International journal of hematology
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Cytogenetically normal acute myeloid leukemia (cn-AML) is a group of heterogeneous diseases. Gene mutations are increasingly used to assess the prognosis of cn-AML patients and guide risk-adapted treatment. In the present study, we analyzed the molecular genetics characteristics of 373 adult cn-AML patients and explored the relationship between TET2 gene mutations or different genetic mutation patterns and prognosis. ⋯ Gene mutations were detected in 76.94 % (287/373) of all patients. In the NPM1m(+) patients, those with TET2 mutations were associated with a shorter median overall survival (OS) as compared to TET2 wild-type (wt) patients (9.9 vs. 27.0 months, respectively; P = 0.023); Interestingly, the TET2 mutation was identified as an unfavorable prognostic factor and was closely associated with a shorter median OS as compared to TET2-wt (9.5 vs. 32.2 months, respectively; P = 0.013) in the NPM1m(+)/FLT3-ITDm(-) patient group. Thus, identification of TET2 combined with classic NPM1 and FLT3-ITD mutations allowed us to stratify cn-AML into distinct subtypes.
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Hematopoietic stem cell transplant (HSCT) recipients are at a high risk of Clostridium difficile-associated disease (CDAD) given frequent hospitalizations, prolonged antibiotic usage and altered integrity of intestinal mucosa. The prevalence and trends of CDAD in HSCT patients have not been extensively studied. In this study, the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes were used to identify CDAD in HSCT patients using a nationwide inpatient sample in the United States from 2000 to 2009. ⋯ In subsequent admissions, there was higher mortality in those with GVHD (OR 4.8). Though the prevalence of CDAD in non-transplant population doubled (from 0.44 % in 2000 to 0.99 % in 2008), it has remained stable in HSCT patients (from 4.8 % in 2000 to 5.6 % in 2008). HSCT and GVHD are independently associated with CDAD though its presence does not affect mortality.
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The genetic modification of autologous T cells with chimeric antigen receptors (CARs) represents a breakthrough for gene engineering as a cancer therapy for hematologic malignancies. By targeting the CD19 antigen, we have demonstrated robust and rapid anti-leukemia activity in patients with heavily pre-treated and chemotherapy-refractory B cell acute lymphoblastic leukemia (B-ALL). We demonstrated rapid induction of deep molecular remissions in adults, which has been recently confirmed in a case report involving a child with B-ALL. ⋯ We review the clinical trial experience targeting B-ALL and CLL and speculate on the possible reasons for the different outcomes and propose potential optimization to CAR T cell therapy when targeting CLL or other indolent NHL. Lastly, we discuss the pre-clinical development and potential for clinical translation for using CAR T cells against multiple myeloma and acute myeloid leukemia. We highlight the potential risks and benefits by targeting these poor outcome hematologic malignancies.
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Beta (β)-thalassemia is characterized by a hypercoagulable state and an increased risk of thrombosis, which can result in significant morbidity and mortality. The coagulation pattern and determinants of thrombosis in patients with β-thalassemia remain largely unknown. The aim of this study was to evaluate the whole blood thromboelastometry (TEM) profile of β-thalassemic children by ROTEM(®). ⋯ Of the patients with β-thalassemia, MCF was higher and clot formation time was shorter in splenectomized subjects than in non-splenectomized subjects on EXTEM and INTEM (p = 0.026, p = 0.002, p < 0.001, p < 0.001, respectively). TEM profiles in β-thalassemic children were more hypercoagulable compared with controls. Larger prospective studies are needed to evaluate the relevance of the association between ROTEM(®) profile and thromboembolic events in patients with β-thalassemia.