Choroid plexus papilloma-A case highlighting the challenges of extrapolating pediatric chemotherapy regimens to adult populations.

The treatment of adults who present with rare pediatric tumors is not characterized well in the literature. We report an instance of a 40-year-old African American woman with a diagnosis of choroid plexus carcinoma admitted to the intensive care unit for severe sepsis seven days after receiving chemotherapy consisting of carboplatin (350 mg/m(2) on Days 1 and 2 plus etoposide 100 mg/m(2) on Days 1-5). Her laboratory results were significant for an absolute neutrophil count of 0/µL and blood cultures positive for Capnocytophagia species. She was supported with broad spectrum antibiotics and myeloid growth factors. She eventually recovered and was discharged in stable condition. The management of adults with malignancies most commonly seen in pediatric populations presents substantial challenges. There are multiple age-specific differences in renal and hepatic function that explain the need for higher dosing in pediatric patients without increasing the risk of toxicity. Furthermore, differences in pharmacokinetic parameters such as absorption, distribution, and clearance are present but are less likely to affect patients. It is expected that the pediatric population will have more bone marrow reserve and, therefore, less susceptible to myelosuppression. The extrapolation of pediatric dosing to an adult presents a problematic situation in treating adults with malignancies that primarily effect pediatric patients. We recommend extrapolating from adult treatment regimens with similar agents rather than extrapolating from pediatric treatment regimens to reduce the risk of toxicity. We also recommend the consideration of adding myeloid growth factors. If the treatment is tolerated without significant toxicity, dose escalation can be considered.

A reevaluation of CD22 expression in human lung cancer.

CD22 is a transmembrane glycoprotein expressed by mature B cells. It inhibits signal transduction by the B-cell receptor and its coreceptor CD19. Recent reports indicate that most human lung cancer cells and cell lines express CD22, making it an important new therapeutic target for lung cancer. The objective of our studies was to independently validate these results with the goal of testing the efficacy of our CD22 immunotoxins on lung cancer cell lines. As determined by quantitative real-time PCR analysis, we found that levels of CD22 mRNA in a panel of human lung cancer cell lines were 200 to 60,000-fold lower than those observed in the human CD22(+) Burkitt lymphoma cells, Daudi. Using flow cytometry with a panel of CD22 monoclonal antibodies and Western blot analyses, we could not detect surface or intracellular expression of CD22 protein in a panel of lung cancer cell lines. In addition, the in vitro proliferation of the lung tumor cell lines was not affected by either CD22 antibodies or our highly potent anti-CD22 immunotoxin. In contrast, CD22(+) Daudi cells expressed high levels of CD22 mRNA and protein, and were sensitive to our CD22 immunotoxin. Importantly, primary non-small cell lung cancers from more than 250 patient specimens did not express detectable levels of CD22 protein as assessed by immunohistochemistry. We conclude that CD22 is not expressed at measurable levels on the surface of lung cancer cells, and that these cells cannot be killed by anti-CD22 immunotoxins.