Although there are high survival rates for children with acute lymphoblastic leukaemia, their outcome is often counterbalanced by the burden of toxic eff ects. This is because reported frequencies vary widely across studies, partly because of diverse defi nitions of toxic eff ects. Using the Delphi method, 15 international childhood acute lymphoblastic leukaemia study groups assessed acute lymphoblastic leukaemia protocols to address toxic eff ects that were to be considered by the Ponte di Legno working group. 14 acute toxic eff ects (hypersensitivity to asparaginase, hyperlipidaemia, osteonecrosis, asparaginase-associated pancreatitis, arterial hypertension, posterior reversible encephalopathy syndrome, seizures, depressed level of consciousness, methotrexate-related stroke-like syndrome, peripheral neuropathy, high-dose methotrexate-related nephrotoxicity, sinusoidal obstructive syndrome, thrombo embolism, and Pneumocystis jirovecii pneumonia) that are serious but too rare to be addressed comprehensively within any single group, or are deemed to need consensus defi nitions for reliable incidence comparisons, were selected for assessment. Our results showed that none of the protocols addressed all 14 toxic eff ects, that no two protocols shared identical defi nitions of all toxic eff ects, and that no toxic eff ect defi nition was shared by all protocols. Using the Delphi method over three face-to-face plenary meetings, consensus defi nitions were obtained for all 14 toxic eff ects. In the overall assessment of outcome of acute lymphoblastic leukaemia treatment, these expert opinion-based defi nitions will allow reliable comparisons of frequencies and severities of acute toxic eff ects across treatment protocols, and facilitate international research on cause, guidelines for treatment adaptation, preventive strategies, and development of consensus algorithms for reporting on acute lymphoblastic leukaemia treatment.
The reduction of spontaneous physical activity (PA) and of muscle tissue are thought to be major causes of fat accretion and metabolic deterioration in Prader-Labhart-Willi syndrome (PWS). We investigated whether a generalized physical training programme in a home setting improves these parameters. The prospective study included 11 prepubertal children (mean age 8.7 years, range 5.9-11.8) with documented PWS and under contir"jus growth hormone treatment for at least 2.8 years. Seven children were enrolled in a training programme for several muscle groups during 4-10 minutes daily. Twelve matched children with PWS served as controls (average age 8.8 years, 6.1-11.3). Before and after training, at 6 months, PA was assessed by measuring walking distance by pedometer registration and by an activity score, and body composition by DEXA expressed as standard deviation scores (SDS) related to height. After training, lean mass (LM) increased from -1.83 to -1.48 SDS, ρ <0.05, whereas the controls showed no change. In the training group, walking distance and PA increased from 4.2 to 4.7 km/d and from 255 to 266 points, respectively, and these rises significantly exceeded those observed in controls. Conclusion: Children with PWS can be motivated by their families to follow a short daily
Obesity and hypothalamic GH deficiency contribute in different ways to the disturbances of body composition in Prader-Willi syndrome (PWS); while both increase the fat compartment, the reduction of lean tissue mass has been attributed mainly to GH deficiency. Therefore, body composition measured by dual-energy X-ray absorptiometry was prospectively studied in 12 overweight children with PWS and weight for height (WfH) SDS >0 before and during 3.5 years of treatment with hGH (0.037 mg/kg/day) on average. In the long term, there is a net reduction of body fat from 3.1 to 1.2 SD, with a minimum at the end of the second year of treatment. WfH SDS correctly reflects body fat mass and its changes. The initial deficit of lean mass (–1.6 SD) is counteracted by GH only during the first year of therapy (increase to –1.25 SD). But in the long term, GH therapy does not further compensate for this deficit, when lean mass is corrected for its growth-related increase. In conclusion, exogenous GH changes the phenotype of children with PWS: fat mass becomes normal, but, at least in the setting studied, GH is not sufficient to normalize lean tissue mass.
Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Bacterial L‐asparaginase has played an important role in ALL treatment for several decades; however, hypersensitivity reactions to Escherichia coli‐derived asparaginases often preclude their use. Inability to receive asparaginase due to hypersensitivities is associated with poor patient outcomes. Erwinia chrysanthemi‐derived asparaginase (ERW) is an effective, non‐cross‐reactive treatment option, but is limited in supply. Consequently, alternative asparaginase preparations are needed to ensure asparaginase availability for patients with hypersensitivities. Recombinant technology can potentially address this unmet need by programming cells to produce recombinant asparaginase. JZP‐458, a recombinant Erwinia asparaginase derived from a novel Pseudomonas fluorescens expression platform with no immunologic cross‐reactivity to E. coli‐derived asparaginases, has the same primary amino acid sequence as ERW, with comparable activity based on in vitro measurements. The efficient manufacturing of JZP‐458 would provide an additional asparaginase preparation for patients with hypersensitivities.
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