In this setting, in which most patients with allergy were switched to another preparation, there was no adverse prognostic impact of clinical or subclinical allergy to asparaginase.

Asparaginase is an effective antileukemic agent and is included in most front-line protocols for pediatric acute lymphoblastic leukemia (ALL) worldwide; however, allergic reactions to asparaginase may be dose-limiting. We evaluated plasma anti-asparaginase antibody concentrations in a cohort of children with newly diagnosed ALL, who did and who did not exhibit clinical hypersensitivity, after Escherichia coli (E. coli) asparaginase therapy. Thirty-five children who received asparaginase 10 000 IU/m 2 i.m. three times weekly for nine doses as part of both multiagent induction and reinduction chemotherapy, and seven monthly doses during the first 7 months of continuation treatment, were studied. Twenty-two patients experienced initial allergic reactions to asparaginase during continuation (n = 20) or reinduction (n = 2) phases and 13 children did not exhibit any reaction. An enzyme-linked immunosorbent assay (ELISA) was used to measure anti-asparaginase antibodies in plasma samples, diluted 1:3200, using E. coli asparaginase as the antigen. The median anti-asparaginase antibody concentration (OD at 1:3200 dilution) increased from 0.039 at induction to 0.506 at reinduction in patients who exhibited clinical hypersensitivity (P = 0.0002). By comparison, median antibody level increased from 0.011 to 0.032 OD at identical time points in patients who did not react to asparaginase (P = 0.02). Both post-induction and post-reinduction anti-asparaginase antibody levels were higher in reacting than in nonreacting patients (P = 0.004 and P = 0.01, respectively). Antibody levels were inversely related to the time elapsed between the reaction and sampling (P = 0.011). Although anti-asparaginase antibody levels increased from the post-induction plasma sample to the post-reinduction sample in 28 of 35 patients regardless of whether they exhibited clinical hypersensitivity, patients with hypersensitivity reactions had higher antibody levels than did identically treated control patients at comparable time points in therapy. Therefore, antibody analysis may be of clinical value in predicting future hypersensitivity.

Changes in plasma somatomedia-C/insulin-like growth factor I (Sm-C/IGF-I) concentrations are a sensitive indicator of the anabolic response of normal human volunteers to alterations in nutritional intake. To determine if measurement of this peptide could be used to monitor the response to nutritional repletion in malnourished patients, six patients were studied while receiving nutritional support for periods of 10-16 days. Plasma Sm-C/IGF-I increased from a mean basal level of 0.67 +/- 0.15 U/ml (+/-1 SD) to a peak of 1.80 +/- 0.44 U/ml on day 10, then declined to a concentration of 1.28 +/- 0.49 U/ml by day 16. All patients entered positive nitrogen balance by day 2 and nitrogen accretion continued throughout the study. Changes in serum concentrations of prealbumin, transferrin, and retinol-binding protein were compared to changes in Sm-C/IGF-I during nutritional support. Prealbumin increased to a posttreatment mean of 121 +/- 23% of control by the end of the study (p greater than 0.05, NS). Likewise, there was minimal change in retinol-binding protein, a peak value of 118 +/- 21% of control being reached by day 12 of treatment (p greater than 0.05, NS). Transferrin also showed minimal change, increasing to a mean value of 110% +/- 13% of control by day 12 (p greater than 0.05, NS). Measurement of plasma Sm-C/IGF-I concentrations appears to be a much more sensitive index of acute directional changes in nutritional status than other plasma proteins commonly used to monitor nutritional responses. The increase of Sm-C/IGF-I correlated temporally with entry into positive nitrogen balance.(ABSTRACT TRUNCATED AT 250 WORDS)

Several formulas for predicting creatinine clearance (Ccr) are used for adjusting drug dosages but limited data are available on their accuracy in patients with significant renal impairment or concurrent disease. We measured 144 Ccr in 103 patients and compared results using four predictive methods. Of nine common diseases in these patients, liver disease was associated with a large (p less than 0.02) prediction error (overprediction). After data from eight patients with liver disease were removed, there was good overall correlation between predicted and measured Ccr (r2 = 0.91 for each method) but only two of the methods (I and IV) were consistently accurate in all ranges of renal function. Methods for predicting Ccr should not be used in patients with liver disease.