Taxanes are among the most active drugs for the treatment of metastatic breast cancer, and, as a consequence, they have also been studied in the adjuvant setting. After breast cancer surgery, women with lymph node–positive disease were randomly assigned to treatment with fluorouracil, epirubicin, and cyclophosphamide (FEC) or with FEC followed by weekly paclitaxel (FEC-P). The primary endpoint of study—5-year disease-free survival (DFS)—was assessed by Kaplan–Meier analysis. Secondary endpoints included overall survival and analysis of the prognostic and predictive value of clinical and molecular (hormone receptors by immunohistochemistry and HER2 by fluorescence in situ hybridization) markers. Associations and interactions were assessed with a multivariable Cox proportional hazards model for DFS for the following covariates: age, menopausal status, tumor size, lymph node status, type of chemotherapy, tumor size, positive lymph nodes, HER2 status, and hormone receptor status. All statistical tests were two-sided. Among the 1246 eligible patients, estimated rates of DFS at 5 years were 78.5% in the FEC-P arm and 72.1% in the FEC arm (difference = 6.4%, 95% confidence interval [CI] = 1.6% to 11.2%; P = .006). FEC-P treatment was associated with a 23% reduction in the risk of relapse compared with FEC treatment (146 relapses in the 614 patients in the FEC-P arm vs 193 relapses in the 632 patients in the FEC arm, hazard ratio [HR] = 0.77, 95% CI = 0.62 to 0.95; P = .022) and a 22% reduction in the risk of death (73 and 95 deaths, respectively, HR = 0.78, 95% CI = 0.57 to 1.06; P = .110). Among the 928 patients for whom tumor samples were centrally analyzed, type of chemotherapy (FEC vs FEC-P) ( P = .017), number of involved axillary lymph nodes ( P < .001), tumor size ( P = .020), hormone receptor status ( P = .004), and HER2 status ( P = .006) were all associated with DFS. We found no statistically significant interaction between HER2 status and paclitaxel treatment or between hormone receptor status and paclitaxel treatment. Among patients with operable breast cancer, FEC-P treatment statistically significantly reduced the risk of relapse compared with FEC as adjuvant therapy.

New therapies are being introduced in reconstructive transplant surgery to enhance composite tissue allograft survival. Alemtuzumab was used in two bilateral hand allograft recipients to cause lymphocyte depletion. Although profound leukopenia and lymphopenia developed, several episodes of acute rejection occurred both in the early and late posttransplant period. Cell-mediated rejection was diagnosed during acute rejection episodes. Intraluminal C4d deposits were found in the capillaries not only accompanying cellular rejection, but also in the absence of clinical rejection. However, their significance is unclear because donor-specific antibodies were absent, there were no pathological signs of injury, allograft function was not impaired, and clinical signs of rejection resolved. These findings suggest that alemtuzumab may not prevent cell-mediated rejection of a hand allograft transplant. Furthermore, C4d deposition warrants attention in clinical composite tissue allotransplants.

Allografts of the forearm are still uncommon in the field of composite tissue allograft transplantation. In November 2007, a right-hand allograft and a left-hand/full-length forearm allograft were transplanted in a 30-year-old man who lost both hands and the vision in his left eye due to an explosion. The patient underwent alemtuzumab and steroid induction therapy. Tacrolimus, mycophenolate mofetil, and low doses of steroids were given to prevent rejection. The allografts were rejected 3 times, but these episodes were controlled successfully. The immunosuppressive regimen was switched from tacrolimus to sirolimus because of increased serum creatinine. The left allograft showed a flexion contracture due to muscle fibrosis that was conjectured to be associated with a perioperative ischemic injury and permitted only a Moberg-type key pinch. In contrast, an excellent grade of function was observed in the right allograft. The Disabilities of the Shoulder, Arm, and Hand score improved from 70.83 to 36.6 and intrinsic musculature returned to both allografts. The patient was able to work 2 years after transplantation. This is the first report of an ischemic injury related to the successful allotransplantation of a composite tissue.