ABSTRACT
Tyrosine kinase inhibitors (TKIs) have significantly improved the survival of patients with chronic myeloid leukemia (CML), however, older patients are often underrepresented in pivotal trials. Approximately 20% of older adults never start treatment and face significant barriers to accomplish favorable outcomes. The treatment goal is to improve survival, prevent progression, and preserve quality of life. This is achieved through optimizing TKI doses and employing discontinuation strategies to attain treatment-free remission (TFR), a goal increasingly pursued by older patients. Imatinib may be favored as the front-line option for older individuals due to its side effect profile and cost. Bosutinib's favorable cardiovascular tolerability makes it a suitable second-line agent, but lower-dose dasatinib may likewise be an attractive option. The prevalence of comorbidities can preclude the use of second generation TKIs in some older patients. Optimal care for older patients with CML centers on personalized treatment, close monitoring, and proactive support.
Subject(s)
Disease Management , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Protein Kinase Inhibitors , Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/mortality , Protein Kinase Inhibitors/therapeutic use , Protein Kinase Inhibitors/adverse effects , Aged , Age Factors , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/adverse effects , Aged, 80 and over , Treatment Outcome , ComorbidityABSTRACT
A novel capillary zone electrophoresis separation coupled to electro spray ionization time-of-flight mass spectrometry method was developed for the simultaneous analysis of six toxic alkaloids: brucine, strychnine, atropine sulfate, anisodamine hydrobromide, scopolamine hydrobromide and anisodine hydrobromide in human plasma and urine. To obtain optimal sensitivity, a solid-phase extraction method using Oasis MCX cartridges (1 mL, 30 mg; Waters, USA) for the pretreatment of samples was used. All compounds were separated by capillary zone electrophoresis at 25 kV within 12 min in an uncoated fused-silica capillary of 75 µm id × 100 cm and were detected by time-of-flight mass spectrometry. This method was validated with regard to precision, accuracy, sensitivity, linear range, limit of detection (LOD), and limit of quantification (LOQ). In the plasma and urine samples, the linear calibration curves were obtained over the range of 0.50-100 ng/mL. The LOD and LOQ were 0.2-0.5 ng/mL and 0.5-1.0 ng/mL, respectively. The intra- and interday precision was better than 12% and 13%, respectively. Electrophoretic peaks could be identified by mass analysis.