Ruxolitinib for Glucocorticoid-Refractory Acute Graft-versus-Host Disease

BACKGROUND: Acute graft-versus-host disease (GVHD) remains a major limitation of allogeneic stem-cell transplantation; not all patients have a response to standard glucocorticoid treatment. In a phase 2 trial, ruxolitinib, a selective Janus kinase (JAK1 and JAK2) inhibitor, showed potential efficacy in patients with glucocorticoid-refractory acute GVHD. METHODS: We conducted a multicenter, randomized, open-label, phase 3 trial comparing the efficacy and safety of oral ruxolitinib (10 mg twice daily) with the investigator's choice of therapy from a list of nine commonly used options (control) in patients 12 years of age or older who had glucocorticoid-refractory acute GVHD after allogeneic stem-cell transplantation. The primary end point was overall response (complete response or partial response) at day 28. The key secondary end point was durable overall response at day 56. RESULTS: A total of 309 patients underwent randomization; 154 patients were assigned to the ruxolitinib group and 155 to the control group. Overall response at day 28 was higher in the ruxolitinib group than in the control group (62% [96 patients] vs. 39% [61]; odds ratio, 2.64; 95% confidence interval [CI], 1.65 to 4.22; P<0.001). Durable overall response at day 56 was higher in the ruxolitinib group than in the control group (40% [61 patients] vs. 22% [34]; odds ratio, 2.38; 95% CI, 1.43 to 3.94; P<0.001). The estimated cumulative incidence of loss of response at 6 months was 10% in the ruxolitinib group and 39% in the control group. The median failure-free survival was considerably longer with ruxolitinib than with control (5.0 months vs. 1.0 month; hazard ratio for relapse or progression of hematologic disease, non-relapse-related death, or addition of new systemic therapy for acute GVHD, 0.46; 95% CI, 0.35 to 0.60). The median overall survival was 11.1 months in the ruxolitinib group and 6.5 months in the control group (hazard ratio for death, 0.83; 95% CI, 0.60 to 1.15). The most common adverse events up to day 28 were thrombocytopenia (in 50 of 152 patients [33%] in the ruxolitinib group and 27 of 150 [18%] in the control group), anemia (in 46 [30%] and 42 [28%], respectively), and cytomegalovirus infection (in 39 [26%] and 31 [21%]). CONCLUSIONS: Ruxolitinib therapy led to significant improvements in efficacy outcomes, with a higher incidence of thrombocytopenia, the most frequent toxic effect, than that observed with control therapy

Науково-практичний коментар Кримінального процесуального кодексу України. Зразки процесуальних документів у кримінальному провадженні [станом на 21 лют. 2020 р.]

Науково-практичний коментар Кримінального процесуального кодексу України. Зразки процесуальних документів у кримінальному провадженні [станом на 21 лют. 2020 р.] / за заг. ред. Чернявського С. С. – Київ : Вид. дім «Професіонал», 2020. – 1288 с. – ISBN 978-966-370-351-0.Надано науково-практичний коментар Кримінального процесуального кодексу України, а саме зразки процесуальних документів у кримінальному провадженні. Науково-практичний коментар розрахований на суддів, прокурорів, слідчих, співробітників оперативних підрозділів та адвокатів для використання в практичній роботі, а також як навчальний посібник для студентів навчальних учбових закладів, які готують фахівців в галузі права.Provided a scientific and practical commentary on the Criminal Procedure Code of Ukraine, namely, samples of procedural documents in criminal proceedings. The scientific and practical commentary is designed for judges, prosecutors, investigators, employees of operational units and lawyers for use in practical work, as well as a textbook for students of educational institutions that train specialists in the field of law.Предоставлен научно-практический комментарий Уголовного процессуального кодекса Украины, а именно образцы процессуальных документов в уголовном производстве. Научно-практический комментарий рассчитан на судей, прокуроров, следователей, сотрудников оперативных подразделений и адвокатов для использования в практической работе, а также как учебное пособие для студентов учебных заведений, которые готовят специалистов в области права

Allogeneic Hematopoietic Stem Cell Transplantation Provides Cure for Adult Patients with Hemophagocytic Lymphohistiocytosis (HLH): A Retrospective Study of The Chronic Malignancies and Inborn ErrorsWorking Parties (CMWP and IEWP) of The EBMT

Transplantation and immunomodulatio