Determinants of lenalidomide response with or without erythropoiesis-stimulating agents in myelodysplastic syndromes:the HOVON89 trial

A randomized phase-II study was performed in low/int-1 risk MDS (IPSS) to study efficacy and safety of lenalidomide without (arm A) or with (arm B) ESA/G-CSF. In arm B, patients without erythroid response (HI-E) after 4 cycles received ESA; G-CSF was added if no HI-E was obtained by cycle 9. HI-E served as primary endpoint. Flow cytometry and next-generation sequencing were performed to identify predictors of response. The final evaluation comprised 184 patients; 84% non-del(5q), 16% isolated del(5q); median follow-up: 70.7 months. In arm A and B, 39 and 41% of patients achieved HI-E; median time-to-HI-E: 3.2 months for both arms, median duration of-HI-E: 9.8 months. HI-E was significantly lower in non-del(5q) vs. del(5q): 32% vs. 80%. The same accounted for transfusion independency-at-week 24 (16% vs. 67%), but similar in both arms. Apart from presence of del(5q), high percentages of bone marrow lymphocytes and progenitor B-cells, a low number of mutations, absence of ring sideroblasts, and SF3B1 mutations predicted HI-E. In conclusion, lenalidomide induced HI-E in patients with non-del(5q) and del(5q) MDS without additional effect of ESA/G-CSF. The identified predictors of response may guide application of lenalidomide in lower-risk MDS in the era of precision medicine. (EudraCT 2008-002195-10).</p

De deltametropool is een grenzeloos gevarieerd parklandschap

De deltametropool is een grensoverschrijdend geheel. De verschillende stedelijke kernen, zoals de Vlaamse ruit, de regio Lille, het Ruhrgebied en de Randstad, vormen samen met het tussengebied een grote global city region. Ze hebben allen een sterk ontwikkeld vervoerspatroon. In dat verstedelijkte gebied wonen en werken ruim 25 miljoen mense

Reflections on urban-rural relationship; a birds [sic] eye view contribution to the urban-rural debate

This paper describes the discussions on a few emerging convergences and divergences in the approaches of urban and rural developments. At first the distinction is made between the urban-rural relationship on the one hand, as a complex of substantial developments, such as densification, sociocultural development, transportation, ecological patterns and structure. On the other hand the emerging soundness of urban-rural partnership is described, defined here as a set of communicative arrangements between actors, under the cover of various existing and established conventions, regulations and other cultural and historic behaviour. The study stresses partnership as the arena in which urban and rural actors operate in concert. The report will show that these terms refer to substantial themes of the urban-rural relationship, allowing to elaborate more specifically the roles of the urban and rural actors in possible partnerships. Recommandations are made - as a contribution to the debate on urban-rural partnership - on instrumental, organizational and institutional incentives