Primary transplantation of allogeneic peripheral blood progenitor cells mobilized by filgrastim (granulocyte colony-stimulating factor)

Transplantation of allogeneic peripheral blood progenitor cells (PBPCs) may have advantages over bone marrow transplantation (BMT) with regards to the speed of hematopoietic and immunologic recovery, which may then shorten the time spent in hospital and decrease costs. The recipient might also profit by an enhanced graft-versus-leukemia reaction exerted by the high number of natural killer cells contained in such grafts. The donor could be spared the discomfort and risks of general anesthesia and marrow harvesting. Primary transplantation of unmanipulated allogeneic PBPCs has not been reported so far because the vast amount of T cells contained in the collection product was thought to cause severe graft-versus-host disease. We present preliminary data on primary transplantation of allogeneic PBPCs in patients who either suffered from advanced leukemia or had a donor unable to undergo general anesthesia. Eight patients with a median age of 42 years suffering from acute myelogenous leukemia (AML) in first remission (n = 3), AML in third remission, AML in relapse (n = 2), acute lymphoblastic leukemia in second remission, or chronic myelogenous leukemia in accelerated phase received myeloablative therapy followed by transplantation of unmanipulated allogeneic PBPCs mobilized with granulocyte colony-stimulating factor (5 to 10 micrograms/kg of body weight of filgrastim administered for 5 to 6 days) in their HLA-identical donors. Hematopoietic reconstitution was achieved in all patients with a median of 15.5 (16.5) days after transplant needed to surpass an absolute neutrophil count of 0.5 (1.0) x 10(9)/L. The median time to an unsupported platelet count greater than 20 (> 50) x 10(9)/L was 19.5 (41) days after grafting. Three patients did not exhibit signs of acute graft-versus-host disease (GVHD), grade I disease was seen in one patient, and three patients experienced grade II disease limited to the skin. The only patient with severe acute GVHD (grade III) refused to take his oral cyclosporin regularly and had ineffective serum levels for most of the time until relapse. Six of eight patients are currently alive without evidence of disease between 61 and 533 days after grafting; two patients grafted for AML in relapse achieved a complete remission after transplantation but relapsed again and died of leukemia on days +48 and +70, respectively. Primary transplantation of unmanipulated allogeneic PBPCs is feasible and results in long-term engraftment without causing detrimental GVHD.

Superior function of a bicuspid over a monocuspid patch for reconstruction of a hypoplastic pulmonary root in pigs.

In an experimental study in pigs, the function of monocuspid and bicuspid patches was compared to improve surgical reconstruction of a hypoplastic pulmonary root. Segments from glutaraldehyde-treated porcine aortic roots served as monocuspid and bicuspid patches. Their leaflets and commissures were marked with radiopaque metal clips. Marker movements were recorded at 100 frames/sec. Quantification of pulmonary insufficiency, right ventricular stroke volume, as well as pressures in the right ventricle, pulmonary artery, and aorta was performed before and after patch plasty. The cyclic motion of the leaflets showed a three-phase pattern in monocuspid and bicuspid patches: (1) a rapid opening motion with a significantly longer distance to be covered in monocuspid patches (7.5 mm in monocuspid versus 4.9 mm in bicuspid patches); (2) a slow closing motion that was significantly greater in monocuspid patches (31.5% of maximal displacement in monocuspid versus 18.2% and 23.8% in bicuspid patches); (3) a similar rapid closure motion in both types of patches. The commissural expansion was less than 6% for monocuspid and bicuspid patches and began 10 to 20 msec before valve opening. Considerable irregularities in the movement of the different leaflet markers, especially in monocuspid patches, indicated leaflet buckling as a result of redundant leaflet tissue. There was a significant pulmonary regurgitant fraction only in monocuspid patches (19% in monocuspid versus 7% in bicuspid patches) that occurred during early diastole. No pressure gradients were observed across either type of patch. In monocuspid patches, a greater leaflet displacement during rapid closure was correlated with an increased pulmonary insufficiency (r = 0.8875). In conclusion, the function of a bicuspid patch is superior to that of a monocuspid patch for repair of a hypoplastic pulmonary root and allows the construction of a competent and stenosis-free valve mechanism.