Current therapies for myeloproliferative neoplasms (MPNs) improve symptoms but have limited effect on tumor size. In preclinical studies, tamoxifen restored normal apoptosis in mutated hematopoietic stem/progenitor cells (HSPCs). TAMARIN Phase-II, multicenter, single-arm clinical trial assessed tamoxifen's safety and activity in patients with stable MPNs, no prior thrombotic events and mutated JAK2, CALR or CALR peripheral blood allele burden ≥20% (EudraCT 2015-005497-38).
View Article and Find Full Text PDFBackground: Multiple-choice exams are not well suited for assessing communication skills. Standardized patient assessments are costly and patient and peer assessments are often biased. Web-based assessment using video content offers the possibility of reliable, valid, and cost-efficient means for measuring complex communication skills, including interprofessional communication.
View Article and Find Full Text PDFChronic graft-versus-host disease (cGVHD) is characterized by a state of profound immunodeficiency in association with alloreactive and autoimmune phenomena. These observations indicate an impairment of immunologic tolerance that could involve both central and peripheral mechanisms. Defective thymic function may contribute to dysregulation of central tolerance, but few studies have addressed peripheral tolerance.
View Article and Find Full Text PDFBackground: After allogeneic hematopoietic stem cell transplantation, donor T cells interact with an antigen-presenting cell environment that is distorted in number, level of activation, and origin. The role of antigen presentation in the development of chronic graft-versus host disease (cGVHD) is unknown.
Methods: The number and origin of peripheral blood immature myeloid (CD19- CD1c+) and plasmacytoid (BDCA-2+) dendritic cells (DCs) was determined in 30 patients at more than 100 days after allogeneic hematopoietic stem cell transplantation.
We describe the toxicity and efficacy of donor lymphocyte infusions (DLIs) given to 81 patients (median age, 50 years) after reduced-intensity conditioning (RIC) transplantations performed at 16 centers in the United Kingdom. The diseases treated included non-Hodgkin lymphoma (NHL; n = 29), chronic myeloid leukemia (CML; n = 12), myeloma (n = 11), acute myeloid leukemia (AML; n = 10), and chronic lymphocytic leukemia (CLL; n = 9). Eighty-eight percent received stem cells from sibling donors.
View Article and Find Full Text PDFA major barrier to successful allogeneic hematopoietic stem cell transplantation is graft-versus-host disease (GVHD). Until recently, the role of antigen presentation in the development of this disorder was unknown. The experimental finding that recipient antigen-presenting cells (APCs) were required for the development of CD8(+) T cell-dependent GVHD has led to a fundamental reappraisal of our ideas concerning the pathogenesis of this disease.
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