Analysis of spontaneous cytomegalovirus clearance after low level reactivation using a pre-emptive treatment threshold of 4,000 IU/mL in allogeneic hematopoietic cell transplant recipients.

BACKGROUND: Cytomegalovirus (CMV) can be a serious complication after allogeneic hematopoietic cell transplant (HCT). CMV viral load is routinely monitored, and pre-emptive therapy is initiated to prevent CMV viremia from developing into CMV organ disease based on institutional thresholds. There is no established universal threshold for pre-emptive therapy and many centers utilize different strategies. METHODS: Allogeneic HCT recipients at WVU Medicine from 2009 to 2021 were routinely initiated on pre-emptive CMV treatment for a PCR viral threshold above 4000 IU/mL. Adult patients with quantifiable values below this threshold, were analyzed to evaluate the rate of spontaneous clearance without initiation of CMV-directed therapy, during their first episode of CMV reactivation. This study excluded any patients that received letermovir prophylaxis. RESULTS: Sixty patients were included in the analysis. The spontaneous clearance rate was 60 %. The risk factors that were associated with a lower spontaneous clearance rate were reactivation within thirty days after transplant (p = 0.031), presence of graft-versus-host-disease (p = 0.031), and CMV PCR values of 2500-4000 IU/mL (p = 0.02). Although these patients had lower rates of spontaneous clearance, they still spontaneously cleared in 42 %, 42 %, and 43 % of the cases, respectively. CONCLUSION: Delaying pre-emptive treatment until a CMV PCR value of 4000 IU/mL is reached appears appropriate and decreases unnecessary treatment toxicity and resistance.

Evaluation of prolonged magnesium infusion after allogeneic hematopoietic cell transplant.

PURPOSE: Calcineurin inhibitor use after allogeneic hematopoietic cell transplantation (allo-HCT) is associated with significant magnesium wasting. Utilization of a prolonged magnesium infusion is thought to lead to a lower serum peak concentration and therefore, decreased renal wasting of magnesium. In November 2017, our institution implemented a modification to our inpatient electrolyte replacement protocol for allo-HCT recipients that extended the magnesium infusion rate from 4 g/2 h to 4 g/4 h based on this theoretical advantage. The primary objective of this study was to compare the median magnesium requirements per day of admission between patients who received magnesium 4 g/2 h to patients who received magnesium 4 g/4 h. Secondary objectives included a comparison of the per-patient median serum magnesium concentration during admission, as well as the median incremental difference in serum magnesium concentration after intravenous replacement per patient per admission. METHODS: Allo-HCT recipients who received prolonged infusion magnesium infusions were compared to a historical cohort of allo-HCT patients who received shorter IV magnesium infusions. Admissions were included if the patient had received an allo-HCT within 100 days prior, was admitted to the Transplant and Cellular Therapy Unit at WVU Medicine J.W. Ruby Memorial Hospital, and received at least one magnesium infusion and one dose of cyclosporine or tacrolimus. Admissions were excluded if the patient received oral magnesium, total parenteral nutrition, aminoglycosides, amphotericin, carboplatin, cisplatin, or foscarnet. RESULTS: The pre-implementation group consisted of 81 admissions (n = 64 patients), while the post-implementation group consisted of 90 admissions (n = 60 patients). Median magnesium requirements per day of admission were not different between groups at 1.4 g of magnesium in the pre-implementation group and 1.9 g of magnesium in the post-implementation group (P = 0.25). Median serum magnesium concentrations and median incremental difference in serum magnesium concentration after intravenous replacement were also not different between groups: 1.65 mg/dL vs 1.60 mg/dL (P = 0.65) and 0.30 mg/dL vs 0.28 mg/dL (P = 0.67), respectively. CONCLUSIONS: Prolonged infusion of magnesium in allo-HCT recipients receiving CNI therapy does not result in improvement in magnesium retention.

30-Day Readmission Reduction in a Skilled Facility Population Through Pharmacist-Driven Medication Reconciliation.

BACKGROUND: Transitions of care can be difficult to manage and if not performed properly, can lead to increased readmissions and poor outcomes. Transitions are more complex when patients are discharged to skilled nursing facilities. PURPOSE: We assessed the impact of pharmacist-led initiatives, including medication reconciliation, on readmission rates between an academic medical center and a local skilled nursing facility (SNF). METHODS: We conducted a two-phase quality improvement project focusing on pharmacist-led medication reconciliation at different points in the transition process. All-cause 30-day readmission rates, medication reconciliation completion rates, and total pharmacist interventions were compared between the 2 groups. RESULTS: The combined intervention and baseline cohorts resulted in a 29.8% relative reduction (14.5% vs. 20.6%) in readmission rates. Medication reconciliation was completed on 93.8% of SNF admitted patients in the first phase and 97.7% of patients in the second phase. Pharmacist interventions per reconciliation were 2.39 in the first phase compared with 1.82 in the second phase. CONCLUSION: Pharmacist-led medication reconciliation can contribute to reduction of hospital readmissions from SNFs and is an essential part of the SNF transition process.

