Fig. 1. Schematic representation of the multiple factors and effects involved in RCM reactions. Taken from (Szebeni, 2004a and Szebeni, 2004b) with permission of the publishers.

Fig. 2. Time course of Doxil induced changes in plasma SC5b-9 in cancer patients and its individual variation. Panels A–D demonstrate data from four subjects displaying different patterns of response. Data are mean ± S.D. for triplicate determinations. (*) Significantly different from baseline, P < 0.05. Reproduced from (Chanan-Khan et al., 2003) with permission.

Fig. 3. Plasma SC5b-9 levels at baseline and at 10 min post-infusion of Doxil in cancer patients displaying (A) or not displaying (B) HSRs to Doxil. Data are mean ± S.D. for triplicate or duplicate determinations. The dashed lines indicate the normal range of SC5b-9, i.e., the normal mean ± 2 S.D. (*) Significantly different from baseline (P < 0.05). The numbers under the bars are the patient ID. Reproduced from (Chanan-Khan et al., 2003) with permission.

Fig. 4. Cryo-TEM images of vitrified specimens of Cremophor EL in saline (PBS) and in human serum. (A) Taxol vial-equivalent CrEL/ethanol stock solution was diluted 10-fold in PBS. The dark spots represent “star” micelles, schematically depicted in the insert. (B) Larger amplification of CrEL micelles. (C) Vitrified specimens of a normal human serum, demonstrating some lipoprotein particles in the chylomicron size range. (D) CrEL was incubated with the same serum for 10 min at 37 °C, leading to the formation of numerous particles of varying size. Reproduced from (Szebeni et al., 2001) with permission.

Fig. 5. Proposed new scheme of hypersensitivity reactions with Revision of the Type 1 category. Partially reproduced from (Szebeni et al., 2002).

Symptoms of IgE-mediated Type I allergy and complement activation-related pseudoallergy

The SC5b-9 assay as predictor of HSRs to Doxil

Patients were classified into four groups according to the concurrent presence (+) or absence (−) of HSR and C reactivity, as follows: true positive (tp: HSR+, C+), false positive (fp: HSR−, C+), true negative (tn: HSR−, C−) and false negative (fn: HSR+, C−). In addition, laboratory reactors were stratified to three categories on the basis of 10 min SC5b-9 values, as specified in column 1. The 0.98 and 1.96 μg/mL cut-off values represent two- and four-times the upper limit of normal SC5b-9 levels (0.49 μg/mL), respectively, and were chosen arbitrarily. The sensitivity, specificity and positive and predictive values of the SC5b-9 assay with regard to HSRs were computed as described (Chanan-Khan et al., 2003).