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Editorials
(steroid-refractory) GvHD were those with elevated pre- References
HCT angiopoietin 2 levels.3 While the overall picture in that setting is more complex, are there potential interactions between elevated ADMA and angiopoietin 2 levels? Or are both elevated because of the same insult? It would have been of interest to see (in the present study) pre-transplant angiopoietin 2 levels and whether there was a correlation with ADMA concentrations.
Additional studies will be necessary to further dissect interactions between ADMA and other molecules, to fol- low ADMA levels longitudinally (for example, do levels change with the development of GvHD?), and to determine whether the time of onset of GvHD might have an impact (there was a wide time span during which GvHD devel- oped). Furthermore, while a global comparison of high- intensity and reduced-intensity conditioning regimens is provided, and early and late disease stages were considered, it would have been interesting to have had more specific data on the conditioning regimens and, for example, treat- ment of diseases prior to transplantation. This is not to diminish the authors’ accomplishments; however, some of these studies will be necessary in order to provide a mech- anistic explanation for the data.
In conclusion, the data must be interpreted with caution. This is particularly important when considering possible interventions. As suggested by the authors, high doses of citrulline may be useful to raise L arginine levels, counter- balancing the effect of ADMA. Could phosphodiesterase-5- inhibitors (such as sildenafil) be useful to force the induc- tion of NO synthase? Additional work should generate interesting data.
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