Evaluation of the Pharmacokinetic Interaction Between Letermovir and Tacrolimus in Allogeneic Hematopoietic Cell Transplantation Recipients.

Data describing the magnitude of the pharmacokinetic interaction between letermovir and tacrolimus in allogeneic hematopoietic cell transplantation (allo-HCT) recipients are limited, and varying outcomes have been reported. The need for empiric dose adjustment of tacrolimus on initiation of letermovir has not been established; instead, guidelines suggest closely monitoring the tacrolimus trough concentration and adjusting the dose as needed. A better understanding of this interaction is imperative to accurately manage the narrow therapeutic window of tacrolimus post-transplantation. The primary objective of this study was to determine the percent change in tacrolimus concentration-to-dose ratio over the 14-day period after initiation of letermovir. Secondary objectives were to describe the frequency of tacrolimus dose adjustments after initiation of letermovir, the percent change in daily tacrolimus dose over the 14-day period after initiation of letermovir, and the incidence of both subtherapeutic and supratherapeutic tacrolimus trough concentrations. This retrospective chart review included adult allo-HCT recipients at our institution who received tacrolimus in combination with oral letermovir and had been taking tacrolimus for at least 5 days before letermovir initiation. Patients receiving strong CYP3A4 inhibitors or i.v. tacrolimus were excluded. Thirty-five patients were included in the analysis. The median percent increase in tacrolimus concentration-to-dose ratio over the 14-day period after initiation of letermovir was 22% on days 2 to 4, 47% on days 5 to 7, 66% on days 8 to 11, and 81% on days 12 to 14. The mean frequency of tacrolimus dose adjustments was 0.66 on days 2 to 4, 0.69 on days 5 to 7, 1.06 on days 8 to 11, and 0.57 on days 12 to 14. The results of this study show that the pharmacokinetic interaction between tacrolimus and letermovir is substantial and continues to affect tacrolimus concentration over the 14-day period after letermovir initiation. Close monitoring of tacrolimus trough concentration on initiation of letermovir should be considered.

Toxicity assessment of concurrent gabapentin/pregabalin administration with high-dose melphalan in autologous hematopoietic cell transplant recipients.

A theoretical pharmacokinetic interaction mediated through L-amino acid transporter 1 and 2 exists between gabapentin (GP) and pregabalin (PG) with melphalan. Peripheral neuropathy is a common toxicity of various multiple myeloma regimens commonly utilized prior to autologous hematopoietic cell transplant (auto-HCT) with high-dose melphalan (HD-Mel). Therefore, it is likely concurrent administration of either GP or PG will occur in patients receiving HD-Mel conditioning for auto-HCT, which could potentially increase cellular uptake and worsen the mucosal injury. A retrospective chart review of adult patients from January 2012 to July 2016 who received HD-Mel (140-200 mg/m2) at West Virginia University Medicine was performed to assess toxicity and outcomes in these patients. A total of 80 patients were included in the study, with 30 patients receiving GP or PG and 50 control patients. There were no significant differences in grade 2 or higher mucositis, admissions for nausea/vomiting/diarrhea, intravenous opioid requirements, oral topical therapies, antidiarrheal medication use, rescue anti-emetics, days of nausea or vomiting, pain scores, neutrophil or platelet engraftment, treatment-related mortality, progression-free survival, or overall survival. Our data suggest that it is safe to continue GP/PG therapy throughout HD-Mel therapy, with no negative transplant outcomes. Prospective studies or evaluations of larger databases are necessary to better characterize the clinical effect of concomitant therapy.

Pharmacist-driven medication reconciliation reduces oral oncolytic medication errors during transitions of care.

PURPOSE: The purpose of this study was to characterize medication errors associated with oral oncolytics as patients with cancer were admitted to the inpatient setting and identify contributing factors that lead to errors. METHODS: A review of patients prescribed a cyclic oral oncolytic who were then admitted to the inpatient setting at a large, academic medical center from July 1, 2013, to June 30, 2018, was conducted. RESULTS: Eighty-one patients were included in the analysis. Thirty-five errors (43%) related to transcription of the oral oncolytic regimen from the outpatient to the inpatient setting were identified. Categorization of errors revealed that 46% were due to delays in treatment. Within this error subset, 75% of the delays were related to unavailability of nonformulary oral oncolytics. There was a significant decrease in error for patients who received medication reconciliation by a pharmacist (P = 0.032) after admission. There were no other significant differences observed among variables that may have led to increased error rates. Three percent of errors were reported to the internal medication safety reporting system at our institution. CONCLUSION: The inability to fully confirm patients' home regimen via chart review poses great risk to accurate medication ordering upon hospital admission. Completion of medication reconciliations by pharmacists serves to decrease rates of errors that may occur during hospital admission in cancer patients undergoing treatment with oral oncolytic therapies.