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Through the APIC-ESTEE (Air Pollution Impacts on Cardiopulmonary Disease in Beijing: An integrated study of Exposure Science, Toxicogenomics and Environmental Epidemiology) project, we have develop...

Cytogenetic analysis of cells from 622 consecutive patients with newly diagnosed acute lymphoblastic leukemia (ALL) and successful G-banding chromosome studies disclosed seven cases with the t(11;14)(p13;q11) and one with the t(11;14)(p15;q11). Leukemia cells in all eight cases had a T-cell immunophenotype. The t(11;14)(p13;q11) occurred in 6.8% and the t(11;14)(p15;q11) in 1% of T-cell ALL cases (n = 103). The t(11;14) was associated with presenting clinical features typical of T-cell ALL: male predominance (n = 6), age greater than 10 years (n = 3), hyperleukocytosis (white blood cells greater than 100 x 10(9)/L, n = 5), relatively high hemoglobin level (median, 10.8 g/dL), high serum lactic dehydrogenase level (median, 3248 U/L), presence of mediastinal mass (n = 6), and central nervous system leukemia (n = 2). While there were no significant differences in presenting features between T-cell ALL cases with or without the t(11;14), leukemic cells from patients with the translocations were more likely to coexpress CD4 and CD8 antigens (6 of 6 v 35 of 86 cases tested, P less than .05). Adverse events have occurred in six patients: three central nervous system relapses [including the one with t(11;14)(p15;q11)], two secondary acute myeloid leukemia, and one hematologic relapse. Our results indicate that the t(11;14)(p13;q11) occurs exclusively in T-cell malignancies of intermediate- or late-stage thymocyte differentiation. Additional studies are needed to determine the prognostic implications of these translocations.

To evaluate its toxicity and clinical efficacy in children with relapsed or refractory leukemia, we performed a phase I trial of 2-chloro-2'-deoxy-adenosine (2-chlorodeoxyadenosine; 2-CDA) given as a continuous 5-day infusion at doses of 3 to 10.7 mg/m2/d. In this study of 31 children with acute leukemia, the only dose-limiting toxicity was myelosuppression. At the highest dose level, three of seven patients developed fatal systemic bacterial or fungal infections. At dose levels above 6.2 mg/m2/d, significant oncolytic responses occurred in all patients. In addition, there was a significant correlation between both the responsiveness by cell type and dose of 2-CDA, such that more oncolytic responses were noted in acute myeloid leukemia (AML) patients than acute lymphoblastic leukemia (ALL) patients (P = .02). Although this was a phase I trial in heavily pretreated patients with refractory disease, two AML patients treated at 5.2 and 10.7 mg/m2/d, respectively, had complete hematologic responses, and one patient treated at 10.7 mg/m2/d had a partial response. In addition, there was a dose-response relationship in all patients with improved cytoreduction of peripheral blast cells at higher doses of 2-CDA. In vitro evaluation of 2-CDA uptake and anabolism by leukemic blast cells from 22 patients demonstrated that 2-chloro-2'-deoxyadenosine (Cld-AMP) and 2-chloro-2'-deoxyadenosine 5'-striphosphate (CldATP) reached concentrations close to steady-state levels within 1 hour. Intracellular nucleotide disappearance rates were high with half-lives of 1.29 and 2.47 hours for CldAMP and CldATP, respectively. This suggests that continuous infusion is necessary to maintain the desired plasma concentration. The results of this study confirm the antileukemic activity of 2-CDA and the lack of prohibitive nonhematologic toxicity. Phase II trials in patients with AML and ALL are warranted.

A system that combines the ease of use of a job-exposure matrix while taking into account job-specific data is needed. This study aimed to produce a detailed method for combining interview data with expert assessments for a large population-based case-control study of Parkinson's disease.An interview-administered core questionnaire with a series of questions that triggers substance-specific questionnaires to gather information on key parameters is administered. Using a job-exposure matrix to generate base estimates, assessors can modify this estimate of exposure intensity using worker-specific data such as the use of control measures, reports of substance-specific acute symptoms, and the quantity of material being processed. Detailed guidance for making adjustments to exposure estimates for these modifiers is presented.The method has been partially validated through the use of a comparison of estimates for a separate cohort with previously validated exposure reconstructions. Agreement was high, with a Spearman's rho of 0.89 (P0.01). The results from a quality assurance system employed as part of the methodology show a high degree of repeatability in generated exposure values both over time (Spearman's rho 0.98, P0.01) and between different assessors (Spearman's rho 0.88, P0.01).The method provides detailed quantitative exposure indices for occupational epidemiology. It has particular strengths both in terms of ease and speed of use. It is hoped that it will provide a useful structure for future epidemiologic work.