Efficacy of delayed pegfilgrastim administration following consolidation therapy with high-dose cytarabine (HiDAC) in acute myeloid leukemia (AML) patients.

PURPOSE: To study the effects of delaying pegfilgrastim administration following high-dose cytarabine (HiDAC) consolidation in AML patients on time to neutrophil count recovery, infectious complications, and survival. METHODS: Single-center retrospective chart review of 55 patients receiving pegfilgrastim as early administration (within 72 h) or delayed administration (after 72 h) of HiDAC. RESULTS: The difference in neutrophil recovery time was similar between the early and delayed groups (18 days versus 19 days, p < 0.28). Infections were seen in four patients in the early administration group following chemotherapy compared to none in the delayed group (p = 0.04). Febrile neutropenia rates were also decreased in the delayed administration group (23.1% versus 10.3%, p = 0.28) as well as a trend towards longer median survival (16 months versus 19 months, p = 0.69) and overall survival (21 months versus 31 months, p = 0.47). CONCLUSION: A difference in time to neutrophil recovery was not observed between the early and delayed administration groups yet decreased infectious complications may support the delayed administration of pegfilgrastim in these patients.

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.

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.