Severe infusion reactions (SIRs) at rates of 5% or less are known side effects of biological agents, including mAbs such as cetuximab. There are currently no prospectively validated risk factors to aid physicians in identifying patients who may be at risk of experiencing an SIR following administration of any of these drugs. A retrospective analysis of 545 banked serum or plasma samples from cancer patients participating in clinical trials of cetuximab was designed to evaluate whether the presence of pretreatment IgE antibodies against cetuximab, as determined by a commercially available assay system, is associated with SIRs during the initial cetuximab infusion. Patients with a positive test indicating the presence of pretreatment antibodies had a higher risk of experiencing an SIR; however, at the prespecified cutoff utilized in this analysis, the test has a relatively low-positive predictive value (0.577 [0.369–0.766]) and a negative predictive value of 0.961 (0.912–0.987) in an unselected patient population. Data collected in this large retrospective validation study support prior observations of an association between the presence of pretreatment IgE antibodies cross-reactive with cetuximab and SIRs. Further analysis of the test's ability to predict patients at risk of an SIR would be required before this assay could be used reliably in this patient population.

We have investigated the effects of open chest and open pericardium on the distribution of myocardial blood flow assessed with the radioactive microsphere technique (15 microns). Five dogs with intact thorax served as controls (group I) and six dogs were studied after a right-sided thoracotomy and pericardiotomy (group II). Global myocardial blood flow (mean +/- S.D.) was 0.73 +/- 0.17 ml.min-1.g-1 in group I and 1.22 +/- 0.09 ml.min-1.g-1 in group II (p less than 0.05). Analysis of transmural blood flow distribution revealed that flow was 44% higher in the right and 60% higher in the left ventricular endocardial layers in the open-chest animals, whereas epicardial flow increased by 105% and 90%, respectively. As a result of the preferential blood flow to the epicardial layers of the right ventricle, the endo/epi ratio was reduced from 1.30 +/- 0.26 in group I to 0.86 +/- 0.11 in the open-chest group (p less than 0.05). Left ventricular endo/epi ratio was 1.27 +/- 0.16 and 1.06 +/- 0.11 (n.s.), respectively. External work and diastolic filling pressure of the right ventricle did not differ between the two groups and therefore cannot account for the redistribution of myocardial blood flow. It is concluded that the distribution of myocardial blood flow, particularly in the RV, is severely disturbed by thoracotomy and pericardiotomy. This is an important aspect for the planning and evaluation of studies under open-chest/open-pericardium conditions.

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The antibody used is a murine monoclonal antibody (IgG2b-type) with specificity against the alpha-and beta-chain of the TCWCD3 receptor molecule; it has been developed and produced by the Behring Company (Marburg, FRG) [l, 21. Characteristically, BMA 031 activates human T-lymphocytes in vitro to a lesser degree than monoclonal antibodies with CD3 specificity of different subclassesWe have used BMA 031 prophylactically in conjunction with triple drug induction treatment in kidney-transplanted patients with an increased immunological risk (preformed lymphocytotoxic antibodies > 30% against test panel or retransplantation following previous graft loss due to immunological causes). Two different immunosuppressive protocols have been applied (protocols 1 and 2) in terms of a phase-I1 trial. t3,41. Protocol INine patients received BMA 031 intravenously at a daily dose of 5 mg over a period of 7 days postoper-Offprint requests to: W. Land atively in conjunction with ciclosporin (6 mg/kg orally), azathioprine (2 mg/kg) and methylprednisolone (500 mg430 mg daily). During or after administration, no major clinical side effects (in particular: high fever, chills, lung edema) were observed whatsoever in contrast to other commercially available agents. The actual 1 year patient survival rate is 100% and the graft survival rate 89%. However, seven of nine patients (78%) developed histologically proven acute rejection episodes, requiring further antirejection treatment (steroids, ALG, ATG). In four patients (a%), rejection occurred either during or immediately after treatment with BMA 031.During application of BMA031, the total lymphocyte number was reduced by 63% within the first 3 days. Lymphocyte subsets labelled with monoclonal antibodies CD3 decreased by 56%, CD4 by 65%, and CD8 by 73%. Normal values were again reached between days 7 and 10 after beginning therapy. With regard to the remarkable absence of clinical side effects but the relatively high incidence of reversible rejection episodes, we changed our immunosuppressive protocol (in terms of approaching immunomodulation) as follows.Protocol 2Ten consecutive patients recently received BMA 031 in terms of a "double-shot'' application: 1st injection of 50 mg intravenously during surgery; 2nd injection of 50 mg intravenously 48 h post-transplantation. In these patients triple drug induction treatment was given as mentioned in protocol 1.Over an observation period from 4.5 months to 2 weeks we observed no rejection episodes in these patients. Graft function is perfect in all cases at the present time (4.5 m; 4 m; 3.5 m; 3 m: 2.5 m; 2 m; 1 m; 1 m; 3 w; 2 w). BMA 031 had a strong impact on total lymphocyte counts. After the first injection, their number was reduced to less than 10% of circulating mononuclear cells. Another reduction was

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