BACKGROUND Patients with transfusion-dependent β-thalassemia need regular red-cell transfusions. Luspatercept, a recombinant fusion protein that binds to select transforming growth factor β superfamily ligands, may enhance erythroid maturation and reduce the transfusion burden (the total number of red-cell units transfused) in such patients. METHODS In this randomized, double-blind, phase 3 trial, we assigned, in a 2:1 ratio, adults with transfusion-dependent β-thalassemia to receive best supportive care plus luspatercept (at a dose of 1.00 to 1.25 mg per kilogram of body weight) or placebo for at least 48 weeks. The primary end point was the percentage of patients who had a reduction in the transfusion burden of at least 33% from baseline during weeks 13 through 24 plus a reduction of at least 2 red-cell units over this 12-week interval. Other efficacy end points included reductions in the transfusion burden during any 12-week interval and results of iron studies. RESULTS A total of 224 patients were assigned to the luspatercept group and 112 to the placebo group. Luspatercept or placebo was administered for a median of approximately 64 weeks in both groups. The percentage of patients who had a reduction in the transfusion burden of at least 33% from baseline during weeks 13 through 24 plus a reduction of at least 2 red-cell units over this 12-week interval was significantly greater in the luspatercept group than in the placebo group (21.4% vs. 4.5%, P<0.001). During any 12-week interval, the percentage of patients who had a reduction in transfusion burden of at least 33% was greater in the luspatercept group than in the placebo group (70.5% vs. 29.5%), as was the percentage of those who had a reduction of at least 50% (40.2% vs. 6.3%). The least-squares mean difference between the groups in serum ferritin levels at week 48 was −348 μg per liter (95% confidence interval, −517 to −179) in favor of luspatercept. Adverse events of transient bone pain, arthralgia, dizziness, hypertension, and hyperuricemia were more common with luspatercept than placebo. CONCLUSIONS The percentage of patients with transfusion-dependent β-thalassemia who had a reduction in transfusion burden was significantly greater in the luspatercept group than in the placebo group, and few adverse events led to the discontinuation of treatment. (Funded by Celgene and Acceleron Pharma; BELIEVE ClinicalTrials.gov number, NCT02604433; EudraCT number, 2015-003224-31.)

EssentialsNonacog beta pegol is a recombinant glycoPEGylated factor IX with an extended half-life. This phase 3 trial investigated its safety/efficacy in previously treated hemophilia B boys ≤ 12 years. A 40 IU kg À1 dose provided effective once-weekly prophylaxis and hemostasis when used to treat bleeds. Nonacog beta pegol was well tolerated in previously treated boys ≤ 12 years with hemophilia B.Summary. Background: Nonacog beta pegol is a recombinant glycoPEGylated factor IX with an extended half-life, developed to improve care for patients with hemophilia B. Objectives: To investigate the safety, efficacy and pharmacokinetics of nonacog beta pegol for the prophylaxis and treatment of bleeds in previously treated children with hemophilia B. Patients/Methods: This phase 3 trial, paradigm TM 5, enrolled and treated 25 children (aged ≤ 12 years) with hemophilia B (FIX ≤ 2%). Patients were stratified by age (0-6 years and 7-12 years), and received once-weekly prophylaxis with 40 IU kg À1 nonacog beta pegol for 50 exposure days. Results: No patient developed inhibitors, and no safety concerns were identified. Forty-two bleeds in 15 patients were reported to have been treated; the overall success rate was 92.9%, and most bleeds (85.7%) resolved after one dose. The median annualized bleeding rates (ABRs; bleeds per patient per year) were 1.0 in the total population, 0.0 in the 0-6-year group, and 2.0 in the 7-12-year group; the estimated mean ABRs were 1.44 in the total population, 0.87 in the 0-6-year group, and 1.88 in the 7-12-year group. For 22 patients who had previously been receiving prophylaxis, the estimated mean ABR was 1.38 versus a historical ABR of 2.51. Estimated mean steady-state FIX trough levels were 0.153 IU mL À1(0-6 years) and 0.190 IU mL À1 (7-12 years). Conclusion: Nonacog beta pegol was well tolerated in previously treated children with hemophilia B; a 40 IU kg À1 dose provided effective once-weekly prophylaxis and hemostasis when bleeds were treated.

OBJECTIVE -To study the prevalence of and risk factors for abnormal glucose tolerance in transfusion-dependent ␤-thalassemic patients.RESEARCH DESIGN AND METHODS -A total of 89 transfusion-dependent ␤-thalassemic patients were interviewed. Diabetes was previously diagnosed in 14 of them. In the remaining 75 patients, 68 participated in an oral glucose tolerance test. Potential risk factors were identified using the independent t test, 2 test, and Fisher's exact test. Logistic regression analysis was used to select the independent risk factors that best predicted abnormal glucose tolerance. A two-tailed P value of Ͻ0.05 was considered to be statistically significant.RESULTS -The prevalence of impaired glucose tolerance was 8.5% (7 of 82) and that of diabetes was 19.5% (16 of 82). Presentation with diabetic ketoacidosis was 31.1% (5 of 16). The risk factors for abnormal glucose tolerance found in transfusion-dependent ␤-thalassemic patients were serum ferritin concentration and hepatitis C infection.

In pediatric posttransplantation patients, CMV viremia mostly occurred within 100 days after transplantation. Risk factors associated with CMV viremia include older diagnostic age, leukemic patients, unrelated donor HSCT, pretransplant ATG use, GvHD, and gastrointestinal GvHD.

The aim of this study was to analyze the renal outcome of pediatric lupus nephritis in the past two decades. We retrospectively reviewed the medical records of patients who fulfilled the 1987 American Rheumatism Association revised criteria for systemic lupus erythematosus who were followed up at the National Taiwan University Hospital between 1980 and 2001. All new patients who were under 18 years of age at the time of diagnosis were enrolled and were followed up until death, loss to follow-up, or till the end of 2002. The response to the treatment and renal outcome were analyzed. Seventy-two children (64 girls and 8 boys) were enrolled in the study. The mean age at diagnosis was 13.93+/-0.35 years (mean +/- SEM). The mean duration of follow-up was 7.12+/-0.51 years. The 5-year renal survival rate (survival without dialysis or transplantation) was 63.13% and the 10-year survival rate was 53.54%. It was significantly better in patients receiving cyclophosphamide (CYC) pulse therapy. The 5-year survival rate for these patients was 87.82% and the 10-year survival rate was 81.06%. The renal survival curve was better in the CYC pulse therapy group than in the no CYC pulse therapy group, with p=0.0022. The duration between the diagnosis of lupus nephritis and end-stage renal disease (ESRD) was significantly longer in the CYC group (9.66+/-1.32 yrs) than in the no CYC group (3.24+/-0.94 yers), p=0.036. In the multivariate analysis, risk factors of developing ESRD were failure to achieve complete remission, higher serum creatinine at the initiation of treatment, and not receiving CYC pulse therapy. The renal survival was significantly better in the CYC pulse therapy group. The CYC pulse therapy was recommended in pediatric lupus nephritis patients and every effort should be made to achieve complete remission.