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Sökning: WFRF:(Heyman B)

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  • Albertsen, B. K., et al. (författare)
  • Intermittent Versus Continuous PEG-Asparaginase to Reduce Asparaginase-Associated Toxicities: A NOPHO ALL2008 Randomized Study
  • 2019
  • Ingår i: Journal of Clinical Oncology. - 0732-183X. ; 37:19, s. 1638-1646
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE Asparaginase is an essential drug in childhood acute lymphoblastic leukemia (ALL) therapy and is frequently given for months to obtain continuous asparagine depletion. We randomly assigned patients to continuous versus intermittent pegylated-asparaginase (PEG-asp) treatment, hypothesizing there would be decreased toxicity with unchanged efficacy. METHODS Children (median age, 4.2 years) treated for non-high-risk ALL according to the Nordic Society for Pediatric Hematology and Oncology ALL2008 protocol received five intramuscular PEG-asp injections (1,000 IU/m(2)) every two weeks and were then randomly assigned to additional three doses (6-week intervals [experimental arm], n = 309) versus 10 doses (2-week intervals [standard arm], n = 316). The primary end point was noninferior (6% margin) disease-free survival. Toxicity reduction was a secondary end point. Occurrence of asparaginase-associated hypersensitivity, pancreatitis, osteonecrosis, and thromboembolism were prospectively registered. RESULTS After a median follow-up of 4.1 years, the 5-year disease-free survival was 92.2% (95% CI, 88.6 to 95.8) and 90.8% (95% CI, 87.0 to 94.6) in the experimental and standard arms, respectively. The 3-year cumulative incidence of any first asparaginase-associated toxicity (hypersensitivity [n = 13]; osteonecrosis [n = 29]; pancreatitis [n = 24]; thromboembolism [n = 17]) was 9.3% in the experimental arm and 18.1% in the standard arm (P = .001). Asparaginase-associated toxicity reduction was confirmed in sex- and risk-group-adjusted Cox regression analysis stratified by age (>= 10 and < 10 years; hazard ratio, 0.48; P = .001). The experimental arm had the lowest incidences of all four toxicities, reaching significance for pancreatitis (6-month risk, 5.8% v 1.3%; P = .002). CONCLUSION The excellent cure rates and reduced toxicity risk support the use of intermittent PEG-asp therapy after the first 10 weeks in future childhood ALL trials that apply prolonged PEG-asp therapy.
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  • Menounos, B., et al. (författare)
  • Cordilleran Ice Sheet mass loss preceded climate reversals near the Pleistocene Termination
  • 2017
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 358:6364, s. 781-784
  • Tidskriftsartikel (refereegranskat)abstract
    • The Cordilleran Ice Sheet (CIS) once covered an area comparable to that of Greenland. Previous geologic evidence and numerical models indicate that the ice sheet covered much of westernmost Canada as late as 12.5 thousand years ago (ka). New data indicate that substantial areas throughout westernmost Canada were ice free prior to 12.5 ka and some as early as 14.0 ka, with implications for climate dynamics and the timing of meltwater discharge to the Pacific and Arctic oceans. Early Bolling-Allerod warmth halved the mass of the CIS in as little as 500 years, causing 2.5 to 3.0 meters of sea-level rise. Dozens of cirque and valley glaciers, along with the southern margin of the CIS, advanced into recently deglaciated regions during the Bolling-Allerod and Younger Dryas.
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