Comparison of High- and Low-Dose Rivaroxaban Regimens in Elderly East Asian Patients With Atrial Fibrillation.

BACKGROUND: In the Rivaroxaban Once-daily oral direct factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) trial, rivaroxaban 20 mg was the on-label dose, and the dose-reduction criterion for rivaroxaban was a creatinine clearance of < 50 mL/min. Some Asian countries are using reduced doses label according to the J-ROCKET AF trial. The aim of this study was to assess the safety and efficacy of a high-dose rivaroxaban regimen (HDRR, 20/15 mg) and low-dose rivaroxaban regimen (LDRR, 15/10 mg) among elderly East Asian patients with atrial fibrillation (AF) in real-world practice. METHODS: This study was a multicenter, prospective, non-interventional observational study designed to evaluate the efficacy and safety of rivaroxaban in AF patients > 65 years of age with or without renal impairment. RESULTS: A total of 1,093 patients (mean age, 72.8 ± 5.8 years; 686 [62.9%] men) were included in the analysis, with 493 patients allocated to the HDRR group and 598 patients allocated to the LDRR group. A total of 765 patients received 15 mg of rivaroxaban (203 in the HDRR group and 562 in the LDRR group). There were no significant differences in the incidence rates of major bleeding (adjusted hazard ratio [HR], 0.64; 95% confidential interval [CI], 0.21-1.93), stroke (adjusted HR, 3.21; 95% CI, 0.54-19.03), and composite outcomes (adjusted HR, 1.13; 95% CI, 0.47-2.69) between the HDRR and LDRR groups. CONCLUSION: This study revealed the safety and effectiveness of either dose regimen of rivaroxaban in an Asian population for stroke prevention of AF. Considerable numbers of patients are receiving LDRR therapy in real-world practice in Asia. Both regimens were safe and effective for these patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04096547.

Hematologic recovery after tandem high-dose chemotherapy and autologous stem cell transplantation in children with high-risk solid tumors.

Although the number of studies using tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/autoSCT) for the treatment of high-risk pediatric solid tumors has been increasing, documentation of hematologic recovery after tandem HDCT/autoSCT is very limited. For this reason, we retrospectively analyzed the hematologic recovery of 236 children with high-risk solid tumors who underwent tandem HDCT/autoSCT. The median numbers of CD34(+) cells transplanted during the first and second HDCT/autoSCT were 4.3 × 10(6)/kg (range 0.6-220.2) and 4.1 × 10(6)/kg (range 0.9-157.6), respectively (P = 0.664). While there was no difference in neutrophil recovery between the first and second HDCT/autoSCT, platelet and RBC recoveries were significantly delayed in the second HDCT/autoSCT (P < 0.001 and P < 0.001, respectively). Delayed recovery in the second HDCT/autoSCT was more prominent when the number of transplanted CD34(+) cells was lower, especially if it was < 2 × 10(6)/kg. A lower CD34(+) cell count was also associated with increased RBC transfusion requirements and a higher serum ferritin level after tandem HDCT/autoSCT. More CD34(+) cells need to be transplanted during the second HDCT/autoSCT in order to achieve the same hematologic recovery as the first HDCT/autoSCT.

Iron chelation treatment with deferasirox prior to high-dose chemotherapy and autologous stem cell transplantation may reduce the risk of hepatic veno-occlusive disease in children with high-risk solid tumors.

BACKGROUND: We evaluated whether iron chelation treatment during induction chemotherapy could safely reduce serum iron levels and thereby reduce the frequency of hepatic veno-occlusive disease (VOD) during high-dose chemotherapy and autologous stem cell transplantation (HDCT/autoSCT) in children with high-risk solid tumors. PROCEDURE: Children diagnosed with high-risk solid tumors between August 2008 and July 2009 were enrolled. Deferasirox treatment (25 mg/kg/day) was initiated when serum ferritin levels increased to more than 1,000 ng/ml during induction chemotherapy. Patients who were diagnosed with the same disease between April 2005 and June 2007 and treated in the same way without any iron chelation treatment formed the control group. Efficacy and toxicity of deferasirox treatment were compared between the two groups. RESULTS: Eighteen of 20 patients enrolled received deferasirox treatment. Deferasirox treatment was completed as scheduled in 11 (61.1%) of them without dose reduction or discontinuation. The serum ferritin levels prior to HDCT/autoSCT were lower in the deferasirox group than in the control group (median 1,268 ng/ml vs. 1,828 ng/ml, P < 0.001), although there was no difference in the RBC transfusion amount between the two groups. While 7 (17.9%) VODs developed during 39 HDCT/autoSCTs in the control group, there was no VOD during 40 HDCT/autoSCTs in the deferasirox group (P = 0.005). However, renal dysfunction (38.9%) including Fanconi syndrome (16.7%) was a frequently observed adverse effect of deferasirox treatment. CONCLUSIONS: Deferasirox treatment during induction chemotherapy reduces the frequency of VOD during HDCT/autoSCT. The development of renal dysfunction should be closely monitored during deferasirox treatment.