$re = '/_ABC(?:(?!_ABC).)+$/m';
$str = '_AB:C-_ABCDEF_ABC:45_ABC:454:
_AB:C-_ABCDEF_ABC:45_ABC_ABC:454:';
$subst = "_CBA";
$result = preg_replace($re, $subst, $str);
echo "The result of the substitution is ".$result;
Please keep in mind that these code samples are automatically generated and are not guaranteed to work. If you find any syntax errors, feel free to submit a bug report. For a full regex reference for PHP, please visit: http://php.net/manual/en/ref.pcre.php