Level set approach to reversible epitaxial growth.

We generalize the level set approach to model epitaxial growth to include thermal detachment of atoms from island edges. This means that islands do not always grow and island dissociation can occur. We make no assumptions about a critical nucleus. Excellent quantitative agreement is obtained with kinetic Monte Carlo simulations for island densities and island size distributions in the submonolayer regime.

Interpretation of resonant photoemission spectra of solid actinide systems.

It is shown that valence-band photoemission (PE) spectra of epitaxial hcp films of U metal may be understood within a one-step model of PE based on an itinerant description of the U 5f states. Particularly, the PE intensities of the f-derived bands are correctly reproduced for photon energies between 60 and 103 eV. It is found that a cross-section minimum of the Fermi-energy feature at h(nu) = 90-94 eV, which previously was assigned to a Fano antiresonance at the 5d-->5f excitation threshold, is mainly caused by a Cooper minimum. Analogous 5f cross-section variations in the region of the 5d-->5f resonances were obtained for UPd3 and Pu metal.

Target dose adjustment of busulfan in pediatric patients undergoing bone marrow transplantation.

Published data suggest that the average concentration of busulfan at steady state (Bu Css) is critical for successful engraftment in children receiving busulfan as a conditioning agent for bone marrow transplantation (BMT). We previously found in children that a Bu Css <600 ng/ml correlated with autologous recovery/mixed chimerism; there was no correlation between Bu Css and regimen-related toxicity (RRT). In a cohort continuous with the previous trial, we prospectively evaluated targeted busulfan concentrations in 32 pediatric patients (age 0.6-18.5 years) with AML (n = 6), CML (n = 6) and non-malignant disorders (n = 20) receiving HLA-closely matched donor grafts. In this trial, individual busulfan pharmacokinetics were performed prior to admission. Busulfan doses were then adjusted to achieve a Bu Css target range of 600-900 ng/ml +/- 10% depending on donor source and disease. A repeat study was done following dose 1 of the conditioning regimen. Thirty of thirty-two (94%) patients achieved target concentrations. Total busulfan doses ranged from 10.9 to 29 mg/kg. Thirty of thirty-two patients (94%) have durably engrafted. Grade 3/4 RRT occurred in seven patients (21%). Targeting Bu Css ranges of 600-900 ng/ml significantly improved our rate of successful engraftment from 74% to 94% (P = 0.043). These results indicate that targeted busulfan dosing optimizes allogeneic engraftment in children.

An evaluation of engraftment, toxicity and busulfan concentration in children receiving bone marrow transplantation for leukemia or genetic disease.

Autologous recovery is a major problem with busulfan as a marrow ablative agent in conditioning children for allogeneic BMT. Data suggest the average concentration of busulfan at steady state (Bu Css) is critical for successful engraftment. We prospectively evaluated busulfan pharmacokinetics in 31 children (age 0.6-18 years) with AML (n = 9), and non-malignant diseases (n = 22) receiving HLA-closely matched (sibling, parent, unrelated) donor grafts. Blood samples were obtained following dose 1 and 13 of a standard 16 dose, 4-day regimen. The busulfan dose varied from 14 to 20 mg/kg. Patients received cyclophosphamide 200-240 mg/kg; 22/31 received 80-90 mg/kg of ATG. Eight patients failed to engraft (26%). ATG did not appear to influence engraftment (P = 0.38). Bu Css levels <600 ng/ml correlated with autologous recovery/mixed chimerism (P = 0.018). There were no graft failures in patients with a Bu Css >600 ng/ml. A correlation between Bu Css levels and regimen-related toxicity (RRT) was not identified for grade 2 or higher toxicities, only 1/31 had a Bu Css >900 ng/ml. Our data support the use of pharmacokinetic monitoring of busulfan.