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It depends whether you're talking about dye migration, or staining.

Dye migration happens when you cure the ink, and it's caused by heat: the polyester dyes sublimating into the ink. Pre-washing won't help.

Staining occurs when the cotton dyes wash out during laundering, and stain the white ink. Pre-washing might help.
 

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Red 50/50s are notorious for bleeding. Unless it's a specialty shirt that can't be substituted with cotton, I'd strongly push the customer towards 100% cotton. If you HAVE to print 50/50, use a low-bleed ink and keep the temperature as low as possible while still reaching a cure temperature.
 
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