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Sökning: WFRF:(Previtali A)

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  • Wiedorn, Max O., et al. (författare)
  • Megahertz serial crystallography
  • 2018
  • Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 9
  • Tidskriftsartikel (refereegranskat)abstract
    • The new European X-ray Free-Electron Laser is the first X-ray free-electron laser capable of delivering X-ray pulses with a megahertz inter-pulse spacing, more than four orders of magnitude higher than previously possible. However, to date, it has been unclear whether it would indeed be possible to measure high-quality diffraction data at megahertz pulse repetition rates. Here, we show that high-quality structures can indeed be obtained using currently available operating conditions at the European XFEL. We present two complete data sets, one from the well-known model system lysozyme and the other from a so far unknown complex of a beta-lactamase from K. pneumoniae involved in antibiotic resistance. This result opens up megahertz serial femtosecond crystallography (SFX) as a tool for reliable structure determination, substrate screening and the efficient measurement of the evolution and dynamics of molecular structures using megahertz repetition rate pulses available at this new class of X-ray laser source.
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  • Abramson, JS, et al. (författare)
  • Lisocabtagene maraleucel as second-line therapy for large B-cell lymphoma: primary analysis of the phase 3 TRANSFORM study
  • 2023
  • Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 141:14, s. 1675-1684
  • Tidskriftsartikel (refereegranskat)abstract
    • This global, phase 3 study compared lisocabtagene maraleucel (liso-cel) with standard of care (SOC) as second-line therapy for primary refractory or early relapsed (≤12 months) large B-cell lymphoma (LBCL). Adults eligible for autologous stem cell transplantation (ASCT) were randomized 1:1 to liso-cel (100×106 CAR+ T cells) or SOC (3 cycles of platinum-based immunochemotherapy followed by high-dose chemotherapy and ASCT in responders). The primary end point was event-free survival (EFS) by independent review. A total of 184 patients were randomized. In this primary analysis with a median follow-up of 17.5 months, median EFS was not reached (NR) for liso-cel versus 2.4 months for SOC (hazard ratio [HR] = 0.356; 95% confidence interval [CI]: 0.243‒0.522). Complete response (CR) rate was 74% for liso-cel versus 43% for SOC (P < .0001) and median progression-free survival (PFS) was NR for liso-cel versus 6.2 months for SOC (HR = 0.400; 95% CI: 0.261‒0.615; P < .0001). Median overall survival was NR for liso-cel versus 29.9 months for SOC (HR = 0.724; 95% CI: 0.443‒1.183; P = .0987). When adjusted for crossover from SOC to liso-cel, median overall survival was NR for liso-cel and SOC (HR = 0.415; 95% CI: 0.251‒0.686). Grade 3 cytokine release syndrome and neurological events occurred in 1% and 4% of patients in the liso-cel arm, respectively (no grade 4/5 events). These data show significant improvements in EFS, CR rate, and PFS for liso-cel over SOC and support liso-cel as a preferred second-line treatment compared with SOC in patients with primary refractory or early relapsed LBCL. (ClinicalTrials.gov; NCT03575351.)
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