The key is to load things up in your test environment and do thorough testing, there are major changes from 12.10 to 12.50, most occurred in the 12.30 release, so you need to be sure everything is working properly. Read all the Release notes and What's new on the interim releases to understand what new features you are getting and what may cause issues etc. Pretty standard development practices is the key to success, test, test, test before you upgrade your production environment and be sure you test environment mimics prod, as if you have any clustered resources in prod, but not in test, then you are not really testing thoroughly in that case.
That gets you the What's New pieces, you will have to download the Release notes to check things there. Again, 12.30 is where most of the big changes occurred, so that is where I would be sure to read up on things, as that is where you are likely to run into issues, the new Skia Graphics Engine, and the other new features in that release are most likely to be where you are going to have issues.
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