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Chakraverty R.,Royal Free Hampstead National Health Service NHS Trust | Orti G.,Royal Free Hampstead National Health Service NHS Trust | Roughton M.,University College London | Shen J.,Millipore | And 18 more authors.
Blood | Year: 2010

In vivo alemtuzumab reduces the risk of graft-versus-host disease (GVHD) and nonrelapse mortality after reduced intensity allogeneic transplantation. However, it also delays immune reconstitution, leading to frequent infections and potential loss of graft-versus-tumor responses. Here, we tested the feasibility of alemtuzumab dose deescalation in the context of fludarabine-melphalan conditioning and human leukocyte antigen (HLA)-identical sibling transplantation. Alemtuzumab was given 1-2 days before graft infusion, and dose reduced from 60 mg to 20 mg in 4 sequential cohorts (total n = 106). Pharmacokinetic studies were fitted to a linear, 2-compartment model in which dose reduction led to incomplete saturation of CD52 binding sites and greater antibody clearance. Increased elimination was particularly evident in the 20-mg group in patients who had CD52-expressing tumors at time of transplantation. The 20-mg dose was also associated with greater risk of severe GVHD (acute grade III-IV or chronic extensive) compared with > 20 mg (hazard ratio, 6.7; 95% CI, 2.5-18.3). In contrast, dose reduction to 30 mg on day -1 was associated with equivalent clinical outcomes to higher doses but better lymphocyte recovery at 12 months. In conclusion, alemtuzumab dose reduction to 30 mg is safe in the context of reduced intensity conditioning and HLA-identical sibling transplantation. This trial was registered at http://www.ncrn.org.uk as UKCRN study 1415. © 2010 by The American Society of Hematology. Source


Skipworth J.R.A.,Royal Free Hampstead National Health Service NHS Trust | Skipworth J.R.A.,University College London | Morkane C.,Royal Free Hampstead National Health Service NHS Trust | Raptis D.A.,Royal Free Hampstead National Health Service NHS Trust | And 11 more authors.
HPB | Year: 2011

Background: Patients with familial adenomatous polyposis (FAP) develop duodenal and ampullary polyps that may progress to malignancy via the adenoma-carcinoma sequence. Objective: The aim of this study was to review a large series of FAP patients undergoing pancreaticoduodenectomy for advanced duodenal and ampullary polyposis. Methods: A retrospective case notes review of all FAP patients undergoing pancreaticoduodenectomy for advanced duodenal and ampullary adenomatosis was performed. Results: Between October 1993 and January 2010, 38 FAP patients underwent pancreaticoduodenectomy for advanced duodenal and ampullary polyps. Complications occurred in 29 patients and perioperative mortality in two. Postoperative histology revealed five patients to have preoperatively undetected cancer (R = 0.518, P < 0.001). Conclusions: Pancreaticoduodenectomy in FAP is associated with significant morbidity, but low mortality. All patients under consideration for operative intervention require careful preoperative counselling and optimization. © 2011 International Hepato-Pancreato-Biliary Association. Source

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