There is a significant (> six-fold) overrepresentation of TPMT deficiency or heterozygosity among patients developing dose-limiting hematopoietic toxicity from therapy containing thiopurines. However, with appropriate dosage adjustments, TPMT-deficient and heterozygous patients can be treated with thiopurines, without acute dose-limiting toxicity.

No abstract

Diff use pollution remains a major threat to surface waters due to eutrophication caused by phosphorus (P) transfer from agricultural land. Vegetated buff er strips (VBSs) are increasingly used to mitigate diff use P losses from agricultural land, having been shown to reduce particulate P transfer. However, retention of dissolved P (DP) has been lower, and in some cases VBSs have increased delivery to surface waters. Th e aims of this review were (i) to develop a conceptual model to enhance the understanding of VBS functioning in terms of DP, (ii) to identify key processes within the model that aff ect DP retention and delivery, and (iii) to explore evidence for the controls on these processes. A greater understanding in these areas will allow the development of management strategies that enhance DP retention. We found evidence of a surface layer in buff er strip soils that is enriched in soluble P compared with adjacent agricultural land and may be responsible for the reported increased DP delivery. Th rough increased biological activity in VBSs, plants and microorganisms may assimilate P from particulates retained in the VBSs or native soil P and remobilize this P in a more soluble form. Th ese conclusions are based on a limited amount of research, and a better understanding of biogeochemical cycling of P in buff er strip soils is required.

BACKGROUND. The combination of gemcitabine and docetaxel has demonstrated promise in sarcomas diagnosed in adults. In the current study, the toxicity and efficacy of this combination were evaluated in pediatric sarcomas. METHODS. A retrospective case review of 22 patients with recurrent or refractory bone or soft‐tissue sarcomas who received gemcitabine (at a dose of 675 mg/m2 intravenously on Days 1 and 8) and docetaxel (at a dose of 75–100 mg/m2 intravenously on Day 8) was undertaken. RESULTS. The patients (ages 8–23 years) received a total of 109 courses of chemotherapy (median, 4 courses; range, 1–13 courses). Seventeen patients had osteosarcoma, 2 patients had Ewing sarcoma family of tumors (ESFT), 1 patient had a malignant fibrous histiocytoma (MFH), 1 patient had a chondrosarcoma, and 1 patient had an undifferentiated sarcoma. Of the 14 patients evaluable for response, the patient with an MFH achieved a complete response (CR), 3 patients with osteosarcoma achieved a partial response (PR), and 2 patients (1 with ESFT and 1 with osteosarcoma) had stable disease (SD). The overall objective response (CR + PR) rate was 29%. Median duration of response (CR + PR + SD) was 4.8 months (range, 1.6‐13 months). The toxicity was manageable and consisted primarily of thrombocytopenia and neutropenia. CONCLUSIONS. In the current study, gemcitabine in combination with docetaxel was found to be well tolerated and demonstrated antitumor activity in children and adolescents with recurrent or refractory osteosarcoma and MFH. Further evaluation of this drug combination is warranted in these patients. Cancer 2008. © 2008 American Cancer Society.

This agent was well tolerated, and its toxicity was acceptable. Future trials should examine the effectiveness of 2-CDA given in combination with other agents effective against AML.

No abstract

Molecular signs of residual leukemia can persist up to 35 months after the cessation of chemotherapy in children with ALL in remission. This suggests that eradication of all leukemia cells may not be a prerequisite for cure.

Patients with solid tumors are increasingly being treated by autologous bone marrow transplantation (BMT). Although response rates appear to be increased, disease recurrence is the commonest cause of treatment failure. Whether relapse is entirely due to residual disease in the patient or arises also from infiltrating malignant cells contained in the autologous marrow transplant has not been resolved. If the latter explanation is correct, then purging would be required as part of the transplantation procedure. We used retrovirally mediated transfer of the neomycin-resistance gene to mark BM harvested from eight patients with neuroblastoma in clinical remission. The marked marrow cells were subsequently reinfused as part of an autologous BMT. At relapse, we sought the marker gene in malignant cell populations. Three patients have relapsed, and in each the marker gene was detected by phenotypic and genetic analyses of resurgent malignant cells at medullary and extramedullary sites. Analysis of neuroblast DNA for discrete marker gene integration sites suggested that at least 200 malignant cells, each capable of tumor formation, were introduced with the autologous marrow transplant and contributed to relapse. Thus, autologous BMTs administered to patients with this solid tumor may contain a multiplicity of malignant cells that subsequently contribute to relapse. The marker-gene technique we describe should permit evaluation of the mechanisms of relapse and the efficacy of purging in patients receiving autologous marrow transplantation for other solid tumors that infiltrate the marrow.