ALBERT

Description: Abstract 2232 Poster Board II-209 Introduction Chronic graft-versus-host disease (cGVHD) is the major long term complication of allogeneic stem cell transplantation and shares similarities with auto-immune diseases, like systemic sclerosis (SSc).Although the contribution of donor T cells in the development of both acute and chronic GVHD is beyond doubt; the role of B cells is less defined. However, two observations suggest that B cells do contribute to chronic GVHD. First, autoantibodies can be detected in 15-90% of chronic GVHD patients. Furthermore, several small-scale retrospective clinical studies demonstrated that in vivo depletion of B cells with the CD20-specific Ab rituximab results in amelioration of chronic GVHD symptoms in heavily pretreated steroid-refractory patients. Objective In order to prospectively investigate B cell depletion as therapy for cGVHD, we have studied the efficacy of the CD20-specific antibody rituximab in patients with steroid-refractory extensive cGVHD. Methods In an ongoing prospective phase I/II study 15 patients with steroid-refractory extensive cGVHD were treated with rituximab (375 mg/m2 per week for 4 consecutive weeks). Clinical responses were monitored monthly for 1 year according to the NIH criteria (EudraCT 2008-004125-42). Results A total of 60 rituximab infusions were administered to 15 patients with steroid-refractory cGvHD. Toxicity was limited to one infectious event and one allergic reaction. Clinical responses were so far analyzed in 12 patients. Median follow-up was 6.5 months (range 1-13). Eight patients showed a partial response (67%) of which 5 patients (42%) had an ongoing response up to 1 year of follow-up and 3 patients (25%) relapsed. Two relapsed patients were retreated with rituximab 8 months after cessation of the initial rituximab treatment and showed again a partial response. In patients with deep sclerosis (n=10), sclerotic features disappeared completely or partially in 8 patients (80%). In patients with involvement of eyes (n=10), mucosa (n=4) and gastro-intestinal tract (n=4) response was observed in 50%, 25% and 25% of patients, respectively. Consequently, prednisone dosage could be reduced in 7 patients (58%). In 4 patients (33%) prednisone treatment was stopped completely. Conclusion Rituximab treatment is a feasible and effective treatment in patients with steroid refractory cGVHD. In addition, also patients with relapse of cGVHD after cessation of rituximab treatment can be successfully treated. Thereby, sclerotic lesions of the skin improved in the majority of patients whereas eye, mucosal and gastro-intestinal tract involvement was less reversible. We speculate that the lack of improvement of eye and mucosal involvement is a consequence of an early and irreversible destruction of lacrimal and salivary glands and this argues for an upfront application of rituximab in patients with cGVHD. Disclosures: Off Label Use: Rituximab, a monoclonal anti-CD20 antibody, is used to deplete B-cells in the treatment of chronic GVHD.

Description: A tropospheric energy budget argument is used to analyze twentieth-century precipitation changes. It is found that global and ocean-mean general circulation model (GCM) precipitation changes can be understood as being due to the competing direct and surface-temperature-dependent effects of external climate forcings. In agreement with previous work, precipitation is found to respond more strongly to anthropogenic and volcanic sulfate aerosol and solar forcing than to greenhouse gas and black carbon aerosol forcing per unit temperature. This is due to the significant direct effects of greenhouse gas and black carbon forcing. Given that the relative importance of different forcings may change in the twenty-first century, the ratio of global precipitation change to global temperature change may be quite different. Differences in GCM twentieth- and twenty-first-century values are tractable via the energy budget framework in some, but not all, models. Changes in land-mean precipitation, on the other hand, cannot be understood at all with the method used here, even if land–ocean heat transfer is considered. In conclusion, the tropospheric energy budget is a useful concept for understanding the precipitation response to different forcings but it does not fully explain precipitation changes even in the global mean.