Letermovir prophylaxis for cytomegalovirus reactivation in allogeneic hematopoietic cell transplant recipients: Single center Canadian data.

BACKGROUND: Cytomegalovirus (CMV) is associated with morbidity and mortality following allogeneic hematopoietic cell transplantation (alloHCT). Letermovir is a novel antiviral agent that prevents CMV reactivation in alloHCT patients, with limited data regarding influence on post-alloHCT outcomes. METHODS: We retrospectively examined 273 alloHCT recipients, 158 in the non-letermovir cohort (NLC), and 115 in the cohort using letermovir prophylaxis (LC). Patients that received letermovir were CMV-seropositive and met criteria for high risk of CMV reactivation. RESULTS: Median start of letermovir was 21 days post-alloHCT, median duration of prophylaxis was 86 days. Letermovir prophylaxis demonstrated a statistically significant reduction in first CMV reactivation (at 200 days post 63.9% in the NLC vs. 35.7% in the LC; p < .001). On univariate analysis at 1 year, overall survival (OS) for NLC was 79.6% and 79.5% for LC (p = .54). Non relapse mortality (NRM) at 1 year for NLC was 12% and 12.3% for LC (p = .69). Cumulative incidence of relapse (CIR) at 1 year was 13.9% for NLC versus 17.1 for the LC (p = .27). On multivariable analysis, there was no significant difference between the two cohorts for OS, NRM, and CIR. CONCLUSIONS: Letermovir prophylaxis started at day +21 post-alloHCT reduced CMV reactivation, with no impact on posttransplant outcomes.

Single center evaluation on the use of conditionally ordered low molecular weight heparins in malignant hematology patients with venous thromboembolism.

BACKGROUND: Cancer and cancer-related treatments are significant independent risk factors for malignant hematology (MH) patients in developing venous thromboembolism (VTE). Treatment of VTE in MH patients at the Princess Margaret Cancer Centre is predominantly initiated with low molecular weight heparin (LMWH) in accordance with guidelines. While guidelines recommend against LMWH use in patients with thrombocytopenia, prescribers may order LMWH conditionally based on platelet values. Currently, there is a lack of consistent practice with variation in both the use of conditional orders as well as the threshold of platelet values for conditional orders. The objectives of the study were to (a) describe the use of conditionally ordered LMWH based on platelet values; (b) determine its safety by measuring administration concordance with conditional orders and bleeding event rates during inpatient admission; and (c) determine its efficacy by measuring the rate of worsening VTE or recurrence during inpatient admission. METHODS: Electronic records of MH inpatients admitted between January 2017 and December 2019 and who were administered at least one dose of an LMWH for the treatment of VTE were screened. RESULTS: One hundred and eight patients were screened to obtain 50 eligible patients with a median age of 59 years (SD = ±18.8 years). The most frequent MH diagnosis was acute lymphoblastic leukemia (30%). Sixty percent (n = 30) of patients received conditional orders. Out of 571 administrations, 543 (95%) were administered concordantly (Χ2(1) = 472, p < 0.0001). In this group of patients, 8 patients had either documented bleeding or experienced a drop in hemoglobin >10 g/L within a 72 h time frame. No patients experienced a recurrent VTE during inpatient treatment (for up to 40 days post-admission). CONCLUSIONS: It appears that conditionally ordered LMWH can be concordantly administered and is safe and effective in the treatment of VTE in MH patients experiencing thrombocytopenia. There were no reports of worsening or new VTE in our small sample.

Evaluation of a patient self-medication program in allogeneic hematopoietic stem cell transplantation.

INTRODUCTION: Patients admitted for allogeneic hematopoietic stem cell transplantation (allo-HSCT) are discharged with multiple new medications. At our institution, a new patient Self Medication Program (SMP) was implemented on the allo-HSCT units. An SMP allows patients to practice self-administration of medications in a controlled environment before discharge. We assessed the impact of the SMP on patient medication knowledge, self-efficacy, adherence, and safety. Patient and staff satisfaction with the SMP was also explored. METHODS: Participants in the SMP group received medication counseling by a pharmacist and self-managed their medications with nursing supervision until discharge. Participants in the pre-SMP group received medication counseling by a pharmacist at discharge. All participants completed a Medication Knowledge and Self-Efficacy Questionnaire before discharge and at follow-up. Safety endpoints were assessed for SMP participants. RESULTS: Twenty-six patients in the pre-SMP group and 25 patients in the SMP group completed both questionnaires. Median knowledge scores in the pre-SMP group versus the SMP group were 8.5/10 versus 10/10 at discharge (p = 0.0023) and 9/10 versus 10/10 at follow-up (p = 0.047). Median self-efficacy scores were 38/39 in the pre-SMP group versus 39/39 in the SMP group at both discharge and follow-up (pdischarge = 0.11, pfollow-up = 0.10). The SMP was associated with at least 1 medication event in 7 participants, but no medication incidents. Patient and staff surveys showed a positive perceived value of the SMP. CONCLUSION: Our results demonstrate that the SMP is associated with durable, improved medication knowledge, a trend towards improved self-efficacy, and largely positive perceptions among both staff and patient participants.

