Genetic analysis of TP53 in childhood myelodysplastic syndrome and juvenile myelomonocytic leukemia

信州大学博士（医学）・学位論文・平成23年3月31日授与（甲第886号)・齋藤章治ArticleLEUKEMIA RESEARCH. 35(12):1578-1584 (2011)journal articl

Low toxicity of a conditioning with 8-Gy total body irradiation, fludarabine and cyclophosphamide as preparative regimen for allogeneic hematopoietic stem cell transplantation in pediatric hematological malignancies

The definitive version is available at www.blackwell-synergy.comWe here report the efficacy and toxicity of a conditioning regimen with fractionated 8-Gy TBI, fludarabine, and cyclophosphamide in allogeneic HSCT for pediatric hematological malignancies. Among 22 children who received related or unrelated HSCT, nine were transplanted with refractory disease and/or from HLA two or more loci-mismatched family donors. None of the patients developed graft failure. The Seattle grading system revealed that 18 patients had no RRT, and the remaining patients had grade I gastrointestinal toxicity alone. The estimated overall survival and leukemia-free survival at two yr were 57.1% and 48.0%, respectively, in 10 patients with acute lymphoblastic leukemia; 91.7% and 71.3%, respectively, in 12 patients with myeloid leukemia. The incidence of TRM was 4.8% at two yr. The rates of RRT above grade II and TRM in an 8-Gy TBI-containing regimen were significantly lower than the data of historical control patients who underwent 12-Gy TBI and cyclophosphamide with or without etoposide. The intermediate-dose TBI-based conditioning regimen may confer successful engraftment combined with minimized RRT, although its efficacy should be further evaluated.ArticlePEDIATRIC TRANSPLANTATION. 13(6):737-745 (2009)journal articl

Empagliflozin in Patients with Chronic Kidney Disease

Background The effects of empagliflozin in patients with chronic kidney disease who are at risk for disease progression are not well understood. The EMPA-KIDNEY trial was designed to assess the effects of treatment with empagliflozin in a broad range of such patients. Methods We enrolled patients with chronic kidney disease who had an estimated glomerular filtration rate (eGFR) of at least 20 but less than 45 ml per minute per 1.73 m(2) of body-surface area, or who had an eGFR of at least 45 but less than 90 ml per minute per 1.73 m(2) with a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of at least 200. Patients were randomly assigned to receive empagliflozin (10 mg once daily) or matching placebo. The primary outcome was a composite of progression of kidney disease (defined as end-stage kidney disease, a sustained decrease in eGFR to < 10 ml per minute per 1.73 m(2), a sustained decrease in eGFR of & GE;40% from baseline, or death from renal causes) or death from cardiovascular causes. Results A total of 6609 patients underwent randomization. During a median of 2.0 years of follow-up, progression of kidney disease or death from cardiovascular causes occurred in 432 of 3304 patients (13.1%) in the empagliflozin group and in 558 of 3305 patients (16.9%) in the placebo group (hazard ratio, 0.72; 95% confidence interval [CI], 0.64 to 0.82; P < 0.001). Results were consistent among patients with or without diabetes and across subgroups defined according to eGFR ranges. The rate of hospitalization from any cause was lower in the empagliflozin group than in the placebo group (hazard ratio, 0.86; 95% CI, 0.78 to 0.95; P=0.003), but there were no significant between-group differences with respect to the composite outcome of hospitalization for heart failure or death from cardiovascular causes (which occurred in 4.0% in the empagliflozin group and 4.6% in the placebo group) or death from any cause (in 4.5% and 5.1%, respectively). The rates of serious adverse events were similar in the two groups. Conclusions Among a wide range of patients with chronic kidney disease who were at risk for disease progression, empagliflozin therapy led to a lower risk of progression of kidney disease or death from cardiovascular causes than placebo