Comparison of transplant outcomes and economic costs between biosimilar and originator filgrastim in allogeneic hematopoietic stem cell transplantation.

From January 2012 to September 2015, 49 patients received biosimilar filgrastim (BF) after allogeneic bone marrow transplantation (BMT, n = 31) or peripheral stem cell transplantation (PBSCT, n = 18) in our institution. To evaluate the clinical impact of BF on transplant outcomes of these patients, we compared hematological recovery, overall survival (OS), disease-free survival (DFS), transplantation-related mortality (TRM), cumulative incidence of relapse (CIR), and acute and chronic graft-versus-host disease (GVHD) with those of control patients who received originator filgrastim (OF) after BMT (n = 31) or PBSCT (n = 18). All cases were randomly selected from a clinical database in our institution. In both the BMT and PBSCT settings, neutrophil recovery (17 vs. 19 days in BMT; 13 vs. 15 days in PBSCT) and platelet recovery (27 vs. 31 days in BMT; 17 vs. 28 days in PBSCT) were essentially the same between BF and OF. They were also comparable in terms of OS, DFS, TRM, CIR, and the incidence of acute GVHD and chronic GVHD. On multivariate analysis, the use of BF in both BMT and PBSCT was not a significant factor for adverse transplant outcomes. Although BF significantly reduced filgrastim costs in both BMT and PBSCT, total hospitalization costs were not significantly different between BF and OF.

Retrospective analysis of clinical outcomes of the patients with chronic myeloid leukemia who stopped administration of tyrosine kinase inhibitors: a single institution experience.

We describe herein the clinical outcomes of 16 patients with chronic myeloid leukemia in the chronic phase who stopped the administration of tyrosine kinase inhibitors (TKI) after maintaining undetectable levels of major BCR-ABL1, based on real-time quantitative polymerase chain reaction, for prolonged periods (undetectable MR for a median of 2,100 days (822-4,068). The reasons for discontinuing TKI were enrollments in a clinical trial testing discontinuation of these agents (n=9), adverse effects (n=2) or financial problems (n=5). After TKI discontinuation, patients were followed for a median of 551 days (154-2,446). A total of 8 patients (50%) experienced molecular relapse after a median of 119 days (28-171). Among them, 6 patients who lost major molecular response (MMR) were treated with imatinib (n=2) or dasatinib (n=4), while 2 patients who lost undetectable MR after discontinuing TKI (1 each had taken bostinib and imatinib) but maintained MMR were carefully monitored without re-administration of TKI. Of 6 patients who re-started TKI, 4 (67%) achieved undetectable MR but the other 2 achieved only MMR. The results of this small, retrospective study may support the current understanding of treatment discontinuation, possibly leading to a sustained deep molecular response in some patients.

Lack of association of the Trp64Arg polymorphism of beta3-adrenergic receptor gene with energy expenditure in response to caffeine among young healthy women.

A close relationship between coffee intake and certain metabolic disorders is known. Caffeine, one of coffee components, can increase energy expenditure (EE), but there are considerable individual differences in the caffeine effects on EE, and the causes have not been fully established in humans. The Arg allele in the beta(3)-adrenergic receptor gene (beta(3)-AR), a marker for obesity-related traits, may be a contributor to individual variations in EE. This study investigated the effect of the Arg allele of beta(3)-AR on caffeine-induced increases in EE. In 44 healthy young women (21 +/- 1 years), physical characteristics, blood pressure, biochemical profiles and dietary nutritional intake were measured. A caffeine-loading test was conducted at a dosage of 4 mg per body weight (kg). EE was measured using an indirect open-circuit calorimeter for a 10-min period before, and at 30 min and 60 min after the caffeine-loading test. The beta(3)-AR Trp64Arg polymorphism was detected with a PCR-restriction fragment length polymorphism method. The frequency of the Arg allele was 24%. The distribution of the Trp/Trp, Trp/Arg, and Arg/Arg genotypes was 58%, 36%, and 6%, respectively. At the baseline, subjects with the Arg/Arg genotype had a significantly lower EE level than those with the Trp/Trp or Trp/Arg genotype. After the caffeine-loading test, there were caffeine-induced increases in EE in all genotypes, but there were no differences in the levels of increase among the genotypes. These findings suggest that the genotypes of beta(3)-AR Trp64Arg polymorphism might be not associated with caffeine-induced increases in EE levels.