<p>After a few months of printing with my Prusa Mk3 (with plans to get a second one soon), I have been wondering about making my third printer a home-built one was a larger print bed than the Mk3. One thing I wondered about is perfectly expressed in the title question.</p>

<p>Are there practical reasons to <strong>not</strong> use a stepper motor with lead screw for the X and or Y axes?</p>

<p>I am certainly happy with the GT2 belts used in my current printer, but I wonder if the design might be simpler with lead-screws on all three axes.</p>

Cost would be the primary reason.  You can engineer a belt driven system that will be equally accurate, faster, and with longer travel for a lower cost.
Lead screws are comparatively expensive. The cost differential dramatically increases with length of travel and speed with equivalent accuracy.
Lead screws do have a significant advantage of being able to carry a much heavier load while maintaining rigidity which is important for something like a CNC mill but isn't as relevant for 3D printing.
This is on the assumption when you say:
Are there practical reasons to
not
use a stepper motor with lead screw for the X and or Y axes?
you meant that you are still planning on using stepper motors but considering a lead screw vs. belts.