Arterial input function calculation in dynamic contrast-enhanced MRI: an in vivo validation study using co-registered contrast-enhanced ultrasound imaging.

OBJECTIVES: Developing a method of separating intravascular contrast agent concentration to measure the arterial input function (AIF) in dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of tumours, and validating its performance in phantom and in vivo experiments. METHODS: A tissue-mimicking phantom was constructed to model leaky tumour vasculature and DCE-MR images of this phantom were acquired. An in vivo study was performed using tumour-bearing rabbits. Co-registered DCE-MRI and contrast-enhanced ultrasound (CEUS) images were acquired. An independent component analysis (ICA)-based method was developed to separate the intravascular component from DCE-MRI. Results were validated by comparing the time-intensity curves with the actual phantom and in vivo curves. RESULTS: Phantom study: the AIF extracted using ICA correlated well with the true intravascular curve. In vivo study: the AIFs extracted from DCE-MRI using ICA were very close to the true AIF. Intravascular component images were very similar to the CEUS images. The contrast onset times and initial wash-in slope of the ICA-derived AIF showed good agreement with the CEUS curves. CONCLUSION: ICA has the potential to separate the intravascular component from DCE-MRI. This could eliminate the requirement for contrast medium uptake measurements in a major artery and potentially result in more accurate pharmacokinetic parameters. KEY POINTS: • Tumour response to therapy can be inferred from pharmacokinetic parameters. • Arterial input function (AIF) is required for pharmacokinetic modelling of tumours. • Independent component analysis has the potential to measure AIF inside the tumour. • AIF measurement is validated using contrast enhanced ultrasound and phantoms.

Intrathecal cytomegalovirus immunoglobulin for CMV encephalitis post allogeneic stem cell transplantation.

We report the outcome of a 43 year old man who developed fatal ventriculoencephalitis due to cytomegalovirus (CMV) infection 7 months post allogeneic stem cell transplant. He failed multiple lines of treatment, including intravenous ganciclovir, foscarnet, and CMV-specific immunoglobulins, without improvement in CSF CMV copies. Novel intrathecal administration of CMV immunoglobulins was given but did not lead to clearance of CMV from CSF. No adverse effects related to intrathecal CMV immunoglobulins were observed. Notably, throughout this period, CMV in blood remained undetectable. This case highlights the difficulty in treating CMV encephalitis, and that novel therapeutic approaches are needed.

Managing chronic pain in older people.

Management of pain in older people should follow the biopsychosocial model, addressing the heterogeneity in their physiological changes, psychological and cognitive aspects, and impact on their social interactions. When deciding on pharmacological treatment, special attention should be given to the side effect profile, drug-drug and drug-disease interactions, as well as route and timing of medication administration. The principle of 'start low, go slow' should be followed, and regular reviews of drug effectiveness and tolerability are required. With the adjunct of non-pharmacological interventions, the treatment plan should be tailored to individual needs, with the aim to ameliorate the burden of pain while preserving quality of life.

Development of a platform for co-registered ultrasound and MR contrast imaging in vivo.

Imaging of the microvasculature is often performed using contrast agents in combination with either ultrasound (US) or magnetic resonance (MR) imaging. Contrast agents are used to enhance medical imaging by highlighting microvascular properties and function. Dynamic signal changes arising from the passage of contrast agents through the microvasculature can be used to characterize different pathologies; however, comparisons across modalities are difficult due to differences in the interactions of contrast agents with the microvasculature. Better knowledge of the relationship of contrast enhancement patterns with both modalities could enable better characterization of tissue microvasculature. We developed a co-registration platform for multi-modal US and MR imaging using clinical imaging systems in order to study the relationship between US and MR contrast enhancement. A preliminary validation study was performed in phantoms to determine the registration accuracy of the platform. In phantoms, the in-plane registration accuracy was measured to be 0.2 ± 0.2 and 0.3 ± 0.2 mm, in the lateral and axial directions, respectively. The out-of-plane registration accuracy was estimated to be 0.5 mm ±0.1. Co-registered US and MR imaging was performed in a rabbit model to evaluate contrast kinetics in different tissue types after bolus injections of US and MR contrast agents. The arrival time of the contrast agent in the plane of imaging was relatively similar for both modalities. We studied three different tissue types: muscle, large vessels and fat. In US, the temporal kinetics of signal enhancement were not strongly dependent on tissue type. In MR, however, due to the different amounts of agent extravasation in each tissue type, tissue-specific contrast kinetics were observed. This study demonstrates the feasibility of performing in vivo co-registered contrast US and MR imaging to study the relationships of the enhancement patterns with each modality.