Busulfan, a bifunctional alkylating agent, has been used as a conditioning regimen prior to allogeneic hematopoietic stem cell transplantation (HSCT). The aim of this study was to derive a novel once-daily intravenous (IV) busulfan dosing nomogram for pediatric patients undergoing HSCT using a population pharmacokinetic (PK) model. A population PK analysis was performed using 2183 busulfan concentrations in 137 pediatric patients (age: 0.6-22.2 years), who received IV busulfan once-daily for 4 days before undergoing HSCT. Based on the final population PK model, an optimal once-daily IV busulfan dosing nomogram was derived. The percentage of simulated patients achieving the daily target area under the concentration-time curve (AUC) by the new nomogram was compared with that by other busulfan dosing regimens including the FDA regimen, the EMA regimen, and the empirical once-daily regimen without therapeutic drug monitoring (TDM). A one-compartment open linear PK model incorporating patient's body surface area, age, dosing day, and aspartate aminotransferase as a significant covariate adequately described the concentration-time profiles of busulfan. An optimal dosing nomogram based on the PK model performed significantly better than the other dosing regimens, resulting in >60% of patients achieving the target AUC while the percentage of patients exceeding the toxic AUC level was kept <25% during the entire treatment period. A novel once-daily busulfan dosing nomogram for pediatric patients undergoing HSCT is useful for clinicians, particularly in a setting where TDM service is not readily available or to optimize the dose on day 1.

At each follow-up, Tnasal IOP was statistically lower than at baseline, although the reduction was not as great as that of Tcenter IOP. A 2 to 3 mm Hg drop in Tnasal up to 6 months after LASIK should be expected. An alternative would be to measure IOP with the Tono-Pen on the nasal side to fit the tip to the relatively unchanged nasal side of the cornea.

Because the optic disc in myopic eyes is different from a normal optic disc, there are many difficulties in examining the optic discs of myopic eyes. To study optic disc change due to myopia, we performed a morphometrical study of stereophotographs of 61 men, 109 eyes, who had no glaucoma history. The range of refractive error was from +0.75 diopter to -12.75 diopter, and all subjects had intraocular pressure below or equal to 21 mmHg. According to the increase in the myopic degree, the temporal slope of the disc cup was significantly decreased, but the ratio of the vertical disc diameter (VDD) to the horizontal disc diameter and the ratio of the width of peripapillary atrophy (PPA) to the VDD were significantly increased. The above results suggests that in high myopia the optic disc was tilted and the rim-cup border was indistinct and there are some problems in the estimation of the morphometric parameters. Also in evaluation of the PPA of myopic glaucoma patients, there may be some difficulty in deciding whether it is due to myopic change or glaucomatous damage.

Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) with post-transplantation cyclophosphamide (PTCy) was performed previously in adults using a nonmyeloablative conditioning regimen and bone marrow as a graft source. In an effort to reduce relapse rates, myeloablative conditioning regimens with higher intensities are now used. We used an intensive daily pharmacokinetic monitoring method for busulfan dosing in children for effective myeloablation and to reduce toxicity. Here, we report the retrospective results of 34 patients (median age 11.1 years) who underwent haplo-HSCT with PTCy using a targeted busulfan-based myeloablative conditioning regimen and peripheral blood as a stem cell source. The donor-type neutrophil engraftment rate was 97.1%, and the cumulative incidence rates of grade II to IV and grade III to IV acute and extensive chronic graft-versus-host disease were 38.2%, 5.9%, and 9.1%, respectively. The overall survival and event-free survival rates, and treatment-related mortality were 85.0%, 79.4%, and 2.9%, respectively. Based on the subgroup analysis of patients with malignancies (n = 23), the relapse incidence rate was 21.7%. Haplo-HSCT using PTCy with targeted busulfan-based myeloablative conditioning and peripheral blood as a stem cell source was a safe and promising therapeutic option for children.

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