A new prognostic scoring system for estimating survival of patients with CML treated with interferon alfa has been developed and validated through use of a large dataset.
Summary. In order to evaluate the natural history of essential thrombocythaemia (ET), clinical data and prognostic factors of 143 patients with ET were retrospectively analysed (mean observation time 6·1 Ϯ 4·6 years). In 42 patients the early phase of the disease with initial platelet counts between 250 and 600 × 10 9 /l was assessed. In most early cases, ET was suggested by clinical symptoms (79%) and increased megakaryopoiesis (95%) with abnormal megakaryocytes in bone marrow histology (n ¼ 34) and cytology (n ¼ 5). Other myeloproliferative disorders and reactive thrombocytosis were excluded according to the diagnostic criteria of the Polycythemia Vera Study Group. During follow-up of the 38 early cases not treated cytoreductively at diagnosis, the platelet counts increased to >600 × 10 9 /l in 28 patients (74%) and remained between 450 and 600 × 10 9 /l in 10 patients (26%). In primarily asymptomatic patients (n ¼ 46) with initial platelet counts above (n ¼ 37) and below 600 × 10 9 /l (n ¼ 9) the rates of increase of symptomatic patients were similar at about 7% per year. No influence of the initial platelet count on survival was seen in multivariate analysis of prognostic factors which included all 143 cases. Survival was mainly influenced by the rate of ET-related complications during follow-up (P ¼ 0·002). Analysing the influence of cytoreductive therapy on symptom-free survival, platelet reduction benefited patients under 60 years (19 cytoreductively treated v 65 untreated patients, P ¼ 0·075). The results demonstrate the possible clinical relevance of the early stages of ET and suggest that the features of pathologic megakaryopoiesis in the bone marrow are a more reliable diagnostic criterion than a definite platelet limit. Therefore, further therapeutic studies should include all stages of the disease and all age groups.Keywords: myeloproliferative disorder, early essential thrombocythaemia, prognostic factors, diagnostic criteria, bone marrow histology.Due to the lack of a specific diagnostic marker, the diagnostic criteria of essential thrombocythaemia (ET) established by the Polycythemia Vera Study Group (PVSG) were directed primarily at the exclusion of other myeloproliferative disorders and of reactive thrombocytosis. For diagnosis of ET, a platelet count of 600 × 10 9 /l was considered as an absolute requirement (Murphy et al, 1986). For protocols involving myelosuppressive agents a platelet count of 1000 × 10 9 /l was determined to restrict the erroneous inclusion of cases with reactive thrombocytosis and to avoid possible overtreatment of cases with a mild course of ET (Murphy et al, 1986(Murphy et al, , 1997. In most of the following studies, patients with lower platelet counts were excluded according to the criteria of the PVSG. Such selectivity is acceptable for therapeutic studies. But in the evaluation of the natural course of ET the exclusion of early stages with moderate thrombocytosis below the limit of 600 × 10 9 /l may lead to incomplete recognition of characteristic features of the di...
Recent advances in the generation of cardiomyocytes (CMs) from human pluripotent stem cells (hPSCs), in conjunction with the promising outcomes from preclinical and clinical studies, have raised new hopes for cardiac cell therapy. We report the development of a scalable, robust, and integrated differentiation platform for large-scale production of hPSC-CM aggregates in a stirred suspension bioreactor as a single-unit operation. Precise modulation of the differentiation process by small molecule activation of WNT signaling, followed by inactivation of transforming growth factor-b and WNT signaling and activation of sonic hedgehog signaling in hPSCs as size-controlled aggregates led to the generation of approximately 100% beating CM spheroids containing virtually pure (∼90%) CMs in 10 days. Moreover, the developed differentiation strategy was universal, as demonstrated by testing multiple hPSC lines (5 human embryonic stem cell and 4 human inducible PSC lines) without cell sorting or selection. The produced hPSC-CMs successfully expressed canonical lineage-specific markers and showed high functionality, as demonstrated by microelectrode array and electrophysiology tests. This robust and universal platform could become a valuable tool for the mass production of functional hPSC-CMs as a prerequisite for realizing their promising potential for therapeutic and industrial applications, including drug discovery and toxicity assays. STEM CELLS
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.