Therapy-related AML: long-term outcome in a large cohort of AML-patients with intensive and non-intensive therapy.

Therapy-related acute myeloid leukemia (t-AML) often exhibits adverse (genetic) features. There is ongoing discussion on the impact of t-AML on long-term outcome in AML. Therefore, we retrospectively analyzed clinical and biological characteristics of 1133 AML patients (225 t-AML patients and 908 de novo AML patients) with a median follow-up of 81.

Adaptive T-cell immunity controls senescence-prone MyD88- or CARD11-mutant B-cell lymphomas.

Aberrant B-cell receptor/NF-κB signaling is a hallmark feature of B-cell non-Hodgkin lymphomas, especially in diffuse large B-cell lymphoma (DLBCL). Recurrent mutations in this cascade, for example, in CD79B, CARD11, or NFKBIZ, and also in the Toll-like receptor pathway transducer MyD88, all deregulate NF-κB, but their differential impact on lymphoma development and biology remains to be determined. Here, we functionally investigate primary mouse lymphomas that formed in recipient mice of Eµ-myc transgenic hematopoietic stem cells stably transduced with naturally occurring NF-κB mutants.

Endothelial damage and dysfunction in acute graft-versus-host disease.

Clinical studies suggested that endothelial dysfunction and damage could be involved in the development and severity of acute graft-versus-host disease (aGVHD). Accordingly, we found increased percentage of apoptotic Casp3+ blood vessels in duodenal and colonic mucosa biopsies of patients with severe aGVHD. In murine experimental aGVHD, we detected severe microstructural endothelial damage and reduced endothelial pericyte coverage accompanied by reduced expression of endothelial tight junction proteins leading to increased endothelial leakage in aGVHD target organs.

Pharmacokinetics of Daclatasvir, Sofosbuvir, and GS-331007 in a Prospective Cohort of Hepatitis C Virus-Positive Kidney Transplant Recipients.

Background: Limited data exist on the pharmacokinetic profile of novel direct-acting antivirals in kidney transplant recipients. Daclatasvir is primarily eliminated through the biliary route and sofosbuvir through the renal route; here, we report the pharmacokinetic profile of combined treatment with these compounds in a prospective study of hepatitis C virus (HCV)-positive kidney transplant recipients (EudraCT: 2014-004551-32).

Methods: In this study, plasma samples of 16 HCV-positive kidney transplant recipients receiving daclatasvir and sofosbuvir were collected at 4 time points at days 1, 7, 14, 21, 56, and 84 after start of treatment.