Clonal hematopoiesis as defined by polymorphic X-linked loci occurs infrequently in aplastic anemia

We evaluated the methylation status of the X-linked gene phosphoglycerate kinase (PGK1) and the DXS 255 locus detected by probe M27 beta to study clonality in acquired aplastic anemia (AA). A total of 30 females were suitable for clonal analysis of peripheral blood polymorphonuclear cells (PMN) and mononuclear cells using a polymerase chain reaction-based procedure in 24 patients and Southern blotting in 9. Overall, 10 of 30 patients exhibited an imbalanced X-inactivation pattern. However, in 4 patients, analysis of constitutional DNA suggested a skewed methylation pattern and 2 further cases had to be excluded because of the lack of an appropriate control. A truly clonal pattern was thus established in 4 of 30 (13%) patients. In 7 patients who later developed clonal disorders of hematopoiesis, X-inactivation analysis did not predict this event in any case. In patients with a paroxysmal nocturnal hemoglobinuria phenotype, there was no correlation between the proportion of phosphatidylinositol glycan anchored protein (PIG-AP)-deficient blood cells and the corresponding X-inactivation pattern. X-inactivation analysis detected clonal hematopoiesis in only 3 of 10 patients with a deficiency in PIG-AP in the cell population under study, but sorting of nucleated cells on the basis of PIG-AP expression showed the clonal nature of PIG-AP-deficient cells. We conclude that the majority of patients with AA show polyclonal hematopoiesis using X-linked clonal analysis, but that minor clonal populations, such as PIG-AP-deficient cells, may not be detected unless sorted cell populations are separately analyzed.     

Thalidomide as salvage therapy for chronic graft-versus-host disease

Thalidomide has been reported to be an effective agent for treatment of chronic graft-versus-host disease (CGVHD). To determine the efficacy of this agent in patients with refractory CGVHD a total of 80 patients who failed to respond to prednisone (PSE) or PSE and cyclosporine (CSA) were treated with thalidomide. Sixteen patients (20%) had a sustained response, 9 with a complete remission and 7 with a partial response. Twenty-nine patients (36%) had thalidomide discontinued because of side effects, which included sedation, constipation, neuritis, skin rash, and neutropenia. Side effects were reversible with drug discontinuation except for mild residual neuritis in one case. Rashes and neutropenia have not previously been reported as thalidomide side effects when used for CGVHD treatment. We conclude thalidomide is immunosuppressive and active in the treatment of CGVHD. A high incidence of reversible side effects limited dose intensity and reduced the number of patients who could benefit from treatment.     

Efficacy of isokinetic exercise on functional capacity and pain in patellofemoral pain syndrome

OBJECTIVE: To assess the effect of an isokinetic exercise program on symptoms and functions of patients with patellofemoral pain syndrome. DESIGN: A total of 22 consecutive patients with the complaint of anterior knee pain who met the inclusion criteria were recruited to assess the efficacy of isokinetic exercise on functional capacity, isokinetic parameters, and pain scores in patients with patellofemoral pain syndrome. A total of 37 knees were examined. Six-meter hopping, three-step hopping, and single-limb hopping course tests were performed for each patient with the measurements of the Lysholm scale and visual analog scale. Tested parameters were peak torque, total work, average power, and endurance ratios. RESULTS: Statistical analyses revealed that at the end of the 6-wk treatment period, functional and isokinetic parameters improved significantly, as did pain scores. There was not statistically significant correlation between different groups of parameters. CONCLUSION: The isokinetic exercise treatment program used in this study prevented the extensor power loss due to patellofemoral pain syndrome, but the improvement in the functional capacity was not correlated with the gained power.