Prospective longitudinal evaluation of treatment-related toxicity and health-related quality of life during the first year of treatment for pediatric acute lymphoblastic leukemia

Background: Pediatric acute lymphoblastic leukemia (ALL) therapy is accompanied by treatment-related toxicities (TRTs) and impaired quality of life. In Australia and New Zealand, children with ALL are treated with either Children’s Oncology Group (COG) or international Berlin-Frankfurt-Munster (iBFM) Study Group-based therapy. We conducted a prospective registry study to document symptomatic TRTs (venous thrombosis, neurotoxicity, pancreatitis and bone toxicity), compare TRT outcomes to retrospective TRT data, and measure the impact of TRTs on children’s general and cancer-related health-related quality of life (HRQoL) and parents’ emotional well-being. Methods: Parents of children with newly diagnosed ALL were invited to participate in the ASSET (Acute Lymphoblastic Leukaemia Subtypes and Side Effects from Treatment) study and a prospective, longitudinal HRQoL study. TRTs were reported prospectively and families completed questionnaires for general (Healthy Utility Index Mark 3) and cancer specific (Pediatric Quality of Life Inventory (PedsQL)-Cancer Module) health related quality of life as well the Emotion Thermometer to assess emotional well-being. Results: Beginning in 2016, 260 pediatric patients with ALL were enrolled on the TRT registry with a median age at diagnosis of 59 months (range 1–213 months), 144 males (55.4%), majority with Pre-B cell immunophenotype, n = 226 (86.9%), 173 patients (66.5%) treated according to COG platform with relatively equal distribution across risk classification sub-groups. From 2018, 79 families participated in the HRQoL study through the first year of treatment. There were 74 TRT recorded, reflecting a 28.5% risk of developing a TRT. Individual TRT incidence was consistent with previous studies, being 7.7% for symptomatic VTE, 11.9% neurotoxicity, 5.4% bone toxicity and 5.0% pancreatitis. Children’s HRQoL was significantly lower than population norms throughout the first year of treatment. An improvement in general HRQoL, measured by the HUI3, contrasted with the lack of improvement in cancer-related HRQoL measured by the PedsQL Cancer Module over the first 12 months. There were no persisting differences in the HRQoL impact of COG compared to iBFM therapy. Conclusions: It is feasible to prospectively monitor TRT incidence and longitudinal HRQoL impacts during ALL therapy. Early phases of ALL therapy, regardless of treatment platform, result in prolonged reductions in cancer-related HRQoL

Modelling the effects of soil properties on the concentration of Cd extracted by 10 mM CaCl2 from soils of the Sydney Basin

Undisturbed surface soils on the peri-urban fringe of the Sydney Basin are mostly acidic, with low concentrations of total cadmium ([Cd.sub.t]) and a wide range of other properties. In taxonomically similar soils on vegetable farms, [Cd.sub.t] is typically about 20-fold greater and undesirably large concentrations of Cd occur in some of the vegetables. We used a sequence of multiple regression models to evaluate how soil properties, taxonomy, and farming affected the behaviour of Cd in surface composites (0-15 cm) from 29 farmed and 12 unfarmed sites in the Basin. The dependent variable was the [log.sub.10] transformation of the concentration of Cd extracted in 1 h by 10mM Ca[Cl.sub.2] solution ([log.sub.10] [Cd.sub.ca]). The range of values of [Cd.sub.Ca] was 0.2-60 [micro]g/L. The independent variables in the base model were p[H.sub.Ca] and [log.sub.10] [Cd.sub.t] ([R.sub.2] = 0.885, r.s.d. = 0.245). The final model contained 2 additional [log.sub.10]-transformed soil properties: effective cation exchange capacity (ECEC) and oxalate-extractable Fe ([Fe.sub.ox]) ([R.sup.2] = 0.974, r.s.d. = 0.121). The effect of [log.sub.l0] Feox was significant (P 5.6, the approximate sorption edge for Cd on goethite. The effects of other soil properties could not be adequately tested because the residual variation was too small. The measured values of [Cd.sub.Ca] had a median error of [+ or -] 17% and a maximum error of [+ or -] 58% relative to the back-transformed fitted values from the final model. The coefficient of [log.sub.10] Cdt in the final model was 1.33 [+ or -] 0.05 for the farmed soils and 1.01 [+ or -] 0.04 for the unfarmed soils, i.e. [log.sub.10] [Cd.sub.Ca] was more sensitive to changes in [log.sub.10] [Cd.sub.t] in the farmed than the unfarmed soils (P < 0.01). This difference is consistent with the effects of the greater load and briefer duration of contact for Cd in the farmed soils. The coefficients of p[H.sub.Ca] and of [log.sub.10] ECEC in our final model had values of 0.49 ([+ or -] 0.03) and 0.69 ([+ or -] 0.08). These values are remarkably similar to those obtained when we fitted our data, using a model that had been used to describe the effects of soil properties on a compilation of Cd-sorption data, and to those in a partitioning model based on the desorption of Cd from contaminated soils. That is, the behaviour of Cd may be influenced by the duration of contact between Cd and the soil, and perhaps the load; however, neither factor appears to change the effects of p[H.sub.Ca] and [log.sub.10] ECEC