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Acute GVHD has remained a significant cause of nonrelapse mortality after allogeneic hematopoietic cell transplantation (HCT) with nonmyeloablative conditioning. The role of TNF-α in the biology of acute GVHD after nonmyeloablative conditioning has not been studied thus far. Here, we measured TNF receptor 1 (TNFR1) as a surrogate marker for TNF-α in 106 patients before the start of the conditioning regimen (baseline) and 7 days after allogeneic HCT with nonmyeloablative conditioning. The nonmyeloablative regimen consisted of 2 Gy TBI alone (n=15), 2 Gy TBI plus fludarabine 90 mg/m2 (n=73), or 4 Gy TBI plus fludarabine 90 mg/m2 (n=18). TNFR1 levels increased significantly from baseline to day 7 after nonmyeloablative HCT (P<0.0001). Patients conditioned with 4 Gy TBI had higher TNFR1 day 7/baseline ratio than those conditioned with 2 Gy TBI (median 1.65 versus 1.25; P=0.01). In a multivariate Cox model, high TNFR1 day7/baseline ratio was associated with grades II–IV (HR=2.2, P=0.01) and grades III–IV (HR=2.9, P=0.007) acute GVHD, but had no impact on overall survival (P=0.8). In summary, our data suggest that nonmyeloablative conditioning induces the generation of TNF-α, and that the magnitude of TNF-α generation depends on the conditioning intensity (2 Gy versus 4 Gy TBI). Further, assessment of TNFR1 levels before and on day 7 after nonmyeloablative HCT provided useful information on subsequent risk of experiencing acute GVHD. [ABSTRACT FROM AUTHOR]

The role of conditioning intensity on occurrence of thrombotic microangiopathy (TMA) after allogeneic hematopoietic cell transplantation (HCT) has remained unclear thus far. Here, we retrospectively compared the incidence of TMA in patients given allogeneic hematopoietic stem cells after either nonmyeloablative (n=176) or high-dose (n=111) conditioning. The 1-year cumulative incidence of TMA was 13% in nonmyeloablative recipients versus 15% in high-dose conditioning recipients (P=0.5). In multivariate Cox analysis, occurrence of grade 3–4 acute graft-versus-host disease (GVHD) (hazard ratio (HR)=2.3, P<0.001), older age (HR=1.01, P=0.045), and unrelated donors (HR=1.6, P=0.01) were each associated with a higher risk of TMA, whereas nonmyeloablative conditioning was associated with a lower risk of TMA (HR=0.6, P=0.01). We conclude that acute GVHD, age, donor type, and conditioning intensity might have a role in the physiopathology of TMA after allogeneic HCT. [ABSTRACT FROM AUTHOR]

Calcium and vitamin D supplementation has been shown to reduce secondary hyperparathyroidism and play a role in the management of senile osteoporosis. In order to define the optimal regimen of calcium and vitamin D supplementation to produce the maximal inhibition of parathyroid hormone secretion, we have compared the administration of a similar amount of Ca and vitamin D, either as a single morning dose or split in two doses, taken 6 hours apart. Twelve healthy volunteers were assigned to three investigational procedures, at weekly intervals. After a blank control procedure, when they were not exposed to any drug intake, they received two calcium-vitamin D supplement regimens including either two doses of Orocal D3 ® (500 mg Ca and 400 IU vitamin D) 6 hours apart or one water-soluble effervescent powder pack of Cacit D3 ® in a single morning dose (1000 mg Ca and 880 IU vitamin D). During the three procedures (control and the two calcium-vitamin D supplementations), venous blood was drawn every 60 minutes for up to 9 hours, for serum Ca and serum PTH measurements. The order of administration of the two Ca and vitamin D supplementation sequences was allocated by randomization. No significant changes in serum Ca were observed during the study. During the 6 hours following Ca and vitamin D supplementation, a statistically significant decrease in serum PTH was observed with both regimens, compared with baseline and with the control procedure. Over this period of time, no differences were observed between the two treatment regimens. However, between the sixth and the ninth hour, serum PTH levels were still significantly decreased compared with baseline with split dose Orocal D3 ® administration, while they returned to baseline value with the Cacit D3 ® preparation. During this period, the percentage decrease in serum PTH compared with baseline was significantly more pronounced with Orocal D3 ® than with Cacit D3 ® (P = 0.0021). We therefore conclude that the administration of two doses of 500 mg of calcium and 400 IU of vitamin D3 6 hours apart provides a more prolonged decrease in serum PTH levels than the administration of the same total amount of Ca and vitamin D as a single morning dose in young healthy volunteers. This might have implications in terms of protection of the skeleton against secondary hyperparathyroidism and increased bone resorption and turnover in elderly subjects. [ABSTRACT FROM AUTHOR]

We have selectively grown InGaAs (0.04 < x < 0.20, 200 − 7000Å) on rectangular growth areas (100 μm by 200 mil) patterned on GaAs substrates with very low etch pit densities (∼200 cm). The edge orientations of the growth areas were varied on the substrate resulting in distinct facet formation on the deposited mesa structures. Layers were grown using Low-Pressure Organometallic Chemical Vapor Deposition (LPOMCVD) and all samples were annealed for 1 hr at 700° C. Indium content and film thicknesses were very uniform across a wafer so that only the facet shape was varied. Observation of Crosshatch defect densities as a function of growth window orientation showed that 2900Å InGaAs mesas with [010] edge orientations exhibited no Crosshatch defects. Identical mesas grown in windows with other edge orientations exhibited varying crosshatch defect densities. Large unpatterned areas of growth were heavily crosshatched. This variation in Crosshatch defect density as a function of mesa orientation appears to be associated with non-area related dislocation nucleation mechanisms at the mesa edges. Proper choice of window orientation for patterned substrate epitaxy will allow the mesa facets to be controlled thereby reducing misfit dislocations in the heterostructure interface. [ABSTRACT FROM AUTHOR]

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A letter to the editor is presented which reports a randomized trial evaluating the impact of cluster of differentiation 8 (CD8) protein depletion of peripheral blood stem cells (PBSCs) on allogeneic hematopoietic cell transplantation (HCT) outcomes after non-myeloablative conditioning.