Safety and efficacy of upfront plerixafor + G‐CSF versus placebo + G‐CSF for mobilization of CD34+ hematopoietic progenitor cells in patients ≥60 and <60 years of age with non‐Hodgkin's lymphoma or multiple myeloma

The efficacy and safety of plerixafor + G‐CSF in enhancing hematopoietic stem cell mobilization and collection has been demonstrated in two phase III studies involving patients with NHL or MM. In these pivotal studies, plerixafor + G‐CSF significantly increased the proportion of patients achieving target stem cell yields, compared to placebo + G‐CSF. In this analysis, we compare the efficacy and safety of plerixafor + G‐CSF versus placebo + G‐CSF in patients enrolled in the two phase III studies, stratified by age: ≥60 years of age and <60 years of age. The proportion of older patients who achieved target stem cell yields was significantly higher in the plerixafor group than in placebo group (NHL: 50.9 vs. 25.4%, P < 0.001; MM: 69.6 vs. 23.7%, P < 0.001). In this older cohort, the median times to neutrophil and to platelet engraftment following autologous stem cell transplant were comparable between the plerixafor and placebo groups. Similar efficacy findings were observed in the younger age group. The most common adverse events (all grades) reported among older patients in the plerixafor group included diarrhea (41.3%), nausea (38.9%), fatigue (30.2%), and injection‐site reaction (29.4%). The frequency of adverse events was similar between the older and the younger age groups. Taken together, our subanalysis demonstrate that plerixafor + G‐CSF can be safely and effectively used in adult patients of all ages, including those ≥60 years, to support optimal stem cell mobilization for autologous stem cell transplantation. Am. J. Hematol. 88:1017–1023, 2013. © 2013 Wiley Periodicals, Inc.     

Antiarrhythmic efficacy and electrophysiologic actions of amiodarone in patients with life-threatening ventricular arrhythmias: Potent suppression of spontaneously occurring tachyarrhythmias versus inconsistent abolition of induced ventricular tachycardia

The antiarrhythmic efficacy and the electrophysiologic effects of amiodarone were determined in 13 consecutive patients with symptomatic life-threatening ventricular arrhythmias resistant to conventional agents. Amiodarone was initially given in high doses (1000 to 1800 mg/daily); electrophysiologic effects including induction of ventricular tachycardia (VT) by programmed electrical stimulation (PES) was undertaken before and after a mean period of 28 (range 14 to 56) days of amiodarone therapy. Plasma drug levels determined by high pressure liquid chromatography were within the “therapeutic” range (0.92 to 11.99 mg/L). Antiarrhythmic efficacy was determined on the basis of the quantitative analysis of 24-hour Holter recordings. Amiodarone reduced heart rate (HR) (?17.6%, p < 0.001), lengthened PR interval (+15%, p < 0.05), AH interval (+19.8%, P < 0.01), and the QT_o by 13.3% (p < 0.01), without effect on the QRS or HV intervals. The atrial effective refractory period (ERP) increased by 31.3% (p < 0.001) and the ventricular ERP by 22.5% (p < 0.001); ERP of the AV node also increased but could not be determined in all patients because of the longer refractory period of the atrium. Before amiodarone, AV Wenckebach during atrial pacing developed at HR of 150 ± 13 bpm and at 117 ± 7.6 bpm during amiodarone therapy (p < 0.01). In all 13 patients, amiodarone reduced the total counts of premature ventricular beats (PVCs) by 95% to 98% and eliminated complex ventricular ectopic activity (VEA) and runs of VT. The effect has been sustained during a mean follow-up period of 12 months and there have been no symptoms. Before amiodarone was given, VT could be induced by PES in 12 of 13 patients (seven sustained, five nonsustained). On amiodarone, VT was provoked in four (three sustained, one nonsustained). Side effects have included photosensitivity, proximal muscle weakness, elevation of hepatic enzymes, halo vision, and corneal deposits but without impaired vision; these could be reduced in severity or avoided by reduction in drug dosage. These data indicate that amiodarone is highly potent in suppressing symptomatic life-threatening ventricular tachycardias (PVCs, VEA, $\text{VT}\text{VF}$) without always being able to prevent the induction of VT by PES of the heart. The drug can be used in this context without the need for invasive electrophysiologic studies.