DCF (docetaxel, cisplatin and 5-fluorouracil) chemotherapy is a promising treatment for recurrent advanced squamous cell anal carcinoma.

BACKGROUND: Squamous cell carcinoma of the anal canal (SCCA) is a rare disease, mostly diagnosed at early stage. After concurrent chemoradiation (CRT) with mitomycin C and 5-fluorouracil (5FU), local or metastatic recurrences occur in >20% of the patients. After treatment failure, cisplatin (CDDP)-based chemotherapy is the standard option, but complete response (CR) is a rare event and the prognosis remains poor. PATIENTS AND METHODS: Eight consecutive patients with advanced recurrent SCCA after CRT were treated with DCF regimen (docetaxel 75 mg/m(2) day 1, CDDP 75 mg/m(2) day 1 and 5FU at 750 mg/m(2)/day for 5 days every 3 weeks). Tumour samples were analysed for human papillomavirus (HPV) genotyping, as well as p16 and p53 expression. RESULTS: After a median follow-up of 41 months, the overall survival rate at 12 months was 62.5% (95% CI 22.9-86.1 months). Four patients achieved a complete remission and remain relapse-free at the time of analysis with a progression-free survival of 19, 33, 43 and 88 months. Three of these patients underwent surgery for all involved metastatic sites. For all of them, pathological CR was confirmed. DCF regimen appeared feasible in these patients previously exposed to pelvic CRT, and no grade IV toxicity occurred. All patients in complete remission had HPV-16-positive SCCA, while HPV could only be detected among 50% of the non-responding patients. Of interest, immunohistochemical study revealed a p16(+)/p53(-) phenotype in these patients, while none of non-responders expressed p16. CONCLUSION: The high level of complete and long-lasting remission among SCCA patients treated with DCF regimen supports the assessment of this strategy in prospective cohorts.

Alloreactivity of ex vivo-expanded T cells is correlated with expansion and CD4/CD8 ratio.

Background We have demonstrated previously that retroviral-mediated transfer of a suicide gene into bone marrow (BM) donor T cells allows an efficient control of graft-versus-host disease (GvHD) after allogeneic BM transplantation. However, the 12 days of ex vivo culture required for the production of gene-modified cells (GMC), including soluble CD3 monoclonal antibody (MAb)-mediated activation and expansion with interleukin (IL)-2, induced a decrease of GMC alloreactivity and a reversal of their CD4/CD8 ratio. Improving the culture protocol in order to maintain the highest alloreactivity is of critical importance in obtaining an optimal graft-versus-leukemia (GvL) effect. Methods Peripheral blood mononuclear cells were activated with soluble CD3 MAb or CD3 and CD28 MAb co-immobilized on beads and expanded for 12 days in the presence of IL-2, IL-7 or IL-15 before analysis of alloreactivity and phenotype. Results Replacing the CD3 MAb by CD3/CD28 beads led to similar in vitro alloreactivity but improved the expansion and in vivo alloreactivity of GMC. Replacing the IL-2 with IL-7, but not IL-15, or decreasing IL-2 or IL-7 concentrations, improved the in vitro alloreactivity of expanded cells but was associated with lower expansion. Indeed, the alloreactivity of expanded cells was negatively correlated with cell expansion and positively correlated with CD4/CD8 ratio and CD8 expression level. Discussion Quantitative (i.e. low CD4/CD8 ratio) and qualitative (e.g. low CD8 expression) defects may account for the decreased alloreactivity of GMC. Using CD3/CD28 beads and/or IL-7 is more beneficial than CD3 MAb and IL-2 for preventing perturbations of the alloreactivity and phenotype of GMC.