of T cells supporting long-term immune reconstitution did not carry the suicide gene and displayed high numbers of naive lymphocytes, suggesting the thymus-dependent development of T cells, occurring only upon TK+ -cell engraftment. Accordingly, after the infusions, we documented an increase in circulating TCR excision circles and CD31+ recent thymic emigrants and a substantial expansion of the active thymic tissue as shown by chest tomography scans. Interestingly, a peak in the serum level of IL-7 was observed after each infusion of TK+ cells, anticipating the appearance of newly generated T cells. The results of the present study show that the infusion of genetically modified donor T cells after HSCT can drive the recovery of thymic activity in adults, leading to immune reconstitution.

The extent of liver resection is limited by the residual functional reserve of the liver (FLR). The introduction of portal vein embolization (PVE), with the rationale of inducing hypertrophy of the FLR has significantly reduced morbidity and in particular the impact of postoperative liver failure (PLF). The objective of the study is to evaluate the feasibility and effectiveness of PVE in patients candidates to liver resections with high risk of PLF. Between January 2006 and December 2009, 62 patients suffering from primary or metastatic liver tumour, underwent PVE at the Department of Surgery-Liver Unit HSR. CT assessment of hepatic volume was performed in each patient, prior and 4 weeks after the procedure. The outcome was evaluated in terms of feasibility of surgery, FLR growth [calculated as: (FLR after PVE - FLR pre PVE) × 100/FLR pre PVE], morbidity and mortality associated with PVE and surgery. Of the 62 patients undergoing PVE, 6 (9.7%) did not benefit from surgery: of these, 4 showed spread of disease in the FLR at CT control, while in the remaining 2 adequate hypertrophy was not reached. The average volume of the FLR at the time of the procedure and after 4 weeks was 437.03 cc (±172.54) and 615.15 cc (± 187.49), respectively, with an average increase of 50.3% (±30.31). During the postoperative period, only 2 patients (3.2%) showed mild and transient signs of the PLF. The technique of PVE allows to performing, in an effective and safe way, major liver resections in patients with high risk of PLF.