Patients In Therapeutic Range Research Articles

Treosulfan Therapeutic Drug Monitoring: Optimizing Conditioning Therapy in Pediatric Hematopoietic Stem Cell Transplantation

One of the major challenges to improving outcomes in hematopoietic stem cell transplantation is to choose the best conditioning regimen to reduce toxicity and Non Relapse Mortality, while maintaining adequate transplant efficacy. The use of Treosulfan, in combination with other chemotherapeutic agents, as part of the conditioning regimen, has progressively increased during the last decade, given its remarkable myeloablative and immunosoppressive properties and more favorable toxicity profile in comparison with Busulfan and Total Body Irradiation. For a therapy to be considered effective and safe, it is necessary to know its pharmacokinetic and pharmacodynamic properties, so that it reaches and maintains adequate concentrations in blood and tissues. Data on the pharmacokinetics of Treosulfan and the relationship between toxicity and efficacy in the pediatric population are still scarce, with reports of high inter-individual variability of Treosulfan concentrations in blood. The aim of this multicenter, prospective study is to develop a therapeutic drug monitoring system for Treosulfan dosing, in children undergoing hematopoietic stem cell transplantation for both malignant and non-malignant disorders, through the investigation of the pharmacokinetics in a large population of children after the first dose of Treosulfan, during the pre-transplant conditioning regimen (proposed cumulative therapeutic target, 'Area Under the Curve' (AUC) 4800 mg*h/L, range 3840 - 6000 mg*h/L). To achieve this aim, we measure the percentage of patients in therapeutic range, make dose adjustments if required, and define the relationship between Treosulfan exposure, early toxicity and efficacy, measured by time to engrafment and donor chimerism percentage after transplant. Of the 24 patients so far enrolled, the first 14 were analysed (Table I). Seven (54%) required a dose adjustment after the first administration of Treosulfan: reduced in three cases (43%) for a cumulative AUC above 6000 mg*h/L, increased in four (57%) for AUC below the therapeutic target, confirming the wide inter-individual variability. Enrollment continues, and follow-up of patients should allow the definition of the relationship between personalized Treosulfan dosing, toxicity and efficacy. Therefore, the development of a drug monitoring system for Treosulfan may be an important tool to optimize outcomes in the pediatric population. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

The Ottawa Hospital Regional Warfarin Anticoagulation Management Service. Efficacy and a Patient Satisfaction Survey

Background: 5% of the population over 65 is on oral anticoagulant therapy. The indications for anticoagulation therapy are wide, not limited to but including treatment of arterial and venous thrombosis, and primary stroke prophylaxis is patients with atrial fibrillation and mechanical cardiac valves. While new oral anticoagulants not requiring monitoring are being more widely prescribed, vitamin K antagonists (VKA) are still being used for many patients in whom the novel agents are contra-indicated (renal failure), not available (funding), or patient/physician preference. Most patients on VKA have their family physicians manage their oral anticoagulants. On average, the time in therapeutic range achieved by family physicians is low (50-55%). There is also a number of patients who have no family physician and are either taking VKA without monitoring, or are having their anticoagulants monitored routinely though emergency room physicians/visits. The Ottawa Hospital (TOH) anticoagulation management service is an e-health solution that offers patients world beating time in therapeutic range (TIR). TOH uses a pharmacy managed DAWN software package (computer-assisted warfarin dosing program). Maintaining patients in therapeutic range for a high percentage of time (greater than 70%) can reduce the risk or recurrent thrombosis (venous or arterial) from under-anticoagulation and the risk of bleeding complications from over-anticoagulation. Well managed VKA therapy has also been suggested to be as safe as therapy with novel oral anticoagulants in some subgroup analysis of studies investigating the novel oral anticoagulants. Objectives/Methods: The purpose of this study was to bring the benefits of the TOH experience to provide a Regional Anticoagulation Management Service across a wide region of eastern Ontario, Canada. This service includes remote blood testing (at a lab near the patient’s home), integrated LIS link to a computerized dosing system (possible through a commercial lab partnership), and communication of dosing and testing instructions via interactive voice recognition (IVRS), email, or live (pharmacist/pharmacist assistant). We administered a patient satisfaction survey to a sample of 111 patients enrolled in the service as well as reported TIR for patients enrolled in our service during the study period (2009-2011). Results: At the beginning of the study, 1400 patients were enrolled in the program. After 2 years, the number has increased to by 66% to 2325. The average TIR for patients in the program as of October 2011 was 76.3% (overall), 77.8% (IVRS), 76.8% (email), and 73.3% (live). The patient satisfaction survey demonstrated that 94% patients prefer VKA anticoagulation monitoring through TOH service compared to their previous experience. 84% patients either satisfied or very satisfied with VKA anticoagulation care through TOH service (compared to 53% satisfaction with anticoagulant care prior to enrolling in our program). Conclusions: The TOH model of anticoagulation management service results in excellent VKA monitoring (high TIR) for a large number of patients across a wide geographical area, as well as a high level of patient satisfaction. This service allows for the safe and efficient management of VKAs in patients in whom VKA therapy is indicated. Disclosures No relevant conflicts of interest to declare.

Guidelines on oral anticoagulation (warfarin): third edition – 2005 update

The British Committee for Standards in Haematology (BCSH) published its third edition of Guidelines on Oral Anticoagulation in 1998 (British Committee for Standards in Haematology, 1998). Most of the recommendations made in 1998 remain unchanged and a fourth edition of the guideline is considered unnecessary at the time of writing (June 2005). However, we draw attention to those areas where new informative data have been published. As in the original guideline, the term ‘oral anticoagulant’ used in this update refers to oral vitamin K antagonists (VKA), such as warfarin. New oral non-VKA are currently being evaluated in clinical trials but are not yet licensed for use in the UK. When these drugs become available new guidance will be issued specifically for the use of those drugs. The guideline group was selected to be representative of UKbased medical experts. The drafting group met and communicated by email. MEDLINE was searched systematically for publications in English from 1998. The writing group convenor (T. Baglin) produced the draft guidelines which were subsequently revised by consensus. The guideline was reviewed by a multidisciplinary sounding board, the BCSH and the British Society for Haematology (BSH) and comments incorporated where appropriate. Criteria used to quote levels and grades of evidence are as in Appendix 3 of the Procedure for Guidelines Commissioned by the BCSH (http://www.bcshguidelines.com/process1.asp#App3). The target audience for this guideline is healthcare professionals involved in the management of patients receiving oral anticoagulant therapy.