SummaryDuring periods of immunosuppression, such as postallogeneic stem cell transplantation (SCT), patients are at significant risk for severe viral infections. Human adenovirus (HAdV) infection is a serious complication post‐SCT, especially in children. Virus‐specific T cells are essential for the clearance of HAdV, as antiviral chemotherapy has revealed limited success. We present feasibility data for a new treatment option using virus‐specific donor T cells for adoptive transfer of immunity to patients with HAdV‐infection/reactivation. Virus‐specific donor T cells were isolated and infused into nine children with systemic HAdV infection after SCT. Isolation was based on γ‐interferon (IFN‐γ) secretion after short in vitro stimulation with viral antigen, resulting in a combination of CD4+ and CD8+ T cells. 1·2–50 × 103/kg T cells were infused for adoptive transfer. Isolated cells showed high specificity and markedly reduced alloreactivity in vitro. Adoptive transfer of HAdV‐specific immunity was successful in five of six evaluable patients, documented by a dose‐independent and sustained in vivo expansion of HAdV‐specific T cells, associated with a durable clearance/decrease of viral copies. T‐cell infusion was well tolerated in all nine patients, except one case with graft‐versus‐host disease II of the skin. In conclusion, induction of a specific T‐cell response through adoptive transfer was feasible and effective. When performed early in the course of infection, adoptive T‐cell transfer may protect from HAdV‐related complications.

Hypothesis Cochleostomy or round window enlargement techniques for cochlear implant electrode insertion result in more abnormal tissue formation in the basal cochlea and are more apt to produce endolymphatic hydrops than round window electrode insertion. Methods Twelve temporal bones from implanted patients were examined under light microscopy and reconstructed with 3D reconstruction software to determine cochlear damage and volume of neo-ossification and fibrosis following electrode insertion. Amount of new tissue was compared between three groups of bones: insertion through the round window (RW), after enlarging the round window (RWE) and cochleostomy (Cochl). The probable role of the electrode was evaluated in each case with hydrops. Results More initial damage occurred in the Cochl and RWE groups than in the RW group, and the difference was significant between RWE and RW in cochlear segment I (p<0.026). The volume of new bone in segment I differed significantly between groups (p<.012) and was greater in the RWE group than in either the Cochl or RW groups (post hoc p’s <.035 and .019). Hydrops was seen in 5 cases, all in the Cochl and RWE groups. Blockage of the duct was due to new tissue formation in 4 of the 5 hydrops cases. Conclusion With the electrodes in this serie, implantation through the round window minimized initial intracochlear trauma and subsequent new tissue formation, while the round window extension technique used at the time of these implantations produced the greatest damage. Future studies may clarify whether today’s techniques and electrodes will produce these same patterns of damage.

SummaryHuman adenovirus (ADV) infection is an important complication post allogeneic stem cell transplantation (SCT), especially in children, with significant morbidity and mortality despite new antiviral treatment strategies. Although the control of infection seems to require T cells, characterization of ADV-specific T cells post-SCT has not been reported to date. Therefore, we prospectively studied the occurrence of ADV-specific T cells in children with (n ¼ 21) and without (n ¼ 25) ADV-infection postallogeneic SCT and in healthy donors (n ¼ 53). ADV-associated mortality occurred in seven of 21 children. After stimulation ex vivo with ADV-lysate, interferon-c-secreting T cells were analysed by flow cytometry. All the patients with ADV-associated mortality had no specific T cells, although reconstitution of absolute lymphocyte counts exceeded 0AE3 · 10 9 /l within 30 d post-transplant. Patients who cleared ADV infection had significantly higher frequencies (mean ± standard deviation, 0AE56 ± 0AE5%) of ADV-specific T cells until day 200 post-SCT, than patients without ADV-infection (0AE12 ± 0AE1%). These data suggest that ADV-specific T-cell reconstitution is protective against life-threatening ADV-infections postallogeneic SCT.

These results show that this option is valid for patients with a fixed footplate and unsuccessful previous surgeries or patients who cannot benefit from a stapedotomy for anatomic reasons. In some cases, access to the round window membrane could represent a limitation. However, these promising initial results establish the need for further works with regard to 3 issues: 1) clinical data studies are needed, including a greater number of patients to confirm these preliminary results; 2) a long-term follow-up must be performed to detect any possible cochlear adverse effects, in particular, on the basilar membrane; 3) the effect of fascia interposition and tip size has to be evaluated in experimental studies.