Haematologica
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Clinical Trial Controlled Clinical Trial
Safety and efficacy of romiplostim in splenectomized and nonsplenectomized patients with primary immune thrombocytopenia.
Primary immune thrombocytopenia is an autoimmune disorder characterized by increased platelet destruction and insufficient platelet production without another identified underlying disorder. Splenectomy may alter responsiveness to treatment and/or increase the risk of thrombosis, infection, and pulmonary hypertension. The analysis herein evaluated the safety and efficacy of the thrombopoietin receptor agonist romiplostim in splenectomized and nonsplenectomized adults with primary immune thrombocytopenia. ⋯ Platelet responses were stable over time in both subgroups. Exposure-adjusted adverse event rates were higher for control versus romiplostim for both splenectomized (1857 versus 1226 per 100 patient-years) and nonsplenectomized patients (1052 versus 852 per 100 patient-years). In conclusion, responses to romiplostim were seen in both splenectomized and nonsplenectomized patients, and romiplostim was not associated with an increase in the risk of adverse events in splenectomized patients. clinicaltrials.gov Identifier: 00111475(A)(B), 00117143, 00305435, 01143038, 00102323, 00102336, 00415532, 00603642, 00508820, 00907478, 00116688, and 00440037.
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For treatment of severe aplastic anemia, immunosuppressive therapy with horse antithymocyte globulin results in superior response and survival compared with rabbit antithymocyte globulin. This relative benefit may be different in the setting of transplantation as rabbit antithymocyte globulin results in more profound immunosuppression. We analyzed 833 severe aplastic anemia transplants between 2008 and 2013 using human leukocyte antigen (HLA)-matched siblings (n=546) or unrelated donors (n=287) who received antithymocyte globulin as part of their conditioning regimen and bone marrow graft. ⋯ Among recipients of unrelated donor transplants, acute graft-versus-host disease was also higher with horse compared to rabbit antithymocyte globulin (42% versus 23%, P<0.001) but not chronic graft-versus-host disease (38% versus 32%, P=0.35). Survival was lower with horse antithymocyte globulin after unrelated donor transplantation, 75% versus 83%, P=0.02. These data support the use of rabbit antithymocyte globulin for bone marrow transplant conditioning for severe aplastic anemia.
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Human rhinoviruses are the most common respiratory viruses detected in patients after hematopoietic cell transplantation. Although rhinovirus appears to occasionally cause severe lower respiratory tract infection in immunocompromised patients, the clinical significance of rhinovirus detection in the lower respiratory tract remains unknown. We evaluated 697 recipients transplanted between 1993 and 2015 with rhinovirus in respiratory samples. ⋯ Mortality after rhinovirus lower respiratory tract infection was similar to that after lower respiratory tract infection by respiratory syncytial virus, parainfluenza virus or influenza in an adjusted model. In summary, transplant recipients with rhinovirus detection in the lower respiratory tract had high mortality rates comparable to viral pneumonia associated with other well-established respiratory viruses. Our data suggest rhinovirus can contribute to severe pulmonary disease in immunocompromised hosts.
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Multicenter Study
Improved survival after acute graft-versus-host disease diagnosis in the modern era.
A cute graft-versus-host disease remains a major threat to a successful outcome after allogeneic hematopoietic cell transplantation. While improvements in treatment and supportive care have occurred, it is unknown whether these advances have resulted in improved outcome specifically among those diagnosed with acute graft-versus-host disease. We examined outcome following diagnosis of grade II-IV acute graft-versus-host disease according to time period, and explored effects according to original graft-versus-host disease prophylaxis regimen and maximum overall grade of acute graft-versus-host disease. ⋯ Considering the total study population, univariate analysis demonstrated significant improvements in overall survival and treatment-related mortality over time, and deaths from organ failure and infection declined. On multivariate analysis, significant improvements in overall survival (P=0.003) and treatment-related mortality (P=0.008) were only noted among those originally treated with tacrolimus-based graft-versus-host disease prophylaxis, and these effects were most apparent among those with overall grade II acute graft-versus-host disease. In conclusion, survival has improved over time for tacrolimus-treated transplant recipients with acute graft-versus-host disease.
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The forkhead transcription factor FOXP1 is generally regarded as an oncogene in activated B cell-like diffuse large B-cell lymphoma. Previous studies have suggested that a small isoform of FOXP1 rather than full-length FOXP1, may possess this oncogenic activity. Corroborating those studies, we herein show that activated B cell-like diffuse large B-cell lymphoma cell lines and primary activated B cell-like diffuse large B-cell lymphoma cells predominantly express a small FOXP1 isoform, and that the 5'-end of the Foxp1 gene is a common insertion site in murine lymphomas in leukemia virus- and transposon-mediated insertional mutagenesis screens. ⋯ Furthermore, overexpression of full-length FOXP1 or this small FOXP1 isoform in primary B cells and diffuse large B-cell lymphoma cell lines resulted in similar gene regulation. Taken together, our data indicate that this small FOXP1 isoform and full-length FOXP1 have comparable oncogenic and transcriptional activity in human B cells, suggesting that aberrant expression or overexpression of FOXP1, irrespective of the specific isoform, contributes to lymphomagenesis. These novel insights further enhance the value of FOXP1 for the diagnostics, prognostics, and treatment of diffuse large B-cell lymphoma patients.